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Biomedical subjects

S Srinivasan

Publications and source records attributed to S Srinivasan.

At least 181 records · Page 10Linked to original sources
PubMed1995

Scorpion envenomation in children in southern India.

The clinical presentation of 32 children with scorpion envenomation was analysed. The most common presentation was cold, clammy extremities with normal blood pressure. Myocarditis was present in 16 children (50%) and encephalopathy in four (12.5%). Two children died. ECG was a sensitive indicator of myocarditis which was subclinical in four children. Left ventricular dysfunction was a transient phenomenon. Myocarditis and encephalopathy were the two lethal complications observed. Serum free fatty acid levels were elevated two to three-fold in all symptomatic patients. Blood glucose levels were only mildly elevated and serum amylase levels and electrolytes were normal in all the children. No specific antivenom was given. In the absence of specific antivenom, early and active supportive treatment reduces the morbidity and mortality due to scorpion envenomation.

Animals↗
PubMed1995

Use of serum bactericidal activity in assessing previous antibiotic therapy in acute lower respiratory tract infection in children.

Bactericidal activity in sera of children with acute lower respiratory tract infection was assayed to determine its effect on the outcome of blood culture. Parental reporting of prior antibiotic therapy was also determined. 14.4% of samples without serum bactericidal activity yielded pathogens from blood culture, whereas only 2.4% of samples with serum bactericidal activity yielded pathogens. A statistically significant correlation was found between isolation of pathogens by blood culture and serum bactericidal activity. Parental reporting could not be relied upon as there was no positive correlation.

Acute Disease↗
PubMed1994

Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34.

A ligand was cloned for murine OX40, a member of the TNF receptor family, using a T cell lymphoma cDNA library. The ligand (muOX40L) is a type II membrane protein with significant identity to human gp34 (gp34), a protein whose expression on HTLV-1-infected human leukemic T cells is regulated by the tax gene. The predicted structures of muOX40L and gp34 are similar to, but more compact than, those of other ligands of the TNF family. Mapping of the muOX40L gene revealed tight linkage to gld, the FasL gene, on chromosome 1. gp34 maps to a homologous region in the human genome, 1q25. cDNAs for human OX40 receptor were cloned by cross-hybridization with muOX40, and gp34 was found to bind the expressed human receptor. Lymphoid expression of muOX40L was detected on activated T cells, with higher levels found on CD4+ rather than CD8+ cells. The cell-bound recombinant ligands are biologically active, co-stimulating T cell proliferation and cytokine production. Strong induction of IL-4 secretion by muOX40L suggests that this ligand may play a role in regulating immune responses. In addition, the HTLV-1 regulation of gp34 suggests a possible connection between virally induced pathogenesis and the OX40 system.

Amino Acid Sequence↗
PubMed1994

Homology modeling of divergent proteins.

A method is presented for homology modeling of proteins bearing weak sequence identity to proteins of known tertiary structure. To accommodate non-identical amino acids in the core region, the backbone of the structurally conserved core of the model protein is allowed to deviate from that of the template protein. We have expanded FOLDER, a distance geometry-based homology modeling method, to allow for such displacements in the structurally conserved core. Models are built by rigidly constraining the interatomic distances within a structurally conserved segment and by allowing the interatomic distances between these segments to vary by a "divergence factor". We test this method by simulating models of the beta-barrel domain D1 of CD4 and a four-helix bundle protein cytochrome b562 using the crystal structures of Bence-Jones protein and cytochrome c' as templates, respectively. In both cases, previously published structure-based sequence alignments were used for simulating models. The root-mean-square (r.m.s.) deviation of the backbone atoms in the common core between the templates and models was found to be a function of the imposed divergence factor. Our results demonstrate that this r.m.s. deviation results from the relative displacements of structurally conserved segments to accommodate the amino acid replacements in the core of the model protein. To test the integrity of the simulated structures we compared them with their respective crystal structures. The r.m.s. deviation of the backbone atoms in the core regions of the simulated models and their respective crystal structures is approximately 1.4 A. The r.m.s. deviation for all the backbone atoms in the models, including those in the structurally variable regions, which are modeled de novo, is 2.4 A for CD4 and 3.2 A for cytochrome b562 when compared with their respective X-ray structures.

Animals↗
PubMed1994

Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor.

A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated. The cytokine, designated interleukin-15 (IL-15), is produced by a wide variety of cells and tissues and shares many biological properties with IL-2. Monoclonal antibodies to the beta chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor.

Amino Acid Sequence↗
PubMed1994

Structural characteristics of CD40 ligand that determine biological function.

