Bcl-2 modulates telomerase activity

Apoptosis is a physiological mechanism of cell death that plays an important role in the regulation of tissue homeostasis. The regulation of apoptosis is a complex process and involves a number of gene products including the survival factor Bcl-2, which has been found to be frequently deregulated in human cancers. In addition to deregulation of apoptosis, the process of neoplasia is also believed to be driven by the activation of telomerase, a ribonucleoprotein complex that adds telomeric repeats (hexanucleotide 5′-TTAGGG-3′) to the ends of replicating chromosomes. Activation of telomerase has been detected in a vast majority of human cancer cells. Although recent studies have demonstrated the wide occurrence of telomerase activation and Bcl-2 deregulation in human cancer cells, it remains unclear whether there is any linkage between the deregulation of Bcl-2 and telomerase activity in cancer cells. In the studies presented here, we report that the stable overexpression of Bcl-2 in human cancer cells with low Bcl-2 expression was accompanied by increased levels of telomerase activity. In addition, using an IL-2-dependent cytotoxic T-cell line, CTLL-2, we demonstrated that IL-2 deprivation (8 h), which is known to down-regulate Bcl-2 expression, also resulted in concurrent inhibition of telomerase activity in the absence of any detectable apoptosis and accumulation of cells in the G0/G1phase of the cell cycle. Re-exposure of IL-2-deprived CTLL-2 cells to the recombinant IL-2 led to the up-regulation of both Bcl-2 expression and telomerase activity. Taken together, these findings establish a close linkage between the modulation of telomerase activity by survival factor Bcl-2, and provide a model to study regulation of telomerase activity by an anti-apoptotic pathway that is widely deregulated in cancer cells

Deep Multi-Branch CNN Architecture for Early Alzheimer's Detection from Brain MRIs

Alzheimer's disease (AD) is a neuro-degenerative disease that can cause dementia and result severe reduction in brain function inhibiting simple tasks especially if no preventative care is taken. Over 1 in 9 Americans suffer from AD induced dementia and unpaid care for people with AD related dementia is valued at $271.6 billion. Hence, various approaches have been developed for early AD diagnosis to prevent its further progression. In this paper, we first review other approaches that could be used for early detection of AD. We then give an overview of our dataset that was from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and propose a deep Convolutional Neural Network (CNN) architecture consisting of 7,866,819 parameters. This model has three different convolutional branches with each having a different length. Each branch is comprised of different kernel sizes. This model can predict whether a patient is non-demented, mild-demented, or moderately demented with a 99.05% three class accuracy.Comment: 11 pages, 7 figure

Study the incidence of abdominal malignancies presenting as acute abdomen: an observational study

Background: Acute abdomen is one of the most common symptoms that bring a patient to an emergency department. An abdominal malignancy may be the cause of acute abdomen at least in a number of cases. The problem with this is the poorer outcome associated with it due to the lack of preoperative evaluation and preparation and also possible contamination that occurs in case of a perforation. This study aimed at studying the incidence of abdominal malignancies in the patients presenting as acute abdomen and the various presentations in which they present. Materials and Methods: The study was conducted in the Department of General Surgery Indira Gandhi Institute of Medical Sciences, Patna, Bihar India. This study was done during from  March 2015 to July 2016.who required surgery for acute abdomen were taken for the study and the incidence of malignancy in these cases were statistically assessed. Results: Out of the 400 patients who were operated for non-traumatic acute abdomen 73 patients i.e. 18.25% were found to have intra-abdominal malignancy. Carcinoma colon was the commonest malignancy, 52.05%. Carcinoma stomach and rectum were the next most common malignancy. Commonest presentation was as a case of intestinal obstruction, 79.45% followed by perforation 23.28%. Conclusions: In the era were the incidence and early detection of abdominal malignancies are on a rise, a significant portion of these cases present with acute abdominal symptoms and the morbidity associated with such a presentation is of importance. Early detection of the disease by screening is the solution forthis.   Keywords: Abdominal malignancies, Incidence, Intestinal obstruction, Perforation

