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Biomedical subjects

V Balasubramanian

Publications and source records attributed to V Balasubramanian.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of pinaverium bromide in south Indian patients with irritable bowel syndrome.

The effect of pinaverium bromide in controlling gastrointestinal symptoms in 61 patients with irritable bowel syndrome was studied, as an open trial. Individually, there was significant relief in abdominal discomfort/pain as well as in bowel symptoms in most of the patients. Abdominal pain was reduced in 49%, stool consistency improved in 74%, straining and urgency decreased in 71% and mucus decreased in 64%. Tolerance to the drug administered was good and side-effects reported were few.

Adult↗
PubMed1998

Interferon-gamma-inhibitory oligodeoxynucleotides alter the conformation of interferon-gamma.

The aptamer mechanism of action involves the direct interaction of oligonucleotide with protein and is responsible for the biological effects of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secondary, tertiary, and quaternary structures of the proteins with which they interact using interferon-gamma and the interferon-gamma-inhibitory aptamer oligonucleotide, 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT, as a model system. CD, fluorescence spectroscopy studies, and antibody binding studies in this system demonstrate that the interferon-gamma-inhibitory aptamer oligonucleotide causes significant changes in secondary and tertiary structures of interferon-gamma. These structural changes do not result in, or resemble, protein denaturation or aggregation, and the results suggest that aptamer oligodeoxynucleotides can significantly alter the structure of the proteins they interact with.

Circular Dichroism↗
PubMed1997

Inhibition of 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation by natural colorants.

Natural colorants such as anthocyanins, betalains, carotenoids, curcuminoids and chlorophylls have been widely used in the food processing industry and in beverages. Most of these colorants constitute part of human dietary components and are considered to be harmless and non-toxic. As a part of the study of natural products to identify non-toxic cancer chemopreventive agents, we have investigated several natural colorant extracts from vegetables and fruits of daily human consumption for their cancer chemopreventive action using the short-term in vitro assay which involves inhibition of Epstein-Barr virus early antigen activation (EBV-EA) induced by phorbol esters. Our study has identified several plant extracts that show profound activity in the EBA assay.

Anticarcinogenic Agents↗
PubMed1997

Anti-tumor promoting effects of naphthoquinone derivatives on short term Epstein-Barr early antigen activation assay and in mouse skin carcinogenesis.

In continuation of our studies of natural and synthetic products as cancer chemopreventive agents, we have examined a number of naphthoquinone derivatives including monomeric, dimeric and tetrameric naphthaquinones occurring in the Diospyros and other selected plant genera. Several synthetic naphthoquinones were also evaluated. Initially these compounds were tested for in vitro anti-tumor promoting effect on Epstein-Barr virus early antigen activation produced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and thereafter in in vivo on two-stage mouse skin carcinogenesis. Our studies show some of these compounds have potent anti-tumor promoting activity.

Animals↗
PubMed1997

Tenderness variation among loin steaks from A and C maturity carcasses of heifers similar in chronological age.

Fifty-two Angus x Gelbvieh rotationally crossed virgin, ovariectomized, or single-calf heifers were slaughtered after 100 d on a high-concentrate diet. Heifers from each treatment were approximately 31, 33, or 35 mo of age, and they produced 31 A, 5 B, and 16 C maturity carcasses. Because of the small number, B maturity carcasses were not included in this study. Number of A maturity carcasses decreased as age increased. No differences (P > .05) in slaughter weight, total weight gain, dressing percentage, longissimus muscle area, or kidney fat percentage existed between carcass maturity groups, but C maturity heifers had 3.56 mm more fat (P < .01) over the longissimus muscle than A maturity heifers. Marbling scores of slight79 and small0 for A and C maturity carcasses, respectively, did not differ (P > .05). The A and C maturity heifers had similar amounts of collagen and hydroxylysyl-pyridinium crosslinks in metacarpal bone cortex and in longissimus muscle. Neither means for panel tenderness nor Warner-Bratzler shear values differed (P > .05) between maturity groups. Coefficients of variation for tenderness were slightly higher in steaks from C maturity carcasses, but CV for shear values between A and C maturity groups were similar. Because inconsistent meat tenderness is a recognized problem in the beef industry, more research on tenderness variability within maturity and marbling groups is needed. This information, in addition to pooled SEM and differences between means, should aid in finding ways to reduce beef tenderness variability.

