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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 235 records · Page 13Linked to original sources
PubMed1993

Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus.

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.

AIDS-Related Complex↗
PubMed1993

Levels of plasma membrane H(+)-ATPase do not change during growth and morphogenesis of Candida albicans.

A transient rise in the PM-ATPase activity was observed at the time of commitment of Candida albicans cells to either bud or hyphal formation. However, the changes in PM-ATPase activity did not correlate with the level of enzyme protein detected by ELISA. It was found to be fairly constant during differentiation, implying that there was no de novo synthesis of the protein. Post-translational modification(s) of enzyme protein is suggested to account for variation in PM-ATPase activity during morphogenesis.

Candida albicans↗
PubMed1993

Prospective trial evaluating immunocytochemical-based sputum techniques for early lung cancer detection: assays for promotion factors in the bronchial lavage.

To confirm the results of a previous report on the use of monoclonal antibodies in immunocytochemical assays of sputums for the early detection of lung cancer, we designed a new prospective trial in an independent clinical trial population. Since well-characterized Stage I resected non-small cell lung cancer patients have a low rate of tumor relapse and a high (1-3%/year) chance of developing a second primary lung cancer, they comprise a very favorable group for conducting an early lung cancer detection trial. The rate of new lung cancer is about 10-fold in excess of a standard "high" risk population of smokers. To optimize the chance for a favorable outcome, all of the technical components for the trial have been systematically evaluated to ensure that optimal procedures are employed. For example, automated immunostaining of the sputum specimens will be performed. Bronchial lavages will be analyzed in a subset of the trial participants to define additional targets for early lung cancer detection. Two markers will be quantitated, including gastrin releasing peptide and peptidyl glycine alpha-amidating monooxygenase activity. These two markers assess the epithelium's capacity to produce growth factors which may be central to the biology of tumor promotion. Since these assays have not been performed in this context before, we attempted to optimize the specimen handling to permit the receipt of the material from a range of collaborating clinical sites in a condition that permits accurate quantitation of these two biomarkers. Efforts to standardize the assay endpoint stimulated the development of computer-assisted methods of immunocytochemical analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of adoptive immunotherapy with autologous CD8+ T lymphocytes on immunologic parameters: lymphocyte subsets and cytotoxic activity.

CD8+ cytotoxic T lymphocytes (CTL) may be an important parameter of host resistance to HIV infection. The present study determined whether CD8+ cells could be purified and propagated in vitro to enhance anti-HIV CTL activity, and the immunologic effects of infusion of these cells into autologous, HIV-infected patients as a potential immunotherapy for AIDS and AIDS-related complex (ARC). CD8+ lymphocytes from five AIDS and ARC patients were purified from leukapheresis preparations in cell culture flasks coated with CD8-specific monoclonal antibodies and propagated in vitro for 3 weeks. The ex vivo propagated cells were 98% (+/- 1%) CD8+ and 43% (+/- 6%) HLA-DR+. The majority of the CD8+ cell preparations had increased lytic activity against autologous B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-IIIb structural proteins gag, pol, or env, relative to that of fresh blood mononuclear cells tested prior to purification and culture. The results also show for the first time that CD8+ CTL from HIV-infected patients can lyse cells expressing the HIV regulatory protein, tat. Enhanced expression of CD56 (natural killer cell marker) and lytic activity against vaccinia virus control vector-infected, autologous targets were also noted in the CD8+ cell preparations. Infusion of the CD8+ CTL into autologous patients was well-tolerated and resulted in low but discernible, temporal increases in circulating cytotoxic activity against the HIV gene-expressing targets.

AIDS-Related Complex↗
PubMed1993

Enhanced expression of human immunodeficiency virus type 1 correlates with development of AIDS.

The progression to AIDS may be significantly related to the level of human immunodeficiency virus type 1 (HIV-1) replication. We have used quantitative cell culture and quantitative DNA and RNA PCR to measure viral load and expression in peripheral blood mononuclear cells obtained cross-sectionally and longitudinally from HIV-1-seropositive homosexual men enrolled in the Multicenter AIDS Cohort Study. Our results indicate that the number of circulating CD4+ T-lymphocytes producing HIV-1 increased as the total number of CD4+ T-cells declined. However, there was no correlation between the number of HIV-1-producing CD4+ cells and the duration of infection. Furthermore, the level of HIV-1 gag RNA increased as the disease progressed and CD4+ cell numbers declined. Subjects who remained asymptomatic with stable CD4+ cell counts, however, maintained a very low level of HIV-1 RNA expression during the entire period of follow-up (38-71 months). In contrast to viral RNA expression, the level of proviral DNA did not change significantly as the disease progressed. However, the level of proviral DNA was significantly higher in AIDS patients than in men who remained asymptomatic. Such increased levels of HIV-1 DNA were detected 34-68 months before the development of AIDS. These results support the role of HIV-1 RNA expression in the development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Epiphyseal stapling for leg equalization in developing countries.

