Biomedical subjects
P K Maiti
Publications and source records attributed to P K Maiti.
Epidemiological aspects of mycetoma from a retrospective study of 264 cases in West Bengal.
Between 1981 and 2000, 264 cases of mycetoma were diagnosed clinically and microbiologically at Calcutta School of Tropical Medicine. Retrospective analysis of the records revealed that the ratio of actinomycetomas and eumycetomas was 197 : 67; the male to female ratio was 183 : 81. Ninety-four cases occurred in the 1980s and 170 in 1990s, with significantly more infections of Actinomadura spp. (P < 0.01) and fewer with Nocardia caviae (P < 0.01) during the last decade. Pricking was the most common injury associated with eumycetomas (P < 0.01). A total of 196 infections were in exposed body parts and 68 in covered areas. The localization of mycetomas differed significantly (P < 0.01) according to sex, incidence of actinomycetomas or eumycetomas, and obvious history of trauma. Exposed area cases were more common among agricultural workers (P < 0.01), while covered area mycetomas were almost always actinomycetomas with a remarkably lower incidence of N. caviae, A. madurae and Madurella grisea infections. The peak age of onset was between 16 and 25 years. The delay of diagnosis for the 80th percentile of cases was around 6 years for cases caused by N. brasiliensis and Streptomyces spp.; 8 years for N. caviae and N. asteroides; and 10 years for M. grisea and Actinomadura spp. From the history of trauma in 130 patients, the 80th percentile incubation period (IP) was calculated for N. brasiliensis, N. caviae and N. asteroides as 3 years; for Actinomadura spp. 7 years and for M. grisea 9 years. The minimum IP for all organisms was around 3 months.
Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4.
Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-dependent Ab-mediated autoimmune disorders, in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1-type cells and costimulatory factors such as CD40 ligand (CD40L) contribute to disease pathogenesis by producing proinflammatory cytokines and by activating autoreactive B cells. In this study we demonstrate the capacity of CD40L blockade to modulate EAMG, and analyze the mechanism underlying this disease suppression. Anti-CD40L Abs given to rats at the chronic stage of EAMG suppress the clinical progression of the autoimmune process and lead to a decrease in the AChR-specific humoral response and delayed-type hypersensitivity. The cytokine profile of treated rats suggests that the underlying mechanism involves down-regulation of AChR-specific Th1-regulated responses with no significant effect on Th2- and Th3-regulated AChR-specific responses. EAMG suppression is also accompanied by a significant up-regulation of CTLA-4, whereas a series of costimulatory factors remain unchanged. Adoptive transfer of splenocytes from anti-CD40L-treated rats does not protect recipient rats against subsequently induced EAMG. Thus it seems that the suppressed progression of chronic EAMG by anti-CD40L treatment does not induce a switch from Th1 to Th2/Th3 regulation of the AChR-specific immune response and does not induce generation of regulatory cells. The ability of anti-CD40L treatment to suppress ongoing chronic EAMG suggests that blockade of CD40L may serve as a potential approach for the immunotherapy of MG and other Ab-mediated autoimmune diseases.
Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18.
Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an important role in interferon gamma (IFN-gamma) production and IL-12-driven Th1 phenotype polarization. Increased expression of IL-18 has been observed in several autoimmune diseases. In this study we have analyzed the role of IL-18 in an antibody-mediated autoimmune disease and elucidated the mechanisms involved in disease suppression mediated by blockade of IL-18, using experimental autoimmune myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both implicated in EAMG development. We show that treatment by anti-IL-18 during ongoing EAMG suppresses disease progression. The protective effect can be adoptively transferred to naive recipients and is mediated by increased levels of the immunosuppressive Th3-type cytokine TGF-beta and decreased AChR-specific Th1-type cellular responses. Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator. Our results suggest that IL-18 blockade may potentially be applied for immunointervention in myasthenia gravis.
Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with 111In.
