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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 271 records · Page 15Linked to original sources

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↗

No increase in relapse in patients with myeloid leukaemias receiving rhGM-CSF after allogeneic bone marrow transplantation.

Twenty patients with leukaemia received recombinant human GM-CSF (rhGM-CSF) after allogeneic bone marrow transplantation (BMT) in a double blind controlled trial, with a significant promotion of granulopoiesis when compared with 20 control patients. The follow-up in survivors is now sufficiently long to assess the potential for promotion of relapse in the patients with myeloid leukaemias. Six patients with myeloid leukaemias are alive 22-38 months after transplantation. Eight other patients with myeloid leukaemias died within 12 weeks of transplantation without active active disease. None of these 14 patients with myeloid leukaemias have relapsed. This study supports the view that rhGM-CSF does not increase the probability of relapse after allogeneic BMT in patients with myeloid leukaemia.

Bone Marrow Transplantation↗

Vanadate-resistant mutants of Candida albicans show alterations in phosphate uptake.

Phosphate uptake studies in different strains of the dimorphic pathogenic yeast Candida albicans were undertaken to show that this yeast actively transported phosphate with an apparent Km in the range of 90-170 microM. The uptake was pH dependent and derepressible under phosphate starvation. Vanadate-resistant (van) mutants of C. albicans showed a 20-70% reduction in the rate of phosphate uptake in high phosphate medium and was associated with an increased Km and reduced Vmax. The magnitude of derepression under phosphate starvation was different between van mutants. These results demonstrate that van mutants may have developed resistance by modifying the rate of entry of vanadate.

Biological Transport↗

Neoadjuvant chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in 69 cases of locally advanced (stage IIIb) breast cancer.

Sixty nine patients with a median age of 45 years, 62.3 per cent of whom were premenopausal, with locally advanced breast cancer (T 4, N 0-3, M 0; Stage IIIb) were treated with 3 cycles of either neoadjuvant cyclophosphamide, doxorubicin and 5-fluorouracil, being the CAF group: 36 patients, or cyclophosphamide, methotrexate and 5-fluorouracil, being the CMF group: 33 patients. Patients achieving complete response or with residual disease of less than 2 cm in diameter received radical radiotherapy while those with more residual disease underwent radical mastectomy. Nine cycles of adjuvant chemotherapy were administered. Complete responses and disease control by radiotherapy with complete breast preservation were more frequently observed after CAF than CMF, being 25 per cent vs 3 per cent (p = 0.025) and 48.5 per cent vs 12 per cent (p = 0.002), respectively. Overall response rates, adverse effects, disease control following radiotherapy/surgery, local relapses and metastases were similar for both regimes. Relapsing patients were young, with a median age of 38 years, 68.4 per cent of relapses occurred at metastatic sites and 42 per cent of relapses occurred during adjuvant chemotherapy. This study suggests that in locally advanced breast cancer, a greater proportion of patients can be rendered disease free after neoadjuvant CAF and radiotherapy compared to neoadjuvant CMF and radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Human immunodeficiency virus isolates from asymptomatic homosexual men and from AIDS patients have distinct biologic and genetic properties.

Human immunodeficiency virus type 1 (HIV-1) isolates from asymptomatic homosexual men and AIDS patients were compared for their in vitro biologic and genetic properties. Most of the HIV-1 isolates from asymptomatic men, but not from AIDS patients, failed to infect CD4+ H9 cells and phytohemagglutinin-stimulated peripheral blood lymphocytes. In a longitudinal study, serial HIV-1 isolates obtained from men who seroconverted to HIV-1 and later developed AIDS were able to infect H9 cells. In contrast, longitudinal isolates from men who remained asymptomatic did not infect H9 cells. HIV-1 isolates from AIDS patients in general exhibited increased production of intracellular viral DNA, RNA, and protein as compared to isolates from asymptomatic men. Cells infected with HIV-1 isolates from asymptomatic men produced very little gp120, p24, and p55 proteins as compared to those from AIDS patients. The overall restriction patterns of HindIII, Sac-1, Pst-1, EcoR1, and BamH1 were very similar between HIV-1 isolates from asymptomatic men and those from AIDS patients. However, the restriction endonuclease pattern of BglII was quite distinct for isolates from asymptomatic men as compared to AIDS patients. Preliminary studies mapped a unique BglII site in the gag region of most of the isolates from asymptomatic men, approximately 2.0 kb from the 5' end. Thus, HIV-1 isolates from asymptomatic subjects and from AIDS patients have distinct biologic and genetic properties which may be related to the various clinical outcomes of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Analysis of alternatively spliced human immunodeficiency virus type-1 mRNA species, one of which encodes a novel tat-env fusion protein.

