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Biomedical subjects

R Das

Publications and source records attributed to R Das.

At least 55 records · Page 3Linked to original sources
PubMed2000

Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.

PURPOSE: To determine immune responses and toxicity to the anti-idiotype vaccine, as well as clinical responses and survival, we initiated a clinical trial for patients with advanced melanoma treated with an anti-idiotype antibody (TriGem) that mimics the disialoganglioside GD2. PATIENTS AND METHODS: Forty-seven patients with advanced melanoma received either 1-, 2-, 4-, or 8-mg doses of TriGem (Titan Pharmaceuticals Inc, South San Francisco, CA) mixed with QS-21 adjuvant (Aquila Biopharmaceuticals, Inc, Worcester, MA) 100 microg subcutaneously weekly for 4 weeks and then monthly until disease progression. Median age was 57 years, there were 32 men and 15 women, 43% of patients had undergone prior therapy for metastatic disease, 55% had disease confined to soft tissue, and 45% had visceral metastasis. RESULTS: Hyperimmune sera from 40 of 47 patients showed an anti-anti-idiotype (Ab3) response. Patient Ab3 was truly Ab1' because it specifically bound purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody consisted of predominantly immunoglobulin (Ig)G, and all IgG subclasses were represented. One patient had a complete response that persisted at 24 months, and 12 patients were stable from 14+ to 37+ months (median, 18+ months). Disease progression occurred in 32 patients on study from 1 to 17 months (median, 5.5 months), and 21 have died at 1 to 16 months (median, 6 months). The Kaplan-Meier-derived overall median survival has not been reached. Median survival has not been reached for the 26 patients with soft tissue disease only and was 13 months for 21 patients with visceral metastasis. Toxicity consisted of local reaction at the site of injection and mild fever and chills. CONCLUSION: TriGem has minimal toxicity and generates robust and specific IgG immune responses against GD2. Objective responses were minimal, but there may be a favorable impact on disease progression and survival that will require prospective randomized trials.

Adolescent↗
PubMed2000

Genome analyses of spirochetes: a study of the protein structures, functions and metabolic pathways in Treponema pallidum and Borrelia burgdorferi.

We perform a comprehensive genome analysis on two spirochetes, T. pallidum and B. burgdorferi. First, we focus on the occurrence of protein structures in these organisms. We find that there are only a few spirochete-specific folds, relative to those in other types of bacteria. The most common fold, by far, in the spirochetes is the P-loop NTP hydrolase, followed by the TIM barrel. These folds also happen to be amongst the most multifunctional of the known folds. We also survey the membrane-protein structures in T. pallidum and find a notable large family with twelve transmembrane (TM) helices, reflecting the prevalence of 12-TM transporters in bacteria. Then we move to analysis of the metabolic pathways and overall metabolism in the spirochetes, using the metabolic-flux-balancing method. We find that the lipid biosynthesis pathway is absent from the spirochetes. This strongly limits the degree to which these organisms can metabolize NADPH. In turn, we find that the spirochetes distribute flux disproportionately through the glycolytic pathway instead of the NADPH-providing pentose phosphate pathway. Further information is available at http://bioinfo.mbb.yale.edu

Bacterial Proteins↗
PubMed2000

Correlations between apoptotic and proliferative indices in cervical intraepithelial neoplasia and carcinoma.

Aims of the present paper was to study cell death by apoptosis and cell proliferation in normal cervical biopsies, cervical intraepithelial neoplasms (CIN) and squamous cell carcinomas of cervix (CaCx). There were each seven cases of normal cervical biopsy, CIN1 and CIN2 along with 10 cases of CIN3 and 14 cases of CaCx. Percentage of apoptotic cells and bodies (i.e. apoptotic index, AI) and mitoses (i.e. mitotic index, MI) and turnover index (TI - AI + MI) were counted in formalin fixed, paraffin embedded, haematoxylin and eosin stained slides. AgNOR stain was done and mean AgNOR dots per cell was also estimated. AI, MI and TI were correlated with histology grade of CIN and invasive carcinoma cervix. Mean AI, MI, TI and AgNOR count increased from lower to higher grades of CIN. AI, MI & TI raised significantly from CIN3 to carcinomas; AI, TI & AgNOR count raised significantly from CIN1 to combined CIM2 & 3; TI & AgNOR count were high in CIN1 to CIN2; AI & TI were significantly raised in normal to CIN1. In conclusion, TI is probably more important for cell kinetic analysis of CIN and carcinoma of cervix because it reflects the frequency of two important events i.e. mitosis and cell death. Sudden increase of AI, MI, TI count from CIN3 to CaCx may indicate the possibility of genetic alteration of cells of CIN3 which induces a frank malignant transformation from CIN3 to CaCx.

