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8,981,846 | 1997-01-16 | 2019-11-01 | 0965-2302 | Accident and emergency nursing | Concepts related to Chinese patients' perceptions of health, illness and person: issues of conceptual clarity. | Shih F J | eng | null | Journal Article, Review | null | null | 8981846, S0965-2302(96)90086-7, 10.1016/s0965-2302(96)90086-7 | Since most health professionals who care for Chinese patients are trained using Western medical educational systems, they are often unaware of the complex Chinese culture that influences their patients' responses to care. Discrepancies often exist between health professionals' and Chinese patients' perceptions of health and evaluations of the quality of care. In order to provide culturally sensitive care for this population, the complex Chinese traditional philosophies, such as the theory of yin and yang and the five phases, as well as the philosophies related to the concept of personhood including Confucianism, Taoism and Buddhism are examined first. This is because these theories and philosophies not only influence Chinese patients' values and beliefs, but also determine their perceptions of health, illness and nursing care. The discussion of implications for surgical cardiovascular nursing practice for this particular population are followed. | Attitude to Health, China, Humans, Medicine, Chinese Traditional, Philosophy, Religion and Medicine, Transcultural Nursing | null |
8,981,847 | 1997-01-16 | 2019-11-01 | 0965-2302 | Accident and emergency nursing | Developments in nursing in accident and emergency services: providing nursing advice to the Scottish Office Department of Health. | Davidson J | eng | null | Journal Article | null | null | 8981847, S0965-2302(96)90089-2, 10.1016/s0965-2302(96)90089-2 | null | Emergency Nursing, Health Planning, Humans, Job Description, Organizational Innovation, Scotland | null |
8,981,848 | 1997-01-16 | 2019-11-01 | 0887-9303 | Critical care nursing quarterly | New ventilatory strategies in acute respiratory failure. | Gowski D T, Miro A M | eng | null | Journal Article, Review | Nitric Oxide | null | 8981848, 10.1097/00002727-199619030-00002 | New management options for acute respiratory failure aim at avoiding ventilator-induced lung injury while maintaining adequate gas exchange. Selected approaches examined in this article include methods to augment carbon dioxide elimination with tracheal gas insufflation, venovenous extracorporeal carbon dioxide removal, and intravascular oxygenation. Improving oxygenation can be accomplished by judicious use of positive end-expiratory pressure, venoarterial extracorporeal membrane oxygenation, and pharmacologic intervention with inhaled nitric oxide. | Acute Disease, Critical Care, Extracorporeal Membrane Oxygenation, Humans, Nitric Oxide, Pulmonary Gas Exchange, Respiration, Artificial, Respiratory Insufficiency | null |
8,981,849 | 1997-01-16 | 2020-12-09 | 0887-9303 | Critical care nursing quarterly | Pressure controlled-inverse ratio ventilation. | Delgado E | eng | null | Journal Article, Review | null | null | 8981849, 10.1097/00002727-199619030-00003 | One of the many challenges in the management of the patient with adult respiratory distress syndrome is optimal application of mechanical ventilation. Pressure controlled-inverse ratio ventilation has surfaced as a possible alternative to conventional ventilation for patients affected by this condition. In pressure controlled-inverse ratio ventilation, the conventional inspiratory-to-expiratory ratio is reversed, allowing the inspiratory phase to lengthen with an accompanying increase in mean airway pressure. When carefully applied, mean airway pressure adjustments can be manipulated without increases in positive end-expiratory pressure and peak airway pressure, thus minimizing the risk of alveolar rupture and worsening of lung injury. | Adult, Clinical Protocols, Critical Care, Humans, Patient Care Planning, Positive-Pressure Respiration, Respiratory Distress Syndrome | null |
8,981,850 | 1997-01-16 | 2019-11-01 | 0887-9303 | Critical care nursing quarterly | Terminal weaning from mechanical ventilation: planning and process. | Tasota F J, Hoffman L A | eng | null | Journal Article, Review | null | null | 8981850, 10.1097/00002727-199619030-00004 | There are two major goals of critical care: (1) to save those with a chance to live and (2) to help patients who are dying have a peaceful and dignified death. If reversal of the disease process is not possible and the patient is experiencing substantial pain and suffering, goals need to be reviewed and potentially redefined. These new goals may be to remove unwanted or nonbeneficial therapy, to provide death with dignity, and to support the family. This article details aspects of the decision-making process regarding withdrawal of mechanical ventilation, including ethical principles; decision-making for autonomous patients and non-autonomous patients; advance directives; planning withdrawal of support; terminal weaning methods; patient comfort; family support; and future directions for research, practice, and education. | Critical Care, Decision Trees, Ethics, Nursing, Euthanasia, Passive, Family, Humans, Patient Care Planning, Terminal Care, Ventilator Weaning | null |
8,981,851 | 1997-01-16 | 2019-11-01 | 0887-9303 | Critical care nursing quarterly | Using drug chronotherapy to wean patients from mechanical ventilation. | Clochesy J M, Petty G M, Paschall F E | eng | null | Case Reports, Journal Article, Review | null | null | 8981851, 10.1097/00002727-199619030-00005 | Discontinuation of positive pressure mechanical ventilation results in decreased intrathoracic pressure. Although there has been extensive research into factors associated with weaning adults from mechanical ventilatory support, little attention has been paid to the role of left ventricular performance. Research also has not focused on interventions that might optimize ventricular performance. The purpose of this article is to explore the potential effect of cardiac dysfunction in weaning and the role of drug chronotherapy as a strategy to modify patients' responses to weaning from mechanical ventilatory support. Biophysical principles involved are reviewed, and the development of a chronotherapeutic intervention is described. Two case examples illustrate the use of drug chronotherapy during the weaning process. | Aged, Chronotherapy, Critical Care, Female, Hemodynamics, Humans, Male, Ventilator Weaning | null |
8,981,852 | 1997-01-16 | 2019-11-01 | 0887-9303 | Critical care nursing quarterly | Respiratory care of the postoperative lung transplantation patient. | George E L, Large A A, Boujoukos A J, Tuttle R P | eng | null | Journal Article, Review | null | null | 8981852, 10.1097/00002727-199619030-00006 | The management of patients receiving lung transplantation has been evolving during the last thirty years. Transplant programs have continued to develop both in United States and internationally. Patient evaluations and experiences with procedures help guide the decision as to which type of transplant would best benefit the patient. To care for lung transplantation patients, nurses need an understanding of the alterations in physiology from the procedure. An understanding of the clinical experiences in the areas of immunosuppression, preoperative conditioning, surgical techniques, preservation techniques, ventilatory management, and nursing care have made significant contributions to patient survival. | Critical Care, Hemodynamics, Humans, Lung Transplantation, Postoperative Care, Respiratory Therapy | null |
8,981,853 | 1997-01-16 | 2019-11-01 | 0887-9303 | Critical care nursing quarterly | High-altitude pulmonary edema: a clinical crisis. | Angerio A D, Kot P A | eng | null | Journal Article, Review | Endothelins, Atrial Natriuretic Factor | null | 8981853, 10.1097/00002727-199619030-00007 | High-altitude pulmonary edema is a serious clinical condition observed in individuals participating in mountain climbing and skiing at high altitudes. High-altitude pulmonary edema is an oncardiogenic form of pulmonary edema. Atrial natriuretic factor and endothelin are implicated and ventilatory support is important in preventing fatalities. | Altitude Sickness, Atrial Natriuretic Factor, Critical Care, Endothelins, Humans, Pulmonary Circulation, Pulmonary Edema | null |
8,981,854 | 1997-01-16 | 2019-12-10 | 0887-9303 | Critical care nursing quarterly | Optimizing outcomes in ventilator-dependent patients: challenging critical care practice. | Kite-Powell D M, Sabau D, Ideno K T, Hartgraves D, Dahlberg C G | eng | null | Journal Article | null | null | 8981854, 10.1097/00002727-199619030-00008 | This article examines the structure and process of a collaborative practice team established specifically to improve the quality and financial outcomes of ventilator-dependent patients in a tertiary care teaching hospital. A brief overview of descriptors regarding ventilator-dependent patients is synthesized from the literature and compared with the population at St. Luke's Episcopal Hospital in Houston, Tex. An analysis of statistically significant physiologic variances that have been found to increase mechanical ventilation time or length of stay is detailed. Focused quality initiatives are discussed. Specific criteria indicative of improved outcomes are presented along with recommendations for future improvements. | Critical Care, Critical Pathways, Humans, Outcome and Process Assessment, Health Care, Patient Care Team, Respiration, Artificial | null |
8,981,855 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Developing practice: the contribution of the master's prepared nurse. | Manley K | eng | null | Editorial | null | null | 8981855, 10.1111/j.1365-2702.1996.tb00265.x | null | Career Mobility, Education, Nursing, Graduate, Humans, Nurse Clinicians, Professional Practice | null |
8,981,856 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | The evolving role of the clinical nurse specialist within the comprehensive breast cancer centre. | Poole K | eng | null | Journal Article, Review | null | null | 8981856, 10.1111/j.1365-2702.1996.tb00266.x | The collaborative functioning of a specialist multidisciplinary team is a fundamental prerequisite in the establishment of designated breast cancer units throughout the U.K. It is, therefore, opportune for clinical nurse specialists to examine carefully their unique contribution to the care of women with breast disease. This article explores the contemporary developments in service provision and identifies potential areas for nursing development. It is only when the role of the breast care nurse is explicitly defined can research begin to determine the effectiveness of nursing practice in terms of women's health. | Breast Neoplasms, Comprehensive Health Care, Female, Health Promotion, Humans, Job Description, Nurse Clinicians, Oncology Nursing | null |
8,981,857 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Introducing primary nursing: nurses' opinions. | Webb C, Pontin D | eng | null | Journal Article | null | null | 8981857, 10.1111/j.1365-2702.1996.tb00267.x | This article reports on one aspect of a research project carried out to monitor and evaluate the introduction of primary nursing on four demonstration wards in one health authority. Nursing staff working on the wards were interviewed to identify how the changes were affecting them and their work. Stress questionnaires were also completed by a sample of nurses on the wards. Responsibility and communication--key concepts emerging from the data--are discussed and related to the literature on primary nursing. | Attitude of Health Personnel, Humans, Job Description, Nursing Methodology Research, Nursing Staff, Hospital, Organizational Innovation, Primary Nursing, Surveys and Questionnaires | null |
8,981,859 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Paediatric nursing and children's autonomy. | Lowes L | eng | null | Journal Article, Review | null | null | 8981859, 10.1111/j.1365-2702.1996.tb00269.x | The topic of children's rights is a wide-ranging and complex subject, and in recognition of this fact this paper specifically addresses the concept of the right of children to make decisions about their own health-care. This paper explores the many factors which may influence a child's right to autonomy, including family relationships and the broader external influences exerted by health-care workers. The discussion highlights the dilemmas which may be faced by nurses when their values and beliefs, or hierarchical position within the health-care structure, inhibit their ability to promote children's autonomy. | Adolescent, Child, Child Advocacy, Ethics, Nursing, Humans, Patient Participation, Pediatric Nursing | Professional Patient Relationship |
8,981,858 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Readability of printed educational materials used to inform potential and actual ostomates. | Coey L | eng | null | Journal Article | null | null | 8981858, 10.1111/j.1365-2702.1996.tb00268.x | This paper is primarily concerned with the use of readability formulas to determine the reading ease of printed education materials (PEMs) given to ostomy patients. Whilst the particular clinical focus is stoma care nursing, the content is relevant to all nurses who use printed text to inform their patients. PEMs have significant advantages in conveying information compared with verbal presentations alone. Methods to calculate readability using the Flesch, FOG and SMOG readability formulas are described. Presentation factors that affect readability are briefly reviewed, including use of 'white space', font size and paper colour. The problem of functional illiteracy and the need for indirect assessment of patient literacy are discussed. PEMs in use are often found to be difficult to read. Stress is identified as a potential factor in further reducing a patient's ability to deal with information. Three commercially available PEMs are evaluated for ease of reading and their score on the FOG index indicates that only about 40% of the UK population would understand them. Nurses are advised to evaluate the readability of their PEMs and to assess indirectly the literacy of their patients, so that they can more sensitively match PEMs to patient ability and need. | Educational Status, Humans, Ostomy, Patient Education as Topic, Reading, Reproducibility of Results, Teaching Materials | null |
8,981,860 | 1997-01-16 | 2019-12-10 | 0962-1067 | Journal of clinical nursing | Coping with rheumatoid arthritis. How can specialist nurses influence it and promote better outcomes? | Newbold D | eng | null | Journal Article, Research Support, Non-U.S. Gov't, Review | null | null | 8981860, 10.1111/j.1365-2702.1996.tb00270.x | Psychological stressors are said to be an important influence on the outcome of chronic illness such as rheumatoid arthritis (Engel, 1977). Helping patients to cope with stressors is identified as a central concept in the delivery of nursing care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology nurses may be key players in the process of coping with rheumatoid arthritis. But in order for rheumatology nurses to be effective players in this process, they need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an overall behaviour pattern linked to a better outcome. Literature showing the link between different coping behaviours and outcome is examined, and cognitive restructuring is emphasized as one method nurses could use. Having identified coping behaviour which is optimal in terms of future outcome, further study of different forms of coping-based educational intervention is suggested, to reveal how such patterns of behaviour can be taught by nurses in the most effective way. | Adaptation, Psychological, Arthritis, Rheumatoid, Health Promotion, Humans, Models, Psychological, Nurse Clinicians, Outcome Assessment, Health Care | null |
8,981,862 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Endotracheal suctioning: an example of the problems of relevance and rigour in clinical research. | Wainwright S P, Gould D | eng | null | Journal Article, Review | null | null | 8981862, 10.1111/j.1365-2702.1996.tb00272.x | Endotracheal suctioning is a routine but potentially dangerous procedure. The literature documenting approaches to minimizing the cardiopulmonary complications of endotracheal suctioning is reviewed. Hyperoxygenation, hyperventilation, hyperinflation and the use of adaptors are all evaluated. The effects of endotracheal suctioning on haemodynamics and oxygen transport are also examined. The traditional dualist approach to the respiratory and cardiovascular systems is contrasted with the recent emphasis on oxygen transport by the cardiopulmonary system. The trade-off between the rigour of laboratory studies (which can be well controlled but are difficult to generalize) and the relevance of clinical research (which is more easily generalized but which often lacks internal validity) is discussed. Although research studies have become both more methodologically and conceptually sophisticated, definitive recommendations for a safe and effective suctioning procedure still remain elusive. | Clinical Nursing Research, Hemodynamics, Humans, Intubation, Intratracheal, Reproducibility of Results, Suction | null |
8,981,861 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | Residents' perspectives of their first 2 weeks in a long-term care facility. | Iwasiw C, Goldenberg D, MacMaster E, McCutcheon S, Bol N | eng | null | Journal Article | null | null | 8981861, 10.1111/j.1365-2702.1996.tb00271.x | This study investigated residents' perspectives of their first 2 weeks in a long-term care facility (LTCF). Twelve residents were interviewed to determine their experiences during the first 2 weeks, their needs, priorities and expectations, and their views about how relocation from home could be facilitated. The constant comparative method of qualitative analysis (Glaser & Strauss, 1967) was used. Qualitative analysis of the audiotaped interviews revealed four main categories: emotional reactions, transition activities, reflecting on their situation, and connecting with a personal philosophy. Residents' responses indicated that if they had actively participated in the decision to be admitted, the adjustments to the LTCF was easier. Connecting with a personal philosophy was also a significant factor. Nursing implications include recognition of the importance of preparing residents for admission, involving them in the decision, and listening to their perspectives throughout the relocation experience. | Adaptation, Psychological, Aged, Aged, 80 and over, Attitude to Health, Female, Health Services Needs and Demand, Humans, Inpatients, Male, Nursing Methodology Research, Patient Participation, Skilled Nursing Facilities, Surveys and Questionnaires | null |
