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At least 109 records · Page 6Linked to original sources
PubMed1985

The sodium/hydrogen exchange system in cardiac cells: its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH.

This paper describes the properties of the amiloride-sensitive Na+/H+ antiporter in chick cardiac cells, compares them with those known in other cellular systems and analyzes the role of the Na+/H+ exchanger in the regulation of internal Na+ concentrations and internal pH. Among the different properties which have been studied one can mention: (i) The external Na+ concentration [( Na+]o) dependence: the activity increases when [Na+]o increases (KNa+ = 20 mM); (ii) The external pH (pHo) dependence: the activity of the exchanger increases when pHo increases (pHmo = 7.05 and Hill coefficient = 1); (iii) The internal pH (pHi) dependence; the activity of the exchanger increases in a cooperative way when internal pH (pHi) decreases (pHmi = 7.35 and Hill coefficient = 3); (iv) There are derivatives of amiloride which are 200 times more potent than amiloride itself (Kethylisopropylamiloride = 30 nM) and which are selective on the Na+/H+ exchange system v. other Na+ transporting system including the Na+/Ca2+ exchange system. Under physiological conditions, the Na+/H+ exchange system contributes little to the regulation of the internal pH of chick cardiac cells. The antiporter then serves as an uptake system for Na+ using the H+ gradient created by other pHi regulatory mechanisms. Treatment of cardiac cells with ouabain inhibits Na+ efflux and produced an increase in intracellular Na+ activity. Ethylisopropylamiloride was used to show that the Na+/H+ exchange system is the main pathway for Na+ entry and accumulation in digitalis action. As expected amiloride derivatives which block Na+ entry via the Na+/H+ antiporter were found to antagonize ouabain action on cardiac cells. When the internal pH of cardiac cells is lowered, the Na+/H+ exchanger becomes the major pHi regulating system. It is the essential system by which cardiac cells recover from cellular acidosis. The situation is due both to an increased activity of the exchanger at acidic pHi and to a decreased activity of other pHi regulatory systems. We propose in this paper that the Na+/H+ exchange system plays a key role in Na+ accumulation followed by Ca2+ accumulation which is observed when ischemic hearts are reperfused.

Acidosis↗
PubMed2000

The brain commission of the international association of academies: the first international society of neurosciences.

International associations of scientists, set up to organize cooperative scientific investigations in an international scope and to lay down global binding standards of research, are of great and still growing importance for the advancement of science. This was also recognized at the beginning of the 20th century by the community of researchers in basic and clinical neurological sciences, who created their first international organization following the trend initiated by scholars in astronomy and geophysics. Thus, the so-called "Brain Commission" of the International Association of Academies was founded in 1903 and was active until the outbreak of the First World War. The Brain Commission had no successor for nearly half a century, until the "International Brain Research Organization" (IBRO) was founded in 1961. Although the Brain Commission could exert an impact on neurosciences only for one decade, this international scientific association inspired and promoted the foundation of a series of Brain Research Institutes, which in part still exist in Europe, and long-lasting innovations in the neurosciences.

Congresses as Topic↗
PubMed2001

Internal anal sphincter achalasia: outcome after internal sphincter myectomy.

BACKGROUND: Internal anal sphincter achalasia (IASA), also referred to as ultrashort segment Hirschsprung's disease (HD), is a clinical condition with presentation similar to HD, but with the presence of ganglion cells on rectal biopsy. The diagnosis of IASA is made on anorectal manometry, which shows the absence of rectosphincteric reflex on rectal balloon inflation. Altered intramuscular innervation has been reported in IASA. The purpose of this study was to review the outcome after internal sphincter myectomy in patients with IASA. METHODS: Fifteen consecutive patients (age range, 2 years to 12 years) with IASA underwent posterior internal sphincter myectomy. All patients presented with severe constipation with or without soiling. The diagnosis of IASA was made by anorectal manometry. HD was excluded in these cases by the presence of ganglion cells and normal acetylcholinesterase activity on suction rectal biopsies. Internal sphincter (IS) specimens were examined using immunohistochemistry for the general neuronal marker PGP 9.5 and synapsin 1 (a presynaptic marker) and using general histochemistry for NADPH-diaphorase. All patients underwent follow-up for periods from 2 years to 6 years. RESULTS: PGP 9.5, synapsin 1 and NADPH-diaphorase positive nerve fibers were either absent or markedly reduced in IASA specimens compared with controls, confirming previous reports of defective intramuscular innervation in IASA. At the time of follow-up, 7 patients have regular bowel motions and are not on any laxatives. Six patients have normal bowel habits but are on small doses of laxatives. One patient is able to stay clean with regular enema regimen. One patient required resection of dilated and redundant sigmoid colon and now has normal bowel habits with laxatives. CONCLUSION: The majority of patients with internal anal sphincter achalasia can be treated successfully by internal sphincter myectomy.

