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At least 73 records · Page 4Linked to original sources
PubMed1993

Clathrin-coated pit-mediated receptor internalization. Role of internalization signals and receptor mobility.

Most signals controlling receptor-mediated endocytosis have been identified by alteration of sequences present in receptors normally internalized via clathrin-coated pits. In the present work we have reconsidered the factors that control internalization the other way around: i.e. by introducing potential internalization sequences in complement receptor 1 (CR1) which does not preferentially associate with clathrin-coated pits. The analysis of the internalization efficiency of NPxY related motifs generated by substituting His2010 and/or Glu2015 by either Phe or Tyr indicates that FxNPxY is the stronger promoter of endocytosis and that the signal efficiency depends on the presence of aromatic residues (including a tyrosine) at both ends of the -xNPx- motif. Moreover, CR1-tyr (substitution of Glu2015 for Tyr) internalization was superposable to that of a receptor composed of the extracellular and transmembrane domains of CR1 fused to the intracytoplasmic tail of the low density lipoprotein (LDL) receptor (including the FxNPxY motif) (CR1-LDL). When analyzed by fluorescence recovery after photobleaching, the surface mobility of CR1-LDL was decreased as compared with that of either CR1-tyr or CR1-wt, despite a similar association with clathrin-coated pits. The role of receptor mobility in internalization was confirmed by the observation that CR1-tl, with a deletion of the cytoplasmic tail, was more mobile and more efficiently internalized than CR1-wt.

Amino Acid Sequence↗
PubMed1994

Characteristics of the internalization signal in the Y543 influenza virus hemagglutinin suggest a model for recognition of internalization signals containing tyrosine.

Several proteins, including the hemagglutinin (HA)-Y543 mutant influenza virus hemagglutinin, are internalized by clathrin-coated pits but do not have a sequence that fits a recently proposed consensus for internalization signals containing tyrosine. To determine whether or not the HA-543 signal is a degenerate form of the internalization signal found in proteins such as the transferrin receptor and mannose 6-phosphate/insulin-like growth factor (IGF) II receptor, we have mutated amino acid positions of HA-Y543 shown to be important for internalization of the two receptors. Our results indicate that the HA-Y543 mutant contains a sub-optimum sequence for a tyrosine-based internalization signal similar to those found in the receptors for transferrin, low density lipoprotein, and mannose 6-phosphate/IGFII. However, amino acids with side chains having very different chemical properties functioned well in positions that are important for the internalization signal. The variety of amino acid side chains found in known internalization sequences suggests that atoms of the polypeptide chain backbone may contribute important interactions for binding proteins to clathrin coats, with many of the side chains serving mainly to permit these interactions, a situation similar to that observed for the binding of peptides by histocompatibility proteins.

Amino Acid Sequence↗
PubMed1993

Contractility of the human internal mammary artery at the distal section increases toward the end. Emphasis on not using the end of the internal mammary artery for grafting.

The distal section of the internal mammary artery (3 to 4 cm proximal to the bifurcation) is often used for coronary grafting. This part of the artery is more pharmacologically responsive to vasoconstrictor agents than is its midsection. The present study was designed to test the hypothesis that the reactivity of the distal section of the internal mammary artery is inversely correlated to the diameter of the artery. The distal section of the human internal mammary artery was collected from aorta-coronary bypass grafts and studied in organ baths at a length of 3 mm. At the optimal point of the length-tension curves determined by a computer-iterative fitting technique, the diameter at 100 mm Hg, the maximal contraction forces and effective concentration causing 50% of the maximal response to vasoconstrictor agents U46619, potassium chloride, alpha-adrenoceptor agonists norepinephrine, methoxamine, and phenylephrine were recorded or calculated. The maximal relaxation and 50% response to glyceryl trinitrate in phenylephrine-precontracted internal mammary artery segments were also calculated. The contraction force was standardized by the circumference (grams per millimeter). Regression analysis between contraction force and diameter revealed that the contraction force induced by U46619 and potassium chloride was inversely correlated to diameter (r2 = 0.2, p < 0.05 in U46619-induced contraction and r2 = 0.2, p < 0.01 in potassium chloride-induced contraction). The contraction force induced by norepinephrine also had a trend inversely correlated to diameter (r2 = 0.2, p = 0.07). Glyceryl trinitrate-induced relaxation was not correlated to diameter. This study demonstrated that the contractility of the distal section of the internal mammary artery is inversely correlated to the diameter; that is, the smaller the diameter, the greater the tendency for spasm to develop. This suggests that trimming off the distal end of the internal mammary artery as much as possible may be the best way to prevent graft spasm and that superior results of left internal mammary artery grafted to the left anterior descending artery or the use of a "free graft" may be related to the shorter length (distal end is trimmed off) and less contractility of the graft.

Coronary Artery Bypass↗
PubMed2001

The Second International Standard for somatropin (recombinant DNA-derived human growth hormone): preparation and calibration in an international collaborative study.

A preparation of somatropin (recombinant DNA-derived human growth hormone) was prepared as lyophilised ampoules according to WHO procedures for international biological standards. The candidate preparation (98/574) was evaluated in an international collaborative study (16 laboratories, nine countries), with the following aims: (i) to determine the suitability of the preparation to serve as the International Standard for somatropin by studying its performance in the current range of physico-chemical and biological assay methods employed for somatropin; (ii) to assign a content in terms of the existing (first) International Standard for somatropin, using the currently recognised assay procedure (Size Exclusion High Performance Liquid Chromatography, SE HPLC); (iii) to confirm the specific biological activity of the candidate preparation; (iv) to confirm the stability of the candidate preparation. On the basis of the collaborative study WHO agreed that: the preparation in ampoules coded 98/574 is suitable to serve as the next WHO International Standard for somatropin; the preparation in ampoules coded 98/574 should be established as the second International Standard for somatropin, with a defined ampoule content of 1.95 mg total somatropin plus somatropin-related proteins per ampoule; the specific activity of the preparation should be defined as 3.0 IU/mg somatropin.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Interns' performances with simulated patients at the beginning and the end of the intern year.