Negative pressure wound therapy in management of abdominal wound dehiscence: a case-control study

Background: Since the 1990’s, negative pressure wound therapy (NPWT) has been used to treat soft tissue defects, burn wounds, and to achieve skin graft fixation. In the field of abdominal surgery, the application of NPWT is increasing in cases with an open abdominal wound requiring temporary wound closure and a second look operation. In the present study, analyzed negative pressure wound therapy in management of abdominal wound dehiscence.Materials and Methods: The study was conducted in the Department of General Surgery Indira Gandhi Institute of Medical Sciences, Patna,Bihar India. This study was done during from Jan 2016 to December 2016.  Institutional ethical approval was obtained before conducting this study.A total of n=100 cases were included in this study.Out of n=100,50were taken as cases in whom intervention was done by applying VAC Therapy and 50 were taken as control in whom only NS dressing was done.Results:In this study major number of patients belonged to the age group between 40-60 years, Abdominal wound dehiscence were more common in males 71 cases (71%) than females 29 cases (29%). Male to female ratio was 2.4:1. The type abdominal wound dehiscence was most commonly partial thickness wound dehiscence 64 case (64%) and full thickness wound dehiscence were 36 (36%).  There was mean wound contraction of 0.82 cm in post VAC patients compared to0.13 cm in post ns dressing. there was significant decrease in wound sepsis of patient by application of negative pressure wound therapy and  patients with negative pressure wound therapy dressing has more number of healing by secondary intention and nil mortalityrate.Conclusion: NPWT significantly reduces the hospital stay of patients, it causes faster and higher degree of wound contraction, reduces wound sepsis thereby reducing morbidity of patient. Keywords: Abdominal wound dehiscence, Negative pressure wound therapy, Vaccum assisted closure

Assessment of Acute biliary pancreatitis: a prospective observational hospital-based study

Background: Pancreatitis is quite common problem, it may present either as abdominal emergency with fulminant course or as an indolent process leading to long-term medical as well as surgical complications often leading to poor prognosis if not intervened timely. Methods:This was a prospective hospital based observational study conducted at  Department of General Surgery, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India.from November 2015 to July 2016. All cases of ABP admitted over a period of one year were included in the study. The clinical presentation, severity and course of the disease, imaging studies, duration of ICU and hospital stay and timing of ERCP and cholecystectomy were studied. Results: A total of 100 cases were included in the study. Average age was 53.45 years. Pain abdomen was the most common symptom at presentation. About 88% patients had mild to moderate disease while the rest had severe disease. The mean duration of intensive care unit stay was 8-10 days. ERCP was done in 12 cases. Cholecystectomy during the same admission was done in 34 cases. Conclusion: Early intervention definitely reduces morbidity, mortality and recurrent admissions in cases of acute biliary pancreatitis. Same admission laparoscopic cholecystectomy is preferable in mild ABP. All cases of severe ABP must undergo early ERCP irrespective of biliary obstruction. Keywords: pneumonia, hyponatremia, sodium level, children

Study of spectrum and clinical profile of benign breast disease in the rural area: an observational study

Background: Recent understanding of pathophysiology and health awareness may have impact on spectrum of benign breast disease (BBD) in rural area. We have analyzed clinical data of 200 cases of BBD for spectrum and clinical profile to compare with present studies.Materials and Methods: This was a clinical study conducted at Department of General Surgery at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. which is located in rural area. This study was done during  from April 2015 to March 2016. Patients presented with different breast related problems like lump in breast, nipple discharge, associated fever and mastalgia were admitted in surgical ward for evaluation.Results: A total of 200 females were included in the study. Fibroadenoma 79(39.5%) and fibroadenosis 49(24.5%) were the commonest diseases, both presenting mostly at 20-30years of age. Left side involvement was most common. The commonest presentation was breast lump which comprised (82%) cases, patients with breast lump 82%, patients with breast pain 36.5% and patients with nipple discharge 3.5%. Conclusion: Benign breast diseases are common problems of 2nd and 3rd decade in females and raises considerable fear of malignancy. The patients of BBDs generally present with one or more of these complaints – breast lump, breast pain or nipple discharge. All the patients with discrete breast lumps should undergo a triple assessment to make an early diagnosis. Key words: Benign breast diseases, Fibroadenoma, Fibrocystic disease, Mastitis

