Search PubMed⌕ Search

Biomedical subjects

S Jacob

Publications and source records attributed to S Jacob.

At least 163 records · Page 9Linked to original sources
PubMed1994

Possible synergistic effect of ACE inhibition and calcium-channel blockade on insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.

So-called insulin resistance is a frequent phenomenon and a marker of increased risk for both type II diabetes mellitus and atherosclerosis. Today, insulin resistance is widely understood as a tissue- and pathway-specific defect of insulin-stimulated glucose uptake into skeletal muscle that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated muscle blood flow and cellular kation balance are presently attracting increasing awareness. Clinical and experimental evidence suggests that angiotensin-converting enzyme (ACE) inhibition ameliorates both insulin-stimulated skeletal-muscle glucose uptake and blood flow in insulin-resistant states by a direct stimulation of cellular glucose uptake, which appears to be kinin-mediated. This improvement of insulin sensitivity could mean not only improvement of glucose metabolism, but also reduction of chronically elevated serum insulin and the ensuing atherogenic consequences (hyper- and dyslipidemia, sympathetic overactivity, growth of vascular smooth-muscle cells, hypertension, etc.). Ca(2+)-channel blockers that do not increase heart rate appear to exert direct antiatherogenic effects while being metabolically neutral. Thus, the combination of Ca(2+)-channel blockade by sustained release verapamil and ACE inhibition by trandolapril in insulin-resistant type II diabetic patients with essential hypertension appears to be promising in terms of possible synergistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Growth and nutrition patterns of infants associated with a nutrition education and supplementation programme in Gaza, 1987-92.

Since 1986, the 28 government community health centres providing primary care in Gaza have paid special attention to growth monitoring, nutrition education, and routine vitamin and iron supplementation in infancy. In 1987-88, 1989 and 1992, respectively, the nursing staff in five of these centres monitored the growth and feeding patterns of 2222, 1899, and 1012 children aged up to 15 months. The growth measures of children aged up to 6 months were similar to standard growth charts, but subsequently deficiencies developed in the study children. There were no differences between the patterns for males and females. Infants from upper socioeconomic categories had growth patterns that were closest to the norm, but this was associated with feeding and supplementation differences. There was improvement in the growth and feeding patterns of the 1989 and 1990-92 birth cohorts compared with the 1987-88 group and with the standard. Feeding patterns showed high levels of compliance with nutrition guidance. Growth monitoring, staff and maternal education, and supplementation with vitamins and, especially, iron were associated with marked improvements in feeding patterns and the growth status of children aged 3-15 months.

Anthropometry↗
PubMed1992

Species differences in 5 alpha-androstane-3 beta,17 beta-diol hydroxylation by rat, monkey, and human prostate microsomes.

The 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by rat prostate microsomes appears to be catalyzed by a single, high-affinity cytochrome P450 enzyme. In the present study we have examined the hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by prostate microsomes from cynomolgus monkeys and from normal subjects and patients with benign prostatic hyperplasia. Our results suggest that although rat, monkey, and human prostate microsomes catalyze the 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol, these pathways of oxidation in monkeys and humans are not catalyzed by a single cytochrome P450 enzyme. The ratio of the three metabolites was not uniform among prostate microsomal samples from individual humans or monkeys. The 6 alpha-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol varied independently of both the 7 alpha- and 7 beta-hydroxylation, which varied in unison. The 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey prostate microsomes appeared to be differentially affected by in vivo treatment of monkeys with beta-naphthoflavone or dexamethasone. Treatment of a monkey with dexamethasone appeared to cause a 2.5-fold increase in both the 7 alpha- and the 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol without increasing the 6 alpha-hydroxylation. The 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by human and monkey prostate microsomes, but not the 6 alpha-hydroxylation, was inhibited by antibody against rat liver NADPH-cytochrome P450 reductase. Similarly, the 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by human prostate microsomes, but not the 6 alpha-hydroxylation, was markedly inhibited (greater than 85%) by equimolar concentrations of the imidazole-containing antimycotic drugs ketoconazole, clotrimazole, and miconazole. These results suggest that the 7 alpha- and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey and human prostate microsomes is catalyzed by a cytochrome P450 enzyme, whereas the 6 alpha-hydroxylation is catalyzed by a different enzyme which may or may not be a cytochrome P450 monooxygenase. The hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by prostate microsomes from normal human subjects was quantitatively and qualitatively similar to its hydroxylation by prostate microsomes from patients with benign prostatic hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstane-3,17-diol↗
PubMed1991

Catabolite repression of the operon for xylose utilization from Bacillus subtilis W23 is mediated at the level of transcription and depends on a cis site in the xylA reading frame.

