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Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
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Zusammenfassung Zellen des Yoshita-Ascitessarkoms wurden mit 25 kr bestrahlt und sofort nach der Bestrahlung mit und ohne Pyruvatzusatz zum Suspensionsmedium unter anaeroben Bedingungen inkubiert. Die bekannte Hemmung der Glykolyse in den Ansätzen mit Brenztraubensäure ist dabei weitgehend aufgehoben; in den Zellen fand sich ein signifikant höherer DPN-Gehalt. Durch Bestimmung von Glykolyse-Zwischenstoffen und ATP konnte nachgewiesen werden, daß der geringe DPN-Anstieg ausreicht, um die Triosephosphatdehydrogenierung auf die Höhe der Kontrollen zu beschleunigen. Damit war gezeigt, daß nur geringe Änderungen der DPN-Konzentration die Triosephosphatdehydrogenierung steuern.
Mit 4 Textabbildungen
Die Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.
Herrn Prof. Butenandt zum 60. Geburtstag gewidmet. 相似文献
Summary Cells of the Yoshida ascites sarcoma were irradiated with 25 kr and immediately thereafter were incubated under anaerobic conditions with and without pyruvic acid being added to the suspension medium. Thereby the known inhibition of glycolysis in the suspensions due to pyruvic acid was eliminated. There was a significantly increased content of DPN in the cells. By determining the intermediate products of glycolysis and ATP, it could be shown that the slight increase in DPN sufficed to accelerate the triose-phosphate dehydrogenation to the level of the controls. It was shown thereby, that only slight changes in the concentration of DPN regulated the triose-phosphate dehydrogenation.
Mit 4 Textabbildungen
Die Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.
Herrn Prof. Butenandt zum 60. Geburtstag gewidmet. 相似文献
5.
Improved Survival for Rural Trauma Patients Transported by Helicopter to a Verified Trauma Center: A Propensity Score Analysis
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Thein Hlaing Zhu MBBS FACE FRCP Lisa Hollister RN MSN Dazar Opoku MPH Samuel M. Galvagno DO PhD MS FCCM Jr. 《Academic emergency medicine》2018,25(1):44-53
Objectives
Recent studies using advanced statistical methods to control for confounders have demonstrated an association between helicopter transport (HT) versus ground ambulance transport (GT) in terms of improved survival for adult trauma patients. The aim of this study was to apply a methodologically vigorous approach to determine if HT is associated with a survival benefit for when trauma patients are transported to a verified trauma center in a rural setting.Methods
The ascertainment of trauma patients age ≥ 15 years (n = 469 cases) by HT and (n = 580 cases) by GT between 1999 and 2012 was restricted to the scene of injury in a rural area of 10 to 35 miles from the trauma center. The propensity score (PS) was determined using data including demographics, prehospital physiology, intubation, total prehospital time, and injury severity. The PS matching was performed with different calipers to select a higher percentage of matches of HT compared to GT patients. The outcome of interest was survival to discharge from hospital. Identical logistic regression analysis was done taking into account for each matched design to select an appropriate effect estimate and confidence interval (CI) controlling for initial vital signs in the emergency department, the need for urgent surgery, intensive care unit admission, and mechanical ventilation.Results
Unadjusted mortalities for HT compared to GT were 7.7 and 5.3%, respectively (p > 0.05). The adjusted rates were 4.0% for HT and 7.6% for GT (p < 0.05). In a PS well‐matched data set, HT was associated with a 2.69‐fold increase in odds of survival compared to GT patients (adjusted odds ratio = 2.69; 95% CI = 1.21–5.97).Conclusions
In a rural setting, we demonstrated improved survival associated with HT compared to GT for scene transportation of adult trauma patients to a verified Level II trauma center using an advanced methodologic approach, which included adjustment for transport distance. The implication of survival benefit to rural population is discussed. We recommend larger studies with multiple trauma systems need to be repeated using similar study methodology to substantiate our findings. 相似文献6.
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Gregory Phillips II Manya Magnus Irene Kuo Anthony Rawls James Peterson Yujiang Jia Jenevieve Opoku Alan E. Greenberg 《AIDS and behavior》2014,18(9):1630-1637
Current advances have added geosocial networking (GSN) mobile phone applications as an option for men who have sex with men (MSM) to meet other men. This is the first study to assess GSN application use and sex-seeking behaviors of MSM recruited using venue-based sampling. Among the 379 MSM in this study, 63.6 % reported using GSN applications to find men in the past year. Nearly one-quarter of MSM had sex with a man met using a GSN application in the prior year; these men were more likely to be under 35 years old and have had sex with a man met on the Internet; they were also less likely to be HIV-positive and have <5 male sex partners in the last year. GSN applications are a viable option for use in sampling and delivering interventions to young MSM who are often missed through other methods. 相似文献
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Simone CS Wolfkamp Caroline Verseyden Esther WM Vogels Sander Meisner Kirsten Boonstra Charlotte P Peters Pieter CF Stokkers Anje A te Velde 《World journal of gastroenterology : WJG》2014,20(10):2664-2672
AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease. 相似文献
9.
Nana Kwame AyisiBoateng Aliyu Mohammed Douglas Aninng Opoku Fred Stephen Sarfo 《Journal of clinical hypertension (Greenwich, Conn.)》2020,22(9):1594
Apparent resistant hypertension (ARH) is rife among people living with hypertension and is associated with significant morbidity and mortality. There is however paucity of data from sub‐Saharan Africa on the burden of ARH. We sought to report on the frequency and factors associated with ARH among a cohort of Ghanaians with hypertension. A cross‐sectional study involving 2912 participants with hypertension enrolled at five health facilities in Ghana. ARH was defined as either office BP ≥ 140/90 mm Hg on 3 or more antihypertensive medications or on 4 or more antihypertensive medications regardless of BP. Factors associated with ARH were evaluated in a multivariate logistic regression model. We found 550 out of 2,912 (18.9%) of study participants had ARH. Out of these 550 subjects, 511 (92.9%) were on 3 or more antihypertensive medications with BP ≥ 140/90 mm Hg and 39 (7.1%) were on 4 or more antihypertensive medications with BP ≥ 140/90 mm Hg. The prevalence of ARH was 15.5% among elderly aged 75 + years (n = 341), 20.7% among 65‐74 years (n = 588), and 18.9% among those ≤ 64 years (n = 1983). The adjusted odds ratio (95% CI) of factors independently associated with ARH was duration of hypertension, 1.05 (1.03‐1.06) for each year rise; eGFR < 60 mL/min, 1.73 (1.33‐2.25); and diabetes mellitus, 0.59 (0.46‐0.76). Attaining secondary level education and residence in a peri‐urban setting were significantly associated with ARH though not in a dose‐dependent manner. ARH is rife among Ghanaians and may negatively impact on cardiovascular outcomes in the long term. 相似文献
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