Biomedical subjects
I Singh
Publications and source records attributed to I Singh.
Bilateral optic neuritis following multiple wasp stings.
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Mycotic aneurysms in intravenous drug abuse.
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Effect of proteolipid protein on central nervous system myelin membrane fluidity.
The effect which intrinsic (proteolipid) protein has on fluidity of central nervous system myelin membrane was measured through differences in temperature-dependent anisotropy of the lipid-soluble fluorescence probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), in multilamellar vesicles (MLV) prepared from total myelin lipids in the presence and absence of proteolipid protein. Very little difference was observed in the anisotropies of DPH incorporated into intact myelin membrane vesicles compared with MLV reconstituted from total myelin lipid plus proteolipid protein but excluding myelin basic protein. In contrast, a significant decrease (P less than 0.01) in anisotropy was observed when MLV prepared from total myelin lipids depleted of proteolipid protein were compared with vesicles containing proteolipid protein. Given the different distributions of myelin basic protein and proteolipid protein suggested by freeze-fracture, neutron and X-ray diffraction studies, and the fact that the hydrophobic DPH probe is known to distribute in the non-polar regions of lipid bilayers, we interpret the marked decrease in anisotropy when proteolipid protein is excluded from MLV to suggest that at least part of the proteolipid is distributed in the hydrocarbon region of the MLV. These findings are consistent with the earlier physical studies and recent postulations that extensive hydrophobic segments exist in proteolipid protein and that these hydrophobic segments are buried in the myelin lipid bilayer and alternate with hydrophilic extra-membrane segments.
Lignoceroyl-CoA ligase activity in rat brain microsomal fraction: topographical localization and effect of detergents and alpha-cyclodextrin.
Lignoceroyl-CoA ligase activity has been detected in microsomal fractions prepared from rat brain. The synthesis of lignoceroyl-CoA from [1-14C]lignoceric acid and CoASH by this enzyme had an absolute dependence on ATP and Mg2+; ATP could not be replaced by GTP [I. Singh, M. S. Kang, and L. Phillips (1982) Fed. Proc. 41, 1192]. The product has been characterized as lignoceroyl-CoA by the following criteria: Rf on thin-layer chromatography; incorporation of [1-14C]lignoceric acid and [3H]CoASH into the product; acid hydrolysis and identification of the radiolabel in lignoceric acid; and methanolysis and identification of the radiolabel in methyl lignocerate by thin-layer chromatography. The optimal concentrations for CoASH, ATP, and Mg2+ were about 100 microM, 10 mM, and 5 mM, respectively. Lignoceric acid, solubilized by alpha-cyclodextrin, Triton X-100, and deoxycholate, was utilized by the lignoceroyl-CoA ligase, but lignoceric acid solubilized by Triton WR-1339 was not. Topographical localization of lignoceroyl-CoA ligase in the plane of rat brain microsomal membranes was determined by the use of Triton X-100, trypsin, and mercury-Dextran, and was compared with the marker enzymes, ethanol acyltransferase and thiamine pyrophosphatase, which are known to be localized on the luminal (inner) surface of the microsomal vesicles. Mercury-Dextran (100 microM) and trypsin (trypsin:microsomes, 1:56 w/w) treatment of the microsomes inhibited the lignoceroyl-CoA ligase activity by 70 and 90% without disrupting the microsomal vesicles. Disruption of the vesicles with Triton X-100 increased the activity of both ethanol acyltransferase and thiamine pyrophosphatase by 400% but there was no increase in lignoceroyl-CoA ligase activity. These results suggest that lignoceroyl-CoA ligase is localized on the cytoplasmic surface of the microsomal vesicles.
Genotoxic effects of potassium dichromate, sodium arsenite, cobalt chloride and lead nitrate in diploid yeast.
4 metal salts, potassium dichromate, sodium arsenite, cobalt chloride and lead nitrate were tested for their genotoxic effects in Saccharomyces cerevisiae. Potassium dichromate was the most potent agent for induction of gene conversion and reverse mutation. Sodium arsenite was virtually ineffective as a convertogen but gave a positive result for reversion. Cobalt chloride was the least toxic, exhibited a convertogenic activity but was only marginally active for reverse mutation. Lead nitrate was the most toxic salt but was genetically inactive.
Vascular smooth muscle cells: a major source of the semicarbazide-sensitive amine oxidase of the rat aorta.