Epiphyseal stapling to arrest growth in the longer limb in growing children has been used in 923 cases over 26 years in the management of leg length inequality. Five hundred and three were assessed at the end of growth. Seventy-one percent had 0.5 cm to 1 cm of shortening and 80% did not need an orthosis. Although other methods are available, this technique is particularly valuable in developing countries because it needs only basic surgical facilities and the financial cost is low.

Adolescent↗
PubMed1993

HIV-1 isolates from children with or without AIDS have similar in vitro biologic properties.

OBJECTIVE: To compare biologic properties of HIV-1 isolates from children with and without AIDS as a measure of viral cytopathogenicity. PATIENTS AND PARTICIPANTS: Virus isolates from peripheral blood mononuclear cells of 13 perinatally infected children were compared for specific in vitro biologic properties. METHODS: Virus isolates were examined for biologic properties as measured by their ability to infect H9 cells and to induce syncytia in susceptible cells. RESULTS: Most of the pediatric HIV-1 isolates failed to infect CD4+ H9 cells and induce syncytia in susceptible cells, regardless of whether they were from children with or without AIDS. All of the isolates, however, grew well in mitogen-stimulated normal adult lymphocytes. These results are in contrast to those with HIV-1 isolates from adults, whose biologic properties were related to the stages of the disease. CONCLUSIONS: These results indicate that, unlike adult HIV-1 isolates, the biologic properties of pediatric isolates are not related to the stages of the disease. The rapid development of disease in children may therefore be due to factors other than intrinsic properties of HIV-1 strains present in children.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Characterization of the 5-hydroxytryptamine receptor mediating the positive inotropic response in guinea-pig isolated left atria.

1. 5-Hydroxytryptamine (5-HT), in the presence of propranolol (1 microM), atropine (3 microM) and ketanserin (1 microM), induced a positive inotropic response of guinea-pig isolated electrically paced left atria (pEC50 = 7.52). The positive inotropic response was mimicked by alpha-methyl-5-HT (pEC50 = 7.26) and 5-carboxamidotryptamine (5-CT; pEC50 = 6.56) but not by sumatriptan or 1-(m-chlorophenyl) piperazine (m-CPP). 2. The 5-HT induced positive inotropic response was competitively antagonized by both mesulergine (pA2 = 7.68) and methiothepin (pA2 = 6.67). Methysergide was a surmountable antagonist at 3 nM producing a rightward shift in the 5-HT concentration-response curve giving an apparent pA2 = 9.2 with no significant reduction in the maximum. At higher concentrations, methysergide behaved as an insurmountable antagonist, significantly reducing the maximum response to 5-HT as well as producing rightward shifts in the 5-HT concentration-response curves. 3. The 5-HT-induced positive inotropic response was not antagonized by either tropisetron (10 microM) or yohimbine (10 microM). 4. The guinea-pig atrial 5-HT receptor does not satisfy the criteria for any of the currently recognised 5-HT receptor subtypes and appears to have some similarities to the atypical 5-HT receptors previously described in other peripheral tissues.

Animals↗
PubMed1993

Clarithromycin therapy of experimental Treponema pallidum infections in hamsters.

Clarithromycin was shown to be effective therapy for Treponema pallidum infections in hamsters. Clarithromycin therapy was effective when initiated either 1 or 8 days after infection. The delay in initiation of therapy allowed an active infection to develop. The treponemal burden in lymph tissue of treated hamsters was eradicated, as determined by dark-field microscopy and by inoculation of lymph material into susceptible hamsters. Treatments with clarithromycin and the 14-hydroxy metabolite of clarithromycin were equally effective. Therapy with clarithromycin and penicillin was not antagonistic and did not appear to be synergistic when the two drugs were given concurrently. Pharmacokinetic evaluation of clarithromycin in hamsters showed that the doses which produced effective therapy yielded concentrations in serum similar to those routinely achieved in human sera. These findings demonstrate that clarithromycin is effective in treating active or incubating syphilis in the hamster model and could be useful in treating humans.

Animals↗
PubMed1993

Efficacy of clarithromycin for treatment of experimental Lyme disease in vivo.

Clarithromycin provided effective therapy against arthritis induced by Borrelia burgdorferi infection in the hamster. In vitro, clarithromycin was at least 1 log more potent than tetracycline against two isolates of B. burgdorferi from human sources, as measured by MICs and 50% inhibitory concentrations. Clarithromycin was effective in preventing the onset of B. burgdorferi-induced arthritis, as determined by several parameters of paw swelling. When administered after the onset of arthritis, clarithromycin therapy reduced the degree of swelling and decreased recovery time. These results suggest that clarithromycin has potential as an effective therapy for Lyme disease.

Animals↗
PubMed1993

Toward assessing trends in oral mucosal lesions: lessons learned from oral cancer.

