Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

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.      

Predicting cubitus varus in supracondylar fractures of the humerus by Baumann's angles in post reduction X-rays

Objectives: The present study presents the technique to predict cubitus varus by post reduction Affected Side and Normal Side Baumann's angle difference (ASBA and NSBA) respectively. It intends to correlate the Baumann's angle to the final carrying angle of the injured elbow and presents the relevant mathematical clinical rule along with its prediction test characteristics. Material and Methods: Total 57 patients of 6.5+/-1.67yrs, 22 were males and 8 females with 19/30 having left side injury. Isolated closed supracondylar fractures of humerus up to 5 days duration included and previous trauma, pathological fracture, other injury, elbow disease were excluded .30/57 completed >1 year follow-up. Results: The Mean NSBA was 74.4+/-4.14 masculine. The mean normal side carrying angles (NSCA) were 9.56 +/- 2.2 masculine. The NSCA IQR (Inter Quartile Range) was 8.8-10 masculine. The ASBA was 79.9+/-9.1 masculine and affected side carrying angles (ASCA) was 0.20+/-8.7 masculine. The ASCA was best predicted by the difference between ASBA-NSBA (ASCA=3.87-0.65(ASBA- NSBA; F=15.91). At a cut off of 8.8 masculine (the lower limit of IQR for NSCA), a value >0 masculine for ASBA- NSBA was 80% predictive of cubitus varus. With pre test probability of varus at 70%, sensitivity was 0.94 and specificity 0.42. Discussion: A prediction rule to predict the final carrying angle from ASBA NSBA difference is presented with a positive predictive value 0.80, specificity of 0.42, and sensitivity of 0.94 at a pre test probability of 0.70.When the diagnosis of cubitus varus is ASCA<8.8 masculine (Lower limit of the IQR for NSCA). Conclusion: If affected side Baumann's Angle - Normal Side Baumann's Angle is equal to or greater than 0 then there was 80% probability of having cubitus varus. Key words: Supracondylar fractures of humerus, Baumann's angle, Complications, Carrying angle, Cubitus Varus.     

中国针灸腧穴与尼泊尔传统医学生命点的对比研究

中国和尼泊尔的传统医学理论体系都有悠久的历史, 且两者的治疗手段都源自相同的哲学和理论基础。在使用自然疗法治疗疾病的过程中, 两种医疗体系均提出了人体的重要位置点的理论, 即中医的经络腧穴理论和尼泊尔传统医学中的生命点理论。初步将中国针灸腧穴以及尼泊尔传统医学中的生命点的进行对比研究, 为今后两者的结合应用提供依据。     

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

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.