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Biomedical subjects

S Das

Publications and source records attributed to S Das.

At least 793 records · Page 44Linked to original sources

Effect of cytokines, dexamethasone and the A/T-signal peptide polymorphism on the expression of alpha(1)-antichymotrypsin in astrocytes: significance for Alzheimer's disease.

Proinflammatory cytokines and acute phase proteins, such as alpha(1)-antichymotrypsin, are over expressed in microglia and astrocytes in brain regions with abundant mature amyloid plaques, suggesting a glial cell-led brain acute phase response in the Alzheimer neuropathology. In this paper, we show that alpha(1)-antichymotrypsin gene expression in human astrocytes is elevated by interleukin-1 and interleukin-6, and further enhanced by glucocorticoid, while the homologous contrapsin gene in rat astrocytes is unaffected by these cytokines. These distinct gene regulation mechanisms might help to explain the differential susceptibility of humans and rodents to amyloid formation of the Alzheimer's type. In addition, we demonstrate that the alpha(1)-antichymotrypsin A-allele that encodes a different signal peptide and is a suggested risk factor for Alzheimer's disease gives rise to a reduced level of immature alpha(1)-antichymotrypsin in transfected cells. The physiological result would be an enhanced ability of the A-encoded alpha(1)-antichymotrypsin protein to become secreted and promote extracellular amyloid formation. We discuss our findings in terms of a model in which cytokine-induced alpha(1)-antichymotrypsin synthesis in astrocytes constitutes a specific inflammatory pathway that accelerates the development of Alzheimer's disease and could at least partly underlie the regional specificity and species restriction of the neuropathology.

Alzheimer Disease↗

Characterization of a 30-kDa Borrelia burgdorferi substrate-binding protein homologue.

A Borrelia burgdorferi chromosomal gene encodes a 30-kDa antigen (P30) that has considerable homology with periplasmic substrate-binding proteins of Gram-negative bacteria, and is recognized by antibodies in sera from a subset of patients with Lyme disease and from B. burgdorferi-infected mice. The p30 gene is 801 nucleotides in length and P30 contains 267 amino acids, with a predicted molecular mass of 30 kDa. The P30 amino acid region 36-258 has homology to conserved domains of the oligopeptide permease A of Gram-negative bacteria. Immunofluorescence studies using murine anti-P30 serum suggest that P30 is on the outer surface of B. burgdorferi. P30 expression could be detected in representatives of all 3 subspecies of B. burgdorferi sensu lato, but not in all of the tested strains. Antibodies to P30 were detected in sera of 18 out of 82 patients (22%) with Lyme disease, including individuals with early- or late-stage infection. Although antibodies to P30 are present in the sera of C3H/HeN mice infected with B. burgdorferi for at least 90 days, immunization with recombinant P30 does not protect mice from infection. We conclude that P30 is a putative substrate-binding protein of B. burgdorferi and is immunologically recognized in human and murine Lyme borreliosis.

Animals↗

Plasma homocysteine concentrations in type II diabetic patients in India: relationship to body weight.

Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease and occurs with a high prevalence in patients with type II diabetes and microvascular disease. In order to determine whether plasma homocysteine concentrations vary with body-mass index in patients with type II diabetes, we measured plasma homocysteine in lean, normal weight, and overweight subjects living in India. Plasma homocysteine concentrations were significantly lower in the lean persons with diabetes when compared to those who were obese and compared to control subjects (p < 0.02). We conclude that plasma homocysteine concentrations are lower in lean persons with type II diabetes and that this efficiency in homocysteine metabolism may contribute towards protection from cardiovascular disease in this population.

Adult↗

Methylation analysis of the fragile X syndrome by PCR.

The fragile X syndrome is predominantly caused by a large expansion of a CGG trinucleotide repeat in the promoter region of the FMR1 gene, which is associated with methylation and downregulation of transcription. The molecular diagnosis of this disorder is based on repeat size and methylation analysis of the FMR1 gene usually by Southern blot analysis. We describe a PCR-based method for the analysis of methylation of the FMR1 gene, which involves bisulfite treatment of DNA prior to amplification. Fifty-two normal and 48 affected, premutation, or mosaic males were analyzed in a blinded study by this method. A prospective study of 30 males suspected of fragile X was also performed. Amplification specific for the methylated FMR1 sequence was readily observed in all individuals with a full mutation, whereas all normal and premutation individuals showed only amplification-specific for the unmethylated sequence, thus, allowing affected and unaffected males to be distinguished. A full mutation in the presence of mosaicism was also detectable by this method. Methylation-specific PCR appears to be a rapid and reliable tool for the diagnosis of fragile X males.

Base Sequence↗

Sympathetic inhibition with methyldopa in heart failure.