Several methods have been used to study the distribution of the semicarbazide-sensitive amine oxidase (SSAO) within the wall of the rat aorta. After separation of the smooth muscle-containing layers of the tunica media from the connective tissue of the tunica adventitia, much higher specific enzyme activity (measured with 1 microM benzylamine) was found in homogenates of the media than of adventitia. Similar results were obtained for MAO-A (with 1 mM 5-HT as substrate). SSAO activity was also considerably higher in homogenates of cells (predominantly smooth muscle) isolated from medial tissue by enzymatic dissociation with collagenase and elastase compared with homogenates of cells (mostly of connective tissue origin) from the adventitia. Histochemical staining resulting from SSAO activity (with benzylamine as substrate) occurred predominantly and intensely over the tunica media in rat aortic sections, although some occasional staining of adventitial sites was also observed. Staining was prevented by the SSAO inhibitors hydroxylamine (1 microM) and semicarbazide (1 mM), but not by the MAO inhibitor, clorgyline (1 mM). These results indicate that SSAO is associated predominantly, although not exclusively, with the smooth muscle cells in the rat aorta. Our findings that beta-aminopropionitrile (BAPN) is a reversible, competitive inhibitor (Ki around 2 X 10(-4)M) of SSAO, in contrast to the irreversible inhibition of the connective tissue lysyl oxidase by BAPN reported by others, provides further evidence that these enzymes are not identical.
The management of elderly patients with acute lower respiratory tract infections: a comparison of pivampicillin and amoxycillin.
In a randomized trial, the efficacy of pivampicillin (500 mg or 1 g twice daily) was compared with that of amoxycillin (250 mg or 500 mg 3-times daily) in 43 elderly hospitalized patients with bronchopneumonia (32 patients) or an acute exacerbation of chronic bronchitis (11 patients). Overall, 13 (57%) out of the 23 patients taking pivampicillin were cured, and the remaining 10 subjects were improved. In the amoxycillin group, there were 9 (45%) cures, 9 improved and 2 failures of treatment. One patient in each treatment group had mild side-effects. Forty (93%) out of the 43 patients in the study expressed a preference for an antibiotic that was given twice daily as opposed to one where 3 doses were taken each day.
Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia.
Three children from unrelated families presented in early childhood with hypoglycemia and cardiorespiratory arrests associated with fasting. Significant hepatomegaly, cardiomegaly, and hypotonia were present at the time of initial presentation. Ketones were not present in the urine at the time of hypoglycemia in any patient; however, dicarboxylic aciduria was documented in one patient at the time of the acute episode and in two patients during fasting studies. Total plasma carnitine concentration was low with an increased esterified carnitine fraction. These findings suggested a defect in mitochondrial fatty acid oxidation, and specific assays were performed for the acyl coenzyme A (CoA) dehydrogenases. These analyses showed that the activity of the long-chain acyl CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver tissue. Activities of the medium-chain, short-chain, and isovaleryl CoA dehydrogenases were not different from control values. With cultured fibroblasts, CO2 evolution from long-chain fatty acids was significantly reduced, while CO2 evolution from medium-chain and short-chain fatty acids was comparable to control values--findings consistent with a defect early in the beta-oxidation sequence. Studies of acyl CoA dehydrogenase activities in fibroblasts and leukocytes from parents of the patients showed levels of long-chain acyl CoA dehydrogenase activity intermediate between affected and control values and indicated an autosomal recessive form of inheritance of this enzymatic defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Nine years' experience in acupuncture & moxibustion therapy.
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Study on the pathogenecity of Bacillus thuringiensis var. israelensis H-14 strain against silkworm, Bombyx mori under laboratory conditions.
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The cerebrohepatorenal (Zellweger) syndrome. Increased levels and impaired degradation of very-long-chain fatty acids and their use in prenatal diagnosis.
The cerebrohepatorenal (Zellweger) syndrome is a fatal autosomal recessive disorder manifested in the neonatal period by profound hypotonia, psychomotor retardation, dysmorphic features, and an enlarged liver. In this study we demonstrate fivefold or greater increases of very-long-chain fatty acid levels, particularly hexacosanoic acid (C26:0) and hexacosenoic acid (C26:1), in plasma and cultured skin fibroblasts from 20 patients. Similar findings in cultured amniocytes from 3 of 14 women in whom the fetus was at risk of the Zellweger syndrome permitted prenatal diagnosis. Oxidation of very-long-chain fatty acids, which normally takes place in the peroxisome, was impaired in homogenates of cultured skin fibroblasts and amniocytes. This observation extends the evidence that the Zellweger syndrome belongs to the newly formulated category of peroxisomal disorders. The pattern of excess very-long-chain fatty acids differs from that demonstrated previously in patients with childhood adrenoleukodystrophy. The study of very-long-chain fatty acids provides a convenient method for the early diagnosis and prenatal detection of the Zellweger syndrome.
Influence of noise on blood coagulation.
A study conducted in rats exposed to a continuous noise of 110 decibels over a period of 3 weeks revealed development of significantly prolonged bleeding time, higher plasma fibrinogen content, and progressively shorter activated partial thromboplastin time in test animals. These changes suggest a coagulopathy induced by noise stress.
Adrenoleukodystrophy: survey of 303 cases: biochemistry, diagnosis, and therapy.
