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Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 271 records · Page 15Linked to original sources
PubMed1996

Antibodies to a conserved-motif peptide sequence of the Plasmodium falciparum thrombospondin-related anonymous protein and circumsporozoite protein recognize a 78-kilodalton protein in the asexual blood stages of the parasite and inhibit merozoite invasion in vitro.

Athrombospondin-related anonymous protein (TRAP) of the human malaria parasite Plasmodium falciparum shares highly conserved amino acid sequence motifs with the circumsporozoite protein of all plasmodia sequenced so far, as well as with unrelated proteins like thrombospondin and properdin. Although it was first described as an asexual blood stages protein, there has been some controversy about its expression in these stages. Pursuant to our interest in the conserved sequences within the malaria antigens, we synthesized an 18-residue peptide (18-mer) representing a conserved motif of TRAP and raised polyclonal antibodies against it. In an immunoblot assay in which we probed proteins from the asexual blood stages of the parasite, we found that this antibody recognized predominantly a 78-kDa protein in the whole parasite lysate. Furthermore, in another immunoblot, the recombinant TRAP constructs containing the conserved-motif sequence were distinctly recognized by the antipeptide antibodies, whereas a construct lacking the motif sequence was not, suggesting that the antibodies specifically cross-reacted with a protein which might be a TRAP-like protein present in the asexual blood stages of the parasite. Also, in an immunofluorescence assay, this antibody brightly stained the acetone-fixed trophozoites of the parasite. Most significantly, anti-18-mer immunoglobulin G, as well as antipeptide antibody against a smaller (nonamer) construct representing the most conserved motif within the 18-mer, inhibited the merozoite invasion of erythrocytes in a dose-dependent manner. These results provide evidence of the expression of TRAP or a TRAP-like protein in the asexual blood stages of the parasite and of a possible role of the conserved motifs in the parasite-host cell interaction during the process of invasion.

Amino Acid Sequence↗
PubMed1996

Huntington's disease: a molecular genetic and CT comparison.

Huntington's disease is a progressive neurodegenerative disease in which the molecular abnormality has recently been described. Before the availability of this molecular marker diagnosis depended on clinical findings, supported in some instances by neuroimaging using CT or MRI. The imaging modalities may show atrophy of the heads of caudate nuclei in affected people. An attempt was made to validate these imaging findings using the molecular test as "gold standard." Retrospective analysis of cranial CT in 16 patients with Huntington's disease and 16 age and sex matched controls was performed. There was a highly significant difference in caudate head size (P < 0.00001) between patients with Huntington's disease and control subjects. However, the sensitivity of diagnosis based on radiological examination alone was only 87.5% in this study. Thus the sensitivity of CT is insufficient to justify its routine use in the investigation of suspected Huntington's disease, unless genetic tests are negative and other diagnoses need to be excluded.

Adult↗
PubMed1996

Morphine modulates migration of monocytes.

Macrophages seem to play an important role in the development of glomerulosclerosis. In the present study we evaluated the effect of morphine, an active metabolite of heroin, on the migration of monocytes across a filter in a modified Boyden chamber. Morphine-mesangial cell interaction enhanced (p < 0.004) the migration of monocytes across the filter (control 14.2 +/- 0.6 vs. morphine 22.1 +/- 1.7 monocytes/HPF). Dimethylthiourea (DMTU), a free radical scavenger, attenuated this effect of morphine. Morphine-monocyte secretory products (MMSP) did not modulate the migration of monocytes. However, the products of interaction between mesangial cells and MMSP enhanced (p < 0.001) the passage of monocytes across the filter. Mesangial cells treated with MMSP showed mRNA expression for monocyte chemoat-tractant peptide-1 (MCP-1). Superoxide also induced mRNA expression for MCP-1 on MC. DMTU attenuated this effect of superoxide. Since morphine activates MC to produce superoxide and DMTU attenuated the effect of superoxide on MC, the effect of morphine on the migration of macrophages may be mediated through superoxide-induced generation of MCP-1. We conclude that morphine enhances the migration of monocytes. This effect of morphine may be contributing to the development of glomerulosclerosis in patients with heroin addiction.