The Bacillus subtilis xyl operon encoding enzymes for xylose utilization is repressed in the absence of xylose and in the presence of glucose. Transcriptional fusions of spoVG-lacZ to this operon show regulation of beta-galactosidase expression by glucose, indicating that glucose repression operates at the level of transcription. A similar result is obtained when glucose is replaced by glycerol, thus defining a general catabolite repression mechanism. A deletion of xylR, which encodes the xylose-sensitive repressor of the operon, does not affect glucose repression. The cis element mediating glucose repression was identified by Bal31 deletion analysis. It is confined to a 34 bp segment located at position +125 downstream of the xyl promoter in the coding sequence for xylose isomerase. Cloning of this segment in the opposite orientation leads to reduced catabolite repression. The homology of this element to various proposed consensus sequences for catabolite repression in B. subtilis is discussed.

Bacillus subtilis↗
PubMed1991

Studies on the mechanism of haloacetonitriles toxicity: quantitative whole body autoradiographic distribution of [2-14C]chloroacetonitrile in rats.

Chloroacetonitrile (CAN), a drinking water disinfectant by-product, possesses mutagenic and carcinogenic properties. The objective of this study was to investigate the biologic fate of CAN, using whole body autoradiographic (WBA) techniques. Male Sprague-Dawley rats were treated with a tracer dose of [2-14C]CAN (i.v., 88 muCi/kg, spec. act 4.07 mCi/mmol). At various time intervals (0.08, 1, 3, 6, 12, 24, and 48 h) after treatment, rats were processed for WBA. Over 12 h after administration, the radioactivity excreted in urine, feces, and exhaled as 14CO2 accounted for 51%, 2.7%, and 12% of the dose, respectively. Only 0.8% of the administered dose was exhaled as unchanged CAN. At an early time interval (5 min) extensive accumulation of radioactivity was observed in liver, kidney, and gastrointestinal (G.I.) walls. In addition, high levels of 14C were detected in the thyroid gland, lung bronchioles, adrenal cortex, salivary gland, and testes. At 1 h following administration, the olfactory bulb, olfactory receptor area of the brain and lumbar cistern showed high accumulations of radioactive CAN or its equivalents. At 3, 6, and 12 h after treatment, the radioactivity diffused homogeneously in all tissues and reconcentrated in several organs at later time periods (24 and 48 h). Our studies indicate extensive metabolic biotransformation of CAN in rats. The retention of radioactivity in the tissues of the thyroid gland, G.I., testes, brain and eye suggest that those organs are potential target sites of CAN toxicity.

Acetonitriles↗
PubMed1991

Comparative disposition and whole-body autoradiographic distribution of [2-14C]azidothymidine and [2-14C]thymidine in mice.

Azidothymidine (AZT) is the only approved drug for treatment of acquired immunodeficiency syndrome caused by human immunodeficiency virus. The drug is known to be metabolized by mammalian systems. The objectives of this study were: 1) to investigate the biologic fate of AZT using whole-body autoradiography; and 2) to compare the biologic fate of AZT with that of the parent molecule thymidine (dThd). Male Sprague-Dawley mice were given (intravenously) a tracer dose of [2-14C]AZT (273 microCi/kg) or [2-14C]dThd (218 microCi/kg). Treated animals were sacrificed at various time periods (2 min, 5 min, 4 hr and 24 hr) and processed for whole-body autoradiography. Tissue distribution of radioactivity in the autoradiographs was quantitated using computer-aided image analysis. The elimination of AZT and dThd was also examined by radiochemical analyses of urine, feces and expired air of treated animals over a 24-hr period. Twenty-four hr following AZT treatment, the radioactivity excreted in urine, feces and in exhaled air (as 14CO2) accounted for 86, 4.6 and 3.7% of the dose, respectively. Within 2 min after administration of AZT, maximum radioactivity was detected in the kidney. The brain, spinal cord and testes were conspicuous because of virtual lack of radioactivity. All other parenchymatous organs (liver, lung, heart and spleen) had apparent similar levels of radioactivity that were higher than those in the connective tissues. At a later time period (4 hr), the radioactivity in most organs was eliminated except in the renal medulla, contents of gastrointestinal tract, urinary bladder and mouth cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Morphometric studies on the development and sexual dimorphism of the submandibular gland of the mouse.

