Seroprevalence of reproductive tract infections in women in northern India-a relatively low prevalence area.
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Adult↗
Biomedical subjects
M Sharma
Publications and source records attributed to M Sharma.
Immune response in HIV-1-infected children with thalassaemia given a primary course of DPT vaccine before acquiring HIV-1 infection.
The effect of HIV infection on immune response to diphtheria and tetanus primary immunisation was investigated in 24 HIV-1-positive multi-transfused (MT) children with thalassaemia and compared with 48 HIV-1-negative MT thalassaemic children and 36 HIV-1-negative non-transfused (NT) children in the community. Diphtheria and tetanus antibody levels in the HIV-1-positive MT group were comparable with the two HIV-negative groups. The proportions of children with antibody titres below the protective level (i.e. <0.01 IU/ml) for antidiphtheria antibodies were 20.8, 16.6 and 16.6%, and 12.5, 12.5 and 13.9% for anti-tetanus antibodies in the three groups, respectively. On the other hand, delayed-type hypersensitivity (DTH) response to diphtheria and tetanus antigens was significantly depressed in the HIV-1-positive group compared with the HIV-negative controls. The mean percentages of both mature (CD20+) and immature (CD10+) B-cell counts were significantly higher in the HIV-1-positive group than in the HIV-negative MT and NT groups (p<0.05). Levels of serum immunoglobulins and spontaneously secreted immunoglobulins were significantly higher in the HIV-1-positive group compared with both HIV-negative groups. The HIV-1-positive group showed a mean (SD) IL-6 of 52.9 (28.8) pg/ml compared with 23.7 (12.1) pg/ml and a detection rate of 54.2% in the HIV-negative MT group, and 23.6 (8.2) pg/ml and a 50% detection rate in the HIV-negative NT group. The IL-2 level was significantly lower (p<0.05) in the HIV-1-positive group [41.7% detection rate and mean (SD) 28.8 (17.1) pg/ml] than in the HIV-negative MT and NT groups [75% and 83.3% detection rates and mean (SD) 57.2 (42.3) pg/ml and 99.3 (51.1) pg/ml, respectively]. During follow-up for 3 years, the frequency of major infections was significantly higher in the HIV-1-positive group than in the other two groups. Acute pneumonia and acute sinusitis were the predominant infections regardless of HIV status while primary bacteraemia, osteomyelitis, pyogenic meningitis and septic arthritis were common in the HIV-1-positive group. We conclude that, in HIV-1-infected children pre-immunised with DPT, DTH response to diphtheria and tetanus antigens might be more reliable than anti-diphtheria and anti-tetanus antibody levels in predicting susceptibility to major bacterial infections.
Adolescent↗
Prolonged underfeeding of sheep increases myostatin and myogenic regulatory factor Myf-5 in skeletal muscle while IGF-I and myogenin are repressed.
The IGF axis is nutritionally sensitive in vivo and IGFs stimulate myoblast proliferation and differentiation in vitro, while myostatin inhibits these processes in vitro. We hypothesised that underfeeding would reversibly inhibit the myogenic activity of satellite cells in vivo together with decreased IGF-I and increased myostatin in muscle. Satellite cell activity was measured indirectly from the expression of proliferating cell nuclear antigen (PCNA) and the myogenic regulatory factors (MRFs), MyoD, Myf-5 and myogenin. Young sheep were underfed (30% of maintenance) and some killed after 1, 4, 12, 17, 21 and 22 weeks. Remaining underfed animals were then re-fed a control ration of pellets and killed after 2 days, and 1, 6 and 30 weeks. Expression of PCNA and MRFs decreased during the first week of underfeeding. This coincided with reduced IGF-I and myostatin mRNA, and processed myostatin. Subsequently, Myf-5, MyoD, myostatin mRNA and processed myostatin increased, suggesting that satellite cells may have become progressively quiescent. Long-term underfeeding caused muscle necrosis in some animals and IGF-I and MRF expression was increased in these, indicating the activation of satellite cells for muscle repair. Re-feeding initiated rapid muscle growth and increased expression of PCNA, IGF-I and the MRFs concurrently with decreased myostatin proteins. In conclusion, these data indicate that IGF-I and myostatin may work in a coordinated manner to regulate the proliferation, differentiation and quiescence of satellite cells in vivo.
