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Biomedical subjects

J Ghosh

Publications and source records attributed to J Ghosh.

At least 19 recordsLinked to original sources

Rapid tyrosine phosphorylation of Grb2 and Shc in T cells exposed to anti-CD3, anti-CD4, and anti-CD45 stimuli: differential effects of aging.

Two adapter proteins, Grb2 and Shc, have recently been implicated in the transmission of activation signals from the stimulated T cell receptor to Ras. We show here that in vitro stimulation of mouse splenic T cells with crosslinked anti-CD3 antibody leads within 30 s to phosphorylation of both Grb2 and Shc. Treatment with crosslinked anti-CD45 antibody leads to phosphorylation of Grb2 and also to a slight retardation in the mobility of this protein in an SDS polyacrylamide gel; both changes are seen within 30 s of crosslinking. Crosslinked anti-CD4 antibody leads to phosphorylation of Shc and to the phosphorylation of a 30-kDa protein that cross-reacts with anti-Grb2 antibodies. Aging leads to a decline in CD3-stimulated phosphorylation of Shc (but not Grb2), and to an increase in CD4-stimulated phosphorylation of Grb2, Shc, and the 30-kDa Grb2-like protein. Increased tyrosine-phosphorylation of Grb2 after exposure to either anti-CD3 or anti-CD45 suggests that Grb2 may be a common substrate for both CD3-linked kinases and the CD45 phosphatase. The differences between T cells from young and old mice suggest that aging may lead to a set of alterations in kinase/substrate coupling that contribute to immune dysfunction in the elderly, and that activation of the Ras pathway might be impaired by aging in T lymphocytes.

Adaptor Proteins, Signal Transducing

Ceramic bracket design: an analysis using the finite element method.

This investigation was designed to generate finite element models for selected ceramic brackets and graphically display the stress distribution in the brackets when subjected to arch wire torsion and tipping forces. Six commercially available ceramic brackets, one monocrystalline and five polycrystalline alumina, of twin bracket design for the permanent maxillary left central incisor were studied. Three-dimensional computer models of the brackets were constructed and loading forces, similar to those applied by a full-size (0.0215 x 0.028 inch) stainless steel arch wire in torsion and tipping necessary to fracture ceramic brackets, were applied to the models. Stress levels were recorded at relevant points common among the various brackets. High stress levels were observed at areas of abrupt change in geometry and shape. The design of the wire slot and wings for the Contour bracket (Class One Orthodontic Products, Lubbock, Texas) and of the outer edges of the wire slot for the Allure bracket (GAC, Central Islip, N.Y.) were found to be good in terms of even stress distribution. The brackets with an isthmus connecting the wings seemed to resist stresses better than the one bracket that did not have this feature. The design of the isthmus for the Transcend (Unitek/3M, Monrovia, Calif.) and Lumina (Ormco, Glendora, Calif.) brackets were found to be acceptable as well. The Starfire bracket ("A" Company, San Diego, Calif.) showed high stresses and irregular stress distribution, because it had sharp angles, no rounded corners, and no isthmus. The finite element method proved to be a useful tool in the stress analysis of ceramic orthodontic brackets subjected to various forces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Oxide

Longitudinal growth changes in the sagittal relationship of maxilla and mandible.

This is a longitudinal study of the growth pattern in sagittal linear measurements at points A, B, and pogonion relative to the pterygoid vertical plane in a Class I sample. Serial cephalometric radiographs were traced and digitized at ages 6, 12, 18, and 24 years. The results indicated that between the ages of 6 and 24 years there was a total growth increment of 6.07, 7.53, and 11.17 mm at points A, B, and pogonion, respectively, in the female Class I sample and 9.49, 11.65, and 16.21 mm at points A, B, and pogonion, respectively, in the male sample. Although the actual change in length of these measurements was larger in the male subjects than in the female subjects, in terms of percentage of growth increment in each of these three measurements from age 6 to 24 years, the anterior movement at point B relative to point A, and at pogonion relative to points B and A was approximately the same for both male and female subjects. When each of the subjects in both male and female samples was rank-ordered according to the size at age 6 years, considerable individual variation was noticeable for most persons within the group. The individual variation in growth pattern in each of the different measurements continues to raise questions about growth prediction and its application in visual treatment objectives.