8,981,863 | 1997-01-16 | 2019-11-01 | 0962-1067 | Journal of clinical nursing | The management of clinician nutrition in NHS hospitals. | Dhoot R, Georgieva C, Grottrup T, Mahdavian R, Poh R, Hindle T | eng | null | Journal Article | null | null | 8981863, 10.1111/j.1365-2702.1996.tb00273.x | null | Cost-Benefit Analysis, Health Services Research, Hospitals, Humans, Nutritional Support, Patient Care Team, State Medicine, Surveys and Questionnaires, United Kingdom | null |
8,981,864 | 1997-01-16 | 2004-11-17 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Positioning adult health nursing for the future. | Fetter M S | eng | null | Editorial | null | null | 8981864 | null | Forecasting, Humans, Internal Medicine, Perioperative Nursing, Societies, Nursing, Specialties, Nursing, United States | null |
8,981,865 | 1997-01-16 | 2005-11-16 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Tubes: a nurse's guide to enteral feeding devices. | Bowers S | eng | null | Journal Article, Review | null | null | 8981865 | Nurses use a variety of sophisticated enteral feeding devices to provide nutritional feedings directly into the gastrointestinal tract. Nurses must be familiar with all aspects of enteral nutrition support to safely provide care. Appropriate care includes identifying high-risk patients, observing for symptoms of malnutrition, administering enteral feedings safely, assessing for possible complications, and monitoring the effectiveness of nutritional care. | Decision Trees, Enteral Nutrition, Humans, Intubation, Gastrointestinal, Nursing Assessment | null |
8,981,866 | 1997-01-16 | 2005-11-16 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Rehabilitating stroke patients in the acute care setting. | Fowler S, Durkee C M, Webb D J | eng | null | Journal Article, Review | null | null | 8981866 | The 1990s has been heralded as the Decade of the Brain. The National Stroke Association refers to stroke as a brain attack. Medical and nursing interventions are aimed at limiting the extent of brain injury, promoting early reperfusion, and preventing complications as a result of secondary injury or hazards of immobility. Medical-surgical nurses play a key role in facilitating collaborative rehabilitation in the acute care setting to achieve expected outcomes for the patient and family. | Acute Disease, Cerebrovascular Disorders, Humans, Nursing Assessment, Patient Care Planning | null |
8,981,867 | 1997-01-16 | 2007-11-15 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Patient and family education: an interdisciplinary process. | Clay J C, Wyatt L K, Norris G M | eng | null | Journal Article | null | null | 8981867 | An interdisciplinary education and discharge plan was developed in a 404-bed teaching hospital to coordinate and integrate the function of patient and family education across disciplines using one common form. This education plan was instrumental in providing improved documentation of patient and family education in both inpatient and outpatient departments. | Family, Humans, Nursing Records, Patient Care Planning, Patient Care Team, Patient Discharge, Patient Education as Topic | null |
8,981,869 | 1997-01-16 | 2005-11-16 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Assessing symptom distress in ambulatory surgery patients. | Swan B A | eng | null | Journal Article, Review | null | null | 8981869 | Symptom distress constitutes a major problem for patients and their families following ambulatory surgery, because managing symptom distress is their responsibility. It is essential that the assessment of symptom distress be an integral part of ambulatory surgery patient care delivery to decrease complications that occur when patients are sent home with unmet care needs. | Ambulatory Surgical Procedures, Humans, Nursing Assessment, Pain, Postoperative, Psychometrics, Reproducibility of Results, Stress, Psychological | null |
8,981,868 | 1997-01-16 | 2005-11-16 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | The nurse's role in facilitating compliance in clients with hypertension. | Eaton L, Buck E A, Catanzaro J E | eng | null | Journal Article, Review | null | null | 8981868 | Afflicting approximately 50 million people, hypertension costs over $500 million per year and accounts for the largest number of physician office visits per year and the greatest use of prescription drugs. Nurses play a vital role in assessing and managing hypertensive clients' and promoting clients' compliance with treatment regimens. | Algorithms, Humans, Hypertension, Life Style, Patient Compliance, Patient Participation | null |
8,981,870 | 1997-01-16 | 2005-11-16 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Oral nutritional supplements. | Bankhead R R | eng | null | Journal Article, Review | null | null | 8981870 | null | Enteral Nutrition, Food, Formulated, Humans, Protein-Energy Malnutrition, Risk Factors | null |
8,981,871 | 1997-01-16 | 2013-11-21 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | New treatment for obesity: dexfenfluramine (Redux). | Bihm B | eng | null | Journal Article | Appetite Depressants, Fenfluramine | null | 8981871 | null | Appetite Depressants, Body Mass Index, Fenfluramine, Humans, Obesity, Patient Selection | null |
8,981,872 | 1997-01-16 | 2004-11-17 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Preferring not-for-profit managed care. | Ott B B | eng | null | Journal Article | null | null | 8981872 | null | Choice Behavior, Ethics, Nursing, Hospitals, Voluntary, Humans, Managed Care Programs, United States | Health Care and Public Health |
8,981,873 | 1997-01-16 | 2006-08-24 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Assisted suicide and terminating life support: the state of the law. | Piotrowicz M S, Leahy W J | eng | null | Case Reports, Journal Article | null | null | 8981873 | null | Adult, Euthanasia, Passive, Humans, Male, Persistent Vegetative State, Suicide, Assisted, United States | Death and Euthanasia, Legal Approach |
8,981,874 | 1997-01-16 | 2007-11-15 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Hormone replacement therapy: helping your patient decide. | Appling S E | eng | null | Journal Article, Review | null | null | 8981874 | null | Decision Making, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Patient Education as Topic | null |
8,981,875 | 1997-01-16 | 2019-12-10 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Integrating guidelines into nursing practice. | Schumacher S B | eng | null | Journal Article | null | null | 8981875 | null | Humans, Nursing Care, Outcome and Process Assessment, Health Care, Patient Care Planning, Practice Guidelines as Topic | null |
8,981,876 | 1997-01-16 | 2004-11-17 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Case management in acute care. | Weston M A | eng | null | Journal Article | null | null | 8981876 | null | Academic Medical Centers, Acute Disease, Case Management, Humans, Models, Nursing | null |
8,981,877 | 1997-01-16 | 2004-11-17 | 1092-0811 | Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses | Moving research-based practice throughout the health care system. | Goode C J, Titler M G | eng | null | Journal Article | null | null | 8981877 | null | Diffusion of Innovation, Humans, Models, Nursing, Nurse Clinicians, Nursing Care, Organizational Innovation | null |
8,981,878 | 1997-01-30 | 2018-11-30 | 0009-921X | Clinical orthopaedics and related research | Tissue reactions to plastic and metallic wear products of joint endoprostheses. | Willert H G, Semlitsch M | eng | null | Biography, Classical Article, Historical Article, Journal Article, Portrait | Biocompatible Materials, Metals, Plastics | IM | 8981878 | null | Austria, Biocompatible Materials, Foreign-Body Reaction, Germany, History, 20th Century, Humans, Joint Prosthesis, Metals, Plastics, Prostheses and Implants | null |
8,981,879 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | The Otto Aufranc Award. Skeletal response to well fixed femoral components inserted with and without cement. | Maloney W J, Sychterz C, Bragdon C, McGovern T, Jasty M, Engh C A, Harris W H | eng | null | Journal Article | null | IM | 8981879 | Previous studies evaluating femoral remodeling after total hip arthroplasty have used clinical radiographs and dual energy xray absorptiometry. Limitation of these techniques make it impossible to quantify the magnitude of bone loss in terms of cortical thinning and cortical bone area and bone mineral density changes. Femoral cortical bone remodeling after cemented and cementless replacement was quantified and possible determinants of bone remodeling in terms of clinical and radiographic variables were evaluated. Forty-eight anatomic specimen femora from 24 patients with unilateral cemented and cementless hip replacements were analyzed. Cortical thickness, cortical bone area, and bone mineral density was assessed in 4 quadrants at 5 discrete levels. The maximum cortical bone loss by level was at the middle section for the cemented femurs and at the midproximal and middle sections for the cementless femurs. However, if one examines individual quadrants, the proximal medial cortex still represents the specific region of maximal bone loss for both types of implant fixation. The posterior cortex had substantially more bone loss, even in the diaphyseal levels, than had been previously appreciated. A strong correlation was noted between the bone mineral density of the control femur and the percentage decrease of bone mineral density in the remodeled femur. Based on this data, it seems that the less dense the bone is before hip replacement surgery, the greater the extent of bone loss after total hip arthroplasty regardless of the fixation type. | Adult, Aged, Aged, 80 and over, Bone Density, Bone Remodeling, Bone Resorption, Cementation, Female, Femur, Hip Prosthesis, Humans, Male, Middle Aged | null |
8,981,880 | 1997-01-30 | 2022-03-21 | 0009-921X | Clinical orthopaedics and related research | The John Charnley Award. Natural history of thromboembolic disease after total hip arthroplasty. | Pellegrini V D, Clement D, Lush-Ehmann C, Keller G S, Evarts C M | eng | null | Journal Article | null | IM | 8981880 | In 1079 consecutive patients undergoing total hip arthroplasty between 1984 and 1992, complications of thromboembolic disease and related anticoagulation were reviewed for 6 months after hospital discharge, including cost data. Of 347 patients having venograms, 78 (22.5%) had positive results and 269 (77.5%) had negative results for deep venous thrombosis. In patients with negative venograms, 3 (1.1%) were readmitted with 2 symptomatic deep venous thromboses and nonfatal pulmonary embolism. There were no readmissions among the 55 patients who had venographically evident deep venous thrombosis diagnosed and treated with outpatient warfarin. Overall, 3 of 324 (0.9%) patients with true positive or negative venograms were readmitted for complications of thromboembolic disease. In contrast, 12 of 732 (1.6%) patients not receiving contrast venography were readmitted, including 9 (1.2%) deep venous thromboses and 3 (0.4%) nonfatal pulmonary embolisms. Four of 23 patients (17.4%) with untreated calf deep venous thrombosis suffered 2 nonfatal pulmonary embolisms resulting in readmission and 2 fatal pulmonary embolisms outside the hospital. Untreated calf deep venous thrombosis after total hip arthroplasty represents a significant threat of extension to more proximal veins and distant embolization. Routine thromboembolic disease prophylaxis combined with screening contrast venography and selective therapeutic anticoagulation is effective in preventing late thromboembolic disease complications and, compared with a strategy of extended prophylaxis for all, is cost effective management by reducing exposure of the elderly population to outpatient anticoagulant therapy. | Aged, Costs and Cost Analysis, Hip Prosthesis, Humans, Middle Aged, Phlebography, Postoperative Complications, Thromboembolism, Thrombolytic Therapy, Time Factors | null |
8,981,881 | 1997-01-30 | 2022-04-08 | 0009-921X | Clinical orthopaedics and related research | The Frank Stinchfield Award. 3-Dimensional sliding/contact computational simulation of total hip wear. | Maxian T A, Brown T D, Pedersen D R, Callaghan J J | eng | AR-43314 (NIAMS NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Polyethylenes | IM | 8981881 | Polyethylene wear in total hip replacements is a complex, multifactorial process. A tribologically grounded finite element formulation was developed to make quantitative estimates of polyethylene wear in total hip arthroplasty, incorporating the combined influences of contact stress, sliding distance, and a surface specific wear coefficient. For loading and sliding distance inputs taken directly from human gait data, the computational model showed a strong direct proportionality between femoral head size and volumetric wear rate. Other factors being equal, reducing the thickness of the polyethylene liner led to increases in the computed wear rates, but the effect was far less pronounced than the strong increases in wear rate that accompanied head size increases. Compared with human gait inputs, the load and sliding distance inputs for a 23 degrees biaxial rocking hip simulator led to computed wear rates that were 1.7 times as large, and in which the direction of wear was near the cup apex rather than within the posterosuperolateral quadrant. In general, the finite element model's results emphasize the importance of articulation kinematics, especially sliding distance, in the complex process of polyethylene wear in total hip arthroplasty. | Computer Simulation, Hip Prosthesis, Humans, Polyethylenes, Prostheses and Implants, Stress, Mechanical | null |
8,981,882 | 1997-01-30 | 2018-11-30 | 0009-921X | Clinical orthopaedics and related research | Crevice corrosion of cemented titanium alloy stems in total hip replacements. | Willert H G, Brobäck L G, Buchhorn G H, Jensen P H, Köster G, Lang I, Ochsner P, Schenk R | eng | null | Address | Alloys, Titanium | IM | 8981882 | Twenty-eight cemented Müller straight femoral stems of titanium forged alloys were mainly revised for causing pain in the patient. The pain pattern differed from aseptic loosening and pain recurred only 14.5 months on average after implantation. The character of pain was dull, permanent, and increased at rest. Some patients reported pain relief while walking. Revisions were performed on average 25.5 months after primary implantation. Data from medical records, radiographs, histology of tissues taken at revision surgery, intraoperative pH measurements, examination of retrieved stems and bone cement fragments were gathered. In the radiographs debonding was visible only in 3 cases; a spindle shaped thickening of the femora occurred 9 months on average after recurrence of pain. After a further 11 months (average), scalloping osteolyses appeared. Abraded particles like metallic titanium alloy, titanium corrosion products, polymethylmethacrylate, xray contrast medium, and polyethylene were detected. Metallic particles dominated in the joint capsule whereas more corrosion products impregnated the cement to bone interface. The distal surfaces of the stems were corroded at a higher rate, whereas the proximal regions more often were subject to abrasion. Measurements of the pH of the corroded stems revealed values of high acidity. Recurrence of pain and subperiosteal apposition of bone are due to diffusion of acid; subsequent scalloping osteolyses develop due to particle induced foreign body granulomas. The mechanism of crevice corrosion of cemented titanium based alloys does not seem applicable to cobalt and iron based implant alloys. Titanium alloys can no longer be recommended for cementation, but are as safe as ever for anchorage without cement. | Adult, Aged, Aged, 80 and over, Alloys, Cementation, Corrosion, Female, Femur, Foreign Bodies, Hip Prosthesis, Humans, Male, Middle Aged, Osteoarthritis, Hip, Prosthesis Design, Prosthesis Failure, Titanium | null |
8,981,884 | 1997-01-30 | 2013-11-21 | 0009-921X | Clinical orthopaedics and related research | Fatigue strength of polyethylene after sterilization by gamma irradiation or ethylene oxide. | Ries M D, Weaver K, Rose R M, Gunther J, Sauer W, Beals N | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Polyethylenes, Ethylene Oxide | IM | 8981884 | The oxidation level of ultrahigh molecular weight polyethylene specimens sterilized by gamma irradiation in either air or Ar gas was compared with that of unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. The fatigue strength of ultrahigh molecular weight polyethylene specimens sterilized by gamma irradiation in air was compared with that of unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. At the specimen surface, oxidation was highest for ultrahigh molecular weight polyethylene gamma irradiated in air, lower for ultrahigh molecular weight polyethylene gamma irradiated in Ar gas, and absent in unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene. At a depth of 3.5 mm below the specimen surface, oxidation levels were equivalent for ultrahigh molecular weight polyethylene gamma irradiated in either air or Ar gas whereas unsterilized and ethylene oxide sterilized specimens were again unoxidized. Thus, even in an inert atmosphere, oxidative degradation of gamma irradiated ultrahigh molecular weight polyethylene occurs. The 10 million cycle fatigue strength was similar for unsterilized and ethylene oxide sterilized ultrahigh molecular weight polyethylene whereas the fatigue strength of gamma irradiated in air ultrahigh molecular weight polyethylene was lower. Results of this study show that ethylene oxide gas does not degrade ultrahigh molecular weight polyethylene whereas gamma radiation in air causes changes in the polymer that adversely affect its mechanical properties. Ethylene oxide gas is a viable alternative to gamma radiation in air that avoids oxidation and fatigue strength degradation known to accompany irradiation of ultrahigh molecular weight polyethylene polymer bearing surfaces in total joint implants. | Biophysical Phenomena, Biophysics, Ethylene Oxide, Gamma Rays, Humans, Infant, Newborn, Joint Prosthesis, Materials Testing, Molecular Weight, Oxidation-Reduction, Polyethylenes, Prostheses and Implants, Sterilization | null |
