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Biomedical subjects

S Sinha

Publications and source records attributed to S Sinha.

At least 433 records · Page 24Linked to original sources
PubMed1988

Soluble antigen of M. leprae coupled with liposomes elicits both "early" and "late" delayed hypersensitivity skin reactions.

The soluble antigen(s) of Mycobacterium leprae was(were) coupled to liposomes and used for skin testing of leprosy patients, hoping that this mode of antigen presentation would be identical to that of integral lepromin. The liposomized antigen(s) elicited both early (24-48 hr) and late (3-4 weeks) delayed-type hypersensitivity reactions, true to the nature of lepromin, unlike the soluble antigen(s) alone which elicit(s) only the early reaction.

Antigens, Bacterial↗
PubMed1987

Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies.

231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha-tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion.

Cerebral Hemorrhage↗
PubMed1987

Inhibition of the interaction of mycobacteria with Schwann cells by antimycobacterial antibodies.

The effect of antimycobacterial serum on the uptake of Mycobacterium w by 33B rat Schwannoma cell line and rat peritoneal macrophages was studied. Incubation of Mycobacterium w with antimycobacterial serum caused a marked inhibition of its uptake by 33B cells but did not diminish its uptake by macrophages. These results suggest that the mechanism of the interaction of mycobacteria with Schwann cells differs from that with macrophages.

Animals↗
PubMed1987

On the dynamics of controlled metabolic network and cellular behaviour.

The existence of elaborate control mechanisms for the various biochemical processes inside and within living cells is responsible for the coherent behaviour observed in its spatio-temporal organisation. Stability and sensitivity are both necessary properties of living systems and these are achieved through negative and positive feedback loops as in other control systems. We have studied a three-step reaction scheme involving a negative and a positive feedback loop in the form of end-product inhibition and allosteric activation. The variety of behaviour exhibited by this system, under different conditions, includes steady state, simple limit cycle oscillations, complex oscillations and period bifurcations leading to random oscillations or chaos. The system also shows the existence of two distinct chaotic regimes under the variation of a single parameter. These results, in comparison with single biochemical control loops, show that new behaviours can be exhibited in a more complex network which are not seen in the single control loops. The results are discussed in the light of a diverse variety of cellular functions in normal and altered cells indicating the role of controlled metabolic network as the underlying basis for cellular behaviour.

Biological Evolution↗
PubMed1987

Transformation of a rat liver cell line: neoplastic phenotype and regulation of gamma glutamyl transpeptidase in tumour tissue.

A continuously dividing but non-transformed rat cell line was transformed by ras oncogenes and by aflatoxin. Transformed lines grew as solid tumours in nude mice with a short latency period. Different phenotypes were obtained from the transformed clones, and covered a wide spectrum of tumour types. While the commonest tumour type obtained was undifferentiated with unorganized spindle shaped and rounded cells, tumours with well formed trabeculae and adenomatous differentiation were also obtained. Gamma glutamyl transpeptidase (GGT), which showed an increase in transformed cells in tissue culture showed a variable expression in nude mouse tumours. While GGT positive cells were seen in all types of tumours they followed no consistent pattern and GGT negative areas were seen with a high frequency. However, in tumours showing adenomatous differentiation it was confined to the membrane on the luminal surface of the glandular structures. The different types of tumours resulting from the transformation of a single cell line provide a model of in vivo tumour development, supporting the possibility of a single stem cell origin of different types of liver neoplasms. This system also demonstrates the complexity of the regulation of GGT in tumour tissue. The influence of GGT on tumorigenesis has also been studied.

Adenoma↗
PubMed1987

A double blind comparison of a new paediatric amino acid solution in neonatal total parenteral nutrition.

All infants requiring parenteral nutrition over a continuous 13-month period were allocated to receive either Vamin or a new paediatric amino acid solution, Paedmin, as their protein source in a double blind prospective study. Those of 32 weeks gestation and less gained weight more rapidly when fed Paedmin than Vamin (P less than 0.004), but there were significant changes in liver function after 14 days nutrition. Babies of 33 weeks gestation and greater gained weight more rapidly when fed Vamin than Paedmin (P less than 0.003) but without liver function changes. There were no differences in the rate of head growth. Amino acid analysis of serum and urine showed a greater urinary loss of amino acids for a given serum concentration in babies of 32 weeks and less for both nutrition groups. The apparent benefit of Paedmin in the immature group of infants must be further evaluated and weighed against changes in liver function.

Amino Acids↗
PubMed1987

A system for transformation of rat liver cells in vitro by acute treatment with aflatoxin.

