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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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R Senior S K Batabyal R N Dutta S Guha S Dutta T D Bhattacharji S C Kundu A K Maity C C Kar 《Indian heart journal》1990,42(1):73-76
25 cases of thalassaemia major were studied by 2D and M-mode echocardiography. A significantly increased (p less than 0.001) mean value (100.8 +/- 27.37 msec, range 80 to 140 msec) of A2-E (early relaxation period) interval on M-mode was observed in thalassemia in comparison to mean level (82.6 +/- 5.7, range 60 to 100 msec) of control population. No significant differences were noted in FS % (fractional shortening) and EF% (ejection fraction) when compared to corresponding normal values respectively. Mean serum iron concentration (142.2 +/- 29.1 micrograms/dl, range 102 to 192 micrograms/dl) was significantly higher in thalassaemia as compared to normal population (mean 106.3 +/- 11.4 micrograms/dl, range 75 to 120 micrograms/dl). There was also a direct correlation between serum iron concentration and A2-E interval. 11 patients (44%) showed abnormal A2-E interval but only 3 patients (12%) showed abnormal percentage of FS and EF. It is therefore concluded that A2-E interval will help to detect early left ventricular dysfunction much before overt and irreversible heart failure becomes manifest and which will also help to optimise transfusion and chelation therapy. 相似文献
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Ni Zhao Douglas A. Bell Arnab Maity Ana‐Maria Staicu Bonnie R. Joubert Stephanie J. London Michael C. Wu 《Genetic epidemiology》2015,39(2):53-64
New high throughput technologies are now enabling simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. A problem of considerable practical interest is identification of large scale, global changes in methylation that are associated with environmental variables, clinical outcomes, or other experimental conditions. However, there has been little statistical research on methods for global methylation analysis using technologies with individual CpG resolution. To address this critical gap in the literature, we develop a new strategy for global analysis of methylation profiles using a functional regression approach wherein we approximate either the density or the cumulative distribution function (CDF) of the methylation values for each individual using B‐spline basis functions. The spline coefficients for each individual are allowed to summarize the individual's overall methylation profile. We then test for association between the overall distribution and a continuous or dichotomous outcome variable using a variance component score test that naturally accommodates the correlation between spline coefficients. Simulations indicate that our proposed approach has desirable power while protecting type I error. The method was applied to detect methylation differences, both genome wide and at LINE1 elements, between the blood samples from rheumatoid arthritis patients and healthy controls and to detect the epigenetic changes of human hepatocarcinogenesis in the context of alcohol abuse and hepatitis C virus infection. A free implementation of our methods in the R language is available in the Global Analysis of Methylation Profiles (GAMP) package at http://research.fhcrc.org/wu/en.html . 相似文献
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Mainak Mukhopadhyay Nandini Chatterjee Pranab Maity Kartik Patar 《Indian Journal of Critical Care Medicine》2014,18(2):110-112
Spontaneous rupture of the spleen with hemoperitoneum is a very rare, but serious manifestation of dengue fever (DF). We report a case of a young female who was presented with atraumatic abdominal pain, hypovolemic shock, anemia, ascites and hepatosplenomegaly with a recent history of a febrile illness. Subsequent investigations proved the presence of hemoperitoneum with spontaneous splenic rupture with seropositivity for DF. Early diagnosis and conservative management in this case resulted in a favorable outcome. 相似文献