Adaptation, Physiological↗
Imipenem resistance in nonfermenters causing nosocomial urinary tract infections.
Nonfermenting gram-negative bacilli (nonfermenters) have emerged as important nosocomial pathogens causing opportunistic infections in immunocompromised hosts. These organisms show high level of resistance to b-lactam agents, fluoroquinolones and aminoglycosides. Imipenem is a carbapenem antibiotic, which can be very useful for treatment of infections caused by nonfermenters. Eighty-five nonfermenters causing nosocomial UTI were tested for MIC to imipenem by agar dilution method. Resistance to other antimicrobial agents was compared between imipenem sensitive (S) and resistance (R) groups. Overall 36.4% of nonfermenters were resistant to imipenem. Forty two percent of P. aeruginosa and 18.5% of Acinetobacter baumanii were imipenem resistant. Other nonfermenters showed variable resistance, resistance in Alcaligenes spp. being very high. More than 70% of the nonfermenters were resistant to ceftazidime, gentamicin and ciprofloxacin. Piperacillin and amikacin had the best in vitro susceptibility. No significant difference was found in the antibiotic susceptibility profile among imipenem sensitive (S) or resistant (R) strains.
Anti-Bacterial Agents↗
Nutritional management of children with cystic fibrosis.
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Adolescent↗
Fluorosis in rural areas of Alwar district.
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Adolescent↗
In vitro control of fasciation in proliferating nucellar embryos of Mangifera indica L. var totapari red small for cloning.
Nucellar tissue contained in ovular halves of young fruits of Mangifera indica L. totapari red small, a dwarfing rootstock, differentiated fasciated embryonal structures in presence of 6-benzylaminopurine [BAP(0.15 mg l(-1))], 6-(gamma-gamma-dimethylallylamino) purine [2iP(0.15 mg l(-1))] and indole-3-acetic acid [(IAA(0.5 mg l(-1))] incorporated in the semisolid medium during 50-60 days. Due to embryonal fasciation, hardly 2-3 well-formed embryos could be obtained per culture of proliferating embryos. Of the 3 ethylene inhibitors [L-alpha-(2-aminoethoxyvinyl)-glycine-HCl (AVG), AgNO3 and salicylic acid (SA)] used, embryonal fasciation and necrosis of intervening tissue was completely controlled by 3-4 subcultures of fasciated mass of embryos under the influence of AVG (0.05 mg l(-1)) in presence of adenine sulphate [AdS (50 mg l(-1))] incorporated in the same medium. Almost synchronized development of isolated embryos, measuring ca 2 cm in length, was observed in a different medium used in liquid stationary state and supplemented, particularly with stress-producing substances [abscisic acid (ABA, 0.01 mg l(-1)); and polyethylene glycol (PEG, 100 mg l(-1))] besides certain other modifications. About 34% convertibility of processed embryos was obtained during a period of 90 days. The plantlets had well-developed roots along with laterals which were longer than leafy shoots. In vitro raised plants survived ex vitro for about 2 months.
Abscisic Acid↗
Pyrogallol-induced hepatotoxicity in rats: a model to evaluate antioxidant hepatoprotective agents.
