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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 397 records · Page 22Linked to original sources
PubMed2000

Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex.

The topical delivery of transgenes to hair follicles has potential for treating disorders of the skin and hair. Here we show that the topical administration of liposome-DNA mixtures (lipoplex) to mouse skin and to human skin xenografts resulted in efficient in vivo transfection of hair follicle cells. Transfection depended on liposome composition, and occurred only at the onset of a new growing stage of the hair cycle. Manipulating the hair follicle cycle with depilation and retinoic acid treatment resulted in nearly 50% transfection efficiency-defined as the proportion of transfected, newly growing follicles within the xenograft. Transgenes administered in this fashion are selectively expressed in hair progenitor cells and therefore have the potential to affect the characteristics of the follicle. These findings form a foundation for the future use of topical lipoplex applications to alter hair follicle phenotype and treat diseases of the hair and skin.

Animals↗
PubMed2000

TNF-alpha-induced apoptosis in neonatal lymphocytes: TNFRp55 expression and downstream pathways of apoptosis.

Previously we have shown decreased Fas-mediated apoptosis in cord blood lymphocyte subsets. In this study, we compared tumor necrosis factor (TNF)-alpha-induced apoptosis in T lymphocytes and their subsets between cord blood and peripheral blood from healthy young controls. The expression of TNF receptor I (TNFR-I) was assessed by flow cytometry and quantitative RT-PCR. The expression of adapter molecules TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD) and TNF-associated factor-2 (TRAF-2) and caspase 3 was analyzed by Western blotting. The activity of caspase 3 and caspase 8 was measured by colorimetric assay. The susceptibility of CD4+ and CD8+ T cells to TNF-alpha-induced apoptosis was measured by terminal deoxytidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Both CD4+ and CD8+ T cell subsets from cord blood demonstrated decreased susceptibility to TNF-alpha-induced apoptosis that was associated with decreased activation of both caspase 8 and caspase 3 as compared to T cell subsets in peripheral blood. Furthermore, expression of TNFR-I, TRADD and caspase 3 was decreased in cord blood lymphocytes as compared to peripheral blood lymphocytes. The significance of these observations is discussed.

Adaptor Proteins, Signal Transducing↗
PubMed2000

P-glycoprotein (encoded by multidrug resistance genes) is not required for interleukin-2 secretion in mice and humans.

P-glycoprotein (encoded by multidrug resistance genes), a member of the ATP-binding cassette transporter protein superfamily, has been shown to play a role in the secretion of cytokines. This conclusion was based upon the inhibition of cytokine secretion by anti-P-gp monoclonal antibodies. In this study, we show that anti-CD3-stimulated lymphocytes from wild-type, mdr1a knock out and mdr1ab double knock out mice produce similar amounts of IL-2, IFN-gamma, IL-4, and IL-10. In addition, Jurkat T cells that lack P-gp and MDR1-transfected Jurkat T cells (JurkatP-gp) as well as purified human peripheral blood CD4+ P-gp+ and CD4+ P-gp- and CD8+ P-gp+ and CD8+ P-gp- T cell subsets produced comparable amounts of IL-2. These data show that P-gp is not required for secretion of IL-2, IFN-gamma, IL-4, and IL-10 secretion in mice and IL-2 secretion in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

An independent assessment of a supraregional pain management programme and comparison of patients' and general practitioners' perceptions of the effects.

This study was designed to evaluate the therapeutic response, as perceived by patients and their general practitioners, to a supraregional residential pain management programme (INPUT). Twenty patients who completed the INPUT programme and their general practitioners, were sent locally designed questionnaires. Eighteen patients and 16 general practitioners responded. Patients were assessed for the effects of the programme on a wide variety of treatment targets reflecting quality of life. General practitioners were questioned about changes in dependence upon healthcare services. The mean time from attending INPUT to assessment was 11.4 (5.7) months. Thirteen patients indicated a moderate or maximal improvement in quality of life. General practitioners reported a reduced use of healthcare services and improvement in quality of life. The majority of our patients attending INPUT gained benefits that improved their quality of life. Healthcare services appeared to benefit from the patients' greater independence in managing their symptoms.

