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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,189 records · Page 66Linked to original sources
PubMed1996

Significance of exercise induced increase in the diastolic pressure as an indicator of severe coronary artery disease.

A total of 100 patients were studied for the diastolic blood pressure response to treadmill exercise testing. No change in the diastolic pressure or lowering of the pressure was considered normal response. Seventy-four patients had normal and 26 patients had abnormal diastolic blood pressure response. Forty patients underwent coronary angiography. Fifty-five per cent of the patients with normal diastolic pressure response had normal coronaries compared to 20% with abnormal response. Eleven per cent with normal response and 40% with an abnormal response had triple vessel disease whereas 10% with abnormal response had left main coronary artery disease. Exercise induced ST segment depression was almost equal in both groups. Hence it can be concluded that abnormal diastolic pressure response to treadmill exercise testing is a fairly good indicator of coronary artery disease irrespective of ST segment changes.

Adult↗
PubMed1996

Studies on prosthetic valve function--a transesophageal echocardiographic assessment.

Haemodynamic assessment was done by colour flow mapping and Doppler interrogation by both Transthoracic (TTE) and Transesophageal echocardiography (TEE) in 40 consecutive patients (mean age 36.6 +/- 12.35 years) with prosthetic valves. There were 30 cases of mitral (MVR) and 12 aortic (AVR) valve replacement. Major purpose of the study was to detect the sensitivity of TEE in detecting prosthetic valve malfunction particularly in comparison to TTE. Pannus was detected in 3 and 8 cases of MVR (p < 0.01) by TTE and TEE respectively; however, TEE was found to be of equal status in detecting pannus over AV (2 cases). Physiological regurgitation in MVR and AVR was detected in 13% and 25% by TTE and 20% and 33% by TEE respectively. Paravalvular leak was detected in 3 cases of MVR by TEE compared to only case by TTE. Though it is difficult to deduce any specific conclusion from this small number of patients, there is definite trend to higher sensitivity in detecting disorders with TEE specially for mitral prostheses.

Adult↗
PubMed1996

Profile of heroin addicts in Nagaland, India.

A total of 395 drug addicts from Nagaland, India during 1992-1993 were studied. Of these, 331 (83.8%) were primary abusers of heroin. Mean age of the group was 21.8 years +/- SD 3.84. Of these 5.2% were females. The majority were unmarried (92.1%) and 52% had completed 10 years of schooling. Drug-related school dropout rate was 72.8%. Unemployment was predominant (90.3%) in the group, of which most were never employed. Christianity was the main religion (90.9%) of the group. The mean age at first use of heroin was 17.6 years +/- SD 3.68. The mean duration of dependence on heroin was 4.4 years +/- SD 2.8. Heroin was injected by 80.9% subjects. Friends were the main source of introduction. Concurrent use of tranquilizers and codeine containing cough syrups was prevalent in the event of a short supply of heroin. The involvement of young, unemployed, unmarried persons in heroin addiction; widespread prevalence of the injection route and needle sharing; chronicity of heroin dependence; paucity of specialized treatment avenues and proximity to the Golden Triangle facilitating illicit traffic, have contributed to emergence of heroin addiction as a major public health problem in Nagaland.

Adolescent↗
PubMed1995

Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast.

CSBP1 and CSBP2 are human homologues of the Saccharomyces cerevisiae Hog1 mitogen-activated protein kinase which is required for growth in high osmolarity media. Expression of CSBP1, but not CSBP2, complemented a hog1 delta phenotype. A CSBP2 mutant (A34V) that complements hog1 delta was isolated and found to have approximately 3-fold lower kinase activity than the wild-type CSBP2. Further analysis revealed that both the kinase activity and tyrosine phosphorylation of CSBP1 and CSBP2 (A34V) is regulated by salt. In contrast, wild-type CSBP2 is constitutively active but dependent on the upstream kinase, Pbs2. Mutagenesis studies showed that reduction or elimination of CSBP2 kinase activity restores salt responsiveness as measured by tyrosine phosphorylation suggesting that too high a level of kinase activity can result in desensitization of the host cell and inability to grow in high salt.

