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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 19 recordsLinked to original sources

Comparative evaluation of Löwenstein-Jensen proportion method, BacT/ALERT 3D system, and enzymatic pyrazinamidase assay for pyrazinamide susceptibility testing of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an important first-line antituberculosis drug because of its sterilizing activity against semidormant tubercle bacilli. In spite of its very high in vivo activity, its in vitro activity is not apparent unless an acidic environment is available, which makes PZA susceptibility testing difficult by conventional methods. The present study was, therefore, planned to assess the performance of the colorimetric BacT/ALERT 3D system and compare the results with those from conventional tests, i.e., the Löwenstein-Jensen (LJ) proportion method (pH 4.85) and Wayne's pyrazinamidase (PZase) assay, using 107 clinical isolates. The concordance among all of these tests was 89.71% after the first round of testing and reached 92.52% after resolution of the discordant results by retesting. Prolonged incubation of the PZase tube for up to 10 days was found to increase the specificity of the PZase test. The concordances between LJ proportion and BacT/ALERT 3D, LJ proportion and the PZase assay, and BacT/ALERT 3D and the PZase assay were found to be 99.06%, 93.46%, and 92.52%, respectively. Using the LJ results as the gold standard, the sensitivities of BacT/ALERT 3D and the PZase assay were 100 and 82.85%, respectively, while the specificity was 98.61% for both of the tests. The difference between the sensitivities of BacT/ALERT 3D and the PZase assay was significant (P = 0.025). The mean turnaround times for the detection of resistant and susceptible results by BacT/ALERT 3D were 8.04 and 11.32 days, respectively. While the major limitations associated with the PZase assay and the LJ proportion method are lower sensitivity in previously treated patients and a longer time requirement, respectively, the BacT/ALERT 3D system was found to be rapid, highly sensitive, and specific.

Amidohydrolases↗

Ionizing radiation enhances therapeutic activity of mda-7/IL-24: overcoming radiation- and mda-7/IL-24-resistance in prostate cancer cells overexpressing the antiapoptotic proteins bcl-xL or bcl-2.

Subtraction hybridization applied to terminally differentiating human melanoma cells identified mda-7/IL-24, a cytokine belonging to the IL-10 gene superfamily. Adenoviral-mediated delivery of mda-7/IL-24 (Ad.mda-7) provokes apoptosis selectively in a wide spectrum of cancers in vitro in cell culture, in vivo in human tumor xenograft animal models and in patients with advanced carcinomas and melanomas. In human prostate cancer cells, a role for mitochondrial dysfunction and induction of reactive oxygen species in the apoptotic process has been established. Ectopic overexpression of bcl-xL and bcl-2 prevents these changes including apoptosis induction in prostate tumor cells by Ad.mda-7. We now document that this resistance to apoptosis can be reversed by treating bcl-2 family overexpressing prostate tumor cells with ionizing radiation in combination with Ad.mda-7 or purified GST-MDA-7 protein. Additionally, radiation augments apoptosis induction by mda-7/IL-24 in parental and neomycin-resistant prostate tumor cells. Radiosensitization to mda-7/IL-24 is dependent on JNK signaling, as treatment with the JNK 1/2/3 inhibitor SP600125 abolishes this effect. Considering that elevated expression of bcl-xL and bcl-2 are frequent events in prostate cancer development and progression, the present studies support the use of ionizing radiation in combination with mda-7/IL-24 as a means of augmenting the therapeutic benefit of this gene in prostate cancer, particularly in the context of tumors displaying resistance to radiation therapy owing to bcl-2 family member overexpression.

Apoptosis↗

Structural and functional outcome of scleral patch graft.

