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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 199 records · Page 11Linked to original sources
PubMed2002

Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women.

BACKGROUND: The objective of this study was to confirm the source and study the acute changes and relationship between inhibins and FSH at surgical menopause. METHODS: Regularly cycling women (42-47 years; n = 10) undergoing bilateral oophorectomy for non-ovarian pathology were recruited for this study. One blood sample was taken before surgery and after removal of the ovaries, samples were taken every 15 min up to 1 h, hourly up to 6 h, after 12 h and daily during the hospital admission (3 days). RESULTS: There were five women in the follicular phase and five women in the luteal phase of the cycle. For women in both phases, levels of inhibin A, inhibin B, estradiol (E(2)) and progesterone decreased after the removal of the ovaries. Serum FSH levels started to rise after 12 h in both follicular and luteal phase women after the surgical menopause. Correlation analysis showed that inhibin A and E(2) were significantly negatively correlated in both phases with FSH concentration. Inhibin B had a negative correlation in the follicular phase and progesterone had a negative correlation in the luteal phase. CONCLUSIONS: This study showed that ovarian inhibin A and B were cleared from the circulation within 12 h of oophorectomy, whereas E(2) and progesterone remain in the circulation for longer. Negative correlation between FSH, inhibin A and inhibin B suggests that inhibins may contribute to the observed early rise in FSH after the surgical menopause.

Adult↗
PubMed2002

Validity of the time trade-off and standard gamble methods of utility assessment in retinal patients.

AIM: To assess the validity of the time trade-off (TTO) and standard reference gamble (SRG) techniques of utility assessment in patients with retinal disease. A cross section of eligible patients was studied and validity was determined through their relation with two logical constructs, visual acuity and scores from the Visual Function 14 (VF-14) index. METHODS: The study consisted of eligible patients presenting to a tertiary retinal facility who completed an interview. All patients had best corrected vision of 20/40 or worse in at least one eye. TTO and SRG utilities, as well as a VF-14 questionnaire, were administered through a standardised interview. Demographic and clinical (including Snellen visual acuity) information was also collected. RESULTS: 323 patients met these study criteria. Significant predictors of TTO utilities in the multivariate analysis were vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.01). Significant predictors of standard gamble utilities were also vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.05). CONCLUSION: Both the standard gamble and TTO methods demonstrate strong validity when evaluated against visual acuity in the better seeing eye and the VF-14 score.

Adolescent↗
PubMed2002

Deferoxamine attenuates iron-induced oxidative stress and prevents mitochondrial aggregation and alpha-synuclein translocation in SK-N-SH cells in culture.

One of the defining characteristics of neurodegenerative diseases, including Parkinson's disease, is an abnormal accumulation of iron in the affected brain areas. By using SK-N-SH, a dopaminergic cell line, we have found that iron (100-250 microM FeSO(4)) decreased cell viability, increased lipid peroxidation, and the said effects were blocked by deferoxamine (DFO: 10 microM). Furthermore, DFO, in the absence of iron, enhanced the level of adenosine triphosphate (ATP), but caused chromatin condensation and cell death. Morphological studies revealed that iron (50-100 microM) altered mitochondrial morphology, disrupted nuclear membrane, and translocated alpha-synuclein from perinuclear region into the disrupted nucleus. The results of these studies suggest that DFO is able to block and attenuate iron-mediated oxidative stress. However, in the absence of excess iron, DFO itself may have deleterious effects on the morphology and hence integrity of dopaminergic neurons.

Adenosine Triphosphate↗
PubMed2002

An audit on the blood transfusion requirements for revision hip arthroplasty.

The hospital transfusion committee of Swindon and Marlborough NHS Trust had formulated a maximum surgical blood ordering schedule (MSBOS) which included the standard practice of 6 units of blood for revision hip arthroplasty. A retrospective audit of 73 patients who underwent revision hip arthroplasty over a year was undertaken to identify current practice and to ensure that the standard was adequate for patient safety. Information regarding the number of units requested, number of units transfused, pre-operative haemoglobin (Hb), lowest postoperative Hb and number of additional units of blood requested within 3 days postoperatively, was collected from patients' case-notes. Of the 73 patients, 80.3% received less than 6 units, 12.2% received 6 units and 7.5% received more than 6 units. Based on pre-operative Hb, blood usage was analysed. Of cross-matched units, 92.3% were used when pre-operative Hb was < 12 g/dl, 64.4% were used when Hb was between 12.1-13.0 g/dl, 54.3% were used when the Hb was between 13.1-14.0 g/dl, 38.9% were used when Hb was between 14.1-15.0 g/dl and 39.7% used with pre-operative Hb of > 15.0 g/dl. Of the total, 14 patients had a postoperative Hb of < 9 g/dl for whom additional units of blood were ordered and given to achieve a Hb of between 10.1-14.2 g/dl prior to discharge. This audit suggests that in patients with pre-operative Hb of 13 g/dl or more, the cross-match could be 4 units instead of 6 units for revisions.