Animals↗
PubMed1996

Blood pressure and the M235T polymorphism of the angiotensinogen gene.

The angiotensinogen gene locus (1q42-43) has been linked to hypertension in affected relative-pair studies (including a previous UK study), but the role of the Met-->Thr polymorphism at position 235 remains controversial. Using this marker, we investigated the relationship between angiotensinogen genotype and blood pressure in two data sets from the East Anglia region of the United Kingdom. Two hundred twenty-three untreated hypertensive and 187 normotensive control subjects were recruited through local general practices. Blood pressure (including pretreatment measurements in the hypertensive group), age, sex, body mass index, alcohol consumption, cholesterol level, and angiotensinogen genotype were recorded for all subjects. The influence of angiotensinogen genotype on blood pressure was assessed with a general linear model ANOVA with adjustment for age, sex, body mass index, and alcohol consumption. There was no evidence for an association between angiotensinogen genotype and blood pressure level in either the hypertensive or normotensive data set. Angiotensinogen genotype did not influence blood pressure in subjects aged < 50 years, women, or those with a body mass index < 26 kg/m2. We conclude that the angiotensinogen Met-->Thr polymorphism is not a marker for blood pressure level in these East Anglian subjects. Further studies are required to confirm the involvement of the 1q locus in the development of hypertension in UK subjects and to delineate the functional variant(s) in this chromosomal region that influences blood pressure.

Angiotensinogen↗
PubMed1996

MR contrast material for vascular enhancement: value of superparamagnetic iron oxide.

OBJECTIVE: The purpose of this study were to quantify abdominal vascular enhancement and to prove the feasibility of iron oxide-enhanced MR angiography in humans using three doses of superparamagnetic iron oxide agent AMI 227. SUBJECTS AND METHODS: Sixteen patients randomly received either 0.8, 1.1, or 1.7 mg Fe/kg of ultrasmall superparamagnetic iron oxide agent AMI 227. T1-weighted breath-hold gradient-echo images were obtained before and 45 min after i.v. administration of AMI 227. Signal intensity was measured in the aorta, the inferior vena cava, the portal vein, and muscle on unenhanced and contrast-enhanced images. Signal-to-noise ratios and enhancement [(SNR after contrast-SNR before contrast) / SNR before contrast] were calculated. Vessels were visually graded before and after administration of AMI 227. RESULTS: All vessels showed statistically significant enhancement 45 min. after administration of AMI 227 by both qualitative and quantitative measures (p < .001). There was no significant increase in noise or signal intensity of muscle after contrast material was administered. The amount of enhancement was not statistically significantly different among the three doses. CONCLUSIONS: AMI 227, which is currently in phase III clinical trials, demonstrates significant vascular enhancement and may prove useful as an MR angiographic contrast agent.

Adult↗
PubMed1996

A comparative study of obstetric outcome of patients with pregnancy induced hypertension: economic considerations.

BACKGROUND: Hypertension in pregnancy is associated with increased maternal and fetal morbidity and mortality. The aim of this prospective study was to evaluate the obstetric outcome of patients with pregnancy induced hypertension (PIH) that delivered at the Maternity Hospital Kuwait within a period of six months and evaluate the economic implications of present management strategies. METHODS: This was a comparative study with age and parity, as matching variables, in 224 pregnant hypertensive women and 224 normotensive controls. RESULTS: During the study period, the incidence of PIH was 4.9 percent. They were more associated with diabetes mellitus and multiple pregnancy than controls (p < 0.02). About 43 percent of the hypertensive parturients used antihypertensive therapy. More of them had induction of labor (p < 0.001), preterm delivery (p < 0.0002) and cesarean section (p < 0.001), and babies with low birthweight (p < 0.01). In the linear regression analysis, hypertension in pregnancy gave rise to more hospitalisation, intrauterine growth retardation and operative deliveries than the normotensive controls. The perinatal mortality was higher (p < 0.001). CONCLUSION: Despite the economic expenditure of about five times more for hypertensive women in pregnancy than in controls, both obstetric and neonatal outcome, are still significantly worse in the former. This study therefore advocates more research into the prevention, prediction and management, including neonatal care, of hypertensive disorders of pregnancy.