PURPOSE: To evaluate the visual and structural outcomes of scleral patch grafting in cases of scleral defect. METHODS: The study was a retrospective interventional case series. Medical records of all patients who underwent scleral patch grafting at a tertiary care centre between 1997 and 2003 for scleral defects were reviewed. After removal of all the devitalized tissue, alcohol-preserved full-thickness sclera was tailored to fit the defect and sutured in place. The graft was covered with a conjunctival flap or amniotic membrane. Structural integrity and visual outcome were assessed as the main outcome measures. RESULTS: A total of 13 eyes of 13 patients required scleral patch grafting for scleral defects of varying aetiologies, the most common being necrotizing scleritis following pterygium surgery (40%). The patients were followed up for 6-60 months, an average period of 24.3 months. Tectonic success was achieved in 10 eyes (76.9%). Three complications were noted: endophthalmitis, graft necrosis, and graft dehiscence with uveal prolapse. However, no regrafts were needed. Epithelialization and vascularization were seen in the remaining eyes after an average duration of 3-4 weeks. Visual acuity remained stable in the majority (9/13, 60%), improved in one and deteriorated in three eyes. CONCLUSIONS: Scleral grafting with overlying conjunctival or amniotic membrane graft is an effective and simple measure for preserving globe integrity both structurally and functionally.

Adolescent↗

Activation of Ras/Raf protects cells from melanoma differentiation-associated gene-5-induced apoptosis.

Melanoma differentiation-associated gene-5 (mda-5) was the first molecule identified in nature whose encoded protein embodied the unique structural combination of an N-terminal caspase recruitment domain and a C-terminal DExD/H RNA helicase domain. As suggested by its structure, cumulative evidences documented that ectopic expression of mda-5 leads to growth inhibition and/or apoptosis in various cell lines. However, the signaling pathways involved in mda-5-mediated killing have not been elucidated. In this study, we utilized either genetically modified cloned rat embryo fibroblast cells overexpressing different functionally and structurally distinct oncogenes or human pancreatic and colorectal carcinoma cells containing mutant active ras to resolve the role of the Ras/Raf signaling pathway in mda-5-mediated growth inhibition/apoptosis induction. Rodent and human tumor cells containing constitutively activated Raf/Raf/MEK/ERK pathways were resistant to mda-5-induced killing and this protection was antagonized by intervening in this signal transduction cascade either by directly inhibiting ras activity using an antisense strategy or by targeting ras-downstream factors, such as MEK1/2, with the pharmacological inhibitor PD98059. The present findings provide a further example of potential cross-talk between growth-inhibitory and growth-promoting pathways in which the ultimate balance of these factors defines cellular homeostasis, leading to survival or induction of programmed cell death.

Adenoviridae↗

Cell death regulation by B-cell lymphoma protein.

Bcl-2 (B Cell Lymphoma) protein is an anti-apoptotic member of Bcl-2 family, which is comprised of pro- and anti-apoptotic members. It regulates cellular proliferation and death by inter- and intra-family interactions. It has a potential to suppress apoptotic cell death under variety of stress conditions by modulating mitochondrial transmembrane potential. However, prevalence of constitutively activated Bcl-2 cellular activity is not always required in cells; a mechanism likely exists in cells, which controls its activity. When expression of Bcl-2 is unregulated, it generates lymphoma like, follicular B-cell lymphoma. This article reviews the structural and functional regulation of Bcl-2 activity at transcriptional, translational, domain, structural and post-translational level, which also accounts for the effects of its deletion and site-directed mutants in the regulation of cellular proliferation and differentiation in vitro and in vivo. This concisely reviewed information on Bcl-2 helps us to update our understanding of cell death and its modulation by Bcl-2 and its mutant's interaction, which has gained therapeutic benefits in cell growth and proliferation, particularly for sensitive human hematopoietic stem cells.

Animals↗

Co-infection by Semliki forest virus and malarial parasite modulates viral multipucation, pathogenesis and cytokines in mice.

Environmental, technological and societal factors continue to have a dramatic effect on infectious diseases worldwide and are considered to be facilitating the emergence of several infectious diseases at a time. Co-infection with different species of viral and malaria infections are currently emerging problems of dual infection in the developing as well as developed countries. Understanding of interactions between the host, malaria and virus infection is of current concern and we have initiated studies to delineate the mechanisms involved during the progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii) infection in mice. Enhanced virus multiplication and up-regulation of cytokine mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post-infection compared to respective controls. Collectively, our observations indicate that malaria infection may influence virus multiplication, pathogenesis and up-regulation of cytokine mRNA during co-infection in mice.

