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661.
662.
Rodríguez-Ballesteros M del Castillo FJ Martín Y Moreno-Pelayo MA Morera C Prieto F Marco J Morant A Gallo-Terán J Morales-Angulo C Navas C Trinidad G Tapia MC Moreno F del Castillo I 《Human mutation》2003,22(6):451-456
Inherited hearing impairment affects one in 2,000 newborns. Nonsyndromic prelingual forms are inherited mainly as autosomal recessive traits, for which 16 genes are currently known. Mutations in the genes encoding connexins 26 and 30 account for up to 50% of these cases. However, the individual contribution of the remaining genes to the whole remains undetermined. In addition, for most of the genes there is a need for studies on genotype-phenotype correlations, to identify distinctive clinical features which may direct the molecular diagnosis to specific genes. Here we present a mutation analysis and a genotype-phenotype correlation study on the gene encoding otoferlin (OTOF), responsible for the DFNB9 subtype of prelingual hearing impairment. Four novel mutations were identified: c.2122C>T (p.Arg708Ter), c.4275G>A (p.Trp1425Ter), c.4362+2T>G, and c.5860_5862delATC (p.Ile1954del). A total of 37 subjects with mutations in OTOF were studied clinically. They were phenotypically homogeneous, having profound hearing impairment with very early onset, as shown by pure-tone audiometry and auditory brainstem responses. Magnetic resonance imaging and computed tomography did not reveal any inner ear malformation. Unexpectedly, transient evoked otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally in 11 subjects. Altogether, clinical data of these subjects met the diagnostic criteria of auditory neuropathy. A total of 10 subjects had been successfully provided with cochlear implants. The results of our study indicate that genetic diagnosis of subjects with auditory neuropathy and profound hearing impairment should be directed to the otoferlin gene. Our data are of concern to universal screening programs which use TEOAEs as the first detection test for hearing impairment in newborns, since this technique may overlook a nonnegligible proportion of cases. 相似文献
663.
Generation of chicken single chain antibody variable fragments (scFv) that differentiate and neutralize infectious bursal disease virus (IBDV) 总被引:1,自引:0,他引:1
Sapats SI Heine HG Trinidad L Gould GJ Foord AJ Doolan SG Prowse S Ignjatovic J 《Archives of virology》2003,148(3):497-515
Summary. Phage-displayed recombinant antibody libraries derived from splenic mRNA of chickens immunized with an Australian strain
of infectious bursal disease virus (IBDV) were constructed as single chain variable fragments (scFv) by either overlap extension
polymerase chain reaction (PCR) or sequential ligation of the individual heavy (VH) and light (VL) chain variable gene segments. Sequential cloning of the individual VH and VL genes into a newly constructed pCANTAB-link vector containing the synthetic linker sequence (Gly4Ser)3 was more efficient than cloning by overlap extension PCR, increasing the library size 500 fold. Eighteen IBDV specific antibodies
with unique scFv sequences were identified after panning the library against the immunizing antigen. Eight of the clones contained
an identical VH gene but unique VL genes. In ELISA analysis using a panel of Australian and overseas IBDV strains, one scFv antibody was able to detect all
strains, whilst 3 others could discriminate between Australian and overseas strains, classical and variant strains and Australian
field strains and vaccine strains. In addition, some scFvs showed significant neutralization titres in vitro. This report shows that generation of chicken antibodies in vitro by recombinant means has considerable potential for producing antibodies of diverse specificity and neutralizing capacity.
Received July 2, 2002; accepted September 23, 2002 相似文献
664.
de Portugal-Alvarez José Clamagirand Carlos Perezagua Souto José M. Catalán Edgardo Vila Trinidad Velasco-Martín Alfonso 《Acta diabetologica》1974,11(1):1-8
Acta Diabetologica - A significant negative correlation has been found in severe cirrhotics between HGH and proteinemia and HGH and albuminemia 60 min after insulin injection, as well as a... 相似文献
665.
666.
Clara Esteban-Jurado Pilar Garre Maria Vila Juan José Lozano Anna Pristoupilova Sergi Beltrán Anna Abulí Jenifer Muoz Francesc Balaguer Teresa Ocaa Antoni Castells Josep M Piqué Angel Carracedo Clara Ruiz-Ponte Xavier Bessa Montserrat Andreu Luis Bujanda Trinidad Caldés Sergi Castellví-Bel 《World journal of gastroenterology : WJG》2014,20(8):1961-1971
Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis. 相似文献
667.
Natalia Zambudio Karim Muffak Trinidad Villegas Antonio Becerra Yillian Fundora Daniel Garrote Antonio Ferrón 《Central European Journal of Medicine》2014,9(4):594-600
Introduction
We review the most recent advances in the management of pancreatitis following publication of the latest clinical practice guidelines. The most significant innovations have taken place in the surgical treatment of pancreatitis, specifically regarding when a patient should be intervened and what procedure should be used. Moreover, changes that have occurred in the classification of pancreatitis seek to harmonize diagnostic criteria and facilitate comparisons among centers.Methods
We reviewed three of the latest guidelines and review articles published since 2008 following an electronic search through Medline, Embase and the Cochrane Library.Conclusions
Although diverse guidelines and review articles coincide on many key points, they need to be updated with regard to the numerous surgical innovations that have emerged recently in the management of pancreatitis. 相似文献668.
