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Biomedical subjects

S Srinivasan

Publications and source records attributed to S Srinivasan.

At least 163 records · Page 9Linked to original sources
PubMed1997

Associations of oral contraceptive use with serum lipids and lipoproteins in young women: the Bogalusa Heart Study.

PURPOSE: Cross-sectional and longitudinal associations of serum lipids and lipoproteins with oral contraceptive (OC) use were examined among white and black women aged 18-27 years in 1985-86 and 1988-1991 in the Bogalusa Heart Study, a study of cardiovascular disease in a Southern community. METHODS: Analyses of covariance. RESULTS: In 1985-1986, white OC users had significantly (p < 0.05) higher adjusted mean total and low density lipoprotein (LDL) cholesterols, and lower high density lipoprotein (HDL) cholesterol compared with nonusers; black OC users had higher triglycerides and LDL cholesterol, and lower HDL cholesterol. In 1988-1991, white OC users had higher total cholesterol, triglycerides, and LDL cholesterol, while black OC users had higher triglycerides. OC use was unrelated to mean HDL cholesterol levels in 1988-1991; however, a lower percentage of white OC users than nonusers in 1988-1991 had HDL cholesterol levels < 35 mg/dl. Longitudinally, white OC nonusers at baseline who used OCs at follow-up had significant increases from baseline levels in total cholesterol, triglycerides, and very low density lipoprotein (VLDL) and LDL cholesterols; black women showed an increase only in LDL cholesterol. White women who stopped using OCs by follow-up had a decrease in VLDL and LDL cholesterols, and an increase in HDL cholesterol. White OC users at both exams also had a significant increase in HDL cholesterol, whereas women who began using OCs by follow-up did not. CONCLUSIONS: The unfavorable lipid profile associated with OC use was not apparent upon discontinued use. Lack of an adverse effect of OC use on HDL cholesterol at follow-up may be the result of changing formulations, and requires further examination.

Adolescent↗
PubMed1997

Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells.

BACKGROUND & AIMS: The pathophysiology of hypergastrinemia in Helicobacter pylori infection is undefined, but the infected antrum shows a marked inflammatory response with local production of cytokines. Hypergastrinemia and inflammatory infiltrate clear with successful eradication. The aim of this study was to examine whether the cytokines tumor necrosis factor alpha or interleukin 8 (IL-8), which are produced in the gastric mucosa of patients with H. pylori-induced peptic disease or H. pylori products, can stimulate gastrin release from isolated cultured canine G cells. METHODS: Canine G cells were isolated by collagenase digestion, enriched by centrifugal elutriation, incubated with cytokines, bacterial components, or both, and gastrin release was measured by radioimmunoassay. RESULTS: IL-8 (1 and 10 nmol/L) stimulated gastrin release by 34% +/- 13% and 43% +/- 23% (P < 0.05) above basal, respectively. H. pylori sonicates, water extract preparations, and lipopolysaccharide had no stimulatory actions, but the sonicates from two of four strains potentiated the effects of IL-8, leading to maximal gastrin release of 230% +/- 130% and 232% +/- 33% above basal, respectively (P < 0.05). CONCLUSIONS: IL-8 stimulated gastrin release from isolated G cells, and the effect was potentiated by H. pylori products. The interaction of cytokines and H. pylori may contribute to the hypergastrinemia seen in vivo.

Animals↗
PubMed1997

Sequence-dependent conformational sampling using a database of phi(i)+1 and psi(i) angles for predicting polypeptide backbone conformations.

A method to sample the conformational space of polypeptides in a sequence-dependent manner was developed and applied to predict backbone conformations of polypeptides. The method uses a database of phi(i)+1 and psi(i) angles sorted into pools corresponding to 400 dimers of naturally occurring amino acids. The pools of phi(i)+1 and psi(i) angles for dimers were further dynamically divided into sub-pools based on the homology of two amino acids on either side of the dimer. Typically, 10000 backbone conformations for every overlapping hexamer of a polypeptide are generated by randomly assigning a set of phi(i)+1 and psi(i) angles for every dimer from the sorted sub-pool for that dimer. The conformational preference for each hexamer is evaluated by superimposing each simulated conformation on a set of pre-selected hexameric templates which are derived from high-resolution crystal structures representing helical, extended and turn conformations. A model is classified as compatible with a template if it has a backbone root mean square deviation of < or = 1 A to that template. The template that has the highest population of compatible models for a given hexamer is interpreted as the most probable conformation of that hexamer. The method was applied to predict backbone conformations that arise primarily from local interactions and the predictions were compared with experimental results. Results from simulations on structurally characterized polypeptides in helical, extended, turn and mixed alphabeta conformations are presented to demonstrate the predictive powers of the method. It is also demonstrated how models of overlapping hexamers can be assembled to obtain near-native models for the entire sequence.

