Search PubMed⌕ Search

Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 127 records · Page 7Linked to original sources
PubMed2002

Left atrial myxoma presenting as pseudobulbar palsy.

A case of left atrial (LA) myxoma presenting as pseudobulbar palsy, due to multiple cerebral infarcts, without any cardiac manifestations, is presented. LA myxoma is rare cause of embolization to CNS causing ischemic infarcts. Due to multiple CNS infarcts patient can present with varied clinical picture and pseudobulbar palsy is not a very common presentation. It was a real diagnostic dilemma before LA myxoma was diagnosed on echocardiography.

Adult↗
PubMed2002

The effects of rehydration on cycling performance after exercise-induced dehydration.

The effects of 7.6% carbohydrate-electrolyte solution (CES) and placebos (P) on rehydration (R) after exercise-induced dehydration and on a subsequent time-trial (TT) of cycling performance were studied. Thirteen male subjects exercised in a thermally-controlled environment (28 degrees C, 63% RH) until 3% of their body weight was lost. After exercise, the subjects moved to a neutral environment (22 degrees C) and rested for 30 minutes prior to a 2-hour R period. During R, subjects were fed CES or P to a maximum volume of 120% of previous body mass loss at 0, 30, and 60 minutes, in bolus-doses of 50%, 40% and 30% respectively. After R, subjects performed a 1-hour TT with no further fluid intake. % R with CES was significantly higher than with P (70 +/- 3% vs 60 +/- 5%; p < 0.01). During the TT, blood glucose dropped in the CES group but not in the P group. It was found that, despite a more effective R with CES, the performance results did not differ between groups (65.1 +/- 2.2 minutes and 65.2 +/- 2.3 minutes for CES and P respectively). It is suggested that an insulin-mediated rebound effect on CHO metabolism during TT, in which no further CHO was supplied, nullified the benefits of rehydration.

Adult↗
PubMed2002

Microwave induced diastereoselective synthesis of spiro[indole-oxiranes] and their conversion to spiro[indole-pyrazoles].

The microwave induced diastereoselective synthesis of spiro[3H-indole-3,2'-oxiranes]-3'-benzoyl-2 (1H)-one is reported. Epoxidation of 3-aroylmethylene indole-2-one 1 with alkaline H2O2 under microwave irradiation in an open vessel under controlled conditions yields a diastereomeric pair of spiro[3H-indole-3,2'-oxiranes]-3'-benzoyl-2 (1H) ones 2 and 3 in 65-85% yield. The stereoselectivity depends upon the reaction time and power output. The spiro[indole-pyrazoles] 4 have been synthesised by the reaction of 2 with hydrazine hydrate. Under the same condition 3 gave the mixture of products. All synthesised compounds have been screened in vitro for their antifungal activity against Rhizoctonia solani, Fusarium oxysporum and Collectotrichum capsici and antitubercular activity against Mycobacterium tuberculosis.

Antifungal Agents↗
PubMed2002

Wasp sting induced neurological manifestations.

Wasp stings generally cause local reactions like pain, wheal, flare, edema and swelling, which are generally self-limiting. Multiple stings can lead to vomiting, diarrhea, generalized edema, dyspnea, hypotension, collapse, renal failure or death. Unusually, they may cause serum sickness, vasculitis, neuritis or encephalitis. We report a case of a 40 year old male who developed focal neurological deficit 10 hours following a wasp sting, which was confirmed to be ponto-cerebellar infarction on MRI scan, and recovered within five days.

Adult↗
PubMed2002

Diagnosis of visceral leishmaniasis: comparative potential of amastigote antigen, recombinant antigen and PCR.