Anal Canal↗
PubMed1999

Internalization of the TXA2 receptor alpha and beta isoforms. Role of the differentially spliced cooh terminus in agonist-promoted receptor internalization.

Thromboxane A2 (TXA2) potently stimulates platelet aggregation and smooth muscle constriction and is thought to play a role in myocardial infarction, atherosclerosis, and bronchial asthma. The TXA2 receptor (TXA2R) is a member of the G protein-coupled receptor family and is found as two alternatively spliced isoforms, alpha (343 residues) and beta (407 residues), which share the first 328 residues. In the present report, we demonstrate by enzyme-linked immunosorbent assay and immunofluorescence microscopy that the TXA2Rbeta, but not the TXA2Ralpha, undergoes agonist-induced internalization when expressed in HEK293 cells as well as several other cell types. Various dominant negative mutants were used to demonstrate that the internalization of the TXA2Rbeta is dynamin-, GRK-, and arrestin-dependent in HEK293 cells, suggesting the involvement of receptor phosphorylation and clathrin-coated pits in this process. Interestingly, the agonist-stimulated internalization of both the alpha and beta isoforms, but not of a mutant truncated after residue 328, can be promoted by overexpression of arrestin-3, identifying the C-tails of both receptors as necessary in arrestin-3 interaction. Simultaneous mutation of two dileucine motifs in the C-tail of TXA2Rbeta did not affect agonist-promoted internalization. Analysis of various C-tail deletion mutants revealed that a region between residues 355 and 366 of the TXA2Rbeta is essential for agonist-promoted internalization. These data demonstrate that alternative splicing of the TXA2R plays a critical role in regulating arrestin binding and subsequent receptor internalization.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Inhibition of AT1 receptor internalization by concanavalin A blocks angiotensin II-induced ERK activation in vascular smooth muscle cells. Involvement of epidermal growth factor receptor proteolysis but not AT1 receptor internalization.

Recent studies of beta(2)-adrenergic receptor suggest that agonist-promoted receptor internalization may play an important role in extracellular signal-regulated kinase (ERK) activation by G protein-coupled receptors. In the present study, we explored the effects of angiotensin II (Ang II) type-1 receptor (AT(1)) internalization on Ang II-induced activation of ERK using the receptor internalization blocker concanavalin A (ConA) and the carboxyl terminus-truncated receptor mutants with impaired internalization. ConA inhibited AT(1) receptor internalization without affecting ligand binding to the receptor, Ang II-induced generation of second messengers, and activation of tyrosine kinases Src and Pyk2 in vascular smooth muscle cells (VSMC). ConA blocked ERK activation evoked by Ang II and the calcium ionophore A23187. Impairment of AT(1) receptor internalization by truncating the receptor carboxyl terminus did not affect Ang II-induced ERK activation. ConA induced proteolytic cleavage of the epidermal growth factor (EGF) receptor at carboxyl terminus and abolished Ang II-induced transactivation of the EGF receptor, which is critical for ERK activation by Ang II in VSMC. ConA also induced proteolysis of erbB-2 but not platelet-derived growth factor receptor. Thus, ConA blocks Ang II-induced ERK activation in VSMC through a distinct mechanism, the ConA-mediated proteolysis of the EGF receptor.

Angiotensin II↗
PubMed1979

Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion.