Arthroplasty, Replacement, Hip↗
PubMed2002

Pneumocystis carinii pneumonia: role of high resolution computed tomography.

Pneumocystis carinii (PC) is a common opportunistic infection in renal transplant recipients and requires an early diagnosis for its successful treatment. For its definitive diagnosis PC needs to be demonstrated in bronchoalveolar lavage (BAL) fluid. At times BAL may not be possible or get delayed. In such conditions typical appearances seen on high resolution CT of the chest help in early diagnosis of PC pneumonia (PCP). This easily performed procedure helped in early diagnosis of PCP in two patients.

Adult↗
PubMed2002

Fermentation of starch to ethanol by an amylolytic yeast Saccharomyces diastaticus SM-10.

A total of fifteen yeast strains were isolated from natural sources including fruits, soil, molasses, honey and a variety of indigeneous fermented foods. Screening of these strains for growth, ethanol production and glucoamylase activity led to selection of a yeast strain SM-10 identified as S. diastaticus having maximum glucoamylase activity (80 units ml(-1)) and ethanol production from starch (3.5%). Ethanol production from wheat flour was found to be 1.75% which could be increased to 5.2% after treatment of wheat flour with pepsin, diastase and glucoamylase.

Ethanol↗
PubMed2001

Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites.

Environmental conditions in early life permanently alter the development of glucocorticoid receptor gene expression in the hippocampus and hypothalamic-pituitary-adrenal responses to acute or chronic stress. In part, these effects can involve an activation of ascending serotonergic pathways and subsequent changes in the expression of transcription factors that might drive glucocorticoid receptor expression in the hippocampus. This paper summarizes the evidence in favor of these pathways as well as recent studies describing regulatory targets on the promoter region of the rat hippocampal glucocorticoid receptor gene.

Animals↗
PubMed2001

Morphine-induced degradation of the host defense barrier: role of macrophage injury.

The effect of morphine on the degradation of the host defense barrier in rats and mice was studied. Mice received either 3 or 11 doses of morphine. Mice receiving 11 doses of morphine showed gram-negative bacteremia and bacterial growth in samples of peritoneal fluid (PF), liver, spleen, kidneys, heart, and lungs; PF and tissue samples from only 1 control mouse showed bacterial growth, and no control mice had bacteremia. Mice receiving 11 doses also had suppressed bone marrow macrophage colony formation. Monocytes and peritoneal macrophages harvested from morphine-treated mice showed greater injury than did those from control mice. Pretreatment of mice with naloxone inhibited morphine-induced macrophage injury and degradation of the host defense barrier. In in vitro studies, morphine attenuated the killing of bacteria phagocytosed by macrophages and also facilitated their escape. This study indicates that morphine-induced monocyte and macrophage injury may be linked to degradation of the host defense barrier.

Analgesics, Opioid↗
PubMed2001

CD4-independent infection of human B cells with HIV type 1: detection of unintegrated viral DNA.

Although B lymphocytes are a major constituent of lymphoid organs and acquire a significantly altered phenotype and function in HIV-infected individuals, it remains unclear whether CD4-negative B cells are a susceptible host for viral entry and long-term productive infection. We screened a number of Epstein-Barr virus (EBV)-positive and-negative Burkitt's lymphoma (BL) B cell lines as well as subpopulations of normal B cells that include tonsillar naive and germinal center/memory B cells for the expression of HIV-1 receptors CD4, CXCR4, and CCR5. Cell lines and resting or activated normal B cells lacked CD4 and CCR5 but expressed CXCR4. We demonstrate HIV-1 infection of a CD4-negative, EBV-negative (BL) cell line, CA46, which remained productively infected yet noncytopathic for more than 36 months in culture. HIV-1 (HTLV-III(B)) infection of CA46 cells was mediated through CXCR4 in a CD4-independent manner and correlated with upregulation of the expression of B cell activation markers CD23 and CD95 (Fas receptor). Despite Fas receptor expression, HIV-1-infected CA46 cells remained resistant to Fas-mediated cell death. CA46-derived, CD4-independent viral isolates were proficient in infecting and causing syncytium formation in Molt4 T cells. The HIV-1 genomic organization in persistently infected CA46 clones was found to be predominantly unintegrated linear and circular DNA. Importantly, naive and germinal center/memory B cells could also be infected by HIV-1 in a CD4-independent manner. Although these B cell subpopulations expressed moderate to high levels of CXCR4, they required activation through CD40 and interleukin 4 receptor for infection. These findings point to B cells as an additional HIV-1 target and suggest a structural evolution of the HIV-1 genome responsible for CD4-independent and noncytopathic infections.

B-Lymphocytes↗
PubMed2001

Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors.

