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11.
Matthew B. Harms Janet Cady Craig Zaidman Paul Cooper Taha Bali Peggy Allred Carlos Cruchaga Michael Baughn Ryan T. Libby Alan Pestronk Alison Goate John Ravits Robert H. Baloh 《Neurobiology of aging》2013
Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue. 相似文献
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Tarun Bali Raghu Nagraj Malhar N Kumar Thomas Chandy 《Indian Journal of Orthopaedics》2015,49(6):615-619
Background:
The treatment of anterior cruciate ligament (ACL) injury consists of arthroscopic ACL reconstruction with patellar tendon or hamstring graft. Satisfactory results have been reported so far in the younger age group. Dilemma arises regarding the suitability of ACL reconstruction in patients aged 50 years and above. This retrospective analyses the outcome of ACL reconstruction in patients aged 50 years and above.Materials and Methods:
55 patients aged 50 years and above presented to our institution with symptomatic ACL tear and were managed with arthroscopic reconstruction with patellar tendon/hamstring graft. 22 patients underwent ACL reconstruction with bone- patellar tendon-bone graft and the remaining 33 with a hamstring graft. Evaluation of functional outcome was performed using International Knee Documentation Committee (IKDC) and Lysholm scoring in the preoperative period, at the end of 1 year and at the final followup. Radiographic evaluation was performed using the Kellgren–Lawrence grading system.Results:
The mean preoperative IKDC score was 39.7 ± 3.3. At the end of 1-year following the operation, the mean IKDC score was 73.6 ± 4.9 and at the final followup was 67.8 ± 7.7. The mean preoperative Lysholm score was 40.4 ± 10.3. At the end of 1-year following the intervention, the mean Lysholm score was 89.7 ± 2.1 and at final followup was 85.3 ± 2.5. Overall, 14 out of 42 patients who underwent radiographic assessment showed progression of osteoarthritis changes at the final followup after the intervention.Conclusion:
In our study, there was a statistically significant improvement in the IKDC and Lysholm scores following the intervention. There was a slight deterioration in the scores at the final followup but the overall rate of satisfaction was still high and most of the patients were able to do their routine chores and light exercises suitable for their age group. Around one-third of patients show progression of radiographic changes in the postoperative period and this requires long term evaluation. 相似文献15.
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Angiotensin and endogenous opioids are important bioactive neuropeptides, which are widely distributed in the brain and peripheral regions to produce diverse biological and neurobiological activities. An endogenous opioid system includes proopiomelanocortin-derived enkephalin, dynorphin and endorphin that act on their specific receptors such as delta (δ), kappa (κ) and mu (μ) receptors. Research evidence demonstrates significant positive as well as negative interactions between renin angiotensin system (RAS) and endogenous opioids in the brain and periphery. The diverse actions of Ang II are possibly mediated indirectly through endogenous opioids, while opioids are also shown to activate RAS components suggesting the up-regulation of each system in concern with each other. On the contrary, there are reports suggesting a negative correlation between RAS and opioid system. Research evidence also supports the notion that Ang II acts as anti-opioid peptide to decrease the actions of opioids. Moreover, opioids-induced decline in angiotensin release and functioning has also been reported. Co-administration of ACE inhibitors with opioids exhibits significant interactions possibly due to decreased metabolism of opioids leading to potentiation of their actions. The present review describes the complexities of positive and negative interactions between RAS and opioids along with possible mechanisms responsible for these interactions. 相似文献
18.
Singla R Caminero JA Jaiswal A Singla N Gupta S Bali RK Behera D 《The European respiratory journal》2012,39(4):956-962
Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB. 相似文献
19.
Regulatory genes linked to the albino locus in the mouse confer competence for inducible expression on the structural gene encoding serine dehydratase. 下载免费PDF全文
M Lia D Bali S Gluecksohn-Waelsch 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(6):2453-2455
A cluster of unlinked genes encoding gluconeogenic enzymes in the mouse is characterized by the failure of normal hormone-inducible expression in animals homozygous for one of several overlapping deletions mapping on chromosome 7 near the albino locus. Previous investigations have shown hormones and their receptors to be normal in the mutants and therefore not responsible for the abnormalities of inducibility. Instead, these studies have implicated a possible failure of the affected structural enzyme genes themselves to attain during prenatal development the competence for inducible gene expression. The results reported here add serine dehydratase (EC 4.2.1.13) and its structural gene to the affected group of gluconeogenic enzymes and their genes. Even though, in deletion homozygotes, serine dehydratase is expressed normally on the constitutive level, hormone-inducible expression fails to develop. The abnormality appears to reside in a defect of prenatal differentiation of cis-acting regulatory elements of the structural gene essential in the pathway of inducible gene expression. 相似文献
20.
M E Estevez L Sen R Vadez L M Bali?a 《International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association》1979,47(4):575-579
Patients with lepromatous leprosy possess a defective lymphocyte function in vivo and in vitro that is less evident in the tuberculoid form. Data concerning their macrophage ability to digest Mycobacterium leprae are controversial. The purpose of this study was to determine whether monocytes from patients with either tuberculoid or lepromatous leprosy were altered in their enzyme systems, that is myeloperoxidase-dependent and myeloperoxidase-independent systems. The ability of adherent blood monocytes to ingest and kill Candida pseudotropicalis after 30 and 60 min of incubation with yeast cells was tested. Mononuclear phagocytic cells from patients with either principal form of leprosy functioned similarly to normal monocytes in phagocytosis while their fungicidal activity for C. pseudotropicalis was statistically significantly altered and was more evident in the lepromatous than in the tuberculoid type. The results indicate that peripheral blood monocytes from patients with leprosy possess an impaired enzymatic candidacidal activity. 相似文献