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A Moser

Publications and source records attributed to A Moser.

At least 109 records · Page 6Linked to original sources
PubMed1990

Search for mediators of the lipogenic effects of tumor necrosis factor: potential role for interleukin 6.

The significance of potential second messengers as mediators of the metabolic effects of tumor necrosis factor (TNF) was explored by studying their role in stimulating hepatic lipogenesis. Platelet-activating factor and prostaglandins have previously been suggested to mediate some of the toxic effects of TNF. An inhibitor of platelet-activating factor (WEB 2086) and two inhibitors of the synthesis of prostaglandins (ibuprofen and aspirin) had no effect on the ability of TNF to increase hepatic lipogenesis or serum triglyceride levels in the rat. Another inhibitor of the toxic effects of TNF, pentoxifylline, also had no effect on lipid metabolism in the rat. Catecholamines are increased after TNF administration, but alpha- and beta-adrenergic blockade did not prevent the lipogenic effects of TNF. However, interleukin 6, a cytokine whose synthesis and secretion are induced by TNF, is able to acutely stimulate hepatic lipogenesis in mice. Interleukin 6 stimulates hepatic lipogenesis by increasing hepatic citrate concentrations, the same mechanism by which TNF stimulates hepatic lipogenesis. These data suggest that interleukin 6, but not platelet-activating factor, prostaglandins, or catecholamines, could potentially mediate the lipogenic effects of TNF.

Animals↗
PubMed1990

Guanine nucleotides regulate the effect of substance P on striatal adenylate cyclase of the rat.

Substance P was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Substance P did not influence basal adenylate cyclase activity or the stimulation of the enzyme by dopamine. No influence of substance P was seen on the effects of calcium and magnesium chloride as a cofactor of adenylate cyclase. Also the inhibition of adenylate cyclase activity by the dopamine antagonist fluphenazine was not influenced by substance P. However, substance P was able to enhance cyclic AMP formation in the presence of guanosine-imidodiphosphate (Gpp(NH)p), whereas the stimulatory effect of guanosine-triphosphate (GTP) was inhibited by substance P. In our study we suggest that substance P interacts with the guanine nucleotide regulatory subunit without directly affecting D-1 dopamine receptors in the caudate-putamen of the rat.

Adenylyl Cyclases↗
PubMed1990

Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action.

To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effect of vasoactive intestinal polypeptide (VIP) on forskolin stimulated adenylate cyclase in the caudate-putamen of the rat.

Vasoactive intestinal polypeptide (VIP) was incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen (CP) tissue of the rat in order to examine the effect of the peptide on forskolin-activated adenylate cyclase in vitro. Forskolin induced an enhancement of cyclic AMP formation that was mediated by an effect on catalytic subunit and stimulatory guanine nucleotide regulatory protein (Ns). In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by dopamine and sodium fluoride but, in the absence of guanylylimidodiphosphate (guanosine 5'-(beta, y-imido)-triphosphate) VIP inhibited the forskolin-stimulation of the enzyme in a noncompetitive manner. Met-encephalin, acting on a D-2 receptor-coupled putative inhibitory guanine nucleotide regulatory protein (Ni), inhibited the adenylate cyclase activity stimulated by forskolin to a slightly greater extent than VIP. When assayed together, these inhibition effects were additive, implying that the peptide receptors are not identical. The Ni-antagonist, MnCl2 completely blocked the inhibition of met-encephalin but had no significant effect on VIP-induced inhibition. In addition, pertussis toxin did not influence the effect of VIP on forskolin-stimulation in contrast to cholera toxin which did antagonize the VIP effect via the stimulatory guanine nucleotide regulatory protein (Ns). Furthermore, specific D-1 and D-2 dopaminergic receptor antagonists alpha(+)-flupentixol and spiperone had no effect on VIP-modulated forskolin-stimulated adenylate cyclase activity. These results suggest that the neuromodulatory effect of VIP is mediated by a Ns distinct from those involved in several adenylate cyclase pools sensitive to stimulation by dopamine and VIP in the rat striatum.

Adenylyl Cyclases↗
PubMed1990

Somatostatin acts through G-proteins on dopaminergic adenylate cyclase in the caudate-putamen of the rat.

Somatostatin was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Somatostatin was able to enhance cyclic AMP formation in the presence of guanylylimidodiphosphate and guanosine-triphosphate. In contrast to this, somatostatin inhibited both dopamine and forskolin-stimulated cyclic AMP accumulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation. Somatostatin was found to antagonize these inhibitory effects of pertussis toxin and cholera toxin. The results suggest that somatostatin acts through a stimulatory as well as an inhibitory guanine nucleotide regulatory protein subtype to affect dopaminergic adenylate cyclase activity.

Adenylate Cyclase Toxin↗
PubMed1990

The effect of oxiferriscorbone on striatal adenylate cyclase of the rat.