The hypothesis that withdrawal of increased sympathetic activity may be beneficial in heart failure was tested by administration of the centrally acting adrenergic inhibitor methyldopa. Fourteen subjects with chronic, stable New York Heart Association Functional Class 2 or 3 heart failure receiving digitalis and diuretics were randomized to methyldopa (n = 8) 500-1000 mg daily or placebo (n = 6). Clinical, hemodynamic, neurohumoral, and platelet alpha 2-receptor effects were studied after chronic (3 weeks) administration. Sympathetic inhibition did not alter symptom status or exercise duration but reduced plasma norepinephrine concentration during exercise and permitted the same level of exercise to be attained at a lower pressure-rate product, indicating reduced myocardial oxygen consumption. Left ventricular ejection fraction and stroke volume tended to increase, and systemic vascular resistance tended to decrease during exercise after methyldopa administration, suggesting enhanced vasodilation. Upright plasma renin activity increased from 8.2 +/- 2.2 to 13.3 +/- 3.0 ng/nl/h (p = 0.03) after methyldopa, but plasma antidiuretic hormone concentration changed insignificantly. In a subset of patients, platelet alpha 2-receptor density and affinity were unaltered. Renal function was also unchanged. Thus, sympathetic inhibition induced by methyldopa in selected patients with chronic, stable heart failure does not worsen symptom status or exercise performance, and may produce a beneficial effect by withdrawal of excess sympathetic activity with reduction of plasma norepinephrine levels.

Adult↗

Molecular differences between RER+ and RER- sporadic endometrial carcinomas in a large population-based series.

Studies, to date, have suggested that there are distinct molecular differences between microsatellite stable (RER(-)) and unstable (RER(+)) solid tumors, such as colorectal carcinoma. We investigated a range of molecular events including mutation frequency of K-ras, microsatellite instability within the coding region of TGF-beta RII, BAX, and IGF-IIR, loss of expression of p53, hMLH1, hMSH2, hMSH6, and PTEN, and methylation of hMLH1, hMSH2, and PTEN within a large population-based series of sporadic endometrial carcinomas to establish whether there are distinct differences between replication error repair (RER(+)) and RER(-) cases. RER(+) endometrial carcinomas tended to be diploid with normal p53 expression, compared with RER(-) cases. Mutations in TGF-beta RII, IGF-IIR, and BAX were rare, but there was a strong association between mutation and RER(+) status. Methylation and loss of hMLH1 expression were significantly more common in RER(+) cases, as was methylation of PTEN. K-ras mutations were equally frequent in RER(+) and RER(-) cases. Despite the absence of distinct clinicopathological differences between RER(+) and RER(-) cases in this series of sporadic endometrial carcinomas, our results confirm that there are molecular differences between RER(+) and RER(-) cases, but the molecular events occurring in RER(+) endometrial carcinomas differ from those seen in RER(+) colorectal carcinomas.

Adaptor Proteins, Signal Transducing↗

Plant lectins as inhibitors of tumour growth and modulators of host immune response.

The antitumour activities of four plant lectins, phytohaemagglutinin, pokeweed mitogen, soybean agglutinin, and wheat germ agglutinin, were evaluated on a murine ascitic lymphoma. The effects of lectin treatment on mitogenic response of peripheral blood lymphocytes and macrophage-mediated tumour cell lysis were also assessed. All four lectins studied were found to be able to restrict tumour growth and to improve the life expectancy of the host. The response of peripheral blood lymphocytes towards mitogenic stimulation was found to be improved and enhancement of tumour cytolysis by peritoneal macrophages was noted following lectin treatment.

Animals↗

Sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients: a 48-week retrospective multicenter study.

BACKGROUND: Nevirapine, a nonnucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients who are treated in clinical practice needs further evaluation. PURPOSE: To evaluate the sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients in routine clinical practice. DESIGN: A multicenter study from January 1997 to December 2000, with follow-up through 48 weeks, was conducted at four different genitourinary medicine clinics in the United Kingdom. Forty-four HIV-infected patients received nevirapine and two nucleoside analogues. Information from case notes regarding age, sex, side effects, viral load, and CD4 lymphocyte counts at baseline, 24 weeks, and 48 weeks was collected and analyzed. Virologic suppression, defined as HIV RNA concentration of less than 400 copies/mL at Weeks 24 and 48, was considered as the main outcome measure. RESULTS: Out of 44 patients, 41 were men with a mean age of 39.3 years (95% CI 36.7-41.8). The baseline viral load was 2.11 x 10(2) to 9.74 x 10(5) copies/mL (median 7.7 x 10(4) and CD4 counts 6 to 605 cells/dL (M = 247; 95% CI 198-295). Of 39 patients who completed 48 weeks of treatment, viral load suppression was attained in 31 patients (79.4%; 95% CI 66.8-92.0) at 24 weeks and in 27 patients (69.2%; 95% CI 54-83) at 48 weeks. The CD4 lymphocyte count increased in 32 (82%) patients (mean 106 cells/dL, 95% CI 73-139, p =.0001, Wilcoxon signed rank test) after 24 weeks and in 33 (84.6%) patients (mean 160 cells/dL, 95% CI 115-204, p =.0001, Wilcoxon signed rank test) after 48 weeks of treatment. Of 20 patients whose baseline viral load was <100000, 16 had viral load suppressed at 24 weeks and 15 at 48 weeks (p =.6, chi-square test). CONCLUSION: A regime of nevirapine with two nucleoside analogues provided durable suppression of plasma viral load in HIV infected patients, with significant improvement in the CD4 cell count.

