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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 1,279 records · Page 71Linked to original sources

[A new agglutination reaction for the diagnosis of the developmental stage of acquired toxoplasmosis].

Agglutination of acetone treated toxoplasma (AC) is different from that one of formalin fixed parasites (HS). Sera from patients with a recently acquired ("acute") infection agglutinate both HS and AC parasites suspensions as well; contrary to sera from patients with past infection ("chronic stage") in which high titers of HS agglutination are often present, while the titres of AC agglutination are lower even negative. This is markedly observed in patients with local lesions (relapsing chorioretinitis, patients with AIDS and brain abscesses). The reason might be that different membrane toxoplasma antigens may induce the synthesis of agglutinating IgG. For example, antigens 35 KD and 27 KD described by E. Handman et al. The antibody specific for 27 KD is apparently present mainly during acute infection, contrary to the antibody specific for 35 KD which might be responsible of the high HS agglutination titre in sera from patients with chronic infection. Even if these hypotheses were not confirmed in the future, comparison of the titre in the HS and AC agglutination test might actually be helpful for practical diagnosis of the stage of toxoplasma infection.

Acute Disease↗

Kinetics of reabsorption of nutrients in renal brush border membrane vesicles from rats with experimental ascending pyelonephritis.

The uptake of nutrients was investigated in the renal cortical brush border membrane (BBM) vesicles at different stages of ascending pyelonephritis. There was significant difference (p less than 0.05) in the uptake of D-glucose, L-alanine, L-aspartate, L-lysine and L-proline 3 days postinfection and onwards in both right unobstructed and left obstructed experimental kidneys as compared to the sham operated control. The uptake of D-glucose, L-lysine and L-proline was found to be significantly decreased (p less than 0.05) during the course of infection. While uptake of L-alanine and L-aspartate increased (p less than 0.05) in early stages and decreased (p less than 0.05) in later stages of infection. The differential effect was attributed to the compensatory measure and different kinds of transport systems for different types of amino acids.

Amino Acids↗

Anterior chemotherapy in esophageal cancer.

Front loading chemotherapy using methotrexate (200 mg/m2) alone or methotrexate (200 mg/m2) with cisplatin (20 mg/m2 daily for 5 days) was used in epidermoid carcinoma of esophagus. Evaluation after two courses showed objective response of 50% or greater in 48% of patients with methotrexate alone. Response rate was increased to 76.2% with addition of cisplatin to methotrexate. Small lesions (less than 10 cm) showed better response as compared to advanced cases. Therapy was generally well tolerated and good palliation was obtained even after the first course. Postchemotherpy treatment either with surgery or radiotherapy was tolerated without any major complications. The data confirm the short-term usefulness of initial chemotherapy with methotrexate and cisplatin in esophageal cancer. Results of prolonged follow-up will help to evaluate the role of front loading chemotherapy on long-term survival.

Adult↗

Diversity of circumsporozoite antigen genes from two strains of the malarial parasite Plasmodium knowlesi.

The complete nucleotide sequence of the coding region of the circumsporozoite antigen gene (CS gene) of the Nuri strain of the malarial parasite Plasmodium knowlesi is presented. The gene from the Nuri strain exhibits a novel form of sequence diversity when compared to the CS gene from the H strain. Instead of the 12 tandem repeating 36-base pair units of the H strain, the Nuri strain contains 16 tandem repeating 27-base pair units of a different nucleotide sequence that encodes a different repeating peptide. In contrast, the 5' and 3' coding and noncoding sequences flanking the repeats are 98 percent conserved in both strains.

Amino Acid Sequence↗

Expression of the major surface antigen of Plasmodium knowlesi sporozoites in yeast.

The circumsporozite protein, a surface antigen of the sporozoite stage of the monkey malarial parasite Plasmodium knowlesi, was expressed in the yeast Saccharomyces cerevisiae by using an expression vector containing the 5' regulatory region of the yeast alcohol dehydrogenase I gene. It was necessary to eliminate the entire 5' upstream region of the parasite DNA to obtain the expression of this protein. Only the circumsporozoite precursor was produced by the yeast transformants, as detected by immunoblotting. About 55 and 20 percent of the circumsporozoite protein produced in yeast was associated wtih the 25,000 g and 150,000 g particulate fractions, respectively. The protein could be solubilized in Triton X-100 and was stable in solubilized extracts.

Animals↗

SV40 T antigen and the exocytotic pathway.

