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Biomedical subjects

N Bhattacharya

Publications and source records attributed to N Bhattacharya.

At least 55 records · Page 3Linked to original sources
PubMed1998

Loss of cyclin-dependent kinase inhibitor p27Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 in localized human prostate cancer. Archival material from 113 radical prostatectomy specimens obtained between 1985 and 1993 was stained immunohistochemically for p27Kip1 protein using a commercially available antibody. Patient charts were reviewed for preoperative serum prostate-specific antigen, clinical and pathological staging, Gleason tumor grade, time to biochemical and clinical recurrence, and survival. Strong p27Kip1 staining was uniformly seen in benign prostatic epithelial components in all tumor sections. p27Kip1 staining was reduced in most prostate cancers and was variable in prostatic intraepithelial neoplasia. Decreased p27Kip1 staining (<25% of nuclei stained positive for p27Kip1) correlated with seminal vesicle involvement (P = 0.0032) and with higher Gleason grade (P = 0.0114). On univariate analysis, low p27Kip1 predicted an increased risk of treatment failure in the node-negative cohort (P = 0.0037) and in the subset who did not receive neoadjuvant hormonal therapy (P = 0.049). Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047). Seminal vesicle involvement (P = 0.034) and positive surgical margins (P = 0.047) were also independent prognostic factors for disease recurrence. In patients who received preoperative neoadjuvant hormonal therapy, low p27Kip1 in the pathological specimen was an even stronger predictor of outcome than it was in the entire group (n = 23, P = 0.015).

Adenocarcinoma↗
PubMed1998

Detection of HIV seropositivity during an outbreak of Japanese encephalitis in Manipur.

An epidemic outbreak of Japanese encephalitis (JE) occurred during mid 1995. Sixteen serum samples from patients with history of febrile headache, convulsions, mental confusion, neck rigidity etc. were sent to the Department of Virology, School of Tropical Medicine, Calcutta, in August, 1995. Twelve (75%) showed HIV antibody against JEV. Out of these 12 sera showing HIV antibody titre between 1:40 and 1:160, eight (66.6%) showed IgM antibody, giving the presumptive diagnosis of recent JEV infection. Five of these 16 sera showed HIV seropositivity (31.25%). Concomitant JEV and HIV infection could be detected in 3 cases. However, in 2 sera HIV titre were less than 1:20. This is probably the first documentation of concomitant JEV and HIV infection in the eastern India.

Adolescent↗
PubMed1997

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Biomarkers, Tumor↗
PubMed1997

Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited.

Breast↗
PubMed1997

HCV activity in Calcutta--a serological study.

HCV infection, a global public health problem is quite prevalent in India. In the present study conducted during February-July 1996 a total of 153 samples of different age groups and of both sexes were tested by ELISA for detection of Anti-HCV antibody. Anti-HCV was found in 13% of multi-transfused cases and in 8.8% cases with multiple needle-stick injury. Maximum seropositivity (20%) could be observed amongst males between 31-40 yrs. age group. HCV activity was noted more in males (13%) than in females (8.2%) and more relatively in subjects without a history of jaundice (11.5%) than those having the features of jaundice (10.5%). An increasing trend has also been observed amongst the multi-transfused cases in Calcutta.

Adolescent↗
PubMed1996

TGF-beta mediated G1 arrest in a human melanoma cell line lacking p15INK4B: evidence for cooperation between p21Cip1/WAF1 and p27Kip1.