CD40 ligand (CD40L) is a 33 kDa type II glycoprotein which is transiently expressed on the surface of T cells following activation. The demonstration that signals delivered by CD40L are essential for the process of affinity maturation and immunoglobulin isotype switching following antigenic challenge came from the study of X-linked hyper-IgM patients whose T cells cannot express functional CD40L. While some of the biological activities of CD40L, especially on B cells, can be mimicked by monoclonal antibodies (MAb) specific for CD40, it is becoming increasingly clear that CD40L also mediates various functional effects on other cell types. Not only are there distinctions between the activities of CD40L and CD40 MAb, but the manner in which CD40 is ligated appears to play an important part in the biological outcome of signaling through this receptor. In this review, we compare and contrast the activities which can currently be ascribed to CD40L and CD40 MAb and consider the role that ligand oligomerization plays in CD40-mediated signal transduction.

Amino Acid Sequence↗
PubMed1994

In vitro and in vivo synergistic effect of isoniazid with streptomycin and clofazimine against Mycobacterium avium complex (MAC).

SETTING: Isoniazid (INH), the powerful antituberculosis drug, has also been used in regimens for treating disease caused by Mycobacterium avium complex (MAC), an important opportunistic pathogen encountered in AIDS patients. Its use for treatment of MAC disease has also been endorsed by the American Thoracic Society. However some controversy has emerged recently in medical literature, discounting its role and even implying that its use is contraindicated in chemotherapy of MAC disease. OBJECTIVE: In view of the controversy, we investigated its in vitro and in vivo activity in combination with streptomycin (SM) and clofazimine (CFM) against MAC. DESIGN: In the in vitro studies, the minimal inhibitory concentrations (MIC) of individual drugs or combinations of INH and SM as well as INH and CFM were determined in a checker-board type study by both conventional and radiometric (BACTEC) methods. In vivo studies assessed the efficacy of chemotherapy with INH alone or in combination with either SM or CFM against MAC infection in beige mice. RESULTS AND CONCLUSIONS: While MICs of INH and SM were 12.5 micrograms/ml and 6.25 micrograms/ml respectively, complete inhibition of growth was seen at 1.56 micrograms/ml with the combination of both drugs. The synergistic effect was observed both in conventional and BACTEC methods. In vivo studies demonstrated elevated activity when INH was given along with SM or CFM. Based on these observations we stress that isoniazid has still a place in chemotherapy of MAC disease, at least until other potent drugs are discovered.

AIDS-Related Opportunistic Infections↗
PubMed1994

Rapid assessment of mycobacterial growth inside macrophages and mice, using the radiometric (BACTEC) method.

SETTING: Conventional methods of determining the growth and drug susceptibility of mycobacteria either in macrophages or in vivo are time consuming and laborious. OBJECTIVE: We sought to develop a simple and rapid method for assessing growth and susceptibility of mycobacteria in macrophages and in vivo. DESIGN: The radiometric (BACTEC) method was compared with the conventional method for rapid assessment of growth and susceptibility of Mycobacterium avium complex (MAC) to clofazimine (CFM) and its two analogues (B4100 and B4101) in macrophages and in beige mice. RESULTS AND CONCLUSIONS: A linear relationship was observed between growth index (GI) readings by the BACTEC method and the colony forming unit (CFU) counts obtained by conventional plating on 7H11 agar in vitro of lysates from infected macrophages and of homogenates from the infected organs. There was also a good agreement between the two methods with respect to susceptibility of MAC to CFM and its analogues both in macrophages and in spleen. The BACTEC method, in addition to being quick and simple, was found to be more consistent. Our studies thus demonstrate that the radiometric method has potential application in rapid screening of drugs for antimycobacterial activity in macrophages and in animals besides its established value in in vitro screening.

Animals↗
PubMed1994

Experimental chemotherapy of tuberculosis using single dose treatment with isoniazid in biodegradable polymers.

In previous studies we showed that a single implant of polylactic-co-glycolic acid (PLGA) polymer as a film containing isoniazid ensured sustained release of the drug for up to 4 weeks. These studies have been extended to PLGA polymer as a rod which is retrievable. Both types of implant gave therapeutically active levels of free isoniazid in liver and urine for prolonged periods. We assessed the in vivo chemotherapeutic efficacy of the rod implant against heavy infections of virulent Mycobacterium tuberculosis in C57Bl/6 mice. The chemotherapeutic data essentially confirmed the bioavailability data. In one chemotherapeutic study, one (7%) out of 15 mice which received the isoniazid polymer implant died within 30 days of bacterial challenge, while none of those receiving daily oral treatment died. In contrast, 14 (93%) of the 15 control mice died during the same period. In a second study similar results were obtained.

Animals↗
PubMed1994

Enteric fever: a changing perspective.

