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Biomedical subjects

J Turk

Publications and source records attributed to J Turk.

At least 127 records · Page 7Linked to original sources
PubMed1991

Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels.

The present experiments were undertaken to examine the hypothesis that glucose-induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been observed in a number of different tissues, including retinal capillary endothelial cells exposed to elevated glucose levels in vitro) and associated activation of protein kinase C may play a role in mediating glucose-induced vascular functional changes. We report here that twice daily instillation of 30 mM glucose over 10 d in a rat skin chamber granulation tissue model induces approximately a 2.7-fold increase in diacylglycerol (DAG) levels (versus tissues exposed to 5 mM glucose) in association with marked increases in vascular clearance of albumin and blood flow. The glucose-induced increase in DAG levels as well as the vascular functional changes are prevented by addition of 3 mM pyruvate. Pharmacological activation of protein kinase C with the phorbol ester TPA in the presence of 5 mM glucose increases microvascular albumin clearance and blood flow, and similar effects are observed with 1-monoolein (MOG), a pharmacological inhibitor of the catabolism of endogenous DAG. A pharmacological inhibitor of protein kinase C (staurosporine) greatly attenuates the rise in microvascular albumin clearance (but not the rise in blood flow) induced by glucose or by MOG. These findings are compatible with the hypothesis that elevated concentrations of glucose increase tissue DAG content via de novo synthesis, resulting in protein kinase C activation, and that these biochemical events are among the factors that generate the increased microvascular albumin clearance.

Alkaloids↗
PubMed1991

Pisa syndrome in an adolescent on neuroleptic medication.

To our knowledge Pisa syndrome in childhood or adolescence has not previously been described. The syndrome developed in an adolescent girl following administration of neuroleptic medication for psychotic features, and was transiently thought to be abnormal illness behaviour. This case emphasises the need for early diagnosis and rapid effective treatment.

Adolescent↗
PubMed1991

Hypotensive properties of the protein kinase inhibitor, staurosporine, in normotensive and spontaneously hypertensive rats.

The protein kinase inhibitor, staurosporine, was examined for hemodynamic actions in conscious rats and for its effects on isolated vascular smooth muscle. In conscious normotensive rats, staurosporine, 0.1 to 1.0 mg/kg intravenous, produced a dose-related decrease in blood pressure. Doses of 0.1 and 0.5 mg/kg produced reflex tachycardia, while heart rate decreased following 1.0 mg/kg. Higher doses of staurosporine (5 and 10 mg/kg), although not significantly altering heart rate, caused a precipitous drop in blood pressure and all rats died within 48 hours of treatment. Spontaneously hypertensive rats were significantly more sensitive than normotensive rats to the blood pressure lowering effects of staurosporine. The depressor activity of staurosporine was also observed in cord-stimulated pithed rats indicating that hypotension is a peripherally- rather than centrally-mediated effect of staurosporine. In ring preparations of rat thoracic aorta, staurosporine (3 nM to 0.1 mM) produced a concentration-dependent inhibition of serotonin-induced contraction, consistent with its ability to lower blood pressure by an effect at a peripheral vascular site. These results provide the first documentation of the potent cardiovascular activity of staurosporine in the conscious rat and support the contention that protein kinases, in particular protein kinase C, may be important in the regulation of vascular tone.

Alkaloids↗
PubMed1990

Polypoid cystitis, pyelonephritis, and obstructive uropathy in a cow.

Polypoid cystitis, pyelonephritis, and obstructive uropathy was found in a cow with hematuria, dysuria, and colic. The cow was treated with penicillin, multiple B vitamin supplementation, and isotonic sodium chloride. Polypoid cystitis, diagnosed in this cow by use of endoscopic examination, is a common response to chronic inflammation of the bladder and can lead to obstructive uropathy. Although endoscopic confirmation of this diagnosis may not always be feasible, recognition of corresponding clinical signs can allow timely, appropriate treatment.

Animals↗
PubMed1990

Effects of insulin secretagogues on protein kinase C-catalyzed phosphorylation of an endogenous substrate in isolated pancreatic islets.