Aging↗
PubMed1996

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis, was constructed by using a twin-pronged approach. Pulsed-field gel electrophoretic analysis enabled cleavage sites for Asn I and Dra I to be positioned on the 4.4-Mb circular chromosome, while, in parallel, clones from two cosmid libraries were ordered into contigs by means of fingerprinting and hybridization mapping. The resultant contig map was readily correlated with the physical map of the genome via the landmarked restriction sites. Over 165 genes and markers were localized on the integrated map, thus enabling comparisons with the leprosy bacillus, Mycobacterium leprae, to be undertaken. Mycobacterial genomes appear to have evolved as mosaic structures since extended segments with conserved gene order and organization are interspersed with different flanking regions. Repetitive sequences and insertion elements are highly abundant in M. tuberculosis, but the distribution of IS6110 is apparently nonrandom.

Chromosome Mapping↗
PubMed1996

Allelic exchange in Mycobacterium tuberculosis with long linear recombination substrates.

Genetic studies of Mycobacterium tuberculosis have been greatly hampered by the inability to introduce specific chromosomal mutations. Whereas the ability to perform allelic exchanges has provided a useful method of gene disruption in other organisms, in the clinically important species of mycobacteria, such as M. tuberculosis and Mycobacterium bovis, similar approaches have thus far been unsuccessful. In this communication, we report the development of a shuttle mutagenesis strategy that involves the use of long linear recombination substrates to reproducibly obtain recombinants by allelic exchange in M. tuberculosis. Long linear recombination substrates, approximately 40 to 50 kb in length, were generated by constructing libraries in the excisable cosmid vector pYUB328. The cosmid vector could be readily excised from the recombinant cosmids by digestion with PacI, a restriction endonuclease for which there exist few, if any, sites in mycobacterial genomes. A cosmid containing the mycobacterial leuD gene was isolated, and a selectable marker conferring resistance to kanamycin was inserted into the leuD gene in the recombinant cosmid by interplasmid recombination in Escherichia coli. A long linear recombination substrate containing the insertionally mutated leuD gene was generated by PacI digestion. Electroporation of this recombination substrate containing the insertionally mutated leuD allele resulted in the generation of leucine auxotrophic mutants by homologous recombination in 6% of the kanamycin-resistant transformants for both the Erdman and H37Rv strains of M. tuberculosis. The ability to perform allelic exchanges provides an important approach for investigating the biology of this pathogen as well as developing new live-cell M. tuberculosis-based vaccines.

Alleles↗
PubMed1996

Growth, carcass, and tenderness characteristics of virgin, spayed, and single-calf heifers.

Fifty-three Angus/Gelbvieh rotationally crossed heifers were slaughtered after 100 d on a high-concentrate diet. The average slaughter age for each of three different groups was 31, 33, or 35 mo, which falls within the USDA's 30- to 42-mo age range for animals producing "B" maturity carcasses. Each age group consisted of five or six heifers that had never been bred (virgin), six heifers ovariectomized at 1 yr of age (spayed), and six heifers that had weaned calves approximately 120 d postpartum (single-calf). Slaughter weight was higher (P < .05) for the virgin heifers but total weight gain in the feedlot was similar among the three groups. Single-calf heifers fed 100 d after weaning calves tended to be fatter than virgin or spayed heifers. Carcass maturity scores for the single-calf, virgin, and spayed heifers were different (P < .05); single-calf heifers produced carcasses that appeared older and spayed heifers produced carcasses that appeared younger. Maturity scores coupled with lighter and shorter metacarpal bone weights indicated single-calf heifers matured earlier (P < .05) than the other groups. Panel tenderness and Warner-Bratzler (WB) shear values of rib roasts from virgin, spayed, and single-calf heifers were determined. No differences among groups of heifers existed but scores within each group varied greatly. Marbling score was correlated (P < .05) with panel tenderness and shear force and the hydroxylysylpyridinium (HP) crosslink of muscle collagen was correlated (P < .05) with shear values. Because no significant (P < .05) correlation existed between HP in bone collagen or HP or WB shear values in muscle, we concluded that collagen maturation processes in muscle and bone occur independently. With the exception of differences in bone maturity scores, few meaningful differences in characteristics of virgin, spayed, and single-calf heifers existed, but these maturity differences could change carcass grade and influence value.

Amino Acids↗
PubMed1994

inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.

Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis and in M. bovis. The wild-type inhA gene also conferred INH and ETH resistance when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG. The InhA protein shows significant sequence conservation with the Escherichia coli enzyme EnvM, and cell-free assays indicate that it may be involved in mycolic acid biosynthesis. These results suggest that InhA is likely a primary target of action for INH and ETH.

