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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 55 records · Page 3Linked to original sources

Distinct phenotype associated with a cryptic subtelomeric deletion of 19p13.3-pter.

Telomeres are gene rich regions with a high recombination rate. Cryptic subtelomeric rearrangements are estimated to account for 5% of mental retardation/malformation syndromes. Here we present the first patient with a deletion of 19p13.3, identified by subtelomeric FISH analysis. His features included a distinctive facial appearance, cleft palate, hearing impairment, congenital heart malformation, keloid scarring, immune dysregulation, and mild learning difficulties. Subtelomeric FISH analysis identified a deletion of 19p13.3-pter. The deletion size was determined to be 1.2 Mb by FISH analysis. It extended from within the chromosomal region covered by BAC RP11-50C6 to 19pter. The deleted area encompassed approximately 60 genes. Fifteen possible candidate genes were considered with respect to the phenotype, including follistatin-related precursor 3 (FSTL3) and serine-threonine kinase 11 (STK-11).

Abnormalities, Multiple↗

The insulin-like growth factor system and colorectal cancer: clinical and experimental evidence.

OBJECTIVE: The aim of this review is to clarify the involvement of the insulin-like growth factor (IGF) system in the development of colorectal malignancy. MATERIALS AND METHODS: Medline searches were used to identify key articles relating the IGF system with the development of colorectal cancer. RESULTS: The IGF system has been linked to colorectal malignancy by a convergence of data from epidemiological, clinical and laboratory-based sources. CONCLUSION: Further work is needed to characterise the IGF system expression in the colon. Such clarification could lead to the identification of targets that can be manipulated for clinical advantage.

Biomarkers, Tumor↗

Policy interventions implemented through sporting organisations for promoting healthy behaviour change.

BACKGROUND: Sporting organisations provide an important setting for health promotion strategies that involve policies, communication of healthy messages and creation of health promoting environments. The introduction of policy interventions within sporting organisations is one strategy to target high risk behaviours such as smoking, alcohol consumption, excess sun exposure, unhealthy eating and discrimination. OBJECTIVES: To review all controlled evaluation studies of policy interventions organised through sporting settings to increase healthy behaviour (related to smoking, alcohol, healthy eating, sun protection, discrimination, safety and access). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsyclNFO, CINAHL, SPORTDiscus, Sociological Abstracts, Dissertation Abstracts, freely available online health promotion and sports-related databases hosted by leading agencies, and the internet using sport and policy-related key words. We identified further studies in the bibliographies of articles and by contacting authors of key articles in the area. SELECTION CRITERIA: We aimed to identify research that had used study designs that incorporated an evaluated intervention and comparison. Uncontrolled studies, meeting other inclusion criteria, were to be reported in an annex to the review. Types of studies: Studies in which sporting organisations were allocated to a policy intervention or control/comparison group. No minimum follow-up required. TYPES OF PARTICIPANTS: People of all ages. Types of interventions: Any policy intervention implemented through sporting organisations to instigate and/or sustain healthy behaviour change, intention to change behaviour, or changes in attitudes, knowledge or awareness of healthy behaviour. Policies must address any of the following: smoking, alcohol, healthy eating, sun protection, access for disadvantaged groups, physical safety (not including injuries), and social and emotional health (e.g.. anti-vilification, anti-discrimination). Types of outcome measures: Behaviour change, intention to change behaviour, change in attitudes, knowledge or awareness of healthy behaviour, and policy presence. DATA COLLECTION AND ANALYSIS: We assessed whether identified citations were controlled evaluation studies and investigated the use of policy implemented in sporting settings. Abstracts were independently inspected by two reviewers and full papers were obtained where necessary. As no controlled evaluation studies were located, no data collection or analysis was undertaken. No uncontrolled studies meeting other inclusion criteria were identified and therefore no annex is presented. MAIN RESULTS: No rigorous studies were located to test the effectiveness of policy interventions organised through sporting organisations to increase healthy behaviours, attitudes, knowledge or inclusion of health oriented policies within the organisations. AUTHORS' CONCLUSIONS: We were unable to find any controlled studies to guide the use of policy interventions used in sporting settings. The search process revealed a number of case studies with anecdotal reporting of outcomes. We strongly recommend that rigorous evaluation techniques are employed more commonly in this field to illuminate the impact of health promoting policy on outcomes, and the contexts and processes which are likely to be effective in reducing harmful behaviours.

Alcohol Drinking↗

Interventions implemented through sporting organisations for increasing participation in sport.

