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Biomedical subjects

S Mahajan

Publications and source records attributed to S Mahajan.

At least 19 recordsLinked to original sources

Urodynamic prolapse reduction alters urethral pressure but not filling or pressure flow parameters.

PURPOSE: To test the hypothesis that advanced stages of pelvic organ prolapse can result in a functional obstruction of the urethra, we studied the effects of manual prolapse reduction on urodynamic and urethral electromyographic parameters in women with stage III and IV pelvic organ prolapse. MATERIALS AND METHODS: Women with advanced pelvic organ prolapse undergoing clinical multichannel urodynamics with concentric needle electromyography of the urethra were invited to participate in this institutional review board approved study. Women underwent filling cystometry and electromyography with prolapse everted and with prolapse reduced. Women were randomized to cystometry order (reduced vs everted). All subjects underwent a third study with prolapse reduction. Maximum urethral closure pressure and quantitative electromyography of the striated urethral sphincter were determined at maximum cystometric capacity. During the pressure flow study voiding parameters, including urethral electromyography quieting, were determined. The nonparametric paired sign test was used to evaluate differences in urodynamic parameters and quantitative electromyography with pelvic organ prolapse reduced and unreduced. Results were considered significant at the 5% level. RESULTS: The 31 participants had mean age of 60 years (range 36 to 78) and 83% were white. There were no clinically significant differences in maximum cystometric capacity, voided volume, maximal flow and detrusor pressure at maximal flow or time to maximal flow between the reduced and everted prolapse states. Prolapse reduction resulted in a clinically and statistically significant decrease in maximum urethral closure pressure (-31%) but it had no impact on quantitative urethral electromyography. CONCLUSIONS: These findings demonstrate that, although prolapse reduction significantly decreases maximum urethral closure pressure, it does not alter intrinsic neuromuscular activity of the striated urethral sphincter. Prolapse reduction does not alter any other filling or pressure flow parameter.

Adult↗

Easily coupled whispering gallery plasmons in dielectric nanospheres embedded in gold films.

A new self-aligned robust method for coupling to whispering gallery modes (WGMs) of submicron microspheres utilizes their periodic arrangement without relying on nanopositioned external coupling devices. The microspheres are embedded in a nanostructured gold surface supporting delocalized plasmonic crystal modes that mediate the coupling, and can be tuned by the geometry. Detailed measurements of the angle- and orientation-dependent reflectivity reveal localized plasmonic WGMs whose energies scale with sphere diameter and agree closely with Mie calculations. Coupling between these plasmonic WGMs leads to mode splitting and the formation of plasmonic minibands of a controllable bandwidth.

Journal Article↗

An efficient and versatile approach for the construction of oligonucleotide microarrays.

A new immobilization chemistry for covalent attachment of phosphorylated oligonucleotides on epoxy-activated glass surface via opening of oxirane ring is described. The proposed strategy results in excellent immobilization efficiency, spot homogeneity, and morphology. The constructed microarray was successfully demonstrated for discrimination of nucleotide mismatches.

Base Pair Mismatch↗

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Adolescent↗

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Adolescent↗

Classic Kaposi's sarcoma in a Nepalese woman from a purportedly nonendemic area.

Kaposis sarcoma (KS) occurs as four types; classic, endemic, immunosuppression-associated, and AIDS-associated. The presence of KS-associated herpesvirus (human herpesvirus 8) DNA in the tissue samples of 95% of all variants of KS has confirmed its role in the aetiopathogenesis of KS. It is now believed that these clinical variants most likely represent different manifestations of the same pathological process. Our case represents the first case of classic KS from our region.

Aged↗

CT appearances of hydatid disease at various locations.

Hydatid disease has characteristic imaging features on CT, which allow accurate preoperative diagnosis in most cases. However, when it occurs at unusual locations the diagnosis is often difficult, especially as the imaging appearance varies at different sites. In this article we have presented a pictorial review of the CT features of disease due to Echinococcus granulosus at various sites in the human body.

Animals↗

The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases.

The cytosolic glutathione S-transferases are a family of structurally homologous enzymes with multiple functions, including xenobiotic detoxification, clearance of oxidative stress products, and modulation of cell proliferation and apoptosis signaling pathways. This wide-ranging functional repertoire leads to several possible therapeutic uses for isoform-specific GST inhibitors. These inhibitors may be used, in principle, to modulate tumor cell drug resistance, as sensitizers to therapeutically directed oxidative stress, to enhance cell proliferation and to augment anti-malarial drugs. With increasing knowledge of GST structural and function, rational design strategies and mechanism-based inhibitors have been exploited successfully. However, design of isoform specificity remains a significant challenge in GST inhibitor development. Strategies for further inhibitor design and their possible limitations, along with potential therapeutic uses, are summarized.