A light microscopic morphometric analysis of the development of the mouse submandibular gland has been carried out from birth up to the age of 6 weeks. At birth the bulk of the gland consists of approximately equal volume proportions of acinar, terminal tubule and non-secretory cells. The granular convoluted tubule is absent at birth. The neonatal female gland resembles that of the male in many respects. With the regression of the terminal tubule at 2 weeks of age the duct system of the gland is seen to differentiate into excretory, striated and intercalated ducts. The volume proportions of the gland constituents of the female are similar to those of the male at 2 weeks. At this age, the acini occupy 55%, the striated duct 20% and the intercalated duct 15% of the total gland volume. Sexual dimorphism is clearly evident in the gland at 4 weeks of age when the duct system is seen to differentiate to form its granular convoluted tubule component. The granular tubule occupied 19% of the gland volume in the male but only 8% in the female at 4 weeks. The proportions of acini are only 41% in the total gland volume of the male mouse but 62% in the female at 4 weeks. In the male gland the proportions of granular convoluted tubule increase from 13% to 21% between 4 and 6 weeks and the secretory granule content of these cells from 6% to 24%. At 6 weeks of age the volume proportion of granular convoluted tubule in the male is 45% and that in the female is only 12%. At this age the acini occupy a proportion of 30% in the male gland as opposed to 57% in the female gland. At 6 weeks the volume of granular convoluted tubule cells is 40% lower in the female (1842 microns 3) than in the male gland (2995 microns 3).

Animals↗
PubMed1989

Effects of hyperthermia on the peripheral metabolism of ammonia and glutamine.

Although there are a number of physiological states associated with an increase in body temperature, eg, nonseptic and septic fever or exercise, the effects of hyperthermia on intermediary metabolism in vivo have received little attention. The current study was undertaken to examine the peripheral metabolism of ammonia and ammonia-related amino acids using a model of exogenously induced mild hyperthermia in nonfebrile subjects. Arteriovenous levels of metabolites were measured in subjects with known cerebrovascular insufficiency. Peripheral exchange of these metabolites was monitored before, during, and after hyperthermia to an average temperature of 38.5 degrees C. All subjects showed an increase in plasma ammonia and glutamate. There was also an associated peripheral production of ammonia and an uptake of glutamine and alanine by the skeletal muscle tissues. The exchange of glutamate was not affected. These findings indicate that hyperthermia is associated with a nitrogen-sparing effect, the mechanism of which is yet unknown.

Acid-Base Equilibrium↗
PubMed1989

Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats.

Degradation of branched-chain amino acids was studied in muscles of unloaded hind limbs from rats subjected to six days of tail-cast suspension. The total production of 14CO2 from uniformly labeled 14C-leucine, isoleucine, or valine, and the fluxes through leucine aminotransferase and alpha-ketoisocaproate dehydrogenase, which were measured using L-1-14C-leucine, were generally greater in the soleus and extensor digitorum longus muscles of unloaded than of weight-bearing hind limbs. Adrenalectomy abolished any difference in flux through the aminotransferase, whereas the administration of cortisol to adrenalectomized animals restored the greater flux in the unloaded soleus muscle. Adrenalectomy partially diminished the greater flux through alpha-ketoisocaproate dehydrogenase in the unloaded soleus, whereas cortisol (2 mg/100 g body weight) treatment increased this difference. In the extensor digitorum longus, adrenalectomy abolished the differences in both enzyme fluxes due to hind limb suspension. In this muscle, cortisol treatment increased these fluxes to a similar extent in both weight-bearing and suspended, adrenalectomized animals so that the normal difference was not restored. These results suggest that leucine catabolism in hind limb muscles of suspended rats was influenced primarily by increased circulating glucocorticoid hormones, which are elevated twofold to fourfold in these animals.

Adrenalectomy↗
PubMed1989

Ultrastructure of the ferret sublingual gland.

The sublingual glands of 2 male and 2 female adult ferrets were examined using electron microscopy. The secretory end piece consisted of mucous tubules, serous and mixed acini. The mucous cells showed two different types of granules. The serous cells contained electron-dense secretory granules. The duct system entirely comprised excretory ducts.

Animals↗
PubMed1989

Microgranular acute promyelocytic leukemia: a proposed role for a greater deformability of the leukemic cell.

A case of microgranular acute promyelocytic leukemia (APL), M-3 variant, is reported in a boy aged 5 years. The disease, which was rapidly fatal, presented with acute disseminated intravascular coagulation (DIC) and leukocytosis. Different cytomorphologic subtypes of promyelocytes were identified on the basis of cytoplasmic granular patterns: the microgranular type with barely visible cytoplasmic granulations and deeply basophilic cytoplasm and the more characteristic type with large promyelocytes containing azurophil granules. We observed a ratio of large promyelocytes to microgranular promyelocytes of 1:1.2 in the marrow and 1:4 in the peripheral blood. To explain this discrepancy, we hypothesize that the microgranular promyelocytes may be more deformable than the typical promyelocyte and that this intrinsic cellular characteristic may promote marrow egress and increase the likelihood of hyperleukocytosis in the M-3 variant.

Bone Marrow↗
PubMed1988

Problems in analysis of data from muscles of rats flown in space.

Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

Adaptation, Physiological↗