Development of simple, economical and non-invasive tests for the early diagnosis of visceral leishmaniasis (VL) or kala-azar (KA) remains a challenge, and serological studies based on antigen prepared from the amastigote stage of Leishmania donovani, the stage that causes infection, are lacking. In the present study, circulating antibodies to total antigen isolated from the promastigote and amastigote stages of the parasite, as well as to recombinant K39 (rK39) antigen, are measured by enzyme-linked immunosorbent assay (ELISA) and the results compared with a polymerase chain reaction (PCR) test for KA diagnosis. In 116 samples of KA examined, the amastigote antigen gave significantly higher mean absorbance values in ELISA than did the promastigote antigen. The sensitivity for KA detection was significantly higher using the amastigote antigen (94%) than the promastigote antigen (90.5%). Analysis in 91 controls showed that specificity was higher with amastigote antigen (92.3%) than with promastigote antigen (86.8-89.0%). Reliability of ELISA diagnosis with amastigote antigen was only marginally lower than that with rK39 ELISA or with the PCR test. Easy availability and low cost of indigenous amastigote antigen, together with the simplicity of ELISA compared with PCR, make ELISA based on amastigote antigen a promising choice for the diagnosis of KA.

Animals↗
PubMed2002

Circadian pattern in cerebro vascular disorders.

Over the last decade, various studies have been reported to evaluate the circadian pattern of cardiovascular and cerebro-vascular diseases. The data from Indian population is lacking. We undertook this prospective observational study to evaluate the circadian variation in disorders like cerebro-vascular accidents and transient ischemic attacks. Total of 146 patients (events) were studied. Only 10 patients had TIA's. 55% had hemorrhage and 45% had infarction. The 24 hours period was divided into 6 equal portions of 4 hours each. The maximum events were seen between 4 am to 8 am and 12 noon to 4 pm (23.28%) each. Minimum events were seen between 12 midnight to 4 am 14/146 - 9.58%). The circadian variation in occurrence of cerebro-vascular disorders was present with two equal peaks.

Cerebral Hemorrhage↗
PubMed2002

Life and past one year stressful events in coronary artery disease.

UNLABELLED: Personality type and role of stressful life events in the etiology of various disease has been a fertile field for research for past few decades. OBJECT STUDY: Very limited studies have been conducted especially for the estimation of stressful life events in Indian population with coronary artery disease (CAD), so a study was conducted to evaluate the same. METHODOLOGY: Ninety patients of CAD (positive for TMT or angiographic proved coronary obstruction) formed the study material. These were evaluated by Jenkin's activity survey (JAS) for personality type and on Presumptive Stressful Life Events (PSLE) scale for life events. SUMMARY OF RESULTS: The mean age of subjects was 57 +/- 8.03 years and male: female ratio was 14:1 Fifty one subjects (57%) had Type A personality while thirty nine subjects (43%) had Type B personality. Mean life time stressful life events were 3.4 +/- 1.92 which were higher (p < 0.001) when compared to respective average score of normal Indian population i.e. 10.34 +/- 5.4 and 1.90 +/- 2.62 respectively. CONCLUSION: Based on the present study it may be concluded that Type A personality is more frequently seen in CAD and also that these subjects had a statistically higher incidence of lifetime and past one year stressful events which could have made these subjects more vulnerable to CAD.

Adult↗
PubMed2002

C-reactive protein (CRP) as an indicator of sepsis in orthopaedic trauma.

In the present study serial estimations of changes in plasma C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total leucocyte count (TLC) and temperature were recorded in 100 patients. Nature and extent of tissue trauma varied from fresh soft tissue or bony injuries to elective orthopaedic procedures, besides acute orthopaedic infections. All the parameters showed a rise from day 1-3 from the normal levels, though the rise in temperature was minimal. However, from third day onwards, CRP level showed a sharp decline in all cases without any septic complication or infective patients who improved with treatment. Decline of ESR levels on the other hand was variable. Similarly, decline of TLC and temperature was also not consistent and sharp. Persistent rise of CRP level beyond third day or any subsequent rise in CRP level was consistent with a septic complication in the patient. CRP was therefore observed to be a sensitive and dependable indicator of orthopaedic sepsis even orthopaedic trauma.