Databases, Factual↗
PubMed1997

Poliomyelitis trends in Pondicherry, south India, 1989-91.

STUDY OBJECTIVES: To assess the poliomyelitis trend, including study of the epidemiological features, and to correlate this with the immunisation coverage of infants. DESIGN: Three annual lameness surveys in children aged 0-60 months employing cluster sampling methods and a series of five cross sectional surveys of immunisation coverage in children aged 12-23 months of age were undertaken. SETTING: Pondicherry, India, 1988-92. SUBJECTS: More than 10,000 children in the age group of 0-60 months took part in the three annual lameness surveys and samples of 210 children aged 12-23 months were covered each year in immunisation coverage surveys. MEASUREMENTS AND MAIN RESULTS: Altogether 50 of 11,461, 24 of 10,093, and 17 of 11,218 children surveyed during 1989, 1990, and 1991 respectively had become lame as a result of poliomyelitis, giving prevalences of 4.4, 2.4, and 1.5 per 1000 children for the three surveys. The corrected prevalences of poliomyelitis were 5.9, 3.2, and 2.0 per 1000 children during 1989, 1990, and 1991 respectively. The proportion of cases aged up to 36 months fell from 48% in 1989 to 12.5% in 1990 and 6% in 1991. The age at onset was less than 1 year in most. The median age at onset was 10.7 months. About 54% of the affected children had received three doses of oral poliomyelitis vaccine (OPV) before the onset of paralysis. In 1988 immunisation coverage for the third dose of OPV was 91% and in 1992 it was 97.6%. The drop out rate for the first versus the third dose of OPV fell from 6.3 in 1988 to 1.9% in 1992. CONCLUSION: Three successive annual lameness surveys showed that poliomyelitis was declining between 1989 and 1991. Five immunisation coverage surveys conducted from 1988 to 1992 showed high initial coverage followed by an improvement in the form of almost universal coverage for OPV.

Age Factors↗
PubMed1997

Eradication of H. pylori in a developing country: comparison of lansoprazole versus omeprazole with norfloxacin, in a dual-therapy study.

OBJECTIVES: Lansoprazole, a newer benzimidazole, is more potent than omeprazole in its anti-Helicobacter pylori effect in vitro. The present study was aimed at assessing its efficacy in a developing country. METHODS: Fifty patients were randomized to receive either lansoprazole or omeprazole, with norfloxacin for 2 wk; the ulcer healing rates, H. pylori eradication rates, and recurrence rates were compared over a 6-month period. RESULTS: Both lansoprazole and omeprazole were equally effective in inducing healing of ulcer (96.1 vs 95.5%, p > 0.05) and eradicating H. pylori (76.9 vs 63.9%, p > 0.05), with very low recurrence rates over a 6-month follow-up period. CONCLUSIONS: Either lansoprazole or omeprazole combined with norfloxacin is effective in eradicating H. pylori in a high percentage of cases of duodenal ulcer, with little difference between the two proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Disruption of three phosphatidylinositol-polyphosphate 5-phosphatase genes from Saccharomyces cerevisiae results in pleiotropic abnormalities of vacuole morphology, cell shape, and osmohomeostasis.

As a result of the genome sequencing project in Saccharomyces cerevisiae, three open reading frames were found in the yeast genome that contain sequences with strong homology to all the domains conserved among the four mammalian phosphatidylinositol-phosphate 5-phosphatases: inpp5bp, ocrl1p, synaptojanin, and ship. In addition, all three yeast gene products shared with synaptojanin regions of homology to the SAC1 gene of yeast. Disruption of each of these genes singly and in pairs produced mutant strains that were viable but demonstrated variable phenotypes of abnormal vacuolar and plasma membrane morphology as well as increased sensitivity to osmotic stress. Total phosphatidylinositol-(4,5)-bisphosphate 5-phosphatase activity was reduced to varying degrees in each of the strains. No defect in carboxypeptidase Y sorting was seen in a processing and targeting assay. Abnormal actin cytoskeleton morphology was present in some of the strains carrying mutations in two of the genes.

