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Biomedical subjects

R Dhar

Publications and source records attributed to R Dhar.

At least 19 recordsLinked to original sources
PubMed2006

High prevalence and level of resistance to metronidazole, but lack of resistance to other antimicrobials in Helicobacter pylori, isolated from a multiracial population in Kuwait.

BACKGROUND: The primary treatment regimen for Helicobacter pylori infection for Kuwaitis does not contain metronidazole, but that for expatriates does. There is also increasing failure of antimicrobial therapy. AIM: To determine the susceptibility of H. pylori from upper gastrointestinal biopsies of Kuwaitis and non-Kuwaitis to find out if differences existed in the susceptibilities of the isolates from the two different populations. METHODS: The susceptibilities of 96 H. pylori isolates were tested against metronidazole, amoxicillin, clarithromycin and tetracycline by the E test. The rdxA gene was analysed from selected metronidazole-susceptible and metronidazole-resistant strains to find out polymorphism and the basis of metronidazole resistance. RESULTS: Approximately, 70% of isolates from both populations were metronidazole resistant with 65% isolates showing high minimum inhibitory concentration values of >256 mug/mL. No resistance to the other three antimicrobials was found. There were novel nonsense and missense mutations with no deletion in the rdxA gene by insertion of mini-IS605. CONCLUSIONS: The prevalence and level of metronidazole resistance in H. pylori in the two populations was high with no difference, in spite of different treatment regimens. Metronidazole resistance in this transitional country appeared to be independent of prior metronidazole use for treatment of H. pylori infection.

Anti-Bacterial Agents↗
PubMed2006

Are rheumatologists' treatment decisions influenced by patients' age?

OBJECTIVES: The objective of this study was to determine whether physicians' treatment preferences are influenced by patients' age. METHODS: We mailed a survey to a random sample of rheumatologists practicing in the US. The survey included a scenario describing a hypothetical patient with rheumatoid arthritis (RA) on hydroxychloroquine, sulfasalazine and low-dose prednisolone, who presents with active disease during a follow-up appointment. The scenario was formulated in two versions that were identical except for the age of the patient. After reading the scenario, respondents were asked to rate (on a 10 cm numerical rating scale) their recommendations for each of the three options: (i) increasing the dose of prednisolone, (ii) adding a new disease-modifying anti-rheumatic drug (DMARD) and (iii) switching DMARDs. Rheumatologists who rated either adding a new DMARD or switching DMARDs higher than increasing the dose of prednisolone were classified as 'preferring aggressive treatment with DMARDs', while the others were classified as 'NOT preferring aggressive treatment with DMARDs'. RESULTS: A total of 480 rheumatologists were mailed a questionnaire; 204 responded, giving a response rate of 42.5%. Overall 163 (80%) respondents were classified as preferring aggressive treatment with DMARDs. Rheumatologists responding to this survey were more likely to prefer aggressive DMARD treatment for the young RA patient vs the older RA patient (87 vs 71%, P= 0.007). CONCLUSIONS: Our findings suggest that rheumatologists' treatment recommendations may be influenced by age. Future educational efforts should increase physician awareness of this possible bias in order to ensure equal service delivery across ages.

Adult↗
PubMed2005

Dielectric spectroscopy of a binary mixture of liquid crystals showing wide temperature range twisted grain boundary phase with re-entrant cholesteric phase.

There are only few materials, which have shown long temperature range twisted grain boundary (TGB) phases. One such material is the chiral binary mixture of 7OCB and 5* CBB (mole ratio 0.8 and 0.2) which shows unique phase sequence of cholesteric ( N*) , a wide temperature range TGBA (approximately 31 degrees C) and reentrant cholesteric (N*re) phases. In the present work we are reporting the dielectric spectroscopy of the above mixture with a chiral analog of earlier reported nematic (N) , smectic- A (SmA) , and reentrant nematic (Nre) phase sequences [Phys. Rev. A 46, 7733 (1992)] for different conditions of molecular orientations. Two modes of dielectric relaxations have been detected in a homeotropically aligned sample with unusually low relaxation frequencies for one of them. Planar oriented molecules in the TGBA phase show a soft mode of relaxation and support the recently proposed theory for the soft mode relaxation of the TGBA phase [Phys. Rev. E 65, 11701 (2001)]. By applying the dc electric field on planar oriented molecules in the TGBA phase, it has been possible to obtain a helix free homeotropically aligned TGBA phase.

Journal Article↗
PubMed2001

Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.

Highly active antiretroviral therapy has decreased human immunodeficiency virus (HIV)-associated mortality; other comorbidities, such as chronic liver disease, are assuming greater importance. We retrospectively examined the causes of death of HIV-seropositive patients at our institution in 1991, 1996, and 1998-1999. In 1998-1999, 11 (50%) of 22 deaths were due to end-stage liver disease, compared with 3 (11.5%) of 26 in 1991 and 5 (13.9%) of 36 in 1996 (P=.003). In 1998-1999, 55% of patients had nondetectable plasma HIV RNA levels and/or CD4 cell counts of >200 cells/mm(3) within the year before death. Most of the patients that were tested had detectable antibodies to hepatitis C virus (75% of patients who died in 1991, 57.7% who died in 1996, and 93.8% who died in 1998-1999; P=NS). In 1998-1999, 7 patients (31.8%) discontinued antiretroviral therapy because of hepatotoxicity, compared with 0 in 1991 and 2 (5.6%) in 1996. End-stage liver disease is now the leading cause of death in our hospitalized HIV-seropositive population.

