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Biomedical subjects

S K Bhatia

Publications and source records attributed to S K Bhatia.

At least 19 recordsLinked to original sources

A heterogeneous model for gas transport in carbon molecular sieves.

A dual resistance model with distribution of either barrier or pore diffusional activation energy is proposed in this work for gas transport in carbon molecular sieve (CMS) micropores. This is a novel approach in which the equilibrium is homogeneous, but the kinetics is heterogeneous. The model seems to provide a possible explanation for the concentration dependence of the thermodynamically corrected barrier and pore diffusion coefficients observed in previous studies from this laboratory on gas diffusion in CMS. The energy distribution is assumed to follow the gamma distribution function. It is shown that the energy distribution model can fully capture the behavior described by the empirical model established in earlier studies to account for the concentration dependence of thermodynamically corrected barrier and pore diffusion coefficients. A methodology is proposed for extracting energy distribution parameters, and it is further shown that the extracted energy distribution parameters can effectively predict integral uptake and column breakthrough profiles over a wide range of operating pressures.

Journal Article↗

High-pressure adsorption capacity and structure of CO2 in carbon slit pores: theory and simulation.

We present new simulation results for the packing of single-center and three-center models of carbon dioxide at high pressure in carbon slit pores. The former shows a series of packing transitions that are well described by our density functional theory model developed earlier. In contrast, these transitions are absent for the three-center model. Analysis of the simulation results shows that alternations of flat-lying molecules and rotated molecules can occur as the pore width is increased. The presence or absence of quadrupoles has negligible effect on these high-density structures.

Journal Article↗

Study of hexane adsorption in nanoporous MCM-41 silica.

We study here the adsorption of hexane on nanoporous MCM-41 silica at 303,313, and 323 K, for various pore diameters between 2.40 and 4.24 nm. Adsorption equilibria, measured thermogravimetrically, show that all the isotherms, that are somewhat akin to those of type V, exhibit remarkably sharp capillary adsorption phase transition steps and are reversible. The position of the phase transition step gradually shifts from low to high relative pressure with an increase in the temperature as well as the pore sizes. The isosteric heats of adsorption derived from the equilibrium information using the Clapeyron equation reveal a gradual decrease with increasing adsorbed amount because of the surface heterogeneity but approach a constant value near the phase transition. A decrease in the pore size results in an increase in the isosteric heat of adsorption because of the increased dispersion forces. A simple strategy, based on the Broekhoff and De Boer adsorption theory, successfully interprets the hexane adsorption isotherms for the different pore size MCM-41 samples. The parameters of an empirical expression, used to represent the potential of interaction between the adsorbate and adsorbent, are obtained by fitting the monolayer region prior to capillary condensation and the experimental phase transition simultaneously, for some pore sizes. Subsequently, the parameters are used to predict the adsorption isotherm on other pore size samples, which showed good agreement with experimental data.

Journal Article↗

Delineation among eight major hematopoietic subsets in murine bone marrow using a two-color flow cytometric technique.

BACKGROUND: Many methods have been developed specifically for identifying hematopoietic progenitor cells in murine bone marrow, but few methods allow rapid identification of multiple bone marrow populations. We describe a new, simple method for identifying simultaneously eight populations in murine bone marrow with two-color flow cytometry and phenotypically define these populations. METHODS: Bone marrow was stained with anti-Ly-6C and anti-B220 (CD45R) in one fluorochrome and wheat germ agglutinin (WGA) in another fluorochrome. The eight populations identified in this way were defined further primarily by four-color flow cytometry. RESULTS: Six of the eight populations were characterized phenotypically as containing erythroid, granulocytic, mast, early B, mature B, and stem cell populations. Two additional populations with phenotypic characteristics of partially differentiated precursor cells also were identified. One population was Ly-6C/B220+ and WGA-. It also expressed markers associated with early B, T, and/or dendritic cell differentiation. The second population was Ly-6C(hi)WGA(hi)Mac-1+ and was negative for numerous other lineage-specific and precursor markers. Its morphology suggested monocytic differentiative potential. CONCLUSIONS: A two-color flow cytometric assay profiles six bone marrow populations with identifiable phenotypes and two additional unique, putative hematopoietic precursor populations.

Animals↗

APC stimulated by CpG oligodeoxynucleotide enhance activation of MHC class I-restricted T cells.

