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Biomedical subjects

J Shemer

Publications and source records attributed to J Shemer.

At least 127 records · Page 7Linked to original sources

Colchicine in the treatment of AA and AL amyloidosis.

Colchicine is an effective medication in the prevention and treatment of amyloidosis of familial Mediterranean fever. Its therapeutic effect depends on the stage of renal disease and the drug dose. To evaluate colchicine effect in AA amyloidosis of other diseases and in primary AL amyloidosis, the literature was reviewed. Findings were that (1) the effect of colchicine in reactive amyloidosis has not been methodically studied, but anecdotal reports suggest it may be beneficial; and (2) the results of studies and case reports on the effect of colchicine in primary amyloidosis are conflicting. Because a therapeutic effect of colchicine in primary and reactive amyloidosis has been shown in sporadic cases, a prospective, controlled, multicenter study assessing the effect of colchicine in all types of amyloidosis appears to be justified. Until such a study is available, the addition of colchicine in an appropriate dose to any therapeutic regimen of patients with AA or AL amyloidosis should be considered.

Adult↗

Efficacy of different doses of immune serum globulin in the prevention of hepatitis A: a three-year prospective study.

Previous studies have shown that the administration of immune serum globulin (ISG) before exposure to hepatitis A virus prevents infection. The precise dose needed and the duration of the protection conferred are unclear, however. In this study, ISG doses of 2 mL and 5 mL were used for preexposure prophylaxis, and their efficacies in reducing the attack rate of hepatitis A among Israel Defence Forces troops serving in field units were compared. The attack rate during the first 4 months of follow-up was low and was similar regardless of the dose administered (0.11/10,000 and 0.15/10,000 for 2 mL and 5 mL, respectively; P = 1.0). In the second and third 4-month intervals after immunization, attack rates were higher (but not significantly so) among soldiers given 2 mL than among those given 5 mL. Twelve months after immunization, the cumulative attack rate for hepatitis A was significantly different for the two groups (2.78/10,000 vs. 1.30/10,000; P < .05). Our data suggest that preexposure immunization with 2 mL of ISG is as effective as that with 5 mL in preventing hepatitis A for 4 months. The advantage of the 5-mL dose is evident 5-12 months after administration.

Dose-Response Relationship, Immunologic↗

The effects of continuous operation in a chemical protective ensemble on the performance of medical tasks in trauma management.

Treating casualties in a chemically hazardous environment constitutes a unique problem. Physical protection of the medical personnel may impair their performance and potentially affect patients' prognoses. The present study examined the effect of prolonged physical protection on the accomplishment of medical tasks related to trauma management. Sixty one emergency medical technicians, acclimatized to operating in protective gear, underwent four rounds of testing during eight hours of continuously wearing either a chemical protective suit or regular fatigues. The quality of the designated medical tasks, including sterility, was maintained throughout the study. A significant reduction in speed of performance was noted (approximately 30% slowing, p < 0.0001 in multivariate analysis) because of protective clothing. There was no additional decrement in performance following a prolonged stay in the protective gear. We conclude that in a chemically contaminated area, fully protected medical personnel are capable of treating trauma patients reasonably well, and for a relatively long period of time. The importance of pretraining and proper instruction is emphasized.

Acclimatization↗

Regulation of insulin-like growth factor (IGF) binding protein-5 in the T47D human breast carcinoma cell line by IGF-I and retinoic acid.

The T47D human breast carcinoma cell line has been shown to synthesize insulin-like growth factor-I (IGF-I) binding proteins (IGFBPs) and IGF-I receptors, and to exhibit a mitogenic response to exogenous IGF-I. We have used T47D cells to investigate the regulation of IGFBPs by IGF-I and retinoic acid (RA), agents that affect cell proliferation and have been shown to regulate IGFBP levels in other cell types. Exposure of T47D cells to IGF-I resulted in the appearance of IGFBP-2, -4, and -5 in conditioned medium but had no effect on the levels of IGFBPs in Triton X-100-extracted cells. This effect was most pronounced for IGFBP-5 and was also elicited by an IGF-I analog that retains affinity for IGFBPs but not by insulin or IGF analogs that have decreased affinity for IGFBPs. Additionally, this effect was not associated with a change in IGFBP-5 messenger RNA (mRNA) levels; however, the appearance of IGFBP-5 in the conditioned medium was inhibited by an anti-IGF-I receptor antibody (alpha IR-3). RA decreased IGFBP-5 mRNA levels and cell-associated IGFBP-5 in both the presence and absence of IGF-I and inhibited the IGF-I-stimulated secretion of IGFBP-5 into T47D cell conditioned medium. These results suggest that IGF-I increases IGFBP-5 levels in the T47D cell line both through direct interaction with IGFBP-5 as well as through a receptor-mediated process that does not require direct interaction with IGFBPs. The latter results are consistent with an effect of IGF-I on a factor that may modulate an IGFBP protease activity. The inhibitory effect of RA, on the other hand, appears to be due primarily to regulation of IGFBP-5 mRNA levels. Thus, IGFBP-5 accumulation appears to be positively regulated by IGF-I, potentially at the level of susceptibility to proteolysis, and negatively regulated at the level of gene expression by RA.