Base Sequence↗
PubMed1995

A genetic approach to idiotypic vaccination for B cell lymphoma.

Idiotypic immunoglobulin expressed by a B cell tumor presents a clear tumor antigen which could be attacked by vaccination of the host. Vaccination with idiotypic protein has been shown to induce protective immunity against lymphoma, but application to patients is limited by the requirement of "personal" vaccines for each patient. A genetic approach enables V-region sequences encoding idiotypic antigen to be rescued from tumor biopsies, and to be assembled as scFv fragments. These can be expressed in bacteria to produce recombinant protein, or used directly as naked DNA vaccines. Intramuscular injection of idiotypic DNA from a mouse B cell lymphoma induces low levels of syngeneic anti-idiotypic antibody in serum. Response can be stimulated by co-injection of DNA plasmids encoding either IL-2 or GM-CSF, and T cells which proliferate in response to idiotypic IgM are generated. However, protection against tumor appears to be blocked by continuing secretion of idiotypic antigen from the persisting vaccine vector, which forms immune complexes with serum antibody. Methods for regulating the level of scFv to engage the immune system, but not to block the effector arm are being investigated. Similar control will be applicable to the cytokine vectors, which can deliver encoded cytokines designed to activate immune pathways for tumor destruction. Experience gained in lymphoma may be extended to other tumors with defined tumor antigens.

Adjuvants, Immunologic↗
PubMed1995

Role of multiple cellular proteases in the execution of programmed cell death.

A family of mammalian homologues of the Caenorhabditis elegans cell death protein Ced-3 has been recently discovered. These mammalian proteins encode novel cysteine proteases with homology to the interleukin-1 beta converting enzyme (ICE). Although several studies support a role for one or more of these proteases in mediating apoptosis, their mechanism of action is far from understood. The presence of multiple mammalian ICE-like proteases, with apparently similar apoptotic function indicates that, despite its conservation during evolution, the cell death pathway is much more complex in mammals than in the worm. In addition to ICE-like proteases, several other proteases of different cleavage specificities have been implicated in apoptosis. There is now a growing body of evidence suggesting that apoptosis involves the activation of a cascade of proteases. This article summarises the presently available evidence and discusses how multiple proteases might be required in the effector phase of cell death.

Animals↗
PubMed1995

ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1.

The ST2/T1 receptor, a homologue of the interleukin 1 receptor (IL-1R), was expressed in COS and Drosophila S2 cells as a human IgG-Fc fusion protein. While a type I IL-1RFc fusion protein bound human IL-1 in vitro, the ST2Fc fusion protein did not. Furthermore, IL-1 stimulated a synthetic interleukin-8 promoter reporter gene that was cotransfected into Jurkat cells with a full-length IL-1R type I (IL-1RI) or a chimeric receptor composed of the IL-1RI extracellular domain and ST2 intracellular domain. In contrast, IL-1 did not stimulate the interleukin-8 promoter when cotransfected with a full-length ST2 or an ST2 extracellular/IL-1R intracellular domain fusion protein. Both IL-1RI and the IL-1R/ST2R chimeric receptor also activated a receptor-associated kinase and CSBP/p38 MAP kinase. Using ST2Fc receptor, we have identified, through receptor precipitation, receptor-dot blot and surface plasmon resonance, a putative ligand of ST2 secreted from Balb/c 3T3 and human umbilical vein endothelial cells. The putative ligand was also able to stimulate CSBP/p38 MAP kinase through the ST2 receptor. These results suggest that the ST2 is not an IL-1 receptor but rather has its own cognate ligand.

3T3 Cells↗
PubMed1995

Refined solution structure of a DNA heteroduplex containing an aldehydic abasic site.