Oligonucleotides containing unmethylated CpG motifs (cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG ODN)) are potent immunostimulatory agents capable of enhancing the Ag-specific Th1 response when used as immune adjuvants. We evaluated the cellular mechanisms responsible for this effect. Development of a CTL response was enhanced when mice were immunized with peptide-pulsed dendritic cells (DCs) treated with CpG ODN. However, in vitro, CpG ODN had no direct effect on highly purified T cells. In vitro, CpG ODN treatment of peptide- or protein-pulsed DCs enhanced the ability of the DCs to activate class I-restricted T cells. The presence of helper T cells enhanced this effect, indicating that treatment with CpG ODN does not obviate the role of T cell help. The enhanced ability of CpG ODN-treated DCs to activate T cells was present but blunted when DCs derived from IL-12 knockout mice were used. Fixation of Ag-pulsed, CpG ODN-treated DCs limited their ability to activate T cells. In contrast, fixation had little effect on DC activation of T cells when DCs were not exposed to CpG ODN. This indicates that production of soluble factors by DCs stimulated with CpG ODN plays a particularly important role in their ability to activate class I-restricted T cells. We conclude that CpG ODN enhances the development of a cellular immune response by stimulating APCs such as DCs, to produce IL-12 and other soluble factors.

Adjuvants, Immunologic↗

Glucose is absorbed in a sodium-dependent manner from forestomach contents of sheep.

Intraruminal glucose is thought to be completely converted to short-chain fatty acids (SCFA) by symbiotic microorganisms. Nevertheless, earlier in vitro studies evidenced the expression of the sodium glucose-linked transporter (SGLT)-1, in the ovine ruminal epithelium. The present study aimed to determine whether the ruminal SGLT-1 is functionally important in vivo. In a first experimental series using the emptied, washed, and isolated reticulorumen of sheep, 6.3% of glucose was absorbed from an intraruminal buffer solution (2 L, 128 mmol/L Na(+), 0.5 mmol/L glucose, 0 mmol/L galactose) within 30 min (P < 0.001). Reducing Na(+) concentration to 10 mmol/L resulted in complete inhibition of glucose absorption, and the addition of 10 mmol/L galactose (at 128 mmol/L Na(+)) induced a small but insignificant inhibition. In a second experimental series, the addition of 12 mmol/L glucose to an initially glucose-free buffer led to an increase in the transruminal potential difference from 34.4 to 37.1 mV within 4 min (P < 0.001). From the 12 mmol/L glucose-containing buffer, 11.0% of glucose was absorbed within 30 min (P < 0.05). In all experiments, microbial glucose degradation in the reticulorumen was prevented by adding cefuroxime (100 mg/L) and colistin methanesulfonate (25 mg/L) to the buffer solution. The effectiveness of antimicrobial treatment was verified by ex vivo incubations of buffer samples drawn from the reticulorumen. We conclude that glucose is absorbed in a sodium-dependent manner from the reticulorumen at low and high glucose concentrations. Absorption at high glucose concentrations is of nutritional importance because it counteracts the genesis of ruminal lactic acidosis.

Analysis of Variance↗

Depression in women: diagnostic and treatment considerations.

Women experience depression twice as often as men. The diagnostic criteria for depression are the same for both sexes, but women with depression more frequently experience guilt, anxiety, increased appetite and sleep, weight gain and comorbid eating disorders. Women may achieve higher plasma concentrations of antidepressants and thus may require lower dosages of these medications. Depending on the patient's age, the potential effects of antidepressants on a fetus or neonate may need to be considered. Research indicates no increased teratogenic risk from in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. SSRIs are effective in treating premenstrual dysphoric disorder and many comorbid conditions associated with depression in women. Psychotherapy may be used alone in women with mild to moderate depression, or it may be used adjunctively with antidepressant drug therapy. Women who have severe depression accompanied by active suicidal thoughts or plans should usually be managed in conjunction with a psychiatrist.

Depression, Postpartum↗

Electroconvulsive therapy during the third trimester of pregnancy.

ECT was administered in two patients during the third trimester of pregnancy. Patient A experienced uterine contractions following the second, third, and sixth treatments. Tocolytic therapy was needed only after the third treatment. Also, following the third treatment, we observed decreased fetal heart rate variability and uterine contraction-related late cardiac deceleration, which indicated fetal compromise. Following the sixth treatment, there was an insignificant drop in biophysical profile score. No such effects were noted with Patient B despite risk factors for premature labor.

Adult↗

Immunostimulatory CpG oligodeoxynucleotides enhance the immune response to vaccine strategies involving granulocyte-macrophage colony-stimulating factor.

Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor (GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13 murine lymphoma system to evaluate the immune response to a combination of these two adjuvants. Immunization using antigen, CpG ODN, and soluble GM-CSF enhanced production of antigen-specific antibody and shifted production towards the IgG2a isotype, suggesting an enhanced TH1 response. This effect was most pronounced after repeat immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days before tumor inoculation prevented tumor growth. CpG ODN enhanced the production of interleukin-12 by bone marrow-derived dendritic cells and increased expression of major histocompatibility complex class I and class II molecules, particularly when cells were pulsed with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN in combination with strategies involving GM-CSF enhances the immune response to antigen and shifts the response towards a TH1 response and that this approach deserves further evaluation in tumor immunization approaches and other conditions in which an antigen-specific TH1 response is desirable.

