Search PubMed⌕ Search

Biomedical subjects

P Das

Publications and source records attributed to P Das.

At least 91 records · Page 5Linked to original sources
PubMed1999

Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-.

Recent evidence indicates that the NO-related species, nitroxyl anion (NO), is produced in physiological systems by several redox metal-containing proteins, including hemoglobin, nitric oxide synthase (NOS), superoxide dismutase, and S-nitrosothiols (SNOs), which have recently been identified in brain. However, the chemical biology of NO- remains largely unknown. Here, we show that NO- -unlike NO*, but reminiscent of NO+ transfer (or S-nitrosylation)- -reacts mainly with Cys-399 in the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor to curtail excessive Ca2+ influx and thus provide neuroprotection from excitotoxic insults. This effect of NO- closely resembles that of NOS, which also downregulates NMDA receptor activity under similar conditions in culture.

Animals↗
PubMed1999

Vitamin E-deficiency induced changes in ovary and uterus.

Female rats at weaning (30 days age) were maintained on vitamin E-deficient diet for 70 days. The vitamin E-deficient and control animals were sacrificed on 100 days of age. To study recovery a group of animals were supplemented with normal diet for last 25 days after initial 45 days of deficient diet or vice versa. The most striking data found were (i) significant drop in uterine weight in deficient group (ii) significant decrease in estrogen, LH and estrogen-induced uterine enzymes alkaline phosphatase and peroxidase and (iii) ovarian dysfunction as noted by degenerating graffian follicles. The significance of these findings is discussed in this report.

Alkaline Phosphatase↗
PubMed1999

Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals.

BACKGROUND: Much is known about the three subfamilies of the TGFbeta superfamily in vertebrates-the TGFbetas, dpp/BMPs, and activins. Signalling in each subfamily is dependent on both shared and unique cell surface receptors and Smads. In invertebrates, mutants for BMP pathway components have been extensively characterized, but thus far, evidence for an activin- or TGFbeta-like pathway has been lacking, preventing the use of the extensive genetic tools available for studying several key issues of TGFbeta signalling. RESULTS: Here we report the identification of dSmad2, a new Drosophila Smad which is most related to the activin/TGFbeta-pathway Smads, Smad2 and Smad3. We show that dSmad2 induces activin responsive genes in Xenopus animal cap assays. dSMAD2 is phosphorylated by ATR-I and PUNT, but not by activated THICK VEINS, and translocates to the nucleus upon activation. Furthermore, we show that dSMAD2 complexes with MEDEA only in the presence of ATR-I and PUNT. dSmad2 is expressed in the imaginal disks and in the outer proliferation centre of the larval brain, suggesting that it may have important proliferative and patterning roles during Drosophila development. CONCLUSION: Our data provide evidence for the existence of an activin/TGFbeta pathway in Drosophila. We show that dSmad2 participates in this pathway, and that it functions with Atr-I and punt. We show that Medea also participates in this pathway, indicating the conservation of roles for Co-Smads in diverse phyla. Expression patterns of dSmad2 suggest that it functions in imaginal disks and in the brain, in tissues that undergo extensive patterning and proliferation.

Activin Receptors↗
PubMed1999

Histological effects of vitamin A on the tail-amputated tadpoles of Polypedates maculatus with special reference to homeotic transformation.

Vitamin A is a very common teratogen causing severe embryonic malformations and changes in pattern formation in amphibians. The effects of vitamin A include the induction of duplication of skeletal structures in the anteroposterior, proximodistal and dorsoventral axes. The purpose of this investigation was to study the histological changes in the regenerating tail of the tadpoles of Polypedates maculatus by treatment with vitamin A. The histological changes brought about by vitamin A included the development of multilayered epidermis and thickened basement membrane, enlargement of the notochord and the nerve cord and the clumping of muscles. In addition, single, paired and supernumerary homeotic limbs were visible from day 20 onwards at ectopic sites. Initially, the limb consisted of only procartilage cells. Muscles and digits appeared from day 48 onwards. In contrast, such observations were not found in the control tails. The significance of such changes is discussed.

Animals↗
PubMed1999

Molecular cloning and sequence analysis of bubaline lactoferrin promoter.

