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Biomedical subjects

J Gupta

Publications and source records attributed to J Gupta.

At least 19 recordsLinked to original sources
PubMed2005

Association of the PIM3 allele of the alpha-1-antitrypsin gene with chronic obstructive pulmonary disease.

OBJECTIVE: The study investigated the association of genetic polymorphism of the alpha1AT gene with COPD. DESIGN AND METHODS: The mutations and polymorphism of alpha1AT gene were investigated by DNA sequence analysis using polymerase chain reaction. RESULTS: The frequency of the PIM3 allele in COPD patients was found to be significantly higher than the controls (P < 0.0001). Five SNPs, including a novel SNP (24_25insA), were observed near the junction of exon-intron I. The occurrence of these SNPs didn't show any association with COPD. However, the PIM3 allele of the alpha1AT gene was found to be associated with COPD. CONCLUSION: The PIM3 allele of the alpha1AT gene is found to have an association with the pathogenesis of COPD in the Indian population.

Adult↗
PubMed2005

A fraction from Escherichia coli with anti-Aspergillus properties.

The products of various strains of Escherichia coli (BL21, DH5alpha, HB101 and XL Blue) were investigated for antimycotic properties using pathogenic isolates of Aspergillus. Co-culture experiments revealed that E. coli strains exhibited variable activity against Aspergillus fumigatus. The lysates prepared from DH5alpha, HB101 and XL Blue strains of E. coli showed inhibitory activity against A. fumigatus in the protein concentration range of 62.50 to 250.00 microg ml(-1). The highest activity was seen in the lysate of BL21, which inhibited the growth of A. fumigatus and Aspergillus flavus completely at a concentration of 31.25 microg protein ml(-1). The MIC of BL21 lysate against Aspergillus niger was found to be 62.50 microg ml(-1). The in vitro toxicity of BL21 lysate was evaluated using a haemolytic assay. A BL21 lysate protein concentration of 1250.00 microg ml(-1) was found to be nontoxic to human erythrocytes. The standard drug amphotericin B lysed 100 % of erythrocytes at a concentration of 37.50 microg ml(-1). SDS-PAGE showed the presence of at least 15 major proteins in the lysate of BL21. Ion-exchange chromatography resolved the BL21 lysate into five fractions and fraction III was found to be endowed with anti-Aspergillus properties. The MIC of this fraction was found to be 3.90 microg ml(-1). Further work on the purification of the active molecule and its characterization is in progress.

Antifungal Agents↗
PubMed2005

In vitro antifungal activity of 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate, a dihydropyrrole derivative.

A novel compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate was isolated from the plant Datura metel L. The in vitro activity of this dihydropyrrole derivative against Aspergillus and Candida species was evaluated by using standard methods approved by the National Committee for Clinical Laboratory Standards. The compound was found to be active against all the species tested, namely Candida albicans, Candida tropicalis, Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. The MIC at which more than 90% of growth was inhibited (MIC(90)) by the compound ranged from 21.87 to 43.75 microg ml(-1) against various fungal species by microbroth dilution assay. Since the compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate has antifungal activity it can be explored further to develop new antimycotic drugs.

Antifungal Agents↗
PubMed2005

Investigations on anti-Aspergillus properties of bacterial products.

AIMS: To investigate the anti-Aspergillus properties of bacterial products. METHODS AND RESULTS: In the present study, 12 bacterial strains were screened for antifungal activity against Aspergilli. The culture supernatant and lysates of Pseudomonas aeruginosa, Bacillus cereus, Escherichia coli (BL21, DH5alpha, HB101, XL Blue), Klebsiella pneumoniae, Streptomyces thermonitrificans, Streptococcus pneumoniae, Enterobacter aerogenes, Staphylococcus aureus and Salmonella typhi were examined for antifungal activity in protein concentration ranging from 1000.0 to 7.8 microg ml-1 using microbroth dilution assay. The lysate of Salm. typhi and E. coli BL21 exhibited the maximum activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Their in vitro minimum inhibitory concentrations (MICs) were found to be 15.6-31.2 microg ml-1 by microbroth dilution and spore germination inhibition assays. In disc diffusion assay, a concentration of 3.1 microg disc-1 of Salm. typhi lysate showed significant activity against Aspergilli. Escherichia coli BL21 exhibited similar activity at 6.2 microg disc-1. The work on identification of molecule endowed with antimycotic properties is in progress. CONCLUSION: The products of Salm. typhi and E. coli demonstrated significant activity against Aspergillus species. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first time that E. coli has been reported for anti-Aspergillus activity. It could be an important source of biologically active compounds useful for developing better new antifungal drugs/or probiotics.

