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Biomedical subjects

S Sinha

Publications and source records attributed to S Sinha.

At least 397 records · Page 22Linked to original sources
PubMed1991

Unintegrated human immunodeficiency virus type 1 DNA in chronically infected cell lines is not correlated with surface CD4 expression.

Using a polymerase chain reaction-based assay on total cell lysates, we have detected unintegrated human immunodeficiency virus type 1 (HIV-1) DNA in chronically infected T-lymphocytic (ACH-2, J1) and promyelocytic (OM-10.1) cell lines. Treatment with 3'-azido-3'-deoxythymidine (AZT) or soluble CD4 inhibited accumulation of unintegrated viral DNA about 10-fold within 72 h; removal of AZT permitted recovery to pretreatment levels within 72 h. Our results indicate that unintegrated HIV-1 DNA is unstable in these cell lines and originates from a continuous process of reinfection. OM-10.1 cells had relatively high levels of surface CD4 by flow cytometry and high levels of unintegrated viral DNA by polymerase chain reaction. ACH-2 cells had very low levels of both surface CD4 and unintegrated viral DNA. However, J1 cells, with surface CD4 below the level of detection of flow cytometry had a high level of unintegrated viral DNA similar to that of OM-10.1 cells. This implies that the number of CD4 receptors is not rate limiting for reinfection.

CD4 Antigens↗
PubMed1991

Association of mycobacterial-specific and Mycobacterium leprae specific antibody levels with clinical activity in tuberculoid leprosy: a comparative study of three serological enzyme-immunoassays.

The ELISAs for polyclonal antibodies against Mycobacterium leprae (ML-ELISA) and specific antibodies against epitopes on 35 kDa protein (SACT-ELISA) and phenolic glycolipid I (PG-ELISA) of M. leprae were evaluated comparatively in a group of 88 tuberculoid leprosy patients. The overall seropositivity rate with a battery of 3 tests (68%) was not significantly higher than that obtained with ML-ELISA alone (55%) for IgG class of antibodies. Seropositivities for SACT-ELISA and PG-ELISA were, respectively, 38% and 26%. ML-ELISA for IgM class of antibodies was least sensitive, showing only 8% positivity. A significant correlation was noted between individual values of the three assays, but the positive proportions overlapped maximally in the case of ML-ELISA (IgG) and SACT-ELISA. Further, positivity for the latter two assays, particularly SACT-ELISA, showed significant associations with the extent of 'active' (largely untreated) infection. Immunoblotting revealed that the main antibody response was directed towards M. leprae antigens in the molecular weight range of 20-40 kDa and the densitometry results of this zone correlated significantly with corresponding SACT-ELISA and ML-ELISA (IgG) values.

Antibodies, Bacterial↗
PubMed1991

On the value of sequential serology with a Mycobacterium leprae-specific antibody competition ELISA in monitoring leprosy chemotherapy.

The Mycobacterium leprae-specific antibody assays--a serum antibody competition test (SACT-ELISA) for the epitope on the 35-kDa protein, and an enzyme immunoassay for the disaccharide epitope of phenolic glycolipid-I (PGDS-ELISA)--were evaluated as tools for the serological monitoring of chemotherapy in 20 lepromatous and 6 tuberculoid leprosy patients. In addition to estimates for M. leprae-specific antibodies, assessments of the bacterial index (BI) and clinical activity of the disease were also carried out prospectively in these patients on two to four occasions over a period of 19 months. In most cases, a decline in the BI, clinical scores, and antibody levels was observed during the course of treatment. The relative rate of decline was steepest and least variable with the SACT-ELISA, followed by the PGDS-ELISA and the BI. In some patients who showed a static or even an increased BI, despite marked clinical improvement, the antibody levels decreased. These data indicate that, unlike the BI, there is a greater dependence of specific antibody levels on the viability of M. leprae. This, combined with the fact that antibody titers would reflect the antigen load in the whole body, makes M. leprae-specific serology a promising tool for monitoring chemotherapy in leprosy patients.

Antibodies, Bacterial↗
PubMed1991

Massive tuberculous mesenteric lymphadenopathy.

Abdominal tuberculosis accounts for 10% of all tuberculosis seen in Papua New Guinea. Nodal tuberculosis is usually associated with intestinal or peritoneal lesions. A case of massive tuberculous mesenteric lymphadenopathy with recurrent intestinal obstruction is presented here with a review of the relevant literature.

Adult↗
PubMed1990

The protease inhibitory properties of the Alzheimer's beta-amyloid precursor protein.

We have expressed the 57-amino acid Kunitz domain of the Alzheimer's beta-amyloid precursor protein (APP751) as a bacterial fusion protein. The protease inhibitory properties of the purified fusion protein, BX9, were virtually identical in all respects tested to those of purified secreted APP751. Both proteins strongly inhibited pancreatic trypsin (Kis = 0.2 and 0.3 nM) and less well epidermal growth factor-binding protein (Kis = 1 and 3.5 nM), alpha-chymotrypsin (Kis = 3 and 6 nM), and the gamma-subunit of nerve growth factor (Kis = 8 and 9 M). Neither protein appreciably inhibited plasma and pancreatic kallikreins, thrombin, lung tryptase, neutrophil elastase, or cathepsin G. The remarkable similarity of the protease inhibitory profile of BX9 to that of secreted APP751 suggests that proper intramolecular disulfide bond formation has occurred in the bacterial fusion protein and leads to the conclusion that the amyloid precursor protein Kunitz domain is a relatively specific inhibitor of only a few trypsin-like arginine esterases.