8,981,883 | 1997-01-30 | 2013-11-21 | 0009-921X | Clinical orthopaedics and related research | Overview of polyethylene as a bearing material: comparison of sterilization methods. | Collier J P, Sutula L C, Currier B H, Currier J H, Wooding R E, Williams I R, Farber K B, Mayor M B | eng | null | Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S. | Polyethylenes, Ethylene Oxide | IM | 8981883 | Polyethylene has been used for more than 30 years as an orthopaedic bearing material; however, there has been recent concern regarding the early failure of a small percentage of the polyethylene bearings. The damage seen in some retrieved polyethylene components has been linked to gamma radiation sterilization in air, which was widely used by the industry for years. Gamma radiation in air has been documented to cause an increase in oxidation and degradation of mechanical properties with time. The degradation of polyethylene initiated by gamma sterilization in air has led the orthopaedic industry toward alternative sterilization methods, including gamma radiation in an inert gas or vacuum environment, ethylene oxide gas sterilization, and gas plasma sterilization. For many of these alternative techniques, little clinical performance data exist. This study is a comparative evaluation of sterilization methods using the same analytic techniques that have been used to document the effects of gamma sterilization in air on polyethylene. Fourier transform infrared spectroscopy, electron spin resonance, and uniaxial tensile testing are used to compare, respectively, the oxidation levels, free radical concentration, and mechanical properties of material sterilized by each method. The polyethylene is evaluated before sterilization, poststerilization, and postartificial aging. All examined alternative sterilization methods, when compared with gamma sterilization in air, caused less material degradation during a component's preimplantation shelf life. | Electron Spin Resonance Spectroscopy, Ethylene Oxide, Gamma Rays, Humans, Materials Testing, Oxidation-Reduction, Polyethylenes, Spectroscopy, Fourier Transform Infrared, Sterilization, Tensile Strength, Weight-Bearing | null |
8,981,885 | 1997-01-30 | 2006-11-15 | 0009-921X | Clinical orthopaedics and related research | Engineering issues and wear performance of metal on metal hip implants. | Chan F W, Bobyn J D, Medley J B, Krygier J J, Yue S, Tanzer M | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Metals | IM | 8981885 | A major concern in total hip arthroplasty is the generation of polyethylene wear particles at the articulating surfaces and resulting macrophage mediated periimplant osteolysis. There is renewed interest in metal on metal bearings as a solution to this problem in view of their potential for greatly improved wear performance. Using a commercially available hip simulator, the wear performance of metal on metal femoral head and acetabular cup combinations was evaluated and various parameters affecting metal on metal implant wear were identified. Nine implants custom manufactured from 2 medical grades of CoCrMo alloy (ASTM F1537-95 and F75-92) were tested within bovine serum as the lubricant to 3 million cycles (equivalent to approximately 3 years of service in vivo). The progressive wear of the components was determined by gravimetric methods at approximately every 300,000 cycles. The wear rates were characterized by an initial period of accelerated wear after which a lower steady state wear rate was observed for subsequent cycles. The presence of calcium phosphate films on the component surfaces, the microstructure of the lower carbon, wrought alloy, and increased effective radii (decreased diametral clearances) were identified as factors that may be favorable to improved wear performance. The extent of the effect on wear of each parameter, however, cannot be discerned at this point and necessitates a study in which parametric changes are more tightly controlled. The present study suggests that the use of metal on metal articulating surfaces may mitigate the problem of osteolysis by offering improved wear performance. | Hip Prosthesis, Humans, Lubrication, Materials Testing, Metals, Osteolysis, Prosthesis Design | null |
8,981,886 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Modern metal on metal articulation for total hip replacements. | Dorr L D, Hilton K R, Wan Z, Markovich G D, Bloebaum R | eng | null | Journal Article | Metals | IM | 8981886 | Between 1991 and 1994, 70 patients received total hip replacements with metal on metal articulation. The results of 54 of these patients with 54 hips who have a 2- to 4-year (2.7-year average) followup are reported. Patients were prospectively evaluated using the Harris hip score, a patient self assessment form, and radiographs. Hip aspiration was performed preoperatively and 6 to 24 months postoperatively in 24 hips with metal on metal articulations. Implant retrieval was obtained from 2 patients. Harris hip score averages increased from 49 to 93. No patient had revision surgery for loosening, but 1 had revision surgery for dislocation. Patient self assessment forms showed 51 of 54 patients scored their results as good or excellent. Serial radiographs did not show loosening or osteolysis. Wear could not be measured radiographically. Synovial fluid samples had metal particles of 1 to 10 microm in 10 hips. Twenty patients had bilateral total hip replacements with 1 hip metal on polyethylene articulation, and patients could not determine any difference between the hips. Compared with historic results of previous metal on metal prostheses, the modern metal on metal articulation investigated in this study did not have early acetabular loosening or clinical symptoms of component impaction. Retrieval implants and synovial fluid analysis suggest early wear was minimal. | Adult, Aged, Aged, 80 and over, Female, Foreign Bodies, Hip Prosthesis, Humans, Male, Metals, Middle Aged, Osteolysis, Prospective Studies, Prosthesis Design, Prosthesis Failure, Synovial Fluid | null |
8,981,887 | 1997-01-30 | 2016-11-24 | 0009-921X | Clinical orthopaedics and related research | Primary hybrid total hip arthroplasty: an interim followup. | Callaghan J J, Tooma G S, Olejniczak J P, Goetz D D, Johnston R C | eng | AR-43314 (NIAMS NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, P.H.S. | null | IM | 8981887 | The senior authors' initial experience with primary hybrid hip replacement in patients with osteoarthritis was studied to evaluate the efficacy of the procedure. Hybrid total hip arthroplasty (uncemented Harris-Galante acetabular component and cemented Iowa precoated femoral component) was performed in 131 consecutive, nonselected hips in 118 patients with the diagnosis of primary osteoarthritis. Followup was performed at 8 to 9 years after the procedure. The average age at the time of the procedure was 68 years (range, 45-87 years). There were 50 men (55 hips) and 68 women (76 hips). At final followup 19 patients (22 hips) had died. The femoral component had been revised for aseptic loosening in 8 hips (6.1%). One additional hip showed definite radiographic loosening. Hence, the prevalence of radiographic femoral failure was 6.9% (9 hips). No acetabular component had been revised for aseptic loosening and no acetabular component had migrated. The senior author continues to perform hybrid total hip arthroplasty in all patients with primary osteoarthritis. However, design modifications have been made in the femoral component that is used. | Aged, Aged, 80 and over, Female, Follow-Up Studies, Hip Joint, Hip Prosthesis, Humans, Male, Middle Aged, Osteoarthritis, Hip, Prosthesis Design, Prosthesis Failure, Radiography, Reoperation, Treatment Outcome | null |
8,981,888 | 1997-01-30 | 2016-11-24 | 0009-921X | Clinical orthopaedics and related research | Hybrid primary total hip arthroplasty: a 5- to 9-year followup study. | Lewallen D G, Cabanela M E | eng | null | Journal Article | null | IM | 8981888 | One hundred fifty-two hips were reviewed at a minimum of 5 years after hybrid primary total hip arthroplasty using uncemented porous coated acetabular components and cemented femoral stems to determine the intermediate term durability of this method of fixation. Five hips (3.6%) have been revised: 1 for dislocation (0.7%), 1 for cup loosening (0.7%), and 3 for femoral loosening (2.2%). Clinical results proved to be extremely reliable in this series with 78% of the patients reporting no pain and 19.7% reporting slight or occasional pain. Radiographic evidence of polyethylene wear was evident in more than 1/2 of cups, but significant osteolysis or component loosening was not commonly seen on the cup side. On the femoral side incomplete radiolucencies were present in 31%, and focal osteolysis in 12.2%, nearly always proximally in Zones 1 and 7. These intermediate term results compare favorably on the femoral side and very favorably on the acetabular side to prior reported series. These results support the continued use of this combination of fixation methods for primary arthroplasty, but polyethylene wear and its effects remain a concern regarding the long term performance of these arthroplasties. | Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, Cementation, Follow-Up Studies, Hip Joint, Hip Prosthesis, Humans, Middle Aged, Osteoarthritis, Hip, Osteolysis, Prosthesis Failure, Radiography, Reoperation, Treatment Outcome | null |
8,981,889 | 1997-01-30 | 2016-11-24 | 0009-921X | Clinical orthopaedics and related research | Hybrid total hip arthroplasty: 7- to 10-year results. | Berger R A, Kull L R, Rosenberg A G, Galante J O | eng | null | Journal Article | null | IM | 8981889 | One hundred fifty consecutive hybrid total hip arthroplasties in 139 patients were performed using an uncemented hemispheric porous coated acetabular component (HGP-I) with screws and a femoral component (Precoat) cemented with contemporary cementing technique. The average patient age was 67 years (range, 39-85 years). No patients were lost to followup. Eighty-six patients (91 hips) were alive for an average clinical followup of 103 months (range, 84-127 months); 81 hips had corresponding radiographic analysis. The average Harris hip score preoperatively was 47 points and increased to 88 points at followup. Ninety-five percent of patients had absent or slight pain. Aseptic loosening occurred in 2 femoral components (1.3%), 1 of which was revised for secondary osteolysis. Both hips had suboptimal cement mantles (C-2 or D grades). No femoral osteolysis was seen in stable components. Two acetabular components migrated; 1 secondary to preoperative irradiation osteonecrosis and 1 secondary to a bulk autogenous graft. Acetabular osteolysis without loosening developed in 2 patients (1.3%). Using revision and radiographic loosening as the end point, the probability of both components surviving 10 years was 96.9%, 98.6% for the acetabular component, and 98.4% for the femoral component. These results show that hybrid total hip arthroplasty offers excellent clinical function and exceptional 10-year survivorship. | Adult, Aged, Aged, 80 and over, Cementation, Female, Follow-Up Studies, Hip Joint, Hip Prosthesis, Humans, Male, Middle Aged, Osteolysis, Prosthesis Failure, Radiography, Treatment Outcome | null |
8,981,890 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Hybrid total hip arthroplasty: a 7- to 11-year followup. | Goldberg V M, Ninomiya J, Kelly G, Kraay M | eng | null | Journal Article | null | IM | 8981890 | A consecutive series of 125 hybrid total hip arthroplasties were performed in 120 patients by a single surgeon and were observed for an average of 8.6 years (range, 7-11 years). There were 38 men and 82 women with an average age of 71 years (range, 25-87 years) at the time of surgery. The diagnoses included primary and secondary osteoarthritis in 112 patients, osteonecrosis in 5 patients, and rheumatoid arthritis in 3 patients. All acetabular components were modular and had a Ti shell fixed with an average of 3 screws. The cemented femoral component was either Precoat or Precoat Plus with a 28-mm modular CoCr femoral head. The patients were prospectively observed clinically using the Harris hip score and radiographically using the Hip Society methods. Of the 125 total hip arthroplasties, 123 were followed for the entire observation period. The average preoperative Harris Hip Score was 37 (range, 15-55) and at the latest followup was 92 (range, 65-100). One acetabular component was revised for recurrent dislocations 3 years after surgery, and 1 stem was revised for mechanical loosening and 1 stem was radiographically loose. There was no evidence of cup migration of more than 1 mm. There were no radiolucencies around any of the screws. Two sockets had polyethylene wear of 2 mm. Localized pelvic osteolysis was noted in 5 hips (4%). The results of this study suggested that hybrid total hip replacement is an excellent procedure for reconstruction of the arthritic hip with minimal evidence of polyethylene wear and pelvic osteolysis. | Adult, Aged, Female, Follow-Up Studies, Hip Prosthesis, Humans, Male, Middle Aged, Osteoarthritis, Hip, Prosthesis Failure, Reoperation, Treatment Outcome | null |
8,981,891 | 1997-01-30 | 2005-11-16 | 0009-921X | Clinical orthopaedics and related research | Hybrid total hip replacement: rationale and intermediate clinical results. | Harris W H | eng | null | Journal Article, Review | null | IM | 8981891 | The decade of the 1980s was considered by many hip surgeons to be the decade of cement versus cementless. An alternate approach was introduced in which the acetabular component used was cementless and the femoral component was fixed with cement. This has been called the hybrid total hip replacement. The rationale for this approach is presented and intermediate term results (average, 6.6-year followup) showed that among 65 consecutive standard hybrid total hip replacements in patients who had an average age of 61 years (range, 23-83 years) at the time of surgery, no femoral component was revised for aseptic loosening and no acetabular component was revised for aseptic loosening. Of the 130 components, 3 were removed in 2 patients. One patient had both components removed because of recurrent dislocation and 1 patient had the acetabular component revised because of failure of fixation of the polyethylene liner. The clinical results of this approach were excellent in the intermediate term and may have promise for the long term. | Cementation, Hip Prosthesis, Humans, Osteolysis, Prosthesis Failure, Reoperation, Treatment Outcome | null |
8,981,892 | 1997-01-30 | 2022-04-09 | 0009-921X | Clinical orthopaedics and related research | Management of limb length inequality during total hip replacement. | Jasty M, Webster W, Harris W | eng | null | Journal Article | null | IM | 8981892 | Significant limb length inequality is not an uncommon problem after total hip replacement. Preoperative measurement of limb length inequality, preoperative planning with radiographic templates, and intraoperative correction with measurements of limb lengths before and after the insertion of the trial components using special calipers can reduce the incidence and magnitude of this problem. A review of 85 consecutive patients who had primary total hip arthroplasty in which these techniques were used by a single surgeon, showed that 43 had limb inequality preoperatively ranging from 0.5 to 7.25 cm, but only 14 (16%) had limb length inequality after surgery. Eleven limbs (13%) had been lengthened 0.5 to 1 cm compared with the contralateral limb. Of the 42 patients with equal limb lengths preoperatively, 3 had a lengthened limb postoperatively compared with their contralateral limb. Four patients were using lifts on the same side because the limb was too short, and 2 were using lifts on the other side because the limb was too long. None of the other patients complained about limb length inequality. The techniques described above are helpful in minimizing limb length inequality during total hip replacements. | Hip Prosthesis, Humans, Leg Length Inequality, Osteoarthritis, Hip, Postoperative Complications, Retrospective Studies, Treatment Outcome | null |
8,981,893 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Effects of leg length discrepancies on the forces at the hip joint. | Brand R A, Yack H J | eng | null | Journal Article | null | IM | 8981893 | The authors questioned whether leg length discrepancies of the magnitude ordinarily seen after total hip reconstruction (<2 cm) would substantially alter hip joint forces. Using conventional gait analysis techniques to ascertain intersegmental resultant hip forces and moments, the authors used lifts to simulate leg length discrepancies of 2.3, 3.5, and 6.5 cm in 7 normal subjects. The 2.3-cm lift produced no changes. On the side of the lift (long limb), the 3.5- and 6.5-cm lifts modestly decreased mean peak intersegmental resultant hip forces by 6% and 12%, respectively, but not moments. The changes were, however, variable, with a few subjects showing increases and the rest showing decreases in selected forces or moments. On the side opposite to the lift (short limb), the 3.5- and 6.5-cm lifts increased mean peak intersegmental resultant hip forces by 2% to 12%, but not moments except in 1 case (8%). It is concluded that leg length discrepancies of the sort commonly seen after total hip reconstruction would likely cause no substantial changes in hip forces. | Adult, Gait, Hip Joint, Humans, Leg Length Inequality, Pilot Projects | null |