The influence of the insulin secretagogues, carbachol and glucose, on protein kinase C activation in isolated pancreatic islets has been examined by determination of the phosphorylation state of an endogenous 80-kDa protein substrate of protein kinase C. The islet 80-kDa protein was identified as the myristoylated alanine-rich C kinase substrate previously described (Stumpo D. J., Graff, J. M., Albert, K. A., Greengard, P., and Blackshear, P. J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 4012-4016) by immunoprecipitation studies. The muscarinic agonist, carbachol (500 microM), induced insulin secretion and a time-dependent increase in the phosphorylation state of this protein in islets. This phosphorylation was maximal (220 +/- 24% of control) at 5 min and was suppressed by the protein kinase C inhibitor, staurosporine. Concentrations of glucose (28 mM) which induce maximal insulin secretion did not induce a statistically significant increase in 80-kDa phosphorylation. The combination of carbachol and a submaximally stimulatory concentration of glucose (10 mM), when added simultaneously, exerted a marked synergistic effect on insulin secretion and a synergistic effect on the phosphorylation of the 80-kDa protein kinase C substrate. These data suggest that the activation of protein kinase C may play an important role in carbachol-induced insulin secretion and in the potentiation by carbachol of insulin secretion induced by glucose. However, the activation of protein kinase C does not appear to be a primary determinant of insulin secretion induced by glucose alone.

Alkaloids↗
PubMed1990

Long-chain fatty alcohol quantitation in subfemtomole amounts by gas chromatography-negative ion chemical ionization mass spectrometry. Application to long-chain acyl coenzyme A measurement.

We describe a simple and sensitive method to identify and quantitate long-chain fatty alcohols. Long-chain fatty alcohols were converted to their pentafluorobenzoyl derivative and analyzed by gas chromatography (GC)-mass spectrometry in the negative ion chemical ionization (NICI) mode with selected ion monitoring. GC resolution was obtained for myristyl, palmityl, heptadecyl, stearyl, oleyl, linoleyl and arachidonyl alcohols. As little as 0.4 fmol of fatty alcohol can be detected, which represents a six order-of-magnitude increase in sensitivity over previously described methods. This assay can be used to measure femtomolar amounts of long-chain acyl coenzyme A thioesters after reduction to the corresponding fatty alcohols with sodium borohydride. Other potential applications of this assay include identification and quantitation of long-chain fatty alcohol production by microorganisms.

Acyl Coenzyme A↗
PubMed1990

Interleukin-1 induces rapid and transient expression of the c-fos proto-oncogene in isolated pancreatic islets and in purified beta-cells.

The effect of interleukin-1 beta (IL-1) on expression of c-fos mRNA in isolated rat pancreatic islets was examined. Accumulation of c-fos mRNA was demonstrable after 30 min of exposure to IL-1, peaked by 60 min, and declined thereafter. Fluorescence-activated cell sorting (FACS) of dispersed islet cells was employed to localize the accumulation of c-fos mRNA to the beta-cell. Cycloheximide did not influence the induction of c fos mRNA by IL-1. Accumulation of c-fos mRNA therefore appears to be an early signal transduction event in the beta-cell and a component of the cellular mechanism(s) by which IL-1 influences beta-cell function.

Animals↗
PubMed1990

Coliform septicemia and pulmonary disease associated with canine parvoviral enteritis: 88 cases (1987-1988).

Parvovirus infection was confirmed by fluorescent antibody staining or viral culturing in 137 (22%) of 615 necropsy accessions from dogs at the Missouri Veterinary Medical Diagnostic Laboratory from Jan 1, 1987 through Sept 30, 1988. Septicemic colibacillosis was diagnosed in 88 (90%) of the 98 canine parvovirus-positive accessions in which liver or lung was cultured bacteriologically. Pulmonary edema or alveolitis similar to that seen in the human adult respiratory distress syndrome was observed in 63 (69%) of the 91 canine parvovirus-positive accessions in which the lungs were examined histologically.

Animals↗
PubMed1990

Diacylglycerol synthesis de novo from glucose by pancreatic islets isolated from rats and humans.