Various hepatic disorders and hepatotoxic agents are associated with increased free radical generation. In the present study, the free radical generator pyrogallol (100 mg/kg i.p.) caused significant hepatic damage. The serum enzymes asparatate aminotransaminase (AST) and alanine aminotransaminase (ALT) increased to 357 +/- 30.7 IU/I and 147.8 +/- 28.4 IU/I, respectively in the pyrogallol-treated group compared with 208.4 +/- 4.1 IU/I and 84.5 +/- 19.5 IU/I, respectively in the control rats. Compared with control rats, the liver tissue in the pyrogallol-treated group showed an increased level of malondialdehyde (MDA) as well as glutathione (GSH). The infiltration of white blood cells into the liver tissue, as seen histologically, further substantiated liver damage. Pretreatment with a standard hepatoprotective drug (silymarin, 100 mg/kg i.p.) afforded significant protection against pyrogallol hepatotoxicity, as evidenced by amelioration of the raised serum markers of hepatic function, markers of oxidative stress and normal liver histology. Thus, pyrogallol-induced hepatotoxicity could be used as an appropriate model to evaluate hepatoprotective agents that have an antioxidant property.
Alanine Transaminase↗
Evaluation of minimum inhibitory concentration of quinolones and third generation cephalosporins to Salmonella typhi isolates.
A total of 323 Salmonella typhi isolates (261 isolates obtained during 1995-99 from Ludhiana and 62 randomly selected isolates obtained between 1980-99 from Chandigarh) were analyzed for drug resistant pattern. S. typhi isolates prior to 1986 were sensitive to all the antimicrobials tested by disc diffusion method. Most common multidrug resistance pattern noticed was ACCo T i.e. resistance to ampicillin, Chloramphenicol, cotrimoxazole and tetracycline. This study has revealed that withdrawal of chloramphenicol due to high level of resistance during 1990-94, has led to re-emergence of 43-93 percent chloramphenicol sensitive mutants during 1995-99. Two S. typhi isolates in 1995 and one in 1999 from Ludhiana depicted resistance to ciprofloxacin. Susceptibility of S. typhi isolates to third generation cephalosporins ranged between 87 to 100 per cent. There was a gradual increase with time period in mean minimum inhibitory concentration (MIC) of ciprofloxacin as it increased from 0.066 ug/ml for 1980-83 S. typhi isolates to 0.13 ug/ml for the 1996-99 isolates. Similarly, cefotaxime mean MIC for 1980-83 isolate was 0.172 ug/ml which further increased up to 0.32 ug/ml for S. typhi isolates encountered between 1996-99. In contrast, mean MIC value of 0.62 ug/ml of Ceftriaxone remained unchanged irrespective of the year of isolation of S. typhi isolates.
Anti-Bacterial Agents↗
The RING domains of the promyelocytic leukemia protein PML and the arenaviral protein Z repress translation by directly inhibiting translation initiation factor eIF4E.
The promyelocytic leukemia protein (PML) is a mammalian regulator of cell growth which is characteristically disrupted in acute promyelocytic leukemia and by a variety of viruses. PML contains a RING domain which is required for its growth-suppressive and antiviral properties. Although normally nuclear, in certain pathogenic conditions, including arenaviral infection, PML is relocated to the cytoplasm, where its functions are poorly understood. Here, we observe that PML and arenavirus protein Z use regions around the first zinc-binding site of their respective RING domains to directly interact, with sub-micromolar affinity, with the dorsal surface of translation initiation factor eIF4E, representing a novel mode of eIF4E recognition. PML and Z profoundly reduce the affinity of eIF4E for its substrate, the 5' 7-methyl guanosine cap of mRNA, by over 100-fold. Association with the dorsal surface of eIF4E and direct antagonism of mRNA cap binding by PML and Z lead to direct inhibition of translation. These activities of the RING domains of PML and Z do not involve ubiquitin-mediated protein degradation, in contrast to many RINGs which have been observed to do so. Although PML and Z have well characterized physiological functions in regulation of growth and apoptosis, this work establishes the first discrete biochemical mechanism which underlies the biological activities of their RING domains. Thus, we establish PML and Z as translational repressors, with potential contributions to the pathogenesis of acute promyelocytic leukemia and variety of viral infections.
