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991.
Clinical Applications and Implications of Common and Founder Mutations in Indian Subpopulations 下载免费PDF全文
C. Alexander Valencia Krishna K. Rayam Manisha M. Kumar Madhuri R. Hegde 《Human mutation》2015,36(1):1-10
South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current‐day Indian population. With the evolving socio‐religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal‐recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first‐hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective. 相似文献
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Manisha K. Shah Iris H. Garcia-Pak Eric M. Darling 《Annals of biomedical engineering》2017,45(8):2036-2047
Understanding the role of mechanophenotype in competitive adherence of cells to other cells versus underlying substrates can inform such processes as tissue development, cancer progression, and wound healing. This study investigated how mechanophenotype, defined by whole-cell, elastic/viscoelastic properties for the perinuclear region, and cellular assembly are intertwined through the mechanosensing process. Atomic force microscopy was used to characterize the temporal elastic/viscoelastic properties of individual and assembled fibroblasts grown on substrates with elastic moduli above, below, or similar to whole-cell mechanophenotypes measured for three, genetically modified cell lines. All cells were at their most compliant immediately after plating but transitioned to distinct, stiffer mechanophenotypes by Day 1 after acclimation. This mechanical state, and cellular assembly/morphology, did not change significantly over the following three days of testing, regardless of substrate compliance or cellular organization (multi-cell nodules/plaques or single cells). Interestingly, cells formed 3D nodules when attached to substrates with elastic moduli less than their own but spread readily on substrates with moduli equal to or greater than their own, suggesting a preference to adhere to the stiffest surface sensed (substrate or cell). This suggests that inherent mechanophenotype plays a role as a competing surface during microenvironment mechanosensing and subsequent cell–cell-substrate organization. 相似文献
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Vinod D. Umare Vandana D. Pradhan Anjali G. Rajadhyaksha Manisha M. Patwardhan Kanjaksha Ghosh Anita H. Nadkarni 《Human immunology》2017,78(2):201-208
The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (?308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α ?308A (OR = 2.3, p = 0.0001, Pc = 0.0003) and LTα +252G (OR = 2.1, p < 0.0001, Pc < 0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR = 12.2, p = 0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α ?308G/A + A/A genotypes (p < 0.01) and LTα +252 A/G + G/G genotypes (p < 0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with ?308G/A + A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR = 3.9, p = 0.0014, Pc = 0.0098) and anti-Sm antibodies (OR = 4.1, p = 0.0002, Pc = 0.0014). The present study suggests TNF-α ?308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients. 相似文献
996.
All cases of cholera that have occurred at our center in north India have been due to Vibrio cholerae O1 serotype Ogawa, including the outbreaks in 2002 and 2004. Here we report the emergence of V. cholerae O1 biotype El Tor serotype Inaba for the first time in this region since July 2004. Fifteen Inaba isolates were obtained from 32 patients suffering from cholera-like illness. The patients lived in Chandigarh and the neighboring states of Punjab, Haryana, and Himachal Pradesh. All strains were resistant to nalidixic acid and trimethoprim, and showed moderate sensitivity to amoxycillin. All were sensitive to ciprofloxacin, tetracycline, cefotaxime, amikacin, and gentamicin. All strains were found to be toxigenic when tested with a commercial reverse passive latex agglutination kit. The last reported Inaba isolate dominance in India was observed in Calcutta in 1989. There is a need to closely watch the spread of serotype Inaba, as it may cause outbreaks in other parts of India; molecular studies are warranted to understand the widespread emergence of Inaba in north India. 相似文献
997.