H11 is a human IgM monoclonal antibody which recognizes a novel tumour-associated antigen expressed on melanoma, glioma, breast cancer, colon cancer, prostate cancer, lung cancer and B-cell lymphoma. In this study, a recombinant single-chain Fv (scFv) fragment of H11 labelled with 111In was investigated for tumour imaging in athymic mice implanted subcutaneously with A-375 human melanoma xenografts. H11 scFv was derivatized with diethylenetriaminepentaacetic acid (DTPA) for labelling with 111In. The immunoreactivity of DTPA-H11 scFv against A-375 cells in vitro ranged from 23% to 36%. 111In-DTPA-H11 scFv was rapidly eliminated from the blood and most normal tissues (except the kidneys) reaching maximum tumour/blood ratios of 12:1 at 48 h post-injection. Tumours were imaged as early as 40 min after injection. The kidneys accumulated the highest concentration of radioactivity (up to 185% injected dose/g). Tumour uptake was 1-3% injected dose/g. The whole-body radiation absorbed dose predicted for administration of 185 MBq of 111In-DTPA-H11 scFv to humans was 37 mSv. The radiation absorbed dose estimates for the kidneys, spleen and intestines were 405 mSv, 698 mSv and 412 mSv, respectively. The results of this preclinical study and a concurrent phase I trial suggest a promising role for H11 scFv for tumour imaging.
In vitro susceptibility pattern of Sporothrix schenckii strains isolated from three centers in India.
BACKGROUND & OBJECTIVES: With the availability of more number of antifungal agents in recent years, drugs other than saturated solution of potassium iodide (SSKI) are being increasingly used to treat sporotrichosis. It was therefore considered pertinent to evaluate in vitro antifungal susceptibility pattern of Sporothrix schenckii strains isolated at three centers in India against five commonly used antifungal agents. METHODS: Agar dilution method was used to evaluate 50 clinical isolates (25 from north, 17 from east and 8 from south India) both in its yeast and mycelial forms against amphotericin-B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole. RESULTS: No resistance was observed in the yeast form of S. schenckii against amphotericin B and azoles. However, 54 per cent strains in the yeast form were resistant to 5-fluorocytosine. None of the strains was susceptible to amphotericin B and ketoconazole, 56 and 10 per cent strains in the mycelial form were susceptible to itraconazole and fluconazole respectively. No significant difference was observed in the antifungal susceptibility pattern among the strains isolated from these three regions in India. INTERPRETATION & CONCLUSION: Clinical isolates of S. schenckii from three regions of India had a more or less uniform antifungal susceptibility pattern. Itraconazole had the best in vitro susceptibility results against the clinical isolates of S. schenckii and has the potential to replace SSKI.
Dimethoate inhibits extrathyroidal 5'-monodeiodination of thyroxine to 3,3',5-triiodothyronine in mice: the possible involvement of the lipid peroxidative process.
The effects of daily administration of dimethoate (2, 4 and 8 mg/kg body weight for 30 days) on thyroid function in mice were investigated. While serum triiodothyronine (T3) concentration was decreased significantly, serum thyroxine (T4) was increased in the medium and highest dose treated groups. However, the serum concentration of thyrotropin was unaltered. Hepatic type-I iodothyronine 5'-monodeiodinase (5'-D) enzyme activity was depressed by the two higher doses of dimethoate. These observations suggest that dimethoate-induced alterations in thyroid function are not mediated through the hypophyseal thyroid axis, but through the changes in extrathyroidal conversion of T4 to T3. To correlate the lipid peroxidation (LPO) with 5'-D activity, hepatic LPO and the activity of antioxidant enzymes, i.e. superoxide dismutase (SOD) and catalase (CAT), were studied. The pesticide increased the activity of SOD and CAT along with hepatic lipid peroxidation. The possible involvement of the lipoperoxidative process in the inhibition of 5'-D activity has been suggested.
Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.
The present study was undertaken to determine the pattern of immunoreactivity of BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3) 28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic). Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a variety of human tumor cell lines including gliomas, melanomas, neuroblastomas, and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic tumor tissue sections (94%), and in some cases, on close to 100% of cells. All malignant cell types, including small anaplastic cells, giant cells, gemistocytic cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non-astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6. There was weak immunoreactivity in a small subset of normal human tissues of epithelial and lymphoid origin, with the exception of adrenal cortex, which exhibited weak to moderate staining. All normal tissues of neuroectodermal and mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be unique in that it recognizes a highly-expressed astrocytic tumor-associated antigen that is present on both low and high grade tumors. This makes it a strong candidate for further studies aimed at establishing its usefulness in the treatment of human astrocytic tumors.
Cadmium induced alterations in extrathyroidal conversion of thyroxine to triiodothyronine by type-I iodothyronine 5'-monodeiodinase in male mouse.