We have studied TGF-beta mediated G1 arrest in WM35, an early stage human melanoma cell line. These cells have lost p15INK4B expression through loss of one chromosome 9 and rearrangement of the other. In asynchronously growing WM35, TGF-beta caused reductions in cyclin D1, cyclin A and cdk4 proteins and their associated kinase activities and an increase in both p21Cip1/WAF1 and p27Kip1. These findings were confirmed in cells released from quiescence in the presence of TGF-beta, in which TGF-beta inhibited or delayed the reduction in the cdk inhibitors that normally occurs in late G1. In contrast to observations in other cell types, there was an increased association of both p21Cip1/WAF1 and p27Kip1 with cyclin D1/cdk4 and with cyclin E/cdk2 during TGF-beta mediated arrest of asynchronously growing cells. Upregulation of p21Cip1/WAF1 preceded that of p27Kip1. Furthermore, p21Cip1/WAF1 and p27Kip1 were not present in the same cdk complexes but bound distinct populations of target cdk molecules. Both p21Cip1/WAF1 and p27Kip1 immunoprecipitates from asynchronously growing cells contained active kinase complexes. These KIP-associated kinase activities were reduced in TGF-beta arrested cells. It has been proposed that in TGF-beta arrested epithelial cells, up-regulation of p15INK4B and of p15INK4B binding to cdk4 serves to destabilize the association of p27Kip1 with cyclin D1/cdk4, promoting p27Kip1 binding and inhibition of cyclin E/cdk2. Our findings demonstrate that this is not a universal mechanism of G1 arrest by TGF-beta. In TGF-beta arrested WM35, which lack p15INK4B, the increased p21Cip1/WAF1 may serve a similar function to that of p15INK4B: initiating kinase inhibition and providing an additional mechanism to supplement the effect of p27Kip1 on G1 cyclin/cdks.

Carrier Proteins↗
PubMed1996

Impact of the cyclin-dependent kinase inhibitor p27Kip1 on resistance of tumor cells to anticancer agents.

A low proliferating fraction in solid tumors limits the effectiveness of cell cycle-dependent chemotherapeutic agents. To understand the molecular basis of such "kinetic" resistance we cultured tumor cells as multicellular spheroids and examined levels of p27Kip1, a cyclin-dependent kinase inhibitor known to be upregulated by intercellular contact in normal cells. When transferred from monolayer to three-dimensional culture, a consistent upregulation (up to 15-fold) of p27 protein was observed in a panel of mouse and human carcinoma cell lines. Antisense-oligonucleotide-mediated downregulation of p27 in EMT-6 mammary tumor cell spheroids reduced intercellular adhesion, increased cell proliferation, sensitized tumor cells to 4-hydroperoxycyclophosphamide, and restored drug- or radiation-induced cell-cycle perturbations repressed in spheroid culture. Our results implicate p27 as a regulator of drug resistance in solid tumors and suggest that tumor-targeted p27 antagonists may be useful chemosensitizers in conjunction with conventional anticancer therapy.

Animals↗
PubMed1995

Serosurvey of chikungunya antibody in Calcutta metropolis.

Since its first isolation in Calcutta, in 1963, there have been many reports about epidemis of chikungunya virus infection in different parts of India. Calcutta experienced a concurrent epidemic of dengue and chikungunya between 1963 and 1965. But after that there is no report about any chikungunya infection in Calcutta. During routine investigations it is found that chikungunya antibody is on the wane. The present survey for chikungunya antibody showed only 4.37% (n = 17) seropositivity out of 389 sera tested. The highest (12.5%) seropositivity was observed in the age group of 51-55 years and no chikungunya antibody was detected in young and young adults. The findings suggest that chikungunya virus is disappearing from the Calcutta population.

Adolescent↗
PubMed1995

Effect of acute haemodilution on right atrial type-B receptor activity in anaesthetized cats.

In order to investigate whether the sensitivity of atrial type-B receptors to its natural stimulus is altered during acute haemodilution, experiments were conducted in nine anaesthetized, artificially ventilated and thoracotomized cats. Haemodilution was achieved by replacement of blood by the same volume of dextran (MW 150000). Atrial receptor activity, arterial blood pressure, right atrial pressure and ECG were recorded. Heart rate was calculated from ECG records. Arterial blood hematocrit was measured. Mean arterial blood pressure and heart rate were not altered by haemodilution even at a hematocrit level of 12.17 +/- 0.93 percent. Average activity of type-B atrial receptors, mean right atrial pressure, right atrial peak 'v' pressure, right atrial initial 'v' pressure and right atrial 'v' wave amplitude were changed significantly (r < 0.05) during acute haemodilution when the hematocrit was 12.17 +/- 0.93 percent but the atrial type-B receptor activity per cycle did not show any significant change. Average activity of type-B receptors increased from 8.56 +/- 1.02 spikes/sec to 9.56 +/- 1.11 spikes/sec. Mean right atrial pressure, right atrial 'v' wave amplitude, right atrial peak 'v' pressure increased significantly (P < 0.05) from respective control values. Right atrial initial 'v' wave pressure decreased significantly. Heart rate changed from 168.11 +/- 5.42 beats/min to 170.89 +/- 5.65 beats/min. Mean arterial pressure changed from 134.33 +/- 0.89 mmHg to 135.67 +/- 1.46 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1995

An institutional outbreak of hepatitis E--reported first time from Calcutta city.