Vassili Valayannopoulos Vera Malinova Tomas Honzík Manisha Balwani Catherine Breen Patrick B. Deegan Gregory M. Enns Simon A. Jones John P. Kane Eveline O. Stock Radhika Tripuraneni Stephen Eckert Eugene Schneider Gavin Hamilton Michael S. Middleton Claude Sirlin Bruce Kessler Christopher Bourdon Simeon A. Boyadjiev Reena Sharma Chris Twelves Chester B. Whitley Anthony G. Quinn 《Journal of hepatology》2014
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Kapil Sharma Sanjay Pant Sriprakash Misra Manisha Dwivedi Alok Misra Sushil Narang Reshu Tewari Ajeet S. Bhadoria 《Saudi Journal Of Gastroenterology》2014,20(4):225-232
Background/Aims:
Minimal hepatic encephalopathy (MHE) implies subtle impairment of cognitive functions in the absence of features of overt encephalopathy. We aimed to determine the prevalence of MHE in patients with liver cirrhosis and to find out the effect of rifaximin, probiotics, and l-ornithine l-aspartate (LOLA) individually in reversal of MHE by comparing it with placebo group.Patients and Methods:
This study was carried out in two phases. Phase I included the recruitment of 250 apparently healthy controls and extraction of normative data utilizing three neuropsychometric tests (NPTs) and critical flicker frequency (CFF) test. Phase II consisted of screening and recruitment of patients of MHE followed by drugs trial. A total of 317 cirrhotics were screened; 111 were excluded and the remaining 206 cirrhotics were screened for MHE using NPTs and/or CFF test. Of these, 124 patients with MHE were randomized to receive LOLA (n = 31), rifaximin (n = 31), probiotics (n = 32), for 2 months and were compared with patients who were given placebo (n = 30).Results:
Out of 206 cirrhotics, 124 (60.19%) had MHE. Among these 124 MHE patients, 87 (70.16%) patients had CFF <39Hz, 112 (90.32%) patients with MHE had two or more abnormal NPTs, and 75 (60.48%) patients had abnormality on both the CFF values and more than two abnormal NPTs. Intention-to-treat analysis showed the number of patients who improved after giving treatment were 67.7% (21/31), 70.9% (22/31), 50% (16/32), and 30% (9/30) for LOLA, rifaximin, probiotics, and placebo, respectively. CFF scores and improvement in psychometric tests after treatment were significantly higher (P < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group.Conclusions:
Prevalence of MHE is high in patients with cirrhosis of liver. Rifaximin, LOLA, and probiotics are better than giving placebo in patients with MHE. 相似文献1000.
Arvind Pandey Satyendra Chandra Tripathi Sutapa Mahata Kanchan Vishnoi Shirish Shukla Sri Prakash Misra Vatsala Misra Suresh Hedau Ravi Mehrotra Manisha DwivediZ Alok C Bharti 《World journal of gastroenterology : WJG》2014,20(22):6860-6868
AIM:To investigate the low gastric cancer incidence rate relative to the highly prevalent Helicobacter pylori(H.pylori)infection;data relevant to H.pylori infection during gastric carcinogenesis in Indian patients is currently lacking.METHODS:The present study examines the prevalence of H.pylori infection in DNA derived from 156endoscopic gastric biopsies of different disease groups that represent gastric pre-cancer[intestinal metaplasia(n=15),dysplasia(n=15)],cancer[diffuse adenocarcinoma(n=44),intestinal adenocarcinoma(n=21)],and symptomatic but histopathologically-normal controls(n=61).This was done by generic ureC polymerase chain reaction(PCR)and cagA-specific PCR that could specifically identify the carcinogenic H.pylori strain.RESULTS:Our analysis showed the presence of H.pylori infection in 61%of symptomatic histopathologically-normal individuals,however only 34%of control tissues were harboring the cagA+H.pylori strain.A similar proportion of H.pylori infection(52%)and cagA(26%)positivity was observed in the tumor tissue of the gastric cancer group.In comparison,H.pylori infection(90%)and cagA positivity(73%)were the highest in gastric pre-cancer lesions.In relation to tobacco and alcohol abuse,H.pylori infection showed an association with tobacco chewing,whereas we did not observe any association between tobacco smoking or alcohol abuse with prevalence of H.pylori infection in the tissue of any of the patient groups studied.CONCLUSION:High incidence of H.pylori infection and carcinogenic cagA positive strain in pre-cancer lesions during gastric carcinogenesis may be associated 相似文献