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61.
Divergent functions of VTI12 and VTI11 in trafficking to storage and lytic vacuoles in Arabidopsis
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Sanmartín M Ordóñez A Sohn EJ Robert S Sánchez-Serrano JJ Surpin MA Raikhel NV Rojo E 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(9):3645-3650
The protein storage vacuole (PSV) is a plant-specific organelle that accumulates reserve proteins, one of the main agricultural products obtained from crops. Despite the importance of this process, the cellular machinery required for transport and accumulation of storage proteins remains largely unknown. Interfering with transport to PSVs has been shown to result in secretion of cargo. Therefore, secretion of a suitable marker could be used as an assay to identify mutants in this pathway. CLV3, a negative regulator of shoot stem cell proliferation, is an extracellular ligand that is rendered inactive when targeted to vacuoles. We devised an assay where trafficking mutants secrete engineered vacuolar CLV3 and show reduced meristems, a phenotype easily detected by visual inspection of plants. We tested this scheme in plants expressing VAC2, a fusion of CLV3 to the vacuolar sorting signal from the storage protein barley lectin. In this way, we determined that trafficking of VAC2 requires the SNARE VTI12 but not its close homologue, the conditionally redundant VTI11 protein. Furthermore, a vti12 mutant is specifically altered in transport of storage proteins, whereas a vti11 mutant is affected in transport of a lytic vacuole marker. These results demonstrate the specialization of VTI12 and VTI11 in mediating trafficking to storage and lytic vacuoles, respectively. Moreover, they validate the VAC2 secretion assay as a simple method to isolate genes that mediate trafficking to the PSV. 相似文献
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Taine V Pechet Maite de le Morena Eric N Mendeloff Stuart C Sweet Steven D Shapiro Charles B Huddleston 《The Journal of heart and lung transplantation》2003,22(2):154-160
BACKGROUND: End-stage lung disease is a rare complication of treatment for hematologic and solid tumors in children. When present, it is generally progressive, resulting in the patient being cured of cancer only to die of respiratory failure. Lung transplantation is believed by some to be of overly high risk in this population because of the pre-existing malignancy as well as the presumed compromised immune status. METHODS: Six children (Group 1), aged 5 to 17 years (mean 12.4 years), underwent lung transplantation at our institution because of either pulmonary fibrosis or bronchiolitis obliterans following treatment for acute leukemia (n = 5) or medulloblastoma (n = 1). All patients received chemotherapy, radiation and bone marrow transplantation in the course of treatment for their malignancies. The average forced expiratory volume in 1 second (FEV(1)) was 16% of the predicted value and forced vital capacity (FVC) was 28% of predicted. These results were compared with a similar group of 13 patients undergoing lung transplantation at our institution during the same time interval (Group 2). RESULTS: There were 2 deaths in Group 1, 1 early and 1 late, for an overall survival of 67% at a mean follow-up of 4.02 years. There were no early and 7 late deaths in Group 2 for an overall survival of 46% at a mean follow-up of 4.8 years. The acute rejection rate in the first post-transplant year was 0.2 episode/patient in Group 1 and 1.8 episode/patient in Group 2 (p <0.01). No patient in Group 1 has developed post-transplant lymphoproliferative disease or a relapse of their primary malignancy. Two patients in Group 1 developed unusual infections-Aspergillus and Mycobacterium chelonae. No such infections occurred in Group 2. CONCLUSIONS: Although this represents a small series, we believe that patients with respiratory failure following treatment of a prior malignancy are suitable candidates for lung transplantation. Although they may have some relative protection from acute rejection episodes by virtue of an already compromised immunologic status while receiving standard immunosuppression, an increased propensity for opportunistic infection may exist. 相似文献
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Vallejo M Hermosillo AG Márquez MF Urquidez AK Sotomayor A Salas E Cárdenas M 《Archives of medical research》2007,38(5):579-583
