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Biomedical subjects

S K Bhatia

Publications and source records attributed to S K Bhatia.

At least 37 records · Page 2Linked to original sources
PubMed1997

Major depression: selecting safe and effective treatment.

Diagnosis and management of major depression, a condition that is frequently encountered by primary care physicians, must take into account such factors as the patient's age, comorbid conditions and specific presenting symptoms. Rational selection of antidepressant medication must also include analysis of potential side effects and drug-drug or drug-food interactions. Psychiatric consultation may benefit a select group of patients. Although some patients may require life-long antidepressant medication, most will be able to discontinue their medication after a period of time. Newer antidepressants are expanding the treatment options available to family physicians.

Antidepressive Agents↗
PubMed1996

Differential expression of CD22 (Lyb8) on murine B cells.

Previous studies have established the distribution, biochemistry and functional attributes of human CD22, a B cell-restricted glycoprotein. Recently, molecular cloning of the murine CD22 equivalent revealed this molecule to be the same as the previously described Lyb8 alloantigen. Using the anti-Lyb8 mAb Cy34.1.2, the present report documents the expression patterns of CD22 within the murine B cell compartment. The results demonstrate that in the bone marrow, murine CD22 is absent on the surface of pro-B cells, pre-B cells and newly emerging IgM+ B cells. CD22 is present at a low density on immature IgMhi B cells and fully expressed on mature recirculating B cells. In the periphery, murine CD22 is expressed at mature levels on all B cell subsets including follicular, marginal zone, B1 and switched B cells. Further studies showed CD22 to be retained on activated murine B cells for extended periods. Finally, in combination with CD23 and heat stable antigen, CD22 can be used to delineate the immature splenic B cells, and distinguish them from follicular and marginal zone cells. Together, the results demonstrate murine CD22 to be a useful pan marker for all mature B cell subsets.

Animals↗
PubMed1996

Effect of pregnancy on thymic T cell development.

PROBLEM: The thymus gland decreases in size during pregnancy. The significance of this alteration is not known. METHOD: In this report, we examined thymic function by evaluating the development of T lymphocytes in the thymus of pregnant Balb/c mice at 15 and 20 days gestation using multi-color flow cytometry. Comparative analysis was made with non-pregnant mice, post-partum lactating mice, and postpartum non-lactating mice. RESULTS: Progressive reduction of thymic size and cellularity during pregnancy was observed. All of the CD4 and CD8 defined subsets were reduced, with a disproportionate loss of CD4+, CD8+ double positive cells. Examination of the CD4-, CD8- double negative compartment revealed a predominance of TCR alpha, beta+ double negative cells, and a striking loss of precursor cells. The CD3-, CD4-, CD8- triple negative thymic subset was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; and CD44-, CD25-) depleted. At 2 weeks postpartum, the subset ratios normalized, and the total cell count showed recovery. CONCLUSION: T cell development is blocked at the precursor level during the mouse pregnancy. These effects are transient, and gradual recovery is observed in the postpartum period.

Animals↗
PubMed1996

Estrogen blocks early T cell development in the thymus.

PROBLEM: Pregnancy and estrogen are known to suppress B lymphopoiesis as well as lead to thymic involution in the mouse. Additionally, estrogen deficiency by oophorectomy reportedly causes a selective increase in the B220+ B cells in the murine bone marrow. The purpose of this study was to determine if estrogens played a regulatory role in T cell development. METHODS: The first experimental group consisted of 5-6-week-old Balb/c mice that received subcutaneous pellets of placebo, estriol, estradiol, or progesterone. The thymus glands were examined 2-4 weeks after treatment. The second group consisted of 6-week-old Balb/c mice who underwent either bilateral oophorectomy or a sham procedure. Two weeks after the surgery, extensive phenotypic characterization of the thymus and spleen cells was performed by flow cytometry using monoclonal antibodies to surface markers of T cell subsets. RESULTS: Estrogen treatment causes a dramatic reduction of thymic size and cellularity. All defined T cell subsets of CD4 and CD8 were reduced, with a disproportionate loss of CD4+CD8+ double positive cells. Examination of the triple negative (CD3-CD4-CD8-) subset revealed a striking loss of TN developmental progression of the early precursor cells. Based on the expression of CD44 (pgp-1) and CD25 (IL-2R alpha) markers, the TN thymic compartment was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; CD44-, CD25-) depleted. In contrast, all T cell developmental stages in the thymus were found to be in normal proportions in the oophorectomized mice, with no differences in the splenic T and B cell subsets. CONCLUSIONS: The study demonstrates that estrogen but not progesterone blocks T cell development in the thymus. However, contrary to our expectation, estrogen deprivation by oophorectomy does not enhance T cell development.

