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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 19 recordsLinked to original sources

Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1.

Although human immunodeficiency virus (HIV) type 1 infection is efficiently transmitted by sexual intercourse, some individuals whose sexual behavior places them at extremely high risk for infection have nevertheless remained HIV-1-seronegative. An investigation was undertaken to determine whether such individuals have circulating T helper cells that are sensitized to HIV-1. Five very high risk men who had recent sexual exposure to HIV-1 were studied. Peripheral blood mononuclear cells from all 5 produced interleukin (IL)-2 in culture in response to synthetic amphipathic HIV-1 envelope peptides. One of the 5 high-risk men has subsequently seroconverted, while 4 have remained seronegative. All were initially culture-negative, and those who have remained seronegative were also virus-negative by polymerase chain reaction (PCR) testing 10 months after they were first studied. These results demonstrate that a cell-mediated immune response to HIV-1 can be detected in the absence of a humoral immune response in individuals recently exposed to HIV-1. Furthermore, IL-2 production by T cells in response to synthetic peptides may be a more sensitive test for exposure to HIV-1 than antibody, lymphoproliferation, or PCR tests.

Amino Acid Sequence

A phase I study of ampligen in human immunodeficiency virus-infected subjects.

Ampligen, poly(I)n:poly(C12U)n, was administered intravenously to 39 human immunodeficiency virus (HIV)-infected subjects, asymptomatic or with early AIDS-related complex (ARC) and with CD4+ cell counts less than 500/mm3 in a phase I dose-escalation study. Six doses ranging from 10 to 570 mg/m2 were administered twice-weekly for 9-25 weeks to groups of 5-7 subjects. There was no significant effect on HIV as measured by serum p24 levels, the proportion of patients from whom HIV could be cocultured from blood, or the concentration of peripheral mononuclear cells positive for the virus. Although patients on 10 and 40 mg/m2 showed a significant decline in CD4+ cell counts, as would be expected in untreated patients, patients who received doses greater than or equal to 120 mg/m2 showed no significant decline in CD4+ cell counts. In addition, there was a significant increase in CD4+ cell counts with respect to dose of ampligen. This effect of ampligen and the fact that it has been shown to act synergistically with zidovudine against HIV in vitro suggest that the combination might be tried clinically in patients.

AIDS-Related Complex

Low prevalence of HIV in high-risk seronegative homosexual men evidenced by virus culture and polymerase chain reaction.

OBJECTIVE: To assess the presence of covert HIV-1 infection. SETTING: High-risk seronegative homosexual men from the Pittsburgh portion of the Multicenter AIDS Cohort Study were examined for the presence of HIV-1 infection. PATIENTS, PARTICIPANTS: Ten men (group 1) were examined prospectively for the presence of HIV-1 in their freshly-obtained peripheral blood mononuclear cells (PBMC). Furthermore, cryopreserved PBMC from 26 men (group 2) at their first visit (1984-1985) were examined retrospectively for the presence of HIV-1. MAIN OUTCOME MEASURES: PBMC samples from groups 1 and 2 were examined for HIV-1 by polymerase chain reaction (PCR) using gag, env and strong-stop (long terminal repeat) specific primers. In addition, fresh PBMC samples from group 1 were examined for HIV-1 by virus culture. RESULTS: None of the 10 PBMC samples from group 1 were positive for virus culture and PCR. Only one of the 26 men from group 2 was positive for gag and strong-stop DNA sequences. This PCR-positive, seronegative subject was found to be negative for HIV-1 by PCR at follow-up visits up to 48 months later. None of 15 seronegative, low-risk homosexual men and 12 seronegative heterosexual men were found to be PCR-positive for HIV-1. However, six HIV-1-seropositive men were positive by PCR for gag, env, and strong-stop HIV-1 DNA sequences. CONCLUSIONS: These results suggest a low prevalence of covert HIV-1 infection in high-risk seronegative homosexual men in our geographic area.

Adult

An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HT1D subtype.

1. Endothelium-dependent and -independent, concentration-related, relaxations to 5-hydroxytryptamine (5-HT) are described in a preparation of guinea-pig isolated jugular vein. 2. An endothelial 5-HT receptor was studied in the presence of mesulergine (at 10.0 microM, a concentration sufficient to antagonize 5-HT2 receptor-mediated contractions and endothelium-independent relaxations to 5-HT). Relaxations mediated by the endothelial 5-HT receptor were resistant to antagonism by mesulergine. 3. Several 5-HT receptor agonists activated the endothelial receptor with the following rank order of potency: 5-carboxamidotryptamine (5-CT) greater than 5-HT greater than methysergide greater than or equal to alpha-methyl-5-HT greater than sumatriptan greater than 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 2-methyl-5-HT. 4. Relaxations to 5-HT were not blocked by (+/-)-pindolol (1.0 microM), (-)-propranolol (1.0 microM), spiperone (1.0 microM), ondansetron (1.0 microM) or ICS 205-930 (10.0 microM). 5. Both 5-HT and sumatriptan evoked endothelium-dependent relaxations which were sensitive to antagonism (pA2 and apparent pA2 values respectively) by methiothepin (8.1 and 8.6), metergoline (7.4 and 7.5), PAPP (8.2 and 8.2), yohimbine (7.1 and 6.8), rauwolscine (6.8 and 6.7), but not by corynanthine (10.0 microM). 6. These observations are consistent with a 5-HT1D receptor-mediated effect, and provide further support for the concept that differences exist between endothelial 5-HT receptors in different tissues and species.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Comparison of three nonradioisotopic polymerase chain reaction-based methods for detection of human immunodeficiency virus type 1.

