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Biomedical subjects

A Bansal

Publications and source records attributed to A Bansal.

At least 37 records · Page 2Linked to original sources

Cytoprotective and immunomodulatory properties of Geriforte, a herbomineral preparation, in lymphocytes.

The study was designed to determine the cytoprotective and immunomodulatory properties of Geriforte, an indigenous herbomineral compound, using lymphocytes as a model system. The possible involvement of free radicals and the ability of Geriforte to inhibit the oxidative process induced by tert-butylhydroperoxide (tert-BHP) was also investigated. The production of free radicals (evaluated by fluorescent probe fluorescein-diacetate), level of malondialdehyde (MDA, as index of lipid peroxidation), and levels of anti-oxidants--reduced glutathione (GSH) and glutathione peroxidase (GPx) were determined. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP (100 microM) over control. Addition of tert-BHP resulted in a marked increase in free radical production and MDA level with a concomitant decrease in GSH level in lymphocytes. Geriforte supplementation reduced cytotoxicity and apoptosis induced by tert-BHP. Further, Geriforte inhibited tert-BHP induced lipid peroxidation and maintained higher anti-oxidant levels. tert-BHP significantly inhibited the lymphocyte proliferation stimulated by mitogens (Lipopolysaccharide/Concanavalin A) and enhanced DNA fragmentation. Geriforte relieved the inhibitory effect of tert-BHP on lymphocyte proliferation and decreased DNA fragmentation appreciably. The results indicate that Geriforte possesses cytoprotective and immunomodulatory properties which could be due to its anti-oxidant activity.

Adjuvants, Immunologic↗

Effect of vitamin E supplementation on hypoxia-induced oxidative damage in male albino rats.

BACKGROUND: There is growing evidence that free radicals mediated oxidative injury due to inadequate oxygen availability is an important factor in various pathologies at high altitude. Since vitamin E is known to protect the cells from oxidative damage due to its potent antioxidant properties, the present study was carried out to explore the effect of vitamin E supplementation on various hematological and biochemical parameters in hypoxia-induced oxidative stress in albino rats. METHODS: The experiments were conducted on male albino rats by intermittently exposing them to a simulated altitude of 7,576 m (25,000 ft), daily for 6 h for 15 d at 32 +/- 2 degrees C. The control group was fed vehicle only (1% Tween 80) and the experimental group was given vitamin E (40 mg per rat x d(-1)) orally, 5 d prior to and during the period of hypoxic exposure. The variables studied include: hemoglobin, hematocrit, RBC deformability index, alpha-tocopherol level, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), lactate dehydrogenase (LDH) and protein level in blood/plasma and various tissues. RESULTS: Significant increase in hematocrit and hemoglobin and decrease in RBC deformability index was observed on exposure to hypoxia while vitamin E supplementation maintained them at the normal level. Hypoxia led to the decrease in plasma vitamin E and blood glutathione (GSH) level and two-fold increase in the plasma malondialdehyde (MDA) level. Vitamin E supplementation, on the other hand, resulted in less of an increase in MDA and increased the GSH concentration significantly. LDH activity, which was elevated on exposure to hypoxia, was arrested on vitamin E supplementation. CONCLUSION: The results indicate that vitamin E supplementation results in preventing oxidative damage due to high altitude stress.

Altitude↗

Mice lacking specific nicotinic acetylcholine receptor subunits exhibit dramatically altered spontaneous activity patterns and reveal a limited role for retinal waves in forming ON and OFF circuits in the inner retina.