8,981,894 | 1997-01-30 | 2022-03-21 | 0009-921X | Clinical orthopaedics and related research | Fixation stability of olecranon osteotomies. | Petraco D M, Koval K J, Kummer F J, Zuckerman J D | eng | null | Clinical Trial, Journal Article, Randomized Controlled Trial | null | IM | 8981894 | Eighteen pairs of fresh frozen human upper extremities were selected and each randomized to 2 of 3 olecranon osteotomy and fixation technique groups: (1) transverse osteotomy with 0.062 Kirschner wire and tension band fixation; (2) chevron osteotomy with 6.5-mm cancellous lag screw and tension band fixation; and (3) oblique intraarticular osteotomy with 3.5-mm cortical lag screw and tension band fixation. The arms were mounted with the elbow at 90 degrees flexion and the wrist constrained; a dual linear displacement transducer across the osteotomy was used to determine angulation, translational displacement, and the total gap size. First the brachialis and then the triceps were incrementally loaded to 10 kg using a pulley and cable system to control force direction; the muscle load versus osteotomy displacement was recorded. Cycling with 10 kg was repeated 20 times with the brachialis and triceps alternately loaded and the osteotomy displacement remeasured. There were no statistically significant differences between the amounts of displacement for the 3 osteotomy and fixation techniques caused by either muscle action. The total displacement caused by the brachialis load for all techniques was appreciably greater than that of the triceps load. No significant increase in displacements occurred after 20 load cycles. These results suggest all 3 olecranon osteotomy and fixation techniques offer comparable stability, so the choice of technique should be left to the surgeon's preference. | Biomechanical Phenomena, Cadaver, Humans, Internal Fixators, Osteotomy, Shoulder | null |
8,981,895 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Long term evaluation of repaired distal biceps brachii tendon ruptures. | Davison B L, Engber W D, Tigert L J | eng | null | Journal Article | null | IM | 8981895 | A long term evaluation was performed on 8 patients who had rupture of the distal biceps tendon repaired using the 2-incision technique. The length of followup ranged from 1 to 11 years with an average of 6 years. Goniometric range of motion and isokinetic strength testing were performed on all patients. All patients attained a full arc of elbow flexion and extension. Supination was diminished more than 30 degrees in 3 patients and pronation was diminished more than 30 degrees in 1 patient. Subjectively, 6 of 8 patients were completely satisfied with the function of their involved arm. Strength and work performed during repetitive exercise were regained to the expected normal levels in elbow flexion. Six of 8 patients continued to have less strength in supination of the injured arm than the uninjured arm. All 8 patients performed less total work with repetitive supination of the injured arm than the uninjured arm. | Adult, Arm Injuries, Elbow Joint, Humans, Male, Middle Aged, Range of Motion, Articular, Rupture, Tendon Injuries, Treatment Outcome | null |
8,981,896 | 1997-01-30 | 2011-11-17 | 0009-921X | Clinical orthopaedics and related research | Physical signs in lumbar disc hernia. | Vucetic N, Svensson O | eng | null | Journal Article, Research Support, Non-U.S. Gov't | null | IM | 8981896 | In a prospective study of 163 consecutive patients operated on because they were thought to have lumbar disc hernia, the authors investigated whether physical signs could predict the degree of hernia (complete hernia, incomplete hernia, protruded disc, and normal disc) found at surgery. Stepwise discriminant analysis showed that there were only 2 physical signs of diagnostic value: lumbar range of motion and crossed Lasegue sign. By these signs, 74% of the uncontained hernias and 68% of the contained hernias could be correctly classified. Discrimination also was made between intact annuli (negative exploration and protruded disc) versus ruptured annuli (incomplete hernias and complete hernias). Again, lumbar range of motion and crossed Lasègue sign were the only significant parameters, predicting 71% of the ruptured annuli and 80% of the intact annuli. These 2 physical signs are important because the degree of the hernia is the most important prognostic factor for the outcome of lumbar disc surgery. The degree of the hernia also has an impact on the choice of invasive therapy: open surgery, percutaneous surgery, or enzymatic nucleolysis. Neurologic signs often were absent, showed low correlation to the degree of the hernia, and had a limited value for predicting the level of the hernia. However, they are important for the differential diagnosis in distinguishing between radicular and referred pain. | Adolescent, Adult, Aged, Discriminant Analysis, Female, Humans, Intervertebral Disc Displacement, Lumbar Vertebrae, Male, Middle Aged, Neurologic Examination, Prospective Studies, Range of Motion, Articular, Scoliosis | null |
8,981,897 | 1997-01-30 | 2016-11-24 | 0009-921X | Clinical orthopaedics and related research | Dysplasia epiphysealis hemimelica of the sacroiliac joint: a case report. | Segal L S, Vrahas M S, Schwentker E P | eng | null | Case Reports, Journal Article | null | IM | 8981897 | Dysplasia epiphysealis hemimelica is a rare developmental abnormality involving aberrant epiphyseal cartilage growth. This is the first known case report describing dysplasia epiphysealis hemimelica arising from the sacroiliac joint. The operative technique described through an indirect computed tomography guided approach limited the exposure and potential morbidity involving the sacroiliac joint. | Bone Neoplasms, Bone Screws, Child, Epiphyses, Humans, Ilium, Male, Osteochondroma, Sacroiliac Joint, Tomography, X-Ray Computed | null |
8,981,898 | 1997-01-30 | 2006-11-15 | 0009-921X | Clinical orthopaedics and related research | Trochanteric osteotomy and wire fixation: a comparison of 2 techniques. | Nercessian O A, Newton P M, Joshi R P, Sheikh B, Eftekhar N S | eng | null | Comparative Study, Journal Article | null | IM | 8981898 | Between 1986 and 1989, 190 patients (214 hips) with the diagnosis of osteoarthritis or posttraumatic arthritis underwent cemented Charnley total hip replacement surgeries via the biplane or single plane transtrochanteric approach. The technique of surgery was identical in every aspect except for the technique of the trochanteric osteotomy and reattachment. The results indicate that there was no significant difference in union rates between the 2 groups. Six (6.4%) patients in the biplane group and 7 (6.2%) patients in the single plane group had obvious evidence of nonunion at the 1-year evaluation. This study suggests no significant difference in union rate between a group of patients with biplane osteotomy and a closely paired group of patients with single plane osteotomy. Other equally important factors also may influence the rate of union of the trochanter in total hip arthroplasty. | Adult, Aged, Aged, 80 and over, Arthritis, Bone Wires, Female, Femur, Hip Prosthesis, Humans, Male, Middle Aged, Osteoarthritis, Hip, Osteotomy, Retrospective Studies, Treatment Outcome, Wounds and Injuries | null |
8,981,899 | 1997-01-30 | 2022-04-08 | 0009-921X | Clinical orthopaedics and related research | Primary cementless hip arthroplasty with a titanium plasma sprayed prosthesis. | Hozack W J, Rothman R H, Eng K, Mesa J | eng | null | Journal Article | Titanium | IM | 8981899 | One hundred two patients underwent 105 primary uncemented total hip arthroplasties and were reviewed at a minimum of 5 years after operation (mean, 6.1 years). The components were titanium alloy with a titanium plasma spray coating. The acetabular revision rate was 11.4%. Acetabular cavitary lytic lesions were identified in 25.5% at 5 years. All acetabular revisions were performed for a combination of wear and osteolysis. One femoral revision was performed to facilitate an acetabular revision, but the femoral revision rate for aseptic loosening was 0%. In addition, no femoral components had subsided or were thought to be loose radiographically. Thigh pain was present in 4% at 5 years. Despite the 25.5% incidence of acetabular osteolysis, distal femoral lysis was not seen and only 5% showed focal osteolysis in the trochanteric region proximal to the circumferential porous coating of the femoral component. Component design features were thought to be critical to the excellent performance of the femoral component and to the poor performance of the acetabular component. | Adult, Aged, Arthritis, Rheumatoid, Cementation, Female, Femur Head Necrosis, Hip Joint, Hip Prosthesis, Humans, Male, Middle Aged, Osteoarthritis, Hip, Osteolysis, Prosthesis Design, Prosthesis Failure, Radiography, Retrospective Studies, Titanium | null |
8,981,900 | 1997-01-30 | 2022-03-09 | 0009-921X | Clinical orthopaedics and related research | Dislocations and the femoral head size in primary total hip arthroplasty. | Hedlundh U, Ahnfelt L, Hybbinette C H, Wallinder L, Weckström J, Fredin H | eng | null | Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't | null | IM | 8981900 | The dislocation rate of 3197 Charnley prostheses with 22 mm head in which the surgery was done between 1979 and 1991 in 2 orthopaedic centers was compared with that of 2875 Lubinus prostheses with 32 mm head in which the surgery was done between 1980 to 1991 in 3 other centers. A 1-year followup showed an equal rate of dislocation (2.4%-2.5%) in the 2 groups and included 75% of the 201 dislocated hips. Almost all of the late dislocations occurred with the Charnley prosthesis, resulting in a total dislocation rate of 3.7% compared with 2.9% with the Lubinus prosthesis. Regardless of the type of prosthesis used, there was a higher risk of dislocation in patients with nonhealed hip fractures and in arthroplasties performed by less experienced surgeons. When these 2 variables were removed, the small femoral head was not associated with an increased risk of dislocation. However, there were 77 of 118 (65%) recurrent dislocations in the Charnley group, compared with 37 of 83 (45%) in the Lubinus group, and the relative risk of a dislocated hip arthroplasty becoming recurrent increased by 2.3 times if the small femoral head was used. The number of reoperations also were doubled in this group. Almost 4 times as many dislocations were documented within 2 weeks after surgery after any type of prosthesis inserted through a posterior approach compared with the transtrochanteric approach, but there was no increase in rate of recurrence or revision. | Aged, Female, Femur Head, Hip Prosthesis, Humans, Logistic Models, Male, Middle Aged, Postoperative Complications, Prosthesis Design, Retrospective Studies | null |
8,981,901 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Catastrophic failure of a conforming type of total knee replacement: a case report. | Li E C, Ritter M A, Montgomery T, Furman B D, Li S, Wright T M | eng | null | Case Reports, Journal Article | Polyethylenes | IM | 8981901 | A case study is presented to illustrate the concept of femoral component failure secondary to polyethylene wear in a 67 year old man, 13 years after he had conforming type total knee replacements. This case illustrates the theory that this observed problem may be a leading cause of failure in conforming and nonconforming total knee replacements in the future. | Aged, Calorimetry, Differential Scanning, Crystallization, Humans, Knee Prosthesis, Male, Polyethylenes, Prosthesis Failure | null |
8,981,902 | 1997-01-30 | 2022-12-07 | 0009-921X | Clinical orthopaedics and related research | Fibrosarcoma of the toe: a destructive lesion of the distal phalanx. | Inoue A, Hasegawa T, Ikata T, Hizawa K | eng | null | Case Reports, Journal Article | null | IM | 8981902 | A rare case of well differentiated fibrosarcoma occurring in the left second toe is described in a 12-year-old boy who presented with a destructive lesion that had almost totally destroyed the distal phalanx, except for the epiphysis. Amputated specimens showed microscopic evidence of proliferation of uniform spindle cells arranged in both fascicles and a characteristic herringbone pattern with a small number of mitotic figures. This tumor did not show any specific immunoreactivity except for vimentin and had basic ultrastructural characteristics of fibroblasts and myofibroblasts. The tumor was treated by amputation at the middle phalanx level and had not recurred 3 years later. From the presenting radiographic features, some benign neoplasms and reactive lesions were considered in the differential diagnosis. Only results from the pathologic examination were useful in reaching a correct diagnosis. | Amputation, Surgical, Child, Fibrosarcoma, Foot Diseases, Humans, Magnetic Resonance Imaging, Male, Toes | null |
8,981,903 | 1997-01-30 | 2022-04-08 | 0009-921X | Clinical orthopaedics and related research | Effect of cefazolin and vancomycin on osteoblasts in vitro. | Edin M L, Miclau T, Lester G E, Lindsey R W, Dahners L E | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Anti-Bacterial Agents, Cephalosporins, Vancomycin, Cefazolin | IM | 8981903 | The effect of cefazolin and vancomycin on osteoblast-like cells was studied. Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 microg/ml. For cefazolin, a second interval was performed between 100 and 1000 microg/ml to define toxic levels more accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined. The results of this study show that local levels of vancomycin of 1000 microg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 microg/ml cause cell death. Concentrations of cefazolin of 100 microg/ml and less have little or no effect on osteoblast replication, 200 microg/ml significantly decrease cell replication, and 10,000 microg/ml cause cell death. The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections. | Anti-Bacterial Agents, Cefazolin, Cell Death, Cell Division, Cephalosporins, Dose-Response Relationship, Drug, Humans, Osteoblasts, Tumor Cells, Cultured, Vancomycin | null |
8,981,904 | 1997-01-30 | 2006-11-15 | 0009-921X | Clinical orthopaedics and related research | Basic fibroblast growth factor promotes bone ingrowth in porous hydroxyapatite. | Wang J S, Aspenberg P | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Bone Substitutes, Drug Carriers, Hydroxyapatites, Fibroblast Growth Factor 2 | IM | 8981904 | The effect of basic fibroblast growth factor on tissue ingrowth and differentiation in porous hydroxyapatite of coralline origin was studied in a bone chamber model. The hydroxyapatite with or without basic fibroblast growth factor was placed in 22 mm3 titanium bone conduction chambers implanted bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of the chamber only at 1 end. It then penetrated the porous hydroxyapatite inside the chamber. The distance that the ingrown tissue had reached into the material then was measured on histologic slides. Because fibrous tissue always reached further into the material than did bone, both total tissue ingrowth and bone ingrowth distances were measured. In implants supplemented with 0.04 microg basic fibroblast growth factor in a hyaluronate gel carrier, the bone ingrowth distance was increased by 70% at 6 weeks, as compared with paired controls in the contralateral leg. The total tissue ingrowth distance also was increased by 58%. When the dose of basic fibroblast growth factor was increased to 1.0 microg, still using the hyaluronate carrier, there was no difference in bone ingrowth compared with controls, but this dose still increased the total tissue ingrowth. In hydroxyapatite with 1.5 microg basic fibroblast growth factor without hyaluronate gel at 4 weeks, no increase in bone ingrowth was shown, but total tissue ingrowth was increased. At 6 weeks, bone ingrowth and total tissue ingrowth were increased by 41% and 33%, respectively. With a lower dose of 0.15 microg without carrier, only the total ingrowth distance was increased. The results suggest that basic fibroblast growth factor may promote tissue ingrowth into porous hydroxyapatite and that bone ingrowth may be increased by appropriate doses. The hyaluronate gel carrier reduced the optimal dose. | Animals, Bone Substitutes, Bone and Bones, Dose-Response Relationship, Drug, Drug Carriers, Fibroblast Growth Factor 2, Hydroxyapatites, Male, Osseointegration, Prostheses and Implants, Rats, Rats, Sprague-Dawley | null |
8,981,905 | 1997-01-30 | 2022-03-30 | 0009-921X | Clinical orthopaedics and related research | Congenital metatarsus adductus in early human fetal development: a histologic study. | Morcuende J A, Ponseti I V | eng | null | Journal Article | null | IM | 8981905 | Two feet with congenital metatarsus adductus from fetuses at early development (16 and 19 weeks of gestation) were studied by making serial histologic sections in the horizontal plane of the foot. It was observed that the shape of the medial cuneiform was altered and the first cuneometatarsal joint tilted toward the medial and dorsal directions. The first metatarsal appeared normal, whereas the other metatarsals were deformed in slight adduction at the metaphyseal level. Subluxation at the other cuneometatarsal joints and naviculocuneiform joint was not observed, and the navicular showed no signs of medial or lateral displacement in relation to the head of the talus. No histologic abnormalities of the joint capsules, ligaments, or tendons were observed. On the basis of these pathologic findings, the possibility of a developmental abnormality of the medial cuneiform as a pathogenic factor for the congenital metatarsus adductus deformity should be considered. | Embryonic and Fetal Development, Foot Deformities, Congenital, Humans, Metatarsus | null |
8,981,907 | 1997-01-30 | 2008-11-20 | 0021-9738 | The Journal of clinical investigation | Surprise? Bacteria glycosylate proteins too. | Tuomanen E I | eng | null | Comment, Editorial | Bacterial Proteins, Glycoproteins | IM | 8981907, 10.1172/JCI119087, PMC507726 | null | Arteriosclerosis, Bacterial Proteins, Chlamydia trachomatis, Glycoproteins, Glycosylation | null |
8,981,906 | 1997-01-30 | 2005-03-03 | 0009-921X | Clinical orthopaedics and related research | Incidental cartilage lesion in a 71-year-old man. | Panicek D M, Healey J H, Huvos A G | eng | null | Case Reports, Clinical Conference, Journal Article | null | IM | 8981906 | null | Aged, Bone Neoplasms, Chondrosarcoma, Diagnosis, Differential, Humans, Humerus, Magnetic Resonance Imaging, Male, Tomography, X-Ray Computed | null |
