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111.
An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation. 总被引:4,自引:0,他引:4
D Bodmer M J Eleveld M J Ligtenberg M A Weterman B A Janssen D F Smeets P E de Wit A van den Berg E van den Berg M I Koolen A Geurts van Kessel 《American journal of human genetics》1998,62(6):1475-1483
Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied. In contrast to the first hit in the generally accepted two-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event leading to (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor-suppressor gene. The risk of developing renal cell cancer may be correlated directly with the extent of somatic (kidney) mosaicism resulting from this loss. 相似文献
112.
Jacques J. H. Hens Marina De Wit Wim E. J. M. Ghijsen A. G. Miriam Leenders †Hendrik W. G. M. Boddeke ‡Roland Kissmehl Victor M. Wiegant §Ulrich Weller Willem-Hendrik Gispen Pierre N. E. De Graan 《Journal of neurochemistry》1998,71(5):1978-1986
Abstract: Neurotransmission requires rapid docking, fusion, and recycling of neurotransmitter vesicles. Several of the proteins involved in this complex Ca2+ -regulated mechanism have been identified as substrates for protein kinases and phosphatases, e.g., the synapsins, synaptotagmin, rabphilin3A, synaptobrevin, munc18, MARCKS, dynamin I, and B-50/GAP-43. So far most attention has focused on the role of kinases in the release processes, but recent evidence indicates that phosphatases may be as important. Therefore, we investigated the role of the Ca2+ /calmodulin-dependent protein phosphatase calcineurin in exocytosis and subsequent vesicle recycling. Calcineurin-neutralizing antibodies, which blocked dynamin I dephosphorylation by endogenous synaptosomal calcineurin activity, but had no effect on the activity of protein phosphatases 1 or 2A, were introduced into rat permeabilized nerve terminals and inhibited Ca2+ -induced release of [3 H]noradrenaline and neuropeptide cholecystokinin-8 in a specific and concentration-dependent manner. Our data show that the Ca2+ /calmodulin-dependent phosphatase calcineurin plays an essential role in exocytosis and/or vesicle recycling of noradrenaline and cholecystokinin-8, transmitters stored in large dense-cored vesicles. 相似文献
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115.
Claire H. den Hoedt Muriel P. C. Grooteman Michiel L. Bots Peter J. Blankestijn Ingeborg van der Tweel Neelke C. van der Weerd E. Lars Penne Albert H. A. Mazairac Renée Levesque Piet M. ter Wee Menso J. Nubé Marinus A. van den Dorpel CONTRAST investigators 《PloS one》2015,10(8)
Background
Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections.Patients and Methods
We used data of the 714 HD patients (age 64 ±14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups.Results
Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88–1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, non-fatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD).Conclusions
HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings.Trial Registration
ClinicalTrials.gov NCT00205556 相似文献116.
Fei Liu Yingju Liu Rui‐Gang Xu Guifu Dai Liu‐Xi Zhao Yafeng Wang Hong‐Min Liu Feng‐Wu Liu Christophe Pannecouque Piet Herdewijn 《化学与生物多样性》2015,12(5):813-822
The synthesis of [(2′,5′‐dihydrofuran‐2‐yl)oxy]methyl‐phosphonate nucleosides with a 2‐substituted adenine base moiety starting from 2‐deoxy‐3,5‐bis‐O‐(4‐methylbenzoyl)‐α‐L ‐ribofuranosyl chloride and 2,6‐dichloropurine is described. The key step is the regiospecific and stereoselective introduction of a phosphonate synthon at C(2) of the furan ring. None of the synthesized compounds showed significant in vitro activity against HIV, BVDV, and HBV. 相似文献
117.
Robert Kaba Alhassan Edward Nketiah-Amponsah Nicole Spieker Daniel Kojo Arhinful Alice Ogink Paul van Ostenberg Tobias F. Rinke de Wit 《PloS one》2015,10(11)
Background
Patient safety and quality care remain major challenges to Ghana’s healthcare system. Like many health systems in Africa, this is largely because demand for healthcare is outstripping available human and material resource capacity of healthcare facilities and new investment is insufficient. In the light of these demand and supply constraints, systematic community engagement (SCE) in healthcare quality assessment can be a feasible and cost effective option to augment existing quality improvement interventions. SCE entails structured use of existing community groups to assess healthcare quality in health facilities. Identified quality gaps are discussed with healthcare providers, improvements identified and rewards provided if the quality gaps are closed.Purpose
This paper evaluates whether or not SCE, through the assessment of health service quality, improves patient safety and risk reduction efforts by staff in healthcare facilities.Methods
A randomized control trail was conducted in 64 primary healthcare facilities in the Greater Accra and Western regions of Ghana. Patient risk assessments were conducted in 32 randomly assigned intervention and control facilities. Multivariate multiple regression test was used to determine effect of the SCE interventions on staff efforts towards reducing patient risk. Spearman correlation test was used to ascertain associations between types of community groups engaged and risk assessment scores of healthcare facilities.Findings
Clinic staff efforts towards increasing patient safety and reducing risk improved significantly in intervention facilities especially in the areas of leadership/accountability (Coef. = 10.4, p<0.05) and staff competencies (Coef. = 7.1, p<0.05). Improvement in service utilization and health resources could not be attributed to the interventions because these were outside the control of the study and might have been influenced by institutional or national level developments between the baseline and follow-up period. Community groups that were gender balanced, religious/faith-based, and had structured leadership appeared to be better options for effective SCE in healthcare quality assessment.Conclusion
Community engagement in healthcare quality assessment is a feasible client-centered quality improvement option that should be discussed for possible scale-up in Ghana and other resource poor countries in Africa. 相似文献118.
Camiel L. M. de Roij van Zuijdewijn Muriel P. C. Grooteman Michiel L. Bots Peter J. Blankestijn Sonja Steppan Janine Büchel Rolf H. H. Groenwold Vincent Brandenburg Marinus A. van den Dorpel Piet M. ter Wee Menso J. Nubé Marc G. Vervloet 《PloS one》2015,10(11)
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time. 相似文献
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120.
Gabriela B. Gomez Nicola Foster Daniella Brals Heleen E. Nelissen Oladimeji A. Bolarinwa Marleen E. Hendriks Alexander C. Boers Diederik van Eck Nicole Rosendaal Peju Adenusi Kayode Agbede Tanimola M. Akande Michael Boele van Hensbroek Ferdinand W. Wit Catherine A. Hankins Constance Schultsz 《PloS one》2015,10(9)