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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 91 records · Page 5Linked to original sources

Detection of free and immune-complexed serine protease and its antibody in TB patients with and without HIV co-infection.

OBJECTIVE: To understand the usefulness of detecting tuberculous IgG antibodies against mycobacterial excretory-secretory 31 kDa serine protease antigen (SEVA TB ES-31) and circulating free and circulating immune-complexed (CIC) serine protease in TB patients with and without HIV infection. DESIGN: Serum was collected from 144 individuals: patients with TB, with TB-HIV co-infection and HIV infection only, and ill and healthy controls. SEVA TB ES-31 antigen, a serine protease isolated from Mycobacterium tuberculosis H37Ra culture fluid, was used in indirect penicillinase ELISA to detect tuberculous antibodies. Similarly, affinity purified anti-ES-31 antibody was used in sandwich ELISA to detect circulating free and CIC serine protease. RESULTS: There was less sensitivity for tuberculous antibody in HIV-infected TB patients (46%) than in those with TB alone (87%) using mycobacterial serine protease. However, the sensitivity of detection of TB in the presence of HIV increased to 87% by concomitant detection of circulating free and CIC serine protease antigen. CONCLUSION: Detection of free and CIC tuberculous serine protease antigen along with antibody is more useful for detecting TB in the presence of HIV co-infection.

Antibody Formation↗

Current status of TNF blocking therapy in heart failure.

Recent experimental studies have shown that tumor necrosis factor alpha (TNF-alpha) has deleterious cardiovascular effects. Tumor necrosis factor alpha antagonists bind to TNF-a and functionally inactivate this cytokine and thereby reverse some of these effects. Various clinical studies of TNF-alpha antagonists have reported conflicting results. The present review analyses all reported clinical trials of TNF-alpha antagonists in congestive heart failure (CHF). The effect of these agents on clinical composite score, CHF hospitalizations, and mortality were compared. Early clinical studies of blocking TNF in patients with heart failure demonstrated promising results. However, recent large-scale, placebo-controlled trials have failed to show any improvement in the clinical status of heart failure. There have in fact, been some reports of worsening of heart failure with these agents. It may be concluded that TNF-alpha antagonists could adversely affect the clinical condition of patients with moderate to severe heart failure.

Antibodies, Monoclonal↗

Comparison of various microbiological tests including polymerase chain reaction for the diagnosis of osteoarticular tuberculosis.

PURPOSE: To evaluate the utility of the polymerase chain reaction (PCR) test for diagnosing osteoarticular tuberculosis (TB). METHODS: Clinical samples (synovial tissue and synovial fluid) obtained from 23 cases of suspected osteoarticular tuberculosis were subjected to Ziehl Neelsen (ZN) smear examination, radiometric BACTEC culture and PCR test for tuberculosis by amplifying 65 kDa antigen coding region of Mycobacterium tuberculosis (M.tb) genome. RESULTS: PCR test was found to be much sensitive than the ZN smear examination and BACTEC culture (p<0.05) in the diagnosis of osteoarticular TB. In synovial fluid samples, PCR was positive in 73.9%, ZN smear examination in 17.39% and BACTEC culture in 39.13% of cases. The positivities were relatively lower with synovial tissue samples, the corresponding figures being 60.8, 8.6 and 26.08% respectively. Moreover, on combining the results of synovial fluid and tissues, the corresponding figures further increased to 78.2, 21.7 and 43.3% respectively. Further, sensitivity and specificity for PCR employing BACTEC culture as the "gold standard" was 100% respectively. Using BACTEC culture, the earliest positivity was seen in three days using synovial tissue specimen and 13 days with synovial fluid, the average detection times being 23.2 days and 32.6 days respectively. On the other hand, PCR test gave a positive result within 24 hours. CONCLUSIONS: PCR test was shown to be much more sensitive than ZN smear examination and BACTEC culture test for diagnosing osteoarticular tuberculosis.

Bacteriological Techniques↗

Driving force and mechanism for spontaneous metal whisker formation.

The room temperature spontaneous growth of low melting point metal whiskers, such as Sn, poses a serious reliability problem in the semiconducting industry; a problem that has become acute with the introduction of Pb-free technology. To date, this 50+ year old problem has resisted interpretation. Herein we show that the driving force is essentially a reaction between oxygen and the sprouting metal. The resulting volume expansion creates a compressive stress that pushes the whiskers up. The model proposed explains our observations on In and Sn whiskers and many past observations. The solution is in principle simple: diffusion of oxygen into the metal must be prevented or slowed down. This was demonstrated by coating the active surfaces with a polymer coating.

