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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 505 records · Page 28Linked to original sources
PubMed1997

The possible role of adrenergic component in ischemic preconditioning.

The role of adrenergic mechanism in the cardioprotective effect of ischemic preconditioning against ischemia-reperfusion induced injury in in vivo dog heart and isolated rat heart was investigated. Anesthetized dogs were subjected to LAD coronary artery ligation for 60 min followed by reperfusion for 4 h. Preconditioning protocol was 5 min of ischemia followed by reperfusion for 10 min. Rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 30 min. Preconditioning protocol was 5 min global ischemia followed by reperfusion for 5 min repeated four times. Infarct size, electrocardiographic changes and release of LDH were estimated to assess the extent of cardiac injury. Preconditioning reduced the infarct size, ST segment elevation and prevented the loss of R wave. Prazosin attenuated the cardioprotective effect of preconditioning in dog. Preconditioning conferred protection against ischemia-reperfusion induced cardiac injury and reperfusion-induced arrhythmias in isolated rat heart. Reserpine pretreatment attenuated this protective effect of preconditioning on reperfusion-induced arrhythmias. These observations suggest the involvement of adrenergic mechanism in the cardioprotective and antiarrhythmic effect of ischemic preconditioning in dog and rat species respectively.

Adrenergic Uptake Inhibitors↗
PubMed1997

Conjunctival impression cytology in xerophthalmia among rural children.

The advent of Conjunctival Impression Cytology (CIC) has opened a new chapter in the detection of Vitamin A deficiency as it is a simplified field technique. The need for such a technique was of paramount importance in India where as estimated 5 to 7 percent children suffer from eye signs of Vitamin A deficiency. In the present study the results of clinical evaluation of apparently healthy children and those having clinical sings and symptoms of Vitamin A deficiency have been compared with CIC results. Serum Vitamin A levels have also been estimated wherever possible. The findings indicate that CIC results are superior to the clinical assessment and it is suggested that CIC can be used as screening tool for children of school going age (and earlier) for early detection and correction of Vitamin A deficiency.

Child↗
PubMed1997

The state of India's neonatal units in the mid-nineties.

BACKGROUND: A previous study in 1987 showed that neonatal care facilities in major hospitals in the country were of a very poor standard. The present study was done to reassess their status. DESIGN: A survey. METHODS: A pretested structured questionnaire was sent to 48 centers in 1994-95. The responses were analyzed. RESULTS: A total of 37 centers returned the questionnaire duly filled. Of them, 22 belonged to the government sector, the rest 15 to the private sector. A nursery bed: nurse ratio of less than 1.0 was reported by only 4 centers. Majority of the centers cited inadequate nursing strength and frequent transferring out of nurses as a major problem. Twenty nine (78%) centers had ventilation facilities. Most of them had 1 or 2 ventilators. Blood gas facility was available with 29 centers and parenteral nutrition was undertaken at 20 (54%) centers. Resuscitation bag(s) were available at all the centers and incubators at all except one. In quantitative terms, the following equipment was available in satisfactory numbers: resuscitation bags, resuscitation bassinet, incubators/open care systems, vital sign monitors, infusion pumps and pulse oximeters in 78.3%, 43.2%, 72.9%, 56.7%, 64.8% and 43.5% centers, respectively. Indigenous products of the following categories were reasonably well accepted: resuscitation bags, resuscitation bassinets, incubators, open care systems and dextrometers. CONCLUSION: The newborn care facilities, particularly the ventilation facilities, have improved in recent years. Almost 10 units were operating at or near level III standard of newborn care. Indigenous equipment of selected categories is replacing the imported equipment. However, most units continue to face problems of shortage of nursing personnel.

Equipment and Supplies, Hospital↗
PubMed1997

A case report of visceral leishmaniasis in Singapore.

Visceral leishmaniasis (Indian kala-azar) caused by infection due to the protozoan Leishmania donovani is endemic in the Indian subcontinent and adjoining regions. Prolonged fever, hepatosplenomegaly, anaemia and pancytopenia, in the appropriate setting, are important clinical markers towards the diagnosis. Diagnosis is established by blood film or bone marrow examination for Leishman Donovan (LD) bodies and/or culture. Treatment with sodium stibogluconate, pentamidine isethionate or even amphotericin B is usually successful. We report the first case of culture-proven visceral leishmaniasis in Singapore, in a 30-year-old Bangladeshi worker who presented with pyrexia of unknown origin (PUO). He had the classical constellation of symptoms and signs as mentioned above. Diagnosis was confirmed by culture on the Novy, NcNeal and Nicolle (NNN) medium. He was successfully treated with 20 days of pentamidine isethionate daily infusions at a dose of 2 mg/kg/day.

Adult↗
PubMed1997

Effects of BN-50730 (PAF receptor antagonist) and physostigmine (AChE inhibitor) on learning and memory in mice.