The yield,reliability, and validity of a postal survey for screening community-dwelling older people
Alessi CA Josephson KR Harker JO Pietruszka FM Hoyl MT Rubenstein LZ 《Journal of the American Geriatrics Society》2003,51(2):194-202
OBJECTIVES: To assess the yield, reliability, and validity of a postal survey developed to identify older persons in need of outpatient geriatric assessment and follow-up services. DESIGN: A longitudinal cohort study. SETTING: Outpatient primary care clinic at a Department of Veterans Affairs teaching ambulatory care center. PARTICIPANTS: Patients (N = 2,382) aged 65 and older who returned a Geriatric Postal Screening Survey (GPSS) that screened for common geriatric conditions (depression, cognitive impairment, urinary incontinence, falls, and functional status impairment). Validity and reliability testing was performed with subsamples of patients classified as high or lower risk based on responses to the GPSS. MEASUREMENTS: Test-retest reliability was measured by percentage agreement and kappa statistic. The diagnostic validity of the 10-item GPSS was tested by comparing single GPSS items to standardized geriatric assessment instruments for depression, mental status and functional status, as well as direct questions regarding falls, urinary incontinence, and use of medications. Validity was also tested against clinician evaluation of the specific geriatric conditions. Predictive validity was tested by comparing GPSS score with 1-year follow-up data on functional status, survival, and healthcare use. RESULTS: Respondents identified as high risk by the GPSS had scores that indicated significantly greater impairment on structured assessment instruments than those identified as lower risk by GPSS. The overall mean percentage agreement between the test and retest surveys was 88.3%, with a mean weighted kappa of 0.70. In comparison with a structured telephone interview and with a clinical assessment, individual items of the GPSS showed good accuracy (range 0.71-0.78) for identifying symptoms of depression, falls, and urinary incontinence. Over a 1-year follow-up period, the GPSS-identified high-risk group had significantly (P <.05) more hospital admissions, hospital days and nursing home admissions than the lower-risk group. CONCLUSION: A brief postal screening survey can successfully target patients for geriatric assessment services. In screening for symptoms of common geriatric conditions, the GPSS identified a subgroup of older outpatients with multiple geriatric syndromes who were at increased risk for hospital use and nursing home admission and who could potentially benefit from geriatric intervention. 相似文献
669.
Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells 总被引:6,自引:0,他引:6
BACKGROUND: Different acid and peptic related gastroduodenal diseases are associated with both increased gastric secretion and Helicobacter pylori infection. Patients with H pylori associated gastritis or duodenal ulcer have increased serum pepsinogen levels which decrease after eradication. The mechanisms of H pylori induced gastric mucosal damage are not completely understood. AIM: To determine the effects of H pylori on pepsinogen secretion from isolated human peptic cells. METHODS: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. H pylori was obtained from gastric biopsies (antrum and body), and cultured in non-selective and selective media. Isolates of H pylori were used at different concentrations (1 - 20 x 10(6) colony forming units (cfu)). RESULTS: H pylori (10(6) - 2 x 10(7) cfu) increased basal pepsinogen secretion in a concentration dependent manner. This stimulus was not observed with Escherichia coli. The increased secretion was in addition to that observed with 0.1 mM histamine and 0.1 mM dibutyryl-cyclic adenosine monophosphate. However, H pylori did not affect either carbamylcholine (0.1-10 microM) or cholecystokinin (1 microM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor N(w)-monomethyl-L-arginine (1 mM) inhibited H pylori induced cGMP generation and pepsinogen secretion, which were also reduced in the absence of extracellular calcium. H pylori induced pepsinogen secretion was not affected by the absence/presence of the cagA gene. CONCLUSIONS: H pylori increases pepsinogen secretion from human peptic cells through a calcium and nitric oxide mediated intracellular pathway. This effect is independent of the H pylori virulent cagA gene, and may be a mechanism of H pylori induced gastric mucosal damage. 相似文献
670.
Nitric oxide production by neutrophils obtained from patients during acute coronary syndromes: expression of the nitric oxide synthase isoforms 总被引:2,自引:0,他引:2
Sánchez de Miguel L Arriero MM Farré J Jiménez P García-Méndez A de Frutos T Jiménez A García R Cabestrero F Gómez J de Andrés R Montón M Martín E De la Calle-Lombana LM Rico L Romero J López-Farré A 《Journal of the American College of Cardiology》2002,39(5):818-825
OBJECTIVES: To analyze the differences in the nitric oxide (NO) forming system between neutrophils obtained from patients during unstable angina (UA) and during acute myocardial infarction (AMI). BACKGROUND: Neutrophils are involved in the regulation of thrombus formation through the release of active substances such as NO. Acute myocardial infarction is the result of an occlusive thrombus; unstable angina is attributed to intermittent thrombus formation. METHODS: We studied 49 patients admitted to hospital within 24 h after the onset of chest pain: 31 experienced AMI and 18 experienced UA. Acute myocardial infarction was defined as CK greater than two-fold the upper limit of normal value of biochemical laboratory, with CK-MB >10% total CK. Unstable angina was defined as transient ST segment changes without significant increases in CK and CK-MB. RESULTS: The amount of NO generated by neutrophils from AMI patients was significantly higher than that generated by neutrophils from UA patients. Neutrophils from UA and AMI patients showed low levels of endothelial-like NO synthase protein expression and a marked expression of the inducible NO synthase (iNOS) isoform. Although neutrophils from patients during acute coronary syndromes generated high amounts of NO, they did not demonstrate an increased ability to stimulate cyclic guanosine monophosphate (cGMP) synthesis in platelets. This lack of activity to release NO by neutrophils from patients during AMI was unrelated to a defect in the platelet cGMP-forming system; sodium nitroprusside, an exogenous NO donor, similarly increased cGMP levels in platelets from AMI patients and healthy donors. CONCLUSIONS: Neutrophils from patients during AMI and UA showed an increased production of NO and a marked expression of the iNOS isoform. However, NO released from these neutrophils showed a deficient functionality. These findings could have clinical implications because they show differences in thrombus growth in patients with UA versus patients with AMI. 相似文献