Aflatoxin B1 (AFB1) induced rat liver cancer is a well studied system of hepatocarcinogenesis. AFB1 has also been used to transform cultured rat liver derived cells in vitro. Cells in culture often have a reduced capacity to metabolise the AFB1 to its active metabolite, and often prolonged periods of exposure to the toxin have to be employed, with a long latency in the appearance of transformed cells in culture. We report here the transformation of a rat liver derived cell line by acute treatment with AFB1. An extrinsic metabolising system of quail microsomes, which convert AFB1 to its epoxide form with high efficiency, was used to activate the AFB1. A dose dependent cytotoxicity was obtained and neoplastic transformation was seen in the higher doses used. The enzyme GGT which has strong association with liver cell transformation both in vivo and in vitro was also elevated in the treated cells.

Aflatoxin B1↗
PubMed1987

Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells.

The intracellular site of cleavage of pro-von Willebrand factor subunit and the subsequent fate of the propolypeptide (von Willebrand antigen II) and of the mature von Willebrand factor (vWf) were investigated. Both the propolypeptide, which was found to be a homodimer of noncovalently linked subunits, and mature vWf were released from Weibel-Palade bodies of endothelial cells following stimulation with secretagogues. The stoichiometry of the two released proteins was essentially equimolar. This indicates that vWf and the propolypeptide were packaged into the Weibel-Palade bodies as one unit, pro-vWf, and that the proteolytic cleavage of pro-vWf is likely to be a post-Golgi event. The association of prosequences into dimers supports their hypothetical role in the multimerization process. After secretion, the two proteins were distributed differently, as based on the following observations. The propolypeptide did not associate with vWf in the culture medium, did not codistribute with vWf in the extracellular "patches of release" on stimulated endothelial cells, and was not detected in the endothelial cell extracellular matrix, which did contain vWf. Additionally, in contrast to vWf, the propolypeptide did not bind to the matrix of human foreskin fibroblasts. Since the propolypeptide does not associate with vWf and does not interact with extracellular matrices in vitro, it is highly unlikely that it would promote platelet adhesion to subendothelium in vivo.

Antibodies↗
PubMed1987

Primary structure of human neutrophil elastase.

The complete amino acid sequence of human neutrophil elastase has been determined. The protein consists of 218 amino acid residues, contains two asparagine-linked carbohydrate side chains, and is joined together by four disulfide bonds. Comparison of the sequence to other serine proteinases indicates only moderate homology with porcine pancreatic elastase (43.0%) or neutrophil cathepsin G (37.2%). In particular, many of the residues suggested to play important roles in the mechanism by which the pancreatic elastase functions are significantly changed in the neutrophil enzyme, indicating alternative types of binding with the human proteinase.

Amino Acid Sequence↗
PubMed1987

Transformation related expression of glutathione-S-transferase P in rat liver cells.

A neutral isoenzyme of glutathione transferase designated glutathione-S-transferase 7-7, but also referred to as glutathione-S-transferase P (GST-P) is absent from adult rat liver hepatocytes, but expressed at a very early stage in chemically induced in vivo hepatocarcinogenesis. The expression of this enzyme in a range of aflatoxin B1 (AFB1) associated hepatocarcinogenic systems has been examined, including in vivo induced preneoplastic and neoplastic liver tissue, cell lines derived from hepatomas, primary hepatocytes in culture and an immortalized rat liver cell line before and after transformation in vitro either by transfection with ras oncogenes or by treatment with metabolically activated AFB1. Analyses of total cytosol proteins using a polyclonal antibody to GST-P did not detect the presence of GST-P protein in cytosols from control or regenerating liver. A low level of expression was detected in the immortalized, non-transformed epithelial cell line, but a greatly induced level occurred subsequent to transformation of these cells by either of the two techniques used. High levels of the protein were detected in in vivo induced preneoplastic and neoplastic tissues, and in the cell lines derived from them. Total RNA fractions isolated from the various cells or tissues, when examined with a cDNA probe for GST-P mRNA, showed it to be absent from control and regenerating rat liver. It was present at low levels in the untransformed cell line and primary hepatocytes after 48 h in culture, but present at greatest abundance in the in vivo and in vitro transformed cells. The results indicate that the highest elevation in expression of this protein is associated with the stage of definitive malignant transformation in in vitro carcinogenesis, and this could have relevance in defining comparable events in the in vivo multistage sequence.

Aflatoxin B1↗
PubMed1987

Immunohistologic comparison between armadillo-derived leprosin and standard lepromin skin tests in leprosy patients.

A comparison was made on the in situ immunological characteristics of dermal infiltrates of early (24-hour) and late (3-4 weeks) skin reactions in leprosy patients. The skin reactions were induced by armadillo-derived leprosin coupled to liposomes and standard Dharmendra lepromin. Most lymphocytes in the early reaction induced by both antigens were positive for Leu 4, Leu 3a, OKT8 and Ia like antigens indicating thereby the presence of activated T cells. The ratio of Leu 3a/OKT8+ cells were similar. In the late reaction elicited by both antigens, the lymphocytes in the granulomas were predominantly activated T lymphocytes expressing Leu 4, Leu 3a, OKT8 and Ia like antigens. Leu 3a+ cells were scattered diffusely amidst the epithelioid cells. In contrast, the OKT8+ cells were present mainly as 'a ring' in the periphery of the granuloma. A similar ratio of Leu 3a+/OKT8+ cells was observed in these granulomas. Macrophages in the granulomas expressed Ia like antigens. These observations indicate that the immunological characteristics of dermal infiltrates in the skin reaction induced by armadillo-derived leprosin coupled to liposomes and standard Dharmendra lepromin appear to be identical.