The present study was designed to investigate the effect of BN-50730, a PAF receptor antagonist, on learning and memory in mice using elevated plus-maze and to delineate the role of acetylcholine in modulating the effect of PAF receptor antagonist on learning and memory. BN-50730 administered immediately after plus-maze training on day 1 induced retrograde amnesia as indicated by a dose-dependent increase in transfer latency (TL) measured on day 2 whereas no such increase in TL was noted when BN-50730 (2.5 mg/kg, i.p.) was administered prior to plus-maze training. Physostigmine (0.5 mg/kg; 1.0 mg/kg, i.p.) administered 30 min prior to plus-maze training attenuated BN-50730-induced increase in TL measured on day 2. These results suggest that BN-50730, a PAF receptor antagonist, produced retrograde amnesia and physostigmine attenuated BN-50730-induced amnesia possibly through increased concentration of cerebral acetylcholine and a consequent increase in PAF release.

Acetylcholine↗
PubMed1997

Pharmacological basis of drug therapy of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disorder primarily manifesting as a loss of memory. Senile plaques and neurofibrillary tangles are the major histopathological alteration in the brain of Alzheimer's disease patients. A considerable deficiency of cholinergic neurons is a consistent finding in Alzheimer's disease. Therefore, many therapeutic strategies to augment cerebral concentration of acetylcholine such as cholinergic precursors, cholinergic receptor agonists, cholinesterase inhibitors and acetylcholine release modulators have been evaluated in Alzheimer's disease. Although cholinesterase inhibitors such as tacrine and galanthamine offer modest clinical benefits, other cholinergic agents have proved to be of limited therapeutic value. Efforts to enhance monoaminergic neurotransmission have also been largely disappointing. Therefore, emphasis is not being put on the use of combination of two class of drugs. Moreover, use of therapeutic agents based on the putative pathogenic etiology of the disease such as excitotoxicity, amyloidosis, aluminium accumulation, inflammatory mechanisms and free radical production is being evaluated. Desferrioxamine, non-steroidal anti-inflammatory drugs, prednisone, dapsone, vitamin E and idebenone are some such agents that are currently under investigation for the preventive or palliative effect in Alzheimer's disease. Neurotrophic factors such as nerve growth factor, brain derived neurotrophic factor and epidermal growth factor have shown promising results in animal studies. However, novel methods for delivering these molecules into the brain required to be developed before launching their clinical trials in man.

Alzheimer Disease↗
PubMed1997

Effect of prenatal haloperidol administration on anxiety patterns in rats.

Haloperidol (0.1 mg/kg, i.p.) treatment was given from day 12 to 20 of gestation to pregnant rats, this being the critical period for neural development in this species. The pups born were subjected to open-field exploratory behaviour, tunnel-board exploratory behaviour, elevated zero-maze and elevated plus maze behaviour tests at 7-8 weeks of age. The results indicate that prenatal haloperidol treatment induces a significant increase in open-field ambulations and rearings, decrease in scratching and licking/washing behaviours whereas grooming and faecal droppings remain unchanged. Significantly reduced activity in the centre and increased activity in the periphery of the tunnel board was noted. These suggest presence of anxiety in these animals. Significant anxiogenic behavioural patterns were also observed on elevated zero-maze and plus-maze in the prenatally haloperidol treated offsprings. The results suggest that prenatal exposure of haloperidol leaves a lasting effect on offsprings resulting in hyper-emotional responsiveness and anxiety state.

Animals↗
PubMed1996

Structure of a Kunitz-type chymotrypsin from winged bean seeds at 2.95 A resolution.

Thc crystal structure of an alpha-chymotrypsin inhibitor (P6(1)22; a = 61.4, c = 210.9 A) isolated from winged bean (Psophocarpus. tetragonolobus) seeds has been determined at 2.95 A resolution by the molecular-replacement method using the 2.6 A coordinates of Erythrina trypsin inhibitor (ETI) as the starting model (57% sequence homology). This protease inhibitor, WCI, belongs to the Kunitz (STI) family and is a single polypeptide chain with 183 amino-acid residues having a molecular weight of 20 244 Da. Structure refinement with RESTRAIN and X-PLOR has led to a crystallographic R factor of 19.1% for 3469 observed reflections (I > 2sigma) in the resolution range 8-2.95 A. A total of 56 water molecules have been incorporated in the refined model containing 181 amino-acid residues. In the refined structure the deviations of bond lengths and bond angles from ideal values are 0.015 A and 2.2 degrees, respectively. The inhibitor molecule is spherical and consists of 12 antiparallel beta-strands with connecting loops arranged in a characteristic folding (a six-stranded beta-barrel and a six-stranded lid on one hollow end of the barrel) common to other homologous serine protease inhibitors in the Kunitz (STI) family as well as to some non-homologous proteins like interleukin-lalpha and interleukin-lbeta. In the structure the conformation of the protruding reactive-site loop is stabilized through hydrogen bonds mainly formed by the side chain of Asnl4, which intrudes inside the cavity of the reactive-site loop, with the side-chain and main-chain atoms of some residues in the loop region. A pseudo threefold axis exists parallel to the barrel axis of the structure. Each of the three subdomains comprises of four beta-strands with connecting loops.