Studies to assess the value of clinical symptoms to predict the head-up tilt test (HUT) outcome in patients with suspicion of vasovagal syncope have shown controversial results. We undertook this study to compare the frequency of symptoms between subjects with and without history of syncope, its association with syncopal spells in those with a history of syncope and positive or negative HUT, and to identify clinical predictors of HUT outcome. Sixty seven subjects with a history of unexplained syncope and 26 subjects without a history of syncope were interviewed using a structured questionnaire before undergoing HUT, which was performed first in a passive phase and, if negative, was repeated with pharmacological challenge using 5 mg of sublingual isosorbide. Questionnaire included the 16 symptoms most frequently reported in previous studies. Only five symptoms were reported more frequently by subjects with history of syncope in comparison with subjects without it: visual blurring, dysesthesia, sighing dyspnea, tremor in fingers, and diaphoresis. Comparison of symptom frequency between patients with history of syncope and positive or negative HUT revealed that only two were significantly different: nausea and hot flashes. However, a detailed analysis of the data indicates that only hot flashes occurring just before the syncope were more common in those with a positive HUT. Although some symptoms were found more frequently in patients with a history of syncope than in those without it, the use of a structured questionnaire in the group of patients failed to predict the outcome of the HUT. 相似文献
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Benavides FG Plana M Serra C Domínguez R Despuig M Aguirre S Soria M Sampere M Gimeno D 《Revista espa?ola de salud pública》2007,81(2):183-190
BACKGROUND: To describe the duration of non-work related sickness absences incidents according to age, sex, economic activity and Autonomous Community. METHODS: The sample of non-work related sick spells included 76,598 incident cases started in 2002 among workers cover by the general regime of the Social Security system, and managed by an insurance company. The median and intercuartils range were estimated by sex, age, economic activities and Autonomous Comunnity. Probability ratio of continuing out of work (PRCOW) were compared among Autonomous Comunities, after adjusting by sexo, age and economic activities, taking Navarra as reference, using a log-logistic regression model with a gamma distribution. RESULTS: The 25% of cases there were returned to work at 40 day, the 50% at 90 day; and the 75% at 26 degrees day. Extremadura (PCOW=2,7; IC95%: 2,4-3,1) and Galicia (2,6; 2,4-2,9) showed the highest differences with Navarra. There were also statistically significant differences among economic activities after adjusting by age and sex. CONCLUSIONS: Return to work after a non-work related sick spell is a complex process, which is influenced by age, sex, economic activities and autonomous community. 相似文献
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Shah JS Hughes DA Sachdev B Tome M Ward D Lee P Mehta AB Elliott PM 《The American journal of cardiology》2005,96(6):842-846
Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme alpha-galactosidase A. More than 60% of patients with AFD have evidence for cardiac involvement; the prevalence and clinical significance of arrhythmia in AFD are unknown. Seventy-eight consecutive patients (mean age 43.5 +/- 15.0 years, range 13.0 to 83.0; 43 men) with AFD were studied for 1.9 years (range 0.25 to 10). All patients underwent clinical evaluation, 12-lead electrocardiography, and echocardiography. Sixty patients (76.9%) underwent 24-hour ambulatory electrocardiographic monitoring. Persistent atrial fibrillation (AF) was present in 3 of 78 patients (3.9%); 8 (13.3%) had paroxysmal AF, and 5 (8.3%) had nonsustained ventricular tachycardia (VT). Patients with nonsustained VT were all men, with a maximal left ventricular (LV) wall thickness >20 mm. Age (p <0.001), left atrial diameter (p = 0.001), maximal LV wall thickness (p = 0.003), LV mass index (p = 0.009), and angina (p = 0.02) were univariate predictors of AF or paroxysmal AF. Using these predictors in a stepwise logistic regression analysis model, age was the only independent predictor of AF or paroxysmal AF (odds ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.001). During follow-up, there was 1 sudden cardiac death, 4 patients received pacemakers for bradyarrhythmia, and 1 received a biventricular pacemaker and an internal cardioverter defibrillator. In conclusion, arrhythmias are common in older patients with AFD. The high incidence of pacemaker implantation and sudden cardiac death suggests that arrhythmia has a significant impact on the natural history of AFD. 相似文献