Recent evidence has suggested that pancreatic islets isolated from rats synthesize 1,2-diacyl-sn-glycerol (DAG) de novo from glucose and that this process may constitute the long-sought link between the metabolism of glucose and the induction of insulin secretion. The cell-permeant diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (200 microM) has been found here to amplify both the first and second phases of insulin secretion from perifused human islets. Measurements of the mass of endogenous DAG in human pancreatic islets by enzymatic and by mass spectrometric methods indicate that levels of 200 microM may be achieved under physiologic conditions. Conversion of [14C]glucose to [14C]DAG has been demonstrated here to occur within 60 s of exposure of rat and human islets to stimulatory concentrations of glucose. This process has been found to be a quantitatively minor contributor to the total islet DAG mass after acute stimulation with glucose, however, and glucose has been found not to induce a rise in total islet DAG content within 20 min of induction of insulin secretion. In contrast to the case with rodent islets, two pharmacologic inhibitors of DAG-induced activation of protein kinase C (staurosporine and sphingosine) have been found not to influence glucose-induced insulin secretion from isolated human islets. These findings indicate that de novo synthesis of DAG from glucose does not participate in acute signal-response coupling in islets.

Alkaloids↗
PubMed1990

Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation.

Recombinant human IL 1 beta inhibits glucose-induced insulin secretion from isolated pancreatic islets and from purified beta-cells obtained by fluorescence-activated cell sorting (FACS) of dispersed islet cells. Brief (1 h) exposure of isolated islets to IL 1 produces sustained inhibition of insulin secretion for at least 17 h after the IL 1 has been removed from the culture medium. An inhibitory effect of IL 1 on insulin secretion is not observed when islets are coincubated with an inhibitor of DNA transcription (actinomycin D). This finding indicates that the inhibitory effect of IL 1 on insulin secretion requires transcription of one or more genes during the first hour of exposure of islets to IL 1. The inhibitory effect of IL 1 on insulin secretion also requires mRNA translation, because three structurally distinct inhibitors of protein synthesis (cycloheximide, anisomycin, and puromycin) prevent IL 1-induced inhibition of insulin secretion when added to islets after the 1-h exposure to IL 1. Two-dimensional gel electrophoresis of islet proteins metabolically labeled with [35S]methionine demonstrates that IL 1 augments the expression of a 65-kD (pl approximately 6.5) protein by greater than 2.5-fold. These findings indicate that biochemical events occurring within 1 h of exposure of islets to IL 1 lead to an inhibition of insulin secretion that persists for at least 17 h after the removal of IL 1. One of the early biochemical effects of IL 1 on islets is gene transcription (0-1 h), which is followed by mRNA translation (after 1 h). Our results suggest that the inhibitory effect of IL 1 on insulin secretion is mediated by protein(s) whose synthesis is induced by IL 1.

Animals↗
PubMed1990

Obsessive-compulsive disorder: case study and discussion of treatment.

A patient's own account of her obsessive-compulsive disorder is presented. She describes her distressing experiences, the impact of the disturbance on her and her family's life and her subsequent improvement using the technique of exposure and response prevention. The treatments available are discussed and the benefits of self-directed behavioural psychotherapy are reviewed. A comment from a general practitioner is appended.

Adult↗
PubMed1990

Segmental intestinal absorption of ranitidine: investigative and therapeutic implications.

The absorption of ranitidine from different segments of the intestinal tract was studied in a subject who had an anatomically divided small intestine. The results indicate that the drug is maximally absorbed from the small bowel rather than the stomach. Subsequent animal studies have shown that absorption of ranitidine in dogs is primarily duodenal followed by jejunal and ileal. The lack of gastric absorption, with predominantly small bowel absorption, may have investigational and therapeutic implications in a variety of gastrointestinal diseases.

Animals↗
PubMed1990

Variations in abundance of the molecular ion of the derivatized cocaine metabolite benzoylecgonine.

Benzoylecgonine (BEG) is the principal urinary metabolite of cocaine. For forensic drug testing, the presence of BEG in urine, suggested by a positive result for a screening immunoassay, must be confirmed by quantitative gas chromatographic/mass spectrometric (GC/MS) analysis, i.e., stable isotope dilution with a deuterium-labeled internal standard. GC/MS criteria for positivity also require appropriate relative abundances of qualifier ions, including the molecular ion, but there is little published information on the observed absolute values for qualifier ion ratios or on the variability of these values. This lack of information creates uncertainty for laboratories initiating programs testing urine for drugs of abuse as to performance criteria for run acceptability and sample positivity. We have observed substantial variability (CV = 50%) in the abundance of the molecular ion of derivatized BEG relative to the base ion in reference materials. This variability can result in a high rate of repetition of runs and generate confusion in the defense of forensic drug-testing results. Normalization of the abundance of the molecular ion of derivatized BEG to that of the deuterium-labeled internal standard in the same sample greatly reduces the apparent variability in this measurement; it is also more reliable than the absolute value of the relative abundance of the molecular ion in determining run acceptability and positive or negative results for a sample.