The proximal promoter for bubaline lactoferin-encoding gene has been isolated, cloned and sequenced. A 468 bp fragment of the 5' flanking region of the lactoferrin gene was PCR amplified and cloned into pUC18 vector. Sequence analysis of the amplified fragment revealed the presence of one TATA box, one TATA like element, two GC boxes and one motif resembling cAMP response element (CRE) in this region. Bubaline lactoferrin promoter shares 93%, 53%, 52% and 48% homology with cattle, pig, mouse and human lactoferrin 5' flanking region, respectively.

Animals↗
PubMed1999

cDNA cloning and sequence analysis of bubaline growth hormone.

The cDNA for Bubalus bubalis growth hormone (GH) has been cloned and sequence determined through RT-PCR approach. The nucleotide sequence of bubaline GH cDNA was in a single reading frame coding for a protein of 191 residues comprising a putative signal sequence of 27 amino acids. Homology comparison of the sequence with other mammalian GH cDNAs showed a very high degree of evolutionary conservation. Bubaline GH sequence shared a homology of 99.5%, 99.5%, 98.6%, 87.6% and 61.9% with that of ovine, caprine, bovine, porcine and human, respectively at amino acid level.

Amino Acid Sequence↗
PubMed1999

Molecular cloning and sequence analysis of the cDNA encoding beta-lactoglobulin in Bubalus bubalis.

The cDNA for bubaline beta-lactoglobulin (beta lg) has been cloned through RT-PCR approach and sequenced. Sequence data showed a single open reading frame coding for a protein of 180 amino acids with a signal sequence of 18 amino acid residues. Comparison with other ruminant beta lg sequences revealed a high homology indicating the protein to be conserved through evolution. The degree of homology, at amino acid level, is 96.1%, 95.6%, 93.9% and 63.7% with goat, sheep, cow and pig, respectively.

Amino Acid Sequence↗
PubMed1999

Hypertension in elderly--an overview.

Hypertension (HT) is a common disease in elderly. It has different pathophysiologic, clinical and therapeutic implications in this age group. Due to loss of arterial wall elasticity with age, major vessels including aorta become stiff and less distensible. As age advances, these stiff vessels also lose beta adrenergic responsiveness with unchanged alpha adrenergic responsiveness. These together raise peripheral vascular resistance and aortic impedance which needs a powerful systolic ejection of left ventricle to maintain cardiac output. Result is rise in systolic blood pressure (SBP) and increase in left ventricular (LV) mass with compromised cardiac output and renal blood flow. Participation of renin-angiotensin system and kidney in HT pathogenesis in elderly are minimum. Diagnosis of HT in elderly is made if SBP > 140 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg or is taking antihypertensive medications. Isolated systolic hypertension (ISH) means SBP > 140 mm Hg with DBP < 90 mm Hg. Measurement of blood pressure (BP) is problematic, mainly due to pseudo HT, postural hypotension and white-coat HT. HT in absence of end organ changes suggest pseudo HT. Postural hypotension must be detected and treated. Systolodiastolic HT, carried over from middle age is the commonest type of HT in elderly. ISH is also common (10%). Atherosclerotic renovascular disease can cause secondary HT. Therapy is always needed in HT in elderly. Chance of coronary artery disease (CAD) and cerebrovascular accident (CVA) are quite high amongst elderly hypertensives. SBP is more dangerous than DBP. Benefits of therapy are more when compared to young. HT should be treated if SBP > 160 mm Hg and/or DBP > 90 mm Hg. ISH needs therapy if SBP > 160 mm Hg. The benefits of therapy becomes less after 80 years. Treatment goal should be to keep BP below 140/90 mm Hg. Therapy should be gradual and stepwise. Na-restriction should be modest. Diuretics (e.g., thiazide 25 mg/day) are the drug of choice unless contra-indicated. Beta blockers are inferior agents compared to diuretics unless angina or acute myocardial infarction (AMI) is present. Angiotensin converting enzyme (ACE) inhibitors are drug of choice only if congestive cardiac failure (CCF) and/or diabetes is present or other drugs are contra-indicated. Calcium entry blockers (CEB) are new but very good alternative to diuretics in elderly. Due to abnormal physiology, pharmacokinetics and drug interactions, side-effects are very common in elderly. They should be detected early and treated.