The effects of oxiferriscorbone on basal and forskolin-stimulated activity of adenylate cyclase in membrane preparations from caudate-putamen of the rat have been studied. Oxiferriscorbone, at 30 microM, stimulated the basal activity of the enzyme, but dose-dependently inhibited forskolin-activated activity of adenylate cyclase. Pertussis toxin was found to antagonize this inhibitory effect of oxiferriscorbone. Dopamine stimulated the activity of adenylate cyclase in the striatum, as described previously. When assayed together, the stimulating effects of dopamine and oxiferriscorbone were were additive, implying that they do not act at identical sites. The D1 receptor antagonist, alpha (+)-flupentixol completely blocked the effect of dopamine but had no significant effect on oxiferriscorbone-induced stimulation. The present results suggest that interaction between oxiferriscorbone and the inhibitory guanine nucleotide subunit. However, further studies are necessary.

2,3-Diketogulonic Acid↗
PubMed1990

[Fronto-basal fractures in the child].

The particularities and the authors' management of frontobasal fractures in children are discussed on the basis of cases treated at the authors' department during the last five years. Fifteen children aged between four and 16 years (mean eight years) made up 14.5% of all frontobasal fractures. The causes of the injury were equally divided between falls from a height of at least 2 m and traffic accidents. All children except one were treated immediately after the accident. The exception was a child with an accident two and a half years before operation and two episodes of late onset meningitis. The diagnoses were mainly made with the help of high resolution computer-tomographies, which permitted a correct localization of the fractures site. The exact course of the fracture was recognized correctly in seven of eleven cases. Each case was managed in interdisciplinary fashion together with the neurosurgeon and the general surgeon. If nonoperative management was chosen, a computer-tomography about six weeks after the injury had to demonstrate the return to normal appearance of the paranasal sinus. If a dural tear was ascertained, a repair with a rhinosurgical approach was favored and, thereby, a definite closure was obtained in seven out of nine cases. One case was primarily managed by a combined rhino- and neurosurgical approach, while two cases were reoperated neurosurgically because of persistent cerebrospinal fluid leakage after the rhinosurgical repair. No other postoperative complications, such as meningitis or a third operation, were encountered. The authors believe that these favorable results were obtained because of individual management of each case by an interdisciplinary team working closely together.

Adolescent↗
PubMed1990

Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature and five case reports.

Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder, is considered to be a lethal neonatal autosomal recessive chondrodysplasia. We report five patients, three of whom survived beyond 1 year, and we summarize the findings in 21 patients from a literature review who survived beyond 1 year. In those patients that survive, there is a high association of spasticity, psychomotor retardation, growth failure, seizures, thermoregulatory instability, feeding difficulty, and recurrent otitis media and pneumonia. Three of our five patients had no radiographic evidence of vertebral body clefts, a finding which has previously been considered invariable in RCDP. Three of our patients had distinctive facies that differ from the classic Conradi-Hunermann facies.

Bone and Bones↗
PubMed1990

Small intestinal fatty acid synthesis is increased in diabetic rats.

Several studies have demonstrated that intestinal triglyceride production and secretion are increased in diabetic animals and may contribute to the hypertriglyceridemia that accompanies diabetes. There are three potential sources of fatty acids for intestinally derived triglycerides; de novo fatty acid synthesis, circulating free fatty acids, or dietarily derived fatty acids. Prior data have demonstrated that de novo cholesterol synthesis is increased in the small intestine of diabetic animals. The primary aim of the present study was to determine the effect of diabetes on small intestinal de novo fatty acid synthesis. We found that de novo fatty acid synthesis in the small intestine is increased approximately 2-fold in streptozotocin-induced diabetic rats. In contrast, hepatic fatty acid synthesis is decreased in the diabetic animals. The increase in intestinal fatty acid synthesis is observed in both the fed and fasting states. Limiting food intake by pair feeding prevents the diabetic-induced increase in small intestinal fatty acid synthesis, a finding similar to previous data on cholesterol synthesis. Thus, the increase in both small intestinal cholesterol and fatty acid synthesis is dependent on the increased food intake that accompanies poorly controlled diabetes. The present study indicates that increases in small intestinal de novo fatty acid synthesis in diabetic animals could play an important role in providing fatty acids for increased small intestinal triglyceride synthesis and secretion.

Animals↗
PubMed1990

Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats.

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1989

Genetic and phenotypic heterogeneity in disorders of peroxisome biogenesis--a complementation study involving cell lines from 19 patients.

Disorders of peroxisomal biogenesis include the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum syndrome, and hyperpipecolic acidemia. These names were assigned before the recognition of the peroxisomal defect and the distinction between phenotypes is uncertain. Recent studies have identified at least four complementation groups, and indicate the presence of at least that number of distinct genotypes. The purpose of the present study was to examine the relationship between genotype and phenotype. We studied cultured skin fibroblasts from 19 patients in whom deficiency of peroxisomes had been established. Complementation analysis was performed with the criterion of complementation being the restoration of the capacity to synthesize plasmalogens when fibroblasts from two patients were fused. Six complementation groups were identified, and consisted of one 13 member group, one two member group, and four groups comprising single cases. The phenotype of each group was examined with respect to age of survival, clinical manifestations, and biochemical alterations. The 13 member group included patients with all of the four currently designated phenotypic entities, while the most common phenotype (Zellweger syndrome) was distributed among five of the six groups. We conclude that the currently used clinical categories do not represent distinct genotypes. Apparently different genes code for a similar phenotype and one defective gene may lead to variant phenotypes. Definitive classification and understanding of these disorders await definition of the specific biochemical defect in each of the genotypes.