A polymerase chain reaction-based analysis was used to define the structures of the mRNAs that encode human immunodeficiency virus type-1 (HIV-1) regulatory and structural proteins in infected H9 cells. Twenty alternatively spliced mRNAs encoding the vif, vpr, env, nef, tat, and rev proteins were characterized. An evaluation of the coding potentials of these transcripts recognized both leaky scanning and reinitiation at downstream initiation codons as mechanisms that may operate during translation of many of the polycistronic messages. Two new splice acceptor sites, one at nt 6018 defining a new mRNA coding for the env and vpu proteins and another at nt 8671 defining a novel tat-env fusion transcript, were characterized. The latter transcript expressed a novel protein p17tev that was immunoprecipitated by both polyclonal tat antibodies and monoclonals directed towards the C-terminal region of gp41. The p17tev protein was able to transactivate transcription from the HIV-1 LTR in transient transfection assays. The use of multiple alternative splice donor and acceptor sites and the generation of novel proteins may confer evolutionary advantages on the viral mutants encoding them and influence the course of clinical disease.

Animals↗

Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients.

Twenty-five patients with AIDS in AIDS Clinical Trials Group Protocol 002 were treated with either low or high dosages of zidovudine. This resulted in moderate, transient increases by 10 and 20 weeks in lymphocyte blastogenesis and interferon-gamma (IFN-gamma) production in vitro in response to phytohemagglutinin with and without recombinant interleukin-2. Immune responses to cytomegalovirus and herpes simplex virus type 1 antigens were augmented less frequently during therapy. Natural killer (NK) cell lysis of uninfected and human immunodeficiency virus-infected cells was also transiently increased by 10 and 20 weeks. IFN-gamma production, the only immune parameter directly associated with increases in numbers of CD4+ T cells, peaked at 10 weeks of treatment. The limited efficacy of zidovudine treatment in AIDS patients is associated with moderate, temporary increases in nonspecific and herpesvirus-specific T lymphocyte responses and NK cell function.

Acquired Immunodeficiency Syndrome↗

Subcellular localization, partial purification, and characterization of a dynorphin processing endopeptidase from bovine pituitary.

An enzyme capable of cleaving dynorphin B-29 to dynorphin B-13 is present in bovine pituitary, with 40- to 50-fold higher specific activity in the posterior and intermediate lobes than in the anterior lobe. Subcellular fractionation of bovine neurointermediate pituitary shows that this enzyme is present in the peptide-containing secretory vesicles. The enzyme has been purified 2,800-fold from whole bovine pituitaries using ion-exchange and gel filtration chromatography. Purified dynorphin-converting enzyme has a neutral pH optimum, and is subsantially inhibited by the thiol-protease inhibitor p-chloromercuriphenylsulfonic acid, but not by serine or metalloprotease inhibitors. The purified enzyme processes dynorphin B-29 at Arg14, producing both dynorphin B-14 and dynorphin B-13 in a 5:1 ratio. No other cleavages are observed, suggesting that the activity is free from other proteases and is specific for single Arg sequences. Purified enzyme also processes dynorphin A-17 at the single Arg cleavage site, generating both dynorphin A-8 and A-9 in a 7:1 ratio. The tissue distribution, subcellular localization, and substrate specificity of this enzyme are consistent with a physiological role in the processing of dynorphin B-29 and dynorphin A-17, and possibly other peptides, at single Arg residues.

4-Chloromercuribenzenesulfonate↗

Ca2+ ion sequestration by guinea-pig tracheal cartilage: its influence on trachealis reactivity to KCl.

