Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (<it>MR</it>), but it is a matter of debate whether <it>MR </it>mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations.</p> <p>Methods and Results</p> <p>We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products.</p> <p>Conclusion</p> <p>mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.</p

Robustness of polyisobutylene for friction coefficients between bearing surfaces of bolted joints

In bolted joints, clamp force must be accurately controlled to secure their reliability. However, the clamp force varies widely in each tightening because friction coefficients at thread surfaces and bearing surfaces vary in each tightening due to lubricants, configuration error of bolts, surface roughness, and surface hardness, among other things. In this study, we investigated the robustness of polyisobutylene and ISO VG46 machine oil during the tightening process for several parameters of tightening conditions. We especially focused on variations of the friction coefficient between bearing surfaces at an appropriate target clamp force of M8 bolt/nut assemblies and change rates of the friction coefficients from the middle to the end of the appropriate target clamp force. Results showed that the friction coefficients at the target clamp force varied widely if ISO VG46 machine oil was used as a lubricant. In contrast, the variations of the friction coefficients in which polyisobutylene was used for tightening were small. Results also showed that the friction coefficients invariably decreased about 20% from the middle to the end of the target clamp force if ISO VG46 machine oil was used for the lubricant. However, if polyisobutylene was used, the friction coefficients were almost constant for all tightening instances. </jats:p

Endovascular Treatment May Be Effective in Preventing Recurrence of Ischemic Stroke in Vertebral Artery Stump Syndrome: A Case Series

Vertebral artery stump syndrome (VASS) is a rare condition that can cause posterior circulation ischemic stroke due to occlusion of the ipsilateral vertebral artery (VA) orifice, resulting in blood flow stagnation and embolus formation. Although there is no established treatment for this condition, we observed 3 cases of VASS out of 326 acute ischemic stroke cases at a single institution from April 2021 to October 2022. Despite the best possible antithrombotic treatment, all 3 patients had recurrent ischemic strokes. One patient underwent drug-eluting stenting of the VA orifice to relieve occlusive flow. The other 2 patients received coil embolization, which resulted in the disappearance of their culprit collateral flow. None of the patients had recurrent ischemic strokes after endovascular intervention. Based on our observations, stenting and coil embolization are effective methods for preventing future recurrences of VASS