Before phototransduction, spontaneous activity in the developing mammalian retina is required for the appropriate patterning of retinothalamic connections, and there is growing evidence that this activity influences the development of circuits within the retina itself. We demonstrate here that the neural substrate that generates waves in the mouse retina develops through three distinct stages. First, between embryonic day 16 and birth [postnatal day 0 (P0)], we observed both large, propagating waves inhibited by nicotinic acetylcholine receptor (nAChR) antagonists and small clusters of cells displaying nonpropagating, correlated calcium increases that were independent of nAChR activation. Second, between P0 and P11, we observed only larger propagating waves that were abolished by toxins specific to alpha3 and beta2 subunit-containing nAChRs. Third, between P11 and P14 (eye opening) we observed propagating activity that was abolished by ionotropic glutamate receptor antagonists. The time course of this developmental shift was dramatically altered in retinas from mice lacking the beta2 nAChR subunit or the beta2 and beta4 subunits. These retinas exhibited a novel circuit at P0, no spontaneous correlated activity between P1 and P8, and the premature induction at P8 of an ionotropic glutamate receptor-based circuit. Retinas from postnatal mice lacking the alpha3 nAChR subunit exhibited spontaneous, correlated activity patterns that were similar to those observed in embryonic wild-type mice. In alpha3-/- and beta2-/- mice, the development and distribution of cholinergic neurons and processes and the density of retinal ganglion cells (RGCs) and the gross segregation of their dendrites into ON and OFF sublaminae were normal. However, the refinement of individual RGC dendrites is delayed. These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the ON and OFF sublamina of the inner plexiform layer.

Action Potentials↗

The predictive value of BRCA1 and BRCA2 mutation testing.

Genetic testing for mutations in BRCA1 and BRCA2, two genes predisposing to breast and ovarian cancers, is available to women with a relevant family history. The aim of this study was to estimate the positive and negative predictive value of clinical sequence analysis of these genes. A reference graph showing positive and negative predictive values over a range of pre-test risk was derived, taking into account the sensitivity and specificity of a full-sequence analysis test. High positive and negative predictive values were found for women with pre-test risk between 4% and 40%, a range of risk commonly seen in clinical testing. The predictive value of full sequence and single-site analysis of BRCA1 and BRCA2, therefore, compares favorably with other diagnostic medical tests. Our results provide a numerical estimate of the predictive value of BRCA testing, and as such, provide a valuable tool to healthcare providers and families as they interpret BRCA1 and BRCA2 test results.

BRCA1 Protein↗

A significant number of human immunodeficiency virus epitope-specific cytotoxic T lymphocytes detected by tetramer binding do not produce gamma interferon.

Despite the seemingly important role of cytotoxic T-lymphocyte (CTL) responses in human immunodeficiency virus (HIV) disease pathogenesis, their measurement has relied on a variety of different techniques. We utilized three separate methodologies for the detection of CTLs in a cohort of HIV-infected individuals who were also human leukocyte antigen A2 (HLA-A2) positive. Among the different CTL assays, a correlation was seen only when the Gag epitope-specific HLA A*0201-restricted tetramer assay was compared with the ELISPOT assay performed after stimulation with the Gag epitope; however, this correlation was of borderline statistical significance. On average, the tetramer reagent detected a 10-fold-higher number of cells than were seen to produce gamma interferon by the ELISPOT assay. The implications of this CTL assay comparison and the possibility of phenotypic differences in HIV-specific CD8(+) T lymphocytes are discussed.

Biopolymers↗

Characterization of the R572T point mutant of a putative cleavage site in human foamy virus Env.

A putative cleavage site of the human foamy virus (HFV) envelope glycoprotein (Env) was altered. Transient env expression revealed that the R572T mutant Env was normally expressed and modified by asparagine-linked oligosaccharide chains. However, this single-amino-acid substitution was sufficient to abolish all detectable cleavage of the gp130 precursor polyprotein. Cell surface biotinylation demonstrated that the uncleaved mutant gp130 was transported to the plasma membrane. The uncleaved mutant protein was incapable of syncytium formation. Glycoprotein-driven virion budding, a unique aspect of HFV assembly, occurred despite the absence of Env cleavage. We then substituted the R572T mutant env into a replication-competent HFV molecular clone. Transfection of the mutant viral DNA into BHK-21 cells followed by viral titration with the FAB (foamy virus-activated beta-galactosidase expression) assay revealed that proteolysis of the HFV Env was essential for viral infectivity. Wild-type HFV Env partially complemented the defective virus phenotype. Taken together, these experimental results established the location of the HFV Env proteolytic site; the effects of cleavage on Env transport, processing, and function; and the importance of Env proteolysis for virus maturation and infectivity.