8,981,909 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury. | Barazzone C, Belin D, Piguet P F, Vassalli J D, Sappino A P | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Amyloid beta-Protein Precursor, Carrier Proteins, Plasminogen Activator Inhibitor 1, Protease Nexins, RNA Probes, RNA, Messenger, Receptors, Cell Surface, Fibrin, Tissue Plasminogen Activator, Urokinase-Type Plasminogen Activator, Oxygen | IM | 8981909, 10.1172/JCI119089, PMC507728, 8368324, 8349806, 8118648, 8133887, 7516275, 7921023, 7614818, 7647157, 7544811, 8544402, 8550840, 8611700, 8647939, 8679214, 8825792, 942051, 143664, 7406333, 6374011, 3838543, 2930999, 3953768, 3087993, 3106085, 2496309, 2788176, 2583099, 2314423, 2230126, 1900311, 1902065, 2024710, 1918385, 1928357, 1489146, 1369169, 8491179, 8254028 | Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury. | Amyloid beta-Protein Precursor, Animals, Bronchoalveolar Lavage, Carrier Proteins, Electrophoresis, Fibrin, Fibrinolysis, Histocytochemistry, Humans, Hyaline Membrane Disease, Hyperoxia, Immunohistochemistry, Infant, Newborn, Lung, Lung Injury, Mice, Mice, Inbred Strains, Oxygen, Plasminogen Activator Inhibitor 1, Protease Nexins, RNA Probes, RNA, Messenger, Receptors, Cell Surface, Tissue Plasminogen Activator, Up-Regulation, Urokinase-Type Plasminogen Activator | null |
8,981,908 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Effects of fluid dynamic forces on vascular cell adhesion. | Konstantopoulos K, McIntire L V | eng | null | Journal Article, Review | Cell Adhesion Molecules, Receptors, Cell Surface, L-Selectin | IM | 8981908, 10.1172/JCI119088, PMC507727, 8551244, 8557755, 8752939, 8704169, 8787668, 347575, 3663936, 1967215, 7506064, 7525838, 7527432, 7532110, 7534768, 7535385, 7542276, 7553859, 8565074 | null | Blood Platelets, Cell Adhesion, Cell Adhesion Molecules, Endothelium, Vascular, Hemodynamics, L-Selectin, Neutrophils, Receptors, Cell Surface | null |
8,981,911 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Proliferation induced by keratinocyte growth factor enhances in vivo retroviral-mediated gene transfer to mouse hepatocytes. | Bosch A, McCray P B, Chang S M, Ulich T R, Simonet W S, Jolly D J, Davidson B L | eng | null | Journal Article, Research Support, Non-U.S. Gov't | DNA Primers, Fgf7 protein, mouse, Fibroblast Growth Factor 10, Growth Substances, Fibroblast Growth Factor 7, Fibroblast Growth Factors, beta-Galactosidase | IM | 8981911, 10.1172/JCI119091, PMC507730, 2911748, 3049582, 2236051, 1828343, 8054972, 7962522, 7981306, 7533647, 7719931, 7597103, 8589717, 1650585, 1656443, 1729724, 1722351, 1543539, 1667366, 1667382, 1315677, 1420448, 1431684, 1279268, 1482704, 8506951, 8348154, 8399488, 8211118, 8291602, 8298650, 8108431, 8134398, 8178942, 8183921, 8186145, 8035504, 833203, 2619882 | Retroviral gene transfer to liver without prior injury has not yet been accomplished. We hypothesized that recombinant human keratinocyte growth factor would stimulate proliferation of hepatocytes and allow for efficient in vivo gene transfer with high titer murine Moloney retroviral vectors. This report shows that 48 h after intravenous injection of keratinocyte growth factor, hepatocyte proliferation increased approximately 40-fold compared to non-stimulated livers. When keratinocyte growth factor treatment was followed by intravenous injection of high titer (1 x 10(8) colony forming units/ml) retrovirus coding for the Escherichia Coli beta-galactosidase gene, there was a 600-fold increase in beta-galactosidase expression, with 2% of hepatocytes transduced. Thus, by exploiting the mitogenic properties of keratinocyte growth factor, retrovirus-mediated gene transfer to liver may be accomplished in vivo without the use of partial hepatectomy or pretreatment with other toxins to induce hepatocyte cell division. | Animals, Cell Division, Cells, Cultured, DNA Primers, Escherichia coli, Fibroblast Growth Factor 10, Fibroblast Growth Factor 7, Fibroblast Growth Factors, Gene Expression, Gene Transfer Techniques, Genetic Vectors, Growth Substances, Immunohistochemistry, Lac Operon, Liver, Mice, Polymerase Chain Reaction, Retroviridae, Transduction, Genetic, beta-Galactosidase | null |
8,981,910 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Identification and localization of polycystin, the PKD1 gene product. | Geng L, Segal Y, Peissel B, Deng N, Pei Y, Carone F, Rennke H G, Glücksmann-Kuis A M, Schneider M C, Ericsson M, Reeders S T, Zhou J | eng | DK-40703 (NIDDK NIH HHS, United States); DK-51050 (NIDDK NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Antibodies, Proteins, Recombinant Fusion Proteins, TRPP Cation Channels, polycystic kidney disease 1 protein | IM | 8981910, 10.1172/JCI119090, PMC507729, 713285, 7759112, 6544882, 2873352, 2239929, 1848046, 1614046, 8340115, 8307555, 8176884, 8196285, 7614844, 7633405, 7653531, 7663510, 7581371, 8554072, 8643665, 2995836 | Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys. | Antibodies, Blotting, Western, Cell Membrane, Cloning, Molecular, Embryo, Mammalian, Gene Expression Regulation, Humans, Immunohistochemistry, Kidney Tubules, Liver, Microscopy, Immunoelectron, Pancreas, Polycystic Kidney, Autosomal Dominant, Proteins, Recombinant Fusion Proteins, Skin, TRPP Cation Channels | null |
8,981,912 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice. | Hicke B J, Watson S R, Koenig A, Lynott C K, Bargatze R F, Chang Y F, Ringquist S, Moon-McDermott L, Jennings S, Fitzwater T, Han H L, Varki N, Albinana I, Willis M C, Varki A, Parma D | eng | null | Journal Article | DNA-Binding Proteins, Deoxyribonucleotides, Lewis X Antigen, Ligands, L-Selectin, Calcium | IM | 8981912, 10.1172/JCI119092, PMC507731, 6866086, 7574500, 2200121, 1714447, 1718992, 1345918, 1374413, 1590996, 1376638, 1382077, 7679406, 7679675, 7680663, 8463234, 7685350, 7692600, 7505206, 7507411, 7513613, 8650187, 8181668, 7515220, 7515914, 7519775, 7522621, 7530461, 7538108, 7775406, 7574477, 2179952 | Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics. | Animals, Binding Sites, Calcium, Cell Adhesion, Cloning, Molecular, DNA-Binding Proteins, Deoxyribonucleotides, Flow Cytometry, L-Selectin, Lewis X Antigen, Ligands, Lymphocytes, Mice, Mice, SCID, Protein Binding, Spectrometry, Fluorescence | null |
8,981,913 | 1997-01-30 | 2022-02-24 | 0021-9738 | The Journal of clinical investigation | Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. | Krinzman S J, De Sanctis G T, Cernadas M, Mark D, Wang Y, Listman J, Kobzik L, Donovan C, Nassr K, Katona I, Christiani D C, Perkins D L, Finn P W | eng | AI-31517 (NIAID NIH HHS, United States); ES-106568 (NIEHS NIH HHS, United States); HL-36110 (NHLBI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Bronchoconstrictor Agents, CD28 Antigens, Immunoglobulin G, Methacholine Chloride, Immunoglobulin E, Ovalbumin | IM | 8981913, 10.1172/JCI119093, PMC507732, 7028842, 7584144, 6406089, 8548844, 8557973, 8596936, 8666782, 13818688, 3514163, 2952723, 2447813, 2501446, 2215562, 2252260, 1714933, 1913281, 1313950, 1626792, 1639794, 1323143, 1496399, 1332070, 8025950, 8046343, 7520604, 7822784, 7882171, 7767542, 7543139, 7550342, 7481803, 7063880 | Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma. | Airway Resistance, Animals, Bronchoalveolar Lavage, Bronchoconstrictor Agents, CD28 Antigens, Cell Division, Disease Models, Animal, Flow Cytometry, Histocytochemistry, Hypersensitivity, Immunoglobulin E, Immunoglobulin G, Immunohistochemistry, Inflammation, Lung, Male, Methacholine Chloride, Mice, Mice, Inbred BALB C, Ovalbumin, T-Lymphocytes | null |
8,981,914 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Induction of neonatal tolerance by plasmid DNA vaccination of mice. | Mor G, Yamshchikov G, Sedegah M, Takeno M, Wang R, Houghten R A, Hoffman S, Klinman D M | eng | null | Journal Article, Research Support, U.S. Gov't, Non-P.H.S. | Epitopes, Malaria Vaccines, Peptide Fragments, Protozoan Proteins, circumsporozoite protein, Protozoan, Interleukin-4, Interferon-gamma, DNA | IM | 8981914, 10.1172/JCI119094, PMC507733, 4860248, 1080789, 4589987, 70310, 3260912, 2646215, 1689762, 1690918, 1988490, 1545867, 1323900, 8423340, 8456302, 8483929, 8350420, 8399489, 8054489, 7937907, 7696207, 7636255, 8596932, 8596933, 8596934, 8610135, 8666919, 8705858, 13099277, 13800711, 4114497 | Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic infections are currently under development. Our labs have shown that a plasmid DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits protective immunity against live sporozoite challenge in adult BALB/c mice. We now find that the same DNA vaccine induces tolerance rather than immunity when administered to 2-5 d-old mice. Neonatally tolerized animals were unable to mount antibody, cytokine or cytotoxic responses when rechallenged with DNA vaccine in vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by the vaccine-encoded, endogenously produced antigen. Mice challenged with exogenous circumsporozoite protein produced antibodies against a different set of epitopes, and were not tolerized. These findings demonstrate important differences in the nature and specificity of the immune response elicited by DNA vaccines versus conventional protein immunogens. | Age Factors, Amino Acid Sequence, Animals, Cell Count, Cells, Cultured, Cloning, Molecular, DNA, Epitopes, Female, Immune Tolerance, Immunization, Interferon-gamma, Interleukin-4, Malaria Vaccines, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Peptide Fragments, Plasmids, Plasmodium yoelii, Protozoan Proteins, Spleen, T-Lymphocytes, Cytotoxic | null |
8,981,916 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. | Pitrak D L, Tsai H C, Mullane K M, Sutton S H, Stevens P | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Granulocyte Colony-Stimulating Factor, DNA, Ethidium, Acridine Orange | IM | 8981916, 10.1172/JCI119096, PMC507735, 2842409, 3578359, 3058816, 2462934, 2921324, 2477084, 2556018, 1688645, 2642173, 2170609, 1710634, 1676268, 1950799, 1554824, 1809356, 1318327, 1382715, 1400472, 1280481, 8098552, 8388425, 8388903, 8347560, 8409750, 7507846, 7522641, 4179068, 6245367, 7014501, 3900944, 3485396, 3487354, 3018919, 2946903, 3791696, 3414726 | Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3 h (22.5+/-11.5 vs. 8.9+/-6.9%, P = 0.015), 6 h (38.1+/-14.2 vs. 18.1+/-4.5%, P = 0.003), and 18 h (71.3+/-19.0 vs. 38.8+/-16.7%, P = 0.002). Viabilities were > or = 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8+/-12.4 vs. 83.5+/-10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance. | Acquired Immunodeficiency Syndrome, Acridine Orange, Apoptosis, CD4 Lymphocyte Count, Cell Size, Cell Survival, DNA, Electrophoresis, Agar Gel, Ethidium, Flow Cytometry, Granulocyte Colony-Stimulating Factor, Histocytochemistry, Humans, Microscopy, Electron, Microscopy, Fluorescence, Neutrophils | null |
8,981,915 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. | Böger R H, Skamira C, Bode-Böger S M, Brabant G, von zur Muhlen A, Frolich J C | eng | null | Clinical Trial, Journal Article, Randomized Controlled Trial | Lipids, Nitrates, Recombinant Proteins, Nitric Oxide, Insulin-Like Growth Factor I, Growth Hormone, Cyclic GMP | IM | 8981915, 10.1172/JCI119095, PMC507734, 6804746, 4369960, 6437507, 2896102, 8174149, 8181036, 8181143, 8187304, 7515738, 8039596, 7918301, 7955442, 7955906, 7964125, 7813598, 7843068, 7843769, 7894657, 7898085, 7721271, 7548389, 7564099, 8616947, 8801862, 8801873, 8548425, 8664144, 8713490, 8772586, 8821467, 2973748, 2566779, 2666112, 2687691, 1973979, 2002647, 2022560, 1675786, 1683971, 1762381, 1559299, 1495990, 1522225, 1327594, 1359261, 8093946, 8427864, 8432773, 8212983, 8222083, 8246764, 7504210, 8126152, 7513035, 4342932, 6426576 | We studied the effects of recombinant growth hormone on systemic nitric oxide (NO) formation and hemodynamics in a double-blind, placebo-controlled trial in adult patients with acquired growth hormone deficiency. 30 patients were randomly allocated to either recombinant human growth hormone (r-hGH; 2.0 IU/d) or placebo for 12 mo. In the subsequent 12 mo, the study was continued with both groups of patients receiving r-hGH. In months 1, 3, 6, 9, and 12 of each year, urine and plasma samples were collected for the determination of urinary nitrate and cyclic GMP as indices of systemic NO production, and of plasma IGF-1 levels. Cardiac output was measured in months 1, 12, and 24 by echocardiography. r-hGH induced a fourfold increase in plasma IGF-1 concentrations within the first month of treatment. Urinary nitrate and cyclic GMP excretion rates were low at baseline in growth hormone-deficient patients (nitrate, 96.8+/-7.4 micromol/mmol creatinine; cyclic GMP, 63.6+/-7.1 nmol/mmol creatinine) as compared with healthy controls (nitrate, 167.3+/-7.5 micromol/mmol creatinine; cyclic GMP, 155.2+/-6.9 nmol/mmol creatinine). These indices of NO production were significantly increased by r-hGH, within the first 12 mo in the GH group, and within the second 12 mo in the placebo group. While systolic and diastolic blood pressure were not significantly altered by r-hGH, cardiac output significantly increased by 30-40%, and total peripheral resistance decreased by approximately 30% in both groups when they were assigned to r-hGH treatment. In the second study year, when both groups were given r-hGH, there were no significant differences in plasma IGF-1, urinary nitrate, or cyclic GMP excretion, or hemodynamic parameters between both groups. In conclusion, systemic NO formation is decreased in untreated growth hormone-deficient patients. Treatment with recombinant human growth hormone normalizes urinary nitrate and cyclic GMP excretion, possibly via IGF-1 stimulation of endothelial NO formation, and concomitantly decreases peripheral arterial resistance. Increased NO formation may be one reason for improved cardiovascular performance of patients with acquired hypopituitarism during growth hormone therapy. | Adult, Blood Pressure, Cardiac Output, Cyclic GMP, Female, Growth Hormone, Heart Rate, Humans, Insulin-Like Growth Factor I, Lipids, Male, Nitrates, Nitric Oxide, Recombinant Proteins, Vascular Resistance | null |
8,981,917 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes. | Sakamoto N, Wu C H, Wu G Y | eng | DK-42182 (NIDDK NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | RNA, Catalytic, RNA, Messenger, RNA, Viral, Luciferases | IM | 8981917, 10.1172/JCI119097, PMC507736, 2440339, 2438771, 2468181, 2523562, 2471397, 2569102, 2175903, 1848704, 1658196, 1310759, 1319062, 1472046, 7680362, 8388503, 8210709, 8260875, 8313379, 8135783, 8188703, 8207402, 8030225, 7933114, 7958986, 7983724, 7528330, 7534504, 7743496, 7781762, 7626129, 4705382, 2441261 | To determine the effects of hammerhead ribozymes against hepatitis C virus (HCV) RNA on viral protein translation, a luciferase reporter gene vector, pCMV/T7-NCRCdelta-luc, was constructed containing the 5'-noncoding region (5'-NCR) and part of the core region of HCV. Four ribozymes, Rz1-Rz4, were designed to cleave at nucleotide positions 136-160, 313-337, 496-520, and 373-388, respectively. Each ribozyme cleaved the target RNA at expected positions under cell-free conditions. Rz2 and Rz4 significantly suppressed translation of NCRCdelta-luc RNA by 71 and 49%, respectively. Translation of control luciferase mRNA lacking viral elements was not affected by the ribozymes. Furthermore, when NCRCdelta-luc RNA and ribozymes were cotransfected into cells, Rz2 and Rz4 significantly suppressed expression by 73 and 56%, respectively. In contrast, cleavage-deficient ribozymes with a point mutation in the hammerhead domain had no significant effect. To determine the effects of endogenously produced ribozymes, eukaryotic expression vectors for Rz2 and Rz4 were constructed. Cotransfection of the vectors with CMV/T7-NCRCdelta-luc showed suppression of luciferase activities to 50 and 61%, respectively. Moreover, transfection of pCMV/T7-NCRCdelta-luc into stable Rz2 and Rz4 producer cells also showed substantial inhibition of luciferase activity. Ribozymes directed against the HCV genome can substantially and specifically inhibit viral gene expression under intracellular conditions. | Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Gene Expression Regulation, Viral, Genes, Reporter, Genetic Therapy, Hepacivirus, Humans, Liver, Luciferases, Nucleic Acid Conformation, Point Mutation, Protein Biosynthesis, RNA, Catalytic, RNA, Messenger, RNA, Viral, Transfection | null |
8,981,918 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. | Serradeil-Le Gal C, Lacour C, Valette G, Garcia G, Foulon L, Galindo G, Bankir L, Pouzet B, Guillon G, Barberis C, Chicot D, Jard S, Vilain P, Garcia C, Marty E, Raufaste D, Brossard G, Nisato D, Maffrand J P, Le Fur G | eng | null | Journal Article | Antidiuretic Hormone Receptor Antagonists, Benzazepines, Morpholines, Spiro Compounds, Hydrochlorothiazide, Arginine Vasopressin, mozavaptan, Furosemide, Sodium, satavaptan, Adenylyl Cyclases, Potassium | IM | 8981918, 10.1172/JCI119098, PMC507737, 6872945, 6824079, 6699132, 3031358, 7929452, 7805841, 7811254, 7853167, 7867583, 7698346, 7629492, 7631834, 7592759, 7473590, 8549062, 8719042, 8840278, 2964201, 3392884, 2476622, 2687422, 1850553, 1827414, 1852013, 1914197, 1560825, 1534149, 1534150, 1593923, 1387020, 1356229, 1336316, 8429910, 8381727, 8383753, 8392086, 8393786, 8404628, 8254021, 8106369, 8123034, 4202581, 942051, 6254391, 7120127, 6960761, 6295785, 6693408 | SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases. | Adenylyl Cyclases, Administration, Oral, Adrenal Glands, Animals, Antidiuretic Hormone Receptor Antagonists, Arginine Vasopressin, Autoradiography, Benzazepines, Binding, Competitive, Furosemide, Hydrochlorothiazide, Kidney, Molecular Structure, Morpholines, Potassium, Rats, Sodium, Spiro Compounds, Urine | null |