Animals↗
PubMed1996

Influence of diet on the induction of experimental autoimmune thyroid disease.

Immunization of CBA/J mice with thryoglobulin (Tg) emulsified in complete Freund's adjuvant induces experimental thyroiditis (EAT), a well-characterized model of Hashimoto's disease. Recent studies have suggested that dietary factors play a role in the modulation of the immune response and that diet can have a profound effect on the induction of autoimmune diseases. In this study, we examined the influence of diet on autoimmune thyroiditis in mice. EAT was induced in mice fed ad libitum one of the three diets, a standard maintenance chow (Agway H1000), Purina 5020 Breeding Chow, and Purina 5010 Autoclavable (unautoclaved) Diet. Tg-immunized mice fed the Agway 1000 diet were found to be resistant to the development of autoimmune thyroid disease, with only 4 out of 25 mice developing mild thyroiditis. In contrast, 16 out of 25 mice fed the Purina 5010 diet developed moderate to severe thyroiditis. Mice fed the 5020 diet were partly susceptible: 7 out of 25 developed a mild to moderate thyroiditis. Histologic examination of thyroid glands of diseased mice fed the 5010 and 5020 diets showed marked lymphocytic infiltration with destruction of follicles, compared with mice fed the Agway diet, the latter showing only mild infiltration with preservation of thyroid follicles. Titers of antibody to Tg did not differ among the groups, and there was no significant difference in the IgG isotype subclass usage. The results demonstrate that diet can markedly affect the severity of autoimmune disease in the EAT model. In contrast, diet has little effect on the humoral autoimmune response in this system. These results implicate diet as a factor in the severity of cell-mediated autoimmune destruction and suggest that dietary modification could decrease pathology in some forms of autoimmune disease.

Animal Feed↗
PubMed1995

The effect of in vivo IL-7 deprivation on T cell maturation.

A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the function of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, F. D. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morrissey. 1993. J. Exp. Med. 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B and immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 wk to determine the effect of in vivo IL-7 deprivation on the thymus. The results demonstrate a > 99% reduction in thymic cellularity after extended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the CD4+, CD8+ subset was most depleted, the CD4 and CD8 single positive cells remained essentially unchanged, and the CD4-, CD8- compartment actually increased to approximately 50% of the thymus. Further examination of the double negative thymocytes demonstrated that IL-7 deprivation did, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportional increase in the CD4-, CD8- compartment was found to be due to an accumulation of CD3+, T cell receptor alpha, beta + double negative T cells. Additional analysis revealed that anti-IL-7 treatment suppressed the audition/selection process of T cells, as shown by a significant reduction of single positive cells expressing CD69 and heat stable antigen. Finally, the effects of IL-7 deprivation on the thymus were found to be reversible, with a normal pattern of thymic subsets returning 4 wk after cessation of treatment. The present results thus indicate a central role for IL-7 in the maturation of thymic-derived T cells.

Animals↗
PubMed1993

Fabrication of surfaces resistant to protein adsorption and application to two-dimensional protein patterning.

Proteins were attached in defined geometric patterns on a surface. A prerequisite to making a pattern of proteins is generation of surfaces resistant to nonspecific protein adsorption. This was accomplished via oxidation of the thiol terminus of an organosilane self-assembled monolayer film by deep ultraviolet (DUV) irradiation. The resultant surface exhibited marked resistance to protein adsorption. Using a mask to protect regions of the silanized surface from irradiation, proteins were selectively adsorbed or attached via covalent linkage at locations protected from the DUV light. Antibodies immobilized in patterns using this procedure retained their antigen-binding capability. Thus chemistry and DUV lithography were combined to create patterns of active biomolecules which could be used in the microfabrication of electronic devices and biosensors.

Adsorption↗
PubMed1992

Four interleukin-2 surface binding proteins detected in rat spleen cells.