Biology↗

Herpes simplex type 1 shedding is associated with reduced hospital survival in patients receiving assisted ventilation in a tertiary referral intensive care unit.

The impact of shedding of herpes simplex virus type 1 (HSV-1) on hospital survival of patients receiving assisted ventilation in an adult tertiary referral, acute trauma intensive care unit was assessed. The study was designed to address a clinical impression linking HSV-1 recovery with poor survival. Two hundred and forty-one males and 152 females were enrolled into a longitudinal cohort study. Combined throat swabs and tracheal secretions were tested for HSV-1 shedding using a nested nucleic acid amplification protocol; patients were ranked as nonshedders, shedders, and high-level shedders. Nonparametric analysis assessed the impact of shedding on hospital survival and logistic regression measured the confounding influence of sex, age, and the Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score. Linear-by-linear association determined the influence of the level of shedding on hospital survival. The observed mortality rate was 113/393 (28.8%). Patients shedding HSV-1 106/393 (27%) had a significant reduction in hospital survival 66/106 (62%) in HSV-1 shedders compared with 217/287 (75.6%) in nonshedders (P = 0.002). This difference remained significant when adjusted for age and sex (P = 0.026). Respective mortality figures for HSV-1 shedders and nonshedders were 43/106 (40.6%) and 70/287 (24.4%) (P = 0.002). HSV-1 shedding was associated with a significant reduction in hospital survival amongst patients receiving assisted ventilation. Hospital mortality in HSV-1 shedders was increased by 16.2% over nonshedders. The role of HSV-1 in this setting needs to be addressed.

Adolescent↗

Association of drug abuse with inhibition of HIV-1 immune responses: studies with long-term of HIV-1 non-progressors.

Recreational drug use has been proposed to affect the course of human immunodeficiency virus (HIV) infections. To investigate the effects of substance abuse on HIV infections, we compared virus-specific cytotoxic T lymphocyte (CTL) responses and the expression of IL-16, TGF-beta1, and CXCR4 in three different cohorts of HIV-infected patients: (1) long-term nonprogressors (LT-NPs) of HIV infection who do not use recreational drugs; (2) nondrugs using normal progressors (NPs), and (3) drugs using NPs. Our results show that LT-NPs manifest increased CTL activity and IL-16 expression and decreased expression of TGF-beta1 and CXCR4 compared to NPs, regardless of recreational drug usage. Furthermore, drugs using NPs showed significantly lower levels of CTL and IL-16 expression and increased TGF-beta1 and CXCR4 expression compared to nondrugs using NPs. Our results suggest that recreational drug use may reduce CTL and IL-16 expression and increase the expression of TGF-beta1 and CXCR4, all of which may facilitate progression of HIV infections.

Blotting, Northern↗

Ameloblastomatous calcifying odontogenic cyst: a rare histologic variant.

Calcifying odontogenic cyst (COC) is an uncommon developmental odontogenic cyst first described by Gorlin in 1962. It is considered as extremely rare and accounts for only 1% of jaw cysts reported. Because of its diverse histopathology, there has always been confusion about its nature as a cyst, neoplasm or hamartoma. Several subclassifications have been proposed. Here, we present a case of calcifying odontogenic cyst with ameloblastic proliferation - an extremely rare histologic variant. The classical histologic features of the lining epithelium in the form of cords and presence of characteristic ghost cells were seen along with ameloblastomatous proliferations. Ameloblastomatous COC microscopically resembles unicystic ameloblastoma except for the ghost cells and calcifications within the proliferative epithelium. The nature of the COC is controversial. The case is presented here for its rarity, and difference between ameloblastomatous COC and ameloblastoma ex COC has been emphasized.

Adult↗

Transcription factor STAT5A is a substrate of Bruton's tyrosine kinase in B cells.