8,981,919 | 1997-01-30 | 2022-03-17 | 0021-9738 | The Journal of clinical investigation | Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. | Unemori E N, Pickford L B, Salles A L, Piercy C E, Grove B H, Erikson M E, Amento E P | eng | null | Journal Article | Enzyme Precursors, Fibronectins, Procollagen, Recombinant Proteins, Transforming Growth Factor beta, Bleomycin, Relaxin, Collagen, Collagenases, procollagenase | IM | 8981919, 10.1172/JCI119099, PMC507738, 4752894, 1512471, 7416606, 6169174, 2580752, 2993365, 2425458, 3822300, 2446608, 3366935, 2846541, 2475571, 2475572, 1494772, 8370965, 7525651, 7525712, 7653512, 7561646, 8527505, 8550840, 6170243, 2162358, 1695506, 2100192, 1883854, 1892646, 1719696, 1540345, 1312720, 1644255, 89815 | Pulmonary fibrosis is the common end stage of a number of pneumopathies. In this study, we examined the ability of the human cytokine, relaxin, to block extracellular matrix deposition by human lung fibroblasts in vitro, and to inhibit lung fibrosis in a bleomycin-induced murine model. In vitro, relaxin (1-100 ng/ml) inhibited the transforming growth factor-beta-mediated over-expression of interstitial collagen types I and III by human lung fibroblasts by up to 45% in a dose-dependent manner. Relaxin did not affect basal levels of collagen expression in the absence of TGF-beta-induced stimulation. Relaxin also blocked transforming growth factor-beta-induced upregulation of fibronectin by 80% at the highest relaxin dose tested (100 ng/ml). The expression of matrix metalloproteinase-1, or procollagenase, was stimulated in a biphasic, dose-dependent manner by relaxin. In vivo, relaxin, at a steady state circulating concentration of approximately 50 ng/ml, inhibited bleomycin-mediated alveolar thickening compared with the vehicle only control group (P < 0.05). Relaxin also restored bleomycin-induced collagen accumulation, as measured by lung hydroxyproline content, to normal levels (P < 0.05). In summary, relaxin induced a matrix degradative phenotype in human lung fibroblasts in vitro and inhibited bleomycin-induced fibrosis in a murine model in vivo. These data indicate that relaxin may be efficacious in the treatment of pathologies characterized by lung fibrosis. | Animals, Bleomycin, Blotting, Western, Collagen, Collagenases, Disease Models, Animal, Electrophoresis, Polyacrylamide Gel, Enzyme Precursors, Fibronectins, Gene Expression Regulation, Histocytochemistry, Humans, Lung, Lung Injury, Mice, Procollagen, Pulmonary Fibrosis, Recombinant Proteins, Relaxin, Transforming Growth Factor beta | null |
8,981,920 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m. | Khare S D, Hansen J, Luthra H S, David C S | eng | AR-39875 (NIAMS NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | DNA Primers, HLA-B27 Antigen, beta 2-Microglobulin | IM | 8981920, 10.1172/JCI119100, PMC507739, 1404160, 1525820, 8326123, 8103147, 8415702, 8228229, 8108441, 8021497, 8026986, 8035391, 8046330, 7930575, 7930576, 7523514, 7964509, 7710096, 7791441, 7612222, 7561043, 7561688, 8568273, 8835511, 4123836, 629602, 6792316, 6358890, 3760563, 2821399, 2467775, 2187471, 2112266, 1697039, 2257626, 2027387, 1922338, 1718288, 1372262, 1561395, 1350326, 1386874, 1425904 | MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs. These mice developed spontaneous arthritis and nail changes in the rear paws. Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area. Transgenic mice expressing HLA-B27 with mouse beta2m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease. Our data demonstrate specific involvement of HLA-B27 'free' HCs in the disease process. | Animals, Arthritis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, DNA Primers, Disease Models, Animal, Electrophoresis, Polyacrylamide Gel, Flow Cytometry, Gene Expression Regulation, HLA-B27 Antigen, Hoof and Claw, Humans, Inflammation, Leukocytes, Major Histocompatibility Complex, Mice, Mice, Transgenic, Models, Biological, Polymerase Chain Reaction, beta 2-Microglobulin | null |
8,981,921 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Muscarinic receptor modulation of basal and beta-adrenergic stimulated function of the failing human left ventricle. | Newton G E, Parker A B, Landzberg J S, Colucci W S, Parker J D | eng | HL-52320 (NHLBI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Adrenergic beta-Agonists, Receptors, Muscarinic, Dobutamine, Atropine, Acetylcholine | IM | 8981921, 10.1172/JCI119101, PMC507740, 4398792, 3183060, 1245024, 956400, 2916675, 2598435, 2332495, 2337181, 2169357, 2171312, 1901530, 1653121, 1661095, 1551195, 1382385, 8418995, 8391399, 8392548, 8397233, 8376699, 8281643, 7910117, 8023978, 8044956, 7529262, 8595572, 8964109, 7192494, 6299120, 6697466, 3973022, 3560238, 3677352, 2832444, 3290256, 2839545, 4330524 | The objective of this study was to evaluate the effect of muscarinic receptor modulation on basal and beta-adrenergic stimulated left ventricular function in patients with heart failure. 21 heart failure patients and 14 subjects with normal ventricular function were studied. In Protocol 1 intracoronary acetylcholine resulted in a 60+/-8% inhibition of the left ventricular +dP/dt response to intracoronary dobutamine in the normal group, and a similar 70+/-13% inhibition in the heart failure group. Acetylcholine also attenuated the dobutamine-mediated acceleration of isovolumic relaxation (Tau) in both groups. Acetylcholine alone had no effect on Tau in the normal group, while it prolonged Tau in the heart failure group. In Protocol 2 intracoronary atropine resulted in a 35+/-10% augmentation of the inotropic response to dobutamine in the normal group, versus a non-significant 12+/-15% augmentation of the dobutamine response in the heart failure group. In Protocol 3, in 6 heart failure patients, both effects of acetylcholine, the slowing of ventricular relaxation and the inhibition of beta-adrenergic responses, were reversed by the addition of atropine. Therefore, in the failing human left ventricle muscarinic stimulation has an independent negative lusitropic effect and antagonizes the effects of beta-adrenergic stimulation. | Acetylcholine, Adrenergic beta-Agonists, Atropine, Catheterization, Dobutamine, Female, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, Receptors, Muscarinic | null |
8,981,922 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Differences in endogenous peptides presented by HLA-B*2705 and B*2703 allelic variants. Implications for susceptibility to spondylarthropathies. | Boisgérault F, Tieng V, Stolzenberg M C, Dulphy N, Khalil I, Tamouza R, Charron D, Toubert A | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Antibodies, Monoclonal, HLA Antigens, HLA-B27 Antigen, Peptide Fragments | IM | 8981922, 10.1172/JCI119102, PMC507741, 1671992, 2342577, 1922338, 1541831, 1327802, 8436905, 8473755, 8415702, 8225441, 8124703, 8191286, 7523146, 7964509, 7846047, 7863326, 7889404, 7895159, 7722439, 7761976, 7791441, 7612222, 7612235, 7664799, 7547104, 7561688, 7594476, 7489765, 7482491, 7500030, 8598039, 8617941, 8622959, 8676065, 8835507, 4688372, 4123836, 6981636, 2459214, 1709722 | The association between HLA-B27 and spondylarthropathies is currently being reinvestigated in the light of HLA-B27 subtyping. At least 11 different subtypes have been described among which B*2703, B*2706, and B*2709 could be less closely associated with disease at the population level. Differences in the presentation of antigenic peptides by these subtypes could be related to differences in disease susceptibility. We focused our work on the comparison of B*2705 and B*2703 which differ at a single position at residue 59 in pocket A of the peptide binding groove. Endogenous peptides from the human C1R line transfected by B*2705 or B*2703 were acid-eluted and separated by HPLC. Major individual fractions were sequenced by Edman NH2-terminal degradation. Differences observed between B*2705 versus B*2703 individual ligands were confirmed in an in vitro stabilization assay with T2-B*2705 or B*2703 transfected cells in the presence of synthetic peptides. One B*2705 associated peptide is derived from the sequence 169-179 in the second extracellular domain of several HLA class I molecules including HLA-B27. This sequence (RRYLENGKETL) is highly homologous to a previously reported sequence (LRRYLENGK) sharing similarities with proteins from enteric bacteria. We show here that it is naturally presented as a major endogenous peptide by B*2705 and B*2702 disease-associated subtypes and not by B*2703. | Amino Acid Sequence, Antibodies, Monoclonal, Autoimmunity, B-Lymphocytes, Binding Sites, Chromatography, High Pressure Liquid, Fluorescence, HLA Antigens, HLA-B27 Antigen, Humans, Molecular Sequence Data, Peptide Fragments, Protein Binding, Sequence Analysis, Spondylitis, Ankylosing, Transfection | null |
8,981,923 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. Inhibition of both extracellular signal-regulated kinase and c-Jun kinase and upregulation of endothelin B receptors. | Mallat A, Préaux A M, Serradeil-Le Gal C, Raufaste D, Gallois C, Brenner D A, Bradham C, Maclouf J, Iourgenko V, Fouassier L, Dhumeaux D, Mavier P, Lotersztajn S | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Endothelin-1, Prostaglandins, RNA, Messenger, Receptor, Endothelin B, Receptors, Endothelin, Viper Venoms, sarafotoxins s6, Colforsin, carboprostacyclin, Epoprostenol, Cyclic AMP, Protein Kinases, Adenylyl Cyclases, Ibuprofen | IM | 8981923, 10.1172/JCI119103, PMC507742, 3898913, 2440339, 2451132, 2513128, 8016110, 8031866, 7518515, 8073500, 7929360, 7943321, 7982659, 7527398, 7992057, 7855889, 7860764, 7864140, 7878738, 7705772, 7709430, 7777549, 7615814, 7622446, 7625997, 7625999, 7629120, 7629196, 7565768, 7481820, 8524841, 8550585, 8566602, 8788566, 8895023, 2211635, 1845867, 1850245, 2024709, 2050334, 1310601, 1644929, 1528080, 1280120, 1447503, 7678793, 8428911, 8483816, 8387497, 8502273, 8325605, 8360195, 8397401, 8408632, 8415690, 8224842, 942051, 603028, 8294432, 8138949, 8177321 | During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated myofibroblast-like phenotype, proliferate, and synthetize fibrosis components. We have shown that endothelin-1 (ET-1) inhibits the proliferation of activated human HSC via endothelin B (ETB) receptors. We now investigate the transduction pathway involved in the growth inhibitory effect of ET-1 in activated HSC. Endothelin-1 and the ETB receptor agonist, sarafotoxin-S6C, increased synthesis of PGI2 and PGE2, leading to elevation of cAMP. The cyclooxygenase inhibitor ibuprofen and the adenylyl cyclase inhibitor SQ22536 both blunted the growth inhibitory effect of ET-1. Analysis of early steps associated with growth inhibition indicated that: (a) similar to ET-1, forskolin decreased c-jun mRNA induction without affecting c-fos and krox 24 mRNA expression; (b) ET-1, sarafotoxin-S6C, as well as forskolin, reduced activation of both c-Jun kinase and extracellular signal-regulated kinase. Finally, forskolin, PGI2, and PGE2 raised by fivefold the number of ET binding sites after 6 h, and increased the proportion of ETB receptors from 50% in control cells to 80% in treated cells. In conclusion, ET-1 inhibits proliferation of activated HSC via ETB receptors, through a prostaglandin/cAMP pathway that leads to inhibition of both extracellular signal-regulated kinase and c-Jun kinase activities. Upregulation of ETB receptors by prostaglandin/cAMP raises the possibility of a positive feedback loop that would amplify the growth inhibitory response. These results suggest that ET-1 and agents that increase cAMP might be of interest to limit proliferation of activated HSC during chronic liver diseases. | Adenylyl Cyclases, Adipocytes, Binding Sites, Cell Division, Cells, Cultured, Colforsin, Cyclic AMP, Endothelin-1, Epoprostenol, Genes, jun, Humans, Ibuprofen, Liver, Prostaglandins, Protein Kinases, RNA, Messenger, Receptor, Endothelin B, Receptors, Endothelin, Up-Regulation, Viper Venoms | null |
8,981,924 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation. The role of N-methyl-D-aspartate receptors. | Bong G W, Rosengren S, Firestein G S | eng | null | Journal Article | Anti-Inflammatory Agents, Excitatory Amino Acid Antagonists, Phenethylamines, Propionates, Purinergic P1 Receptor Antagonists, Receptors, Glutamate, Receptors, N-Methyl-D-Aspartate, Receptors, Purinergic P1, 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine, Adenosine-5'-(N-ethylcarboxamide), 3,7-dimethyl-1-propargylxanthine, N-Methylaspartate, 6-Cyano-7-nitroquinoxaline-2,3-dione, Dexamethasone, Carrageenan, Peroxidase, Adenosine, Theobromine | IM | 8981924, 10.1172/JCI119104, PMC507743, 8380395, 7522223, 1347551, 1704282, 1361220, 2556044, 7662029, 2323375, 8018857, 8102041, 1472964, 7602536, 14677603, 1963110, 2451003, 2907698, 3010074, 3431917, 7730646, 7680175, 2558391, 1358641, 6142434, 2194223, 1448186, 6100110, 12106256, 6149943, 2906426, 2600819, 7904298, 8380674, 1454389, 7906027, 3016449, 2570339, 2167912 | The effect of spinal adenosine receptor ligation on peripheral leukocyte accumulation was studied in two rat models of inflammation. Neutrophil infiltration into dermal inflammatory sites was signficantly reduced by adenosine A1 receptor agonists injected through intrathecal catheters. These effects were reversed by N-methyl-D-aspartate (NMDA), and were mimicked by (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), a glutamate NMDA receptor antagonist. Peripheral adenosine levels, as measured in air pouch exudates, decreased markedly in inflamed pouches but remained near normal after intrathecal treatment with AP-5. Moreover, the antiinflammatory effects of intrathecal A1 receptor agonists and AP-5 were reversed by an adenosine A2 receptor antagonist administered intraperitoneally. Hence, central NMDA receptor activity can regulate neutrophil accumulation in peripheral inflammatory sites by reducing local levels of adenosine, an antiinflammatory autacoid which inhibits neutrophil function through A2 receptor activation. This represents a previously unknown pathway by which the central nervous system influences inflammatory responses. | 6-Cyano-7-nitroquinoxaline-2,3-dione, Adenosine, Adenosine-5'-(N-ethylcarboxamide), Animals, Anti-Inflammatory Agents, Carrageenan, Catheterization, Central Nervous System, Dexamethasone, Excitatory Amino Acid Antagonists, Inflammation, N-Methylaspartate, Neutrophils, Peroxidase, Phenethylamines, Propionates, Purinergic P1 Receptor Antagonists, Rats, Receptors, Glutamate, Receptors, N-Methyl-D-Aspartate, Receptors, Purinergic P1, Signal Transduction, Skin, Spinal Cord, Theobromine | null |
8,981,925 | 1997-01-30 | 2022-03-30 | 0021-9738 | The Journal of clinical investigation | Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. | Redmon J B, Olson L K, Armstrong M B, Greene M J, Robertson R P | eng | K08-DK02134 (NIDDK NIH HHS, United States); R01-DK38325 (NIDDK NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, P.H.S. | Calmodulin-Binding Proteins, Immunosuppressive Agents, Insulin, RNA, Messenger, Chloramphenicol O-Acetyltransferase, Calcineurin, Phosphoprotein Phosphatases, Tacrolimus | IM | 8981925, 10.1172/JCI119105, PMC507744, 4551514, 7689268, 7052089, 2997172, 3902821, 2442255, 3071361, 2771659, 2808335, 1979979, 1702904, 1702911, 1703352, 1848110, 1710218, 1682135, 1935821, 1721286, 1721372, 1721391, 1721395, 1371575, 1373536, 1809963, 1374016, 7691065, 7693684, 7694879, 7907998, 7520433, 7926339, 7821736, 7539960, 7568086, 7491105, 1377361, 1618871, 1379032, 1322137, 1383067, 7678356, 8093878, 8326016, 8393444, 6270673 | FK506 (tacrolimus) is an immunosuppressive drug which interrupts Ca2+-calmodulin-calcineurin signaling pathways in T lymphocytes, thereby blocking antigen activation of T cell early activation genes. Regulation of insulin gene expression in the beta cell may also involve Ca2+-signaling pathways and FK506 has been associated with insulin-requiring diabetes mellitus during clinical use. The purpose of this study was to characterize the effects of FK506 on human insulin gene transcription, insulin mRNA levels, and insulin secretion using as a model the HIT-T15 beta cell line. FK506 had no acute effect on insulin secretion in the HIT cell, but caused a reversible time- and dose-dependent (10(-9)-10(-6) M) decrease in HIT cell insulin secretion. Decreased insulin secretion in the presence of FK506 was also accompanied by a dose-dependent decrease in HIT cell insulin content, insulin mRNA levels, and expression of a human insulin promoter-chloramphenicol acetyl transferase (CAT) reporter gene. FK506 decreased HIT cell expression of the human insulin promoter-CAT reporter gene by 40% in the presence of both low (0.4 mM) at high (20 mM) glucose concentrations. Western blot analysis of HIT cell proteins gave evidence for the presence of calcineurin in the HIT cell. These findings suggest that FK506 may have direct effects to reversibly inhibit insulin gene transcription, leading to a decline in insulin mRNA levels, insulin synthesis, and ultimately insulin secretion. | Blotting, Northern, Blotting, Western, Calcineurin, Calmodulin-Binding Proteins, Cells, Cultured, Chloramphenicol O-Acetyltransferase, Gene Expression Regulation, Genes, Reporter, Humans, Immunosuppressive Agents, Insulin, Insulin Secretion, Islets of Langerhans, Phosphoprotein Phosphatases, RNA, Messenger, Tacrolimus, Transfection | null |
8,981,926 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation. | Kohsaka H, Carson D A, Rassenti L Z, Ollier W E, Chen P P, Kipps T J, Miyasaka N | eng | AR-25443 (NIAMS NIH HHS, United States); AR-41897 (NIAMS NIH HHS, United States); CA-49870 (NCI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | DNA Probes, Immunoglobulin G, Immunoglobulin M, Immunoglobulin Variable Region | IM | 8981926, 10.1172/JCI119106, PMC507745, 8454861, 8454853, 8099917, 8344352, 8228225, 8233786, 8301127, 7514412, 8200991, 7920635, 7921761, 7759877, 7779254, 7631137, 7631158, 7486533, 7486537, 7486567, 8621797, 3118465, 3358796, 2170112, 2130118, 2130119, 2130120, 1717620, 1940794, 1740665, 1588274, 1404388, 1438230, 1334971, 7678110, 7678601, 8426111, 8431211, 8506275 | The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly understood. Studies on monozygotic twins have helped discern the contributions of genetic versus environmental factors on expressed traits. In the present experiments, we applied a novel anchored PCR-ELISA system to compare the heavy chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes from ten pairs of adult monozygotic twins, including eight pairs who are concordant or discordant for rheumatoid arthritis. The results disclosed that the relative expression of each Ig V(H) gene subgroup is not precisely proportional to its relative genomic size. The monozygotic twins had more similar IgM V(H) gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires. Finally, the V(H) gene repertoire remained stable over time. Collectively, these data reveal that genetic factors predominantly control V(H) gene repertoire formation. | Adult, Aged, Arthritis, Autoimmunity, B-Lymphocytes, DNA Probes, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Immunoglobulin G, Immunoglobulin M, Immunoglobulin Variable Region, Male, Middle Aged, Polymerase Chain Reaction, Sequence Analysis, Transcription, Genetic, Twins, Monozygotic | null |