Amino Acid Substitution↗

Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins.

Both benign prostatic hyperplasia and prostate-specific antigen (PSA) have been shown to increase with age and with prostate volume in men, but the influence of heredity on these relationships is not completely understood. This study has two aims: 1) to investigate the inter-relationships of age, PSA, and various zonal measurements in the prostate; and 2) to assess the impact of heritable influences on total PSA. Eighty-four monozygotic twin pairs and 83 dizygotic twin pairs were studied, and serum total PSA, free PSA, and PSA-alpha1-antichymotrypsin were measured. Their prostate volumes [total (TV), transition zone (TZ), and peripheral zone) were quantitated using transrectal ultrasound. Total PSA is significantly correlated with all zonal prostate measurements (TZ, peripheral zone, TV, and TZ/TV) and with age. When linear regression was applied, only age and TZ were retained in the final model. The proportion of variability in total PSA explained by these two factors, however, is below 24%. In contrast, estimates of heritability show that approximately 45% of the variability in total PSA can be explained by inherited factors. Whereas age and TZ are linearly related to total PSA, their influence is much less than that of familial and genetic factors. It is uncertain whether these factors predispose also to prostate cancer or if they are independent of those, whether they confound the accuracy of using total serum PSA level as a diagnostic tool.

Adult↗

Impact of correlated factors on bone density in individuals with a family history of osteoporosis.

Previous studies have suggested that 14-47% of the variation in bone mineral density (BMD) can be predicted using clinical risk factors. The aim of our study was to determine, for the first time, the importance of these factors in individuals with evidence of a genetic predisposition to the disease. The subjects studied were 147 female and 86 male Caucasians, all with a family history of osteoporosis. Linear regression was used to determine whether age, height, weight, and years of reduced estrogen exposure were significant predictors of BMD. Males and females were examined separately, and BMD was measured at the hip and spine. The results show that these risk factors, known to be at work in the general population, are equally important in those with a family history of osteoporosis. It is clear, therefore, that they must be taken into account, and corrected for in genetic studies of the disease.

Adult↗

A low density genome-wide search for loci involved in alcohol dependence using the transmission/disequilibrium test, sib-TDT, and two combined tests.

The transmission/disequilibrium test (TDT), sib-TDT and two combined tests have been implemented in an attempt to identify loci across the genome that may be involved in alcohol dependence. Since these tests are based on the existence of association between marker and disease loci, the low-density map used (13 cM) will have missed any disease loci situated between markers. Nevertheless, genome-wide suggestive linkage results were found at three markers--D6S474, D8S1715, and D12S372--two of which also gave nominally significant evidence by two-point linkage analysis. These are regions that deserve further investigation with respect to their involvement in alcohol dependence, and in order to evaluate the relative efficacy of the different methods used.

Alcoholism↗

Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa.

Serum levels of interleukin-10 (IL-10) are elevated in a proportion of patients with untreated chronic hepatitis C, and this may compromise the host immune response to the virus. The capacity for IL-10 production varies according to the genetic composition of the IL-10 locus. We examined the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with chronic hepatitis C and their association with response to treatment with interferon alfa (IFN-alpha). After adjusting for potential confounding variables, a highly significant relationship was found between inheritance of the IL-10 promoter -592*A and -819*T alleles or the ATA haplotype and response to IFN-alpha therapy (P =.016). Response to treatment was also associated with viral genotype 3a, a low viral load, and less fibrosis on liver biopsy. Following in vitro stimulation of peripheral blood mononuclear cells, the IL-10 promoter haplotypes, GCC, ACC, and ATA, were associated with high, intermediate, and low IL-10 production, respectively. These findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis C to IFN-alpha therapy. Patients who are genetically predisposed to high IL-10 production have a poor response to IFN-alpha and may benefit from additional treatment strategies designed to enhance a T-helper type 1 (Th1) response.

Adult↗

Familial associations between cancer sites.