The solution structure of the DNA duplex d(C1G2C3G4A5D6A7C8G9C10C11)-d (G22C21G20C19T18A17T16G15C14G13-G12), with D indicating a deoxyribose aldehyde abasic site and numbering from 5' to 3', has been determined by the combined use of NMR and restrained molecular dynamics. The 31P and 31P-1H correlation data indicate that the backbones of these duplex DNAs are regular. One- and two-dimensional 1H NMR data indicate that the duplexes are right-handed and B-form. Conformational changes due to the presence of the abasic site extends to the base pairs adjacent to the lesion site with the local conformation of the DNA being dependent on whether the abasic site is in the alpha or beta configuration. When the sugar of the abasic site is in the beta configuration the deoxyribose is within the helix, whereas when the sugar is in the alpha configuration the deoxyribose is out of the helix. The base of residue A17 in the position opposite the abasic site is predominantly stacked in the helix in both cases. A water molecule can apparently form a hydrogen bond bridge between the beta abasic site and A17.

Aldehydes↗
PubMed1995

Detection and kinetic studies of triplex formation by oligodeoxynucleotides using real-time biomolecular interaction analysis (BIA).

Real-time biomolecular interaction analysis (BIA) has been applied to triplex formation between oligodeoxynucleotides. 5'-Biotinylated oligonucleotides were immobilised on the streptavidin-coated surface of a biosensor chip and subsequently hybridised to their complementary strand. Sequence-specific triplex formation was observed when a suitable third-strand oligopyrimidine was injected over the surface-bound duplex. In addition, a single-stranded oligonucleotide immobilised on the chip surface was able to capture a DNA duplex by triplex recognition. The presence of spermine increases the rate of association between the third strand and immobilised duplex, but at elevated spermine concentrations non-specific association is observed. A preliminary kinetic analysis of triplex formation at pH 5.2 by an 11mer third strand containing thymine, cytosine and uracil is reported. Values for the association and dissociation rate constants were determined to be (1.9 +/- 0.2) x 10(3) M-1 s-1 and (8.1 +/- 1.9) x 10(-5) s-1, respectively.

Base Sequence↗
PubMed1995

Irradiation induces up-regulation of E9 protein (CD105) in human vascular endothelial cells.

The use of MAb E-9 raised against tissue-cultured endothelial cells (EC) has shown marked heterogeneity in vascular EC lining the blood vessels of normal and tumour tissues. MAb E-9 is human EC-specific and the protein recognized by it is a homodimer with a molecular mass of 97 kDa. The E-9 protein is resistant to treatment by 3 mM sodium periodate, but is sensitive to 10% trichloroacetic acid and 70% ethanol. E-9 protein has been assigned to a new cluster, CD105, and mapped to human chromosome 9q3. It has approximately 70% homology with type-III cell-surface receptor for transforming growth factor beta (TGF-beta). Recently CD105 has been reported to be the gene in patients with hereditary haemorrhagic telangiectasia. We have examined the effects of radiation on its expression in normal human umbilical-vein endothelial cells (HUVEC) and brain-tumour-derived endothelial cells (BTEC). Irradiation induced dose- and time-dependent up-regulation in the expression of the E-9 protein on the plasma membranes of EC, and also resulted in greater increase in the expression of the E-9 protein in semi-confluent (proliferating) as compared with confluent (non-proliferating) EC. It may well be that, following radiotherapy in cancer patients, E-9 protein is also up-regulated. The presence of increased amounts of E-9 protein in EC makes it an attractive target in the control of angiogenesis, especially after radiotherapy in cancer patients. The time scale involved in the up-regulation of E-9 protein following irradiation has led us to suggest that it may be a secondary event, the primary being the production and release of mitogenic factors (such as basic fibroblast growth factor) from irradiated EC.

Antibodies, Monoclonal↗
PubMed1995

Human nuclear and mitochondrial Mt element-binding proteins to regulatory regions of the nuclear respiratory genes and to the mitochondrial promoter region.