OBJECTIVE: To determine whether interns' performances of technical, preventive, and communication aspects of patient care improve during the intern year. DESIGN: A descriptive study. At the beginning and end of the intern year, interns' consultations with three simulated (standardized) patients were videotaped and scored according to explicit criteria set by an expert panel. Problems simulated were urinary tract infection, bronchitis, and tension headache. SETTING: The casualty outpatient department in a general teaching hospital in New South Wales, Australia. PARTICIPANTS: Twenty-eight interns rotated to the casualty department. RESULTS: Little improvement over the intern year in technical competence or preventive care was observed, even though initial levels of compliance with criteria were quite low for some items. Greater improvement was apparent in the area of communication skills. CONCLUSIONS: The results suggest that the internship should be restructured to more adequately teach the skills required for primary care.

Adult↗
PubMedDate not supplied

[Education, investigation and action in international health: Unit of International Studies in Public Health, Mexico].

The internationalization of health causes, conditions, and responses require the consolidation of a vigorous academic and pragmatic tradition of international health. The Unit for International Studies in Public Health constitutes an interinstitutional effort for the training of human resources, research, consulting and practice in health needs and actions that go beyond national borders and that affect two or more countries. The main objectives of the Unit are, on the one hand, to develop a conceptual framework and consolidate international health as a field of public health and, on the other, to foster international technical cooperation among the national institutions that conform the Unit and foreign universities, governments of developing and developed countries, and international organizations. The strategies of the Unit are: interinstitutional and intrainstitutional collaboration, consolidation of multidisciplinary teams, integration of research-teaching-service, and external resources fund-raising. The functioning of the Unit is based on an academic program and on an international technical cooperation program.

Curriculum↗
PubMed1990

The on-call experience of interns in internal medicine. Medical Education Task Force of Henry Ford Hospital.

As part of an effort to examine the structure and content of our residency program in internal medicine, we assessed interns' activities on call to identify problems with workload scheduling, supervision, or learning. Eleven interns were observed continuously during a 34-hour on-call period. Interns averaged 5.6 hours at the bedside, with 57 minutes of that time under direct supervision of a resident or attending physician. Nearly half of new patient examinations continued after midnight despite a special night admission team that evaluated all patients admitted after 11 pm. The interns averaged 21 beeps per 30 hours. They slept an average of 2.5 hours with two interruptions. They read about their patients an average of 4 minutes during the 34-hour period. Most supervision was away from the bedside (82/139 minutes). Bedside supervision occurred predominantly during rounds (45/57 minutes). Attending physicians averaged only 12 minutes of bedside interaction with the intern. Many of these findings were unanticipated. Structural defects in the training program were defined and are being addressed. Other training programs should consider similar analyses before making fundamental changes.

Clinical Competence↗
PubMed1996

Preparation and applications of the International Aquatic Animal Health Code and Diagnostic Manual for Aquatic Animal Diseases of the Office International des Epizooties.

The Office International des Epizooties (OIE) has recently prepared an International Aquatic Animal Health Code, based on the principles set out in the corresponding OIE International Animal Health Code for terrestrial animals. The principal aim of the Code and the companion Diagnostic Manual for Aquatic Animal Diseases is to harmonise health guarantees for international trade in aquatic animals (fish, molluscs, crustaceans) and aquatic animal products, and to guide state Veterinary Services and/or other competent authorities in the preparation of appropriate health certificates. The Aquatic Animal Health Code and Manual provide detailed information on definitions, notifications, ethics in connection with certification, import risk analysis and import/export procedures. By these means, the preparation of international health certificates can be based on a uniform approach to health control in aquatic animal populations, using the standardised methods described in the Diagnostic Manual. In general, health certification under the Aquatic Animal Health Code is required only for diseases notifiable to the OIE. In addition to such notifiable diseases, however, the Code establishes a list of other significant diseases which need consideration. The listed diseases are recognised as serious transmissible diseases of socio-economic and/or public health importance, in relation to which the international trade of aquatic animals and their products poses a significant risk of transfer between countries. The current status of the Code and Manual is described in detail.

Animals↗
PubMed1993

Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study.

Analyses to predict the growth response to recombinant human growth hormone (GH) in prepubertal children during the first year of treatment were performed on data from 472 patients with idiopathic GH deficiency (IGHD), 202 children with Turner's syndrome, 327 children with idiopathic short stature (ISS) and 135 children with intrauterine growth retardation (IUGR). In IGHD, 56% of the variability of the response could be predicted from a model based on six variables. These variables could be ranked in order of importance as follows: target height SDS minus height SDS, chronological age, frequency of GH injections, dose of GH, weight-for-height index, and birth weight SDS. When the model for IGHD was applied to Turner's syndrome, ISS and IUGR, there was a high degree of similarity between the predicted and achieved growth response in ISS and IUGR. However, an uneven distribution within the plot of Studentized residuals in ISS and IUGR suggested heterogeneity within these populations. Prediction of growth in Turner's syndrome was greatly exaggerated by the model for IGHD, suggesting a different pathogenesis as the basis of the growth disorder. Specific prediction models were therefore developed for Turner's syndrome, ISS and IUGR. In all three disorders, the dose of GH was found to be the most important predictor, suggesting that, in contrast to IGHD, first-year growth is governed less by the difference between height and the presumed genetically determined target height. Again, in contrast to IGHD, this suggests that catch-up phenomena are not involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