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Biomedical subjects

S Sinha

Publications and source records attributed to S Sinha.

At least 379 records · Page 21Linked to original sources
PubMed1992

Analysis of circulating immune complexes from leprosy patients for Mycobacterium leprae antigens.

Circulating immune complexes (CICs) from 31 leprosy patients (16 tuberculoid, 15 lepromatous) and 12 healthy volunteers, precipitated by 3.5% polyethylene glycol, were individually subjected to SDS-PAGE and immunoblotting using a variety of monoclonal and polyclonal antibodies against Mycobacterium leprae. A common mycobacterial antigen of an apparent molecular size of 65 kDa was identified in CICs from about 40% of the patients. No correlation was observed between the positivity for this antigen and any of the following parameters: bacterial index, M. leprae-specific antibody titers, motor nerve involvement, duration of disease or treatment. Nevertheless, patients with a relatively recent and massive infection were more frequently positive for antigen than the others.

Antibodies, Bacterial↗
PubMed1992

Detection of gene deletion in patients of Duchenne muscular dystrophy/Becker muscular dystrophy using polymerase chain reaction.

Polymerase chain reaction (PCR) was used to study the presence of gene deletion (the most prominent type of mutations) in some families afflicted by Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD). The results clearly demonstrate deletion in the central part of the DMD gene in two of the three families studied. This information can be useful for genetic counselling with particular reference to prenatal diagnosis and carrier analysis.

Base Sequence↗
PubMed1991

Conversion of the Alzheimer's beta-amyloid precursor protein (APP) Kunitz domain into a potent human neutrophil elastase inhibitor.

Site-specific mutagenesis techniques have been used to construct active site variants of the Kunitz-type protease inhibitor domain present in the Alzheimer's beta-amyloid precursor protein (APP-KD). Striking alteration of its protease inhibitory properties were obtained when the putative P1 residue, arginine, was replaced with the small hydrophobic residue valine. The altered protein was no longer inhibitory toward bovine pancreatic trypsin, human Factor XIa, mouse epidermal growth factor-binding protein, or bovine chymotrypsin, all of which are strongly inhibited by the unaltered APP-KD (Sinha, S., Dovey, H. F., Seubert, P., Ward, P. J., Blacher, R. W., Blaber, M., Bradshaw, R. A., Arici, M., Mobley, W. C., and Lieberburg, I. (1990) J. Biol. Chem. 265, 8983-8985). Instead, the P1-Val-APP-KD was a potent inhibitor of human neutrophil elastase, with a Ki = 0.8 nM, as estimated by the inhibition of the activity of human neutrophil elastase measured using a chromogenic substrate. It also inhibited the degradation of insoluble elastin by the enzyme virtually stoichiometrically. Replacement of the P1' (Ala) and P2' (Met) residues of P1-Val-MKD with the corresponding residues (Ser, Ile) from alpha 1-proteinase inhibitor resulted in an inactive protein, underscoring the mechanistic differences between the serpins from the Kunitz-type protease inhibitor family. These results confirm the importance of the P1 arginine residue of APP-KD in determining inhibitory specificity, and are also the first time that a single amino acid replacement has been shown to generate a specific potent human neutrophil elastase inhibitor from a human KD sequence.

Amino Acid Sequence↗
PubMed1991

Enhanced axial symmetry at the Fe(3+)-heme center of peroxidase by ascorbate: a basis for the ascorbate-dependent peroxidase action.

In the absence of its substrate hydrogen peroxide, peroxidase exhibits perturbations in its Fe(3+)-heme center, when incubated with ascorbic acid. The electron paramagnetic pattern sprang towards a higher g-value side, denoting a sharpening of the rhombic axial symmetry around the heme-center. The interpretation is that the ascorbate dependent peroxidase action starts with the formation of an Fe(3+)-ascorbate charge transfer complex intermediate.

Ascorbic Acid↗
PubMed1991

Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome)

Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases.

Adolescent↗
PubMed1991

Isolation of baculovirus-derived secreted and full-length beta-amyloid precursor protein.

We have expressed two forms of the Alzheimer's beta-amyloid precursor protein (beta APP), the 695-amino acid form (695 beta APP), and the 751-amino acid form (751 beta APP) in a baculovirus system. Both forms were expressed as full-length precursor, and were subsequently processed in vivo to release extracellular secreted proteins. The secreted forms were cleaved from the full-length beta APP in a manner analogous to the cleavage of beta APP during constitutive secretion in mammalian cells (Weidemann, A., König, G., Bunke, D., Fischer, P., Salbaum, J. M., Masters, C. L., Beyreuther, K. (1989) Cell 57, 115-126; Oltersdorf, T., Ward, P. J., Henriksson, T., Beattie, E. C., Neve, R., Lieberburg, I., and Fritz, L. J. (1990) J. Biol. Chem. 265, 4492-4497). High levels of expression of 20-50 mg/liter were achieved. Both full-length and secreted forms of the beta-amyloid precursor proteins were purified using a combination of ion-exchange and immunoaffinity chromatography using a monoclonal antibody directed against beta APP. The 751 beta APP-derived full-length and secreted forms, which contain the Kunitz protease inhibitor domain, were shown to be as active in the inhibition of trypsin as is mammalian-derived secreted beta APP. The availability of purified full-length beta APP from the baculovirus system will be valuable for biochemical and cell biological analyses that may elucidate the mechanism of the inappropriate processing that leads to beta-amyloid formation in Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1991

Over-expression of superoxide dismutase and lack of surface-thiols in spermatozoa: inherent defects in oligospermia.

The infertility associated with oligospermia had been suspected to be a direct consequence of the impairment in fertilizing ability of the spermatozoa rather than the presence of low sperm number per se. This study defines some of these impairments, which include an over expression of superoxide dismutase, poor superoxide anion radical generation capacity and a lack of sperm-surface thiols in oligospermia. The abnormal biochemical make-up of spermatozoa could explain their low fertilizing ability in case of oligospermia.

Cell Membrane↗
PubMed1991

Vitamin E supplementation and periventricular hemorrhage in the newborn.

In a randomized controlled trial preterm babies received 20 mg vitamin E/kg im soon after birth (day 0) and at 24 and 48 h. The mean +/- SD plasma vitamin E level on day 0 was identical in supplemented and control groups (9.98 +/- 4.88 mumol/L) and rose progressively only in supplemented babies reaching a peak of 69.2 +/- 21.36 mumol/L at 72 h. Supplemented babies had a lower incidence of intraventricular hemorrhage (IVH) diagnosed by ultrasound (9/102, 8.8%) than the control group (37/108, 34.3%; 95% CI for difference in incidence, 15-36%). In a subsequent uncontrolled study using the same vitamin E preparation, a single dose of 20 mg/kg was given soon after birth to preterm babies. The peak mean +/- SD plasma level was 32.97 +/- 13.47 mumol/L at 48 h. The incidence of IVH (16/121, 13.2%) was lower than in historical control from the randomized trial (95% CI for difference; 10.2-31.8%) in spite of the single-dose group having more clinical risk factors for IVH. We conclude that vitamin E protects against IVH in preterm babies.

Birth Weight↗