Adult↗
PubMed2001

Consumer research: in search of identity.

Although the consumer research field has made great progress over the past 30 years with respect to the scope, quality, and quantity of research, there are still significant disagreements about what consumer research is, what its objectives are, and how it should differ from related disciplines. As a result, the field appears to be rather fragmented and even divided on some fundamental issues. In this review we first examine the original vision for the field and its limitations. In the second section we explore the consequences of the ambiguity about the domain and identity of consumer research and the multidisciplinary influences on the field. In particular, we review key trends and "camps" in consumer research, which represent complementary and, in some cases, conflicting views regarding the main topics of investigation and how research is conducted. This review is based in part on systematic analyses of articles that have been published in the leading consumer research journals over the past 30 years. Finally, in the third section we revisit the question of what might differentiate the field from related disciplines, as well as the role of theory testing, studies of substantive phenomena, and relevance in consumer research.

Cognition↗
PubMed2000

Anopheles gambiae salivary gland proteins as putative targets for blocking transmission of malaria parasites.

Anopheles gambiae is the primary vector of human malaria in sub-Saharan Africa. Invasion of Anopheles salivary glands by Plasmodium sporozoites is a necessary step in the transmission of malaria and is likely to be mediated by specific receptor-ligand interactions. We are interested in identifying putative an A. gambiae salivary gland receptor or receptors for sporozoite invasion as a possible target for blocking malaria transmission. By using monoclonal antibodies against female-specific A. gambiae salivary gland proteins, two molecules, one of 29 kDa and one of 100 kDa, were identified and characterized with respect to the age and blood-feeding process of mosquitoes. In an in vivo bioassay, the monoclonal antibody against the 100-kDa protein inhibited Plasmodium yoelii sporozoite invasion of salivary glands >/=75%. These results show that A. gambiae salivary gland proteins are accessible to monoclonal antibodies that inhibit sporozoite invasion of the salivary glands and suggest alternate targets for blocking the transmission of malaria by this most competent of malaria vectors.

Animals↗
PubMed2000

The prevalence and clonal diversity of penicillin-resistant Streptococcus pneumoniae in Kuwait.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence polymerase chain reaction (REP-PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pnuemoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77 % to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP-PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

DNA, Bacterial↗
PubMed2000

Mex67p of Schizosaccharomyces pombe interacts with Rae1p in mediating mRNA export.

We identified the Schizosaccharomyces pombe mex67 gene (spmex67) as a multicopy suppressor of rae1-167 nup184-1 synthetic lethality and the rae1-167 ts mutation. spMex67p, a 596-amino-acid-long protein, has considerable sequence similarity to the Saccharomyces cerevisiae Mex67p (scMex67p) and human Tap. In contrast to scMEX67, spmex67 is essential for neither growth nor nuclear export of mRNA. However, an spmex67 null mutation (Deltamex67) is synthetically lethal with the rae1-167 mutation and accumulates poly(A)(+) RNA in the nucleus. We identified a central region (149 to 505 amino acids) within spMex67p that associates with a complex containing Rae1p that complements growth and mRNA export defects of the rae1-167 Deltamex67 synthetic lethality. This region is devoid of RNA-binding, N-terminal nuclear localization, and the C-terminal nuclear pore complex-targeting regions. The (149-505)-green fluorescent protein (GFP) fusion is found diffused throughout the cell. Overexpression of spMex67p inhibits growth and mRNA export and results in the redistribution of the diffused localization of the (149-505)-GFP fusion to the nucleus and the nuclear periphery. These results suggest that spMex67p competes for essential mRNA export factor(s). Finally, we propose that the 149-505 region of spMex67p could act as an accessory factor in Rae1p-dependent transport and that spMex67p participates at various common steps with Rae1p export complexes in promoting the export of mRNA.

Active Transport, Cell Nucleus↗
PubMed1999

p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.

Binding Sites↗
PubMed1999

Regulation of mRNA export by nutritional status in fission yeast.

We have isolated a mutation in nup184(nup184-1) that is synthetically lethal with the mRNA export defective rae1-167 mutation in Schizosaccharomyces pombe. The consequence of the synthetic lethality is a defect in mRNA export. The predicted Nup184p is similar to Nup188p of Saccharomyces cerevisiae, and a Nup184p-GFP fusion localizes to the nuclear periphery in a punctate pattern. The Deltanup184 null mutant is viable and also is synthetically lethal with rae1-167. In a rae1(+) background, both the nup184-1 and Deltanup184 mutations confer sensitivity to growth in nutrient-rich medium (YES) that is accompanied by nuclear poly(A)+ RNA accumulation. Removal of the cAMP-dependent protein kinase, Pka1p, relieved the growth and mRNA export defects of nup184 mutants when grown in nutrient-rich medium. The activation of Pka1p is necessary, but not sufficient, to cause the severe poly(A)+ RNA export defects when nup184 mutant cells are incubated in YES, suggesting nutritional status can also regulate poly(A)+ RNA export. Our results suggest that the regulation of poly(A)+ RNA export by Pka1p kinase appears to be indirect, via a translation-dependent step, but post-translationally in response to YES.