Animals↗
PubMed1987

Interaction of mouse macrophage elastase with native and oxidized human alpha 1-proteinase inhibitor.

Native and oxidized alpha 1-proteinase inhibitor (alpha 1-PI) were compared as substrates for the metalloproteinase macrophage elastase. At substrate concentrations at which native alpha 1-PI was readily degraded by macrophage elastase, oxidized alpha 1-PI was hardly degraded at all. Incubation of macrophage elastase with oxidized alpha 1-PI before the addition of native alpha 1-PI showed that oxidized alpha 1-PI was not an inhibitor of macrophage elastase. Competition experiments with up to twofold excess oxidized alpha 1-PI did not interfere with the degradation of native alpha 1-PI by macrophage elastase. Sequence analysis of amino acids in degraded native alpha 1-PI showed that macrophage elastase attacked a single peptide bond between Pro-357 and Met-358, the latter representing the P1 reactive-site residue of alpha 1-PI. In oxidized alpha 1-PI, Met-358 was converted to methionine sulfoxide and macrophage elastase hydrolyzed the bond between Phe-352 and Leu-353. These data suggest that methionine may be the primary cleavage site for macrophage elastase and not leucine, as previously thought.

Amino Acid Sequence↗
PubMed1987

Comparative study of immunizing and delayed hypersensitivity eliciting antigens of Mycobacterium leprae, M. tuberculosis, M. vaccae, and M. bovis (BCG).

A variety of mycobacterial antigens have been associated with the delayed-type hypersensitivity (DTH) reactions in human beings and animals. An attempt has been made in the present study to identify the major antigen fractions of Mycobacterium leprae and M. tuberculosis responsible for the elicitation of DTH and to evaluate their specificity by a comparison with the antigens of two closely related mycobacteria, BCG and M. vaccae. Guinea pigs and mice were sensitized with native or heat-killed M. leprae, M. tuberculosis, M. vaccae, and BCG. Four fractions each of the latter three mycobacteria, obtained by preparatory polyacrylamide slab gel electrophoresis, were used for elicitation of DTH. Three fractions of M. leprae (MY1, MY2, and MLSE) were obtained by affinity chromatography using monoclonal antibodies. Heat-killed M. leprae and M. vaccae proved to be better sensitizers for DTH compared to their native counterparts, whereas there were no significant differences between the efficacies of autoclaved and unautoclaved M. tuberculosis or BCG. The best DTH responses were recorded with a 16-24 kD fraction of M. tuberculosis, a 20-27 kD fraction of BCG, and MLSE of M. leprae. The purified molecules of M. leprae, MY1 (12 kD) and MY2 (35 kD), did not elicit a DTH reaction. Although none of the fractions of M. tuberculosis or BCG exhibited species specificity, fraction II (15-24 kD) of M. vaccae and MLSE might be comprised of species-specific determinants.

Animals↗
PubMed1987

Detection of residual murine LPC-1 myeloma cells from bone marrow cell mixture after purging by 4-hydroperoxycyclophosphamide.

Mixtures of BALB/c bone marrow (5 X 10(6) and LPC-1 myeloma (2 X 10(6) cells have been purged in vitro with 100 microM 4-hydroperoxycyclophosphamide (4HC) for 30 min at 37 degrees C. Elimination of tumor cells was assessed by monitoring newly synthesized tumor-specific IgG 2a kappa in vitro and by reinjecting the cells subcutaneously into the hindlegs of mice. Drug-treated LPC-1 cells had no detectable tumor production and did not reproduce tumors. Untreated cells regrew as solid tumors and killed the host within 3-4 weeks. Bone marrow cell suspensions purged of tumor cells were then used to reconstitute lethally pretreated mice injected 24 h earlier with 300 mg/kg cyclophosphamide (CY). Mice injected with CY alone died within 10 days. Those reconstituted with bone marrow cells or with purged bone marrow-tumor cell mixture lived longer than 7 months. Mice reconstituted with untreated bone marrow-tumor cell suspension grew tumors, had detectable tumor-specific IgG 2a kappa in their serum, and died by day 44. These studies demonstrate that the success of myeloma cell purging can be determined by monitoring newly secreted tumor protein and that 4HC successfully eliminates malignant plasma cells in vitro without impairment of normal bone marrow stem cell functions.

Animals↗