Adrenoleukodystrophy↗
PubMed1988

Identification of phytoestrogens in the urine of male dogs.

It is becoming increasingly apparent that dietary factors may play a role in the etiology of hormone dependent neoplasias. It has been hypothesized that estrogens play some role in the etiology of benign prostatic hyperplasia (BPH) in the canine. The presence of estrogen receptor binding activity in a fraction of canine urine purified by high performance liquid chromatography (HPLC) that did not correspond to estriol, estradiol, estrone or any of their primary metabolites was observed in the present study. We used thermospray-mass spectrometry and GC-MS to identify the phytoestrogens daidzein, equol, formononetin and genistein in HPLC purified fractions of urine obtained from male beagles. Using the same techniques we also confirmed the presence of daidzein and genistein in the commercial diet fed to these same dogs. Using the immature rat uterine cytosol estrogen receptor assay, relative binding affinities of 0.08, 1.1, less than 0.01 and 3.9% were obtained for daidzein, equol, formononetin and genistein, respectively when compared to estradiol (100%). In conclusion, phytoestrogens are present in urine of male beagles. Moreover, the commercial diet fed to these dogs contains isoflavones which can be converted to equol by intestinal microflora. These results suggest the need for investigations of phytoestrogens (e.g. equol) excreted into the urine daily and its relationship to the incidence and severity of BPH in the dog.

Animal Feed↗
PubMed1988

Biochemical abnormalities in rhizomelic chondrodysplasia punctata.

Biochemical studies with emphasis on peroxisomal functions were conducted in six patients with well-documented rhizomelic chondrodysplasia punctata (RCDP) and compared with findings in patients with Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. Other peroxisomal functions were normal, including levels of very long chain fatty acids, pipecolic acid, and bile acid intermediates, and immunoblot studies of peroxisomal acyl-CoA oxidase and bifunctional enzyme in postmortem liver. Unlike what is observed in Zellweger syndrome and neonatal ALD, catalase activity in cultured skin fibroblasts was sedimentable, indicating that peroxisome structure is not grossly deficient in RCDP. The biochemical abnormalities in RCDP were consistent and set it apart from all the other known peroxisomal disorders.

Acetyl-CoA C-Acyltransferase↗
PubMed1988

Zellweger syndrome amniocytes: morphological appearance and a simple sedimentation method for prenatal diagnosis.

Zellweger syndrome is the prototype of a growing group of genetic diseases caused by an absence or deficiency of peroxisomes. The defect causes the enzyme catalase to remain in the cytosol instead of being packaged into peroxisomes. This mislocalization can be easily detected by sedimentation analysis. Amniocytes were homogenized and then centrifuged to pellet organelles. Catalase was found to sediment with the peroxisomes in the homogenates of normal cells, but to remain in the supernatant with Zellweger syndrome amniocyte homogenates. This striking difference is unambiguous and reproducible, and provides a simple method for prenatal diagnosis. Moreover, it allows one to differentiate diseases in which peroxisomes are deficient from other peroxisomal diseases in which the organelle is intact, but one enzyme is defective. Electron microscopic observations support the biochemical determinations. Normal amniocytes contain small peroxisomes in which a weak cytochemical reaction for catalase may be demonstrated. Zellweger amniocytes appear to lack these organelles, although some cells have rare structures that might be residual or abnormal peroxisomes.

3,3'-Diaminobenzidine↗
PubMed1987

Dopamine and somatostatin modulated adenylate cyclase activity in the rat caudate-putamen following unilateral cortical ablation.

Dopamine and somatostatin-14 (SRIF) were incubated with a membrane fraction of rat caudate-putamen (CP) tissue in an adenylate cyclase assay in order to examine the D-1-receptor coupled adenylate cyclase activity 5 days and 3 weeks after unilateral ablation of the left frontal and lateral cortex. Five days after decortication the ipsilateral basal and dopamine stimulated adenylate cyclase activity was increased by about 30% compared to that of the contralateral side. Three weeks after decortication no significant difference could be seen. On either side basal and dopamine stimulated adenylate cyclase activity was not significantly decreased compared to sham operated controls. Somatostatin (10(-7) mol/l) reduced basal adenylate cyclase activity of the ipsilateral CP five days following lesioning and reduced the maximal stimulation induced by dopamine. The effects of somatostatin were most marked in the absence and at low concentrations of dopamine (10(-7)-10(-6) mol/l). The effects of somatostatin in the lesioned CP were no longer apparent three weeks following surgery. These results do not favour a presynaptic localization of D-1-receptors on cortico-striate projection fibers and suggest that somatostatin is involved in the interaction of the cortico-striate and nigro-striatal projection systems and may play a role in the regulation of D-1-receptor linked adenylate cyclase.

Adenylyl Cyclases↗