Apoptosis↗
PubMed1999

Rapid detection of Mycobacterium bovis on its lipid profile by thin layer chromatography.

Sixteen Mycobacterium bovis (M. bovis) strains isolated from bovine tissues and one standard reference strain of M. bovis AN5 alongwith other species of mycobacteria for comparison were investigated for the presence of phenolic glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) for rapid identification of M. bovis by thin-layer chromatography (TLC). The study indicated presence of PGL with an Rf value of 0.75 in chloroform-methanol solvent in all 17 M. bovis strains. The dimycocerostate A corresponding to spot A was the major constituent among all the three spots in M. bovis strains. TLC appeared to be a promising alternative to conventional biochemical methods for identification of M. bovis taking into consideration both PGL and PDIM lipids.

Animals↗
PubMed1999

Phenylalanyl-tRNA synthetase from the archaeon Methanobacterium thermoautotrophicum is an (alphabeta)2 heterotetrameric protein.

Phenylalanyl-tRNA synthetase from the methanogenic archaeon Methanobacterium thermoautotrophicum was purified to apparent homogeneity. The catalytically active enzyme is a heterotetramer composed of two subunits, alpha and beta. N-terminal sequence data were obtained for both subunits and the open reading frames MT770 and MT742 of the genome sequence of M. thermoautotrophicum were identified as coding for these proteins. Two ORFs with similarity to non-archaeal PheRSs alpha-subunits had previously been found in the genome sequence, but these results show that only one of them, MT742, is part of the active PheRS.

Amino Acid Sequence↗
PubMed1999

Resolution of the mammalian E complex and the ATP-dependent spliceosomal complexes on native agarose mini-gels.

A great deal of progress in elucidating the mechanisms of spliceosome assembly has been achieved by analyzing the A, B, and C spliceosomal complexes on native polyacrylamide gels. In contrast, progress in understanding the earliest spliceosomal complex E has been hampered because this complex dissociates on native gels and is difficult to detect by other methods. Here we report conditions for resolving the spliceosomal complex E using a native horizontal agarose mini-gel system. This system also provides a simple alternative to polyacrylamide gels for resolving the ATP-dependent spliceosomal complexes.

Adenosine Triphosphate↗
PubMed1999

L-NAME inhibits Mg(2+)-induced rat aortic relaxation in the absence of endothelium.

1 L-NG-nitro-arginine methyl ester (L-NAME; 100 microM), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 microM acetylcholine (ACh) and 2-10 mM Mg2+ in endothelium-intact (+E) rat aortic rings precontracted with 1 microM phenylephrine (PE). In PE-precontracted endothelium-denuded (-E) rat aorta, 3 microM ACh did not, but Mg2+ caused relaxation which was reversed by L-NAME, but not by D-NAME. 2 The concentration response profiles of L-NAME in reversing the equipotent relaxation induced by 5 mM Mg2+ and 0.2 microM ACh were not significantly different. 3 L-NAME (100 microM) also reversed Mg(2+)-relaxation of -E aorta pre-contracted with 20 mM KCl or 10 microM prostaglandin F2alpha (PGF2alpha). L-NG-monomethyl-arginine (L-NMMA; 100 microM) was also effective in reversing the Mg(2+)-relaxation. 4 Addition of 0.2 mM Ni2+, like Mg2+, caused relaxation of PE-pre-contracted -E aorta, which was subsequently reversed by 100 microM L-NAME. 5 Reversal of the Mg(2+)-relaxation by 100 microM L-NAME in PE-precontracted -E aorta persisted following pre-incubation with 1 microM dexamethasone or 300 microM aminoguanidine (to inhibit the inducible form of NOS, iNOS). 6 Pretreatment of either +E or -E aortic rings with 100 microM L-NAME caused elevation of contractile responses to Ca2+ in the presence of 1 microM PE. 7 Our results suggest that L-NAME exerts a direct action on, as yet, unidentified vascular smooth muscle plasma membrane protein(s), thus affecting its reactivity to divalent cations leading to the reversal of relaxation. Such an effect of L-NAME is unrelated to the inhibition of endothelial NOS or the inducible NOS.

Acetylcholine↗
PubMed1999

Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen.