Adult↗
PubMed2000

The single dose pharmacokinetics of ribavirin in subjects with chronic liver disease.

AIMS: The primary objective of this study was to describe the single dose pharmacokinetics of ribavirin in subjects with normal liver function and those with various degrees of stable chronic liver disease. Additionally this study assessed the safety and tolerability of ribavirin in this population. METHODS: Single oral 600 mg doses of ribavirin were administered to healthy male and female volunteers (n = 6) and patients with stable chronic liver disease (n = 17), in a parallel group study. Pharmacokinetic sampling and tolerability assessments were performed up to 168 h post dose. RESULTS: Single oral doses of 600 mg ribavirin were well tolerated by healthy volunteers and patients with varying degrees of hepatic dysfunction. Although mean Cmax increased with the severity of hepatic dysfunction, there was no change in extent of absorption or renal clearance of ribavirin. CONCLUSIONS: There are no pharmacokinetic reasons for initial dose adjustment of ribavirin in patients with hepatic dysfunction.

Adult↗
PubMed2000

Nuclear grooves in intermediate cells in cervical smears.

One thousand cervical smears from women who took part in a hospital-based screening programme for early detection of cervical cancer were studied for the presence of nuclear grooves. Grooved nuclei were frequently detected in intermediate cells in all phases of the menstrual cycle, although their frequency of occurrence was slightly lower in the luteal and premenstrual phases. The mean number of nuclear grooves varied from 3.6 to 4.2 in different phases of the menstrual cycle. The differences, however, were not statistically significant. The presence of nuclear grooves in cervical cells appears to be a nonspecific finding at present.

Adult↗
PubMed2000

Isolation, purification and characterization of xylanasefrom Staphylococcus sp. SG-13 and its application in biobleaching of kraft pulp.

A haloalkalophilic Staphylococcus sp. SG-13 produced an alkalistable xylanase in wheat bran medium. A 12-fold purification was achieved by using standard purification techniques. The purified xylanase exhibited a dual pH optima of 7.5 and 9.2. The optimum temperature for enzyme activity was 50 degrees C. The enzyme was stable at 50 degrees C for more than 4 h. The xylanase exhibited Km and Vmax values of 4 mg ml-1, 90 micromol min-1 per mg for birchwood xylan and 7 mg ml-1, 55 micromol min-1 per mg for oatspelt xylan, respectively. The substrate binding affinity of xylanase was more for oatspelt xylan but birchwood xylan was hydrolysed more rapidly. The xylanase activity was stimulated by Fe2+, Ni2+, Cu2+ and dithiothreitol up to 60% and was strongly inhibited in the presence of Co2+, Hg2+, Pb2+, phenyl methane sulphonyl fluoride, ethylenediaminetetraacetic acid, and acetic anhydride up to 100%. The xylanase dose of 1.8 U g-1 moisture free pulp, exhibited bleach boosting of kraft pulps optimally at pH 9.5-10.0 and 50 degrees C after 4 h of reaction time. Pretreatment of pulp with xylanase and its subsequent treatment with 8% hypochlorite, reduced the kappa number by 30%, enhanced the brightness and viscosity by 11% and 1.8%, respectively, and improved the paper properties such as tensile strength and burst factor up to 10% and 17%, respectively.

Chlorine Compounds↗
PubMed2000

Involvement of Fas (APO-1/CD-95) during photodynamic-therapy-mediated apoptosis in human epidermoid carcinoma A431 cells.