We have found that Mt element-binding proteins (MtEBPs) with the same binding capability are present in the nuclei and mitochondria of human, bovine, and rat cells. MtEBPs purified from the human nuclei and mitochondria with Mt element-specific DNA affinity chromatography contained 4 different polypeptides, respectively. A UV-induced DNA cross-linking study showed that 47- or 55-kDa of the nuclear MtEBP recognizes Mt in the 5'-flanking region of the human cytochrome c1 gene and that both 140- and 180-kDa polypeptides of the mitochondrial (mt) MtEBPs bind Mts in the human mt promoter region. Mt MtEBPs recognized a Mt4 element-like sequence within the mt transcription factor A binding site for the heavy-strand promoter. These results suggest a MtEBP-mediated coordination mechanism between nuclear and mt genetic systems.

Animals↗
PubMed1995

Adenosine-induced coronary vasodilation during transesophageal Doppler echocardiography. Rapid and safe measurement of coronary flow reserve ratio can predict significant left anterior descending coronary stenosis.

BACKGROUND: Less invasive methods are replacing traditional invasive means of measuring coronary flow reserve (CFR). Transesophageal echocardiography (TEE) is becoming a useful tool for evaluation of coronary artery disease and has recently been used to measure CFR. This has always been done using dipyridamole, but adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole. This study was done to evaluate the hypothesis that adenosine is safe, rapid, and accurate in measuring coronary blood flow reserve by TEE Doppler. METHODS AND RESULTS: Forty-nine patients who had recently undergone angiography had a transesophageal echocardiogram with visualization of the coronary arteries and measurement of blood flow velocity in the left anterior descending coronary artery (LAD) during adenosine infusion of 0.14 mg/kg per minute. Angiograms were analyzed by quantitative coronary angiography, and significant stenosis was defined as > 70% lumenal diameter narrowing. Thirty-nine of the 49 patients did not have a significant LAD stenosis (group 1); the remainder had significant disease (group 2). Good spectral Doppler recordings of blood flow velocity in the LAD were obtained in 41 of 46 patients (89%). There were no significant differences in baseline coronary blood flow velocities between the two groups. Hyperemic to baseline flow ratios were significantly higher in patients without significant LAD stenosis for peak (2.83 +/- 1.04 versus 1.78 +/- 0.36) and mean (2.68 +/- 0.96 versus 1.75 +/- 0.39) diastolic velocity. A CFR ratio > 2.1 had a sensitivity of 86%, a specificity of 79%, a positive predictive value of 46%, and a negative predictive value of 96% for the absence of critical LAD stenosis. The infusion was well tolerated. It had to be prematurely terminated in only 3 patients (6.5%), and they were asymptomatic. No patient experienced chest pain, palpitations, or flushing. Intraobserver and interobserver variabilities were low, and reproducibility of data was good (< 4%). CONCLUSIONS: Adenosine Doppler TEE is an effective, rapid, safe, and superior means of measuring CFR ratio. This method is convenient for serial measurements of CFR as well as in clinical settings such as evaluation of syndrome X, cardiomyopathy, and aortic regurgitation.

Adenosine↗
PubMed1995

AP-1 DNA-binding activity is inhibited by selenite and selenodiglutathione.

The binding of the transcription factor AP-1 to DNA has been shown to be modulated by redox control mechanisms. Selenite and selenodiglutathione (GS-Se-SG), inhibit mammalian cell growth and are efficient oxidants of reduced thioredoxin and reduced thioredoxin reductase. Here, we report that selenite and GS-Se-SG efficiently inhibited AP-1 DNA-binding in nuclear extracts from 3B6 lymphocytes. A GS-Se-SG concentration of 0.75 microM resulted in 50% inhibition of AP-1 DNA-binding, whereas the same effect was achieved with 7.5 microM selenite. Nuclear extracts prepared from human 3B6 lymphocytes exposed for 4 h to 10 microM selenite showed a 50% reduction of AP-1 binding. These data suggest that selenite and selenodiglutathione inactivate the AP-1 factor and provide a mechanism by which selenium compounds inhibit cell growth.

Amino Acid Sequence↗