1. The effects of alterations of the intracellular ionic composition on the properties of anomalous (or inward) rectification of the egg membrane of the starfish, Mediaster aequalis, were studied by using an intracellular perfusion technique. The following results were obtained, analysing the membrane current with the voltage-clamp technique. 2. The inward rectification of the K conductance depends only on the membrane potential, V, when the K equilibrium potential, VK, is altered by changing the internal K+ concentration at a fixed external K+ concentration, while it depends on V-VK when VK is altered by changing the external K+ at a fixed internal K+ concentration. 3. From the above the conclusion is reached that the gating of the K channel of the inward rectification depends on V and external but not internal K+ concentration. 4. The conductance of the K channel at a given voltage is roughly proportional to the square root of [K+]i when the latter is altered at a fixed external K+ concentration. 5. Since the conductance is proportional to the square root of [K+]o when this is altered at a fixed internal K+ concentration, the final conclusion is that this conductance is proportional to the geometric mean of the external and internal K+ concentrations. 6. Intracellular Na+ ions are necessary for the activation of inward rectification; the K conductance increases sharply with internal Na+ concentration, reaching saturation at 200 mM. 7. A similar potentiating effect is found for Li+, although it is weaker. Rb+, Cs+ and organic cations such as arginine+ do not have this effect.

Animals↗
PubMed1983

International collaborative study for the establishment of the second International Reference Preparation of plasmin.

An international collaborative study involving seven laboratories was undertaken to assess the suitability of a freeze-dried preparation of human plasmin to replace the current International Reference Preparation (IRP) for plasmin. Chromogenic and fibrinolytic assays were used by all participating laboratories to assess the potencies of the Proposed International Reference Preparation (PIRP) and two other freeze-dried plasmins, one of human and one of porcine origin. The data suggest that the PIRP is a more suitable standard for plasmin than the IRP in that the former binds to fibrin whereas only 50% of the latter binds. The PIRP compared well to other plasmin preparations and the potency assays were independent of the assay procedure and substrate used. Degradation studies indicated that the PIRP was far more stable than the glycerol solution of the IRP, surviving for 12 months at 37 degrees C with no significant loss in either amidolytic or fibrinolytic activity. The International Committee for Thrombosis and Haemostasis (Bergamo, 1982) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the second International Reference Preparation for Plasmin with a defined potency of 10 International Units of Plasmin per ampoule.

Fibrinolysin↗
PubMed1993

[Anatomical measurements of the internal anal sphincter--the relative site of the dentate line in the internal anal sphincter].

Not only the length and the width of the internal anal sphincter but also the relative site of the dentate line in the internal anal sphincter were investigated in 62 resected specimens obtained by abdominoperineal resection of the rectum for malignancy. Mean length and width of the internal sphincter were 25.8 +/- 4.1mm (mean +/- standard deviation) and 4.0 +/- 1.1mm, respectively. The length of the internal sphincter from its distal end to the level of the dentate line was 11.3 +/- 3.1mm, which corresponded to 44% of the total length of the internal sphincter. The individual difference in the site of the dentate line in the internal sphincter was objectively demonstrated. It seems to be therefore important to modulate the extent of sphincterotomy in order to minimize postoperative anal dysfunction on the surgery for fissure or fistula-in-ano, in which sphincterotomy is widely practiced up to the level of the dentate line.

Adult↗
PubMed1990

International Standards for salmon calcitonin, eel calcitonin, and the Asu1-7 analogue of eel calcitonin: calibration by international collaborative study.

Regulatory specifications in most countries require that the potency of salmon calcitonin (sCT) clinical products be expressed in International Units (IU) defined by the World Health Organization (WHO) International Standard. The first ampouled standard was prepared in 1972 and has been distributed world-wide since then. A batch of ampoules to serve as the replacement standard is now required. Other piscine calcitonins, eel calcitonin (eCT) and an amino-suberic acid analogue of eCT (Asu1-7 eCT) are now clinical products in some countries and international standards are required for these peptides which are similar to, but not identical with, sCT. This paper describes the preparation of three new ampouled standards and their biological calibration by international collaborative study comprising 17 participants from 10 countries. Following the recommendations in the final report of the collaborative study, the 2nd International Standard (IS) for sCT, the 1st IS for eCT and the 1st IS for Asu1-7 eCT were recently established by WHO, each with an assigned potency in IU, and are now available for issue.

Animals↗
PubMed1995

External carotid endarterectomy with internal carotid artery transposition flap angioplasty for symptomatic internal carotid artery occlusion.