Adolescent↗
PubMed2001

Immunization with wild-type p53 gene sequences coadministered with Flt3 ligand induces an antigen-specific type 1 T-cell response.

We examined the ability of immunization with sequential adenovirus/plasmid DNA vectors expressing human wild-type p53 to stimulate a type 1 T-cell response and induce protection against challenge from a metastatic tumor that expresses mutated murine p53. We found that tumor protection and an antigen (Ag)-specific immune response were enhanced by prior injection of Flt3 ligand (Flt3L) at a dose and schedule that significantly increased dendritic cell (DC) number and frequency. Preliminary studies using enzyme-linked immunospot and Winn assays suggested that Ag-specific CD8 cells, with their significant increase in IFN-gamma-secreting activity (Tc1 cells), were responsible for the tumor protection. The delayed-type hypersensitivity response to p53 was increased in mice immunized with p53 alone or p53 and Flt3L compared with a negative control. In contrast, spleen cells from mice immunized with p53 and Flt3L exhibited a higher Ag-specific proliferative response than mice immunized with p53 alone. The frequencies of Ag-specific IFN-gamma and interleukin (IL)-4-secreting cells were determined using an enzyme-linked immunospot assay, which demonstrated that the frequency of IFN-gamma-secreting cells was significantly higher in mice immunized with p53 and Flt3L than in mice receiving Flt3L, excipient, or p53 treatment alone. In contrast, the frequency of IL-4-secreting cells did not differ significantly among these groups. We also observed an increased frequency of IL-12 and IFN-gamma-secreting cells (but not IL-4 or IL-10) in the spleens of mice immediately after 10 days of Flt3L treatment, which was also the day of p53 priming. This observation supports the likelihood that there are multiple mechanisms of Flt3L adjuvant activity, including expansion of DC and type 1 T-cell number. Overall, these results suggest that immunization with p53 genetic sequences after in vivo expansion of DC, using Flt3L, provides a useful strategy to induce p53-specific, and protective, type 1 T-cell responses.

Adenoviridae↗
PubMed2001

Ectopic expression of a Chlamydomonas mt+-specific homeodomain protein in mt- gametes initiates zygote development without gamete fusion.

The molecular mechanisms that activate expression of zygote genes after fertilization are obscure. In animals, receptor-ligand interactions during sperm-egg membrane fusion as well as delivery of putative regulatory molecules by the sperm into the egg cytoplasm are proposed to activate zygote development and subsequent transcription of zygote genes. The mechanisms of activation of zygote development in higher plants also are mysterious, in part because of the difficulty of isolating female gametes of higher plants. In the unicellular, biflagellated green alga Chlamydomonas, the early steps in zygote development are much more accessible to investigation. Within minutes after mating type plus (mt+) and mating type minus (mt-) gametes fuse, expression of several zygote-specific transcripts is induced independently of protein synthesis. Here, we show that ectopic expression in mt- gametes of an mt+ gamete-specific, homeodomain protein, GSP1, induces a zygote-like phenotype and activates expression of zygote genes. One of the genes, zsp2, expressed in these "haploid zygotes" encodes a zygote cell surface adhesion molecule that promotes formation of multicellular aggregates. In total, expression of six out of seven zygote genes examined was induced by ectopic expression of GSP1. Our experiments show that in addition to contributing their genomes to the zygote cytoplasm, gametes also deliver proteins that can activate gene transcription.

Animals↗
PubMed2001

Quantal density functional theory of excited states.

We explain by quantal density functional theory the physics of mapping from any bound nondegenerate excited state of Schrödinger theory to an S system of noninteracting fermions with equivalent density and energy. The S system may be in a ground or excited state. In either case, the highest occupied eigenvalue is the negative of the ionization potential. We demonstrate this physics with examples. The theory further provides a new framework for calculations of atomic excited states including multiplet structure.

Journal Article↗
PubMed2001

Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor.