Three nonradioisotopic polymerase chain reaction (PCR)-based detection techniques were evaluated for sensitivity and specificity in detecting human immunodeficiency virus type 1 (HIV-1) proviral DNA in peripheral blood mononuclear cells. The Roche prototype HIV-1 PCR assay, the Du Pont enzyme-linked oligonucleotide sandwich assay (ELOSA), and the Gen-Probe hybridization protection assay (HPA) were compared with a standard radioisotopic oligonucleotide solution hybridization (OSH) technique. A panel of 111 well-characterized clinical samples that included peripheral blood mononuclear cells from 48 healthy, low-risk, HIV-1 antibody-negative subjects, 24 antibody-positive subjects with stable CD4 counts of less than 200/mm3, and 39 antibody-positive subjects with stable CD4 counts of greater than 800/mm3 were studied. Each method demonstrated good specificity, ranging between 96 and 100%; those of the OSH and ELOSA (Du Pont) were 100%, those of the HPA (Gen-Probe) were 100% with one probe and 96% with the other probe, and that of the HIV-1 PCR assay (Roche) was 96%. Sensitivities ranged from 96 to 100% for the low-CD4-count group, with the OSH, the HIV-1 PCR assay (Roche), and the HPA (Gen-Probe) all attaining a sensitivity of 100%. For the high-CD4-count group, sensitivities ranged from 69 to 97%, with the OSH attaining a sensitivity of 97% and the HPA attaining sensitivities of 97% with one probe and 95% with the other probe. These data indicate that the nonradioisotopic techniques are sensitive and specific for the detection of HIV-1 proviral DNA in clinical samples.

Base Sequence

Regulation of the adrenal renin angiotensin system in cultured bovine zona glomerulosa cells: effect of catecholamines.

The renin-angiotensin system consists of two main enzymes, renin and angiotensin-converting enzyme, which lead to the formation of angiotensin-II. Angiotensin-II is a potent vasoconstrictor and stimulates the production of aldosterone. In this study we examined the effect of ACTH, potassium, (Bu)2cAMP (dbcAMP), and catecholamines on the adrenal renin-angiotensin system. To study the production of renin and aldosterone in vitro, we developed a monolayer culture of bovine zona glomerulosa cells in serum-free medium. Collagenase-dispersed zona glomerulosa cells were incubated in Pasadena Foundation for Medical Research-4 medium containing 10% fetal calf serum for 72 h, and the medium was replaced with serum-free medium for the next 24 h of the experimental period. The cells during this 24 h were exposed to various doses of ACTH, potassium, dbcAMP, and sympathomimetic agents. ACTH and dbcAMP stimulated aldosterone secretion, and this secretion was associated with an increase in renin activity in cells and medium. Aldosterone was also stimulated by high doses of potassium, and potassium had a stimulatory effect on the secretion of renin in medium. Catecholamines had a weak stimulating effect on aldosterone secretion and were potent stimulators of adrenal renin activity in cells and medium. Dopamine had no significant effect on basal aldosterone secretion or renin activity in cells and medium. In conclusion, these data indicate that adrenal renin is synthesized in bovine zona glomerulosa cells in vitro, and that ACTH and dbcAMP stimulate adrenal renin and aldosterone production. Furthermore, adrenal renin, like renal renin, may be under the control of the sympathetic nervous system.

Adrenocorticotropic Hormone

Transforming growth factor-beta 1 inhibits aldosterone and stimulates adrenal renin in cultured bovine zona glomerulosa cells.

Transforming growth factors-beta (TFG beta s) are multifunctional peptides that affect proliferation, differentiation, and many other functions in a variety of cell types. In this study we examined the effect of TGF beta 1 on aldosterone and adrenal renin production using cultured bovine adrenal zona glomerulosa cells. Collagenase-dispersed zona glomerulosa cells were incubated in PFMR-4 medium containing 10% fetal calf serum for 72 h, and the medium was replaced with serum-free medium for the next 24 h. The cells during this 24-h period were exposed to TGF beta 1, ACTH, and (Bu)2cAMP (dbcAMP). It was observed that TGF beta 1 at 1 nM 1) inhibited basal aldosterone secretion from 680.0 +/- 40.0 to 270.0 +/- 10.0 pg/10(6) cells.h, 2) inhibited ACTH- and dbcAMP-stimulated aldosterone production, 3) increased levels of active renin in the cells from 17.8 +/- 2.5 to 70.7 +/- 4.4 pg angiotensin-I/10(6) cells.h and prorenin from 270.0 +/- 5.0 to 970.0 +/- 90 pg angiotensin-I/10(6) cells.h, 4) stimulated prorenin in the medium synergistically in combination with ACTH and dbcAMP, and 5) had no significant effect on basal cAMP production, but significantly inhibited the ACTH-stimulated production of cAMP. These observations show that TGF beta 1 is a potent inhibitor of basal and ACTH- and cAMP-stimulated aldosterone production and inhibits ACTH-stimulated cAMP production. Contrary to its effect on aldosterone, TGF beta 1 stimulates the synthesis and release of adrenal renin and prorenin. TGF beta 1 may act as an autocrine or paracrine regulator of aldosterone production.