The external carotid artery is an important collateral pathway for cerebral perfusion when the internal carotid artery is occluded. After internal carotid artery occlusion, there is a definite risk of ipsilateral neurological events. The authors retrospectively examined their experience with endarterectomy of the external carotid artery for symptomatic internal carotid artery occlusion. Results based on the authors' experience and on historical data show external carotid endarterectomy to be a safe procedure. Obliteration of the cul-de-sac appears to be a very important factor in the prevention of reocclusion or recurrence of symptoms after external carotid endarterectomy. Use of the internal carotid artery stump for patching of the endarterectomized external carotid artery is both safe and effective in treating symptomatic internal carotid artery occlusion.

Aged↗
PubMedDate not supplied

Internal Medicine chief residents suggest need to improve health care delivery and public policy education. Internal Medicine Center to Advance Research and Education.

The primary objective in medical training remains skill development in the delivery of medical care through the understanding of bedside data collection, natural history of disease, use of diagnostic tools and the influence of therapy--all applied to a specific patient. More recently, also considered important is training on the broader issues of health care delivery and public policy, especially since the environment of medicine is changing rapidly. With limited curricular time these issues must compete with the traditional and important clinical training. To evaluate how these subjects have been included in internal medicine training, the Resident Physicians Section (RPS) of the American Society of Internal Medicine (ASIM) sponsored a survey of United States internal medicine chief residents which was conducted by the Internal Medicine Center to Advance Research and Education (IMCARE). The objectives of the study were to 1) study the extent of training on health care delivery and public policy issues offered to residents by internal medicine residency programs; 2) assess training opportunities now available; and 3) determine areas of study not fulfilling perceived needs. The questionnaire contained 12 questions. Chief residents rated the 1) quality of their program in preparing residents on health care delivery, public policy issues and practice management; 2) level of instruction provided on 12 topics; and 3) degree of priority these same topics should have. Respondents were asked to identify 1) any other relevant areas their residency program covered particularly well; 2) the amount of time which should be devoted to these socioeconomic topics in each year of training; and 3) the most appealing formats for learning about these topics. Despite the rapidly growing influence of socioeconomic issues on medical practice, many chief residents perceive that important topics are not being addressed adequately. This study provides information on areas addressed well and topics that should receive greater attention. Recommendations are made for further studies and strategies to increase the emphasis on socioeconomic topics during medical education.

Attitude of Health Personnel↗
PubMed1987

[Extracranial internal carotid occlusion and coexisting ipsilateral intracranial internal carotid aneurysm].

A rare case of extracranial internal carotid occlusion with a coexisting ipsilateral internal carotid aneurysm is reported. A 50-year-old male had a sudden onset of severe headache, vomiting and right motor weakness on May 14, 1984. Two days later the patient was transferred to our hospital. On admission he was alert but presented with nuchal rigidity and right moderate hemiparesis. He had an episode of a blunt head injury 12 years previously, but no history of hypertension, diabetes mellitus or cerebral stroke. A computed tomography revealed mild subarachnoid hemorrhage and mild ventricular dilatation. A cerebral angiography did not demonstrate any aneurysms but it revealed occlusion of the right internal carotid artery at the cervical bifurcation. The repeated angiography on May 31 disclosed a saccular aneurysm arising anteromedially at the level of the junction of the right posterior communicating artery and the internal carotid artery. The cervical internal carotid artery remained occluded at the same site. The middle cerebral artery was supplied through the well-developed posterior communicating artery, and the right anterior cerebral artery was supplied through the anterior communicating artery. Clipping of the aneurysm was attempted but it was forcibly trapped because of premature bleeding on June 5. The right V-P shunt was performed for the progressive ventricular dilatation on June 12. The patient was discharged with no paresis on June 20. It has been well known that the uni- or bilateral carotid occlusion, whatever the origins are, are often associated with cerebral aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Artery Diseases↗
PubMed1989

Women in internal and international migration, with special reference to Latin America.

