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PubMed1989

[A case report of hypoplasia of the root portion and the intermediate portion of the left internal carotid artery associated with an unusual primitive collateral circulation between the left internal carotid artery and the left external carotid artery].

The internal carotid artery is one of the most stable arteries and its absence is very rare. We reported a case of hypoplasia of the root portion and the intermediate portion of the left internal carotid artery associated with an usual primitive collateral circulation between the left internal carotid artery and the left external carotid artery. A 57-year-old male developed right hemiparesis of sudden onset 3 days prior to admission. On admission, right hemiparesis and right minimal facial palsy was observed. The left direct carotid angiogram revealed that the root portion and the intermediate portion of the left internal carotid artery were hypoplastic. There was an unusual primitive collateral circulation between the left internal carotid artery and the left external carotid artery. From an embryological point of view, normally, the internal carotid artery is derived from the third aortic arch and the dorsal aorta when the embryo is attained the 3-mm stage. The root portion of the internal carotid artery is formed from the third aortic arch. The dorsal aorta between the third and the first aortic arch form the intermediate portion. The distal part of the internal carotid artery originates from the dorsal end of the first aortic arch. The common carotid artery begins to form in the 12-mm to 14-mm embryo, following involution of portion of the ventral aortic root between the third and the fourth aortic arch. The external carotid artery arises from the aortic sac and migrate up to the third aortic arch.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Thoracic↗

PubMed1992

Receptor-mediated internalization of bradykinin. DDT1 MF-2 smooth muscle cells process internalized bradykinin via multiple degradative pathways.

This study was undertaken to evaluate the role of internalization in the action of the peptide autacoid bradykinin (BK). At 4 degrees C [3H]BK binds to an apparently single class of B2 kinin receptors on DDT1 MF-2 smooth muscle cells (C. M. Munoz, S. Cotecchia, and L. M. F. Leeb-Lundberg, manuscript submitted). At this temperature the [3H]BK binding was confined exclusively to the cell surface. On the other hand, at 37 degrees C the B2 receptor-specific cell surface [3H]BK binding was rapidly followed by a receptor-specific internalization of [3H]BK (t1/2 approximately 9 min). The internalization reached a steady-state level after 30-40 min that was 80-100% of the level of specifically bound [3H]BK on the cell surface at 4 degrees C, and this level was maintained for greater than or equal to 2 h. Internalized [3H]BK was routed via at least two intracellular degradative pathways which were distinguished primarily based on subcellular localization but also on a small but significant difference in the rate of [3H]BK degradation. One pathway was localized in a plasma membrane-enriched fraction and had a relatively high degradative capacity. Another pathway was localized in a microsomal fraction and had a relatively low degradative capacity. The internalized [3H]BK activity was rapidly released into the media (t1/2 approximately 24 min). Following a single round of internalization, the released activity consisted almost exclusively of small [3H]BK fragments (less than [3H]BK(1-5)). In contrast, at steady-state [3H]BK represented 30-40% of the released activity. While chloroquine (100 microM) did not alter the rate of [3H]BK internalization or release or the intracellular distribution of [3H]BK, this agent significantly decreased the rate of [3H]BK degradation in both pathways. In all, these results show that B2 kinin receptor-mediated internalization of BK is a process integral to the interaction of BK with DDT1 MF-2 smooth muscle cells and may be a mechanism for terminating BK actions by rapidly removing extracellular free and receptor-bound BK and accessing various intracellular BK degradative pathways.

Amino Acid Sequence↗

PubMed1992

Rabies vaccine standardization: International Collaborative Study for the Characterization of the fifth International Standard for Rabies Vaccine.

