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101.
Molly A. Hall Shefali S. Verma John Wallace Anastasia Lucas Richard L. Berg John Connolly Dana C. Crawford David R. Crosslin Mariza de Andrade Kimberly F. Doheny Jonathan L. Haines John B. Harley Gail P. Jarvik Terrie Kitchner Helena Kuivaniemi Eric B. Larson David S. Carrell Gerard Tromp Tamara R. Vrabec Sarah A. Pendergrass Catherine A. McCarty Marylyn D. Ritchie 《Genetic epidemiology》2015,39(5):376-384
Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset. 相似文献
102.
103.
Kunal Pradip Verma MBBS David Adam MBBS FRACP 《Pacing and clinical electrophysiology : PACE》2018,41(10):1381-1383
A 62‐year‐old male presented to his treating cardiologist for routine interrogation of his implantable cardiac defibrillator on the background of severe ischemic cardiomyopathy and end‐stage kidney disease on hemodialysis. The device log revealed multiple paroxysms of atrial fibrillation; however, upon scrutinizing these episodes it was evident that they always corresponded to episodes of hemodialysis while dialyzing through a chronic dialysis catheter, but not while dialyzing via an arteriovenous fistula. We report the novel finding of inappropriate sensing of current leak from the catheter by a lead with a floating atrial dipole. 相似文献
104.
Harmanjot?Kaur Shanti?Choudhary Devendra?Pathak Opinder?Singh Ramneek?Verma Ratan?K.?ChoudharyEmail author 《Proceedings of the National Academy of Sciences, India. Section B.》2018,88(1):23-32
Water buffaloes are the principle source of milk in south Asia and Africa. Mammary gland repeatedly undergoes the cycles of growth and regeneration during pregnancy, lactation and involution. It is assumed that buffalo mammary gland has mammary stem and progenitor cells that regulate gland growth and regeneration. In the present study the authors analyzed percentage of cellular composition, proliferation status and putative mammary stem/progenitor cell population. Identification of putative buffalo mammary stem/progenitor cells was attempted using immunohistochemical staining with Musashi1 (MSI1), an adult stem cell marker and fibronectin type III domain containing 3B (FNDC3B), a mammary stem and cancer cell marker. Immunolocalization of MSI1 and FNDC3B showed nuclear and cytoplasmic staining of alveolar and ductal mammary epithelial cells (MEC) and a few stromal cells. The percentage of MSI1-positive MEC in non-lactating (3.31 ± 1.11 %), lactating (2.73 ± 0.78 %) and mastitic glands (3.30 ± 0.97 %) were equivalent, indicating that the proportion of putative stem/progenitor cell population did not differ during various physiological stages. Likewise, the percentage of FNDC3B-positive MEC in non-lactating (12.40 ± 3.22 %) tended to be higher than lactating (8.19 ± 2.71 %) and mastitic glands (4.88 ± 2.37 %). In some cases, expression of MSI1 and FNDC3B was exceptionally high with high proliferative indices (37.6 ± 2.4 %)-an indication of tumor cells. This is the first report on expression of MSI1 and FNDC3B in buffalo mammary gland. Identification of buffalo mammary stem cells using MSI1 and FNDC3B requires further studies and functional validation. 相似文献
105.
