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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

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

Retrospective controlled study of inpatient ECT: does it prevent suicide?

BACKGROUND: This study examined the use of ECT among inpatients who committed suicide at a provincial psychiatric hospital. METHODS: A total of 45 psychiatric in-patients who committed suicide at a provincial psychiatric hospital were compared with a gender, age and admission diagnosis matched group of 45 hospitalized patients to examine the use of electroconvulsive therapy during the last 3 months of hospitalization. RESULTS: No difference in the utilization of ECT was found in the two groups. LIMITATIONS: Retrospective design and small sample size. CONCLUSIONS: We failed to demonstrate that ECT had prevented suicide in hospitalized patients. Future prospective studies with large sample size are needed to further examine this question.

Adult↗
PubMed1999

Ultrasound-guided needle aspiration of lateral masticator space abscess.

Shortly after admission with facial space infection, ultrasound-guided needle aspiration of lateral masticator space abscess was carried out in 2 adult patients. One abscess was associated with pericoronitis and the other with post-extraction infection. Successful aspiration of pus was followed by an instantaneous improvement in the ability to open the mouth for a period of at least 24 hours. This obviated the need for conscious nasoendoscopic intubation and allowed orotracheal intubation for conventional drainage. We concluded that ultrasonography can be beneficial in the management of orofacial infections.

Adult↗
PubMed1999

Isolation of efficient antivirals: genetic suppressor elements against HIV-1.

The development of general approaches for the isolation of efficient antivirals and the identification and validation of targets for drug screening are becoming increasingly important, due to the emergence of previously unrecognized viral diseases. The genetic suppressor element (GSE) technology is an approach based on the functional expression selection of efficient genetic inhibitors from random fragment libraries derived from a gene or genome of interest. We have applied this technology to isolate potent genetic inhibitors against HIV-1. Two strategies were used to select for GSEs that interfere with latent virus induction and productive HIV-1 infection based on the expression of intracellular and surface antigens. The selected GSEs clustered in seven narrowly defined regions of the HIV-1 genome and were found to be functionally active. These elements are potential candidates for the gene therapy of AIDS. The developed approaches can be applied to other viral pathogens, as well as for the identification of cellular genes supporting the HIV-1 life cycle.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Thermal response to serotonergic challenge and aggression in attention deficit hyperactivity disorder children.

Body temperature change in response to the serotonergic (5-HT) enhancer, d,l-fenfluramine (FEN), was examined in 27 prepubescent boys diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) to determine (1) the utility of this measure as an index of central serotonergic function; and (2) if the magnitude of temperature change is associated with aggression. FEN, 1 mg/kg, produced a significant increase in body temperature, the magnitude of which was correlated with plasma levels of the FEN metabolite, norfenfluramine (NORFEN). Furthermore, a significant inverse relationship was found between temperature response to FEN and teacher ratings of aggression. Parent ratings of aggression were not significantly correlated with the hyperthermic response to FEN. Interestingly, the magnitude of the hyperthermic response was unrelated to changes in plasma levels of prolactin and cortisol, suggesting that thermal and neuroendocrine responses are mediated by distinct 5-HT mechanisms. The agreement of these finding with those of studies using other procedures to assess the relationship between 5-HT and aggression suggests that decreased central 5-HT is associated with increased aggression.

Aggression↗
PubMed1999

A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study.

The use of gonadotrophin-releasing hormone analogues (GnRHa) has resulted in improved pregnancy rates in in-vitro fertilization (IVF) treatment cycles. Traditionally, short-acting analogues have been employed because of concerns over long-acting depot preparations causing profound suppression and luteal phase defects adversely affecting pregnancy and miscarriage rates. We randomized 60 IVF patients to receive a short-acting GnRHa, nafarelin or buserelin, or to receive a depot formulation, leuprorelin, all commenced in the early follicular phase and compared their effects on hormonal suppression and clinical outcome. We found that on day 15 of administration there was a significant difference in the suppression of oestradiol from initial concentrations, when patients on buserelin were compared with patients on nafarelin or leuprorelin (54 versus 72 and 65%; P < 0.05) and also in the number of patients satisfactorily suppressed, (80 versus 90 and 90%; P < 0.05), though there were no differences between the analogues by day 21. Similarly there was no difference in hormonal suppression during the stimulation phase or in implantation, pregnancy or miscarriage rates in comparing the three agonists. We conclude that with nafarelin and leuprorelin, stimulation with gonadotrophins may begin after 2 weeks of suppression and that long-acting GnRHa are as effective as short-acting analogues with no detrimental effects on the luteal phase.