All the cases of enteric fever admitted between 1988-1992 were studied. There was a gradual rise in the number of admitted cases. Central nervous system (CNS) complications like encephalopathy (14.9%), meningitis (8.8%), seizures (8.5%) and cerebellitis (3.4%) were noted more during 1991 and 1992. Other complications like myocarditis (4.6%), hepatitis (9.5%) and gastrointestinal bleeding were noted in increasing numbers during 1991-1992. Multidrug resistant (MDRT) cases were 46.3% in 1991 and 33.5% in 1992. There was a significant difference in the time taken for defervescence (a gradual rise) between the years but between the individual drugs there was no such significant difference. Deaths were noted only in 1991 and 1992 in cases of MDRT with complications. There has been an increase in resistance of S. typhi to commonly used drugs like ampicillin, chloramphenicol and cotrimoxazole. S. typhi resistant to ciprofloxacin was cultured in 2 cases each from 1990-1992. Further, the time taken for defervescence with ciprofloxacin also showed a gradual rise from 3.5 days in 1990 to 6.2 days in 1992. Nevertheless, ciprofloxacin is still the drug of choice for treatment of complicated cases of MDRT.

Anti-Bacterial Agents↗
PubMed1994

Lexical methods for managing variation in biomedical terminologies.

Access to biomedical terminologies is hampered by the high degree of variability inherent in natural language terms and in the terminologies themselves. The lexicon, lexical programs, databases, and indexes included with the 1994 release of the UMLS Knowledge Sources are designed to help users manage this variability. We describe these resources and illustrate their flexibility and usefulness in providing enhanced access to data in the UMLS Metathesaurus.

Biology↗
PubMed1993

An automated method for modeling proteins on known templates using distance geometry.

We present an automated method incorporated into a software package, FOLDER, to fold a protein sequence on a given three-dimensional (3D) template. Starting with the sequence alignment of a family of homologous proteins, tertiary structures are modeled using the known 3D structure of one member of the family as a template. Homologous interatomic distances from the template are used as constraints. For nonhomologous regions in the model protein, the lower and the upper bounds for the interatomic distances are imposed by steric constraints and the globular dimensions of the template, respectively. Distance geometry is used to embed an ensemble of structures consistent with these distance bounds. Structures are selected from this ensemble based on minimal distance error criteria, after a penalty function optimization step. These structures are then refined using energy optimization methods. The method is tested by simulating the alpha-chain of horse hemoglobin using the alpha-chain of human hemoglobin as the template and by comparing the generated models with the crystal structure of the alpha-chain of horse hemoglobin. We also test the packing efficiency of this method by reconstructing the atomic positions of the interior side chains beyond C beta atoms of a protein domain from a known 3D structure. In both test cases, models retain the template constraints and any additionally imposed constraints while the packing of the interior residues is optimized with no short contacts or bond deformations. To demonstrate the use of this method in simulating structures of proteins with nonhomologous disulfides, we construct a model of murine interleukin (IL)-4 using the NMR structure of human IL-4 as the template. The resulting geometry of the nonhomologous disulfide in the model structure for murine IL-4 is consistent with standard disulfide geometry.

Algorithms↗
PubMed1993

The relation of atherosclerotic lesions to antemortem and postmortem lipid levels: the Bogalusa Heart Study.

Although postmortem lipid levels have been used as surrogates for levels during life, it is uncertain whether atherosclerotic lesions are related similarly to antemortem and postmortem lipid values. In a sample of 23 children and young adults who had been examined for cardiovascular disease risk factors and subsequently died from violent causes, we examined the relation of (a) postmortem lipid levels to values obtained 1 to 14 years earlier, and (b) atherosclerotic lesions to antemortem and postmortem lipid levels. Postmortem levels of triglycerides and very-low-density lipoprotein cholesterol (VLDLC) were higher than levels during life, but postmortem levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLC) and high-density lipoprotein cholesterol (HDLC) were related to antemortem levels (rs > 0.40). After excluding eight persons who likely received large volumes of intravenous fluids before death, the within-person variability between antemortem and postmortem levels of LDLC and HDLC was similar to the antemortem variability. Furthermore, the relation of atherosclerotic lesions to antemortem and postmortem lipid levels differed only slightly for TC, LDLC and HDLC. In contrast, lesions in the coronary arteries showed the strongest association with antemortem VLDLC levels, but were not associated with postmortem VLDLC levels. Despite the very small number of subjects, our results suggest that if intravenous fluids are not administered before death, postmortem levels of TC, LDLC and HDLC are fairly representative of levels during life. Postmortem levels of VLDLC or triglycerides, however, should not be used as surrogates for antemortem levels.

Adolescent↗