Adrenergic beta-Antagonists↗
PubMed1998

Putative dengue virus receptors from mosquito cells.

Dengue viruses are arthropod-borne, single-stranded RNA viruses. Aëdes aegypti and Aëdes albopictus are the principal vectors. In order to understand the molecular basis of dengue virus infections we explored the biochemical identity of dengue-2 (DEN-2) virus receptors in the Aëdes albopictus-derived cell line C6/36. We show here that DEN-2 interacts with two major polypeptides of 80 and 67 kDa. Polyclonal anti-C6/36 membrane antibodies block DEN-2 binding to intact C6/36 monolayers as well as to membrane extracts. Our results strongly suggest that the identified polypeptides are part of the DEN-2 receptors.

Aedes↗
PubMed1998

HLA-DQ6/8 double transgenic mice develop auricular chondritis following type II collagen immunization: a model for human relapsing polychondritis.

We have generated transgenic (tg) mice expressing HLA-DQ8alphabeta (DQA1*0301/DQB*0302) or HLA-DQ6alphabeta (DQA1*0103/DQB1*0601) molecules lacking endogenous murine class II expression (A beta0) to investigate the ability of these HLA class II to present type II collagen (CII) and induce collagen-induced arthritis. The DQ8alphabeta tg mice responded strongly to CII, developing severe arthritis, while DQ6alphabeta tg mice were nonresponsive to CII. The addition of the mixed haplotype DQ8alpha6beta molecule did not significantly influence CII reactivity. To examine the interaction of DQ6alphabeta and DQ8alphabeta molecules in vivo, we generated double tg DQ6alphabeta/8alphabeta (A beta0) mice expressing both the alpha- and beta-chains of DQ6 and DQ8 molecules by mating DQ6alphabeta (A beta0) and DQ8alphabeta (A beta0) tg mice. CII-immunized DQ6alphabeta/8alphabeta tg mice developed severe experimental polychondritis, exhibiting both polyarthritis and auricular chondritis. The clinical, serologic, and histologic manifestations of experimental polychondritis are similar to those symptoms in human relapsing polychondritis. The susceptibility of DQ6alphabeta/8alphabeta tg mice compared with resistance in the parental strains suggests that expression of both the DQ6alphabeta and DQ8alphabeta tgs, unique to the DQ6alphabeta8alphabeta tg strain, is important in susceptibility to experimental polychondritis. The DQ6alphabeta/8alphabeta tg mice provide a model to investigate putative autoantigens and the mechanisms of pathogenesis involved in relapsing polychondritis as well as the influence of the expression of multiple HLA class II molecules on the disease process.

Animals↗
PubMed1998

Deletion of transmembrane domain 12 of CDR1, a multidrug transporter from Candida albicans, leads to altered drug specificity: expression of a yeast multidrug transporter in baculovirus expression system.

Cdr1p, an ATP-binding cassette transporter from the pathogenic yeast Candida albicans, confers resistance to several unrelated drugs including anti-Candida drugs (Prasad et al., 1995b). We demonstrate that the deletion of 237 bp (79 aa) from the 3' end of CDR1 (which encompasses the transmembrane domain (TM) 12 of the putative transporter) did not result in the total loss of its ability to efflux cytotoxic agents. While the expression of deltaCDR1 in yeast resulted in impaired sensitivity to drugs like cycloheximide, anisomycin, sulfomethuron methyl and antifungal nystatin, its ability to confer resistance remained unaltered to drugs such as o-phenanthroline, 4-nitroquinoline-N-oxide, cerulenin, azoles, oligomycin, erythromycin, and benomyl. Similar to human MDR1p. Cdr1p might also have localized drug binding sites in TM 12, but that might not be the case for all the drugs. The TM 12 deletion also did not lead to any significant impairment in NTPase activities. Both ATPase and UTPase activities of complete Cdr1p and deltaCdr1p were not significantly altered, as was the case with respect to their ability to efflux Rh123 and steroid hormone like [3H]-beta-estradiol. To further dissect the functionality of Cdr1p, its truncated version was overexpressed in a baculovirus-insect cell expression system. The synthesis of deltaCdr1p in Sf9 cells was temporally regulated as a function of the baculovirus polyhedrin gene promoter. The Sf9 derived deltaCdr1p was approximately 130 kDa, which was lower than the expected size, probably due to the differences in glycosylation. This, however, did not affect the functionality of deltaCdr1p. The deletion of TM 12 did not affect the targeting of the protein and deltaCdr1p was exclusively localized in plasma membrane of Sf9 cells as detected by immunofluorescence. The expression of deltaCdr1p in the baculovirus-insect expression system generated a high drug-stimulated plasma membrane-bound ATPase activity which was not demonstrable when deltaCdr1p was expressed in yeast.