Journal Article↗

Estrogen, heat shock proteins, and NFkappaB in human vascular endothelium.

BACKGROUND: We hypothesized that estrogen would increase HSP72 in human coronary artery endothelial cells (HCAEC), and that these would be more sensitive to estrogen than our previous observations in myocytes. METHODS AND RESULTS: HCAEC were treated with 17beta-estradiol or tamoxifen, ranging from physiological to pharmacological(1 nM to 10 micromol/L) for either 24 hours (early) or 7 days (chronic). HSP expression was assessed by Western blots. Both early and chronic 17beta-estradiol and tamoxifen increased HSP72. Electromobility shift assays (EMSA) showed activation of HSF-1 with early, but not chronic, 17beta-estradiol. 17beta-Estradiol activated NFkappaB within 10 minutes, and the ER-alpha selective inhibitor, ICI 182 780, abolished this effect. Transcription factor decoys containing the heat shock element blocked HSP72 induction. Estrogen pretreatment decreased lactate dehydrogenase release with hypoxia. This protective effect persisted despite blockade of HSF-1 by decoys. However, an NF-kappaB decoy prevented the increase in HSP72 and abolished the estrogen-associated protection during hypoxia. CONCLUSIONS: 17beta-Estradiol upregulates HSP72 early and chronically via different mechanisms in HCAEC, and provides cytoprotection during hypoxia, independent of HSP72 induction. NF-kappaB mediates the early increase in HSP72, suggesting that estrogen activates NF-kappaB via a nongenomic, receptor-dependent mechanism, and this leads to activation of HSF-1. Activation of NF-kappaB was critical for estrogen-associated protection. Further studies are needed to elucidate the involved signaling pathways. We hypothesized that estrogen would increase HSP72 in human coronary artery endothelial cells (HCAEC). Both early and chronic treatment increased HSP72. EMSA showed activation of HSF-1 with early, but not chronic, 17beta-estradiol. Transcription factor decoys blocked estrogen-related HSP72 induction. Estrogen decreased LDH release with hypoxia. An NF-kappaB decoy blocked the HSP72 increase and estrogen-associated protection.

Binding, Competitive↗

Genome wide identification and classification of alternative splicing based on EST data.

MOTIVATION: Alternative splicing is currently seen to explain the vast disparity between the number of predicted genes in the human genome and the highly diverse proteome. The mapping of expressed sequences tag (EST) consensus sequences derived from the GeneNest database onto the genome provides an efficient way of predicting exon-intron boundaries, gene structure and alternative splicing events. However, the alternative splicing events are obscured by a large number of putatively artificial exon boundaries arising due to genomic contamination or alignment errors. The current work describes a methodology to associate quality values to the predicted exon-intron boundaries. High quality exon-intron boundaries are used to predict constitutive and alternative splicing ranked by confidence values, aiming to facilitate large-scale analysis of alternative splicing and splicing in general. RESULTS: Applying the current methodology, constitutive splicing is observed in 33,270 EST clusters, out of which 45% are alternatively spliced. The classification derived from the computed confidence values for 17 of these splice events frequently correlate (15/17) with RT-PCR experiments performed for 40 different tissue samples. As an application of the confidence measure, an evaluation of distribution of alternative splicing revealed that majority of variants correspond to the coding regions of the genes. However, still a significant fraction maps to non-coding regions, thereby indicating a functional relevance of alternative splicing in untranslated regions. AVAILABILITY: The predicted alternative splice variants are visualized in the SpliceNest database at http://splicenest.molgen.mpg.de

Algorithms↗

A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer.

The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination in unresectable gall bladder cancer patients. The secondary objectives were to evaluate the toxicity, time to progressive disease, and overall survival. Chemonaïve patients with histologically proven, unresectable bidimensionally measurable gall bladder cancer were enrolled into this study. All patients were required to have a Zubrod's performance status <or=2, no prior radiotherapy, and adequate major organ function. Patients received gemcitabine (1000 mg x m(-2) intravenously over 30-60 min) on days 1 and 8, and cisplatin (70 mg x m(-2) intravenously over 2 h) on day 1, every 21 days. Response assessment was done by a CT scan after every other cycle of chemotherapy. In all, 30 patients were eligible for efficacy and toxicity analysis. There were four (13.3%) complete responders, seven (23.3%) partial responders, and seven (23.3%) with stable disease, with four (13.2%) patients showing disease progression. The median time to progression was 18 weeks (95% confidence interval (CI) 14-24 weeks), and the median duration of response was 13.5 weeks (range 5.5-104 weeks). The median overall survival was 20 weeks (95% CI 14-31 weeks), with 1-year survival rate of 18.6%. WHO grade 3 or 4 anaemia was seen in seven (23.3%) and four (13.3%) patients, respectively. Five (16.6%) patients each experienced grade 3 or 4 neutropenia, and grade 3 or 4 thrombocytopenia was seen in three (10%) and two (6.6%) patients, respectively. The present study shows that gemcitabine/cisplatin combination is well tolerated and active in advanced unresectable gall bladder cancer.