The Utah Population Database links together genealogical records, the Utah Cancer Registry, and Utah death certificates and allows identification of cancer clusters. Groups of individuals with cancers of some types tend to fall into related clusters within the genealogy. We examine the apparent tendency of cases of two types of cancer to cluster together and distinguish real clusters from chance occurrences. Some established associations are found, whereas some are surprisingly absent. Some new associations are also suggested.

Cluster Analysis↗

Biochemical and immunological changes on oral glutamate feeding in male albino rats.

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32 +/- 2 degrees C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

Administration, Oral↗

Heritability of the symptoms of benign prostatic hyperplasia and the roles of age and zonal prostate volumes in twins.

OBJECTIVES: Both benign prostatic hyperplasia and lower urinary tract symptoms (LUTS) have been shown to increase with age in men, but a causal relationship between prostate volume and symptoms has not been established. This study had two aims, to investigate the inter-relationships of age, symptoms, and various zonal measurements in the prostate and to assess the impact of heritable influences on symptom score. METHODS: Eighty-three monozygotic twin pairs and 83 dizygotic twin pairs were studied to determine age and LUTS as assessed by the American Urological Association symptom score. Their prostate volumes (total, transition zone, and peripheral zone) were measured by transrectal ultrasound. RESULTS: There was significant evidence of pairwise correlation between transition zone and symptom score (P = 0.04) and between age and symptom score (P = 0.03). Age also showed significant correlation with all volume measurements. Heritability appears to account for 82.6% of the variability in symptom score in men older than 50 years. CONCLUSIONS: This study provides evidence that age and transition zone volume play a role in LUTS, but also that their influence is not strong. Estimates of heritability suggest that hereditary factors contribute substantially to LUTS.

Adult↗

Phacoemulsification of white hypermature cataract.

PURPOSE: To evaluate the safety of phacoemulsification of white hypermature cataract, which is common in developing countries. SETTING: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS: In a teaching hospital setting, a prospective evaluation of phacoemulsification in 25 eyes of 25 consecutive patients with hypermature cataract was done. Patients with good pupil dilation, optimal endothelial cell count, and disease-free ocular and systemic status were included. High magnification, sodium hyaluronate, and a Utrata capsulorhexis forceps were used to perform continuous curvilinear capsulorhexis (CCC). The stop and chop technique was used for nuclear emulsification. A 5.5 mm optic allpoly(methyl methacrylate) intraocular lens (IOL) was implanted, and wound closure was sutureless. RESULTS: Successful CCC was performed in 23 of 25 cases. In 2 cases, the CCC edge extended toward the periphery and a Vannas scissors was used to achieve an even cut. No complications were seen during nuclear emulsification and IOL implantation. Eighty percent of the patients had a visual acuity of 20/40 or better on the first postoperative day. Five patients had significant corneal edema that resolved within 1 week in all cases. CONCLUSION: Phacoemulsification was successfully and safely performed in appropriately selected patients with white hypermature cataract.

Aged↗

An endoplasmic reticulum retrieval signal partitions human foamy virus maturation to intracytoplasmic membranes.

Among all retroviruses, foamy viruses (FVs) are unique in that they regularly mature at intracytoplasmic membranes. The envelope glycoprotein of FV encodes an endoplasmic reticulum (ER) retrieval signal, the dilysine motif (KKXX), that functions to localize the human FV (HFV) glycoprotein to the ER. This study analyzed the function of the dilysine motif in the context of infectious molecular clones of HFV that encoded mutations in the dilysine motif. Electron microscopy (EM) demonstrated virion budding both intracytoplasmically and at the plasma membrane for the wild-type and mutant viruses. Additionally, mutant viruses retained their infectivity, but viruses lacking the dilysine signal budded at the plasma membrane to a greater extent than did wild-type viruses. Interestingly, this relative increase in budding across the plasma membrane did not increase the overall release of viral particles into cell culture media as measured by protein levels in viral pellets or infectious virus titers. We conclude that the dilysine motif of HFV imposes a partial restriction on the site of viral maturation but is not necessary for viral infectivity.

Animals↗