ATP-Binding Cassette Transporters↗
PubMed1998

TGF-beta signaling, Smads, and tumor suppressors.

The transforming growth factor-beta (TGF-beta) superfamily is used throughout animal development for regulating the growth and patterning of many tissue types. During the past few years, rapid progress has been made in deciphering how TGF-beta signals are transduced from outside the cell to the nucleus. This progress is based on biochemical studies in vertebrate systems and a combination of genetic studies in Drosophila and Caenorhabditis elegans. These studies have identified a novel family of signaling proteins, the Smad family. Smads can act positively and be phosphorylated by TGF-beta-like receptors or can act negatively and prevent activation of the positively acting group. The positively acting Smads translocate to the nucleus, bind DNA, and act as transcriptional activators. Thus, genetic and biochemical studies suggest a very simple signaling pathway, in which Smads are the primary downstream participant.

Animals↗
PubMed1998

Dermatophytes isolated from selected ruminants in India.

A survey was carried out in different areas of Uttar Pradesh for isolating and identifying dermatophytes from ruminants. Out of 102 skin scrapings, collected from various animals, 4/22 cattle, 1/9 buffalo, 14/44 sheep and 2/28 goats were KOH positive. In respect of the cattle, the culture positive samples yielded one strain each of Trichophyton mentagrophytes, T. rubrum, T. simii and two strains of Microsporum gypseum. From the buffaloes examined, only one case yielded a dermatophyte and it was identified as T. mentagrophytes. In respect of the sheep, two samples were culture positive and the dermatophyte was T. mentagraphytes (2). Of the 28 goat scrapings, only two harboured dermatophytes viz., M. gypseum and T. mentagrophytes. Fungi other than dermatophytes isolated from the ruminants were Alternaria species, Aspergillus species, Beauveria bassiana, Chrysosporium keratinophilum, Curvularia species, Penicillium species, Pseudoarachniotus roseus and T. terrestre. Isolation of T. rubrum from the skin lesion of one of the cattle is noteworthy, since this dermatophyte is better known as an anthrophilic species.

Animals↗
PubMed1998

The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling.

Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.

Amino Acid Sequence↗
PubMed1997

Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras.

The pathways by which mammalian Ras proteins induce cortical actin rearrangement and cause cellular transformation are investigated using partial loss of function mutants of Ras and activated and inhibitory forms of various postulated target enzymes for Ras. Efficient transformation by Ras requires activation of other direct effectors in addition to the MAP kinase kinase kinase Raf and is inhibited by inactivation of the PI 3-kinase pathway. Actin rearrangement correlates with the ability of Ras mutants to activate PI 3-kinase. Inhibition of PI 3-kinase activity blocks Ras induction of membrane ruffling, while activated PI 3-kinase is sufficient to induce membrane ruffling, acting through Rac. The ability of activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important in Ras transformation of mammalian cells and essential in Ras-induced cytoskeletal reorganization.

3T3 Cells↗
PubMed1997

Involvement of host factors in transcription from baculovirus very late promoters -- a review.

The baculovirus expression vector system has emerged as the system of choice for the expression of a number of heterologous genes of both prokaryotic and eukaryotic origin. This system utilizes the baculovirus very late, hyperactive polyhedrin and p10 promoters to drive the transcription of foreign genes. Regulation of transcription from these promoters is presently not well understood even though a number of viral gene products that may be important for transcription have been identified. Fresh insight into host-virus interactions during baculovirus pathogenesis is now offered by the identification of insect host factors that interact with transcriptionally essential motifs of these promoters as well as cis-acting enhancer-like elements upstream from the promoter.

Base Sequence↗