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Sexual risk factors for cervical cancer among rural Indian women: a case-control study.
BACKGROUND: The association between sexual behaviour and cervical cancer is well established. Despite a high incidence of cervical cancer in India, its role has not been widely investigated in Indian women among whom the rate of sexual promiscuity is known to be very low. A hospital-based case-control study was carried out to investigate the role of sexual risk factors in cervical cancer among rural Indian women. METHODS: A case-control design was used in which a total of 268 subjects, comprising 134 women with invasive cervical cancer as cases and 134 control women were studied. A multiple logistic regression model was used to analyse the data. RESULTS: The risk factors found to be associated with cervical cancer were early age at first coitus, extramarital sex partners of women and the time interval since first exposure. In a multiple logistic regression model, independent effects were observed for early age at first coitus, showing maximum risk in women who reported their first intercourse at < 12 years of age, compared to that of women at > or = 18 years (odds ratio [OR] = 3.5. 95% confidence interval [CI]: 1.1-10.9). Increased risk was also seen for women who had extramarital sex relationships (OR = 5.5, 95% CI: 1.5-19.5). The significant effect of early age at first coitus persisted after adjustment for latency period which also showed its independent risk association with cervical cancer in the multivariate analysis. CONCLUSION: These findings confirm the association between early age at first coitus and cervical cancer in women with a low rate of sexual promiscuity and define the role of these risk factors in cervical carcinogenesis among rural Indian women.
Antibiotic sensitivity patterns of actinomycetes isolated from patients of actinomycetoma.
The effectiveness of eight antibiotics against 30 human isolates of actinomycetoma agents belonging to 7 different species were tested by agar dilution and disc diffusion methods to evaluate the susceptibility patterns and to study drug resistance among the organisms. It was found that many of the isolates had developed partial or complete resistance to conventionally used antibiotics like cotrimoxazole, streptomycin and ampicillin, but almost all were sensitive to amikacin and ciprofloxacin. The two methods were equally effective for detecting sensitivity patterns of the Nocardia isolates.
Lead induced thyroid dysfunction and lipid peroxidation in the fish Clarias batrachus with special reference to hepatic type I-5'-monodeiodinase activity.
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Dimethoate induced lipid peroxidation and inhibition of type-I iodothyronine 5'-monodeiodinase activity in young cockerel.
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Free radical mediated membrane perturbation and inhibition of type-I iodothyronine 5'-monodeiodinase activity by lead and cadmium in rat liver homogenate.
The possible involvement of lipid peroxidation (LPO) in the lead (Pb) and cadmium (Cd) induced thyroid dysfunction with special reference to type-I iodothyronine 5'-monodeiodinase (5'-D) activity was studied in rat liver homogenate. Peroxidative reactions involving membrane components were found to be markedly stimulated by chronic administration of Pb and Cd in rats. Metal induced inhibition in 5'-D activity was also observed. Since LPO is primarily an outcome of free radical generation, we suggest metal induced free radical mediated inhibition of 5'-D activity in rat liver homogenate. In addition, serum triiodothyronine (T3) and thyroxine (T4) concentrations were also decreased by metals.
Loss of membrane integrity and inhibition of type-I iodothyronine 5'-monodeiodinase activity by fenvalerate in female mouse.
The possible involvement of lipid peroxidation (LPO) in the fenvalerate-induced thyroid dysfunction with special reference to type I 5'-monodeiodinase (5'-D) activity has been worked out. Fenvalerate (40, 80 and 120 mg/kg body weight) enhanced LPO in biomembranes of liver and kidney leading to a decrease in membrane integrity. 5'-D activity and serum concentration of triiodothyronine (T3) were reduced by the highest dose. Serum thyroxine (T4) concentration was decreased in all the three fenvalerate-treated groups, indicating the sensitivity of thyroid gland to this pesticide. A marginal increase in T4 concentration in highest dose-treated group compared to that of the lower one supports the view that the monodeiodination of the phenolic ring of T4 is inhibited by fenvalerate. We suggest the possible inactivation of 5'-D by the generated free radicals in pesticide-treated animals.
Characterization of the epitope recognized by a mAb that reacts differentially with murine suppressor T cells.