8,981,927 | 1997-01-30 | 2020-12-22 | 0021-9738 | The Journal of clinical investigation | Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy. | Becker J C, Varki N, Gillies S D, Furukawa K, Reisfeld R A | eng | CA-42508 (NCI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Antibodies, Gangliosides, Interleukin-2, Recombinant Fusion Proteins | IM | 8981927, 10.1172/JCI119107, PMC507746, 6981814, 7777545, 3264384, 2514231, 2196590, 1831615, 1916847, 7612229, 7543536, 7547695, 8642346, 8755561, 1741398, 8439974, 7904900, 8293465, 7937974, 7826525, 7848515, 7897222, 7741031, 3793267 | A major goal of tumor immunotherapy is the induction of tumor-specific T cell responses that are effective in eradicating disseminated tumor, as well as mounting a persistent tumor-protective immunity. We demonstrate here that a genetically engineered fusion protein consisting of human/mouse chimeric anti-ganglioside GD2 antibody and human interleukin-2 is able to induce eradication of established B78-D14 melanoma metastases in immunocompetent syngeneic C57BL/6J mice. This therapeutic effect is mediated by host immune cells, particularly CD8+ T cells and is associated with the induction of a long-lived immunity preventing tumor growth in the majority of animals when challenged up to four months later with B78-D14 cells. This effect was tumor-specific, since no cross-protection against syngeneic, ganglioside GD2+ EL-4 thymoma cells was observed. Furthermore, this tumor-specific protection can be transmitted horizontally to naive, syngeneic SCID mice by passive transfer of CD8+ T lymphocytes derived from immune animals. These results suggest that antibody-targeted delivery of cytokines provides a means to elicit effective immune responses against established tumors in the immunotherapy of neoplastic disease. | Animals, Antibodies, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Gangliosides, Immunity, Immunohistochemistry, Immunotherapy, Interleukin-2, Melanoma, Mice, Mice, SCID, Neoplasm Metastasis, Neoplasms, Experimental, Recombinant Fusion Proteins, Tumor Cells, Cultured | null |
8,981,928 | 1997-01-30 | 2018-12-17 | 0021-9738 | The Journal of clinical investigation | Prolonged exposure of human beta cells to elevated glucose levels results in sustained cellular activation leading to a loss of glucose regulation. | Ling Z, Pipeleers D G | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Insulin, Proteins, Tyrosine, DNA, Glucose | IM | 8981928, 10.1172/JCI119108, PMC507747, 8420817, 1425483, 8307250, 7515006, 8070607, 7821725, 7821741, 7635965, 7593639, 4613593, 6134752, 6203798, 2862019, 3512603, 2422950, 2941762, 2452071, 3287379, 2535989, 2684709, 2559866, 2204282, 2226113, 2254465, 1729264, 1548342, 1532777, 1612191, 1612193, 1400446, 1401063, 8359576 | Human beta cells can be maintained in serum-free culture at 6 mmol/liter glucose, with 80% cell recovery and preserved glucose-inducible functions after 1 wk. Between 0 and 10 mmol/liter, glucose dose-dependently increases the number of beta cells in active protein synthesis (15% at 0 mmol/liter glucose, 60% at 5 mmol/liter, and 82% at 10 mmol/liter), while lacking such an effect in islet non-beta cells (> 75% activated irrespective of glucose concentrations). As in rat beta cells, this intercellular difference in glucose sensitivity determines the dose-response curves during acute glucose stimulation of human beta cells. During 2-h incubations, human beta cells synthesize 7 fmol insulin/10(3) cells at 0 mmol/liter glucose, 20 fmol at 5 mmol/liter, and 31 fmol at 10 mmol/liter. Culture at higher (10 or 20 mmol/liter) glucose does not affect beta cell recovery but decreases by 50-85% the net effect of glucose upon insulin synthesis and release. These reduced responses to glucose are not caused by diminished cellular activities but are the consequence of a shift of beta cells to a state of sustained activation. The presence of more activated cells at low glucose eliminates glucose-dependent cell recruitment as a mechanism for adjusting beta cell responses to acute variations in glucose concentration. It leads to elevated basal biosynthetic (3-fold) and secretory (10-fold) activities, and, hence, to a 4-fold reduction in the beta cell insulin content and the amount of insulin released at maximal glucose stimulation. Prolonged exposure of human beta cells to high glucose can thus lead to a loss of their glucose regulation as a consequence of sustained cellular activation, without signs of glucose-induced toxicity or desensitization. | Analysis of Variance, Cells, Cultured, DNA, Glucose, Humans, Immunohistochemistry, Insulin, Insulin Secretion, Islets of Langerhans, Proteins, Tyrosine | null |
8,981,929 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | An N-linked high-mannose type oligosaccharide, expressed at the major outer membrane protein of Chlamydia trachomatis, mediates attachment and infectivity of the microorganism to HeLa cells. | Kuo C, Takahashi N, Swanson A F, Ozeki Y, Hakomori S | eng | CA-42505 (NCI NIH HHS, United States); EY-00219 (NEI NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, P.H.S. | Bacterial Outer Membrane Proteins, Glycopeptides, Mannosides, Polysaccharides, Bacterial, Porins, omp1 protein, Chlamydia trachomatis, Ovalbumin, Amidohydrolases, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase | IM | 8981929, 10.1172/JCI119109, PMC507748, 4718924, 179950, 62678, 7048000, 7141712, 7152681, 6841322, 4055037, 3407923, 3149518, 2298489, 2373685, 1645328, 1724547, 8335979, 8262634, 7494492 | The structure of the carbohydrate of the 40-kD major outer membrane component of Chlamydia trachomatis and its role in defining infectivity of the organism were investigated. The oligosaccharides were released from the glycoprotein by N-glycanase digestion, coupled to a 2-aminopyridyl residue, and subjected to two-dimensional sugar mapping technique. The major fractions consisted of "high-mannose type" oligosaccharides containing 8-9 mannose residues. Bi- and tri-antennary "complex type" oligosaccharides having terminal galactose were detected as minor components. These oligosaccharides were N-linked and contained no sialic acid. This structural profile is consistent with our previous characterization based on lectin-binding and glycosidase digestion. Functional specificity of identified chlamydial oligosaccharides was analyzed using glycopeptides fractionated from ovalbumin and structurally defined oligosaccharides from other sources. The glycopeptide fraction having high-mannose type oligosaccharide, as compared to those having complex or hybrid-type, showed a stronger inhibitory effect on attachment and infectivity of chlamydial organisms to HeLa cells. Among high-mannose type oligosaccharides, the strongest inhibition was observed with mannose 8 as compared with mannose 6, 7, or 9. These results indicate that a specific high-mannose type oligosaccharide linked to the major outer membrane protein of C. trachomatis mediates attachment and infectivity of the organism to HeLa cells. | Amidohydrolases, Bacterial Adhesion, Bacterial Outer Membrane Proteins, Carbohydrate Conformation, Carbohydrate Sequence, Chlamydia trachomatis, Chromatography, Chromatography, Affinity, Glycopeptides, HeLa Cells, Humans, Mannosides, Molecular Sequence Data, Molecular Structure, Ovalbumin, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Polysaccharides, Bacterial, Porins | null |
8,981,930 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. | Wing M G, Moreau T, Greenwood J, Smith R M, Hale G, Isaacs J, Waldmann H, Lachmann P J, Compston A | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm, CD11 Antigens, Cytokines, Immunoglobulin G, Immunoglobulin M, Interleukin-6, Receptors, IgG, Tumor Necrosis Factor-alpha, Alemtuzumab, Interferon-gamma | IM | 8981930, 10.1172/JCI119110, PMC507749, 2904526, 3262381, 2713487, 2786029, 7879212, 7718516, 8624684, 2500254, 2532305, 2109379, 2358784, 2366834, 2165283, 1700001, 2122929, 2253684, 2148808, 1824981, 1999225, 1856593, 1833456, 1533898, 1534096, 1356177, 8477804, 8099991, 8344347, 8363726, 8200988, 8009586, 7914262, 200563, 222847, 7041358, 6833758, 6427338, 2831292, 3127726, 3260938, 3065089 | The administration of the immunosuppressive humanized monoclonal antibody CAMPATH 1-H, which recognizes CD52 on lymphocytes and monocytes, is associated with a first-dose cytokine-release syndrome involving TNFalpha, IFNgamma, and IL-6 clinically. In vitro models have been used to establish the cellular source and mechanism responsible for cytokine release, demonstrating that cytokine release is isotype dependent, with the rat IgG2b and human IgG1 isotype inducing the highest levels of cytokine release, which was inhibited with antibody to CD16, the low affinity Fc-receptor for IgG (FcgammaR). Cross-linking antibody opsonized CD4 T lymphocytes failed to stimulate TNFalpha release, which together with the observation that TNFalpha release by purified natural killer (NK) cells stimulated by fixed autologous CAMPATH 1-H-opsonized targets was inhibited with anti-CD16, indicates that cytokine release results from ligation of CD16 on the NK cells, rather than Fc-receptor (FcR)-dependent cross-linking of CD52 on the targeted cell. Since the hierarchy of isotypes inducing cytokine release in these cultures matches that seen clinically, we conclude that ligation of CD16 on NK cells is also responsible for cytokine release after injection of CAMPATH 1-H in vivo. | Alemtuzumab, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm, CD11 Antigens, CD4-Positive T-Lymphocytes, Cytokines, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G, Immunoglobulin M, Interferon-gamma, Interleukin-6, Killer Cells, Natural, Leukocytes, Receptors, IgG, Tumor Necrosis Factor-alpha | null |
8,981,932 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Congenital hypothyroid goiter with deficient thyroglobulin. Identification of an endoplasmic reticulum storage disease with induction of molecular chaperones. | Medeiros-Neto G, Kim P S, Yoo S E, Vono J, Targovnik H M, Camargo R, Hossain S A, Arvan P | eng | DK-02113 (NIDDK NIH HHS, United States); DK-40344 (NIDDK NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | HSP70 Heat-Shock Proteins, Membrane Proteins, Molecular Chaperones, glucose-regulated proteins, Thyrotropin, Thyroglobulin | IM | 8981932, 10.1172/JCI119112, PMC507751, 7822419, 8373082, 3624800, 8513503, 7593451, 1714445, 2460739, 2061316, 1400441, 1772654, 8626865, 8325250, 2924725, 8470055, 8366105, 8625414, 8636208, 1470006, 1384031, 3084497, 3472203, 1991788, 14731479, 2882514, 3304148, 1373378, 8214027, 8358794, 1563355, 7790376, 8636228, 8050126, 4036506, 2510935, 7553864, 8179819, 1731198, 1493376, 2614017, 5378589, 1439881, 1157342, 7690463, 7495572, 2190988, 7553863, 2495820, 8106466, 4022126, 1353499, 3745406, 2573430, 3803305, 7513695 | Recent advances in understanding the molecular pathogenesis of congenital hypothyroid goiter in cog/cog mice, have raised important questions concerning the maturation of thyroglobulin (the thyroid prohormone) in certain human kindreds with congenital goiter. We have now examined affected siblings from two unrelated families that synthesize an apparently normally glycosylated, > 300 kD immunoreactive thyroglobulin, yet have a reduced quantity of intraglandular thyroglobulin and that secreted into the circulation. From thyroid tissues of the four patients, light microscopic approaches demonstrated presence of intracellular thyroglobulin despite its absence in thyroid follicle lumina, while electron microscopy indicated abnormal distention of the endoplasmic reticulum (ER). We have confirmed biochemically that most intrathyroidal thyroglobulin fails to reach the (Golgi) compartment where complex carbohydrate modification takes place. Moreover, the disease in the affected patients is associated with massive induction of specific ER molecular chaperones including the hsp90 homolog, GRP94, and the hsp70 homolog, BiP. The data suggest that these patients synthesize a mutant thyroglobulin which is defective for folding/assembly, leading to a markedly reduced ability to export the protein from the ER. Thus, these kindreds suffer from a thyroid ER storage disease, a cell biological defect phenotypically indistinguishable from that found in cog/cog mice. | Animals, Electrophoresis, Polyacrylamide Gel, Endoplasmic Reticulum, Gene Expression Regulation, Glycosylation, Goiter, HSP70 Heat-Shock Proteins, Humans, Hypothyroidism, Immunoassay, Immunoblotting, Immunohistochemistry, Membrane Proteins, Mice, Mice, Inbred Strains, Microscopy, Electron, Molecular Chaperones, Mutation, Thyroglobulin, Thyroid Gland, Thyrotropin | null |
8,981,931 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Repertoire cloning of lupus anti-DNA autoantibodies. | Roben P, Barbas S M, Sandoval L, Lecerf J M, Stollar B D, Solomon A, Silverman G J | eng | null | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Antibodies, Antinuclear, Autoantibodies, DNA-Binding Proteins, Immunoglobulin Fab Fragments, Immunoglobulin Idiotypes, Immunoglobulin Variable Region, Recombinant Proteins, DNA | IM | 8981931, 10.1172/JCI119111, PMC507750, 4168098, 1431128, 303258, 7463697, 3760566, 3553329, 2441044, 3681981, 3396540, 3263866, 2785132, 2497186, 2786910, 2295800, 2107394, 2640629, 1696733, 2212009, 2120334, 2124678, 1826052, 2562243, 1903540, 8459218, 8478936, 7683424, 8496598, 8704103, 8098941, 7686009, 7688492, 8360495, 8228225, 8228264, 7505018, 8301145, 8003058, 8011289, 8040259, 7520375, 7923886, 7527936, 7699336, 7708679, 7759880, 7615813, 7617031, 7639802, 7673735, 7486538, 7484462, 8651982, 1908883, 1893617, 1556192, 1589019, 1617110, 1512540, 1402653, 1420357, 1427920, 4168731 | To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has a targeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with Vlambda light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies. | Amino Acid Sequence, Antibodies, Antinuclear, Autoantibodies, Autoimmunity, B-Lymphocytes, Cloning, Molecular, DNA, DNA-Binding Proteins, Female, Genes, Humans, Immunoglobulin Fab Fragments, Immunoglobulin Idiotypes, Immunoglobulin Variable Region, Lupus Erythematosus, Systemic, Molecular Sequence Data, Nucleic Acid Hybridization, Recombinant Proteins, Serology, Twins, Monozygotic | null |
8,981,933 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction. | Tang W, Geba G P, Zheng T, Ray P, Homer R J, Kuhn C, Flavell R A, Elias J A | eng | AI-34593 (NIAID NIH HHS, United States); HL-36708 (NHLBI NIH HHS, United States); HL-54989 (NHLBI NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, P.H.S. | Interleukin-11, Proteins, SCGB1A1 protein, human, Scgb1a1 protein, mouse, Methacholine Chloride, Uteroglobin | IM | 8981933, 10.1172/JCI119113, PMC507752, 2457008, 7962549, 1542323, 1502977, 7904069, 8551213, 1586873, 8368645, 1734808, 8238534, 1530960, 2361391, 7700748, 13508884, 7735629, 7963541, 8133053, 8244270, 7512836, 7611596, 8567963, 7743829, 8145045, 2223105, 2798426, 835591, 8071352, 7767192, 8314838, 8430954, 8613544, 1530827, 7275793, 8408003, 2145578, 8163655, 7835281, 2202246, 5116699, 8241910, 2595637, 8270885, 4683325, 2301351, 1634515, 8274749, 3411939 | Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders. | Airway Obstruction, Airway Resistance, Animals, Blotting, Northern, Blotting, Southern, Cloning, Molecular, Disease Models, Animal, Gene Expression Regulation, Histocytochemistry, Immunohistochemistry, Interleukin-11, Lung, Methacholine Chloride, Mice, Mice, Transgenic, Microscopy, Electron, Promoter Regions, Genetic, Proteins, Pulmonary Fibrosis, Uteroglobin | null |
8,981,934 | 1997-01-30 | 2022-03-17 | 0021-9738 | The Journal of clinical investigation | Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. | Krown K A, Page M T, Nguyen C, Zechner D, Gutierrez V, Comstock K L, Glembotski C C, Quintana P J, Sabbadini R A | eng | 2SO6 GM-45765 (NIGMS NIH HHS, United States); HL-25073 (NHLBI NIH HHS, United States); HL-46345 (NHLBI NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, P.H.S. | Benzoxazoles, Ceramides, Quinolinium Compounds, Sphingolipids, Tumor Necrosis Factor-alpha, 1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium, Hydrogen Peroxide, Sphingosine | IM | 8981934, 10.1172/JCI119114, PMC507753, 1508712, 6477583, 8521959, 7867010, 7511048, 1349327, 8609343, 7778672, 8335952, 8637856, 8027608, 7664414, 8051401, 8140617, 2195340, 7955152, 7644533, 7877644, 8390056, 8456305, 8512573, 7520371, 7878464, 7644501, 7654318, 3345800, 1376309, 7511719, 2732671, 8294493, 7635940, 7664431, 7779860, 7880735, 8381327, 7724728, 8026044, 14732063, 7757297, 1334847, 2156431, 8265785, 8210329, 1873812, 7929838, 7753834, 7988686, 8048575, 8144969, 8569201, 7727142, 7878463, 7692288, 3462188 | In the present study, it was shown that physiologically relevant levels of the proinflammatory cytokine TNFalpha induced apoptosis in rat cardiomyocytes in vitro, as quantified by single cell microgel electrophoresis of nuclei ("cardiac comets") as well as by morphological and biochemical criteria. It was also shown that TNFalpha stimulated production of the endogenous second messenger, sphingosine, suggesting sphingolipid involvement in TNFalpha-mediated cardiomyocyte apoptosis. Consistent with this hypothesis, sphingosine strongly induced cardiomyocyte apoptosis. The ability of the appropriate stimulus to drive cardiomyocytes into apoptosis indicated that these cells were primed for apoptosis and were susceptible to clinically relevant apoptotic triggers, such as TNFalpha. These findings suggest that the elevated TNFalpha levels seen in a variety of clinical conditions, including sepsis and ischemic myocardial disorders, may contribute to TNFalpha-induced cardiac cell death. Cardiomyocyte apoptosis is also discussed in terms of its potential beneficial role in limiting the area of cardiac cell involvement as a consequence of myocardial infarction, viral infection, and primary cardiac tumors. | Analysis of Variance, Animals, Apoptosis, Benzoxazoles, Cell Nucleus, Cells, Cultured, Ceramides, DNA Damage, Electrophoresis, Agar Gel, Hydrogen Peroxide, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Myocardial Ischemia, Myocardium, Quinolinium Compounds, Rats, Signal Transduction, Sphingolipids, Sphingosine, Tumor Necrosis Factor-alpha | null |