Adrenoleukodystrophy (ALD) is a genetically determined disorder associated with progressive central demyelination and adrenal cortical insufficiency. All affected persons show increased levels of saturated unbranched very-long-chain fatty acids, particularly hexacosanoate (C26:0), because of impaired capacity to degrade these acids. This degradation normally takes place in a subcellular organelle called the peroxisome, and ALD, together with Zellweger's cerebrohepatorenal syndrome, is now considered to belong to the newly formed category of peroxisomal disorders. Biochemical assays permit prenatal diagnosis, as well as identification of most heterozygotes. We have identified 303 patients with ALD in 217 kindreds. These patients show a wide phenotypic variation. Sixty percent of patients had childhood ALD and 17% adrenomyeloneuropathy, both of which are X-linked, with the gene mapped to Xq28. Neonatal ALD, a distinct entity with autosomal recessive inheritance and points of resemblance to Zellweger's syndrome, accounted for 7% of the cases. Although excess C26:0 in the brain of patients with ALD is partially of dietary origin, dietary C26:0 restriction did not produce clear benefit. Bone marrow transplant lowered the plasma C26:0 level but failed to arrest neurological progression.
Induction of gene conversion and reverse mutation by manganese sulphate and nickel sulphate in Saccharomyces cerevisiae.
Manganese sulphate and nickel sulphate were tested for the induction of gene conversion at the trp5 locus and reverse mutation at the ilv1 locus in D7 strain of Saccharomyces cerevisiae. Nickel sulphate was more toxic than manganese sulphate but did not induce any reverse mutation and gave a weak positive response for conversion. Manganese sulphate was also only slightly mutagenic and convertogenic.
Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy.
The deficient oxidation and accumulation of very-long-chain fatty acids in the Zellweger cerebro-hepato-renal syndrome (CHRS) and X chromosome-linked adrenoleukodystrophy (ALD), coupled with the observation that peroxisomes are lacking in CHRS, prompted us to investigate the subcellular localization of the catabolism of lignoceric acid (C24:0). Peroxisomal and mitochondrial-rich fractions were separated from rat liver crude mitochondria by sucrose density gradient centrifugation. Enzyme activity for the oxidation of [1-14C]palmitic acid to water-soluble acetate was 2- to 3-fold higher in the mitochondrial than in the peroxisomal-rich fraction whereas [1-14C]lignoceric acid was oxidized at a 2- to 3-fold higher rate in the peroxisomal than in the mitochondrial fraction. Moreover, unlike palmitic acid oxidation, lignoceric acid oxidation was not inhibited by potassium cyanide in either rat liver fractions or human skin cultured fibroblasts, showing that lignoceric acid is mainly and possibly exclusively oxidized in peroxisomes. We also conducted studies to clarify the striking phenotypic differences between CHRS and the childhood form of ALD. In contrast to CHRS, we found normal hepatocellular peroxisomes in the liver biopsy of a childhood ALD patient. In addition, in the presence of potassium cyanide, the oxidation of palmitic acid in cultured skin fibroblasts was inhibited by 62% in control and X chromosome-linked ALD patients compared with 88% in CHRS and neonatal ALD. This differential effect may be related to differences in peroxisomal morphology in those disorders.
Adrenoleukodystrophy: impaired oxidation of very long chain fatty acids in white blood cells, cultured skin fibroblasts, and amniocytes.
We compared the formation of 14CO2 from [I-14C]fatty acids in homogenates of cultured skin fibroblasts and white blood cells from 25 patients with adrenoleukodystrophy (ALD) and from 24 controls. The ALD group included 16 boys with childhood ALD, five men with adrenomyeloneuropathy (AMN), and two boys and two girls with neonatal ALD. The substrates were unbranched saturated fatty acids ranging in chain length from 16-26 carbons. From C24:0, the radioactive CO2 production by homogenates of ALD fibroblasts and white blood cells was 17% and 37% of control, respectively, and from C26:0 it was 17% of control in ALD fibroblasts. The CO2 evolution from palmitate (C16:0) in the ALD was identical to the control group; for C18:0, the value for ALD cells was 76% of control, and fatty acids with chain lengths between C18:0 and C24:0 gave intermediate results. Results for childhood ALD patients were similar to those for the AMN patients. More limited studies with cultured amniocytes of fetuses with childhood ALD gave results similar to those obtained with cultured skin fibroblasts, and results with neonatal ALD patients appeared to be the same as for childhood ALD and AMN. Studies of three women who were carriers for childhood ALD gave values intermediate between ALD and control. The total C26:0 levels in ALD cultured skin fibroblasts and white blood cells were 4-6 times that of control; the total C24:0 levels were increased 10-30%, whereas the C22:0 levels were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone marrow transplant in adrenoleukodystrophy.
An allogeneic bone marrow transplant (BMT) from a normal HLA identical sibling donor was performed in a 13-year-old boy with rapidly progressive adrenoleukodystrophy (ALD). Engraftment and complete hematologic recovery occurred within 4 weeks, but neurologic deterioration continued. The patient died of an adenovirus infection 141 days after BMT. ALD is characterized by abnormally high plasma levels of very long chain fatty acids (VLCFA) as a result of impaired capacity to degrade them. Ten days after BMT, the white blood cell VLCFA levels and enzyme activity became normal; after 3 months, there was progressive reduction of plasma VLCFA to levels only slightly above normal.