Adult↗

Site of H atom attack on uracil and its derivatives in aqueous solution.

Hydrogen atoms from the radiolysis of water at pH 1.6 add to the 5,6-double bond of pyrimidines. The preferential site of attack is the C(5) position (values in brackets) in the case of 6-methyluracil (87%), 1,3-dimethyluracil (71%), uracil (69%) and poly(U) (60%). This reaction yields a radical of reducing properties which can be monitored by its reaction with tetranitromethane in a pulse radiolysis experiment. In thymine (37%), thymidine (32%) and 1,3-dimethylthymine (25%) H-addition no longer preferentially occurs at C(5), but addition is now mainly at C(6). Hydrogen abstraction from the methyl groups or the sugar moiety is negligible (less than or equal to 5.5%). A comparison is made with literature values for the equivalent reactions of OH radicals.

Chemical Phenomena↗

Plasma lipids and lipoprotein cholesterol in undernourished diabetic subjects and adults with protein energy malnutrition.

Estimation of triglycerides (Tg), total cholesterol (Tc), HDLs, LDLc, and VLDLc was carried out in 46 undernourished diabetic subjects (UND); 21 untreated and 25 on insulin; 44 well-nourished diabetic subjects (WND); 22 untreated and 22 on insulin; together with 25 patients with protein energy malnutrition (PEM) and 25 healthy controls less than 50 yr of age. Compared with controls, in the untreated diabetic subjects Tg, Tc, LDLc, and VLDLc were significantly higher in both classes, while HDLc was lower only in WND. Among the treated diabetic subjects, Tg were higher in WND, LDLc lower in UND, and VLDLc higher in both. With regard to relative distribution of cholesterol in the untreated patients, HDLc/Tc was lower in WND, but this was not so in UND. HDLc/Tc was higher in treated UND. Between undernourished and well-nourished groups of diabetic subjects in the untreated patients, HDLc was significantly higher and LDLc lower in the former. Both Tc and LDLc were lower in UND on insulin compared with WND. HDLc/Tc was higher and LDLc/Tc lower in both untreated and treated UND. In adults with PEM, mean values of Tg, Tc, and LDLc were much lower than in controls, as well as in both groups of UND. On the other hand, values of HDLc/Tc were higher and LDLc/Tc lower in PEM compared with controls, but this was not so for treated UND. It is evident from the results of this study that the undernourished have lower levels of plasma lipids and a favorable distribution of cholesterol among the lipid fractions from the point of view of vulnerability to development of atherosclerosis.

Adult↗

Application of new technology in clinical hyperthermia.

Two areas of technical progress related to hyperthermic oncology are presented: (1) numerical modelling of absorbed power and temperature distributions; and (2) non-invasive thermometry using magnetic resonance imaging. The results represent achievements made during the past 5 years at Duke University Medical Center's Departments of Radiation Oncology and Radiology. They represent examples of progress in the technology of hyperthermia that have potential for greatly improving the delivery, monitoring and assessment of clinical hyperthermia.

Body Temperature↗

A pilot study on neuroepidemiology in urban Bengal.

A pilot survey was undertaken in an urban district population of West Bengal, to study the magnitude of problems of Neurological disorders in the Community. The study was performed by Professionals, headed by a Neurologist, using accepted WHO protocol (1981) for neuroepidemiological survey. Point prevalence rate was found to be 75 per 1000. Sensitivity and specificity of the case study came out to be 98.97% and 99.6% respectively.

Adult↗

Laparoscopic surgery for female urinary incontinence: prudence shall prevail.

Advances in laparoscopic techniques continue to seek new domains and new indications with the sole objective of providing maximum benefit in a minimally invasive manner. During the last decade, several innovative laparoscopic procedures have evolved for the management of female urinary incontinence. At this juncture, prudence dictates a careful analysis of the principles behind and performance of these procedures so that our treatment recommendations for this common ailment can be based on unbiased scientific pragmatism. In this review, we attempt to analyze the available data and provide constructive criticism and recommendations toward the continued pursuit in this area of development in laparoscopy.