A chimeric gene consisting of DNA coding for the 15-amino acid signal peptide of influenza virus hemagglutinin and the C-terminal 694 amino acids of SV40 large T antigen was inserted into a bovine papilloma virus (BPV) expression vector and introduced into NIH-3T3 cells. Cell lines were obtained that express high levels (approximately 5 X 10(6) molecules/cell) of the chimeric protein (HA-T antigen). The biochemical properties and intracellular localization of HA-T antigens were compared with those of wild-type T antigen. Wild-type T antigen. Wild-type T antigen is located chiefly in the cell nucleus, although a small fraction is detected on the cell surface. By contrast, HA-T antigen is found exclusively in the endoplasmic reticulum (ER). During biosynthesis, HA-T antigen is co-translationally translocated across the membrane of the ER, the signal peptide is cleaved and a mannose-rich oligosaccharide is attached to the polypeptide (T antigen contains one potential N-linked glycosylation site at Asn154). HA-T antigen does not become terminally glycosylated or acylated and little or none reaches the cell surface. These results suggest that T antigen is incapable of being transported along the exocytotic pathway. To explain the presence of wild-type T antigen on the surface of SV40-transformed cells, an alternative route is proposed involving transport of T antigen from the nucleus to the cell surface.

Amino Acid Sequence↗

Serum-free conditions for the growth of avian granulocyte and monocyte clones and primary leukemic cells induced by AMV, and the apparent conversion of granulocytic progenitors into monocytic cells by a factor in chicken serum.

The supportive activity of chicken serum for the soft-agar growth of chicken granulocyte and monocyte clones could be replaced with defined ingredients [bovine serum albumin (BSA), conalbumin, selenium, linoleic acid and for routine work, a liquid soy lecithin preparation (59% phospholipids, 39% linoleic acid, and less than 2% of inositol and choline)]. The lecithin preparation could be replaced with L-alpha-phosphatidylcholine. The source of colony-stimulating factor was medium conditioned by fibroblasts cultured under protein-free conditions. AMV-induced leukemic cells could be cloned under identical conditions. In the presence of both chicken serum (10%) and the replacement ingredients, most of the proliferative clones produced were monocytic (84%). In the presence of serum alone, all of them were monocytic. Under serum-free conditions, all the clones produced were granulocytic when a day-3 conditioned medium (CM) was used; monocytic ones were also present when a day-6 CM was used. When the serum was serially diluted in the presence of the replacement ingredients, the number of proliferative monocytic clones progressively decreased while the number of proliferative granulocytic clones progressively increased and the kinetics of each were essentially the same, only opposite in direction. Moreover, the total number of proliferative clones did not change more than 33% at any dilution (or in the absence of serum). We postulate the existence in the chick system of a serum macrophage differentiation factor (M-DF) which converts early granulocytic progenitors (or exclusively diverts a common progenitor) into monocytic cells.

Animals↗

The impact of combined therapeutic modalities in head, neck, and esophageal cancer.

Nearly 50% of head and neck cancers and two-thirds of patients with esophageal cancer generally present late for initial treatment. The patterns of failure are generally locoregional with around 10% showing distant dissemination. Surgery alone and in combination with pre-operative radiation has not significantly increased salvage in these groups of cancer. The availability of increasingly effective drugs (Cisplatinum, MTX., Bleomycin), for head, neck and esophageal cancers have produced dramatic initial responses with excellent palliative relief of symptoms enabling adequate definitive radiotherapy or surgery for advanced T3, T4 lesions. Cisplatinum 20 mg/m2 daily X 5 - twice at the interval of 10 days with MTX 25 mg/m2 and Bleomycin 15 mg/m2 weekly X 2 have been used for T3 and T4 Head and Neck Cancers and Cisplatinum in the same dosage and MTX 200 mg twice in 10 days have been used for esophageal cancers. 88% responses in 35 patients have been noted in head and neck cancers and when the chemotherapy was followed by definitive radiotherapy, complete responses were achieved in 16 out of 25 patients (64%). This is a very significant response rate for T3, T4 cancers. Patients who were in a reasonably acceptable general condition after this regimen were further considered for two more courses of consolidative chemotherapy. Response rates in esophageal cancer was 78% (26 of 34 evaluable patients) - 6 of the 26 showed a complete response and all are alive from 8 months to 26 months. Our failure to obtain increasing cures at 3 and 5 years may be due to our ignorance of the capacity of dormant cells to proliferate, tumor cell kinetics, more effective use of chemotherapy or the biology of the host. These areas need further investigation.

Antineoplastic Combined Chemotherapy Protocols↗