1. The contractile response of guinea-pig isolated trachealis to KCl has been studied in the presence and absence of cartilage. 2. Dissection of cartilage from the trachealis resulted in both a rightward displacement of the concentration-response curve to KCl (EC50 value: intact strip, 26.9 +/- 3.7 mM n = 5; dissected strip, 38.7 +/- 2.6 mM n = 5; P less than 0.05), and a reduction in the contractile response to KCl (30 mM) observed in a nominally Ca(2+)-free medium. 3. Removal of cartilage from the trachealis did not alter the responsiveness of the tissue to CaCl2 (2.5 mM) when added to K+ depolarized tissues. 4. Muscle-denuded cartilage rings were prepared by surgical removal of the trachealis muscle. Autoradiographic studies, and a direct comparison of Ca2+ (2.5 mM) uptake with that of sorbitol (2.5 mM) showed that cartilage per se had a high capacity to accumulate Ca2+ ions by a process which was resistant to iodoacetate (100 microM), diflunisal (100 microM) and boiling. 5. The uptake of 45Ca into isolated cartilage was unaltered by the addition of orthovanadate (500 microM), verapamil (10 microM), diltiazem (10 microM) or Bay K 8644 (10 microM), but was significantly reduced (P less than 0.05) in the presence of LaCl3 (1-10 mM). 6. We conclude, like previous studies, that cartilage may supply a pool of Ca2+ ions to airway smooth muscle during the generation of tension in a noninally Ca(2+)-free medium, and that LaCl3 may provide an experimental tool to elucidate further the role of non-muscle Ca(2+)-depots in smooth muscle contraction.

Animals↗

Prospective multicenter study on isolation of human immunodeficiency virus type 1 from homosexual men after seroconversion.

A prospective multicenter study was undertaken to isolate human immunodeficiency virus type 1 (HIV-1) from 45 homosexual men for a period of 30 months after seroconversion. Efficiency of HIV-1 isolation from peripheral blood mononuclear cells was relatively stable over time, ranging from 64% at the time of seroconversion to more than 82% after 18 months of seroconversion. However, Kaplan-Meier analysis of HIV-1 culture data indicates that the cumulative proportion of HIV-1 culture positivity at 3, 6, 12, and 18 months after seroconversion was 62, 65, 84, and 92%, respectively. No significant correlation was observed between the presence of HIV-1 p24 antigen in serum, or numbers of CD4+ and CD8+ blood lymphocytes, and HIV-1 isolation within this period of time. These data suggest that HIV-1 viremia in homosexual men gradually increases to almost 100% culture positivity by 18 months after seroconversion.

HIV Seropositivity↗

Evaluation of social marketing of oral rehydration therapy.

Attempts, at social marketing of oral rehydration therapy (ORT) through television, in changing the knowledge and practice of mothers with regard to its use was assessed. One hundred and eighty seven consecutive mothers (38 excluded due to non use of ORT) were administered a preplanned questionnaire to assess their socio-economic profile, educational status, concept of diarrhea and correct use of ORT. Fifty nine mothers who watched these programmes on TV regularly formed the study group. These were compared with 90 mothers who had gained such knowledge from non-television sources. The correct application of knowledge of ORT was significantly better in study group compared with control group. The educational status of mothers had a positive impact on motivation to use ORT at home in the study group. Mass media campaigns through "TV spots" is an effective way of improving knowledge of mothers on ORT in a developing country.

Adult↗

Hypophosphatasia.

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Child, Preschool↗

Isolation, purification and kinetic characterization of plasma membrane H(+)-ATPase of Candida albicans.

The plasma membrane ATPase of Candida albicans was solubilized by Tween 40 and purified to homogeneity on glycerol step gradient. The purified protein appeared as a single band of 100 +/- 4 KDa, represented greater than 98% of the total pure protein on densitometer scan. The purified PM-ATPase which was very specific to MgATP, had Km of about 0.77 mM and a sharp pH optimum at 6.6. Orthovanadate was able to inhibit the enzyme in a non-competitive manner, however, at higher concentrations the nature of inhibition changed to uncompetitive type. Based on molecular size, immuno cross-reactivity and sensitivity to different inhibitors, PM-ATPase of C. albicans appears to be similar to other ion pumps.

Adenosine Triphosphate↗