BACKGROUND: There is now compelling scientific evidence that increased levels of physical activity can bring wide-ranging health benefits. These benefits can extend beyond physical health and include other positive impacts relating to mental health and personal development. The sport and recreation sector is viewed as a priority area for increasing rates of physical activity. Participation rates have been shown to be lower in females, decline with age, and are reduced in lower socio-economic and minority groups. It is important to determine the most effective interventions that sporting organisations can use to increase participation. OBJECTIVES: To review all controlled evaluation studies of interventions organised through sporting settings to increase participation. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsyclNFO, CINAHL, SPORTDiscus, Sociological Abstracts, Dissertation Abstracts, and a number of freely-available online health promotion and sports-related databases. The internet was used extensively to search for studies and locate information generated by sporting bodies throughout the world. SELECTION CRITERIA: Types of studies: Controlled evaluation studies. No minimum follow-up required. Uncontrolled studies, meeting other inclusion criteria, were to be reported in an annex to the review. TYPES OF PARTICIPANTS: People of all ages. Types of interventions: Any intervention designed to increase active and/ or non-active participation in sport. These could include: mass media campaigns; information or education sessions; management or organisational change strategies; policy changes, for example to improve the socio-cultural environment to encourage people of specific age, gender or ethnicity to participate; changes to traditional or existing programs, for example club or association-initiated rule modification programs; provision of activities beyond traditional or existing programs, for example 'Come and Try' initiatives (teaser or taster programs); skill improvement programs; volunteer encouragement programs. Types of outcome measures: Change in the number of (active and non-active) participants in organised sport, change in status from non-participating to non-active or active participation, change in status from non-active to active participation. DATA COLLECTION AND ANALYSIS: We assessed whether identified citations were controlled evaluation studies which investigated the use of interventions implemented in sporting settings to increase participation. Two reviewers independently inspected abstracts. We obtained full papers where necessary. As no controlled evaluation studies were located, no data collection or analysis was undertaken. No uncontrolled studies meeting other inclusion criteria were identified and therefore no annex is presented. MAIN RESULTS: Despite a thorough review of the published and unpublished literature, we were unable to locate any rigorous studies which tested the effects of interventions organised through sporting organisations to increase participation in sport. AUTHORS' CONCLUSIONS: There is an absence of high quality evidence to support interventions designed and delivered by sporting organisations to increase participation in sport. Interventions funded and conducted in this area must be linked to a rigorous evaluation strategy in order to examine overall effectiveness, sociodemographic differentials in participation and cost-effectiveness of these strategies.

Exercise↗

Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats.

In the present study, the effect of mangiferin (a xanthone glucoside, isolated from the leaves of Mangifera indica) on the atherogenic potential of streptozotocin (STZ)-diabetes was investigated. In addition, the effect of mangiferin on oral glucose tolerance in glucose-loaded normal rats was also determined. The chronic intraperitoneal (i.p.) administration of mangiferin (10 and 20 mg/kg) once daily (o.d.) for 28 days exhibited antidiabetic activity by significantly lowering fasting plasma glucose level at different time intervals in STZ-diabetic rats. Further, mangiferin (10 and 20 mg/kg, i.p.) showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels coupled together with elevation of high-density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index in diabetic rats. In addition, the chronic administration of mangiferin (10 and 20 mg/kg, i.p.) for 14 days significantly as well as markedly improved oral glucose tolerance in glucose-loaded normal rats suggesting its potent antihyperglycemic activity. The accumulating evidences suggest that both pancreatic and extrapancreatic mechanisms might be involved in its antidiabetic or antihyperglycemic action. In conclusion, the present study demonstrates that mangiferin possesses significant antidiabetic, antihyperlipidemic and antiatherogenic properties thus suggesting its beneficial effect in the treatment of diabetes mellitus associated with hyperlipidemia and related cardiovascular complications.

Animals↗

Diuretic usage in heart failure: a continuing conundrum in 2005.

Several large well-designed clinical trials have shown that the use of diuretics is beneficial in patients with hypertension. However, similarly robust data regarding their role in chronic heart failure are lacking. Historically, diuretics were developed for treatment of sodium and water retention in oedematous disorders and clinically, they remain the most potent drugs available to relieve symptoms and eliminate oedema in the congested patient with heart failure. In the non-congested patient, however, diuretics continue to be used on a purely clinical basis without sufficient characterization of benefits, adverse effects, and potential influence on mortality. There are also concerns that chronic diuretic usage can cause adverse vascular effects, unfavourable neuroendocrine activation, electrolyte imbalances, and life-threatening arrhythmias. In this article, we review the limited evidence available regarding the benefits and perils of using diuretics in heart failure.

Arrhythmias, Cardiac↗

Robust non-homomorphic approach for speckle reduction in medical ultrasound images.

