Biomedical subjects
Publications and source records attributed to A Swaroop.
We report a case of isolated prolapse of the tricuspid valve producing gross incompetence as documented by Doppler examination. This case shows that hemodynamically significant tricuspid regurgitation can occur from isolated prolapse of valvar leaflets.
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Human cDNA clones encoding the extracellular calcium-binding, acidic glycoprotein known as SPARC, osteonectin, or BM-40 were isolated from a placental cDNA library. Two polyadenylated transcripts of 2.2 and 3.0 kb were detected in human tissues and cultured cells by Northern blot analysis, and cDNAs for both transcripts were characterized. The 2133-bp sequence of the more abundant (major) transcript contains an open reading frame for 303 amino acids. The deduced polypeptide has extensive amino acid sequence identity with mouse SPARC. The larger and minor 3.0-kb cDNA has an identical coding region but utilizes a downstream polyadenylation signal. Gene localization studies have revealed a single chromosomal site at 5q31-q33 by somatic cell hybrid analysis and in situ chromosomal hybridization. Furthermore, pulsed-field gel electrophoresis of human genomic DNA cleaved with different rare-cutting restriction enzymes and hybridized with SPARC cDNA probes revealed single or double fragments of less than 50 to about 150 kb. The evidence is consistent with a single locus for SPARC in humans. The gene was found to be differentially expressed in many human tissues and in an osteogenic sarcoma, but not in other transformed cells.
The complete cDNA sequence for the Glued gene of wild-type Drosophila melanogaster contains an open reading frame encoding 1319 amino acids, which constitute the Glued polypeptide. The secondary predicted from the deduced sequence of the Glued polypeptide has extensive alpha-helical internal domains, which contain heptad-repeat sequences characteristic of an elongated coiled-coil conformation. There are striking sequence and conformation similarities between the Glued alpha-helical domains and those found in certain filamentous proteins from various organisms, particularly in muscle fibers and intermediate filaments. The possible role of the Glued polypeptide as an architectural filamentous component of Drosophila cells and tissues is discussed. Two of the five Glued exons are located in the 5' untranslated region of the cDNA. One of the introns interrupting the Glued open reading frame encodes at least two polyadenylylated transcripts, suggesting that other genes might map within the span of the Glued gene.
Generation of H2O2 by rat brain mitochondria using succinate and glycerol-1-phosphate as substrates has been demonstrated. Earlier workers were unable to detect this activity in sucrose-Tris buffer. We found that this was due to a lag in the expression of activity in sucrose medium. Using phosphate buffer (50 mM), good rates are now obtained. Generation of H2O2 by rat brain mitochondria required the presence of antimycin A and was dependent on the substrates succinate and glycerol-1-phosphate. Low rates were obtained with NAD+-linked substrates and none with choline, glutamate, and NADH. The Km and Vmax values for H2O2 generation were considerably lower than the corresponding values for the respective dehydrogenase activity, measured by dye reduction. Oxygen-radical scavengers inhibited H2O2 generation, suggesting oxygen radical involvement. Depletion of ubiquinone from mitochondria resulted in loss of H2O2 generation. Reconstitution of such depleted particles with ubiquinone restored the capacity to generate H2O2 in a concentration-dependent manner. Levels of H2O2 production were found to be maximal in cerebellum. Brain mitochondria from rabbit, hamster, mouse, and guinea pig also have the capacity to generate H2O2 on oxidation of glycerol-1-phosphate.
The Glued locus of Drosophila melanogaster is genetically defined as the functional unit which is affected by the dominant Glued mutation Gl. Genomic DNA was cloned from the region of the Glued locus, at 70C2 on chromosome 3, by using a P element insertion in the region as a molecular marker. Three genes encoding polyadenylated transcripts were detected within a 30-kilobase span of the cloned DNA. The gene nearest the P element insertion site was identified as a Glued gene on the basis of alterations in its DNA and encoded transcript associated with the Gl mutation and with reversions of Gl which eliminate the dominant effect by inactivation of the mutant allele. Expression of the wild-type Gl+ gene is temporally regulated during development; the amount of the encoded transcript is highest in the embryonic stage, decreasing in the first and second larval instars, and then increasing in the third instar and pupal stages. There is a maternal contribution of the Gl+ transcript to the embryo, which probably accounts for the maternal lethal effect of Glued mutations on early development. In situ hybridizations of Gl+ DNA to RNA in tissue sections showed that the Gl+ transcript is present in virtually all tissues of the embryo, late larva, and pupa. The general distribution of this transcript is consistent with genetic evidence indicating that the Glued locus controls a generally essential cell function (P. J. Harte and D. R. Kankel, Genetics 101:477-501, 1982). Different Glued mutations produce distinct phenotypic effects, including adults with severe visual defects, larvae lacking imaginal discs, and early lethality. These diverse mutant phenotypes are discussed in terms of quantitative changes in the Glued function. Closely adjacent to Gl+ is another gene which is transcribed in a divergent direction and expressed coordinately with Gl+ throughout Drosophila development. It remains to be determined whether this gene is also involved with the Glued function.