Amino Acid Sequence↗
PubMed1996

A new DSP-based multichannel EMG acquisition and analysis system.

This paper describes the design of a digital signal processor based system for a personal computer for EMG data acquisition to monitor muscle activity during gait and to estimate the power spectrum of the acquired data under normal and pathological conditions. It also gives the hardware details of the velocity meter which is used to monitor the muscle activity with speed of walking. Software has been developed for system initialization, data acquisition, processing of acquired data, and data display for five channels. The developed equipment will be useful to clinicians for enhancing the understanding of a patient's dynamic performance.

Analog-Digital Conversion↗
PubMed1995

Biochemical characterization of related microtubule proteins in Drosophila melanogaster and adult rat brain.

We describe the biochemical characteristics of three proteins isolated from Drosophila embryos and the rat brain. We refer to these proteins as DMAPs (Drosophila microtubule-associated proteins) since they were identified by monoclonal antibodies generated against microtubule protein (MTP) purified from Drosophila melanogaster embryos. DMAP-45 is a 45 kDa protein that binds microtubules in an ATP dependent manner. Preliminary biochemical evidence suggests that DMAP-45 may be an actin-related protein. DMAP-55 is a 55 kDa protein and based on its molecular weight and isoelectric point, may be a novel isoform of tubulin. DMAP-66 is a 66 kDa protein that binds strongly to microtubules in vitro and has multiple isoforms. Analyses of proteins in rat brain tissue extracts and purified rat brain MTP identified proteins of similar molecular weight and isoelectric points and are designated DMAP-45R, -55R and -66R. The presence of proteins with common biochemical properties in these widely divergent animal species suggests that they are related proteins.

Adenosine Triphosphate↗
PubMed1995

Antibodies directed against microtubule proteins from Drosophila melanogaster cross react with similar proteins in the rat brain.

Monoclonal antibodies (Mabs) were used to delineate the localization of three proteins in rat cerebral cortex, hippocampus and cerebellum. The proteins were identified by Mabs directed against Drosophila melanogaster microtubule proteins (MTP). We have provisionally designated these proteins as Drosophila microtubule-associated proteins (DMAPs). The corresponding monoclonal antibodies are designated Mab DMAP-45, -55 and -66 indicating the molecular weights of each protein. All three Mabs cross-react with proteins of similar molecular weights in the rat brain. Correspondingly, these rat proteins are designated DMAPRs. DMAP-45 binds microtubules in an ATP-dependent manner. The molecular weight and subcellular localization of DMAP-45R differs significantly from previously described mammalian brain MAPs suggesting that it represents a novel MAP. Biochemical evidence suggests it may be an actin-related protein. DMAP-55R co-purifies stoichiometrically with rat brain microtubules and appears to be a previously undescribed isoform of tubulin. DMAP-66, which co-purifies stoichiometrically with Drosophila microtubules, does not do so in the rat brain. Immunohistochemistry performed with all three Mabs revealed a general pattern of staining of cell somata and dendrites in the cortex, hippocampus and cerebellum. Mab DMAP-55 also stained axons. In cerebral cortex all three Mabs preferentially, but not exclusively, stained layer V neuronal somata and dendrites. In hippocampus, Mabs DMAP-45 and -66 stained cell somata and dendrites in all hippocampal subfields, particularly the subiculum and CA3, whereas Mab DMAP-55 was most prevalent in mossy fibers. All three Mabs stain Purkinje cells in cerebellum with additional staining of cerebellar basket cells and Golgi cells observed with Mab DMAP-66.

Animals↗
PubMed1995

The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo. We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro. This novel protein, FXR2, is very similar to FMR1 (60% identity). FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm. The FXR2 gene is located on human chromosome 17 at 17p13.1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1. Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers. FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome.

Amino Acid Sequence↗
PubMed1995

Fumarate reductase: a target for therapeutic intervention against Helicobacter pylori.