Trend data on oral mucosal lesions are limited. The literature is comprised of a large number of studies documenting the prevalence of various lesions in different populations. Trend data on cancers of the oral cavity and pharynx are the exception. An overview of the international epidemiologic studies of these cancers is provided. General conclusions across studies and countries for trend data of these cancers cannot easily be drawn, since variations exist in data collection methods, risk factors, and other characteristics of the study populations. This paper also reviewed the available prevalence data for oral mucosal lesions in general as well as data on leukoplakia, recurrent herpes labialis, and recurrent aphthous ulcers. A few studies of the incidence of leukoplakia are described. In order to explore the potential for future trend data on oral mucosal lesions, this paper discusses issues related to the feasibility and structure of monitoring these lesions. Criteria that could be used to identify which conditions should be monitored in the future were discussed, such as, those that present a public health problem, those that are sentinel events for serious conditions, and infectious lesions. Once lesions are identified, it is clear that international consensus for diagnostic criteria of these lesions is needed in order to permit comparisons to be made among studies. Finally, strategies for monitoring these conditions and factors that may affect future trends are reviewed.

Canada↗
PubMed1993

Transforming growth factor-beta 1 inhibits aldosterone biosynthesis in cultured bovine zona glomerulosa cells.

Transforming growth factors (TGF beta s) are emerging as possible autocrine regulators of steroidogenesis in a variety of steroid hormone-producing cells. Our laboratory has recently shown that TGF beta 1 is a potent inhibitor of basal and ACTH- and (Bu)2cAMP-stimulated aldosterone production. In this study, we investigated the effects of TGF beta 1 on potassium- and angiotensin-II (A-II)-stimulated aldosterone and the mechanisms by which TGF beta 1 inhibits aldosterone biosynthesis. Cultured zona glomerulosa cells were incubated in serum-free PFMR-4 medium in the presence and absence of TGF beta 1. To investigate the effects of TGF beta 1 on the early pathway of aldosterone biosynthesis, we studied the production of pregnenolone in the presence of the cyanoketone derivative WIN 19,578, which blocks the conversion of pregnenolone to progesterone. TGF beta 1 inhibited pregnenolone production from 133.9 +/- 30.1 to 68.7 +/- 25.4 ng/10(6) cells.h, and the ACTH-stimulated production of pregnenolone was inhibited from 764.6 +/- 127.7 to 141.0 +/- 2.2 ng/10(6) cells.h. In contrast, TGF beta 1 did not inhibit 25-hydroxycholesterol-stimulated pregnenolone production. To study the late pathway of aldosterone production, we added the steroid precursors deoxycorticosterone and corticosterone. TGF beta 1 significantly inhibited deoxycorticosterone- and corticosterone-stimulated aldosterone production by over 50%. TGF beta 1 inhibited the AII- and potassium-induced synthesis of aldosterone. These observations show that TGF beta 1 inhibits AII- and potassium-induced aldosterone synthesis and the early pathway of aldosterone biosynthesis by interfering with the transport of cholesterol across the mitochondrial membrane as well as inhibiting the late pathway of aldosterone biosynthesis.

Aldosterone↗
PubMed1993

Neonatal pain.

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Crying↗
PubMed1993

Delta virus infection in cirrhotics in a north Indian hospital.

Forty patients of HBV related cirrhosis of the liver were studied for the presence of delta infection and subsequently the clinical features, course and outcome of these delta infected cases was compared with those of delta uninfected cases. Out of 40 patients studied, only four patients (10%) were reactive for anti-delta antibodies. The incidence of delta infection was common in the younger age group (31.25 +/- 4.78 years) as compared to the older age group (48 +/- 7.25 years) at p < 0.001. Hepatic Encephalopathy was seen in only 13.88% of delta negative patients as compared to 75% of delta infected patients (p < 0.05). During follow up period of 1 year, 75% of patients died in the delta virus infected group as compared to 22.22% in the delta negative group. The mortality was significantly higher in Child's class C (P < 0.01). So delta virus infection is associated with a more severe course of illness and a poorer prognosis in HBV related cirrhotics.

Adolescent↗
PubMed1993

Feasibility and efficacy of maintenance chemotherapy following autologous bone marrow transplantation for first remission acute lymphoblastic leukaemia.

Thirty-eight patients with poor risk ALL in first remission received maintenance chemotherapy following ABMT. Patients were conditioned for ABMT with high-dose melphalan and single fraction total body irradiation. Maintenance chemotherapy was commenced in a total of 26 patients and was tolerated to a median daily dose of 6-mercaptopurine of 40.5 mg/m2 and a median weekly dose of MTX 8.3 mg/m2. Twenty patients remain alive in first remission with a projected disease-free survival of 50% and a median follow-up in survivors of 200 weeks (range 48-387 weeks). Eleven patients have relapsed at a median of 4.5 months from ABMT. These patients were compared with remission patients with ALL receiving conventional chemotherapy on the United Kingdom Medical Research Council trials UKALL X and XA. After stratifying for major risk factors and allowing for the delay from remission to transplant, we have shown a significant reduction in the risk of relapse after ABMT (p = 0.04). Disease-free survival was not significantly increased due to transplant-related toxicity. This study suggests that maintenance chemotherapy to prevent relapse after ABMT for ALL is well tolerated and warrants assessment in a formal controlled trial.

Adolescent↗