The recommendations for further action made by the International Conference on Population (Mexico City, 1984) in the area of population distribution and internal and international migration continue to be an accurate reflection of the current state of scientific and political thinking in Latin America, except for the 1 topic on which they are deficient--female migration. An increasing body of research findings demonstrates the importance of women migrants--especially women as independent migrants. The predominance of women in Latin American rural-to-urban migration flows is well known, but female majorities are found in other important flows (e.g., in some inter-urban and international flows) as well. In general, female migrants tend to be younger than their male counterparts. The kinds of employment most commonly sought by women migrants are related to their traditional roles in the home and in child-rearing. The problems faced by migrant women differ from those confronting men who migrate and vary greatly over a wide range of conditions.

Age Factors↗
PubMed1992

Internalization of glycosyl-phosphatidylinositol (GPI)-anchored lymphocyte proteins. II. GPI-anchored and transmembrane molecules internalize through distinct pathways.

Ly-6A.2 (T cell-activating protein, TAP) and Thy-1 are glycosyl-phosphatidyl-inositol (GPI)-anchored proteins expressed on the surface of murine T lymphocytes. We have found that Ly-6A.2 (TAP) and Thy-1 are internalized by T cells. In the present study we have investigated whether these GPI-anchored proteins enter cells by endocytosis through coated pits. Two lines of evidence argue against the involvement of coated pits in the internalization of Ly-6A.2 (TAP) and Thy-1. First, drugs that effectively blocked the endocytosis of transferrin receptor and H-2 class I molecules, (which are known to be internalized via coated pits) did not inhibit the internalization of the GPI-anchored proteins. Second, in ultrastructural analyses, Ly-6A2 (TAP) and Thy-1, in contrast to the transferrin receptor, were rarely found in coated pits or vesicles. These observations suggest that the GPI-anchored proteins on T lymphocytes are internalized by a distinct pathway that does not involve endocytosis through coated pits.

Animals↗
PubMed1985

The International Standard for Human Growth Hormone for Bioassay: calibration and characterization by international collaborative study.

Two preparations of human growth hormone (hGH) were prepared as candidates for the International Standard for Human Growth Hormone for Bioassay and were studied by 22 laboratories in 10 countries in an international collaborative study. The 2 candidate preparations, freeze-dried in ampoules coded 80/505 and 80/521, were assayed against the International Standard for Growth Hormone, bovine, for Bioassay (ISbGH), by in vivo assays; against the International Reference Preparation of Growth Hormone, human, for Immunoassay (IRP hGH), by receptor-, immunoassays and other in vitro methods; and against each other by various methods. Both preparations contained the 2 recognized main growth hormone components (22 kDa and 20 kDa forms) and other components, but that in ampoules coded 80/505 had less deamidated hGH and contaminant hormones and pyrogen than that in ampoules coded 80/521. The estimates by in vivo bioassays, using immature hypophysectomized rats, of the potency of 80/505 in terms of the IS bGH were heterogeneous (1-6 IU/ampoule), probably because of the dissimilarity of the preparations of bovine and human GH. Estimates with receptor- and immunoassays of 80/505 against the IRP hGH were also heterogeneous (3-9 IU/ampoule). Nevertheless, the majority of estimates from all assays tended to be between 3 and 6 IU/ampoule. Although 80/521 and 80/505 differed in relatively minor respects, assays of one directly against the other gave relative potency estimates with in vivo assays which were significantly different from estimates with in vitro methods. With the agreement of the participants in the study, the WHO Expert Committee on Biological Standardization established the preparation in ampoules coded 80/505 as the First International Standard for Human Growth Hormone for Bioassay, with the defined potency of 4.4 IU/ampoule. This corresponds to an approximate 2.5 IU/mg of hGH extract and maintains reasonable continuity of the unit.

Biological Assay↗
PubMed1992

A bifunctional HBED-derivative for labeling of antibodies with 67Ga, 111In and 59Fe. Comparative biodistribution with 111In-DPTA and 131I-labeled antibodies in mice bearing antibody internalizing and non-internalizing tumors.

