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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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Peak oxygen intake and cardiac mortality in women referred for cardiac rehabilitation 总被引:3,自引:0,他引:3
Kavanagh T Mertens DJ Hamm LF Beyene J Kennedy J Corey P Shephard RJ 《Journal of the American College of Cardiology》2003,42(12):2139-2143
OBJECTIVES: This study investigated the prognostic importance of measured peak oxygen intake (VO(2peak)) in women with known coronary heart disease referred for outpatient cardiac rehabilitation. BACKGROUND: Exercise capacity is a powerful predictor of prognosis in men with known or suspected coronary disease. Similar findings are described in women, but fewer studies have utilized measured VO(2peak), the most accurate measure of exercise capacity. METHODS: A single-center design took data from 2,380 women, age 59.7 +/- 9.5 years (1,052 myocardial infarctions, 620 coronary bypass procedures, and 708 with proven ischemic heart disease), who underwent cardiorespiratory exercise testing. They were followed for an average of 6.1 +/- 5 years (median 4.5 years, range 0.4 to 25 years) until cardiac and all-cause death. RESULTS: We recorded 95 cardiac deaths and 209 all-cause deaths. Measured VO(2peak) was an independent predictor of risk, values > or =13 ml/kg/min (3.7 multiples of resting metabolic rate) conferring a 50% reduction in cardiac mortality (hazard ratio [HR] 0.5, p = 0.001). Considered as a continuous variable, a 1 ml/kg/min advantage in initial VO(2peak) was associated with a 10% lower cardiac mortality. Adverse predictors were diabetes (HR 2.73, p = 0.0005) and antiarrhythmic therapy (HR 3.93, p = 0.0001). CONCLUSIONS: As in men, measured VO(2peak) is a strong independent predictor of cardiac mortality in women referred for cardiac rehabilitation. 相似文献
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Kayode O. Kuku Hector M. Garcia-Garcia Edward Koifman Alexandre H. Kajita Sameer Desale Viana Azizi Gebremedhin Melaku Anh Bui Yael F. Meirovich Solomon Beyene Aaphtaab Dheendsa Blaine Schneider Ron Waksman On behalf of the CELLO study investigators 《The international journal of cardiovascular imaging》2018,34(3):345-352
The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) registry included patients treated with modified excimer laser catheters for the endovascular treatment of peripheral artery disease affecting the superficial femoral artery (SFA) and proximal popliteal artery. The aim of this study was to assess, via intravascular ultrasound (IVUS) the dissections in the vessel wall following treatment with the laser catheters. IVUS grayscale images from the CELLO registry were systematically reviewed for dissections in the treated vessel segments by two investigators. Images from 33 patients; 66 pullbacks (1867 IVUS frames in 2 phases), were successfully matched frame-to-frame to evaluate identical segments of the treated vessels in the two phases; post-2 mm Turbo-Elite laser pilot channel creation and post Turbo-Booster laser atherectomy. Dissections were categorized as; (1) intimal, (2) medial, (3) intramural hematoma, and (4) adventitial according to the ACC Clinical Expert Consensus Document classification of dissections. An average of 57 frames was evaluated per pullback, giving a total of 3734 frames (1867 matched for pre-ablation (post channel creation) and post-ablation phases). Treatments with the modified Excimer laser catheters resulted in a significant increase in lumen area of 5.5?±?3.2-mm2 (95% CI 4.3–6.8, p?<?0.0001) and reduction in plaque plus media volume of ?10.6?±?36.0 mm3 (95% CI ?25.8 to 4.6, p?=?0.1619) whilst giving rise to mainly intramural hematoma formations post Turbo-Booster laser treatment in 55% of frames assessed and 24% medial dissections with less than 1% adventitial disruption. The Excimer laser based Turbo-Booster treatment of peripheral artery lesions resulted in significant plaque debulking and increased lumen diameter with negligible degree of adventitial layer injury. 相似文献
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Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia 总被引:1,自引:0,他引:1
Deribe K Hailekiros F Biadgilign S Amberbir A Beyene BK 《Tropical medicine & international health : TM & IH》2008,13(3):328-333
Objective To determine the prevalence of and factors associated with defaulting from antiretroviral treatment (ART) in Jimma, Ethiopia. Methods Unmatched case control study: cases were individuals who had missed two or more clinical appointments (i.e. had not been seen for the last 2 months) between January 2005 and February 2007; controls were individuals who had been on ART at least for 1 year and were rated as excellent adherers by the providers. Data were collected from patient records, and by telephone call and home visit to identify the reason for defaulting. Results Of 1270 patients who started ART, 915 (72.0%) were active ART users and 355 (28.0%) had missed two or more clinical appointments. The latter comprised 173 (13.6%) defaulters, 101 (8.0%) who transferred out, 75 (5.9%) who died, and 6 (0.5%) who restarted ART. Reasons for defaulting were unclear in most cases. Reasons given were loss of hope in medication, lack of food, mental illness, holy water, no money for transport, and other illnesses. Tracing was not successful because of incorrect address on the register in 61.6% of the cases. Taking hard drugs (cocaine, cannabis and IV drugs), excessive alcohol consumption, being bedridden, living outside Jimma town and having an HIV negative or unknown HIV status partner were associated with defaulting ART. Conclusion A significant proportion of patients defaulted from ART treatment. ART clinics should ensure that patients’ addresses are correct and complete. Programmatic and counseling efforts to decrease ART defaulting should address illicit drug and excessive alcohol use, decentralise ART services, institute home‐based treatment options for seriously ill and bedridden patients, and address patients concerns. 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
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Rong?Chu Edward?J?Mills Joseph?Beyene Eleanor?Pullenayegum Celestin?Bakanda Jean?B?Nachega P?J?Devereaux Lehana?ThabaneEmail author 《AIDS research and therapy》2013,10(1):19