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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 217 records · Page 12Linked to original sources
PubMed1995

Effect of a 5-HT1 receptor agonist, CP-122,288, on oedema formation induced by stimulation of the rat saphenous nerve.

Neurogenic oedema formation in the rat hind paw skin induced by electrical stimulation of the saphenous nerve and measured by extravasation of [125I]-albumin, was inhibited by the 5-HT1B receptor agonist, CP-93,129, and the novel tryptamine analogue, CP-122,288. Significant inhibition of up to 66% of control was observed with CP-122,288 (2 x 10(-14) - 2 x 10(-7) mol kg-1) and CP-93,129 (5 x 10(-7) - 5 x 10(-6) mol kg-1), with the minimum effective dose for CP-122,288 being about 10(7) fold less than that for CP-93,129. Oedema formation induced by the intradermal administration of exogenous mediators (substance P and histamine) in rat dorsal skin was not inhibited by CP-122,288 (2 x 10(-10) mol kg-1). These results suggest that CP-122,288 is a potent inhibitor of neurogenic inflammation in rat skin and that the effect may be due to a prejunctional inhibition of neuropeptide release.

Analysis of Variance↗
PubMed1995

Quantitation of human immunodeficiency virus type 1 DNA and RNA by a novel internally controlled PCR assay.

A novel internally controlled PCR (ICPCR) assay was developed to accurately quantitate human immunodeficiency virus type 1 (HIV-1) DNA and RNA in peripheral blood mononuclear cells and plasma. The ICPCR assay was sensitive and reproducible within a linear range of amplification of 10(0) to 10(3) copies for HIV-1 DNA and 10(1) to 10(4) copies for HIV-1 RNA. The assay detected HIV-1 RNA in plasma and peripheral blood mononuclear cells from all HIV-1 subjects regardless of disease stage. ICPCR was compared with a branched-DNA signal amplification assay for subjects beginning antiretroviral therapy. The reductions in plasma HIV-1 RNA in response to therapy were comparable with the two assays. The ICPCR assay should be useful in monitoring HIV-1 RNA levels both in natural history studies and in clinical trials of antiretroviral agents.

DNA, Viral↗
PubMed1995

Conservation of an intact human immunodeficiency virus type 1 vif gene in vitro and in vivo.

Replication of vif-negative human immunodeficiency virus type 1 (HIV-1) is attenuated in certain cell lines and highly impaired in peripheral blood lymphocytes in vitro. To determine whether intact vif is positively selected during natural HIV-1 infection and to determine vif sequence variability, we employed PCR amplification, cloning, and sequencing to investigate the vif region of replicating virus in short-term-passage HIV-1 primary isolates from five asymptomatic individuals and from five persons with AIDS. A total of 46 vif clones were obtained and analyzed. Recombinant proviruses were constructed from selected vif clones from one patient and found to be fully infectious. We found that 38 of the 46 clones sequenced carried open vif reading frames and that there was a low degree of heterogeneity of vif genes within isolates from the same individual and among isolates from different donors. The cysteines previously found to be essential for vif protein function were conserved in all clones. A phylogenetic tree constructed from all available vif nucleotide sequences resulted in a virus grouping similar to those of gag and env. Direct sequencing of vif amplified by PCR from uncultured lymphocytes of 15 individuals at various stages of progression toward AIDS demonstrated vif open reading frames in 13 of 15 samples tested. There was no obvious correlation between disease status and the presence of an intact vif within this sample group at the time of sample procurement. The conservation of the vif open reading frame in vitro and in vivo and its limited variability following virus transmission in vitro are consistent with a role for vif in natural HIV-1 infection.

Amino Acid Sequence↗
PubMed1995

Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-, and potassium-stimulated aldosterone secretion.

The zona glomerulosa cells of the adrenal gland have an intrinsic renin-angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells. Zona glomerulosa cells were cultured in PFMR-4 medium containing 10% fetal calf serum for 72 hours, and the medium was replaced with serum-free medium for the next 24-hour experimental period. DuP 753 (10 mumol/L) inhibited basal aldosterone secretion (from 88.6 +/- 7.1 to 54.8 +/- 9.6 pg/10(6) cells per hour; 38% inhibition). EXP 3174, an active metabolite of DuP 753, also inhibited aldosterone dose dependently (from 88.6 +/- 7.1 to 55.9 +/- 8.4 at 1 mumol/L and 88.6 +/- 7.1 to 21.7 +/- 3.3 at 100 mumol/L; 37% and 75% inhibition, respectively). Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition). DuP 753 inhibited Ang II (100 nmol/L)-stimulated aldosterone production in a dose-dependent fashion, with a 30% reduction at 100 nmol/L and complete inhibition at 100 mumol/L. DuP 753 also inhibited potassium (12 nmol/L) and corticotropin (1 nmol/L) stimulation of aldosterone in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Extrapyramidal symptoms in a BMT recipient with hyperintense basal ganglia and elevated manganese.