Adult↗
PubMed1996

Clinical profile and risk factors for oral candidosis in sick newborns.

OBJECTIVES: To provide the clinical profile and assess the significance of various risk factors contributing to the occurrence of oral candidosis in newborns. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit (NICU). SUBJECTS: Twenty newborns with oral candidosis and an equal number of age and weight matched controls. INTERVENTIONS: All cases of oral candidosis were treated with local application of 1% Clotrimazole. RESULTS: Oral candidosis was documented in 3.2% (20/650) cases in the NICU. Acute pseudomembranous candidosis was the most common presentation. The mean age of onset was 10.5 days. Candida albicans was isolated in 50% cases in addition to C. tropicalis, C. paratropicalis, C. krusei, C. glabrata and C. parapsilosis. On univariate analysis, male sex, birth asphyxia and prolonged antibiotic therapy had a significant correlation with occurence of oral candidosis in neonates. Out of these, birth asphyxia was the only factor significantly associated with oral candidosis (OR 8.09, 95% CI 1.34-48.8, p = 0.0226) on multivariate analysis. CONCLUSIONS: C. albicans was the predominant isolate in this series of oral candidosis. Clinical manifestations were evident in the second week of life and birth asphyxia was the most important associated perinatal event.

Antifungal Agents↗
PubMed1996

Peak expiratory flow rate of carpet weaving children.

OBJECTIVE: To assess the adverse influence of carpet weaving on lung functions and the nurtritional status of children employed in such factories. DESIGN: Comparison of the peak expiratory flow rate (PEFR) of the study group with controls of similar socio-economic status and correlate it with anthropometric values. SETTING: Field study. SUBJECTS: One hundred and ten boys, 6-15 years of age engaged in 23 carpet weaving factories of Jaipur city. OUTCOME MEASURES: Linear regression analysis using age, height and weight as independent variables and PEFR as the dependent variable. RESULTS: PEFR of carpet weaving children were significantly lower (p < 0.05) than controls for all except 6-7 years group. The height, weight and chest circumference of these children were also lower (p < 0.05). PEFR did not show significant difference when children were grouped according to their height. CONCLUSIONS: Children working in carpet weaving factories are shorter and lighter compared to normal school going children. As a consequence of the growth retardation, their PEFR values were also lower as compared to normal children.

Adolescent↗
PubMed1996

[Laparoscopic cholecystectomy in acute cholecystitis].

Laparoscopic cholecystectomy was fulfilled in 108 patients admitted to the clinic with acute cholecystitis. Operations were made on 73% of them during the first four days from the beginning of the disease, 18.5% were operated upon within 5-7 days, 8.5% - 8 days later. Endoscopic papillotomy with removing the stones from the choledochus was performed in 10% of the patients before operation. Serious problems during taking the gallbladder from the inflammatory infiltration were observed in 29% of the patients. Technical problems took place more often if the patients were operated upon 5 days after the beginning of the disease. Change for open laparoscopy and standard cholecystectomy were necessary in 9 patients (8.3%). There were no lethal outcomes after laparoscopic cholecystectomy. Complications were observed in 12 patients (11.1%). The average period of staying at the hospital was (5.2 +/- 2.1) days. Laparoscopic cholecystectomy can be successfully performed in patients with acute cholecystitis by a sufficiently experienced surgeon.

Acute Disease↗
PubMed1995

Effect of growth environment on the stability of a recombinant shuttle plasmid, pCPPS-31, in Escherichia coli.

