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81.
Dixon-Salazar TJ Silhavy JL Udpa N Schroth J Bielas S Schaffer AE Olvera J Bafna V Zaki MS Abdel-Salam GH Mansour LA Selim L Abdel-Hadi S Marzouki N Ben-Omran T Al-Saana NA Sonmez FM Celep F Azam M Hill KJ Collazo A Fenstermaker AG Novarino G Akizu N Garimella KV Sougnez C Russ C Gabriel SB Gleeson JG 《Science translational medicine》2012,4(138):138ra78
The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders. 相似文献
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Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration 总被引:1,自引:0,他引:1
Beraza N Marqués JM Martínez-Ansó E Iñiguez M Prieto J Bustos M 《Hepatology (Baltimore, Md.)》2005,41(3):460-469
Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis. 相似文献
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There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p < 0.0001), while there was little relationship between arterial pH and arterial carbon dioxide tensions (p = 0.08). The arterial carbon dioxide tension increased 1.2 torr for each 1.0 mEq/l increment in plasma bicarbonate or base excess (95% confidence interval, 1.1 - 1.3 torr). This 1.2 torr increase amounts to a ~ 50% greater degree of espiratory compensation (hypoventilation) to primary metabolic alkalosis than has been reported in prior smaller studies. 相似文献
87.
Belén Sanz-Barbero María Eugenia Prieto-Flores Laura Otero-García Analía Abt-Sacks Mariola Bernal Naiara Cambas 《Gaceta sanitaria / S.E.S.P.A.S》2014
Objective
To analyze the perception of the Spanish population of risk factors for cancer.Methods
Data were extracted from the OncoBarometro 2010 survey. Multivariate logistic models were applied to analyze the perception of the population on the importance of various risk factors: smoking, alcohol, sun, food, weight, sexually transmitted diseases, family history, radiation exposure, exposure to toxic substances and air pollution. The answers were rated on a 0 to 10 scale and were converted to low (0-6) and high (7-10) categories. The measure of association used was the prevalence ratio (PR).Results
The greatest importance was assigned to smoking (high importance: 83.1%), whereas the least importance was assigned to weight (26.5%). In general, the probability of perceiving risk factors as important was lower among men (PR sun: 0.87; PR sexually transmitted diseases: 0.78) and increased among people who received professional advice on cancer prevention (PR alcohol: 1.11; PR sun: 1.18; PR food; 1.31; PR weight: 1.92). In particular, knowledge of symptoms and extreme fear of cancer were associated with perceiving smoking as an important risk factor, whereas a high perceived vulnerability to cancer was associated with perceiving exposure to toxic substances, pollution and smoking as important risk factors.Conclusions
Greater awareness is required of the association of cancer with overweight and sexually transmitted diseases. The recommendations given by health professionals on cancer prevention are key to increasing the population's awareness of risk factors for cancer. 相似文献88.
Cinthia M. Mazzanti Roselia Spanevello Musthaq Ahmed Luciane B. Pereira Jamile F. Gonçalves Maisa Corrêa Roberta Schmatz Naiara Stefanello Daniela B.R. Leal Alexandre Mazzanti Adriano T. Ramos Tessie B. Martins Cristiane Cademartori Danesi Dominguita L. Graça Vera M. Morsch Maria Rosa C. Schetinger 《International journal of developmental neuroscience》2009
The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I—Control (saline), II—(canola); III—(Ebs), IV—(Vit E); V—(EB); VI—(EB + Ebs) and VII—(EB + Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p < 0.05) and in the ST it was reduced in groups III and V (p < 0.05) when compared to the control group. At 21 days after the EB injection, AChE activity in the CC was significantly reduced in groups III, IV and V, while in groups VI and VII a significant increase was observed when compared to the control group. In the HC and ST, AChE activity was significantly reduced in groups V, VI and VII when compared to the control group (p < 0.05). In the erythrocytes, at 3 days after the EB injection, AChE activity was significantly reduced in groups III, IV, V, VI and VII and at 21 days there was a significant reduction only in groups VI and VII (p < 0.05) when compared to the control group. In conclusion, this study demonstrated that Ebs and Vit E interfere with the cholinergic neurotransmission by altering AChE activity in the different brain regions and in the erythrocytes. Furthermore, treatment with Vit E and Ebs protected against the demyelination lesion caused by EB. In this context, we can suggest that ebselen and Vit E should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with demyelinating events. 相似文献
89.
Roberta Schmatz Cinthia Melazzo Mazzanti Roselia Spanevello Naiara Stefanello Jessi Gutierres Paula Acosta Maldonado Maisa Corrêa Cíntia Saydelles da Rosa Lara Becker Margarete Bagatini Jamile Fabbrin Gonalves Jeandre Dos Santos Jaques Maria Rosa Schetinger Vera Maria Morsch 《Brain research bulletin》2009,80(6):371-376
The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5′-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n = 8): control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline; diabetic/RV 10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5′-nucleotidase activities were significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5′-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p < 0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p < 0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p < 0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5′-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes. 相似文献
90.
Castillo Paola de la Oliva Jorge Alos Silvia Perez Francisco Vega Naiara Vilaseca Isabel Marti Carles Ferrer Ada Alos Llucia 《Clinical oral investigations》2022,26(3):2587-2595
Clinical Oral Investigations - This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral... 相似文献