Neurologic syndromes attributed to conditioning or medications have been reported in BMT recipients. A patient is presented who developed extrapyramidal symptoms on day +56 after allogeneic BMT. Brain magnetic resonance images of this patient demonstrated hyperintense basal ganglia, which has been associated with manganese (Mn) toxicity. The patient had received total parenteral nutrition (TPN) with standard trace element supplementation and had been cholestatic. Serum Mn was elevated, and continued to be so 5 months after BMT, long after discontinuation of TPN. Cholestatic patients and those on long-term TPN have been found to have high blood or serum levels of Mn, but generally are asymptomatic. When other cholestatic BMT patients were reviewed, all had elevated serum Mn. Manganese supplementation in TPN requires evaluation for BMT recipients.

Basal Ganglia↗
PubMed1995

Nosocomial outbreak of Salmonella typhimurium infection in a nursery intensive care unit (NICU) and paediatric ward.

A nosocomial outbreak of multidrug resistant Salmonella typhimurium in a Nursery Intensive Care Unit (NICU) and Paediatric ward is reported. Eight (16.6%) out of a total of 48 babies taken ill during this outbreak expired. Clinical manifestations included diarrhoea and fever. The organism was isolated from stool samples/rectal swabs of all the 48 cases and blood of 6 cases. An investigation was undertaken to trace the source of infection. The organism was isolated in pure cultures from three suction machines of NICU. The epidemic was immediately controlled with identification of the source but the question of how the suction machines were infected by this organism remained unsolved.

Child, Preschool↗
PubMed1995

Lung functions in malnourished children aged five to eleven years.

Lung functions including FVC, FEV1, PEFR, %FEV1/FVC and Empey Index were measured using P.K. Morgan's pocket spirometer on 122 children of both sexes in the age group of five to eleven years. There were 80 (65.57%) malnourished children according to the Indian Academy of Pediatrics classification. FVC and FEV1 were significantly (p < 0.02) reduced in malnourished children. FVC (r = 0.67, p < 0.001), FEV1 (r = 0.68, p < 0.001) and PEFR (r = 0.53, p < 0.001) showed linear relationship with body surface area in all age groups. Empey index was less than 10 in both healthy and malnourished children. Abnormal respiratory functions should be interpreted with caution in malnourished children.

Body Surface Area↗
PubMed1994

Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations.

Drug resistance conferred by specific human immunodeficiency virus type 1 (HIV-1) pol gene mutations has been associated with clinical progression in HIV-infected patients receiving anti-retroviral therapy. This study examined drug susceptibilities and pol mutations of HIV-1 strains from patients treated for 1 year with zidovudine, didanosine (ddI), or zidovudine and ddI. Ten (42%) of 24 patients receiving combination therapy versus 8/26 (31%) receiving only zidovudine had HIV-1 strains with phenotypic zidovudine resistance or a zidovudine resistance pol mutation at codon 215 (P = .6). In contrast, a ddI resistance mutation at codon 74 was less common among patients receiving combination therapy (2/24) than among those receiving ddI only (17/26; P < .001). Two patients receiving combination therapy developed resistance to zidovudine and ddI; they had HIV strains with amino acid mutations at codons 62, 75, 77, 116, and 151. Combination therapy with zidovudine and ddI selects for zidovudine-resistant HIV-1 strains lacking a ddI resistance mutation and for multidrug-resistant strains containing novel pol mutations.

Amino Acids↗
PubMed1994

A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine.

OBJECTIVE: A Phase I study of subcutaneous recombinant interleukin-2 (rIL-2). DESIGN: Sixteen patients with advanced HIV infection receiving 600-1200 mg zidovudine per day were divided into three groups, which received sequentially 0.2 x 10(6), 0.7 x 10(6) or 2 x 10(6) units/m2 per day of rIL-2 subcutaneously 5 consecutive days. SETTING: Five-day admission to an academic tertiary care hospital. PATIENTS, PARTICIPANTS: Sixteen unblinded, non-randomized volunteers. INTERVENTIONS: Subcutaneous rIL-2. MAIN OUTCOME MEASURES: Tolerance, toxicity, hematologic, immunologic and antiviral responses. RESULTS: rIL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rIL-2 administration, with rebound within 48 h after rIL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rIL-2 receptor levels increased transiently during and immediately following rIL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rIL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden. CONCLUSIONS: Subcutaneous rIL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.

Adult↗
PubMed1994

The early detection of second primary lung cancers by sputum immunostaining. LCEWDG Investigators. Lung Cancer Early Detection Group.

STUDY OBJECTIVE: To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. DESIGN SETTING/PARTICIPANTS: Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non-small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen). INTERVENTIONS: Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up. MEASUREMENTS AND RESULTS: Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date. CONCLUSIONS: Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue.