Breast Neoplasms↗

[Glucose polymer solutions and prolonged exertion in the heat].

The effect of glucose polymer solutions on physical performance has been extensively investigated, mainly under controlled laboratory conditions. The influence of such beverages on fluid balance and on glycemic state in the field, during prolonged exercise of moderate intensity (a 134 km march) in the heat (32-41 degrees C, 60-14% relative humidity) was therefore studied. 48 endurance-trained men were randomly assigned to drink either a 7.2% glucose polymer (GP) electrolyte beverage or tap water (TW); there were 24 in each group. Each group was then divided into subgroups that either consumed fluid ad libitum, or were instructed to consume 1000 ml/hr. Mean fluid consumption of all subgroups was similar. There was a greater change in plasma volume for the TW than for the GP group (+7.9% vs. +4.8%, respectively; p less than 0.05). However, in neither the GP nor the TP group did dehydration exceed 2% of body weight. Blood glucose concentration increased significantly in subjects ingesting GP (p less than 0.01) while it decreased on each day of march in those drinking TW. It is concluded that the fluid intake recommended at present by the IDF is adequate to maintain hydration within the normal range during physical effort in the heat. The differences between the GP and the TW groups in this study do not justify the substitution of glucose-polymer solutions for water during prolonged, moderate exercise.

Adult↗

Evolutionary origins of intercellular communication systems: implications for mammalian biology.

Traditionally, the two major systems of intercellular communication (i.e. the nervous and endocrine systems) were considered separate functional and anatomical entities. Recent studies have provided evidence that the biochemical elements of these systems have common early phylogenetic origins and have suggested that, with the exception of their anatomical diversity, all the systems of intercellular communication are biochemically similar. On the basis of these findings, we suggest that the overlaps between the nervous and endocrine systems, the widespread tissue production of hormones, and other phenomena are now more easily understood.

Animals↗

Tissue-specific transcription start site usage in the leader exons of the rat insulin-like growth factor-I gene: evidence for differential regulation in the developing kidney.

The production of insulin-like growth factor-I (IGF-I) in extrahepatic tissues supports both autocrine and paracrine functions and is regulated differently from that in liver, which supports endocrine function. In rat liver, transcription initiation primarily occurs at four distinct, widely separated sites in exon 1 of the IGF-I gene, whereas in exon 2, transcription initiation occurs at a cluster of sites. To understand the molecular basis for tissue-specific regulation of IGF-I gene expression, we have mapped transcription start site usage in the following extrahepatic tissues: testes, lung, kidney, heart, brain, muscle, and stomach, with liver serving as a control. In adult rats, kidney and brain exhibited a pattern of exon 1 transcription similar to that seen in liver, i.e. roughly equivalent use of start sites 2 and 3. In contrast, testes and lung preferentially used start site 3, while stomach, heart, and muscle predominantly used start site 3. Start sites 1 and 4 were used in all tissues at extremely low levels. In those tissues studied in which exon 2 transcripts are expressed (testes, lung, stomach, and kidney), the pattern of exon 2 transcription initiation was identical to that in adult rat liver. During postnatal development, the use of all transcription start sites in exons 1 and 2 was coordinate in lung and stomach. Selection of transcription start sites in the kidney, on the other hand, was subject to regulation during postnatal development. Specifically, within exon 1, start site 3 was expressed constitutively throughout peri- and postnatal development. In contrast, the usage of start site 2 was not detected at late fetal or early postnatal stages, but appeared and rapidly increased only at the stage of weaning. Exon 2 transcripts in kidney also did not appear until the postnatal period. These data suggest tissue-specific and developmentally regulated transcription factors regulating IGF-I promoter activity or, alternatively, tissue-specific and developmental stage-dependent differences in the stability of IGF-I mRNAs resulting from the use of different transcription start sites. These different mRNAs may be of significance in the differential regulation of IGF-I production for autocrine or paracrine function.