PURPOSE: We generated an anti-idiotype antibody, designated CeaVac, that is an internal image of the carcinoembryonic antigen (CEA). We previously demonstrated that the majority of patients with advanced colorectal cancer generate specific anti-CEA responses. The purpose of the current study was to treat patients with surgically resected colon cancer with CeaVac to determine the immune response and clinical outcome to treatment with vaccine. We also compared the immune responses between patients treated with fluorouracil (5-FU) chemotherapy regimens plus vaccine versus vaccine alone. PATIENTS AND METHODS: Thirty-two patients with resected Dukes' B, C, and D, and incompletely resected Dukes' D disease were treated with 2 mg of CeaVac every other week for four injections and then monthly until tumor recurrence or progression. Fourteen patients were treated concurrently with 5-FU chemotherapy regimens. RESULTS: All 32 patients entered onto this trial generated high-titer immunoglobulin G and T-cell proliferative immune responses against CEA. The 5-FU regimens did not have a qualitative or quantitative effect on the immune response. Three of 15 patients with Dukes' B and C disease progressed at 19, 24, and 35 months. Seven of eight patients with completely resected Dukes' D disease remained on study from 12 to 33 months; one patient with resected Dukes' D disease relapsed at 9 months. One patient with incompletely resected Dukes' D disease remained on study at 14 months without evidence of progression; eight experienced disease progression at 6 to 31 months. CONCLUSION: CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.

Adjuvants, Immunologic↗
PubMed1998

Digital radiology in skeletal trauma: assessment of casualty officers' performance.

Radiographic images can now be produced without the requirement of film processing and development, and can be displayed rapidly on a computer monitor. We assessed junior doctors' performance in interpreting images from 25 patients being investigated for possible fracture and also compared the diagnostic abilities of casualty officers with those of radiology specialist registrars. For interpretation of images viewed at a workstation or as filmed laser images, respectively, sensitivities were 75% and 78%, and specificities were 65% and 76%. These differences were not significant. There was a tendency for radiology specialist registrars to be less specific when reviewing images at a workstation. The demonstration that there is no loss in diagnostic quality when casualty officers interpret fracture images in a purely digitally acquired and viewed format forms a robust basis for economic evaluation of the technology.

Clinical Competence↗
PubMed1998

Treatment of severe falciparum malaria with artesunate and mefloquine.

AIM: To study the therapeutic efficacy of low dose intravenous artesunate followed by oral mefloquine in severe falciparum malaria in Singapore. METHODOLOGY: Retrospective review of 4 cases of severe falciparum malaria admitted for treatment in a private hospital in the first six months of this year. Patients were considered cured when no malaria parasites were detected in the blood film on discharge and remained afebrile at 28 days. RESULTS: This drug regimen was well tolerated, rapidly reduced parasitaemia and achieved 100% cure in all four patients. CONCLUSION: Low dose intravenous artesunate followed by mefloquine was found to be well tolerated and rapidly effective in treating severe falciparum malaria contracted in Indonesia and India. There was no relapse of clinical disease in all four cases after 28 days.

Adult↗
PubMed1997

Tamoxifen inhibits prolactin signal transduction in ER - NOG-8 mammary epithelial cells.

Tamoxifen (TAM), an antiestrogen, also acts as an antilactogen in mammary cells. In the present study we analyze the effect of TAM on the signal transduction pathway for prolactin (Prl). TAM bound specifically to NOG-8, an estrogen receptor-negative mammary cell line. Within 5 min of Prl treatment, raf-1, MEK and MAP kinase were induced 2-3-fold over the control level. TAM completely inhibited this Prl-induced activation of kinases as well as Prl binding and cell growth. These results indicate the potential role of TAM as an antilactogen in Prl responsive systems.

Animals↗
PubMed1997

Fine-needle aspiration biopsy in fungal infections.

To evaluate the role of fine-needle aspiration biopsy (FNAB) in diagnosis of fungal infections, a retrospective analysis of 26 cases of fungal infection is described. The spectrum of various fungi encountered on cytologic microscopy of aspirated material and fungal culture was as follows: Aspergillus sp (16 cases), Cryptococcus neoformans (six cases), Mucorales (one case), Candida sp (one case), Phialophora parasiticus (one case), Sporothrix schenkii and Cladosporium sp (the last two isolated from a single case). In majority (71%) of cases, fungal infection was not clinically suspected but was picked up on cytologic material in all the cases. An accurate diagnosis based on morphology could be made in 21 cases (80%). Predisposing factor was found in three patients, two of them had diabetes mellitus and one was on immunosuppression. HIV serology was negative in seven cases tested. Commonest tissue reaction (75%) was foreign body giant cells with foamy macrophages and variable amount of necrosis. Although FNAB is helpful in the rapid diagnosis of fungal infections, culture is essential for more accurate identification.

Adolescent↗