Alphavirus Infections↗

Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life.

OBJECTIVES: To determine, first, the prevalence and severity of various symptoms related to estrogen deficiency in women within a few years of receiving treatment for breast cancer, second, how women perceive the effects of these symptoms on their quality of life and, third, what measures have been taken to relieve vasomotor symptoms. METHODS: Two hundred women (aged 29-65 years) who had received treatment for breast cancer within the last 5 years were included in this cross-sectional survey. Information was collected about their breast cancer treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects of menopausal symptoms on their and their partner's quality of life and any treatments they were receiving for hot flushes. RESULTS: All but one woman reported at least one symptom related to the menopause (95.9% vasomotor; 83.3% psychological; 89.7% somatic). Current treatment with tamoxifen or previous chemotherapy did not influence the prevalence or the severity of hot flushes. Current antidepressant treatment was, however, significantly associated with a higher prevalence and severity of most menopausal symptoms, including hot flushes and sweats (p = 0.008). The severity of hot flushes and sweats was significantly correlated with self-assessed effects on overall quality of life (r(s) = 0.47); 56.4% of the respondents believed that menopausal symptoms had affected their partner's quality of life, the strongest correlations being with severity of sexual symptoms (r(s) = 0.56) and vaginal dryness (r(s) = 0.5). Only 21% of women experiencing hot flushes were receiving any treatment for hot flushes, with most women describing no knowledge or poor knowledge of treatment options. CONCLUSIONS: The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partner's quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.

Adult↗

Mid-age health in women from the Indian subcontinent (MAHWIS): general health and the experience of menopause in women.

OBJECTIVES: First, to examine the experience of menopause and quality of life in a migrated Asian population from the Indian subcontinent living in Birmingham, UK, and, second, to compare their experience with a matched sample of Caucasian women living in the same geographical area and also with a sample of Asian women with similar socioeconomic background living in Delhi, India. METHODS: In this cross-sectional study of 153 peri- and postmenopausal women aged 45-55 years, 52 Asian women originating from the Indian subcontinent living in Birmingham (UKA, mean age 51.4 years), 51 Caucasian women (UKC, mean age 52.3 years) and 50 Asian women living in Delhi, India (DEL, mean age 49.72 years) were interviewed to collect information about their lifestyle, general health, menopause experience and help-seeking behavior. The Women's Health Questionnaire and the Menopause Representation Questionnaire (both translated and linguistically validated in Hindi) were used to examine the prevalence of physical and emotional symptoms and the extent to which these were attributed to the menopause. RESULTS: The two Asian groups (UKA, DEL) reported poorer health and generally more physical and emotional symptoms than the UKC group. However, for menopausal symptoms (hot flushes and night sweats) there was a different pattern; the DEL group reported significantly fewer symptoms compared to the UKA and UKC groups (hot flushes: UKC 60.8%, UKA 75%, DEL 32% (p < 0.001); night sweats: UKC 50%, UKA 56.9%, DEL 24% (p = 0.002)). The prevalence of vaginal dryness was highest in the UKA group and lowest in the DEL group (UKC 21.6%, UKA 38.2%, DEL 7.3% (p = 0.005)). The number of symptoms attributed to menopause was significantly lower in the DEL group (9.3 +/- 7.8) compared to the two UK groups (UKC 18.9 +/- 7.4, UKA 19.8 +/- 10.7), but the UKA women tended to attribute some physical symptoms to the menopause such as breathlessness, weight gain and stiff joints that might have other causes. CONCLUSIONS: The UK Asian women's experience of the menopause is more similar to the Caucasian women in the UK than that of the women in Delhi. However, Asian women living in the UK and the Indian subcontinent shared the experience of poor health and reports of more physical and emotional symptoms in general. The possible reasons for these differences are discussed.

Asian People↗

Rubrivivax benzoatilyticus sp. nov., an aromatic, hydrocarbon-degrading purple betaproteobacterium.