Adolescent

Suramin, an experimental chemotherapeutic drug, irreversibly blocks T cell CD45-protein tyrosine phosphatase in vitro.

Suramin has long been used for the treatment of Gambian and Rhodesian trypanosomiasis and oncocerciasis. More recently, the demonstration that suramin inhibits DNA polymerases, reverse transcriptase and the lymphocyte terminal deoxynucleotidyl transferase has led to its clinical trials for the treatment of AIDS and cancer. The precise nature of suramin's anti-neoplastic action is not clear at this time. Suramin rapidly alters the tyrosine-specific phosphorylation of cellular proteins in many cancer cell lines. Here we demonstrate that suramin strongly inhibits the activity of CD45, the principal tyrosine specific protein phosphatase of T lymphocytes. Suramin-induced inactivation of CD45 is noncompetitive, irreversible and complete within 10 min. The ability of suramin to block CD45 mediated phosphatase function provides both new insight into the mechanism of action of this agent and a useful new probe for studies of T cell activation.

Animals

Pattern association and retrieval in a continuous neural system.

This paper studies the behavior of a large body of neurons in the continuum limit. A mathematical characterization of such systems is obtained by approximating the inverse input-output nonlinearity of a cell (or an assembly of cells) by three adjustable linearized sections. The associative spatio-temporal patterns for storage in the neural system are obtained by using approaches analogous to solving space-time field equations in physics. A noise-reducing equation is also derived from this neural model. In addition, conditions that make a noisy pattern retrievable are identified. Based on these analyses, a visual cortex model is proposed and an exact characterization of the patterns that are storable in this cortex is obtained. Furthermore, we show that this model achieves pattern association that is invariant to scaling, translation, rotation and mirror-reflection.

Animals

Allosteric modulation of Leishmania donovani plasma membrane Ca(2+)-ATPase by endogenous calmodulin.

The plasma membrane of the human pathogen Leishmania donovani possesses a high-affinity transmembrane Ca(2+)-ATPase that has its catalytic site oriented toward the cytoplasmic milieu (Ghosh, J., Ray, M., Sarkar, S., and Bhaduri, A. (1990) J. Biol. Chem. 265, 11345-11351). When the enzyme is studied in its more authentic, physiologically relevant, membrane-associated form, it exhibits pronounced sigmoidal kinetics with Ca2+ (K0.5 approximately 700 nM) in a trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid buffering system that effectively complexes all available Mg2+. Addition of exogenous Mg2+ (60 microM) completely abolishes sigmoidicity and establishes strictly hyperbolic kinetics, and the Km for Ca2+ reduces to 100 nM. Mg2+ can be replaced by heterologous calmodulin. The exclusive dependence of the enzyme on only Ca2+ for its activity and its positive allosteric modulation by Mg2+ distinguish this enzyme from other well-characterized plasma membrane Ca(2+)-ATPases. Employing this Ca(2+)-ATPase as the assay system, a soluble endogenous activating protein factor was purified that, by several criteria, corresponds to authentic calmodulin. The parasite calmodulin shifts the kinetics to hyperbolic kinetics, increases the Vmax 2-fold, and most important lowers the Km (approximately 100 nM) to a physiological level. The interaction with endogenous calmodulin thus converts the enzyme from a totally inactive to a fully active state.

Adenosine Triphosphate

A high affinity Ca2(+)-ATPase on the surface membrane of Leishmania donovani promastigote.