The potential of fumarate reductase as a therapeutic target against the human pathogen Helicobacter pylori was investigated by studying the cytotoxicity of morantel, oxantel, and thiabendazole, known to inhibit the enzyme in parasitic worms. Nuclear magnetic resonance spectroscopy was employed to investigate the effects of the inhibitors on the fumarate reductase activity of laboratory-adapted and wild-type bacterial strains. Production of succinate from fumarate in H. pylori cells was inhibited by morantel, oxantel, and thiabendazole. Cell growth and viability techniques were used to examine the bacteriostatic and bactericidal effects of the three anthelmintics. Each of the antiparasites arrested growth and produced cell death in liquid cultures, although the minimal inhibitory and bactericidal concentrations of these compounds are such that they would not be of therapeutic use. The strength of the effects as measured by minimal inhibitory and bactericidal concentrations was oxantel > thiabendazole > morantel. The findings suggested that fumarate reductase is an essential component of the metabolism of H. pylori and as such constitutes a possible target for therapeutic intervention in the treatment of the bacterium.

Aconitate Hydratase↗
PubMed1995

FXR1, an autosomal homolog of the fragile X mental retardation gene.

Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1.

Amino Acid Sequence↗
PubMed1995

Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins.

Hek is a member of the eph subfamily of receptor tyrosine kinases whose members include elk, hek2, sek, eph and eck among others. Using a soluble form of hek consisting of the extracellular region of the receptor fused to the Fc domain of human IgG1 and an expression cloning strategy, we have isolated two different but related cDNAs from the human T-lymphoma line HSB-2 that encode ligands for hek. The cDNAs encode proteins of 238 and 201 amino acids (44% amino acid identity) that are anchored to the membrane by glycosylphosphatidylinositol (GPI)-linkage. The proteins encoded by these cDNAs are bound by hek with affinity constants of 2 x 10(8) M-1. These proteins also bind the elk tyrosine kinase receptor. These cDNAs are related to other cDNAs that we have recently isolated from a human placental library that encode ligands for both hek and elk and define an emerging family of ligands for eph-related kinases (LERKs).

Amino Acid Sequence↗
PubMed1995

Modeling protein loops using a phi i + 1, psi i dimer database.

We present an automated method for modeling backbones of protein loops. The method samples a database of phi i + 1 and psi i angles constructed from a nonredundant version of the Protein Data Bank (PDB). The dihedral angles phi i + 1 and psi i completely define the backbone conformation of a dimer when standard bond lengths, bond angles, and a trans planar peptide configuration are used. For the 400 possible dimers resulting from 20 natural amino acids, a list of allowed phi i + 1, psi i pairs for each dimer is created by pooling all such pairs from the loop segments of each protein in the nonredundant version of the PDB. Starting from the N-terminus of the loop sequence, conformations are generated by assigning randomly selected pairs of phi i + 1, psi i for each dimer from the respective pool using standard bond lengths, bond angles, and a trans peptide configuration. We use this database to simulate protein loops of lengths varying from 5 to 11 amino acids in five proteins of known three-dimensional structures. Typically, 10,000-50,000 models are simulated for each protein loop and are evaluated for stereochemical consistency. Depending on the length and sequence of a given loop, 50-80% of the models generated have no stereochemical strain in the backbone atoms. We demonstrate that, when simulated loops are extended to include flanking residues from homologous segments, only very few loops from an ensemble of sterically allowed conformations orient the flanking segments consistent with the protein topology. The presence of near-native backbone conformations for loops from five different proteins suggests the completeness of the dimeric database for use in modeling loops of homologous proteins. Here, we take advantage of this observation to design a method that filters near-native loop conformations from an ensemble of sterically allowed conformations. We demonstrate that our method eliminates the need for a loop-closure algorithm and hence allows for the use of topological constraints of the homologous proteins or disulfide constraints to filter near-native loop conformations.

Amino Acid Sequence↗
PubMed1995

Cardiac involvement and scorpion envenomation in children.

Cardiac complications of 32 children with scorpion envenomation, during a 1-year period from August 1990 to August 1991 were studied. Sixteen children (50 per cent) were diagnosed as having myocarditis; of these in four children the presentation was subclinical. ECG changes were seen in 63 per cent of children envenomed and was a sensitive indicator of myocarditis. Sixty-nine per cent of children with myocarditis had left ventricular dysfunction as shown by echocardiography. Though statistically not significant, there was a correlation between prolonged QTc and LV dysfunction, which needs to be studied further. In those children who came for follow-up, the left ventricular function reversed to normal.

Animals↗