Administration, Inhalation↗
PubMed1999

The influence of donated gametes on the incidence of hypertensive disorders of pregnancy.

Pregnancies achieved from oocyte, sperm or embryo donation are unique, since they have resulted from donor gametes that are immunologically foreign to the mother. Thus, studying the obstetric outcome of such pregnancies may shed some light on the pathophysiology of preeclampsia, particularly in women conceiving with donated embryos, since the entire fetal genome is allogenic in these pregnancies. In this retrospective cohort study, a total of 144 women were studied. Of these, 72 were infertility patients who had conceived as a result of sperm, ovum or embryo donation and the other 72 women were age- and parity-matched control patients who became pregnant with their own gametes, either spontaneously, or following intrauterine insemination with their partner's spermatozoa. Study patients were divided into three groups depending on the origin of the donated gametes. Group 1 consisted of pregnancies achieved by intrauterine insemination with washed donor spermatozoa (n = 33). Group 2 included women who conceived using donated oocytes (n = 27) and group 3 consisted of women who conceived as a result of embryo donation (n = 12). The incidence of pregnancy-induced hypertension in the donated gametes study group was 12.5% (9/72) compared with 2.8% (2/72) in the control group. In addition, pre-eclampsia was diagnosed in 18.1% (13/72) of the donated gametes study group compared to 1.4% (1/72) in the age- and parity-matched controls. The increased incidence of gestational hypertension in pregnancies resulting from donated gametes gives evidence for a maternal genetic component, with an equally strong fetal influence, in the complicated aetiology of gestational hypertension, and pre-eclampsia in particular.

Cohort Studies↗
PubMed1999

TGF-beta1 DNA polymorphisms, protein levels, and blood pressure.

Transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine with fibrogenic properties, has been implicated in the pathogenesis of the vascular and target organ complications of hypertension. TGF-beta1 may also regulate blood pressure via stimulation of endothelin-1 and/or renin secretion. Herein we explored the hypothesis that circulating levels of TGF-beta1 protein (quantified using a TGF-beta1-specific sandwich ELISA) are correlates of blood pressure levels. This hypothesis was tested in 98 stable end-stage renal disease (ESRD) patients. (The use of ESRD patients as the study cohort eliminates renal function-dependent alterations in circulating levels of TGF-beta1 protein.) In addition, in view of the previously reported correlation among TGF-beta1 DNA polymorphisms and systolic blood pressure, TGF-beta1 codon 25 genotype and alleles were identified in 71 hypertensive subjects and 57 normotensives using amplification refractory mutation system polymerase chain reaction. Our studies demonstrate for the first time that TGF-beta1 levels (209+/-13 ng/mL, mean+/-SEM) are positive correlates (Pearson correlation analysis) of mean arterial pressure (P=0.008), systolic pressure (P=0.02), and diastolic pressure (P=0. 01). We also report that a higher percentage of hypertensives (92%) compared with normotensives (86%) are homozygous for the arginine allele at codon 25. Our observations support the idea that genetically determined TGF-beta1 protein concentrations may play a role in blood pressure regulation in humans.

Amino Acid Substitution↗
PubMed1999

Role of pin traction in wound closure.

This study examined the role of pin traction in wound closure. Forty patients comprised the study population. Wounds treated were on legs, thighs, and forearms. Kirschner wires were passed around margins of the wound and interconnected with stainless steel wires, which were gradually tightened to approximate the wound edges to healing. Final results were excellent in 18 (45%), good in 13 (32.%), fair in 5 (12.%), and poor in 4 (1%) patients. The main complication was cutting through the wires. The results were unsatisfactory in old, scarred, and large wounds.

Adolescent↗
PubMed1999

Familial gliomas : a case report.