A collaborative study was carried out to establish a replacement for the International Standard for Rabies Vaccine, the stocks of which are exhausted. Three rabies vaccines for human use derived from different rabies virus strains and prepared on different cell culture substrates were compared with the International Standard for Rabies Vaccine using in vivo and in vitro assay methods in a collaborative study involving 14 participants. The proposed fifth International Standard (PISRAV) which was derived from the same virus strain as the present international standard preparation, the Pitman Moore (PM) strain, was found to be approximately twice as potent relative to the International Standard in immunogenicity assays as in antigenicity assays. On the other hand another vaccine, derived from the LEP strain, was considerably more potent in antigenicity assays than in immunogenicity assays. The glycoprotein of the proposed replacement standard measured in antigenicity assays appeared to be stable at +37 degrees C for 245 days, whereas the immunogenicity of the proposed replacement vaccine was sensitive to this heat treatment and the vaccine lost 66% of its immunogenic potency. The results of this study indicate that the NIH protection test should continue to form the primary basis for potency assay of rabies vaccine as glycoprotein content does not appear to correlate with immunogenic potency for different types of vaccine. The vaccine coded PISRAV has been established as the fifth International Standard for Rabies Vaccine and a potency of 16 International Units of Rabies Vaccine (based on the immunogenicity assays) assigned to the contents of each ampoule. Each ampoule has also been assigned a unitage of 10 IU of PM Rabies Virus Glycoprotein and 135 IU of PM Rabies Virus Ribonucleoprotein.

Animals↗

PubMed1983

Ligand/receptor internalization: a kinetic, flow cytometric analysis of the internalization of N-formyl peptides by human neutrophils.

Fluorescence flow cytometry was used to measure the internalization of the fluorescent ligand N-formyl-nle-leu-phe-nle-tyr-lys-fluorescein by human neutrophils. The internalization process was monitored by the accessibility of the receptor-bound fluorescent ligand to quenching following a change in the pH of the extracellular medium from 7.4 to 3.0. In such a pH change, extracellular ligand or fluorescein are quenched immediately (excitation 488 nm). In contrast, intracellular fluorescein (derived from fluorescein diacetate) or intracellular ligand are quenched with half-times of approximately 20 or approximately 40 sec, respectively, at 37 degrees C. The fraction of internalized ligand is calculated by resolving the fast and slow components of the quenching process. Temporal resolution of the internalization process in this system depends upon two factors. We have previously shown that it is possible to examine essentially continuously the kinetics of ligand binding in the nM concentration range without removing the free ligand (Sklar LA, Finney DA, Cytometry 3:161, 1982). We have now modified a Becton Dickinson FACS IV sample head assembly to permit direct addition of reagents into the cell suspension while on-line. This enables us to change the suspension pH and evaluate internalization with a time resolution of a few seconds. We observe that internalized ligand can be detected within 1 min and that the rate is proportional to the number of receptors occupied. The rate is essentially linear over the first few minutes and approximately 60% of the receptor-bound ligand is internalized after 3 min.

Flow Cytometry↗

PubMed1982

Ligand/receptor internalization: a spectroscopic analysis and a comparison of ligand binding, cellular response, and internalization by human neutrophils.

We have compared the kinetics of the responses of neutrophils to the kinetics of ligand-receptor interaction and internalization, using as a model ligand the fluoresceinated hexapeptide N-CHO-Nle-Leu-Phe-Nle-Tyr-Lys-Fluorescein (Nle, norleucine). Cellular responses, ie, membrane depolarization, enzyme (elastase) secretion, and superoxide anion (O-2) generation, are all initiated within 10 sec of the exposure of cells to stimulus. In the cases of membrane depolarization and secretion (in cytochalasin B-treated cells), full responses are elicited by binding which occurs within 15 sec of peptide addition. Ligand binding and internalization have been analyzed over the same time frame with new spectroscopic techniques. The association of ligand and receptor is monitored using an antibody to fluorescein. The antibody to fluorescein specifically quenches the ligand which is in solution, but receptor-bound ligand is inaccessible to the antibody. The internalization of the receptor-bound ligand is monitored by the accessibility of the fluoresceinated peptide to quenching by an external pH change (7.4 leads to 4.0). Ligand which is either outside or on the cell surface is instantaneously quenched while intracellular peptide (or intracellular fluorescein derived from fluorescein diacetate) is only slowly quenched. No internalization is observed until 1 min after binding begins and internalization proceeds at a rate of up to 5,000 receptors/min/cell following a near optimal stimulatory ligand concentration (approximately 1 nM) while the occupied receptors are being cleared from the surface. A comparison of the kinetics of internalization and the cellular responses suggests that internalization of the ligand is too slow to be involved in the triggering of the cellular responses.