Antifungal Agents↗
PubMed2004

Upper gastrointestinal cancer pathology reporting: a regional audit to compare standards with minimum datasets.

AIMS: Accurate pathological (pTNM) staging of oesophageal and gastric cancer provides important prognostic information. The aim of this study was to compare the standard of pathology reporting of oesophageal and gastric cancer resections from a cancer network with standards set by the Royal College of Pathologists. METHODS: All reports for oesophageal and gastric cancer resections from the five hospitals in the cancer network in 2001 were collected. Individual items of information were compared with minimum datasets provided by the Royal College of Pathologists. Items were classified as "complete", "partially complete", or "absent". RESULTS: One hundred and ten reports were audited (54 oesophageal and 56 gastric). Fourteen gastric and 17 oesophagectomy reports were over 75% complete. Clinically important missing data occurred most frequently for the pM component of TNM staging (pMx omitted in 87 reports) and completeness of resection expressed as a bold statement (absent in 50 reports). Twelve reports could not be classified because the specimen contained no residual tumour after neoadjuvant treatment. CONCLUSION: The use of a standard proforma for reporting upper gastrointestinal cancers based on a minimum dataset provided by the Royal College of Pathologists is recommended, with modifications to allow for specimens with no tumour after neoadjuvant treatment.

England↗
PubMed2004

The annual risk of tuberculous infection in the eastern zone of India.

SETTING: Rural and urban areas of eight selected districts in the eastern zone of India. OBJECTIVES: To estimate the annual risk of tuberculous infection (ARTI). STUDY DESIGN: A community-based, cross-sectional tuberculin survey was conducted among children aged 1-9 years residing in a sample of rural and urban areas. Stratified two-stage cluster sampling was adopted for selection of rural and urban clusters. A total of 40964 children in 515 clusters underwent tuberculin testing and reading with 1TU PPD RT23 with Tween 80; the maximum transverse diameter of induration was measured about 72 h after the test. RESULTS: A bacille Calmette-Gúerin (BCG) scar was observed in 51.5% of the test-read children. The frequency distribution of tuberculin reaction size among 19332 children without BCG scar was found to be bimodal, with the mode of reactions attributable to infection with tubercle bacilli at 20 mm. The prevalence of infection was estimated as 6.9%. The ARTI computed from the estimated prevalence was 1.3%. Children residing in the urban areas were found to be at a significantly higher risk of infection than those residing in rural areas. CONCLUSION: The high rate of ARTI in the eastern zone of India suggests a need for committed, sustained action in provision of quality tuberculosis control services.

BCG Vaccine↗
PubMed2004

A novel antifungal pyrrole derivative from Datura metel leaves.

Phytochemical investigation of the leaves of Datura metel Linn. led to the isolation of a new pyrrole derivative 1 which was characterised as 2beta-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1'-methylethyl pentanoate on the basis of spectral data analyses and chemical reactions. Compound 1 was endowed with antifungal activity and its MIC was found to be 87.5 microg/ml. Two proteins having molecular weights of 42 and 58 kD of Aspergillus fumigatus are potential targets for compound 1.

Antifungal Agents↗
PubMed2003

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗
PubMed2003

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Adult↗
PubMed2003

Colorectal mass lesions masquerading as chronic inflammatory bowel disease on mucosal biopsy.

AIMS: We bring to the attention of diagnostic pathologists a further cause of mimicry of chronic inflammatory bowel disease on mucosal biopsy, namely intramural and subserosal colorectal mass lesions. METHODS AND RESULTS: In a 10-year prospective study in one centre, we describe 26 cases in which the initial colonoscopic biopsies suggested a diagnosis of chronic inflammatory bowel disease, whereas subsequent information indicated that the mucosal changes were due to underlying mass lesions, without evidence of chronic inflammatory bowel disease. These mass lesions included underlying primary adenocarcinoma, metastatic carcinoma, pneumatosis, endometriosis and complicated diverticular disease. CONCLUSIONS: In the colon and rectum, intramural and subserosal mass lesions are a significant cause of chronic inflammatory bowel disease mimicry. Possible pathogenic mechanisms include mechanical effects, lymphatic obstruction by underlying tumour, relative mucosal ischaemia and mucosal prolapse. Since the changes seen on mucosal biopsies are a secondary phenomenon, we tentatively suggest that 'secondary colitis' may be an appropriate appellation.