Animals↗

Normal renin-aldosterone-insulin and potassium interrelationship in FMF patients and amyloid nephropathy.

The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure.

Adult↗

Medical limitations of gas masks for civilian populations: the 1991 experience.

Using a gas mask (GM) may involve considerable inconvenience, impairment of respiration and communication, and serious psychological reactions. The medical literature is primarily focused on the occupational aspects of using the GM by young and healthy workers. In contrast, there is hardly any information concerning the use of GMs by large, unselected populations, including children, the elderly, and the sick. Issuing GMs to all residents of Israel prior to Operation Desert Storm created an urgent need to define the populations whose health might be jeopardized by using the standard GM. Adding an active air supply system (AASS) to a standard GM may ease the burden on this high-risk group. We evaluated the physiological aspects of breathing with a GM, with and without AASS, in respect to pathophysiology of diseases, and reached a set of criteria for identifying those who may be endangered by a GM and are expected to benefit from the AASS. The method used to sort and identify those entitled to the AASS is described.

Chronic Disease↗

The Ural train-gas pipeline catastrophe: the report of the IDF medical corps assistance.

Following the destruction of two trains in the Urals 2000 km east of Moscow, as a consequence of the conflagration caused by an explosion from a leaking natural gas pipeline, 3000 people were injured;* most of them (2200) died* immediately and the others (about 800) were badly burned. At the request of the Soviet Union Government a medical military delegation was sent to give assistance to the injured people. This report describes the treatment given by the delegation to 40 patients with burns of between 40 and 90 per cent TBSA during a period of 10 days. An insight into a Soviet Union Trauma Center is given and the good treatment given by the Soviet colleagues is emphasized.

Blast Injuries↗

Insulin and IGF-I stimulate phosphorylation of their respective receptors in intact neuronal and glial cells in primary culture.

Previous studies have shown that insulin and IGF-I bind to their respective receptors and stimulate autophosphorylation of the receptor beta subunits in detergent extracts of neuronal and glial cells. In the present study, intact neuronal and glial cells in primary culture have been utilized to characterize insulin- and IGF-I-stimulated phosphorylation of their receptors. Following [32P]orthophosphate labelling and stimulation by insulin or IGF-I, the cells were solubilized and the phosphorylated receptors were partially purified on wheat germ agglutinin--agarose columns, and immunoprecipitated using anti-phosphotyrosine or anti-insulin receptor antibodies. Insulin stimulated the phosphorylation of its receptor beta subunit (95 kD phosphoprotein) in a dose-dependent manner, within at least 20 seconds in both neuronal and glial cells. Additionally, a 102-kD phosphoprotein was observed in insulin-stimulated neuronal cells. Maximal stimulation of receptor phosphorylation occurred at 1 minute for the glial cells, and 10 minutes for the neuronal cells. IGF-I stimulated the phosphorylation of two phosphoproteins in intact neuronal and glial cells; a 95-kD protein and a 102-kD protein, in a dose-dependent manner. These observations demonstrate that both insulin and IGF-I stimulate the phosphorylation of the beta subunits of their respective receptors in brain cells in a similar fashion to their effects on receptors from nonneural tissues.

Animals↗

Liver insulin receptor tyrosine kinase activity in a rat model of type II diabetes mellitus and obesity.

Spontaneous hypertensive-corpulent rats (SHR/N-corpulent), homozygous for the corpulent gene (cp/cp), are obese, hyperinsulinemic and exhibit abnormal glucose tolerance and thus represent a model for type II diabetes and obesity. In view of their overall insulin resistance, we examined liver insulin receptor binding and tyrosine kinase activity from corpulent rats and lean littermates fed purified diets containing 54% sucrose or starch for about 12 wk. Specific 125I-insulin binding to crude liver membranes from female corpulent rats fed either starch or sucrose was reduced to approximately 50% of that seen in lean rats (14 vs. 7%). Affinity of insulin receptors was similar in all groups, suggesting that hyperinsulinemic corpulent rats possess fewer hepatic insulin receptors than do lean rats. Using similar numbers of wheat germ agglutinin-agarose (WGA)-purified insulin receptors with similar affinities for insulin, it was found that basal and insulin-stimulated phosphorylation of the synthetic tyrosine-specific kinase substrate poly(Glu, Tyr)4:1 was similar in lean and obese rats fed sucrose or starch. It is suggested that the contribution of the liver to the insulin resistance in obese SHR/N-cp rats probably lies distal to the insulin receptor tyrosine kinase.