A brown-coloured bacterium was isolated from photoheterotrophic (benzoate) enrichments of flooded paddy soil from Andhra Pradesh, India. On the basis of 16S rRNA gene sequence analysis, strain JA2(T) was shown to belong to the class Betaproteobacteria, related to Rubrivivax gelatinosus (99 % sequence similarity). Cells of strain JA2(T) are Gram-negative, motile rods with monopolar single flagella. The strain contained bacteriochlorophyll a and most probably the carotenoids spirilloxanthin and sphaeroidene, but did not have internal membrane structures. Intact cells had absorption maxima at 378, 488, 520, 590, 802 and 884 nm. No growth factors were required. Strain JA2(T) grew on benzoate, 2-aminobenzoate (anthranilate), 4-aminobenzoate, 4-hydroxybenzoate, phthalate, phenylalanine, trans-cinnamate, benzamide, salicylate, cyclohexanone, cyclohexanol and cyclohexane-2-carboxylate as carbon sources and/or electron donors. The DNA G+C content was 74.9 mol%. Based on DNA-DNA hybridization studies, 16S rRNA gene sequence analysis and morphological and physiological characteristics, strain JA2(T) is different from representatives of other photosynthetic species of the Betaproteobacteria and was recognised as representing a novel species, for which the name Rubrivivax benzoatilyticus sp. nov. is proposed. The type strain is JA2(T) (=ATCC BAA-35(T)=JCM 13220(T)=MTCC 7087(T)).

Base Composition↗

Hydrophobic interactions are the prevalent force in bromelain:Fab' complex.

Antibromelain polyclonal antibodies against stem bromelain were raised in male albino rabbits and the Fab monomers isolated from the IgG of the immune sera as reported in our earlier communication (Gupta, P., Khan, R. H., and Saleemuddin, M. (2003) Biochim. Biophys. Acta, 1646, 131-135). Further, as evident from that communication bromelain:Fab complex has 1 : 1 stoichiometry. The stability of bromelain:Fab complex (1 : 1 stoichiometry) was investigated by far and near-UV CD and fluorescence measurements. Addition of up to 1.8 M NaCl caused no significant changes in fluorescence signals and near-UV CD peak pattern. However, the spectral studies together with gel filtration studies suggest dissociation of the complex beyond 5% (v/v) methanol. These results show that hydrophobic interactions play a pronounced role in the binding of Fab to bromelain while electrostatic interactions may be less crucial.

Animals↗

Complete ureteral avulsion.

Complete avulsion of the ureter is one of the most serious complications of ureteroscopy. It requires open or laparoscopic intervention for repair. This case report emphasizes its management and presents recommendations for prevention in current urological practice.

Adult↗

Gene expression patterns of trembling aspen trees following long-term exposure to interacting elevated CO2 and tropospheric O3.

Expression of 4600 poplar expressed sequence tags (ESTs) was studied over the 2001-2002 growing seasons using trees of the moderately ozone (O(3))-tolerant trembling aspen (Populus tremuloides) clone 216 exposed to elevated CO(2) and/or O(3) for their entire 5-yr life history. Based on replication of the experiment in years 2001 and 2002, 238 genes showed qualitatively similar expression in at least one treatment and were retained for analysis. Of these 238 genes, 185 were significantly regulated (1.5-fold) from one year to the other in at least one treatment studied. Less than 1% of the genes were regulated 2-fold or more. In the elevated CO(2) treatment, relatively small numbers of genes were up-regulated, whereas in the O(3) treatment, higher expression of many signaling and defense-related genes and lower expression of several photosynthesis and energy-related genes were observed. Senescence-associated genes (SAGs) and genes involved in the flavonoid pathway were also up-regulated under O(3), with or without CO(2) treatment. Interestingly, the combined treatment of CO(2) plus O(3) resulted in the differential expression of genes that were not up-regulated with individual gas treatments. This study represents the first investigation into gene expression following long-term exposure of trees to the interacting effects of elevated CO(2) and O(3) under field conditions. Patterns of gene-specific regulation described in this study correlated with previously published physiological responses of aspen clone 216.