An Application of Artificial Neural Network (ANN) for Landslide Hazard Mapping, Susceptibility and Early Warning System: A Review

An Application of ANN for Landslide Early Warning System in Darjeeling hill regio

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

Homeostasis in colonic epithelial cells is regulated by the balance between proliferative activity and cell loss by apoptosis. Because epithelial cells at the apex of colonic crypts undergo apoptosis and proliferative activity is usually restricted to the base of the crypts, it has been proposed that the limited availability of growth factor-signals at the upper portions of the crypts may trigger apoptosis. In the present studies, we investigate the mechanism of apoptosis mediated by growth factor deprivation in colorectal carcinoma cells by delineating the possible involvement of Bax and its subcellular localization. We report that inhibition of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity and downregulation of EGFR by anti-EGFR mAb 225 induces apoptosis in human colorectal carcinoma DiFi and FET cells. Induction of apoptosis was preceded by enhanced expression of newly synthesized Bax protein, and required protein synthesis. In the mAb 225-treated cells, Bax was redistributed from the cytosol to the nucleus and subsequently, to the nuclear membranes. The observed induction of Bax expression by mAb 225 was not associated with p53 induction. However, mAb 225 treatment also triggered relocalization of p53 from the cytosol to a nuclear membrane-bound form. Induction of Bax and its redistribution to the nucleus of DiFi cells during apoptosis was also demonstrated in response to butyrate, a physiological relevant molecule in colonic epithelial cells as it is the principal short-chain fatty acid produced by bacterial fermentation of dietary fiber in colonic epithelium. Using immunofluorescence and confocal microscopy, we observed that Bax is predominantly localized in the cytosol, but during apoptosis it is localized both inside and along the nuclear membrane. Taken together, these findings suggest that apoptosis induced by growth factor-deprivation or butyrate may involve the subcellular redistribution of Bax in human colorectal carcinoma cells

Heregulin induces expression, DNA binding activity and transactivating functions of basic leucine zipper activating transcription factor 4

Heregulin β1 (HRG), a combinatorial ligand for human epidermal growth factor receptor 3 and human epidermal growth factor receptor 4 receptors, is a regulatory secretory polypeptide with distinct biological effects such as growth stimulation, differentiation, invasiveness and migration in breast cancer cells. The mechanism underlying the diverse functions of HRG is not well established, but it is believed to be dependent on the induced changes in expression of specific cellular gene products, their modification, or both. The binding of basic leucine zipper transcription factors to the cAMP response element is known to activate a variety of gene products with a role or roles in growth regulation. In the studies presented here, we identified basic leucine zipper Activating Transcription Factor (ATF) 4 as one of the HRG-inducible gene product. We demonstrated that HRG stimulation of human cancer cells induces expression of ATF4 mRNA and protein, ATF4 DNA binding activity and ATF4 transactivating function. Consistent with its role as a transcriptional activator, HRG-stimulated ATF4 protein stimulated the transcription from an artificial promoter with three tandem ATF sites or from a naturally occurring promoter with ATF4 sites such as E-selectin. We also demonstrated a preferential role of the HRG-stimulated mitogen-activated protein kinase pathway, but not the phosphatidylinositol 3′-kinase pathway, in supporting the observed increase in ATF4 DNA binding activity and transcription from E-selectin promoter in HRG-stimulated cells. Because ATF4 binding sites are present in a variety of growth-regulating cellular genes, these findings suggest that the stimulation of ATF4 expression and its transactivating functions may constitute an important mechanism of HRG-mediated regulation of putative genes with diversified functions. The present study is the first demonstration of regulation of expression and transactivation ability of ATF4 by any polypeptide growth factor