Adult↗

Wavelet-based statistical approach for speckle reduction in medical ultrasound images.

A novel speckle-reduction method is introduced, based on soft thresholding of the wavelet coefficients of a logarithmically transformed medical ultrasound image. The method is based on the generalised Gaussian distributed (GGD) modelling of sub-band coefficients. The method used was a variant of the recently published BayesShrink method by Chang and Vetterli, derived in the Bayesian framework for denoising natural images. It was scale adaptive, because the parameters required for estimating the threshold depend on scale and sub-band data. The threshold was computed by Ksigma2/sigma(x), where sigma and sigma(x) were the standard deviation of the noise and the sub-band data of the noise-free image, respectively, and K was a scale parameter. Experimental results showed that the proposed method outperformed the median filter and the homomorphic Wiener filter by 29% in terms of the coefficient of correlation and 4% in terms of the edge preservation parameter. The numerical values of these quantitative parameters indicated the good feature preservation performance of the algorithm, as desired for better diagnosis in medical image processing.

Algorithms↗

Zoosporangia survival, dehiscence and zoospore formation, and motility in the green alga Rhizoclonium hieroglyphicum as affected by different factors.

Urea at 200 ppm (probably serving as a nitrogen source), liquid Bold's basal medium at pH 7.5, temperature of about 22 degrees C and light intensity of about 40 micromol m(-2) s(-1) for 16 h a day induced rapid and/or abundant zoospores formation and zoosporangia dehiscence and favored zoospore liberation, speed and motility time period in the green alga Rhizoclonium hieroglyphicum. However, factors such as water stress (2 and 4 % agarized media, liquid media with 0.2-0.4 mol/L NaCl, 5-60 min blot-dryness of filaments), pH extremes of liquid media (at < or =6.5 and > or =9.5), temperature shock in liquid media (5 and 35 degrees C for > or =5 min), UV exposure (0.96-3.84 kJ/m2), lack of all nutrients from liquid medium (double distilled water), darkness, and presence of "heavy" metals (1-25 ppm Cu, Fe, Zn, Hg, Ni, Co) or organic substances (200-600 ppm captan or DDT, 800 and 1000 ppm 2,4-D, 50 and 400 ppm indole-3-acetic acid (3-IAA), 1000 and 2000 ppm urea, 100 and 200 ppm thiourea) in liquid media decreased and/or delayed at various levels either zoosporangia survival, zoospore formation or zoosporangia dehiscence and/or the rate of zoospore liberation from zoosporangia, zoospore speed and time period of motility in the media or totally inhibited all these processes. 3-IAA at 50 and 400 ppm induced zoosporangial papilla to grow into a tube-like projection of about 30-120 microm in length. Zoosporangial dehiscence rather than zoospore formation or zoosporangia survival, and zoospore motility period rather than zoospore speed are probably more sensitive to various adverse environmental factors. The rate of zoospores liberation from zoosporangium (possibly related directly to some extent on the zoospore number inside) is probably independent of zoospore speed in the medium.

Chlorophyta↗

Vegetative survival and reproduction under submerged and air-exposed conditions and vegetative survival as affected by salts, pesticides, and metals in aerial green alga Trentepohlia aurea.

Trentepohlia aurea vegetative cells do not survive submerged conditions for more than 5 months, but can survive air-exposed conditions for more than 1 year. Disintegration and rapid death of algal cells was observed to a higher extent under submerged than air-exposed condition. Under submerged conditions T. aurea did not form any sporangium while prolific formation occurred under air-exposed conditions. Under submerged conditions algal cells formed few-celled, filamentous, cytoplasmic type setae. Vegetative cells were resistant to some extent to various levels of salt (NaCl, < or = 0.8 mol/L), pesticides (DDT, 2,4-D or captan, 2000 ppm) and 'heavy' metals (zinc or nickel, 200 ppm; cobalt, < or = 100 ppm.)