Adjuvants, Immunologic↗

Concurrent administration of clozapine and ECT: a successful therapeutic strategy for a patient with treatment-resistant schizophrenia.

A male patient with a 4-year history of schizophrenic disorder, treated in the past with several conventional neuroleptics, atypical antipsychotics, as well as adjunctive therapies, was hospitalized because of treatment resistance/intolerance to pharmacotherapy. During 60 weeks of hospitalization, the patient was treated with conventional neuroleptics or clozapine monotherapy and with concurrent bilateral electroconvulsive therapy (ECT). The patient showed inadequate response to conventional neuroleptics or clozapine without ECT. Concurrent administration of pimozide and ECT resulted in a brief period of improvement. However, concurrent administration of clozapine and ECT resulted in substantial improvement. Our observation suggests that combination treatment with clozapine and ECT can be safe and effective.

Adult↗

Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization.

Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes.

Amino Acids↗

Antibody immobilization using heterobifunctional crosslinkers.

Covalent attachment of functional proteins to a solid support is important for biosensors. One method employs thiol-terminal silanes and heterobifunctional crosslinkers such as N-succinimidyl 4-maleimidobutyrate (GMBS) to immobilize proteins through amino groups onto glass, silica, silicon or platinum surfaces. In this report, several heterobifunctional crosslinkers are compared to GMBS for their ability to immobilize active antibodies onto glass cover slips at a high density. Antibodies were immobilized at densities of 74-220 ng/cm2 with high levels of specific antigen binding. Carbohydrate-reactive crosslinkers were also compared to GMBS using a fiber optic biosensor to detect fluorescently-labeled antigen. At the concentrations tested, the antibodies immobilized with carbohydrate-reactive crosslinkers bound more antigen than GMBS immobilized antibodies as indicated by the fluorescence signal.

Biosensing Techniques↗

Inhibition of interleukin-10 during pregnancy results in neonatal growth retardation.

PROBLEM: Interleukin 10 is considered to be important in the survival of the fetus in murine pregnancies that are known to be at risk for fetal wastage. The function of IL-10 in a normal pregnancy is not known. METHODS: In this report, we attempted to neutralize Interleukin 10 by administering anti IL-10 monoclonal antibodies (mAb) to pregnant mice that have a low background risk for fetal resorptions. The first group of mice was sacrificed on gestation day 18 to study the fetal effects of anti IL-10 administration. The second group of mice was allowed to deliver to study the effects on the neonatal outcome. RESULTS: Administration of anti IL-10 mAb did not affect the duration of gestation or the fetal outcome. Neonates exposed to anti IL-10 mAb in utero showed signs of transient growth deficiency starting at 4 weeks of age that spontaneously corrected by 6 weeks of age. CONCLUSIONS: Administration of anti IL-10 mAb does not alter the duration of gestation or the fetal outcome in normal murine pregnancies; however, it appears to be associated with transient neonatal growth problems.

Animals↗

Estrogen inhibits fetal thymocyte development in vitro.

PROBLEM: Transient involution of the maternal thymus in mice is known to occur during pregnancy. We have previously reported that the hormone responsible for this involution is estrogen. Interestingly, although estrogen crosses the placenta, fetal thymus gland enlarges with advancing gestational age. It is not known if fetal thymocytes are resistant to estrogen or if there are other factors that prevent estrogen from exerting an effect on the development of fetal thymocytes. Therefore we studied the effect of estrogen on isolated fetal thymic glands in vitro. METHOD OR STUDY: Pregnant Balb/c mice were sacrificed at 15 days gestation and fetal thymic lobes were obtained from all fetuses. The glands were cultured in vitro using either control medium or medium to which estrogen was added in two concentrations of 0.5 mg/ 100 ml and 1.0 mg/100 ml. After 12 days of organ culture, total thymocyte counts and phenotypic analysis by three color flow cytometry were performed by using monoclonal antibodies to surface markers of T cells subsets. RESULTS: Estrogen treatment caused a marked suppression of the total number of fetal thymocytes. All CD4 and CD8 defined T cell subsets were reduced with a disproportionate loss of CD4+ single positive (SP), CD8+ SP: CD4+CD8+ double positive (DP) cells. The early thymocyte developmental stages, based on CD44 and CD25 expression, revealed the CD4-CD8-CD3- triple negative compartment (TN) to be composed of almost entirely the earliest population (CD44+CD25-) with the remaining maturational stages depleted. CONCLUSIONS: This study demonstrates that fetal thymus removed from the intact fetus is susceptible to the inhibitory effects of estrogen. Since the fetal thymus enlarges with advanced gestational age, it is clear that the intact fetus invokes a regulatory mechanism which neutralizes the anti-lymphopoietic action of estrogen observed in the adult female.

Animals↗