Exposure of rats to heat (39 +/- 1 degree C) decreased H2O2 generation in mitochondria of the liver, but not of the kidney or the heart. The effect was obtained with three substrates, succinate, glycerol 1-phosphate and choline, with a decrease to 50% in the first 2-3 days of exposure, and a further decrease on longer exposure. The dehydrogenase activity with only glycerol 1-phosphate decreased, which is indicative of the hypothyroid condition, whereas choline dehydrogenase activity remained unchanged and that of succinate dehydrogenase decreased on long exposure. The serum concentration of thyroxine decreased in heat-exposed rats. Thyroxine treatment of rats increased H2O2 generation. Hypothyroid conditions obtained by treatment with propylthiouracil or thyroidectomy caused a decrease in H2O2 generation and changes in dehydrogenase activities similar to those with heat exposure. Treatment of heat-exposed or thyroidectomized rats with thyroxine stimulated H2O2 generation by a mechanism apparently involving fresh protein synthesis. The results indicate that H2O2 generation in mitochondria of heat-exposed animals is determined by thyroid status.
The organization of the Drosophila locus Glued containing the dominant allele Gl was shown to differ from that of the normal locus by an insertion of a 9-kilobase-pair DNA segment near the 3' end of a transcribed region. The insertion causes the formation of a truncated polyadenylylated transcript of 5.1 kilobases instead of the normal 6.0 kilobases. The inserted DNA segment has the properties of a transposon and was identified by its corresponding restriction map as B104, which is a retrovirus-like transposon with direct terminal repeats. B104 appears to be oriented in Gl with the same polarity of transcription as Gl. The truncated Gl transcript terminates prematurely inside the 5' terminal repeat of B104, in the region of a putative polyadenylylation signal. We discuss the general implications of this finding for transposon- and retrovirus-induced mutagenesis and for the origin of dominant mutations.
Treatment of rats with noradrenaline stimulated H2O2 generation in liver mitochondria using succinate, choline or glycerol 1-phosphate as substrate. The dehydrogenase activity with either succinate or choline as substrate showed no change, whereas that with glycerol 1-phosphate increased. The effect was obtained with noradrenaline, but not with dihydroxyphenylserine. Phenoxybenzamine and yohimbine, but not propranolol, prevented the response to noradrenaline treatment. Phenylephrine could stimulate H2O2 generation, whereas isoprenaline had only a marginal effect. Theophylline treatment slightly decreased the generation of H2O2 in liver mitochondria, but treatment with pargyline, Ro4-1284 and dibutyryl cyclic AMP had little effect. These studies showed that noradrenaline might possibly be acting through the alpha 2-adrenergic system.
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Generation of H2O2 by rat liver mitochondria with choline, glycerol 1-phosphate and proline as substrates has been shown by using high-concentration phosphate buffer. Rates obtained under these conditions were higher and more consistent as compared with the earlier reports with high-concentration mannitol/sucrose/Tris buffer. Sulphate ions could replace phosphate indicating a requirement for a high concentration of oxygen-containing anions. H2O2 generation was dependent on the presence of native mitochondria and substrate. Maximal rates with various substrates were found to be the same as with succinate. Values of Km and Vmax for H2O2 generation were considerably less than those obtained for respective dehydrogenase activities, measured by dye reduction. Scavengers of O2-. and OH. inhibited generation of H2O2. ATP, ADP, thyronine derivatives and a number of phenolic compounds also showed very potent inhibitory effects of H2O2 generation, whereas phenyl compound had no effect. Phenolic compounds did not have any effect on mitochondrial superoxide dismutase and choline dehydrogenase activities as well as on O2-. generation by the xanthine-xanthine oxidase system. Inhibition by phenolic compounds may have potential for regulation of the intracellular concentration of H2O2, that is not considered to have a "second messenger' function.
The oxidation of NADH by mouse liver plasma membranes was shown to be accompanied by the formation of H2O2. The rate of H2O2 formation was less than one-tenth the rate of oxygen uptake and much slower than the rate of reduction of artificial electron acceptors. The optimum pH for this reaction was 7.0 and the Km value for NADH was found to be 3 X 10(-6) M. The H2O2-generating system of plasma membranes was inhibited by quinacrine and azide, thus distinguishing it from similar activities in endoplasmic reticulum and mitochondria. Both NADH and NADPH served as substrates for plasma membrane H2O2 generation. Superoxide dismutase and adriamycin inhibited the reaction. Vanadate, known to stimulate the oxidation of NADH by plasma membranes, did not increase the formation of H2O2. In view of the growing evidence that H2O2 can be involved in metabolic control, the formation of H2O2 by a plasma membrane NAD(P)H oxidase system may be pertinent to control sites at the plasma membrane.
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Byssinosis is an occupational hazard for the workers exposed to cotton dust. In this study 616 cotton textile workers were studied; out of which 149 had byssinosis; 37 (24.7%) had grade-1/2, 78 (52.7%) grade-1, 25 (16.6%) grade-2 and 9 (6.0%) of grade-3 byssinosis. Majority of the byssinotics were of age group between 36-40 years and had developed disease after 16 years of exposure. Disease was more common among smokers and severe, in whom consumption was more than 15 cigarettes/bidis per day for more than 10 years. Ventilatory function tests were markedly abnormal compared with non-byssinotic. On clinical examination and laboratory investigation (specially eosinophilia) and, radiological investigation (x-ray chest) no positive finding was detected. The high prevalence rate of the disease in this study was apparently due to poor working conditions of the workers.