Although reliable antibodies are available that distinguish human suppressor T (Ts) cells from CTL and other T cells, few are available for murine Ts cells. We have developed a mAb (984D4.6.5) that, in the presence of complement, depletes alloantigen-specific Ts cells but not CTL. This antibody recognizes activated Ts cells but not their precursors. In these studies, flow cytometric analysis demonstrates that 984D4.6.5 reacts with several Ts cell hybridomas, cloned Ts cell lines and WEHI-3 (a myelomonocytic tumor cell line). Reactivity was not detected with BW5147, Th cell hybridomas, cloned Th cells, CTL lines and hybridomas, B cell lines, thymocytes, splenocytes, bone marrow cells nor a variety of tumor cells. Among 984D4.6.5 positive lines, expression is heterogeneous and the number of cells expressing high levels of the epitope is increased when the hybridomas are maintained at a relatively high cell density. Neuriminidase and pronase deplete the epitope recognized by mAb 984D4.6.5. Protein synthesis and glycosylation inhibitors also reduce expression of this epitope. These observations suggest that the epitope recognized by 984D4.6.5 is a carbohydrate linked to a polypeptide. This antibody was tested by ELISA for binding to a large panel of carbohydrates and glycolipids coupled to BSA. The only one that bound 984D4.6.5 was LS tetrasaccharide c (NeuNAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc), an O-linked carbohydrate. Comparative analysis shows that both the sequence and the linkage of these sugars are essential to the reactivity with the 984D4.6.5 antibody. This epitope is expressed by a glycoprotein of approximately 200 kDa, as shown by Western blots. The identity of this glycoprotein remains to be determined, but indirect evidence suggests that it is not CD45.
Human monoclonal antibody BT32/A6 and a cell cycle-independent glioma-associated surface antigen.
The purpose of this study was to ascertain how various growth parameters may influence the labeling of SK-MG-1, a human glioma cell line, by BT32/A6, a human immunoglobulin M monoclonal antibody (MAb). By growing SK-MG-1 cells at different culture split ratios, significant trends in cell growth rate, culture viability, and cell cycle state were produced. Labeling of SK-MG-1 cells by BT32/A6, however, was shown to be unaffected by culture split ratio (p > 0.05) and is therefore independent of cell growth rate, culture viability, and cell cycle state. Using flow cytometry and fluorescence-activated cell sorting, BT32/A6 was shown to label a cell surface antigen on viable, clonogenic cells of SK-MG-1. Approximately 100% of SK-MG-1 cells were shown by flow cytometry to express the BT32/A6 antigen. The recognition of a glioma-associated, cell cycle-independent surface antigen by MAb BT32/A6 makes it a promising candidate for further studies aimed at elucidating its usefulness as an adjunct in the treatment of human malignant gliomas.
The suppressor factor of T suppressor cells induced by tolerogenic conjugates of ovalbumin and monomethoxypolyethylene glycol is serologically and physicochemically related to the alpha beta heterodimer of the T cell receptor.
Ovalbumin-specific, H-2Kd restricted, CD8+ Ts cells of clone 17.2 were shown to produce an OVA-specific Ts cell factor (TsF17.2) possessing the same Ag specificity and MHC restriction as those of the intact Ts cells. The Ts cell clone was generated from a single cell of the spleen of a mouse which had been immunosuppressed by injection of tolerogenic OVA(mPEG)12 conjugate. For the elucidation of the nature of TsF17.2, it was characterized by serologic, physicochemical, and Western blot analyses. It was found that 1) the OVA-specific suppression of in vitro antibody production by TsF17.2 could be blocked by mAb H28-710 which binds to an epitope of the constant region of the alpha-chain of TCR; 2) the TsF17.2 could be sequestered by, and eluted from, immunosorbents prepared by coupling to Affi-Gel Hz the H28-710 mAb or the mAb H57-597 and F23.1 which are specific, respectively, for an epitope of the constant region of the beta-chain and an epitope of the V beta 8 region of the TCR; and 3) the TsF17.2 had a pl of 7.0, m.w. of 84,000, and consisted of two disulfide-linked subunits of 42,000 each. After electroelution from the SDS-PAGE gel, the m.w. 84,000 molecule retained its capacity to suppress in vitro antibody production in an OVA-specific manner. From all these results it was concluded that this Ts cell factor may represent a soluble form of the alpha beta heterodimer of TCR of cloned Ts cells.