A sudden outbreak of hepatitis occurred in a micro-epidemic form, amongst the staff members of the School of Tropical Medicine, Calcutta, during May-June, 1995. A total of 21 persons developed jaundice, out of whom 11 members who attended the Virology Department and were tested for detection of different serological markers of hepatitis by ELISA. All the sera (N = 11) showed evidence of non-A, non-B infection by process of exclusion and 9 of the above sera showed evidence of anti-HEV when tested specifically. This is the first documented outbreak of viral hepatitis in respect of Calcutta.

Adult↗
PubMed1994

(-)-Deprenyl alters the survival of adult murine facial motoneurons after axotomy: increases in vulnerable C57BL strain but decreases in motor neuron degeneration mutants.

The effect of (-)-deprenyl on the survival of axotomized adult murine facial motoneurons was investigated. Previously, (-)-deprenyl was shown to increase the number of rat facial motoneurons (FMns) surviving after axotomy at postnatal day 14, apparently by compensating for the loss of muscle-derived trophic factor. In the present study, three different strains of adult mice--A/J, C57BL/6J, and a congenic substrain of the C57BL/6J mice, the C57BL/Mnd mutants--underwent unilateral facial nerve transection. FMns were counted from serial sections taken through the entire length of the facial nuclei ipsilateral and contralateral to the facial nerve transections in animals sacrificed 21 days after axotomy. Subgroups of C57BL/6J and Mnd mutants were treated with either saline or 1.0 mg/kg (-)-deprenyl for 21 days. Another subgroup of Mnd mutants were treated with the metabolites of (-)-deprenyl, a mixture of (-)-amphetamine and (-)-methamphetamine, at a dosage equimolar to 1.0 mg/kg (-)-deprenyl. The number of surviving facial motoneurons in the A/J strain was 90% of unlesioned, control values which supports previous findings that adult FMns receive adequate trophic support and thus can survive loss of muscle-derived trophic support. In the C57BL/6J strain, the facial motoneuron survival was 35% and (-)-deprenyl increased the survival to 50.5%. Mnd mutants showed 62.4% survival; however, (-)-deprenyl decreased the number of motoneurons to 54.9% and amphetamine and methamphetamine treatment further decreased the motoneuron survival to 41.1%. These findings show that FMns in the Mnd mutants and their parental strain, C57BL/6J mice, show greater vulnerability to axotomy as compared to other adult strains of mice. The vulnerability is similar to that found in early postnatal life. (-)-Deprenyl increases the survival of the axotomized C57BL/6J FMns but its major metabolites, (-)-methamphetamine and (-)-amphetamine, further decrease FMn survival in the C57BL/Mnd mutants, possibly due to the induction of neurotoxic proteins causing programmed neuronal death. The efficacy of (-)-deprenyl in increasing the survival of damaged neurons would be expected to decrease as dosage increased above the dosage sufficient to induce maximum neuronal rescue (approximately 0.01 mg/kg) but would decrease as the dosage exceeded that necessary to produce toxic concentrations of the metabolites of (-)-deprenyl (1.0 mg/kg in this study).

Amphetamine↗
PubMed1994

Synthetic images by subspace transforms. I. Principal components images and related filters.

The principal component (PC) approach offers compressions of an image sequence into fewer images and noise suppressing filters. Multiple MR images of the same tomographic slice obtained with different acquisition parameters (i.e., with different TR, TE, and flip angles), time sequences of images in nuclear medicine, and cardiac ultrasound image sequences are examples of such input image sets. In this paper noise relationships of original and linearly transformed image sequences in general, and specifically of original, PC, and PC-filtered images are discussed. As the spinoff, it introduces locally weighted PC transforms and filters, nonlinear PC's, and a single-image based filter for suppression of noise. Examples illustrate increased perceptibility of anatomical/functional structures in PC images and PC-filtered images, including extraction of physiological functional information by PC loading curves. Generally, the more correlated the original images are, the more effective is the PC approach.

Diagnostic Imaging↗