Vikas Kumar Kalicharan Sharma Bahar Ahmed F. A. Al-Abbasi Firoz Anwar Amita Verma 《RSC advances》2018,8(32):18180
Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases. A wide range of chemical constituents, such as triterpenoid saponin, kauren diterpene, and coumestans, has been isolated from the plant. Conversely, no published literature is available in relation to the isolation of wedelolactone (WEL) for its anti-diabetic effect. The aim of the present study was to isolate the bioactive phyto-constituent from Wedelia calendulacea and to scrutinize the antidiabetic effect with its possible mechanism of action. The structure of the isolated compound was elucidated by different spectroscopy techniques. Proteins, such as dipeptidyl peptidase-4 (DPPIV), glucose transporter 1 (GLUT1), and peroxisome proliferator-activated receptors-γ (PPARγ), were also subjected to in silico docking. Later, this isolated compound was scrutinized against α-glucosidase and α-amylase enzyme activity along with an oral glucose tolerance test (OGTT) for estimation of glucose utilization. Streptozotocin (STZ) was used for the induction of type II diabetes mellitus (DM) in Wistar rats. The rats were divided into different groups and received the WEL (5, 10, and 20 mg kg−1, b.w.) and glibenclamide (2.5 mg kg−1, b.w.) for 28 days. The blood glucose level (BGL), plasma insulin, and body weight were determined at regular time intervals. The serum lipid profile hypolipidemic effect for the different antioxidant markers and hepatic tissue markers were scrutinized along with an inflammatory mediator to deduce the possible mechanism. With the help of spectroscopy techniques, the isolated compound was identified as wedelolactone. In the docking study, WEL showed docking scores of −6.17, −9.43, and −7.66 against DPP4, GLUTI, and PRARY, respectively. WEL showed the inhibition of α-glucosidase (80.65%) and α-amylase (93.83%) and suggested an effect on postprandial hyperglycemia. In the OGTT, WEL significantly (P < 0.001) downregulated the BGL, a marker for better utilization of drugs. In the diabetes model, WEL reduced the BGL and enhanced the plasma insulin and body weight. It also significantly (P < 0.001) modulated the lipid profile; this suggested an anti-hyperlipidemia effect. WEL significantly (P < 0.001) distorted the hepatic tissue, acting as an antioxidant marker in a dose-dependent manner. WEL significantly (P < 0.001) downregulated the C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) level. On the basis of the available results, we can conclude that WEL can be an alternative drug for the treatment of type II DM either by inhibiting the production of inflammatory mediator or by the downregulation of oxidative stress. Wedelia calendulacea has a long history of use in the Indian Ayurvedic System of Medicine for the treatment, prevention, and cure of a diverse range of human diseases such as diabetes obesity, and other metabolic diseases. 相似文献
106.
Saurabh Shukla Anil Kumar Tripathi Shailendra Prasad Verma Deependra Kumar Yadav R. K. Tripathi Shweta Maurya Nidhi Awasthi 《Indian journal of hematology & blood transfusion》2021,37(2):210
Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA. 相似文献
107.
Enes Elvin Gul MD Rajiv A. Kabadi MD Santosh K. Padala MD Paula Sanchez Somonte MD Jordana Kron MD Richard K. Shepard MD Jayanthi N. Koneru MD Gautham Kalahasty MD Maria Terricabras MD Bernice Tsang MD Yaariv Khaykin MD Zaev Wulffhart MD Alfredo Pantano MD Kenneth A. Ellenbogen MD Atul Verma MD 《Journal of cardiovascular electrophysiology》2021,32(9):2515-2521
108.
109.
U. Blmer T. Kafri L. Randolph-Moore I. M. Verma F. H. Gage 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(5):2603-2608
Bcl-xL suppresses apoptotic cell death induced by diverse stimuli in cell lines in vitro. To examine the mechanism by which axotomized cholinergic neurons die in vivo, lentiviral vectors expressing Bcl-xL, human nerve growth factor (hNGF), or green fluorescent protein were injected into the septum 3 weeks before transection of the fimbria fornix. Three weeks after transection, Bcl-xL- and hNGF-injected animals showed significantly higher numbers of spared cholinergic neurons compared with control (green fluorescent protein) injected animals. These results provide evidence that adult axotomized cholinergic neurons die of apoptotic death that can be prevented by local delivery of hNGF or intracellular delivery of Bcl-xL. 相似文献
110.
Airway responsiveness to inhaled histamine in chronic obstructive airways disease. Chronic bronchitis vs emphysema 总被引:1,自引:0,他引:1
Airway responsiveness to inhaled histamine was examined in two groups of carefully selected patients with nonasthmatic chronic obstructive airways disease (COAD). Twelve patients with chronic bronchitis and airflow obstruction but little emphysema and 13 with predominantly emphysema and airflow obstruction but little bronchitis were selected based on history, chest roentgenogram, and diffusing capacity for carbon monoxide (Dsb). Emphysema patients had less cough, less sputum, less chronic bronchitis, lower Dsb, and more radiographic evidence of vascular deficiency. There was no difference in anthropometric features, smoking history, atopic skin sensitivity, hemoglobin, blood eosinophilia, PaO2, PaCO2, ECG, lung volumes, or expiratory flow rates. The two groups had similar airway responsiveness to inhaled histamine; the geometric mean provocation concentrations producing a 20 percent FEV1 fall (PC20) was 0.56 mg/ml for the bronchitis patients and 0.28 mg/ml for the emphysema patients (p greater than 0.20). Regression of log histamine PC20 vs percent predicted FEV1 showed a high correlation in both groups (r = 0.73, p less than 0.01 in bronchitis and r = 0.79, p less than 0.001 in emphysema). The regression lines were almost identical. These data suggest that in COAD bronchial responsiveness to inhaled histamine is mainly due to the altered airway geometry, and that there is no difference in histamine responsiveness between patients with emphysematous COAD and nonemphysematous COAD with chronic bronchitis. 相似文献