Amino Acid Sequence↗
PubMed1990

Survey of adolescents with severe intellectual handicap.

A diagnostic survey was undertaken of children aged 11 to 19 years in Tameside with severe learning difficulties (intelligence quotient less than or equal to 50). Eighty-two children were identified and their medical records reviewed. A specific diagnosis for the retardation was documented in 25 (30%) of the children, 18 of whom had Down's syndrome. A probable aetiology or a disorder of unknown aetiology had been identified in a further 21 (26%) children. To confirm the existing diagnosis, identify new diagnoses, and offer genetic counselling, the parents of 63 children were offered detailed reassessment of their child. Fifty three children were reviewed, and a specific disorder identified in 25 out of 31 previously undiagnosed children. The most frequent diagnoses made were fragile X syndrome and Rett's syndrome. On completion of the survey, 61 of the 82 children (74%) had a specific diagnosis or probable aetiology identified, 12 (15%) had associated disorders such as cerebral palsy, and in only nine of the 82 children (11%) were there no clues at all to the cause of their retardation.

Adolescent↗
PubMed1990

Effect of steroidal fraction of seeds of Abrus precatorius Linn. on rat testis.

Dose-dependent degenerative changes in the testicular weights, sperm count, later stages of spermatogenesis and Leydig cells are observed in testis of rats treated with steroidal fraction of seeds of A. precatorius. These are correlated with the dose-dependent decrease in the enzyme activity of 3 alpha, 3 beta, 17 beta-hydroxysteroid dehydrogenases, glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase and leucine aminopeptidase. The steroidal fraction may also exert its influence indirectly at the pituitary level by a feedback mechanism, leading to decrease in production and release of testosterone which results in significant alterations in the testis.

Animals↗
PubMed1990

Enhancing magnetic resonance images using water bags.

Fascial planes between tissues are separated by connective tissue, fat, and blood vessels. Magnetic resonance imaging displays surface anatomy and soft tissues. Our team has been successful in demonstrating brachial plexus nerves as a model of magnetic resonance anatomy. Radiologists have devised methods to increase the resolution of images by suppressing noise and increasing the sharpness of the image. We added water bags to a 0.3 tesla permanent magnet suppressing the noise and increasing the signal to image our patients. The images proved to be sharper.

Humans↗
PubMed1989

The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II.

The A4 protein (or beta-protein) is a 42- or 43-amino-acid peptide present in the extracellular neuritic plaques in Alzheimer's disease and is derived from a membrane-bound amyloid protein precursor (APP). Three forms of APP have been described and are referred to as APP695, APP751 and APP770, reflecting the number of amino acids encoded for by their respective complementary DNAs. The two larger APPs contain a 57-amino-acid insert with striking homology to the Kunitz family of protease inhibitors. Here we report that the deduced amino-terminal sequence of APP is identical to the sequence of a cell-secreted protease inhibitor, protease nexin-II (PN-II). To confirm this finding, APP751 and APP695 cDNAs were over-expressed in the human 293 cell line, and the secreted N-terminal extracellular domains of these APPs were purified to near homogeneity from the tissue-culture medium. The relative molecular mass and high-affinity binding to dextran sulphate of secreted APP751 were consistent with that of PN-II. Functionally, secreted APP751 formed stable, non-covalent, inhibitory complexes with trypsin. Secreted APP695 did not form complexes with trypsin. We conclude that the secreted form of APP with the Kunitz protease inhibitor domain is PN-II.

Alzheimer Disease↗
PubMed1989

Characterization of four homologous L chain variable region genes that are related to 6B6.6 idiotype positive human rheumatoid factor L chains.

A significant proportion of monoclonal IgM rheumatoid factors (RF) from patients with mixed cryoglobulinemia express a KIIIa L chain-associated cross-reactive idiotype, termed 6B6.6. Previously, we reported the isolation from a patient with a monoclonal RF of a Vk gene, termed Humkv328, whose deduced amino acid sequence differs by three and seven residues from the L chains of the 6B6.6-positive RF Les and Pom, respectively. To further delineate the genetic basis of the 6B6.6 cross-reactive idiotype, we isolated from the same patient another Vk gene, termed Humkv329, which differs from kv328 by only three bases over a stretch of 1331 nucleotides sequenced. However, kv329 has a stop codon at amino acid position 94, and is thus a pseudogene. Therefore, we screened a second genomic library from an unrelated individual and isolated two potential function Vk genes (i.e., Humkv328h2 and Humkv328h5) which are highly homologous to Humkv328. All three potential functional Vk genes differ from each other by one to six bases over a 1331-bp stretch and all encode the same Vk region amino acid sequence. Among the six bases by which Humkv328h5 differs from Humkv328, two are in the conserved pentadecanucleotide region, which is known to be important in the regulation of k L chain transcription. In the future it will be important to ascertain the potential association of polymorphisms in the conserved pentadecanucleotide region with RF associated autoimmune and lymphoproliferative diseases.

Amino Acid Sequence↗