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31.
J G Sutcliffe R J Milner F E Bloom R A Lerner 《Proceedings of the National Academy of Sciences of the United States of America》1982,79(16):4942-4946
Several randomly selected cDNA clones made from rat brain polyA+RNA have unusual properties. Although the cDNA inserts are 500-1,250 base pairs long, they hybridize to a 160-nucleotide RNA species that is present in brain but not in liver or kidney. Nucleotide sequence studies of two of the clones and hybridization studies show that a common 82-nucleotide sequence is responsible for the hybridization. The same sequence is located in the second intron of a rat growth hormone gene. These studies suggest that signals called "ID sequences" may be carried in the introns of genes and prescribe their tissue-specific expression. 相似文献
32.
Nabila Seddiki Chansavath Phetsouphanh Sanjay Swaminathan Yin Xu Sudha Rao Jasmine Li Elissa L. Sutcliffe Gareth Denyer Robert Finlayson Linda Gelgor David A. Cooper John Zaunders Anthony D. Kelleher 《European journal of immunology》2013,43(2):510-520
The fine control of T‐cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1/Prdm1) is highly expressed in CD4+ T cells from chronically HIV‐infected (CHI) patients compared to cells from long‐term nonprogressors or healthy controls. Stimulation through the T‐cell receptor in the presence ofIL‐2 induces Blimp‐1 protein expression. We show here that Blimp‐1 levels are translationally regulated by microRNA‐9 (miR‐9). Overexpression of miR‐9 induces Blimp‐1 repression, restoring IL‐2 secretion in CD4+ T cells via reduction in the binding of Blimp‐1 to the il‐2 promoter. In CHI patients where IL‐2 expression is reduced and there is generalized T‐cell dysfunction, we show differential expression of both miR‐9 and Blimp‐1 in CD4+ cells compared with levels in long‐term nonprogressors. These data identify a novel miR‐9/Blimp‐1/IL‐2 axis that is dysregulated in progressive HIV infection. 相似文献
33.
Whether or not mechanisms underlying circadian locomotor rhythms and learning are related anatomically through the mushroom bodies (MBs) was investigated by monitoring behavioral rhythmicity in flies with MB lesions induced by chemical ablation and by mutations in five different genes. All flies tested were later examined histologically to assess (1) MB neuroanatomy, and (2) the condition of the putative pacemaker cells -- the ventral Lateral Neurons (LN v s) and their terminals that project to the vicinity of the MB calyces. All groups of flies had normal rhythms except for mushroom body miniature ( mbm ; only in a wild-type Berlin genetic background) and mushroom body defect ( mud ). MB ablation had no effect on the gender-specific differences in the rhythmic activity profile that are typical of wild-type flies. However, ablated males had a slightly longer period than untreated males and were more active under constant dark conditions. LN v s and their arborization patterns appeared normal in MB-ablated and in most mutant flies. Activity defects of mbm flies were attributed to genetic background rather than to the mutation alone. Misrouted LN v projections and ~14% arrhythmia of mud flies were uncorrelated and attributed to pleiotropy rather than to specific effects of MB lesions. Our results imply that MBs are not involved in circadian activity rhythms but that they do have an inhibitory effect on activity levels of male flies. 相似文献
34.
Bash RO; Crist WM; Shuster JJ; Link MP; Amylon M; Pullen J; Carroll AJ; Buchanan GR; Smith RG; Baer R 《Blood》1993,81(8):2110-2117
Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study. 相似文献
35.
Influence of Smoking Dosage and Chronic Obstructive Lung Disease on the Incidence of Appropriate Therapies and Mortality in Patients with Structural Heart Disease and an Implantable Cardioverter Defibrillator 下载免费PDF全文
36.
37.
Narendra Battula Dimitrios Tsapralis David Mayer John Isaac Paolo Muiesan Robert P Sutcliffe Simon Bramhall Darius Mirza Ravi Marudanayagam 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(2):157-163
Objectives: Isolated intrahepatic recurrence is noted in up to 40% of patients following curative liver resection for colorectal liver metastases (CLM). The aims of this study were to analyse the outcomes of repeat hepatectomy for recurrent CLM and to identify factors predicting survival.Methods: Data for all liver resections for CLM carried out at one centre between 1998 and 2011 were analysed.Results: A total of 1027 liver resections were performed for CLM. Of these, 58 were repeat liver resections performed in 53 patients. Median time intervals were 10.5 months between the primary resection and first hepatectomy, and 15.4 months between the first and repeat hepatectomies. The median tumour size was 3.0 cm and the median number of tumours was one. Six patients had a positive margin (R1) resection following first hepatectomy. There were no perioperative deaths. Significant complications included transient liver dysfunction in one and bile leak in two patients. Rates of 1-, 3-and 5-year overall survival following repeat liver resection were 85%, 61% and 52%, respectively, at a median follow-up of 23 months. R1 resection at first hepatectomy (P = 0.002), a shorter time interval between the first and second hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were associated with significantly worse overall survival.Conclusions: Repeat resection of CLM is safe and can achieve longterm survival in carefully selected patients. A preoperative knowledge of poor prognostic factors helps to facilitate better patient selection. 相似文献
38.
Keith J Roberts Georgina Blanco Jonathan Webber Ravi Marudanayagam Robert P Sutcliffe Paolo Muiesan Simon R Bramhall John Isaac Darius F Mirza 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(9):814-821
Objectives
Total pancreatectomy (TP) is associated with significant morbidity and mortality. The severity of postoperative diabetes and existence of ‘brittle diabetes’ are unclear. This study sought to identify quality of life (QoL) and diabetes-specific outcomes after TP.Methods
Patients who underwent TP were matched for age, sex and duration of diabetes with patients with type 1 diabetes. General QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire QLQ-C30 and the PAN26 tool. Diabetes-specific outcomes were assessed using the Problem Areas in Diabetes (PAID) tool and an assessment of diabetes-specific complications and outcomes.Results
A total of 123 patients underwent TP; 88 died (none of diabetic complications) and two were lost to follow-up. Of the remaining 33 patients, 28 returned questionnaires. Fourteen general and pancreas-specific QoL measurements were all significantly worse amongst the TP cohort (QLQ-C30 + PAN26). However, when diabetes-specific outcomes were compared using the PAID tool, only one of 20 was significantly worse. HbA1c values were comparable (P = 0.299), as were diabetes-related complications such as hypoglycaemic attacks and organ dysfunction.Conclusions
Total pancreatectomy is associated with impaired QoL on general measures compared with that in type 1 diabetes patients. Importantly, however, there was almost no significant difference in diabetes-specific outcomes as assessed by a diabetes-specific questionnaire, or in diabetes control. This study does not support the existence of ‘brittle diabetes’ after TP. 相似文献39.
Cardiovascular Risk Factors in Women With Primary Sjögren's Syndrome: United Kingdom Primary Sjögren's Syndrome Registry Results 下载免费PDF全文
40.
Celestino-Soper PB Violante S Crawford EL Luo R Lionel AC Delaby E Cai G Sadikovic B Lee K Lo C Gao K Person RE Moss TJ German JR Huang N Shinawi M Treadwell-Deering D Szatmari P Roberts W Fernandez B Schroer RJ Stevenson RE Buxbaum JD Betancur C Scherer SW Sanders SJ Geschwind DH Sutcliffe JS Hurles ME Wanders RJ Shaw CA Leal SM Cook EH Goin-Kochel RP Vaz FM Beaudet AL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):7974-7981
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. 相似文献