To investigate whether bifunctional ligands containing chelating structures other than EDTA and DTPA and metallic radiotracers other than 111In will reduce the non-specific radioactivity uptake in the liver during immunoscintigraphy, we synthetized an isothiocyanato-substituted phenolic polyaminocarboxylic acid (HBED-CI) for labeling of MAbs with 67Ga, 111In and 59Fe. Biodistribution of HBED-CI-labeled MAbs was compared to that of 131I and 111In-DTPA labeled MAbs in nude mice bearing tumors, which differ with regard to intracellular internalization and catabolism of the corresponding MAb-antigen complex. In the liver a continuous radioactivity excretion for 67Ga-HBED-CI-labeled MAbs was observed with kinetics that parallel 131I clearance after administration of 131I-MAbs, while 111In-HBED-CI-labeling led to a constant 111In liver level quite similar to that of 111In-DTPA-MAbs. In tumors, 67Ga-HBED-CI-MAb uptake again paralleled that of 131I-MAbs, showing continuous accumulation in tumor tissues when internalization of the MAb-antigen complex was not involved. A much lower uptake, which peaked between 24 and 48 h, was found in the case of MAb-antigen internalization. 111In of 111In-HBED-CI- and 111In-DTPA-labeled MAbs continuously accumulated in both types of tumors. Compared with 111In-DTPA-MAbs, an improvement in tumor-to-liver ratios, due to the reduced liver radioactivity associated with 67Ga-HBED-CI-labeled MAbs, could only be obtained with non-internalizing tumors. The time course of radioactivity distribution in the liver and in MAb-internalizing tumors after administration of 67Ga-HBED-CI-, 111In-HBED-CI- and 111In-DTPA-labeled MAbs further indicates a dominating influence of the metallic radiotracer rather than the ligand on retention or excretion of radioactivity in MAb-catabolizing tissues.

Animals↗
PubMed1997

The International Continence Society "Benign Prostatic Hyperplasia" Study: international differences in lower urinary tract symptoms and related bother.

PURPOSE: We investigated the international differences in the reporting of lower urinary tract symptoms and related bother in patients with symptoms suggestive of bladder outlet obstruction. MATERIALS AND METHODS: Multiple logistic regression analysis was used to evaluate international differences in the reporting of lower urinary tract symptoms and related bother in 1,271 patients from 12 countries who participated in the International Continence Society "benign prostatic hyperplasia" study. RESULTS: Country of origin was significantly associated with the prevalence of a large number of lower urinary tract symptoms (10 of 20), even after adjusting for potentially confounding variables, including physical and socio-demographic factors. Country of origin was also significantly associated with the reporting of bother but for a much smaller number of symptoms (2). CONCLUSIONS: In different countries lower urinary tract symptoms may be reported to different extents. Therefore, the results of studies in particular countries may not be generally applicable to other countries. It is likely that symptom scores will conceal this variation, necessitating consideration of individual symptoms (as in the International Continence Society "benign prostatic hyperplasia" study) or the development of country specific scoring systems. An alternative would be to focus on bother, which appeared to be much less sensitive to international differences.

Aged↗
PubMed2002

Prevalence and age of onset for drug use in seven international sites: results from the international consortium of psychiatric epidemiology.

This study compares lifetime prevalence and age of first use (onset) for alcohol, cannabis, and other drugs in six international sites. Data from seven epidemiologic field surveys that used compatible instruments and study designs were compiled for cross-site analyses by the International Consortium of Psychiatric Epidemiology (ICPE). The world health organization's composite international diagnostic instrument (WHO-CIDI) and additional items were used to ascertain drug use in each site. Lifetime use rates were estimated for alcohol, cannabis, and other illicit drugs. Survival analyses were used to estimate age of onset. Study settings and main results: use of alcohol twelve or more times ranged in descending order from the Netherlands (86.3%), United States (71.7%), Ontario, Canada (71.6%); São Paulo, Brazil (66.1%), Munich, Germany (64.9%), Fresno, California (USA) (51.9%), to Mexico City (43.2%). Use of cannabis five or more times in a lifetime ranged from 28.8 in the United States to 1.7% in Mexico City, and other drugs ranged from United States (19.4%) to Mexico City (1.7%). Age of first use was similar across study sites. This study demonstrates the fundamental uniformity of onset patterns by age as contrasted with wide variations in lifetime prevalences across sites. Study findings suggest that drug use patterns may change among emigrating populations from low consumption nations as a consequence of international resettlement in nations with higher rates. Methodological limitations of the study along with recommendations for future international comparative research are discussed.

Adolescent↗