Analysis of Variance↗
PubMed1989

Comparison of effects of phorbol esters and glucose on protein kinase C activation and insulin secretion in pancreatic islets.

The tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) induces insulin secretion from isolated pancreatic islets, and this suggests a potential role for protein kinase C in the regulation of stimulus-secretion coupling in islets. In the present study, the hypothesis that the insulinotropic effect of TPA is mediated by activation of protein kinase C in pancreatic islets has been examined. TPA induced a gradual translocation of protein kinase C from the cytosol to a membrane-associated state which correlated with the gradual onset of insulin secretion. The pharmacologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate did not mimic this effect. TPA also induced a rapid time-dependent decline of total protein kinase C activity in islets and the appearance of a Ca2+- and phospholipid-independent protein kinase activity. Insulin secretion induced by TPA was completely suppressed (IC50 approximately 10 nM) by staurosporine, a potent protein kinase C inhibitor. Staurosporine also inhibited islet cytosolic protein kinase C activity at similar concentrations (IC50 approximately 2 nM). In addition, staurosporine partially (approximately 60%) inhibited glucose-induced insulin secretion at concentrations (IC50 approximately 10 nM) similar to those required to inhibit TPA-induced insulin secretion, suggesting that staurosporine may act at a step common to both mechanisms, possibly the activation of protein kinase C. However, stimulatory concentrations of glucose did not induce down-regulation of translocation of protein kinase C, and the inhibition of glucose-induced insulin release by staurosporine was incomplete. Significant questions therefore remain unresolved as to the possible involvement of protein kinase C in glucose-induced insulin secretion.

Alkaloids↗
PubMed1989

Secretagogue-induced diacylglycerol accumulation in isolated pancreatic islets. Mass spectrometric characterization of the fatty acyl content indicates multiple mechanisms of generation.

Diacylglycerol accumulation has been examined in secretagogue-stimulated pancreatic islets with a newly developed negative ion chemical ionization mass spectrometric method. The muscarinic agonist carbachol induces islet accumulation of diacylglycerol rich in arachidonate and stearate, and a parallel accumulation of 3H-labeled diacylglycerol occurs in carbachol-stimulated islets that had been prelabeled with [3H]glycerol. Islets so labeled do not accumulate 3H-labeled diacylglycerol in response to D-glucose, but D-glucose does induce islet accumulation of diacylglycerol by mass. This material is rich in palmitate and oleate and contains much smaller amounts of arachidonate. Neither secretagogue influences triacylglycerol labeling, and neither induces release of [3H]choline or [3H]phosphocholine from islets prelabeled with [3H]choline. These observations indicate that the diacylglycerol that accumulates in islets in response to carbachol arises from hydrolysis of glycerolipids, probably including phosphoinositides. The bulk of the diacylglycerol which accumulates in response to glucose does not arise from glycerolipid hydrolysis and must therefore reflect de novo synthesis. The endogenous diacylglycerol which accumulates in secretagogue-stimulated islets may participate in insulin secretion because exogenous diacylglycerol induces insulin secretion from islets, and an inhibitor of diacylglycerol metabolism to phosphatidic acid augments glucose-induced insulin secretion.

Animals↗
PubMed1989

Interleukin-1 inhibits glucose-induced Ca2+ uptake by islets of Langerhans.

Recombinant interleukin-1 (rIL-1) is known to inhibit glucose-induced insulin secretion by islets of Langerhans, a novel target tissue of cytokine. We have investigated whether rIL-1 pretreatment affects biochemical mechanisms known to be involved in the regulation of Ca2+ homeostasis during glucose-induced insulin secretion. Glucose-induced Ca2+ uptake by intact islets through the plasma membrane was dramatically inhibited (96%) by rIL-1 (2 nM). rIL-1, however, did not affect Ca2+ uptake by, or Ins 1,4,5-P3-induced Ca2+ efflux from, the endoplasmic reticulum in digitonin-permeabilized islets, although glucose-induced accumulation of inositol trisphosphates was inhibited (38%). These results suggest that perturbation of intracellular Ca2+ homeostasis in islets is involved in inhibition of insulin secretion by rIL-1.

Animals↗