Amino Acid Sequence↗
PubMed1994

Pathogenesis of tuberculosis: pathway to apical localization.

We have examined the published work of investigators which dealt with the pathogenesis of tuberculosis, especially the following: the infective dose, the yield of bacilli from the primary lesion and primary complex, the predominant location of the minimal lesion, the hypotheses of a vulnerable region in the lung and the specific pathways (endogenous or exogenous) by which tubercle bacilli cause disease. More knowledge of the pathogenic pathway to tuberculosis would provide clues to the development of new vaccines and drug regimens that can intervene at a specific stage in the pathogenesis. Based on the examination of the literature on pathogenesis of human tuberculosis and our findings in a guinea-pig model of experimental airborne tuberculosis, we have proposed an hypothesis which integrates the endogenous and exogenous pathways to tuberculosis. This hypothesis is based on the following observations: 1. The infectious dose is very low, usually 1-5 tubercle bacilli. 2. The first implant can occur anywhere in the lungs. 3. The cavitary lesion, characteristic of tuberculous disease, is often located in the apical regions in the lungs. 4. Whereas the primary implant can occur anywhere in the lungs, for the progression from infection to disease, the tubercle bacilli must gain access to the 'vulnerable' regions in the apex of the lungs. Our hypothesis states that in areas of the world where there is a low risk of infection with tubercle bacilli low incidence of vaccination or sensitization to environmental mycobacteria, or high incidence of high virulent isolates, the virulent tubercle bacilli reach the vulnerable region via a bacillemia during the first infection. In areas of the world where there is a high risk of infection with tubercle bacilli, high incidence of vaccination or sensitization to environmental mycobacteria or a high incidence of low virulent isolates, the tubercle bacilli reach the vulnerable region via the airway, which requires repeated episodes of infection as the probability of a first implant occurring in the vulnerable regions is low.

Animals↗
PubMed1994

Mycobacterial infection in guinea pigs.

We described published reports of the chaos which exists in research concerning laboratory animal models for assay of tuberculosis (TB) vaccines and proposed a "rational animal model" as a solution to the problem. This animal model, an aerosol challenge model in guinea pigs, was recently applied to the problem of differences in growth characteristics of sputum isolates of low and high virulence. The same model was used to investigate the protective effect of high dose BCG given aerogenically. Based on studies in the guinea pig model of experimental airborne TB, and a review of the literature on pathogenesis of human TB, we described an "integrated model" for the pathogenesis of TB, a model which includes a role for both the endogenous reactivation and the exogenous reinfection pathways. Our hypothesis is that tubercle bacilli must be able to gain access to the "vulnerable region" in the lung apex in order to survive the effects of the CMI response. In endogenous reactivation TB (virulent tubercle bacilli), this access occurs via the bloodstream. Whereas in exogenous reinfection TB, access to the vulnerable region occurs via multiple exposures via the respiratory tract. Central to our perspective is the acceptance of the evidence that during first infection with virulent organisms, tubercle bacilli enter the bloodstream via the efferent lymphatics. We believe the hypotheses we have proposed have the potential to lead to a further increase in our knowledge of these mechanisms and are a prerequisite to studies aimed at the development of new vaccines.

Animals↗
PubMed1993

BCG-induced protection in guinea pigs vaccinated and challenged via the respiratory route.

Since studies on cellular immune responses have demonstrated the role of the mucosal lymphoid system of the respiratory tract, we have studied responses obtained from the local respiratory route, compared to the systemic intradermal route, of BCG immunization. Guinea pigs vaccinated with different doses of BCG via both routes served to follow lymphoid cell proliferation, hilar lymph node and lung BCG clearance, lung granuloma formation and protection induced after virulent challenge. Results demonstrate that the aerogenic route of vaccination with BCG has no harmful side-effects for the host. In comparison with the intradermal route of vaccination, aerogenic vaccination with 10(5) BCG cfu induced higher local cellular immune responses and a substantially improved protective effect.

Administration, Inhalation↗
PubMed1992

Virulence of Mycobacterium tuberculosis for guinea pigs: a quantitative modification of the assay developed by Mitchison.