Aged↗
PubMed1994

Diffusible factors from the murine cell line M2-10B4 support human in vitro hematopoiesis.

Significantly more primitive human hematopoietic progenitors are maintained and differentiate when cultured separately from the stroma by a microporous membrane ("stroma-noncontact" cultures) than when cultured in direct contact with stromal layers ("stroma-contact" cultures). This suggests that diffusible stroma-derived factors may be sufficient for the in vitro induction of progenitor proliferation and differentiation. To further characterize stroma-derived factors that maintain long-term bone marrow culture initiating cells (LTBMC-IC), we compared the hematopoietic supportive capacity of human marrow stroma with that of the murine marrow stroma-derived fibroblast cell line M2-10B4 as well as two embryonic fibroblast cell lines, the human FHS-173-WE and the murine NIH-3T3 cell lines. We demonstrate that LTBMC-IC, present in human CD34+/HLA-DR- (DR- cells), are maintained equally well and give rise to similar numbers of committed progenitors, that is--colony-forming cells (CFC)--when cultured in contact with human marrow stroma or any cell line feeder (stroma-contact cultures). LTBMC-IC, cultured in marrow stroma or M2-10B4 stroma-noncontact cultures, were maintained significantly better and gave rise to significantly more CFC than when cultured in human marrow stroma or M2-10B4 contact cultures. However, LTBMC-IC maintenance and differentiation in FHS-173-WE or NIH-3T3 noncontact cultures was significantly less than in human marrow stroma or M2-10B4 noncontact cultures. These studies indicate that systematic comparison of diffusible growth stimulatory factors in conditioned media from M2-10B4 cells and FHS-173-WE may lead to the characterization of growth regulatory factors required for in vitro maintenance and differentiation of human primitive LTBMC-IC. Since diffusible factors from the M2-10B4 cell line can support human hematopoiesis, our observations may also have important implications for in vitro stem cell expansion protocols.

Animals↗
PubMed1994

High and low dose clonidine tests for the diagnosis of growth hormone deficiency.

The growth hormone (GH) response to three provocative stimuli was assessed in 15 short normal children (ISS) and 5 children with GH deficiency (GHD). The pharmacologic agents used were insulin 0.1 unit/kg IV (IHT), oral clonidine 0.15 mg/m2 (HDCT) and 25 micrograms irrespective of age and weight (LDCT). Blood glucose and GH were measured at 0, 30, 60, 75, 90 and 120 minutes; and BP and serum cortisol levels were measured during clonidine tests. A steep rise in GH levels were found between 60 and 90 minutes during HDCT and LDCT. The peak GH levels were 29.5 +/- 5.7 ng/ml in HDCT compared to 17.9 +/- 5.7 ng/ml during IHT and 6.7 +/- 2.9 ng/ml during LDCT (p < 0.01). The peak GH levels above 7 ng/ml were seen in 60% children with ISS during LDCT. No significant adverse effects were noticed during HDCT and LDCT except transient drowsiness. The peak GH levels were not related to the fall in BP or cortisol levels. LDCT appears to be a reasonably effective stimulator of GH release. It can be used for screening children with reduced growth velocity as an outpatient procedure. Those with an abnormal response will need a more definite testing such as HDCT.

Administration, Oral↗
PubMed1994

Ketorolac.

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Analgesics, Non-Narcotic↗
PubMed1994

Detection of beta-thalassaemia mutations in eastern Indian population by polymerase chain reaction.

We report here the application of a non-radioactive amplification refractory mutation system (ARMS) for the direct detection of beta-thalassaemia using polymerase chain reaction. Seven beta-thalassaemia mutations accounting for 89 per cent (71 of 80) of the alleles in eastern Indian population have been identified and majority (67.5%) were due to IVS-1 nt 5 (G-C) mutation. Interestingly, 9 cases did not reveal any of the 17 common mutations reported so far from Indian population.

Alleles↗
PubMed1994

Abnormal pattern of lung functions in rubber factory workers.

The influence of suspended particulate matter, benzo(e) pyrene, benzo(e) pyrene and benzo(a) anthracene concentration on pulmonary lung functions ie, residual volume, total lung capacity, residual volume/total lung capacity, forced residual capacity were studied in 667 rubber factory workers during 1990-91. The respirable fraction of the particulate size (< 0.5 micron) showed high mean concentration of suspended particulate matter, benzo(a) pyrene, benzo(e) pyrene and benzo(a) anthracene in the compounding section (group III), when compared with vulcanising (group II) and packing loading (group I) units. While comparing the lung functions amongst these groups, the higher results of residual volume, residual volume/total lung capacity ratio, forced respiratory capacity and lower values of total lung capacity were observed in group III workers as compared with other two groups. And also these results seem to be correlated with the high pollutant concentrations to which group III workers were exposed, and reflect a clear combination of obstructive and restrictive pattern of lung functions in them.

Air Pollutants, Occupational↗