Aerobiosis↗

Significance of incidental desmoids identified during surgery for familial adenomatous polyposis.

PURPOSE: The behavior of intra-abdominal desmoids in familial adenomatous polyposis is incompletely understood. Findings range from typical mass lesions to flat sheets, termed the desmoid reaction or desmoid precursor lesion. The latter often are incidental findings of uncertain significance. The study was designed to describe the natural history of incidental intra-abdominal desmoid tumors with particular reference to the desmoid reaction. METHODS: Patients who underwent laparotomy for familial adenomatous polyposis at the Cleveland Clinic Foundation were identified. The incidence of incidental intra-abdominal desmoid tumors was determined by review of operative records. Intra-abdominal desmoid tumors were classified as mass lesions if three-dimensional or desmoid reaction if two-dimensional. The incidence of clinically apparent intra-abdominal desmoid tumors (typical mass lesions on physical examination or cross-sectional imaging in symptomatic patients) was determined by chart review. The incidence of clinical intra-abdominal desmoid tumors between groups was compared by Fisher's exact test. RESULTS: A total of 266 patients (153 females; median age, 26 (range, 9-63) years) underwent abdominal surgery for familial adenomatous polyposis. Incidental intra-abdominal desmoid tumors were identified in 34 patients: 8 at the index surgery and 26 at relaparotomy. These lesions influenced the planned procedure in eight cases (26 percent), including preventing ileoanal pouch in 3 of 19 patients in whom this was intended. The median follow-up from the time of identification of intra-abdominal desmoids was 42 (range, 2-178) months at which point four patients (11 percent) had developed clinical intra-abdominal desmoid tumors. There was no significant difference in incidence of clinical intra-abdominal desmoid tumors between mass and desmoid reaction groups ( P = 0.27). CONCLUSIONS: Incidental intra-abdominal desmoid tumors are a common finding at relaparotomy in patients with familial adenomatous polyposis. These lesions influence planned surgery in a minority of cases. Desmoid reaction may have little bearing on the subsequent development of clinically significant intra-abdominal desmoid tumors.

Adenomatous Polyposis Coli↗

Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: a case report.

Fibrosing cholestatic hepatitis (FCH) is an uncommon complication of renal transplantation. It is usually associated with hepatitis B and C viral infection. It is further rare in renal transplantation in absence of HBV and HCV infection. To the best of our knowledge, only three cases of FCH in renal transplantation, which were both HBV and HCV negative, have been reported to date. Out of these, two cases were diagnosed to have CMV infection and the third was attributed to azathioprin. We are presenting another case of FCH in a renal transplant recipient with CMV infection.

Adult↗

Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient.

Renal transplantation (RT) recipients are at a high risk of developing tuberculosis (TB) following transplantation. Effectiveness of isoniazid (INH) in preventing TB is well documented in immunocompetent as well as immunocompromised persons. There is paucity of data on role of INH prophylaxis in RT recipients. Thus, a prospective randomised trial of INH in RT recipients was carried out to determine the efficacy of daily INH monotherapy in the prevention of TB in these patients. Patients of end stage renal disease (ESRD) taken for RT formed the subjects of study. Patients with active TB and active hepatitis at the time of RT were excluded from the study. Patients were randomised to receive INH 300 mg with pyridoxine 20 mg daily from the day of RT. The duration of the treatment was planned for 1 year or till the development of TB, which ever was earlier. Between October 1998 and September 2000, 114 RT were done at our hospital. Of these, 24 (21%) patients had active TB at the time of RT and thus were excluded. Patients included were randomised with 1:2 ratio of treatment and control group. Of the 90 patients thus enrolled, 30 were randomised in treatment group and 60 in control group. Of the included patients five patients had very early graft loss (three in treatment and two in control group) within days and thus excluded from the analysis. Three of the 27 (11.1%) patients in treatment group and 15 (25.8%) in control group developed TB (P = 0.10). The risk ratio of (RR) of INH versus control group of TB was 0.36 (95% CI, 0.10-1.32) but the difference was not statistically significant (P = 0.12). Only one patient developed INH induced hepatitis. In conclusion, with INH prophylaxis, there was a trend towards protection from TB, though it was not statistically significant. Further, all patients tolerated INH and hepatotoxicity was not a major problem in this group of patients.

Antitubercular Agents↗

The possibilities of uncemented glenoid component--a finite element study.