Adenocarcinoma↗
PubMed2003

Inducible nitric oxide synthase regulates production of isoprostanes in vivo during chlamydial genital infection in mice.

Urinary nitrite and F(2)-isoprostanes, an index of oxidant stress, were elevated during chlamydial genital infection of mice. Enhancement of urinary nitrite and F(2)-isoprostanes was observed in phagocyte oxidase-deficient mice. Inhibition of inducible nitric oxide synthase reduced isoprostane excretion. We conclude that nitrogen radicals induce F(2)-isoprostane production and excretion during murine chlamydial genital infection.

Animals↗
PubMed2001

Asymmetric structure of the cystic fibrosis transmembrane conductance regulator chloride channel pore suggested by mutagenesis of the twelfth transmembrane region.

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel contains 12 membrane-spanning regions which are presumed to form the transmembrane pore. Although a number of findings have suggested that the sixth transmembrane region plays a key role in forming the pore and determining its functional properties, the role of other transmembrane regions is currently not well established. Here we assess the functional importance of the twelfth transmembrane region, which occupies a homologous position in the carboxy terminal half of the CFTR molecule to that of the sixth transmembrane region in the amino terminal half. Five residues in potentially important regions of the twelfth transmembrane region were mutated individually to alanines, and the function of the mutant channels was examined using patch clamp recording following expression in mammalian cell lines. Three of the five mutations significantly weakened block of unitary Cl(-) currents by SCN(-), implying a partial disruption of anion binding within the pore. Two of these mutations also caused a large reduction in the steady-state channel mean open probability, suggesting a role for the twelfth transmembrane region in channel gating. However, in direct contrast to analogous mutations in the sixth transmembrane region, all mutants studied here had negligible effects on the anion selectivity and unitary Cl(-) conductance of the channel. The relatively minor effects of these five mutations on channel permeation properties suggests that, despite their symmetrical positions within the CFTR protein, the sixth and twelfth transmembrane regions make highly asymmetric contributions to the functional properties of the pore.

Amino Acid Sequence↗
PubMed2001

Role for inducible nitric oxide synthase in protection from chronic Chlamydia trachomatis urogenital disease in mice and its regulation by oxygen free radicals.

It has been previously reported that although inducible nitric oxide synthase (iNOS) gene knockout (NOS2(-/-)) mice resolve Chlamydia trachomatis genital infection, the production of reactive nitrogen species (RNS) via iNOS protects a significant proportion of mice from hydrosalpinx formation and infertility. We now report that higher in vivo RNS production correlates with mouse strain-related innate resistance to hydrosalpinx formation. We also show that mice with a deletion of a key component of phagocyte NADPH oxidase (p47(phox-/-)) resolve infection, produce greater amounts of RNS in vivo, and sustain lower rates of hydrosalpinx formation than both wild-type (WT) NOS2(+/+) and NOS2(-/-) controls. When we induced an in vivo chemical block in iNOS activity in p47(phox-/-) mice using N(G)-monomethyl-L-arginine (L-NMMA), a large proportion of these mice eventually succumbed to opportunistic infections, but not before they resolved their chlamydial infections. Interestingly, when compared to WT and untreated p47(phox-/-) controls, L-NMMA-treated p47(phox-/-) mice resolved their infections more rapidly. However, L-NMMA-treated p47(phox-/-) mice lost resistance to chronic chlamydial disease, as evidenced by an increased rate of hydrosalpinx formation that was comparable to that for NOS2(-/-) mice. We conclude that phagocyte oxidase-derived reactive oxygen species (ROS) regulate RNS during chlamydial urogenital infection in the mouse. We further conclude that while neither phagocyte oxidase-derived ROS nor iNOS-derived RNS are essential for resolution of infection, RNS protect from chronic chlamydial disease in this model.

Animals↗
PubMed2000

Perceptions of and constraints upon pregnancy-related referrals in rural Rajasthan, India.