Most existing wavelet-based image denoising techniques are developed for additive white Gaussian noise. In applications to speckle reduction in medical ultrasound (US) images, the traditional approach is first to perform the logarithmic transform (homomorphic processing) to convert the multiplicative speckle noise model to an additive one, and then the wavelet filtering is performed on the log-transformed image, followed by an exponential operation. However, this non-linear operation leads to biased estimation of the signal and increases the computational complexity of the filtering method. To overcome these drawbacks, an efficient, non-homomorphic technique for speckle reduction in medical US images is proposed. The method relies on the true characterisation of the marginal statistics of the signal and speckle wavelet coefficients. The speckle component was modelled using the generalised Nakagami distribution, which is versatile enough to model the speckle statistics under various scattering conditions of interest in medical US images. By combining this speckle model with the generalised Gaussian signal first, the Bayesian shrinkage functions were derived using the maximum a posteriori (MAP) criterion. The resulting Bayesian processor used the local image statistics to achieve soft-adaptation from homogeneous to highly heterogeneous areas. Finally, the results showed that the proposed method, named GNDShrink, yielded a signal-to-noise ratio (SNR) gain of 0.42dB over the best state-of-the-art despeckling method reported in the literature, 1.73dB over the Lee filter and 1.31dB over the Kaun filter at an input SNR of 12.0dB, when tested on a US image. Further, the visual comparison of despeckled US images indicated that the new method suppressed the speckle noise well, while preserving the texture and organ surfaces.

Algorithms↗

Motility and survival of Euglena ignobilis as affected by different factors.

Euglena ignobilis cells in natural puddle water of pH 7.8, when kept at 21 +/- 2 degrees C and under continuous light (intensity of approximately 30 micromol m(-2) s(-1)) in a culture chamber, decreased their speed of movement from > or = 78000 microm/min (after a 12-h cultivation), to 850-1300 microm/min after 18 h. Simultaneously initiated were changes in morphology from the usual elongated motile forms to round motile ones by curving and contraction. Water stress (2 and 4 % agarized puddle water, puddle water with 0.2-1 mol/L NaCl), temperature shock (< or = 10 degrees C, > or = 30 degrees C), darkness and low-light intensity, UV exposure (0.96-2.88 kJ/m2), pH extremes (< or = 6.5 and > or = 10), presence of 'heavy' metals (1-100 ppm Fe, Cu, Zn, Co, Ni, Hg) or organic substances in puddle water (25-1000 ppm 2,4-D, captan, urea, DDT, thiourea), all these factors rapidly (after 5 to 30 min) decreased the speed of the elongated motile form to < or = 300 microm/min, and induced all morphological changes leading to formation of round motile and round nonmotile forms. These features in the alga (i.e. sudden speed reduction and morphological changes from elongate motile to round motile form) may thus be suggested to be used in assessing water quality.

Animals↗

A mathematical model for a new mechanism of phenotypic variation in malaria.

The Py235 merozoite rhoptry protein of the rodent malaria agent Plasmodium (yoelii) yoeli is encoded by the Py235 multigene family whose members are transcribed during the parasite's asexual life-cycle in a fashion where single schizonts subsequently give rise to sets of merozoites containing distinct Py235 transcripts. Homologues of Py235 are found in other malaria species, and antibodies to both Py235 and P. falciparum homologues inhibit merozoite invasion, suggesting a unique survival strategy involving immune evasion and host adaptation. Using a mathematical approach to model this free-living stage of Plasmodium in interaction with specific antibodies and a heterogeneous red blood cell population, we investigate if, and under what conditions, this mechanism of clonal phenotypic variation can play a role in immune evasion and adaptation to a dynamic erythropoietic environment.

Animals↗

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial.

Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m2), the most effective agent for MM, and G-CSF (10 microg/kg/day) for mobilization. End points were safety, adequacy of CD34+ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34+ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34+ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N=48) was 0.0009% (range 0-0.1) and 0.21 x 10(4) cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.

Adult↗

Role of NF-kappaB signaling pathway in increased tumor necrosis factor-alpha-induced apoptosis of lymphocytes in aged humans.

In human aging, lymphocytes display increased sensitivity to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. TNF-alpha induces both survival and apoptotic signals. The survival signal is mediated by the activation of NF-kappaB. Although a role of certain proapoptotic molecules in aging has been reported, a role of altered NF-kappaB signaling pathway has not been explored in detail. In this study, we have compared TNF-alpha-induced activation of NF-kappaB, phosphorylation of IkappaBalpha, and the expression of IKKbeta between lymphocytes from young and aged humans. Furthermore, we have explored a role of IKKbeta in increased susceptibility of lymphocytes from aged humans to TNF-alpha-induced apoptosis. Lymphocytes from aged humans displayed decreased activation of NF-kappaB, reduced phosphorylation of IkappaBalpha, and decreased expression of IKKbeta. In addition, overexpression of IKKbeta in lymphocytes from aged humans normalized TNF-alpha-induced apoptosis to the level of young subjects. These data suggest a deficiency of NF-kappaB signaling pathway and a role of IKKbeta, at least in part, for increased sensitivity of lymphocytes from aged humans to TNF-alpha-induced apoptosis.