Adrenocorticotropic Hormone

Transport of acidic amino acids in Candida albicans.

In Candida albicans ATCC 10261, two kinetically different amino acid transport systems with a high (S1) and a low (S2) affinity for aspartic acid (asp) and glutamic acid (glu) were identified. The S1 for the two acidic amino acids was characterized by low Kt values while Kt values of S2 were 30 to 40 times higher. Based on competitive studies of both systems, S1 was found to be specific and common to both asp and glu while S2 was relatively less specific. The S1 and S2 systems were also different in their sensitivity to respiratory inhibitors, mercurials and a K+ channel blocker. Both systems, however, showed maximum transport rates during the mid-exponential growth phase.

Aspartic Acid

Chest radiographs in neonatal septicemia.

Chest radiographs of 63 culture proven cases of neonatal septicemia were evaluated in this prospective study. Gram negative septicemia was responsible for 76.2% cases. Radiological abnormalities were observed in 27 cases (42.8%). Seven of these had no respiratory distress. The findings were right sided infiltrates (27%); hyperinflation (7.9%), bronchopneumonia (6.3%) and pneumothorax (1.6%). Increasing gestational age, late onset of illness (greater than 3 days) and presence of respiratory signs of distress had a positive correlation with presence of X-ray findings. Term newborns with respiratory distress of late onset sepsis (greater than 3 days) had significantly higher number (p less than 0.05) of abnormal radiographs. Presence of radiological abnormality neither influenced the clinical outcome nor was affected by the causative organisms. The practice of doing a chest radiograph routinely in cases of neonatal septicemia is justified irrespective of presence of respiratory signs of distress.

Bacteremia

Prognostic score for kerosene oil poisoning.

Ninety five consecutive children with kerosene oil poisoning were studied, the first 70 retrospectively (internal group) and the rest 25, prospectively (external group) over a period of 3 years and 8 months. Based on clinical features and severity of illness in initial 70 cases, a weighted scoring system to determine the outcome was evolved. This included: (i) fever--absent 0, present 1; (ii) severe malnutrition--absent 0, present 1; (iii) respiratory distress--absent 0, present 2, with cyanosis 4; and (iv) neurological symptoms--absent 0, present 2, with convulsions 4. The scores ranged from 0 to 10 in the internal group. Using discriminate function analysis, a score of 4 or more was found to be associated with prolonged hospital stay and complications. The risk of dying increased if the score was equal to or more than 8. The predictive value of the score was 85.7%. For validation, this scoring was applied to the external group as well and 84% of cases could be correctly predicted.

Child, Preschool

Kerosene oil poisoning--a childhood menace.

This study documents 3-year retrospective analysis of accidental kerosene oil poisoning in 70 children with regard to clinical profile, radiological changes and outcome. About 77% of cases were between 1 and 3 years old. Fifty children (71.4%) developed significant symptoms, with onset soon after to within 10 hours of ingestion. These included breathlessness (55.7%), fever (47.1%), cough (31.4%), restlessness (25.7%) and abdominal distension (15.7%). Chest X-rays were obtained in 65 children. Abnormal radiographs were seen in 45 (69.2%) children with right basal infiltrates being the commonest picture (21.4%). Ingestion of more than one ounce of kerosene oil adversely affected the clinical and radiological profile. Severely malnourished children had extensive radiological changes and poorer clinical outcome. One case developed myocarditis, a complication which has not been reported to the best of our knowledge. Mortality rate was 4.3%. All deaths occurred within 48 hours of admission.

Accidents, Home

A phase II trial of cyclophosphamide, doxorubicin, and cisplatin in advanced breast cancer.

Twenty-five patients (19 premenopausal women, 5 postmenopausal women, and 1 male) with advanced breast cancer were treated with a combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) at 3- to 4-week intervals. The median age of patients was 39 years (range 28-60). Twelve patients received treatment as first-line, and 13 as second-line, therapy. Of the 13 (52%) patients who responded, seven (28%) had complete response (CR). The median disease-free survival (DFS) was 6+ months. The response rate was highest for metastases in the pleura (80%), followed by liver (71%) and lymph nodes (62%). The overall response rate (83% versus 23%, p less than 0.01) was higher in previously untreated than in previously treated patients. Complete response rates of 50% and 8% and median DFS of 8.5+ months and 2 months, respectively, were observed in the two groups of patients. Severe anemia occurred more frequently in previously treated patients. The present study suggests a role for cisplatin combination chemotherapy as first-line therapy in the management of advanced breast cancer.

Adult