Arenavirus↗
Molecular analysis of coagulase-negative Staphylococcus isolates from blood cultures: prevalence of genotypic variation and polyclonal bacteremia.
Fifty-seven coagulase-negative Staphylococcus isolates from 22 inpatients who had > or =2 blood cultures that were positive for Staphylococcus within 24 hours were analyzed to determine the frequency of polyclonal bacteremia. Patients were considered to have bacteremia (14 patients) or contamination of sample (8 patients) on the basis of clinical criteria. Nine colonies were randomly selected from each blood culture and genotyped by means of SmaI digestion/pulsed-field gel electrophoresis. Relatedness was determined by calculation of the Dice coefficient of banding-pattern similarity (S(AB)). Analysis of bacteremic isolates demonstrated the presence of a single species in 35 of 41 blood cultures, 1 related variant in 5 blood cultures (87%-92% S(AB)), and an unrelated strain in 1 blood culture (79% S(AB)). Analysis of contaminated samples demonstrated the presence of a single strain in 10 of 16 blood cultures and 1-3 variants (28%-97% S(AB)) in the remainder. Genotype diversity was significantly more common in the contaminated samples (P=.036). Almost all coagulase-negative Staphylococcus bacteremias were monoclonal.
Adult↗
PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA.
The promyelocytic leukemia protein PML is organized into nuclear bodies which mediate suppression of oncogenic transformation and of growth. The biochemical functions of PML bodies are unknown, despite their involvement in several human disorders. We demonstrate that eukaryotic initiation factor 4E (eIF4E) directly binds the PML RING, a domain required for association with bodies and for suppression of transformation. Nuclear eIF4E functions in nucleocytoplasmic transport of a subset of transcripts including Cyclin D1. Present studies indicate that some PML requires the evolutionarily older eIF4E protein for association with nuclear bodies. Further more, PML RING modulates eIF4E activity by drastically reducing its affinity for its substrate, 5' m(7)G cap of mRNA. We demonstrate that eIF4E requires cap binding for transport of Cyclin D1 mRNA and subsequent transformation activity. Additionally, PML reduces the affinity of eIF4E for m(7)G mRNA cap, causing a reduction in Cyclin D1 protein levels and consequent transformation inhibition. PML is the first factor shown to modulate nuclear eIF4E function. These findings provide the first biochemical framework for understanding the transformation suppression activity of PML.
Cell Nucleus↗
Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family.
Estrogen acting through the estrogen receptor (ER) is able to regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors. Ligand-activated ER binds DNA and transactivates the promoters of estrogen target genes. In addition, ligand-activated ER can interact with other factors to alter the physiology and growth of cells. Using a yeast two-hybrid screen, we have identified an interaction between ER alpha and the proapoptotic forkhead transcription factor FKHR. The ER alpha-FKHR interaction depends on beta-estradiol and is reduced significantly in the absence of hormone or the presence of Tamoxifen. A glutathione S-transferase pull-down assay was used to confirm the interaction and localized two interaction sites, one in the forkhead domain and a second in the carboxyl terminus. The FKHR interaction was specific to ER alpha and was not detected with other ligand-activated steroid receptors. The related family members, FKHRL1 and AFX, also bound to ER alpha in the presence of beta-estradiol. FKHR augmented ER alpha transactivation through an estrogen response element. Conversely, ER alpha repressed FKHR-mediated transactivation through an insulin response sequence, and cell cycle arrest induced by FKHRL1 in MCF7 cells was abrogated by estradiol. These results suggest a novel mechanism of estrogen action that involves regulation of the proapoptotic forkhead transcription factors.
Amino Acid Sequence↗
A participatory evaluation of community-based rehabilitation programme in North Central Vietnam.