Photodynamic therapy is a promising treatment modality for a variety of cutaneous neoplasms and other skin disorders. Studies suggest an involvement of multiple pathways during photodynamic-therapy-mediated cell death. A complete knowledge of the mechanisms involved in photodynamic therapy may lead to an improvement in its therapeutic efficacy. In vitro as well as in vivo studies have shown the involvement of apoptosis during photodynamic- therapy-mediated cell death. The pathways by which photodynamic therapy causes this are not fully understood. In this study, employing human epidermoid carcinoma (A431) cells and silicon phthalocyanine 4 photodynamic therapy, we show that the cell surface death receptor Fas (also known as APO-1 or CD-95) pathway is an important contributor to photodynamic-therapy-mediated apoptosis. Employ- ing flow cytometric analysis and confocal microscopy we first established that silicon phthalocyanine 4 photodynamic therapy results in a significant induction of apoptosis in A431 cells. Immunoblot analysis revealed a significant time-dependent increase in the protein expression of Fas at 5, 15, 30, and 60 min post-photodynamic therapy followed by a decrease at later time-points (2 and 3 h post-photodynamic therapy). A Fas enzyme-linked immunosorbent assay demonstrated an increase in this protein in cell culture medium starting at 1 h post-photodynamic therapy and showing a time-dependent response up to 3 h following therapy, suggesting a diffusion of soluble Fas from cells into the medium from 1 h after photodynamic therapy. Silicon phthalocyanine 4 photodynamic therapy also resulted in a time-dependent increase in (i) the multimerization of Fas protein, (ii) the protein expression of Fas ligand, (iii) FADD, an adapter molecule for Fas, and (iv) the binding of FADD with Fas. Silicon phthalocyanine 4 photodynamic therapy also caused a significant activation of FLICE, as evident from the appearance of cleaved products of pro-caspase 8. Further, a pretreatment of cells with rhFas:Fc fusion protein or general caspase inhibitor Z-VAD-FMK followed by silicon phthalocyanine 4 photodynamic therapy resulted in a significantly enhanced cell survival. Taken together, our data, for the first time, delineate an involvement of the Fas pathway as an important contributor to photodynamic-therapy-mediated apoptosis of cancer cells. These observations may be important for improving the efficacy of photodynamic therapy for the treatment of skin cancer and possibly other skin disorders. J Invest Dermatol 115:1041-1046 2000

Apoptosis↗
PubMed2000

Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis.

Transforming growth factor beta (TGF-beta) is a pivotal driver of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. Because TGF-beta also plays important anti-inflammatory and antiproliferative roles in mammalian systems, there has been a recent drive to elucidate downstream mediators of TGF-beta's pro-fibrotic effects with the ultimate goal of developing new anti-fibrotic strategies for treatment of chronic diseases. Connective tissue growth factor (CTGF) belongs to the CCN family of immediate early response genes. Several lines of evidence suggest that CTGF is an important pro-fibrotic molecule in renal disease and that CTGF contributes to TGF-beta bioactivity in this setting. CTGF expression is increased in the glomeruli and tubulointerstium in a variety of renal disease in association with scarring and sclerosis of renal parenchyma. In model systems in vitro, mesangial cell CTGF expression is induced by high extracellular glucose, cyclic mechanical strain and TGF-beta. Recombinant human CTGF augments the production of fibronectin and type IV collagen by mesangial cells and the effects of high glucose on mesangial cell CTGF expression and matrix production are attenuated, in part, by anti-TGF-beta antibody. In aggregate, these observations identify CTGF as an attractive therapeutic target in fibrotic renal diseases.

Connective Tissue Growth Factor↗
PubMed2000

Suction blister induction time: 15 minutes or 150 minutes?

BACKGROUND: The literature on suction blister is somewhat confusing regarding suction blister induction time (SBIT). To date, various factors influencing the SBIT have not been discussed comprehensively. OBJECTIVE: To determine the effect of diameter of suction syringes/cups on SBIT and review the factors influencing SBIT. METHODS: Five young patients (four females, one male; age range 16-27 years, average age 23 years) were selected for the study. Five suction syringes of 2, 5, 10, 20, and 50 ml capacity (diameter 1, 1. 4, 1.7, 2.2, and 3.2 cm, respectively) were applied on the lateral aspect of the thigh and observed for production of unilocular blister at 15 minute intervals. RESULTS: The average SBIT was 63, 72, 98, 123, and 208 minutes in 2, 5, 10, 20, and 50 ml syringes, respectively. CONCLUSIONS: The SBIT is directly proportional to the diameter of the suction syringe. A literature review suggests that the site of the suction blister, age of the subject, amount of vacuum created, temperature, intradermal injection of saline, corticosteroid-induced atrophy, and pretreatment of the site with PUVA are the important factors influencing the SBIT. Use of 10 or 20 ml syringes as suction cups and -300 mmHg pressure are appropriate choices for suction blister induction and produce blisters in about 1-2 hours.