One of the more accepted methods of assay of virulence of tubercle bacilli is one developed by Mitchison in which guinea pigs were infected by the intramuscular route with 1.0 mg of tubercle bacilli freshly harvested from Lowenstein Jensen medium and in which virulence was based on a subjective score of the extent of gross disease in the animal 6 weeks after infection. Due to the practical difficulties involved in such an assay when routinely performed, the following modifications were made: frozen stocks of the culture were prepared prior to the date of infection, the inoculum was quantitated by means of colony forming units, and virulence was based on the number of tubercle bacilli recovered from the spleen of infected animals 6 weeks after infection. A significant correlation was obtained between the findings from the Mitchison assay of virulence and the modification. The latter assay is recommended for its quantitative and objective features.

Animals↗
PubMed1992

Development and characterization of a whole-cell radioligand binding assay for [125I]gp120 of HIV-1.

The binding of HIV-1 envelope glycoprotein, gp120, to the CD4 receptor is an important step in productive infection. The development of agents which interrupt this binding phenomenon should be of therapeutic interest. The present study characterizes a whole cell gp120/CD4 radioligand binding assay (radioligand binding assay) modified for use in a high volume screening format. Modifications include the use of human CD4 receptor stably expressed in a Chinese hamster ovary cell line and the gentle fixation (paraformaldehyde) of the CD4 receptor just prior to assay. Binding of [125I]gp120 to fixed CD4 was of high affinity (KD = 6 nM), saturable, reversible, and specific. The kinetics of binding were identical to those of viable (non-fixed) CD4 receptor. [125I]gp120 binding was inhibited by unlabeled recombinant gp120, soluble CD4, and the anti-CD4 monoclonals OKT4A and LEU3A. A number of compounds reported to inhibit gp120 binding and/or gp120 induced syncytium formation were also active in this assay. This modified radioligand binding assay was developed to initiate a rational and extensive screening program to assist in the identification of potential chemotherapeutic agents based on their ability to inhibit gp120 binding to host cells.

Animals↗
PubMed1992

Growth characteristics of recent sputum isolates of Mycobacterium tuberculosis in guinea pigs infected by the respiratory route.

The consideration of virulence must distinguish between infectivity and the ability to cause progressive disease once the infection is established. Several investigators have reported the presence of naturally occurring isolates which differ in virulence for guinea pigs. Isolates from south India which differed with respect to gross disease and number of bacilli recovered from spleen after an intramuscular infection also differed in their efficiencies to initiate an infection, once inhaled and retained. Also, this difference was correlated with differences in the rate of multiplication at the site of implantation and rate of multiplication at sites of hematogenous seeding, as well as the extent of hematogenous seeding. The number of metastatic foci was identified as a quantitative measure of hematogenous seeding, which was not confounded by the rate of multiplication of bacilli. Even allowing for the fourfold-reduced efficiency of low-virulence tubercle bacilli to produce a lesion, this measure clearly revealed a significantly reduced ability of the low-virulence tubercle bacilli to disseminate via the bloodstream.

Aerosols↗
PubMed1991

A guinea pig model of experimental airborne tuberculosis for evaluation of the response to chemotherapy: the effect on bacilli in the initial phase of treatment.

The purpose of this study was to develop and evaluate a guinea pig model of experimental airborne tuberculosis for its ability to assess chemotherapeutic regimens for their efficacy against virulent tubercle bacilli in vivo during the initial phase of treatment. The tissues examined included primary lung lesions and the metastatic foci in lung and spleen which result from the naturally occurring bacillaemia. The treatments examined, INH + RIF, INH + EMB, EMB + RIF, were initiated 4 weeks after infection and were continued for 8 weeks. Although minor differences were observed in the time of onset of a significant bactericidal effect or in the rate of decline in the microbial population, all three treatment combinations resulted in a significant reduction in the number of M. tuberculosis H37Rv recovered from primary lung lesions, primary lesion-free lung lobes and spleen. X-rays taken of excised inflated lung lobes showed a relationship between the degree of calcification of primary lung lesions and the number of surviving bacilli.

Animals↗
PubMed1991

Bilateral papillitis with anti-neutrophil cytoplasmic antibodies associated with coeliac disease.

A 39 year old woman with untreated coeliac disease presented with some of its complications and bilateral papillitis. She was found to have antineutrophil cytoplasmic antibodies (ANCA) in high titres. Following institution of gluten-free diet the complications resolved. The papillitis, however, persisted and needed a course of prednisolone to resolve, and a fall in the ANCA titres was noted. We believe that this is the first report of an association of coeliac disease and ANCA.

Adult↗