Two non-twin brothers were found to have intracranial malignant neoplasms. The age of presentation was third and fourth decade but the onset was simultaneous, at the same time. Diagnosis in each of them was made by computed tomography and confirmed by histopathology. Elder among them had cellular ependymoma and the younger had oligodendroglioma. Both the brothers received radiotherapy post operatively and were surviving asymptomatically without any neurological deficit, leading active life as police constable, 12 months after surgical treatment.

Adult↗
PubMed1999

Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus.

Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.

Animals↗
PubMed1999

Electroencephalographic study of the effect of neurotoxin DSP-4 in iron model of chronic focal epilepsy.

The effect of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on electroencephalographic activity (EEG) was studied in the model of chronic focal epilepsy induced by intracortical injection of FeCl3 in the rat. EEG activity was recorded from the epileptogenic focus (ipsilateral and contralateral) in chronic experiments before and after DSP-4 treatment. In some experiments EEG activity was also simultaneously recorded from the cortical epileptogenic focus and locus coeruleus before and after DSP-4 treatment to study the effect of iron-induced seizure activity and of DSP-4 on the locus coeruleus electrical activity. The results showed that DSP-4 aggravated the iron-induced epileptiform activity as well as the locus-coeruleus electrical activity. The data also showed that, induction of epilepsy by FeCl3 is accompanied by enhancement of the locus coeruleus electrical activity. Our study demonstrates that DSP-4 intensifies and modifies the epileptic activity in the iron-induced chronic epilepsy model and that the effects of toxin persist for a longer duration.

Animals↗
PubMed1999

Treatment of bipolar mixed state with olanzapine.

OBJECTIVE: An open trial was conducted to determine the efficacy of olanzapine in the treatment of bipolar mixed state. PARTICIPANTS: Nine inpatients at a provincial psychiatric hospital who met the DSM-IV criteria for bipolar I disorder, most recent episode mixed. INTERVENTION: Olanzapine was added to the existing drug regime in patients who had failed to respond to adequate trials of mood stabilizers used alone or in combination with neuroleptics. OUTCOME MEASURES: Patients were administered the Clinical Global Impression (CGI) Scale, the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) Scale before the initiation of olanzapine. These scales were repeated and patients were rated on the improvement subscale of the CGI at the time of discharge. RESULTS: Pretreatment means (and standard deviations [SD]) for the CGI scale, BPRS and GAF were 5.7 (1.1), 60.7 (13.7) and 17.8 (7.5), respectively. Post-treatment means and SD for the scales were 1.9 (0.6), 6.3 (3.3) and 71.7 (5.6), respectively. Paired t-tests on all measures indicated significant improvement in symptoms with t = 9.43, p < 0.001 for CGI; t = -13.28, p < 0.001 for BPRS; t = -21.83, p < 0.001 for GAF. The mean improvement subscale score of the CGI was 1.3 (SD 0.5) at discharge. CONCLUSIONS: Olanzapine was well-tolerated and was effective in the acute treatment of bipolar mixed state.

Adult↗
PubMed1998

Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.

BACKGROUND: . Mycobacterium tuberculosis is the single most deadly human pathogen and is responsible for nearly three million deaths every year. Recent elucidation of the mode of action of isoniazid, a frontline antimycobacterial drug, suggests that NAD metabolism is extremely critical for this microorganism. M. tuberculosis depends solely on the de novo pathway to meet its NAD demand. Quinolinic acid phosphoribosyltransferase (QAPRTase), a key enzyme in the de novo biosynthesis of NAD, provides an attractive target for designing novel antitubercular drugs. RESULTS: . The X-ray crystal structure of the M. tuberculosis QAPRTase apoenzyme has been determined by multiple isomorphous replacement at 2.4 A resolution. Structures of the enzyme have also been solved in complex with the substrate quinolinic acid (QA), the inhibitory QA analog phthalic acid (PA), the product nicotinate mononucleotide (NAMN), and as a ternary complex with PA and a substrate analog, 5-phosphoribosyl-1-(beta-methylene)pyrophosphate (PRPCP). The structure of the nonproductive QAPRTase-PA-PRPCP Michaelis complex reveals a 5-phosphoribosyl-1-pyrophosphate-binding site that is different from the one observed in type I phosphoribosyltransferases (PRTases). The type II PRTase active site of QAPRTase undergoes conformational changes that appear to be important in determining substrate specificity and eliciting productive catalysis. CONCLUSIONS: . QAPRTase is the only known representative of the type II PRTase fold, an unusual alpha/beta barrel, and appears to represent convergent evolution for PRTase catalysis. The active site of type II PRTase bears little resemblance to the better known type I enzymes.