STAT5A is a molecular regulator of proliferation, differentiation, and apoptosis in lymphohematopoietic cells. Here we show that STAT5A can serve as a functional substrate of Bruton's tyrosine kinase (BTK). Purified recombinant BTK was capable of directly binding purified recombinant STAT5A with high affinity (K(d) = 44 nm), as determined by surface plasmon resonance using a BIAcore biosensor system. BTK was also capable of tyrosine-phosphorylating ectopically expressed recombinant STAT5A on Tyr(694) both in vitro and in vivo in a Janus kinase 3-independent fashion. BTK phosphorylated the Y665F, Y668F, and Y682F,Y683F mutants but not the Y694F mutant of STAT5A. STAT5A mutations in the Src homology 2 (SH2) and SH3 domains did not alter the BTK-mediated tyrosine phosphorylation. Recombinant BTK proteins with mutant pleckstrin homology, SH2, or SH3 domains were capable of phosphorylating STAT5A, whereas recombinant BTK proteins with SH1/kinase domain mutations were not. In pull-down experiments, only full-length BTK and its SH1/kinase domain (but not the pleckstrin homology, SH2, or SH3 domains) were capable of binding STAT5A. Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity. In BTK-competent chicken B cells, anti-IgM-stimulated tyrosine phosphorylation of STAT5 protein was prevented by pretreatment with the BTK inhibitor LFM-A13 but not by pretreatment with the JAK3 inhibitor HI-P131. B cell antigen receptor ligation resulted in enhanced tyrosine phosphorylation of STAT5 in BTK-deficient chicken B cells reconstituted with wild type human BTK but not in BTK-deficient chicken B cells reconstituted with kinase-inactive mutant BTK. Similarly, anti-IgM stimulation resulted in enhanced tyrosine phosphorylation of STAT5A in BTK-competent B cells from wild type mice but not in BTK-deficient B cells from XID mice. In contrast to B cells from XID mice, B cells from JAK3 knockout mice showed a normal STAT5A phosphorylation response to anti-IgM stimulation. These findings provide unprecedented experimental evidence that BTK plays a nonredundant and pivotal role in B cell antigen receptor-mediated STAT5A activation in B cells.

Agammaglobulinaemia Tyrosine Kinase↗

Glyceroneogenesis and the source of glycerol for hepatic triacylglycerol synthesis in humans.

Glyceroneogenesis, i.e. the synthesis of the glycerol moiety of triacylglycerol from pyruvate, has been suggested to be quantitatively important in both the liver and adipose tissue during fasting. However, the actual contribution of glyceroneogenesis to triacylglycerol synthesis has not been quantified in vivo in human studies. In the present study we have measured the contribution of glycerol and pyruvate to in vivo synthesis of hepatic triacylglycerol in nonpregnant and pregnant women after an overnight fast. Five nonpregnant women were administered [(13)C(3)]glycerol tracer as prime constant rate infusion, and the appearance of tracer in plasma glucose and triacylglycerol was quantified using gas chromatography-mass spectrometry. The contribution of pyruvate to hepatic triacylglycerol was quantified in nonpregnant and pregnant women using the deuterium labeling of body water method. The appearance of [(2)H] in hydrogens on C(1) and C(3) of triacylglycerol was measured following periodate oxidation of the glycerol isolated from hydrolyzed triacylglycerol. After a 16-h fast, approximately 6.1% of the plasma triacylglycerol pool was derived from plasma glycerol, whereas 10 to 60% was derived from pyruvate in nonpregnant women and pregnant women early in gestation. Our data suggest that glyceroneogenesis from pyruvate is quantitatively a major contributor to plasma triacylglycerol synthesis and may be important for the regulation of very low density lipoprotein triacylglycerol production. Our data also suggest that 3-glycerol phosphate is in rapid equilibrium with the triosephosphate pool, resulting in rapid labeling of the triose pool by the administered tracer glycerol. Because the rate of flux of triosephosphate to glucose during fasting far exceeds that to triacylglycerol, more glycerol ends up in glucose than in triacylglycerol. Alternatively, there may be two distinct pools of 3-glycerol phosphate in the liver, one involved in generating triosephosphate from glycerol and the other involved in glyceride-glycerol synthesis.

Blood Glucose↗

Simple time weighted average level air-monitoring method for sulfur mustard in work places.

A simple air-monitoring method was developed and validated for vesicant sulfur mustard (HD) in the work place at time weighted average levels. XAD-2 adsorbent was used for the collection of HD vapours for 8 h followed by liquid desorption with carbon tetrachloride. The trace level analysis was carried out by gas chromatography-photoionization detection and was confirmed by gas chromatography-mass spectrometric detection in the selected ion mode.

Air Pollutants, Occupational↗

The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms.

Angiomyolipomas are benign tumors of the kidney derived from putative perivascular epithelioid cells, that may undergo differentiation into cells with features of melanocytes, smooth muscle, and fat. To gain further insight into angiomyolipomas, we have generated the first human angiomyolipoma cell line by sequential introduction of SV40 large T antigen and human telomerase into human angiomyolipoma cells. These cells show phenotypic characteristics of angiomyolipomas, namely differentiation markers of smooth muscle (smooth muscle actin), adipose tissue (peroxisome proliferator-activator receptor gamma, PPARgamma), and melanocytes (microophthalmia, MITF), thus demonstrating that a single cell type can exhibit all of these phenotypes. These cells should serve as a valuable tool to elucidate signal transduction pathways underlying renal angiomyolipomas.

Actins↗