PURPOSE: The purpose of this study was to conduct a participatory evaluation of the community-based rehabilitation (CBR) programme in North Central Vietnam to ascertain the extent of success with the World Health Organization (WHO) model. In 1992, for the first time a non-governmental organization (NGO) was formed in this region to plan and implement the CBR approach based on the WHO model for meeting the needs of persons with disabilities (PWD). The programme is currently being implemented in ten districts and has been able to affect 24.6% of PWD in this region. METHODS: A framework of strengths, weaknesses, opportunities and threats (SWOT) analysis was used. Participatory data collection was done at the village, commune, district, provincial, and central levels using semi-structured interviews and focus group discussions. The data were examined against the five principles of the WHO model: available resource utilization, knowledge transfer, community participation, referral services strengthening and multisectoral coordination. RESULTS: The strengths, weaknesses, opportunities, and threats across all levels were collated and presented. CONCLUSION: Specific strengths have been found in three out of five principles of the WHO Model. The programme would benefit by consolidating on the positive aspects in years to come.
Activities of Daily Living↗
Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK.
Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene was localized to human chromosome 1q32 by fluorescent in situ hybridization. SNARK was translated in vitro to yield a single protein band of approx. 76 kDa; Western analysis of transfected baby hamster kidney (BHK) cells detected two SNARK-immunoreactive bands of approx. 76-80 kDa. SNARK was capable of autophosphorylation in vitro; immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK fibroblasts. These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress.
Adenosine Monophosphate↗
SMAD3 represses androgen receptor-mediated transcription.
The androgen-signaling pathway is important in the growth and progression of prostate cancer. Androgen ablation therapy, which may result in programmed cell death, is often used to treat advanced prostate cancer. The growth-promoting effects of androgen are mediated mostly through the androgen receptor (AR). Transforming growth factor beta (TGF-beta) plays critical roles in controlling prostate cell proliferation, differentiation, and apoptosis. Normal transcripts and proteins of TGF-beta receptors are frequently lost in prostate cancer cells, especially in advanced stages of the disease. However, the mechanisms by which TGF-beta inhibits proliferation and induces apoptosis in prostate cancer cells is not clear. We investigated the molecular mechanism by which TGF-beta inhibits transcriptional activation mediated by AR. Using transient transfection systems, we demonstrated that Smad3 specifically represses transcriptional activation mediated by AR on two natural androgen-responsive promoters. This repression is transmitted through TGF-beta signaling and can be regulated by other Smad proteins. A protein-protein interaction between AR and Smad3 was identified in vitro and in vivo, and the transcription activation domain of AR and the MH2 of Smad3 were identified as being responsible for binding. Additional functional experiments showed that the repression of AR by Smad3 is mediated solely through the MH2 domain. These results provide fresh insight for understanding the mechanism by which TGF-beta regulates the androgen-signaling pathway in prostate cancer cells.
Androgen Receptor Antagonists↗
Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6.
The androgen receptor (AR) is a hormone-dependent transcription factor that plays important roles in male sexual differentiation and development. Transcription activation by steroid hormone receptors, such as the androgen receptor, is mediated through interaction with cofactors. We recently identified a novel AR-interacting protein, provisionally termed PAK6, that shares a high degree of sequence similarity with p21-activated kinases (PAKs). PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac interactive binding motif and a carboxyl-terminal kinase domain. A domain-specific and ligand-dependent interaction between AR and PAK6 was further confirmed in vivo and in vitro. Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues. Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen. Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription. This report identifies a novel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with AR pathways to regulate AR function in normal and malignant prostate cells.
Amino Acid Sequence↗
Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment.
Recent reports suggest the involvement of free radicals in the pathophysiology of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brain is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energy metabolism, it is not known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are associated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340 g] were injected with intracerebroventricular STZ [3 mg/kg] bilaterally stereotaxically under ketamine anesthesia [70 mg/kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learning and memory behavior was analyzed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The behavioral tests were performed on day 17, 18 and 19. The rats developed significant deficits in learning, memory and cognitive behavior, indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development of oxidative stress in the brain as indicated by significant elevations in malondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dementia.
Animals↗