Journal Article↗
PubMed1996

Concerted repression of an immunoglobulin heavy-chain enhancer, 3' alpha E(hs1,2).

The transcription factor, B-cell-specific activator protein (BSAP), represses the murine immunoglobulin heavy-chain 3' enhancer 3' alpha E(hs1,2) in B cells. Analysis of various 3'alpha E deletional constructs indicates that sequences flanking a and b BSAP-binding sites are essential for appropriate regulation of the enhancer. An octamer motif 5' of the a site and a specific G-rich motif 3' of the b site were identified by competition in electrophoretic mobility-shift assays and methylation-interference foot-printing analysis. Site-directed mutagenesis of either the octamer or G-rich sites resulted in the complete release of repression of 3' alpha E(hs1,2), implicating these two motifs in the repression of this enhancer in B cells. However, when both BSAP-binding sites were mutated, the octamer and G-rich motifs functioned as activators. Moreover, in plasma cells, when BSAP is not expressed, 3' alpha E(hs1,2) is active, and its activity depends on the presence of the other two factors. These results suggest that in B cells, 3' alpha E (hs1,2) is down-regulated by the concerted actions of BSAP, octamer, and G-rich DNA-binding proteins. Supporting this notion of concerted repression, a physical interaction between BSAP and octamer-binding proteins was demonstrated using glutathione S-transferase fusion proteins. Thus, concerted repression of 3' alpha E (hs1,2) in B cells provides a sensitive mechanism by which this enhancer, either individually or as part of a locus-controlling region, is highly responsive to any of several participating factors.

Animals↗
PubMed1996

Regulation of 3' IgH enhancers by a common set of factors, including kappa B-binding proteins.

Targeted disruption of the p50 subunit of NF-kappa B resulted in isotype class switch defects resembling those observed in mice in which the downstream IgH enhancer 3'alpha E(hs1,2) was deleted. We postulated that kappa B binding proteins may regulate class switching by interacting with 3'alpha E(hs1,2) or with other IgH 3' enhancers with which 3'alpha E(hs1,2) synergizes. kappa B binding sites were identified in 3'alpha E(hs1,2) and 3' alpha-hs4, the distal 3' IgH enhancer. A kappa B binding site within 3'alpha E(hs1,2) contributes to at least half the activity of the enhancer in plasma cells, while the same kappa B binding site participates in the complex repression of the enhancer in B cells. In the case of 3'alpha-hs4, a kappa B binding complex activates the enhancer in pre-B, B cells and plasma cells. Additional binding sites within 3'alpha-hs4 for factors known to regulate 3'alpha E(hs1,2), including Oct-1 and BSAP, were identified, and their contribution to 3'alpha-hs4 regulation during B cell development was assessed. Oct-1 positively regulates the enhancer in pre-B and B cells, while BSAP is a repressor in pre-B cells and an activator at the B cell stage. These studies identify kappa B binding proteins as key modulators of 3'alpha E(hs1,2) and 3'alpha-hs4, and suggest coregulation of the two enhancers by a common set of factors.

Animals↗
PubMed1996

B cell lineage-specific activator protein (BSAP). A player at multiple stages of B cell development.

B cell lineage-specific activator protein (BSAP), encoded by the Pax 5 gene, is a critical modulator of early B cell differentiation. Binding sites for BSAP have been identified in the promoters of multiple genes as well as at multiple sites within the IgH locus. While in vivo target sites critical for early B cell differentiation have not yet been identified, candidate sites include a 3 IgH enhancer that is active early in B cell development. BSAP may play an additional role later in development, such as in the regulation of isotype class switching.

Animals↗
PubMed1996

The PRP31 gene encodes a novel protein required for pre-mRNA splicing in Saccharomyces cerevisiae.

The pre-mRNA splicing factor Prp31p was identified in a screen of temperature-sensitive yeast strains for those exhibiting a splicing defect upon shift to the non- permissive temperature. The wild-type PRP31 gene was cloned and shown to be essential for cell viability. The PRP31 gene is predicted to encode a 60 kDa polypeptide. No similarities with other known splicing factors or motifs indicative of protein-protein or RNA-protein interaction domains are discernible in the predicted amino acid sequence. A PRP31 allele bearing a triple repeat of the hemagglutinin epitope has been generated. The tagged protein is functional in vivo and a single polypeptide species of the predicted size was detected by Western analysis with proteins from yeast cell extracts. Functional Prp31p is required for the processing of pre-mRNA species both in vivo and in vitro, indicating that the protein is directly involved in the splicing pathway.

Cloning, Molecular↗