Adaptation, Physiological↗

Ternary amorphous composites of celecoxib, poly(vinyl pyrrolidone) and meglumine with enhanced solubility.

The present study highlights the development of ternary amorphous composites to enhance the solubility of a poorly soluble crystalline drug, celecoxib (CEL). These systems comprised of an 'amorphous drug,' and its 'stabilizer' and 'solubilizer.' The ternary amorphous system of CEL, poly(vinyl pyrrolidone) (PVP) and meglumine (MEG) (7:2:1 w/w) enhanced CEL solubility by approximately equal to 10.2-fold over that for the crystalline drug, and maintained the thermodynamic stability of the amorphous drug. However, MEG alone was unable to stabilize the amorphous CEL against thermally-induced crystallization, and so gave no solubility advantage. The PVP-MEG combination provided a 'synergistic' enhancement of CEL solubility, as compared to their use alone in the amorphous systems. Phase-solubility studies provided greater insight into molecular mechanisms underlying stability and solubility of these amorphous systems. MEG exhibited phase-specific interaction with CEL molecules, when stabilized by PVP in the amorphous state. The higher solubility of CEL from ternary amorphous systems was also thermodynamically favored, as analyzed by van't Hoff plots. A possible molecular level interaction of MEG with PVP-stabilized amorphous CEL seems to be responsible for the solubility advantage of the CEL-PVP-MEG ternary amorphous system.

Calorimetry, Differential Scanning↗

Antiviral profile of Nyctanthes arbortristis L. against encephalitis causing viruses.

The ethanolic extracts, various fractions and two pure compounds isolated from the plant N. arbortris were tested against Encephalomyocarditis Virus (EMCV) and Semliki Forest Virus (SFV). Pronounced in vitro virus inhibitory activity was observed with the ethanolic and n-butanol fractions as well as with the pure compounds arbortristoside A and arbortristoside C. In addition, ethanolic extracts and n-butanol fraction protected EMCV infected mice to the extent of 40 and 60% respectively against SFV at a daily dose of 125 mg/kg body weight.

1-Butanol↗

Electron screening and kinetic-energy oscillations in a strongly coupled plasma.

We study equilibration of strongly coupled ions in an ultracold neutral plasma produced by photoionizing laser-cooled and trapped atoms. By varying the electron temperature, we show that electron screening modifies the equilibrium ion temperature. Even with few electrons in a Debye sphere, the screening is well described by a model using a Yukawa ion-ion potential. We also observe damped oscillations of the ion kinetic energy that are a unique feature of equilibration of a strongly coupled plasma.

Journal Article↗

The antifilarial activity of a marine red alga, Botryocladia leptopoda, against experimental infections with animal and human filariae.

The antifilarial activity of the marine red alga Botryocladia leptopoda against rodent and human lymphatic filarial parasites is described. The animal filarial species included Litomosoides sigmodontis and Acanthocheilonema viteae maintained in cotton rats and Mastomys coucha, respectively, while a subperiodic strain of the human lymphatic filarial parasite Brugia malayi was maintained in M. coucha. The crude extract and its hexane fraction brought about a marked reduction in the peripheral microfilarial level in both of the rodent filarial parasites L. sigmodontis and A. viteae. The microfilaricidal effect began slowly from day 8 or 15 after initiation of treatment and increased with time with a very high efficacy at the end of the observation period against both rodent filariids. The microfilaricidal efficacy was, however, not as prominent in the case of B. malayi. The antifilarial activity, which occurred in the hexane fraction, exerted action at a much lower dose. The product killed a significant proportion of A. viteae and L. sigmodontis adult parasites. In the case of B. malayi, although the macrofilaricidal efficacy was much less than that of the rodent parasites, it (hexane fraction) caused sterilization of a significant proportion of the surviving female parasites. The present findings indicate the possibility of developing an adulticidal and female sterilizing agent against filarial parasites from a marine red alga.

Animals↗