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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
5.
Rats were treated with the chlorocarbon analogs chlordecone or mirex (200 ppm) for 8 days and the adrenal glands removed for catecholamine analysis and ultrastructural examination. Total catecholamine content was reduced 54% from 22.07 ± 2.8 (SE) to 10.26 ± 1.2 μg per gland after chlordecone but was not significantly changed after mirex. There was a selective decrease in epinephrine of 63% and an increase in norepinephrine of 28% after chlordecone but not after mirex. Phenylethanolamine-N-methyl transferase, the enzyme that converts norepinephrine to epinephrine was not inhibited by chlordecone in vitro. The biochemical data were supported by electron microscopy after the use of two different fixation methods. Perfusion of the adrenal glands in control rats with glutaraldehyde-formaldehyde, “postosmification” and block-staining gave good general preservation with well-defined epinephrine and norepinephrine cells. Block-fixation in glutaraldehyde-dichromate also resulted in easily identified epinephrine and norepinephrine cells. After chlordecone, the catecholamine-containing granules of the epinephrine cells, but not of the norepinephrine cells, became depleted as visualized by both methods. Mirex had no morphological effect on epinephrine or norepinephrine granules. Thus, distinct differences between the two closely related structural analogs chlordecone and mirex were demonstrated on the catecholamine contents and epinephrine cell ultrastructure in the rat adrenal medulla. These differences are speculated to result from differential effects on mitochondrial and/or granular Mg2+-ATPase and on adrenal corticosteroid levels. 相似文献
6.
Travis P. Baggett Samantha S. Liauw Stephen W. Hwang 《Journal of the American College of Cardiology》2018,71(22):2585-2597
Cardiovascular disease (CVD) is a major cause of death among homeless adults, at rates that exceed those in nonhomeless individuals. A complex set of factors contributes to this disparity. In addition to a high prevalence of cigarette smoking and suboptimal control of traditional CVD risk factors such as hypertension and diabetes, a heavy burden of nontraditional psychosocial risk factors like chronic stress, depression, heavy alcohol use, and cocaine use may confer additional risk for adverse CVD outcomes beyond that predicted by conventional risk estimation methods. Poor health care access and logistical challenges to cardiac testing may lead to delays in presentation and diagnosis. The management of established CVD may be further challenged by barriers to medication adherence, communication, and timely follow-up. The authors present practical, patient-centered strategies for addressing these challenges, emphasizing the importance of multidisciplinary collaboration and partnership with homeless-tailored clinical programs to improve CVD outcomes in this population. 相似文献
7.
Baggett HC Hennessy TW Rudolph K Bruden D Reasonover A Parkinson A Sparks R Donlan RM Martinez P Mongkolrattanothai K Butler JC 《The Journal of infectious diseases》2004,189(9):1565-1573
BACKGROUND: Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) reports are increasing, and infections often involve soft tissue. During a CO-MRSA skin infection outbreak in Alaska, we assessed risk factors for disease and whether a virulence factor, Panton-Valentine leukocidin (PVL), could account for the high rates of MRSA skin infection in this region. METHODS: We conducted S. aureus surveillance in the outbreak region and a case-control study in 1 community, comparing 34 case patients with MRSA skin infection with 94 control subjects. An assessment of traditional saunas was performed. S. aureus isolates from regional surveillance were screened for PVL genes by use of polymerase chain reaction, and isolate relatedness was determined by use of pulsed-field gel electrophoresis (PFGE). RESULTS: Case patients received more antibiotic courses during the 12 months before the outbreak than did control subjects (median, 4 vs. 2 courses; P=.01) and were more likely to use MRSA-colonized saunas than were control subjects (44% vs. 13%; age-adjusted odds ratio, 4.6; 95% confidence interval, 1.7-12). The PVL genes were present in 110 (97%) of 113 MRSA isolates, compared with 0 of 81 methicillin-susceptible S. aureus isolates (P<.001). The majority of MRSA isolates were closely related by PFGE. CONCLUSION: Selective antibiotic pressure for drug-resistant strains carrying PVL may have led to the emergence and spread of CO-MRSA in rural Alaska. 相似文献
8.
George Watt Adele Lacroix Orathai Pachirat Henry C. Baggett Didier Raoult Pierre-Edouard Fournier Pierre Tattevin 《The American journal of tropical medicine and hygiene》2015,92(4):871-874
Prospectively collected, contemporary data are lacking on how the features of infective endocarditis (IE) vary according to region. We, therefore, compared IE in Rennes, France and Khon Kaen, Thailand. Fifty-eight patients with confirmed IE were enrolled at each site during 2011 and 2012 using a common protocol. Compared with French patients, Thais had a lower median age (47 versus 70 years old; P < 0.001) and reported more animal contact (86% versus 21%; P < 0.001). There were more zoonotic infections among Thai than France patients (6 and 1 cases; P = 0.017) and fewer staphylococcal infections (4 versus 15 cases; P = 0.011). Underlying rheumatic heart disease was more prevalent in Thai than in French patients (31% and 4%; P = 0.001), whereas prosthetic heart valves were less prevalent (9% and 35%; P = 0.001). Our data strengthen previous observations that IE in the tropics has distinctive demographic characteristics, risk factors, and etiologies and underscore the need for improved prevention and control strategies. 相似文献
9.
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
10.
Levine OS O'Brien KL Deloria-Knoll M Murdoch DR Feikin DR DeLuca AN Driscoll AJ Baggett HC Brooks WA Howie SR Kotloff KL Madhi SA Maloney SA Sow S Thea DM Scott JA 《Clinical infectious diseases》2012,54(Z2):S93-101
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery. 相似文献