Animals↗

Characterization of the altered oligosaccharide composition of the insulin receptor on neural-derived cells.

Typical insulin receptors are present on neuroblastoma cell lines. High affinity binding for insulin was present in membrane preparations from NG108 (a hybrid mouse neuroblastoma-rat glioma) as well as in membranes from SK-N-MC and SK-N-SH, two human neuroblastoma cell lines. Specific [125I]insulin binding was 24.4% for NG108, 16.9% for SK-N-MC and 5.2% for SK-N-SH at membrane protein concentrations of 0.4 mg/ml. IC50 for [125I]insulin binding was 3.4 nM in NG108 membrane preparations and 0.9 nM for SK-N-SH and 1.8 nM in SK-N-MC membranes. Apparent mol. wt. for the alpha subunits (identified by specific immunoprecipitation using the anti-insulin receptor antiserum B10) on SDS PAGE was 134 kDa for NG108; 124 kDa for SK-N-MC and 120 kDa for SK-N-SH. Neuraminidase digestion increased the mobility of the alpha subunit from both NG108 and SK-N-MC receptors to 120 kDa, whereas that from SK-N-SH were unaffected. Endoglycosidase H and endoglycosidase F digestions increased the mobility of the alpha subunits of all 3 cell lines to varying degrees, suggesting the presence of N-linked glycosylation. Insulin induced autophosphorylation of the insulin receptor beta subunit in WGA-purified membranes from all 3 cell lines. In addition, phosphorylation of a protein with an apparent mol. wt. 105 kDa was stimulated by insulin in WGA purified membranes from NG108. Tyrosine-specific kinase activity was present in the membranes from each cell line and was stimulated by insulin in a dose-dependent manner from 10(-9) to 10(-6) M. Proinsulin was about 100 times less potent in stimulating phosphorylation of the artificial substrate poly (Glu, Tyr)4:1 when compared to insulin in accordance with its lower binding affinity to the insulin receptor. Hexose transport was stimulated by insulin in all 3 cell lines. These results indicate that neuroblastoma cells contain specific insulin receptors and that they may be useful as models for studying the role of insulin in nervous tissue.

Binding, Competitive↗

Insulin receptors in the brain: structural and physiological characterization.

The present study was conducted to characterize insulin receptors and to determine the effects of insulin in synaptosomes prepared from adult rat brains. Binding of 125I-insulin to synaptosome insulin receptors was highly specific and time dependent: equilibrium binding was obtained within 60 minutes, and a t1/2 of dissociation of 26 minutes. Cross-linking of 125I-insulin to its receptor followed by SDS-PAGE demonstrated that the apparent molecular weight of the alpha subunit of the receptor was 122,000 compared with 134,000 for the liver insulin receptor. In addition, insulin stimulated the dose-dependent phosphorylation of exogenous tyrosine containing substrate and a 95,000 MW plasma membrane associated protein, in a lectin-purified insulin receptor preparation. The membrane associated protein was determined to be the beta subunit of the insulin receptor. Incubation of synaptosomes with insulin caused a dose-dependent inhibition of specific sodium-sensitive [3H]norepinephrine uptake. Insulin inhibition of [3H]norepinephrine uptake was mediated by a decrease in active uptake sites without any effects in the Km, and was specific for insulin since related and unrelated peptides influenced the uptake in proportion to their structural similarity with insulin. These observations indicate that synaptosomes prepared from the adult rat brain possess specific insulin receptors and insulin has inhibitory effects on norepinephrine uptake in the preparation.

Animals↗

Insulin-related materials in the nervous system of vertebrates and non-vertebrates: possible extrapancreatic production.

Studies from multiple laboratories with a range of methods raised the possibility that insulin production occurs naturally at extrapancreatic sites. Part A covers the presence of insulin-related materials in organisms that do not have an endocrine pancreas, including unicellular prokaryotes and eukaryotes as well as multicellular non-vertebrate animals (insects et al.) and plants. Part B covers possible production of insulin by extrapancreatic tissues of vertebrates that are remote from a source of pancreatic insulin e.g. early chick embryos and mammalian cells in culture. Part C covers possible extrapancreatic insulin production in mammals in vivo. Each section ends with an outline summary with evidence in favor of and against the hypothesis.

Amino Acid Sequence↗