Adult↗

Inclusion body myositis (IBM).

Clinical, histological, immunohistochemical and ultrastructural features of 5 cases of inclusion body myositis -4 sporadic (s-IBM) and one hereditary (h-IBM) form are described. These patients (3 men, 2 women) had chronic progressive weakness of varying severity in all 4 extremities with sparing of cranial muscles. Elevation of CPK was noted in 2 patients. Electromyography revealed features of myopathy in 4 and additional neurogenic changes in 2 subjects. Clinical diagnosis was often other than inclusion body myositis. Presence of characteristic eosinophilic inclusions within the vacuoles established the diagnosis. The inclusions were congophilic and showed positivity to ubiquitin, beta-amyloid and SMI-31 in the sporadic cases while congophila was absent in the hereditary form. Immunostaining to hyperphosphorylated-tau was negative in both s-IBM and h-IBM. Membraneous whorls were observed at ultrastructural level. None of the patients improved with steroids and trial with other immunosuppressants was unsuccessful.

Adult↗

Thyroid calcitonin cells and parathyroid gland of the Indian rhesus monkey Macaca mulatta in response to experimental hypercalcaemia.

Rhesus monkey (Macaca mulatta) were subjected to hypercalcaemia by daily intramuscular injections of vitamin D2 (100,000 IU) and by providing them gram soaked in 1% CaCl2 solution for eating and 1% CaCl2 solution (prepared in tap water) for drinking. After 10, 15, 20 and 30 days of such treatment the serum calcium level recorded a rise (18.24 +/- 0.56, 26.20 +/- 1.30, 17.25 +/- 0.25 and 20.50 +/- 0.55 mg/dl respectively) as compared to those of control animals (12.80 +/- 1.00, 12.30 +/- 0.50, 12.70 +/- 0.20 and 12.30 +/- 0.30 mg/dl). Serial sections of thyroid parathyroid complex and isthmus were subjected to selective staining for lcalising the C cells. The structure and behaviour of these cells both under normal and experimental conditions has been studied. Hypercalcaemia resulted in the increase of these cells. Mitotic figures of the C cells were also encountered after 10 days of hypercalcaemia. The specimens subjected to 30 days treatment showed complete degranulation of these cells. Chronic hypercalcaemia inhibits the activity of parathyroid cells which display degenerative changes. The anterior and posterior poles, the peripheral regions of thyroid and isthmus are completely devoid of calcitonin cells.

Adult↗

Histopathological changes in gallbladder mucosa in cholelithiasis: correlation with chemical composition of gallstones.

BACKGROUND: Cholelithiasis produces diverse histopathological changes in gallbladder mucosa namely acute inflammation, chronic inflammation, glandular hyperplasia, granulomatous inflammation, cholesterosis, dysplasia, and carcinoma. Gallstones have different chemical composition. They may be cholesterol, pigment or mixed stones. The aim of this prospective study was to see if any correlation existed between the chemistry of gallstones and any particular histopathologic picture. METHODS: Between May 1997 and December 1997 we diagnosed and operated on 40 patients with cholelithiasis. Diagnosis was established by ultrasound. After operation gallstones were sent for chemical analysis to detect presence of calcium bilirubinate and cholesterol. Serial sections of gallbladder from fundus to neck were stained by haematoxylin and eosin, and studied. RESULTS: Out of 40 patients (n = 40) 29 were females and 11 were males. The mean age of our patients was 38 +/- 21 years with a median of 40 years. Median age of males was 48 years compared to 38 years for females. Twenty-eight patients had mixed stones, 8 had pigment stones and 4 had cholesterol stones. Out of 28 patients with mixed stones 14 had histological picture of chronic cholecystitis, 8 had granulomatous cholecystitis, 4 had adenomatous hyperplasia, 1 had dysplasia and 1 had carcinoma. All 8 patients having pigment gallstones had chronic cholecystitis. Out of 4 patients with cholesterol gallstones, 2 had chronic cholecystitis, 1 had adenomatous hyperplasia and 1 had cholesterosis. Gallbladder having pigment stones were devoid of Rokitansky-Aschoff sinuses. CONCLUSION: Adenomatous hyperplasia and Rokitansky-Aschoff sinuses were not seen in gallbladder containing pigment stones but seen in gallbladders containing mixed and cholesterol stones in our study. Cholesterol may be a more potent stimulus for glandular hyperplasia or glandular hyperplasia may responsible for formation of cholesterol rich stones.

Adult↗