The effect of environmental growth conditions on the segregational stability of a recombinant Escherichia coli-Bacillus subtilis shuttle plasmid pCPPS-31 which expresses carboxymethyl cellulase (CMCase) and contains the neomycin resistance gene (Ner), was studied in E. coli DH5 alpha. The stability increased with the decrease in medium complexity. Lowering culture temperatures had a negative effect on stability. Stability was maximum at 100 rpm and a medium/flask volume ratio of 1:10. A pH range of 5-8 had no significant effect on stability. The recombination (rec) and gyrase (gyr) backgrounds of E. coli hosts had no apparent effect on plasmid stability. The plasmid was structurally stable under all circumstances.

Aerobiosis↗
PubMed1995

Fine specificity of immune responses to epitopic sequences in synthetic peptides containing B and T epitopes from the conserved Plasmodium falciparum blood-stage antigens.

Immunisation with two chemically synthesised, linear, multiple epitope peptides (MEP) containing B and T cell epitopes from two conserved blood-stage antigens of the human malaria parasite, Plasmodium falciparum, induced high levels of circulating antibodies without the use of a carrier protein. Immunisation of BALB/c mice with MEP constructs (P1 and P2) induced antibodies against the various epitope sequences included in their structures, although the immune response was focused more towards the N terminal and the middle portion of the peptides. In vitro T cell proliferation assays indicated that only one of the two Th epitopes included in P1 and P2 are functional. Both P1 and P2, based on P. falciparum sequences, cross-reacted with sera from P. yoelii-infected mice. Immunisation with P1 in CFA, but not with P2, provided partial protection to BALB/c mice against P. yoelii challenge infection. Peptide P1 was highly immunogenic in alum also, and a somewhat higher level of protection was observed as compared to CFA immunisation. We found that immunisation with P1 induced antibody responses in different strains of mice, although to different extents. These results suggest that linear, multiple epitope peptides may offer attractive alternatives as subunit vaccine candidate molecules, but at the same time highlight the fact that the design principles are far from being clear and have yet to be worked out.

Amino Acid Sequence↗
PubMed1995

Conversion disorder revisited.

Fifty four consecutive subjects diagnosed as Hysteria (300.1 according to ICD-9), were taken up for study, to examine the usefulness and validity of Lazare's criteria and explore its clinical utility in diagnosing conversion disorders. Lazare's validation score was computed for each subject, and the specificity, sensitivity, positive predictive validity and misclassification rates were computed for different cut off scores. A cut off score of 5 on Lazare's validation criteria gave good sensitivity (75%) but only modest specificity (41%). The individual criteria showed variation in presence between 18% and 68%, and some of these such as "disturbed sexuality" and "secondary gain" were felt to require redefining. The study of patterns of previous history of organic illness, physical findings on clinical examination, lateralization of symptoms, handedness and followup status indicated important association between hysteria and organicity.

Adolescent↗
PubMed1995

Platelet ultra-structure study in Budd-Chiari syndrome.

Morphologic characteristics of circulating platelets were studied in 20 patients with primary Budd-Chiari syndrome (BCS) without any known etiology, using transmission electron microscopy (TEM). Significant platelet ultrastructural changes were observed in all the patients (in 10-->90% platelets) as compared to 20 normal healthy controls (in up to 4% of their platelets). The prominent changes in the platelets were paucity or absence of alpha granules, hypertrophy of the open canalicular systems (OCS) and clumping and fusion of the granules and other organelles in the centre of platelets. Some other changes observed in platelets were dilated channels of OCS, pseudopodial protrusion of cytoplasm and presence of prominent masses of glycogen particles. Platelets from 20 normal controls processed along with the patients' platelets showed only a few such abnormalities. Most of these changes observed in patients' platelets were akin to the changes observed in platelets undergoing activation. Assay of plasma beta-thromboglobulin showed significantly higher levels in all the patients (p < 0.001) further confirming on-going in vivo platelet activation with morphologic changes most likely reflecting the thrombotic process present in BCS patients.

Adolescent↗