Naturally occurring variations in maternal licking/grooming influence neural development and are transmitted from mother to female offspring. We found that the induction of maternal behavior in virgin females through constant exposure to pups (pup sensitization) was significantly shorter in the offspring of High compared with Low licking/grooming mothers, suggesting differences in maternal responsivity. In randomly selected females screened for individual differences in maternal responsivity and subsequently mated, there was a significant and negative correlation (r = -0.73) between the latency to exhibit maternal behavior in the pup sensitization paradigm and the frequency of pup licking/grooming during lactation. Females that were more maternally responsive to pups and that showed increased levels of pup licking/grooming also showed significantly higher oxytocin receptor levels in the medial preoptic area, the lateral septum, the central nucleus (n.) of the amygdala, the paraventricular n. of the hypothalamus, and the bed n. of the stria terminalis. Intracerebroventricular administration of an oxytocin receptor antagonist to mothers on postpartum day 3 completely eliminated the differences in pup licking/grooming, suggesting that differences in oxytocin receptor levels are functionally related to maternal behavior. Finally, estrogen treatment of virgin females significantly increased oxytocin receptor binding in the medial preoptic area and lateral septum of female offspring of High, but not Low, licking/grooming mothers. These findings suggest that maternal licking/grooming influences the development of estrogen sensitivity in brain regions that regulate maternal behavior, providing a potential mechanism for the intergenerational transmission of individual differences in maternal behavior.

Animals↗
PubMed2001

Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression.

The NF-kappaB family of transcription factors functions broadly in the host control of immunoregulatory gene expression, inflammation, and apoptosis. Using Jurkat T cells engineered to inducibly express a transdominant repressor of IkappaBalpha, we examined the role of NF-kappaB in the regulation of cytokine and apoptotic gene expression. In this T cell model, as well as in primary T lymphocytes, expression of TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-kappaB binding activity. TRAIL acts through membrane death receptors to induce apoptosis of activated T lymphocytes and can be up-regulated by a variety of physiological and pharmacological inducers. However, regulation of TRAIL gene expression has not been defined. Treatment with TCR mimetics (PMA/ionomycin, PHA, and anti-CD3/CD28 Abs) resulted in a rapid increase in the expression of TRAIL mRNA and cell surface TRAIL protein. Induction of the transdominant repressor of IkappaBalpha dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-kappaB in the regulation of TRAIL. The induced expression of TRAIL was linked to a c-Rel binding site in the proximal TRAIL promoter at position -256 to -265; mutation of this site or an adjacent kappaB site resulted in a complete loss of the inducibility of the TRAIL promoter. The regulation of TRAIL expression by NF-kappaB may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes.

Amino Acid Substitution↗
PubMed2001

Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.

The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes,was evaluated in SV40 large T-antigen transgenic mice that develop bilateral multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the axillary lymph node region led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced survival. SLC injection led to significant increases in CD4 and CD8 lymphocytes as well as DC at the tumor sites, lymph nodes, and spleen. The cellular infiltrates were accompanied by the enhanced elaboration of Type 1 cytokines and the antiangiogenic chemokines IFN-gamma inducible protein 10, and monokine induced by IFN-gamma (MIG). In contrast, lymph node and tumor site production of the immunosuppressive cytokine transforming growth factor beta was decreased in response to SLC treatment. In vitro, after stimulation with irradiated autologous tumor, splenocytes from SLC-treated mice secreted significantly more IFN-gamma and granulocyte macrophage colony-stimulating factor, but reduced levels of interleukin 10. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for additional evaluation of SLC in regulation of tumor immunity and its use in lung cancer immunotherapy.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Purification of diacylglycerol kinase from Microsporum gypseum and its phosphorylation by the catalytic subunit of protein kinase A.

Diacylglycerol (DG) kinase (EC 2.7.1.107) was purified to homogeneity from the soluble extract of Microsporum gypseum, a dermatophyte. Purified enzyme showed a final specific activity of 2172 pmol/min/mg protein and its apparent molecular weight on SDS-PAGE was found to be 93 kDa. The activity of purified enzyme was inhibited in a dose-dependent manner in the presence of DG-kinase inhibitor (D5919, Sigma). DG-kinase activity was found to be stimulated in the presence of phosphatidylcholine, phosphatidylethanolamine, and cardiolipin while the activity was alleviated in the presence of phosphatidic acid and arachidonic acid. Kinase activity was partially inhibited when assayed after prior treatment with alkaline phosphatase. Treatment of DG-kinase with the catalytic subunit of protein kinase A (PKA)-stimulated DG-kinase activity in a dose-dependent manner. Incubation of DG-kinase with the catalytic subunit of PKA led to the phosphorylation of DG-kinase as revealed by autoradiography. The phosphorylated band disappeared completely in the presence of specific PKA inhibitor. Increased activity of DG-kinase on incubation with the catalytic subunit of PKA was possibly due to the phosphorylation of the former by the latter. Whether this in vitro phosphorylation and activation of DG-kinase occurs under physiological conditions remains to be elucidated.

Adenosine Triphosphate↗