Cell Nucleus↗
PubMed1999

Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission-blocking antibodies.

Immunological intervention, in addition to vector control and malaria chemotherapy, will be needed to stop the resurgence of malaria, a disease with a devastating impact on the health of 300 to 500 million people annually. We have pursued a vaccination strategy, based on DNA immunization in mice with genes encoding two antigens present on the sexual stages of Plasmodium falciparum, Pfs25 and Pfg27, to induce biologically important antibodies that can block development of the parasite in the Anopheles mosquito and thus transmission of the disease. DNA encoding Pfs25 when administered by the intramuscular route, either alone or with DNA encoding Pfg27, had the most potent transmission-blocking effects, resulting in up to a 97% decrease in oocyst numbers in mosquito midguts and a 75% decrease in rate of infection. Immunization with DNA encoding a Pfg27-Pfs25 fusion protein was less effective and DNA encoding Pfg27 elicited antibodies in sera that had only modest effects on the infectivity of the parasite. These results show for the first time that DNA vaccination can result in potent transmission-blocking antibodies in mice and suggest that the Pfs25 gene should be included as part of a multicomponent DNA vaccine.

Animals↗
PubMed1999

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.

Anticarcinogenic Agents↗
PubMed1998

Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions.

Neem (Azadirachta indica) has been shown to possess anti-malarial activity. In this study we systematically evaluated extracts of neem seeds and purified fractions further enriched in polar or non-polar constituents for their effect on in vitro growth and development of asexual and sexual stages of the human malaria parasite Plasmodium falciparum. Use of synchronized stages of parasites suggested trophozoites/schizonts as the susceptible target stages to various neem extracts. In addition, all the maturation stages of gametocytes were also killed by various neem fractions tested. The anti-plasmodial effect of neem components was also observed on parasites previously shown to be resistant to other anti-malarial drugs, i.e. chloroquine and pyrimethamine suggesting a different mode of action. Neem seed fractions are thus active not only against the parasite stages that cause the clinical infection but also against the stages responsible for continued malaria transmission.

Animals↗
PubMed1998

Evaluation and comparison of two immunodiagnostic assays for Helicobacter pylori antibodies with culture results.

Several commercially available serological kits have been used as an alternative to endoscopy for the diagnosis of Helicobacter pylori infection. We evaluated the performance of two such kits, Serion H. pylori immunotab kit (Serion, Wurzberg, West Germany) and Pyloragen H. pylori test kit (Hypcor Biomedical Inc., Irvine, CA). Gastric biopsy and serum samples were collected from 345 consecutive dyspeptic patients. The culture and or direct smear of the biopsy was positive for H. pylori in 228 patients (66%), whereas 117 patients (34%) were found to be H. pylori negative. We determined the serological response of the patients using the two kits, both of which are based on the principle of enzyme-linked immunosorbent assay. Comparing the serum immunoglobin G (IgG) and IgA (in a limited number of cases) responses to H. pylori status, the sensitivity, the specificity, positive predictive value, and negative predictive value were calculated. The corresponding data for the different tests were 64%, 79%, 84%, and 56% for Serion IgC, 32%, 94%, 88%, and 52% for Serion IgA, and 88%, 17%, 62%, and 46% for Pyloragen IgG, respectively. We conclude that there is a poor correlation between the presence of H. pylori infection and the antibody response, which could be explained either because of low sensitivities and specificities of the commercial kits used for the measurement of antibodies to H. pylori in the serum or because of poor immunological response in our patients to H. pylori antigens.

Adolescent↗
PubMed1997

The human RAE1 gene is a functional homologue of Schizosaccharomyces pombe rae1 gene involved in nuclear export of Poly(A)+ RNA.

A Schizosaccharomyces pombe temperature-sensitive mutant, rae1-1, was previously identified by us as being defective in nuclear export of Poly(A)+ RNA when grown at restrictive temperature. Here, we report the isolation of the human homologue of the S. pombe rae1 gene. The RAE1 genes are highly conserved in evolution in both structure and function. The human RAE1 cDNA, when expressed from the CMV-promoter, can suppress partially the temperature sensitivity of the rae1-1 mutant. This is also reflected by increased Poly(A)+ RNA export at a restrictive temperature. An epitope tagged human Rae1p localizes to both the nucleus and the cytoplasm in transiently transfected HeLa cells. We discuss the potential role of Rae1p in nuclear cytoplasmic trafficking in yeast and higher eukaryotic cells.

Biological Transport↗