Mortality associated with complications of pregnancy and childbirth remains disproportionately high in the developing world. This paper reports on a study into the reasons for the poor uptake of referrals to specialist medical units in a group of 276 women in a rural area in the state of Rajasthan, India. Of the 276 cases that were referred, 242 (88%) of the women failed to attend for specialist consultation. In-depth personal interviews were conducted and a series of focus group discussions was held with the women and with their spouses and spouses' mothers. A range of geographic, cultural, socio-economic and medico-administrative factors was identified as influencing decisions to attend referral units. Recommendations for improving uptake include improving facilities at referral units, providing additional training for healthcare staff (covering technical, managerial and behavioural aspects) and in counselling techniques, a better defined role for traditional birth attendants, improved understanding of the mother's needs by her family (particularly the spouse and his mother) and increasing public awareness of the importance of referral. Finally, there is the requirement that women are encouraged to realize and understand their own needs.

Adolescent↗
PubMed1998

Dissociation of telomere dynamics from telomerase activity in human thyroid cancer cells.

Prevention of telomere erosion through acquisition of telomerase activity is thought to be an essential mechanism in most human cancer cells for avoidance of cellular senescence and crisis. It has been generally assumed that once telomerase has been activated, no further telomere shortening should ensue. We show here, however, that a much more complex pattern of telomere dynamics can exist in telomerase-positive immortal cancer cells. Using a panel of subclones derived from a human thyroid cancer cell line, K1E7, we found that some clones show persistent decline in mean telomere restriction fragment (TRF) length by up to 2 kb over 450 population doublings (pd), despite sustained high telomerase activity (as assessed by the in vitro "TRAP" assay). TRF length subsequently stabilized at around 5 kb, but with no corresponding increase in telomerase activity. One clone showed an even more unexpected biphasic time course, with the mean TRF length initially increasing by 1.5 kb over 90 pd, before "plateauing" and then returning over a similar period to its original value, again without any correlation to TRAP activity. Such dissociations between telomere dynamics and telomerase activity support the existence of additional controls on telomere length in the intact cell. Our observations are consistent with current negative-feedback models of telomere length regulation by telomere binding proteins and these cell lines should prove useful experimental tools for their further evaluation.

Humans↗
PubMed1996

Development of retinoblastoma in the absence of telomerase activity.

BACKGROUND: The length and stability of telomeres (essential functional structures at the end of eukaryotic chromosomes) have been implicated in the control of cell lifespan. Most somatic cells lack telomerase, the enzyme that synthesizes telomeric DNA, and their telomeres shorten with cell division. Cells immortalized in vitro, on the other hand, express telomerase and maintain their telomeres. Telomerase activity has also been detected in the large majority of tumors from a variety of cancers. These observations have suggested that telomere maintenance is required for unlimited cell proliferation and that telomerase is a marker for cell immortality in vitro and in vivo. PURPOSE: We investigated whether telomerase is activated during the development of retinoblastoma. This is a childhood eye cancer associated with a limited number of mutations in an embryonic tissue and thus likely to develop in cells that have long telomeres. The ease of detection of retinoblastoma makes it possible to screen relatively small tumors before extensive proliferation of the malignant cells. METHODS: We measured telomerase activity in 34 samples of retinoblastoma, four retinoblastoma-derived cell lines, and six cell lines derived from other cancers. Only three of the cell lines from other cancers expressed the retinoblastoma protein. Telomerase activity was assayed by a polymerase chain reaction protocol in extracts prepared from tumors or cell lines. The level of enzyme activity in cell extracts was quantified at several protein concentrations and expressed relative to that in a positive control, after normalization for the amount of protein. Telomere length was measured by Southern blot hybridization of genomic DNA with a telomere-specific probe. Average values of telomere length in telomerase-positive and telomerase-negative tumors and in cell lines were compared by two-sided, two-sample Student's t test. RESULTS: No telomerase activity was detected in 17 (50%) of 34 retinoblastomas. Assays of cell lines derived from other cancers revealed no association between the presence or the level of the enzyme activity and the expression of the retinoblastoma protein. Telomeres were significantly longer in telomerase-negative tumors than in telomerase-positive tumors (P = .0008). CONCLUSIONS: Our results indicate that retinoblastoma can develop when telomeres are still relatively long and in the absence of telomerase. Telomerase activity associated with short telomeres is, however, observed in 50% of the retinoblastomas and in retinoblastoma-derived cell lines. IMPLICATIONS: Telomerase may not be a marker for acquisition of the malignant phenotype in the case of tumors that are derived from cells with long telomeres and that are associated with a low number of mutations.

Base Sequence↗