Four specific interleukin-2 (IL-2) surface binding proteins can be detected by covalent cross-linking of [125I]IL-2 to rat spleen cells that have been activated with various stimuli including concanavalin A (Con A), phytohaemagglutinin (PHA), calcium ionophore, and phorbol dibutyrate (PDB) with or without calcium ionophore. These four cross-linked proteins could not be demonstrated in either unstimulated T cells or in activated T cells when binding was performed in the presence of a 20-100-fold excess of unlabelled IL-2. The molecular weights of the four cross-linked proteins, after subtraction of the molecular weight contribution of IL-2 are: 53,000, 70,000, 90,000 and 118,000. The 53,000 MW protein was identified as the rat IL-2 receptor (IL-2R) alpha-chain by immune precipitation. Additionally, results suggest that the rat IL-2R alpha-chain is tightly complexed to both the 118,000 and 90,000 MW IL-2 binding proteins. Purification of surface labelled proteins from activated cells using IL-2 affinity chromatography yields four proteins with similar molecular weight to those identified by cross-linking plus an additional non-ligand cross-linked protein of 46,000 MW. The 46,000 MW band may be a non-binding associated protein since it was not seen following [125I]IL-2 binding cross-linking. Tryptic digests and two-dimensional separation of the affinity-isolated proteins indicate that unique peptide maps are generated for the 46,000, 53,000 and 70,000 MW proteins and excludes the possibility that the bands identified by cross-linking represents cross-linking of multiple ligands to the 53,000 MW subunit. However, the 90,000 and 118,000 MW bands yield peptide maps that closely resemble each other suggesting that these binding proteins may be related. These results suggest that at least four IL-2 surface binding proteins may constitute the rat IL-2R system.

Animals↗
PubMed1991

Stereospecific synthesis of antitumor active thioether PAF analogs.

A novel stereospecific synthesis of antitumor active thioether analogs of platelet-activating factor (PAF) is reported. The synthesis is based upon: i) the use of D-serine to provide the chiral center for the construction of the optically active phospholipid molecule; ii) development of the sn-1-thioalkyl function via thioacetate displacement of methanesulfonate-activated primary hydroxyl group followed by alkylation of the sn-1-thiolate function; and iii) introduction of the phosphocholine moiety through the 2-chloro-2-oxo-1,3,2-dioxaphospholane/trimethylamine sequence. The entire scheme relies on the use of a single protecting group. The synthetic thioether phospholipid 1-S-hexadecyl-2-N-acetamidodeoxy-sn-glycero-3-phosphocholine has been shown to be a potent antitumor active phospholipid, exhibiting tumor cytotoxicity against a lymphoblastoid lymphoma (Li-A) cell line and a malignant histiocytic (DHL-4) cell line of human origin at the same level of potency as ET-18-OMe and 1-O-octadecyl-2-N-acetamidodeoxy-sn-glycero-3-phosphocholine. The synthetic method described has a great deal of flexibility, providing a convenient general route to a wide range of thioether PAF analogs.

Antineoplastic Agents↗
PubMed1989

Use of thiol-terminal silanes and heterobifunctional crosslinkers for immobilization of antibodies on silica surfaces.

A procedure for covalent immobilization of functional proteins on silica substrates was developed using thiol-terminal silanes and heterobifunctional cross-linkers. Using this procedure, a high density of functional antibodies was bound to glass cover slips and silica fibers. The amount of anti-IgG antibody immobilized was determined to be in the range of 0.66 to 0.96 ng/mm2 using radiolabeled antibody. The relative amount of IgG antigen bound by the immobilized antibody (0.37 to 0.55 mol antigen/mol antibody) was three to five times greater than other investigators have reported. In addition, the amount of protein nonspecifically adsorbed to the antibody-coated surface was further reduced by the addition of blocking agents so that nonspecific adsorption of protein antigens represented only 2-6% of the total antigen binding. With this low background, IgG antigen binding could be measured at levels as low as 150 fmol when an antigen concentration of 3 pmol/ml was applied. The process for antibody immobilization is straightforward, easy to perform, and adaptable for modifying mass quantities of biosensor components.

Antibodies↗
PubMed1987

Hormone receptor studies in axillary metastases from occult breast cancers.

The authors describe 11 patients with occult breast carcinoma, who initially presented with axillary nodal metastases of unknown origin. In all 11 cases, physical examination and mammography results were normal. Steroid hormone receptor studies were done on tissue from all 11 axillary masses and 2 masses underwent lactalbumin staining as well. In 8 of the 11 patients these studies were positive, suggesting breast as the primary tumor site. Estrogen (30 to 445 fmol/g) or progesterone (30 to 1059 fmol/g) receptors, or both, were positive in seven cases. Although a breast carcinoma was subsequently found in all 11 patients, receptor studies on the primary tumor could not be done in every instance. The authors concluded that performing steroid hormone receptor assays on axillary metastases from occult tumors not only may provide information regarding the identity of the primary tumor but also may be the sole opportunity to determine its hormone receptor status.

Adenocarcinoma↗
PubMed1984

Phenol metabolism, phytoalexins, and respiration in potato tuber tissue treated with Fatty Acid.