Poxviruses express a family of secreted proteins that bind with high affinity to chemokines and antagonize the interaction with their cognate G protein-coupled receptors (GPCRs). These viral inhibitors are novel in structure and, unlike cellular chemokine receptors, are able to specifically interact with most, if not all, CC-chemokines. We therefore sought to define the structural features of CC-chemokines that facilitate this broad-spectrum interaction. Here, we identify the residues present on human monocyte chemoattractant protein-1 (MCP-1) that are required for high-affinity interaction with the vaccinia virus 35-kDa CC-chemokine binding protein (VV-35kDa). Not only do these residues correspond to those required for interaction with the cognate receptor CCR2b but they are also conserved among many CC-chemokines. Thus, the results provide a structural basis for the ability of VV-35kDa to promiscuously recognize CC-chemokines and block binding to their receptors.

Amino Acid Sequence↗
PubMed2001

Role for tissue factor pathway in murine model of vascular remodeling.

Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay between TF and TFPI and the regulation of vascular thrombogenicity in a model of vascular remodeling. To determine the levels and pattern of vascular expression of TF and TFPI associated with vascular remodeling, a murine model of flow cessation was studied. TF activity of the arteries increased after ligation (P<0.05). Quantitative analysis of homogenates of remodeled carotid arteries revealed increased TF expression but unchanged TFPI expression compared with normal carotid arteries, resulting in enhanced TF activity. To determine the potential therapeutic role of TFPI in this thrombogenic state, mice were treated with intravascular adenoviral delivery of either murine TFPI (Ad-mTFPImyc) or a control adenovirus (Ad-DeltaE1). Overexpression of TFPI decreased vascular TF activity compared with viral control (P<0.01). Overexpression of TFPI inhibited neointimal formation (P=0.038), resulting in enhanced luminal area (P=0.001) 4 weeks after flow cessation. In this murine model of vascular remodeling, an imbalance between TF and TFPI expression is generated, resulting in increased TF activity. Overexpression of TFPI in this model inhibits vascular TF activity and results in attenuation of vascular remodeling associated with flow interruption.

Animals↗
PubMed2001

Comparative analysis of PAH:DNA adducts formed in lung of mice exposed to neat coal tar and soils contaminated with coal tar.

7H-Benzo[c]fluorene (benzo[c]fluorene) is a major DNA adduct forming component of coal tar in lung of mice. The present study evaluated the types of PAH:DNA adducts formed from different neat coal tar samples and soils contaminated with coal tar. Mice were fed diets containing coal tar either neat or as a contaminant in an environmental soil sample for 14 days, and the types of chemical:DNA adducts formed in lung were evaluated using 32P-postlabeling and HPLC analysis. Three major DNA adducts derived respectively from benzo[b]fluoranthene (B[b]F), benzo[a]pyrene (B[a]P), and benzo[c]fluorene were detected in three of the four neat coal tar samples evaluated. In contrast, only a single major DNA adduct derived from benzo[c]fluorene was observed with the remaining tar sample. Ingestion of coal tar contaminated soil resulted in DNA adducts primarily derived from benzo[c]fluorene and B[b]F; a B[a]P derived DNA adduct was not detected. The DNA adducts derived from benzo[c]fluorene and B[b]F but not B[a]P were also observed with animals fed methylene chloride extracts of three of these soils but not the one designated A1000H soil. However, the extract of A1000H resulted in a B[a]P:DNA adduct being detected along with adducts formed from B[b]F and benzo[c]fluorene. The selective formation of the benzo[c]fluorene:DNA adduct with coal tar contaminated soils indicates that the in vivo systemic bioavailability and/or metabolism of benzo[c]fluorene is relatively high when compared to other DNA adducting hydrocarbons within coal tar. Benzo[c]fluorene may play a critical role in the potential of contaminated soil to induce a toxicological response in animals.

Administration, Oral↗
PubMed2001

Potentiation of nitric oxide-induced apoptosis of MDA-MB-468 cells by farnesyltransferase inhibitor: implications in breast cancer.