Cell Membrane↗

PubMed1983

Internalization and recycling of plasma membrane glycoconjugates during pinocytosis in the macrophage cell line, P388D1. Kinetic evidence for compartmentation of internalized membranes.

An analysis was made of the pinocytosis-derived internalization and recycling of membrane in the macrophage cell line, P388D1. Plasma membrane glycoconjugates, reversibly labelled with [3H]galactose, were used as a membrane marker. Label internalized with the plasma membrane was no longer accessible to release by externally added beta-galactosidase and could therefore be distinguished quantitatively from label remaining on the cell surface. Direct experimental evidence for membrane recycling was obtained by demonstrating that previously internalized label reappeared at the cell surface. The composition of labelled membrane glycoconjugates, as analysed by SDS-polyacrylamide gel electrophoresis, remained unaltered before and after internalization. The label remained membrane-bound in an unmodified way during the entire period of 8 h investigated, corresponding to about twenty-four cycles of membrane flow. Membrane flow led to a steady-state distribution of label between the plasma membrane and intracellular membranes. The redistribution of label occurred with biphasic kinetics, which could be described as the sum of two exponential functions. This behavior is explained by presenting a model of membrane flow between the plasma membrane and two consecutive intracellular membrane compartments, which we assume to consist of pinosomal membranes and of pinosome-derived membrane of secondary lysosomes. The relative membrane surface areas turn out to be in the ratio of 100:12.5:7.3, respectively. At the observed rate of pinocytosis, the equivalent of the plasma membrane is internalized once every 21 min, in the form of primary pinosomes of the size 0.24 micrometer. The residence time of membranes in the pinosome compartment is about 3 min. The rate at which membranes enter the lysosomal compartment is 31 times lower than the rate of membrane internalization. We conclude that only 3% of the amount of membrane internalized at any one time subsequently enters the secondary lysosome compartment. After a residence time of 49 min this membrane fraction is finally recycled to the cell surface. The results are discussed in terms of mixing and sorting-out of pinosomal and lysosomal membranes.

Animals↗

PubMed1992

Role of acidic subcellular compartments in the degradation of internalized insulin and in the recycling of the internalized insulin receptor in liver cells: in vivo and in vitro studies.

Upon interaction with liver cells, insulin is internalized along with its receptor into nonlysosomal endocytic structures termed endosomes. In this work, the biochemical evidence supporting the role of endosomal acidity in the degradation of internalized insulin and in the recycling of the internalized insulin receptor is described. Treatment of rats by chloroquine and/or quinacrine, two acidotropic drugs, increases by 5-10 fold the amount of endogenous insulin associated with endosomal fractions and, in rats injected by 125I-labeled or native insulin, the endosomal uptake of these ligands at late times after injection. With 125I-insulin, these drugs inhibit the degradation of internalized hormone as judged on physical, biological and immunological criteria. Chloroquine and quinacrine treatment also increases the insulin receptor content of endosomal fractions and, in rats injected by native insulin, the ligand-induced accumulation of receptors in endosomal fractions at late times after injection. Subfractionation of endosomal fractions on Percoll gradients shows that chloroquine treatment shifts the distribution of both insulin and the insulin receptor towards higher densities, the receptor shift being slightly more pronounced in insulin-injected rats. Incubation of isolated endosomes containing internalized insulin at 30-37 degrees C results in a rapid degradation of this ligand, with a maximal at pH 5-6. Addition of ATP, by decreasing the endosomal pH, stimulates insulin degradation above pH 7, whereas addition of chloroquine and quinacrine, by elevating endosomal pH, exerts opposite effects. These data indicate that endosomal acidity is required for optimum degradation of internalized insulin within endosomes and recycling of the internalized receptor.

Animals↗

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↗

PubMed1974