OBJECTIVE: (1) Determine the initial stress distributions within an uncemented implanted glenoid during elevation of the arm and to investigate whether failure is caused by stresses generated within this implant-bone structure. (2) Compare stress patterns between the uncemented design and two basic models of cemented prostheses. DESIGN: The uncemented component consists of a polyethylene cup with a metal-backing. All material interfaces were assumed to be fully bonded. BACKGROUND: Cemented glenoid components have been frequently vulnerable to failure within itself and at the cement-bone interface. A 3-D finite element analysis of an uncemented design is required to investigate whether clinical observations on failure can be better explained with a stress analysis. METHODS: A 3-D finite element submodel an uncemented prosthesis was generated using CT-scan data and realistic loading conditions (humeral abduction, 30-180 degrees ). The submodelling approach was based on an overall solution of a complete scapula acted upon by all muscles, ligaments and joint reaction forces. RESULTS: High Von Mises stresses (20-70 MPa) were generated in the metal-backing during abduction. Stresses were reduced in the polyethylene cup by 17-20% as compared to the cemented designs. Stresses in the underlying bone were substantially lower than to the natural glenoid. Stress-shielding can be observed in the trabecular bone underlying the prosthesis. The implant-bone interface is secure against interface failure at moderate loads, although the implant-bone (metal-bone) interface around the superior edge of the prosthesis is subject to high stresses (normal: 11.85 MPa, shear: 6.67 MPa) as compared to the cemented prosthesis. Whereas, the cement-bone interface, appears more likely to fail either at locations adjacent to the keel or at locations around the superior edge of the cemented design. The uncemented design therefore appeared to be a reasonable alternative to fixation with cement. RELEVANCE: Results of this study strongly agree with clinical and radiographic findings. Although indications of stress-shielding and separation of modular parts of the prosthesis were apparent, the implant-bone interface seems less likely to fail as compared to cemented designs. Once initial fixation of the implant is achieved, the uncemented design appears to have better prospects than cemented ones.

Equipment Failure Analysis↗

Stress analysis of cemented glenoid prostheses in total shoulder arthroplasty.

Glenoid component loosening is the most-frequently encountered problem in the total shoulder arthroplasty. The purpose of the study was to investigate whether failure of the glenoid component is caused by stresses generated within the cement mantle, implant materials and at the various interfaces during humeral abduction, using 3-D FE analyses of implanted glenoid structures. FE models, one total polyethylene and the other, metal backed polyethylene, were developed using CT-scan data and submodelling technique, which was based on an overall solution of a natural scapula model acted upon by all the muscles, ligaments and joint reaction forces. Material interfaces were assumed to be fully bonded. Based on the FE stress analysis, the following observations were made. (1) The submodelling technique, which required a large-size submodel and the use of prescribed displacements at cut-boundaries located far away from the glenoid, was crucial for evaluations on glenoid component. (2) Total polyethylene results in lower-peak stresses (tensile: 10 MPa, Von-Mises: 8.31 MPa) in the cement as compared to a metal-backed design (tensile: 11.5 MPa, Von-Mises: 9.81 MPa). The maximum principal (tensile) stresses generated in the cement mantle for both the designs were below its failure strength, but might evoke crack initiation. (3) The cement-bone interface adjacent to the tip of the keel seemed very likely to fail for both the designs. In case of metal-backed design, this interface adjacent to the tip of the keel appears even more likely to fail. (4) High metal-cement interface stresses for a moderate load might indicate failure at higher load. (5) It appears that both the designs were vulnerable to failure in some ways or the other. A part of the subchondral bone along the longitudinal axis of the glenoid cavity should be preserved to strengthen the glenoid structure and to reduce the use of cement.

Arthroplasty, Replacement↗

Cost-effective control of SO2 emissions in Asia.

Despite recent efforts to limit the growth of SO(2) emissions in Asia, the negative environmental effects of sulphur emissions are likely to further increase in the future. This paper presents an extension of the RAINS-Asia integrated assessment model for acidification in Asia with an optimisation routine that can be used to identify cost-effective emission control strategies that achieve environmental targets for ambient SO(2) concentrations and sulphur deposition at least costs. Example scenarios developed with this optimisation module demonstrate a potential for significant cost savings in Asia, if emission controls are allocated to those sources that have the largest environmental impact and are cheapest to control. It is shown that strategies that simultaneously address harmful population exposure and the risk of vegetation damage from acid deposition result in the most cost-effective use of resources spent for emission controls.

Air Pollutants↗