Amino Acid Sequence↗
PubMed1998

Biochemical characterization of MIP-1 alpha nuclear protein.

A family of hematopoietic specific transcription factors, MIP-1 alpha nuclear protein (MNP) family, has recently been identified. They are intimately involved in regulating the transcription of the huMIP-1 alpha gene in monocytes, T-cells, and transformed B-cells. One member of the family (MNP-1) is essential for promoter activity in monocytes and B-cells, while another (MNP-2) is required for full promotor activity in T-cells. A third member of the family (MNP-3) is expressed in PMA induced HL60 cells and probably has a role in monocyte differentiation. In this communication we demonstrate by two techniques that MNP-1 and MNP-2 are distinct but related factors, and we present further evidence to show that MNP-1 acts as a heterodimer.

Base Sequence↗
PubMed1998

Carbohydrate specificity and quaternary association in basic winged bean lectin: X-ray analysis of the lectin at 2.5 A resolution.

The structure of basic Winged Bean Agglutinin (WBAI) with two dimeric molecules complexed with methyl-alpha-D-galactopyranoside in the asymmetric unit, has been determined by the molecular replacement method and refined with 2.5 A X-ray intensity data. The polypeptide chain of each monomer has the characteristic legume lectin tertiary fold. The structure clearly defines the lectin-carbohydrate interactions. It reveals how the unusually long variable loop in the binding region endows the lectin with its characteristic sugar specificity. The lectin forms non-canonical dimers of the type found in Erythrina corallodendron lectin (EcorL) even though glycosylation, unlike in EcorL, does not prevent the formation of canonical dimers. The structure thus further demonstrates that the mode of dimerisation of legume lectins is not necessarily determined by the covalently bound carbohydrate but is governed by features intrinsic to the protein. The present analysis and our earlier work on peanut lectin (PNA), show that legume lectins are a family of proteins in which small alterations in essentially the same tertiary structure lead to wide variations in quaternary association. A relationship among the non-canonical modes of dimeric association in legume lectins is presented.

Amino Acid Sequence↗
PubMed1998

Studies on an affinity label for the sulfuryl acceptor binding site in an aryl sulfotransferase.

Active site-directed affinity labeling was utilized to elucidate peptide sequences at the binding site for sulfuryl acceptors in rat hepatic aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase, EC 2.8.2.9). The affinity labeling reagent, N-bromoacetyl-4-hydroxyphenylamine, was designed on the basis of substrate specificity studies with para-substituted phenols, utilization of a bromoacetamido group for reactivity with active site amino acid residues and its similarity to acetaminophen, a known substrate for aryl (phenol) sulfotransferases. AST IV utilized N-bromoacetyl-4-hydroxyphenylamine as a substrate with kinetic constants that compared favorably to those obtained with acetaminophen. Incubation of AST IV with N-bromoacetyl-4-hydroxyphenylamine at pH 7.0 in the absence of PAPS and other substrates resulted in an irreversible inactivation of the enzyme that was both time- and concentration-dependent. [14C]-N-bromoacetyl-4-hydroxyphenylamine was synthesized and used to analyze the regions of protein sequence that were involved in the binding of the affinity label. AST IV was incubated with [14C]-N-bromoacetyl-4-hydroxyphenylamine, hydrolyzed with endoproteinase Lys-C and the labeled peptides were purified by HPLC. Control incubations of AST IV with the affinity label in the presence of 4-propylphenol and PAP were utilized to ascertain the specificity of the interaction. Sequence analysis of the labeled peptides, carried out by automated Edman degradation, revealed labeling sites on cysteine (Cys-232, Cys-283 and Cys-289) and lysine (Lys-286) residues near the C-terminus of the protein. The locations of these labeling sites were further evaluated both by sequence-alignment with other sulfotransferases and by theoretical calculations on predicted secondary structure.

Affinity Labels↗