Adolescent↗

Effect of ochratoxin A on broiler chicks challenged with Salmonella gallinarum.

1. A study was conducted to evaluate the effects of ochratoxin A (OA) on broiler chicks challenged with Salmonella gallinarum. 2. One hundred and seventy-six 1-d-old broiler chicks were divided into two groups of 88 chicks each, with one group fed on a control mash diet and the other given a mash diet containing 2 ppm OA. On d 14, each group was further subdivided into two groups with one group infected with S. gallinarum and the other uninfected. 3. Following S. gallinarum inoculation on d 14, 4 birds from each group were killed at 1, 2, 3, 5, 7, 10, 14 and 21 d post inoculation. 4. S. gallinarum infection caused dullness, depression, weakness, increased thirst, droopy wings, ruffled feathers and greenish-yellow diarrhoea. S. gallinarum infection in the absence of OA caused 11.5% mortality which increased to 28.8% in the presence of OA. 5. Decreased body weight and reduced feed intake were observed in chicks fed on the diet containing OA. S. gallinarum infection also reduced the body weights of chicks, with the effects being more marked in chicks receiving OA. The OA diet led to increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, uric acid and creatinine, and decreased levels of total proteins, albumin, globulins, calcium and phosphorus. S. gallinarum infection did not cause significant alteration in any of the serum biochemical parameters. 6. Mortality and the severity of S. gallinarum infection in broiler chicks were increased by the presence of OA in the diet.

Alanine Transaminase↗

Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 351125, a CCR5 antagonist.

The identification and relative contribution of human cytochrome P450 enzyme(s) involved in the metabolism of SCH 351125 were investigated. In human liver microsomes, O-deethylation was the major metabolic pathway, whereas aromatization of a piperidine ring to pyridine and the reduction of the N-oxide moiety were minor routes. Recombinant human CYP3A4 and CYP2C9 both exhibited catalytic activity with respect to the formation of rotameric O-deethylated metabolites (M12, M13), the metabolites resulting from aromatization (M22/M24) and N-oxide reduction (M31). Using the relative activity factor (RAF) approach, the relative contributions of CYP3A4 and CYP2C9 to M13 formation were estimated to be 76 and 24%, respectively. There was a high correlation (r>0.96) between the rate of formation of M12 and M13 and 6 beta-hydroxylation of testosterone catalysed by CYP3A4/5. Ketoconazole (2microM) and CYP3A4/5-specific inhibitory monoclonal antibody inhibited the formation of M12 and M13 from human liver microsomes by approximately 60 and 71%, respectively. The results demonstrate that the in vitro metabolism of SCH 351125 is mediated primarily via CYP3A4 and that CYP2C9 plays a minor role. Clinical study designs should encompass these enzymology data to address any potential drug interactions.

Biotransformation↗

An audit of patients investigated by Hysterosalpingo-Contrast-Sonography (HyCoSy) for infertility.

We reviewed 171 case notes of patients investigated by HyCoSy for sub-fertility in South Manchester University Hospital to assess HyCoSy as a screening test for tubal occlusion, in low risk infertile women and to evaluate the performance of HyCoSy in our unit by confirming its results with the results of laparoscopy & dye test in those patients who had both procedures. We also assessed the prognostic significance of HyCoSy, for fertility outcome over a follow-up period ranging from 12 to 63 months. An audit proforma was designed to collect data on maternal age, type of infertility (primary or secondary), duration of infertility and parity. History suggestive of ovulatory factors (PCO), pelvic inflammatory disease and endometriosis was noted. Findings of standard trans-vaginal scan, hysterosalpingography and HyCoSy were recorded. In total 333 tubes were examined in 171 patients. There were 121/171 diagnoses of bilateral patent tubes, 24/171 bilateral blocked tubes and 26/171 findings of one patent tube. In 15 (8.8%) women, laparoscopy and dye test was performed after HyCoSy and 19 patients had laparoscopy and dye test before HyCoSy. The findings in both investigations were similar. 70 additional uterine and adnexal pathologies were detected. Out of 171 40.9% (n=70) women conceived, 62 of these women had both tubes patent and 8 had one patent tube. In conclusion we have found that HyCoSy is a valuable cost effective screening test for low risk couples. Its results in our hands are as good as demonstrated by other studies. HyCoSy can be offered as a screening test for low risk infertile women as it is an effective alternative for laparoscopy and dye test.

Adolescent↗