High amounts of nitric oxide (NO) produced by activated macrophages or NO donors are required to induce cytotoxicity and apoptosis in pathogens and tumor cells. High concentrations of NO may lead to nonspecific toxicity thereby limiting the use of NO donors in the treatment of cancer. In this study, we tested the possibility of potentiating the apoptotic action of NO in a human breast cancer cell line, MDA-MB-468, by combining it with a farnesyltransferase inhibitor (FTI), which has been shown to induce apoptosis in some other cancer cell lines with minimal toxicity to normal cells. DETA-NONOate, a long acting NO donor which has a half-life of 20 h at 37 degrees C, was used in this study. DETA-NONOate (1 mM), which releases NO in the range produced by activated macrophages, induced apoptosis after 36 h in MDA-MB-468 cells via cytochrome c release and caspase-9 and -3 activation. FTI (25 microM) potentiated the action of lower concentrations of DETA-NONOate (25-100 microM) by inducing apoptosis in these cells within 24 h by increasing cytochrome c release and caspase-9 and -3 activation. This effect was observed preferentially in the cancer cell lines studied with no apoptosis induction in normal breast epithelial cells. This novel combination of FTI and NO may emerge as a promising approach for the treatment of breast cancer.

Alkyl and Aryl Transferases↗
PubMed2001

Stabilization of active-site loops in NH3-dependent NAD+ synthetase from Bacillus subtilis.

The NH(3)-dependent NAD(+) synthetase (NADS) participates in the biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) by transforming nicotinic acid adenine dinucleotide (NaAD) to NAD(+). The structural behavior of the active site, including stabilization of flexible loops 82-87 and 204-225, has been studied by determination of the crystal structures of complexes of NADS with natural substrates and a substrate analog. Both loops are stabilized independently of NaAD and solely from the ATP-binding site. Analysis of the binding contacts suggests that the minor loop 82-87 is stabilized primarily by a hydrogen bond with the adenine base of ATP. Formation of a coordination complex with Mg(2+) in the ATP-binding site may contribute to the stabilization of the major loop 204-225. The major loop has a role in substrate recognition and stabilization, in addition to the protection of the reaction intermediate described previously. A second and novel Mg(2+) position has been observed closer to the NaAD-binding site in the structure crystallized at pH 7.5, where the enzyme is active. This could therefore be the catalytically active Mg(2+).

Amide Synthases↗
PubMed2001

Glycosaminoglycan binding properties of the myxoma virus CC-chemokine inhibitor, M-T1.

Poxviruses encode a number of secreted virulence factors that function to mitigate or modulate the host immune response. M-T1 is a secreted 43-kDa glycoprotein produced by the myxoma virus, a poxvirus pathogen of rabbits, that binds CC-chemokines with high affinity, blocks binding to their cognate G-protein coupled receptors, and thereby inhibits chemokine-induced leukocyte chemotaxis. The present study indicates that M-T1, but not the related vaccinia virus 35-kDa CC-chemokine-binding protein, can localize to cell surfaces through an interaction with glycosaminoglycan molecules. In addition to biochemically characterizing the nature of this interaction, we demonstrate that M-T1 can also simultaneously interact with CC-chemokines while bound to heparin, suggesting that the binding sites on M-T1 for chemokines and heparin are distinct. Furthermore, using recombinant baculovirus-expressed M-T1 truncation and internal deletion mutants, we localize the heparin-binding region of M-T1 to the C terminus of the protein, a region that contains a high abundance of basic residues and includes two clusters of basic amino acid residues that resemble Cardin and Weintraub heparin-binding consensus sequences. The ability of M-T1 to simultaneously interact with chemokines and glycosaminoglycans may enable M-T1 to tether to endothelial surfaces or extracellular matrix and capture host chemokines that are expressed close to sites of virus infection.

Amino Acid Sequence↗