Adolescent↗
PubMed2000

Predictors of event-free survival after repeat intracoronary procedure for in-stent restenosis; study with angiographic and intravascular ultrasound imaging.

AIMS: Lumen enlargement during repeat percutaneous coronary intervention for in-stent restenosis has been shown to be the result of both stent over-expansion and decrease in neointimal tissue. How these two different mechanisms of action may influence outcome and target lesion revascularization after repeat intervention for in-stent restenosis is unclear. METHODS: Intravascular ultrasound guided repeat intervention for in-stent restenosis was carried out either with balloon angioplasty, or with a combination of rotational atherectomy plus balloon angioplasty. Clinical follow-up at 1 year, including death, myocardial infarction, or need for revascularization, was obtained. RESULTS: Seventy patients were included in this study; 40 were treated by balloon alone, and 30 by combination of rotational atherectomy plus balloon. Event-free survival probability was 76+/-5%. The mechanism of lumen enlargement, be it stent over-expansion or tissue removal, had no influence on long-term clinical evolution. The only independent predictor was the minimal lumen cross-sectional area at the end of the procedure, the larger the lumen cross-sectional area, the higher the event-free probability. The cut-off point of the lumen cross-sectional area was set at 4.7 mm(2)by discriminant analysis. Event-free survival was 69+/-15% in patients with <4.7 mm(2)lumen cross-sectional area and 91+/-8% in patients with >4.7 mm(2)lumen cross-sectional area (P=0. 008). CONCLUSIONS: This study showed that the only independent predictor of late clinical outcome after percutaneous re-intervention for in-stent restenosis was final lumen size, no matter which means were used to achieve it.

Angioplasty, Balloon, Coronary↗
PubMed2000

Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes.

Biliary phospholipid secretion is tightly coupled to the secretion of free cholesterol and bile salts. The secretion of phospholipids across the canalicular membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P-glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and phospholipid secretion has not been elucidated. The aims of this study were to determine the effects of bile acid structure on the expression of mdr2 in vitro and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50 micromol/L) increased mdr2 messenger RNA (mRNA) levels in the following order: taurocholate (TCA) (288 +/- 36%, P <. 005) = taurodeoxycholate (TDCA) (276 +/- 36%, P <.025) > taurochenodeoxycholate (TCDCA) (216 +/- 34%, P <.025) > tauroursodeoxycholate (TUDCA) (175 +/- 28%, P <.05) of control levels. The increase in mdr2 mRNA levels by TCA was both time and concentration dependent. Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary diversion (CBD) decreased mdr2 mRNA levels to 66 +/- 9% (P <.025) of sham-operated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls. A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% +/- 2 (P <.001) of pair-fed controls. Squalestatin (1 micromol/L), an inhibitor of cholesterol biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P <.005) in hepatocyte cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2 transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro and in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Cavernous haemangioma of cavernous sinus associated with an internal carotid artery aneurysm.

A 50-year-old woman developed a sudden onset of ophthalmoplegia. CT and MRI showed a massive middle cranial fossa tumour encasing the intracavernous sinus carotid artery. The tumour extended into Meckel's cave and sella, and had eroded the lateral wall of the orbit. Angiography showed a faint tumour blush and an aneurysm of the distal part of cavernous segment of internal carotid artery. On exploration, an extremely vascular, entirely intracavernous sinus cavernous haemangioma was completely excised and the aneurysm was clipped. The literature on this relatively rare and surgically formidable condition is reviewed.

Aneurysm↗