8,981,935 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Functional analysis of the mutations in the human cardiac beta-myosin that are responsible for familial hypertrophic cardiomyopathy. Implication for the clinical outcome. | Sata M, Ikebe M | eng | AR41653 (NIAMS NIH HHS, United States); HL47530 (NHLBI NIH HHS, United States); HL56218 (NHLBI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Actins, DNA Primers, DNA, Complementary, Myosin Light Chains, Recombinant Proteins, Adenosine Triphosphatases, Myosins | IM | 8981935, 10.1172/JCI119115, PMC507754, 4254541, 3547135, 2440339, 2969919, 3417683, 8611530, 8780515, 2466845, 2704627, 2614840, 2362820, 1975517, 2249844, 1552912, 1638703, 8509418, 8514894, 8316857, 8316858, 8370124, 8281650, 8282798, 8294404, 8182105, 7805259, 7731997, 7614728, 7619795, 7648684, 8618824, 8614836, 4737963, 125854, 7142219, 6746912, 3156404, 3158349, 2932443, 3516992, 3803348, 2952363 | More than 30 missense mutations in the beta-cardiac myosin heavy chain gene have been shown to be responsible for familial hypertrophic cardiomyopathy. To clarify the effects of these point mutations on myosin motor function, we expressed wild-type and mutant human beta-cardiac myosin heavy chains in insect cells with human cardiac light chains. The wild-type myosin was well purified with similar enzymatic and motor activities to those of the naturally isolated V3 cardiac myosin. Arg249-->Gln and Arg453-->Cys mutations resulted in decreased actin translocating activity (61 and 23% of the wild-type, respectively) with decreased intrinsic ATPase activity. Arg403-->Gln mutation greatly decreased actin translocating activity (27% of wild type) with a 3.3-fold increased dissociation constant for actin, while intrinsic ATPase activity was unchanged. Val606-->Met mutation only mildly affected the actin translocating activity as well as ATPase activity of myosin. The degree of deterioration by each mutation was closely correlated with the prognosis of the affected kindreds, indicating that myosin dysfunction caused by the point mutations is responsible for the pathogenesis of the disease. Structure/function relationship of myosin is discussed. | Actins, Adenosine Triphosphatases, Baculoviridae, Binding Sites, Cardiomyopathies, Cloning, Molecular, DNA Primers, DNA, Complementary, Electrophoresis, Polyacrylamide Gel, Gene Expression, Genetic Vectors, Humans, Models, Molecular, Myocardium, Myosin Light Chains, Myosins, Point Mutation, Recombinant Proteins, Structure-Activity Relationship | null |
8,981,939 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | 1996 ASHG Presidential Address. Toward the 21st century. | Epstein C J | eng | null | Address | null | IM | 8981939, PMC1712556, 7500515, 8250037, 7477396, 7500511 | null | Forecasting, Genetics, Medical, Humans, Science, Sociology | null |
8,981,937 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Increased expression of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of noninsulin-dependent diabetes mellitus subjects. | Federici M, Zucaro L, Porzio O, Massoud R, Borboni P, Lauro D, Sesti G | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Insulin, Insulin-Like Growth Factor I, Receptor, IGF Type 1, Receptor, Insulin | IM | 8981937, 10.1172/JCI119117, PMC507756, 942051, 8522066, 2859121, 3894418, 3525587, 3021758, 2877871, 2435731, 3033021, 2824266, 3289989, 2645308, 2722845, 2546949, 2480779, 2557329, 1698059, 2211678, 1535055, 1469083, 8452530, 8463272, 8325952, 8227340, 8250456, 7895674, 7720646, 7781591, 7796985, 2983222 | Insulin receptors (IR) and IGF-I receptors (IGF-IR) have been shown to form hybrid receptors in tissues coexpressing both molecules. To date there is no information about the distribution of hybrids in tissues of normal or diabetic subjects. We developed a microwell-based immunoassay to quantitate hybrids in small human tissues samples. Microwells were coated with MA-20 anti-IR antibody or alpha-IGF-IR-PA antibody directed against the IGF-IR alpha-subunit, and incubated with skeletal muscle extracts of patients with noninsulin-dependent diabetes mellitus (NIDDM) and normal controls. Immobilized receptors were incubated with 125I-insulin or 125I-IGF-I in the presence or absence of the two unlabeled ligands. Hybrids were quantified as the fraction of 125I-IGF-I binding immunoadsorbed with MA-20 and expressed as percentage of total IGF-IR (type I+hybrids) immobilized with alpha-IGF-IR-PA. The immunoassay was validated using Western blotting analysis. Relative abundance of hybrids detected in NIDDM patients was higher than in controls. The percentage of hybrids was negatively correlated with IR number and in vivo insulin sensitivity measured by an insulin tolerance test, whereas the percentage was positively correlated with insulinemia. Insulin binding affinity was lower in NIDDM patients than in controls, and was correlated with the percentage of hybrids. Maximal IGF-I binding was significantly higher in muscle from NIDDM patients compared to controls and was positively correlated with the percentage of hybrid receptors whereas IGF-I binding affinity did not differ between the two groups. These results raise the possibility that alterations in expression of hybrid receptors may contribute to decreased insulin sensitivity, and to increased sensitivity to IGF-I. Because IGF-I has been proposed as a hypoglycemic agent in NIDDM, these results are relevant to the development of new approaches to the treatment of insulin resistance of NIDDM. | Binding, Competitive, Blotting, Western, Diabetes Mellitus, Type 2, Humans, Immunoassay, Insulin, Insulin Resistance, Insulin-Like Growth Factor I, Muscle, Skeletal, Protein Conformation, Receptor, IGF Type 1, Receptor, Insulin | null |
8,981,938 | 1997-01-30 | 2022-03-09 | 0021-9738 | The Journal of clinical investigation | Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin. | Benn S I, Whitsitt J S, Broadley K N, Nanney L B, Perkins D, He L, Patel M, Morgan J R, Swain W F, Davidson J M | eng | AG-06528 (NIA NIH HHS, United States); AR-41943 (NIAMS NIH HHS, United States) | Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S. | DNA, Complementary, Transforming Growth Factor beta, alpha 1-Antitrypsin | IM | 8981938, 10.1172/JCI119118, PMC507757, 7798248, 7991604, 7849530, 7708743, 4170654, 5544593, 225559, 6426853, 3877308, 2424019, 2440339, 2442813, 3498859, 2461367, 3237091, 2708352, 2736960, 2137615, 1690918, 2350783, 2395327, 2119055, 2175906, 1654338, 1793583, 1314170, 1606665, 1322148, 8421714, 2562644, 8382374, 8456302, 8494924, 8504067, 8506285, 8342593, 7504271, 8248168, 8248169, 8294500, 8186268, 8186288, 7929819, 7935686, 7937761, 7524619, 7968161, 7981306, 7849094 | Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta1 expression vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct. Transfection of rat skin with constitutively active, mutant porcine TGF-beta1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion. The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta1 expression constructs. | Animals, Biolistics, Blotting, Southern, DNA, Complementary, Diabetes Mellitus, Gene Expression Regulation, Gene Transfer Techniques, Genes, Reporter, HeLa Cells, Humans, Immunohistochemistry, Keratinocytes, Polymerase Chain Reaction, Promoter Regions, Genetic, Rats, Skin, Transforming Growth Factor beta, Wound Healing, alpha 1-Antitrypsin | null |
8,981,936 | 1997-01-30 | 2018-11-13 | 0021-9738 | The Journal of clinical investigation | Local anesthetics as effectors of allosteric gating. Lidocaine effects on inactivation-deficient rat skeletal muscle Na channels. | Balser J R, Nuss H B, Orias D W, Johns D C, Marban E, Tomaselli G F, Lawrence J H | eng | K11 HL02639 (NHLBI NIH HHS, United States); R01 HL50411 (NHLBI NIH HHS, United States); R01 HL52768 (NHLBI NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Anesthetics, Local, Sodium Channels, Lidocaine | IM | 8981936, 10.1172/JCI119116, PMC507755, 5112659, 1375395, 4541340, 1081138, 300786, 334262, 21711, 591912, 271968, 306437, 687766, 728531, 6264305, 233568, 6270629, 6306139, 6207484, 6094703, 3881765, 2446150, 2448487, 3323813, 2458625, 2543931, 1321496, 1668345, 1332059, 1332060, 14343300, 7683789, 8391996, 8396459, 8110459, 8120809, 8161454, 8013069, 8085162, 7807060, 7744852, 7612823, 7641328, 7651517, 7491499, 8569709, 8620612, 8786355, 8786356, 8740377, 8744297, 8833340, 8842001, 8874003, 12991237, 2553292, 2554301, 2559760, 2155011, 2306494, 2173138, 1656476, 1660285, 1316936, 4541078 | Time- and voltage-dependent local anesthetic effects on sodium (Na) currents are generally interpreted using modulated receptor models that require formation of drug-associated nonconducting states with high affinity for the inactivated channel. The availability of inactivation-deficient Na channels has enabled us to test this traditional view of the drug-channel interaction. Rat skeletal muscle Na channels were mutated in the III-IV linker to disable fast inactivation (F1304Q: FQ). Lidocaine accelerated the decay of whole-cell FQ currents in Xenopus oocytes, reestablishing the wild-type phenotype; peak inward current at -20 mV was blocked with an IC50 of 513 microM, while plateau current was blocked with an IC50 of only 74 microM (P < 0.005 vs. peak). In single-channel experiments, mean open time was unaltered and unitary current was only reduced at higher drug concentrations, suggesting that open-channel block does not explain the effect of lidocaine on FQ plateau current. We considered a simple model in which lidocaine reduced the free energy for inactivation, causing altered coupling between activation and inactivation. This model readily simulated macroscopic Na current kinetics over a range of lidocaine concentrations. Traditional modulated receptor models which did not modify coupling between gating processes could not reproduce the effects of lidocaine with rate constants constrained by single-channel data. Our results support a reinterpretation of local anesthetic action whereby lidocaine functions as an allosteric effector to enhance Na channel inactivation. | Allosteric Regulation, Anesthetics, Local, Animals, Cloning, Molecular, Electrophysiology, Lidocaine, Microinjections, Muscle, Skeletal, Mutagenesis, Site-Directed, Oocytes, Patch-Clamp Techniques, Rats, Sodium Channels, Xenopus | null |
8,981,940 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | Variable expressivity of patched mutations in flies and humans. | Bale A E | eng | null | Editorial | Drosophila Proteins, Hedgehog Proteins, Insect Hormones, Membrane Proteins, Patched Receptors, Proteins, Receptors, Cell Surface, Trans-Activators, ptc protein, Drosophila, hh protein, Drosophila | IM | 8981940, PMC1712536, 4960000, 5279523, 332332, 7446524, 2081453, 1910262, 1347096, 1347116, 1348213, 8483937, 8488837, 8042672, 7712637, 7743921, 7577671, 8528259, 8658128, 8681379, 8755929, 8782823 | null | Animals, Basal Cell Nevus Syndrome, Drosophila, Drosophila Proteins, Germ-Line Mutation, Hedgehog Proteins, Humans, Insect Hormones, Membrane Proteins, Patched Receptors, Proteins, Receptors, Cell Surface, Trans-Activators | null |
8,981,941 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | Using genetics to dissect cognition. | Pennington B F | eng | null | Comment, Editorial | null | IM | 8981941, PMC1712539, 4170865, 6828864, 2083497, 7939663, 7751558, 8981944, 14846691 | null | Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 6, Cognition, Dyslexia, Genetic Linkage, Humans, Speech, Visual Perception | null |
8,981,942 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | Empirical evidence that genetic counseling is directive: where do we go from here? | Bernhardt B A | eng | null | Editorial, Comment | null | IM | 8981942, PMC1712550, 8981945, 11654229, 11651283, 11651279, 11657407, 7645300, 1681352, 8500262, 8153035, 7801980, 3348219 | null | Genetic Counseling, Humans, Person-Centered Psychotherapy | null |
8,981,943 | 1997-01-23 | 2020-11-13 | 0002-9297 | American journal of human genetics | Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident. | Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G | eng | null | Journal Article, Research Support, Non-U.S. Gov't | Membrane Proteins, PTCH1 protein, human, Patched Receptors, Patched-1 Receptor, Receptors, Cell Surface | IM | 8981943, PMC1712561, 3547011, 1650914, 1653906, 1594239, 8326488, 8287482, 8306973, 8145818, 8042673, 8049467, 8075640, 8001963, 7493024, 8595881, 8647801, 8658145, 8681379, 8755919, 6209716 | The human homologue of the Drosophila segment polarity gene patched is implicated in the development of nevoid basal cell carcinoma syndrome (NBCCS) and in the genesis of sporadic basal cell carcinomas. In order to examine the phenotypic variability in NBCCS and to highlight functionally important domains of the PTCH protein, we have now screened 71 unrelated NBCCS individuals for mutations in the PTCH exons. We identified 28 mutations that are distributed throughout the entire gene, and most (86%) cause protein truncation. As part of this analysis, we demonstrate that failure of one NBCCS family to show clear linkage to chromosome 9q22.3-31 is most likely due to germinal mosaicism. We have identified three families bearing identical mutations with variable phenotypes, suggesting phenotypic variability in NBCCS is a complex genetic event. No phenotype genotype correlation between the position of truncation mutations and major clinical features was evident. Two missense mutations have been identified, and their location within transmembrane domains supports the notion that PTCH may have a transport function. The preponderance of truncation mutants in the germ line of NBCCS patients suggests that the developmental defects associated with the disorder are most likely due to haploinsufficiency. | Basal Cell Nevus Syndrome, Exons, Female, Genotype, Germ-Line Mutation, Humans, Male, Membrane Proteins, Molecular Sequence Data, Mosaicism, Patched Receptors, Patched-1 Receptor, Pedigree, Phenotype, Polymorphism, Single-Stranded Conformational, Receptors, Cell Surface, Transcription, Genetic | null |
8,981,944 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. | Grigorenko E L, Wood F B, Meyer M S, Hart L A, Speed W C, Shuster A, Pauls D L | eng | HD21887 (NICHD NIH HHS, United States); MH00508 (NIMH NIH HHS, United States); MH39239 (NIMH NIH HHS, United States) | Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S. | Genetic Markers | IM | 8981944, PMC1712535, 6828864, 7425998, 6614001, 6616125, 6587361, 3741977, 3652490, 3657975, 3422543, 3344216, 3359167, 2465364, 2929597, 2703785, 2794763, 2589323, 2376893, 2377495, 2076492, 2017389, 2020562, 1861069, 1880884, 8101276, 8352272, 8314032, 8314036, 8006506, 8016089, 7545953, 4765237, 1158987, 7939663, 7874172, 7762577, 7581452, 7493020, 773516 | Six extended dyslexic families with at least four affected individuals were genotyped with markers in three chromosomal regions: 6p23-p21.3, 15pter-qter, and 16pter-qter. Five theoretically derived phenotypes were used in the linkage analyses: (1) phonological awareness; (2) phonological decoding; (3) rapid automatized naming; (4) single-word reading; and (5) discrepancy between intelligence and reading performance, an empirically derived, commonly used phenotype. Two-point and multipoint allele-sharing analyses of chromosome 6 markers revealed significant evidence (P < 10(-6)) for linkage of the phonological awareness phenotype to five adjacent markers (D6S109, D6S461, D6S299, D6S464, and D6S306). The least compelling results were obtained with single-word reading. In contrast, with chromosome 15 markers, a LOD score of 3.15 was obtained for marker D15S143 at theta = 0.0 with single-word reading. Multipoint analyses with markers adjacent to D15S143 (D15S126, D15S132, D15S214, and D15S128) were positive, but none reached acceptable significance levels. Chromosome 15 analyses with the phonological awareness phenotype were negative. Parametric and nonparametric linkage analyses with chromosome 16 markers were negative. The most intriguing aspect of the current findings is that two very distinct reading-related phenotypes, reflecting different levels in the hierarchy of reading-related skills, each contributing to different processes, appear to be linked to two different chromosomal regions. | Adolescent, Adult, Chromosome Mapping, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 6, Dyslexia, Female, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Humans, Male, Pedigree | null |
8,981,945 | 1997-01-23 | 2020-08-24 | 0002-9297 | American journal of human genetics | Nondirectiveness in genetic counseling: an empirical study. | Michie S, Bron F, Bobrow M, Marteau T M | eng | null | Journal Article, Research Support, Non-U.S. Gov't | null | IM | 8981945, PMC1712566, 7241540, 6743923, 4031436, 3815882, 3348219, 1971875, 2282112, 1877608, 1393159, 7589944, 474624, 455018, 11651283, 11657407, 11653028, 843571, 874463 | Nondirectiveness is considered an essential part of genetic counseling, yet there is no generally accepted definition nor data documenting its impact on counselees. This study is an empirical investigation of directiveness, using ratings from transcripts of consultations and comparing these with counselor-reported and counselee-reported directiveness. Rated directiveness was defined as advice, expressed views about or selective reinforcement of counselees' behavior, thoughts, or emotions (advice, evaluation, and reinforcement). Analysis of 131 transcripts revealed a mean of 5.8 advice statements per consultation, 5.8 evaluative statements, and 1.7 reinforcing statements. When asked to describe their counseling style, none of the 11 counselors rated it as "not at all" directive. Half the counselees who faced a decision felt steered by the counselor. Items of rated directiveness showed satisfactory interrater reliability (kappa = .63). Factor analysis revealed that they formed one factor (eigenvalue 1.72). There were no associations either between counselor-reported, counselee-reported, and rated directiveness or between these measures and counselee anxiety and concern, satisfaction with information, or the meeting of counselees' expectations. Rated directiveness was the only measure to be associated with other process measures of the consultation, being associated with longer consultations, more blocks of speech, more social and emotional issues being raised, and fewer concerns being followed up. Advice was more likely to be given to counselees of lower socioeconomic status and to counselees judged by counselors to be highly concerned. Evaluative statements were more likely to be made by counselors who had received counseling training. These results show that genetic counseling was not characterized--by counselors, counselees, or a standardized rating scale--as uniformly nondirective. | Genetic Counseling, Humans, Person-Centered Psychotherapy | null |
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