A Ca2(+)-dependent ATP-hydrolytic activity was detected in the crude membrane ghost of the promastigote or vector form of the protozoal parasite Leishmania donovani, the pathogen responsible for kala azar. The Ca2(+)-ATPase was purified to apparent homogeneity after solubilization with deoxycholate. The enzyme consists of two subunits of Mr = 51,000 and 57,000 and has an apparent molecular weight of 215,000 +/- 12,000. The enzyme activity is exclusively dependent on Ca2+, and the pure enzyme can hydrolyze 1.6 mumol of ATP/min/mg of protein. The apparent Km for Ca2+ is 35 nM, which is further reduced to 12 nM in the presence of heterologous calmodulin. The enzyme is sensitive to vanadate, but is insensitive to oligomycin and ouabain. The enzyme is strongly associated with the plasma membrane and has its catalytic site oriented toward the cytoplasmic face. The enzyme spans across the plasma membrane as surface labeling with radioiodine shows considerable radioactivity in the completely purified enzyme. The localization and orientation of this high affinity, calmodulin-sensitive Ca2(+)-ATPase suggest some role of this enzyme in Ca2+ movement in the life cycle of this protozoal parasite.

Adenosine Triphosphate

A study on the effect of vitamin A deficiency and supplementation on tumorigenesis in mice.

The effect of vitamin A deficiency and supplementation on the incidence of tumors, tumor growth and life expectancy was assessed in a murine model. Although the nature of response varied with respect to the tumor types studied, in general an increase in incidence of tumor take and further growth was noted with a concomitant fall in the survival rates in the group maintained on a vitamin A deficient diet. Supplemental vitamin A produced a prolongation of the latent period and delayed appearance of the tumor, reduced incidence and growth and improved life expectancy. Such effects seem to be mediated by a direct action of the vitamin on tumor cells, as well as through the host immune system, as revealed by nucleic acid synthetic patterns and nature of changes in the lymphocyte/neutrophil ratio, thymus weight and PHA-induced blastogenesis of peripheral lymphocytes.

Animals

Role of vitamin A in prevention and treatment of sarcoma 180 in mice.

The effect of deficiency of vitamin A and its supplementation on growth of murine sarcoma 180 was evaluated. The efficacy of cyclophosphamide under depleted and supplemented condition of the vitamin was also scrutinized. Supplemental vitamin A helped to check progression of tumour growth and also increased the effectiveness of chemotherapy. The action is possibly mediated through the host immune system.

Animals

Postharvest production of ochratoxin A by Aspergillus ochraceus and Penicillium viridicatum in barley with different protein levels.

The production of ochratoxin A (OA) in barley by Aspergillus ochraceus and Penicillium viridicatum was measured at 12 and 25 degrees C. The grain had been fertilized with various amounts of nitrogen fertilizer (0, 90, or 240 kg/ha) and contained (at crop maturity) 9.1, 10.4, or 12.0% protein, respectively. The production of OA by both fungi increased as the protein concentration increased. Glutamic acid and proline were enriched relative to other amino acids as the protein concentration increased. The differences in OA production could not be explained by a differential effect of protein or amino acids on fungal growth in barley. However, glutamic acid and proline enhanced OA production in liquid cultures of both A. ochraceus and P. viridicatum.

Amino Acids

Evaluation of vitamin A and C status in normal and malignant conditions and their possible role in cancer prevention.

A comparative study has been made on the levels of vitamins A and C in normal and malignant conditions in human and murine subjects. Further, the effect of supplemental vitamins A and C on tumor take, host-survival and tumor growth have been studied in a number of transplantable and induced tumors in mice. The vitamins were assayed in sera samples from normal subjects, patients with cancer of the uterine cervix or ovary, and leukemia and lymphoma patients. Among the murine group the tumors included sarcoma 180 in solid and ascitic form, benzo[a]pyrene-induced fibrosarcoma, Dalton's ascitic lymphoma and Schwartz lymphoblastic leukemia. The serum level of vitamin C was found to be lower than that of the normal controls in all cases studied. The level of vitamin A was found to be higher in cancer patients in the human group and lower in the murine group when compared with their normal controls. Studies on murine tumors showed that supplementary vitamins administered at the initial phase of tumor development reduced the percentage tumor take and the rate of tumor growth, and improved host survival, indicating that these vitamins have a protective role in the murine system.

Animals