Potato (solanum tuberosum L. cv Katahdin) tuber discs treated with arachidonic acid become necrotic and accumulate sesquiterpenoid phytoalexins. The arachidonic acid also causes increases in both phenylalanine ammonia lyase and lignin, but no change in total alcohol-soluble phenols. Linoleic acid does not alter any of these parameters. A high concentration of nonanoic acid promotes both necrosis and accumulation of low levels of phytoalexins, but decreased levels of phenols, phenylalanine ammonia lyase, and lignin. The respiration of the control discs and those treated with linoleic acid declines by 24 hours after treatment, but the respiration of arachidonic acid-treated discs remains constant for at least 48 hours.

Journal Article↗
PubMed1983

Inhibition of phytoalexin synthesis in arachidonic Acid-stressed potato tissue by inhibitors of lipoxygenase and cyanide-resistant respiration.

Arachidonic acid-stressed potato tuber discs synthesized the phytoalexin rishitin. This synthesis was inhibited by salicylhydroxamic acid (SHAM), and to a lesser extent by tetraethylthiuram disulfide (disulfiram). Disulfiram was less effective apparently because it was inactivated in the tuber discs. Disulfiram and SHAM both inhibited cyanide-resistant respiration of whole potato discs and lipoxygenase extracted from these discs. When low disulfiram concentrations were used, the lipoxygenase inhibition was quickly overcome, again because the disulfiram apparently was inactivated by oxidation.

Journal Article↗
PubMed1981

Emotional problems in the adolescent: depression.

The rapid physiological and psychological changes observed during the adolescent period and the associated need for a continuous adjustment to those changes result in an extraordinary load to be borne by the maturing adolescent under not always optimal circumstances. This article discusses depression in the adolescent and provides guidelines for early diagnosis, therapy and prevention.

Adolescent↗
PubMed1980

Ammonia anabolizing enzymes in cattle and buffalo fed varied nonprotein nitrogen and carbohydrates.

Adult male fistulated crossbred cattle and buffalo, four each, were on rations with rations of nonprotein nitrogen to carbohydrates of 1:45, 1:37.5, and 1:30 and a control of no urea in a 4 x 4 Latin square switchover design. The influence of various test diets on enzymes assimilating ruminal ammonia was elucidated to find an optimum ratio of nonprotein nitrogen to soluble carbohydrates for efficient utilization of dietary nitrogen. Inclusion of urea in graded amounts in the ration induced activities of amino-stransferases. Specific activities of trans-aminases were higher in cattle and buffalo for rations with ratios of 1:45 and 1:30 compared to control and 1:37.5 (nonprotein nitrogen to carbohydrate ratio). This indicates a better adaptation of rumen microbes on two former rations which did not differ in augmentation of enzyme activities. Peak enzyme activity of cattle and buffalo at 2 h postfeeding did not differ for microbial enzymes. The ration with narrowest nonprotein nitrogen and carbohydrate ratio (1:30) may be optimum for microbial synthesis of amino acid. It will be worthwhile to study whether a still narrower ratio can make feeding of ruminants more economical.

Amino Acids↗
PubMed1979

Microbial transaminase activities and their relationship with bovine rumen metabolites.

Two each adult male crossbred cattle and murrah buffalo were fed a diet of alfalfa hay, chopped wheat straw, and concentrate mixture. Total rumen transaminase activity of cattle was higher than that of buffalo. Rumen protozoal fractions showed higher total transaminase activity than bacterial fractions in both ruminant species. Besides generally studied glutamate oxalacetate transaminase and glutamate pyruvate transaminase, a large number of other microbial transaminases also have been detected in the rumen of both the ruminant species. Bacterial fractions of rumen liquor were devoid of transaminases utilizing tryptophan, threonine, and lysine as their substrates. Ruminal ammonia and nonprotein nitrogen were correlated positively with microbial transaminases in both species. Transamination reactions may be important for assimilation of ruminal ammonia to cellular proteins.

Alanine Transaminase↗
PubMed1978

Transmural myocardial infarction with the prolapsing mitral-leaflet syndrome and normal coronary arteries.

Clinical and electrocardiographic evidence of transmural myocardial infarction developed in two patients (a woman, age 38, and a boy, age 17) with prolapsing mitral-leaflet syndrome. Both had normal coronary angiograms and normal plasma lipid levels. Left ventricular angiography showed dyskinetic areas in both patients. Coronary artery embolism or prolonged coronary artery spasm may have been the underlying mechanism of production of myocardial infarction.

Acute Disease↗