Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD‐95

PSD‐95 is one of the most abundant proteins of the postsynaptic density of excitatory synapses. It functions as the backbone of protein supercomplexes that mediate signalling between membrane glutamate receptors and intracellular pathways. Homozygous deletion of the Dlg4 gene encoding PSD‐95 was previously found to cause a profound impairment in operant and Pavlovian conditioning in Dlg4^?/? mice studied in touch screen chambers that precluded evaluation of PSD‐95's role in shaping more subtle forms of learning and memory. In this study, using a battery of touch screen tests, we investigated cognitive behaviour of mice with a heterozygous Dlg4 mutation. We found that in contrast to learning deficits of Dlg4^?/? mice, Dlg4^+/? animals demonstrated enhanced performance in the Visual Discrimination, Visual Discrimination Reversal and Paired‐Associates Learning touch screen tasks. The divergent directions of learning phenotypes observed in Dlg4^?/? and Dlg4^+/? mice also contrasted with qualitatively similar changes in the amplitude and plasticity of field excitatory postsynaptic potentials recorded in the CA1 area of hippocampal slices from both mutants. Our results have important repercussions for the studies of genetic models of human diseases, because they demonstrate that reliance on phenotypes observed solely in homozygous mice may obscure qualitatively different changes in heterozygous animals and potentially weaken the validity of translational comparisons with symptoms seen in heterozygous human carriers.     

Electrohydraulic lithotripsy and rendezvous nasal endoscopic cholangiography for common bile duct stone: A case report

BACKGROUND In patients with large stones in the common bile duct(CBD),advanced treatment modalities are generally needed.Here,we present an interesting case of a huge CBD stone treated with electrohydraulic lithotripsy(EHL)by the percutaneous approach and rendezvous endoscopic retrograde cholangiography(ERC)using a nasal endoscope.CASE SUMMARY A 91-year-old woman underwent ERC for a symptomatic large CBD stone with a diameter of 50 mm.She was referred to our institution after the failure of lithotomy by ERC,and after undergoing percutaneous transhepatic biliary drainage.We attempted to fragment the stone by transhepatic cholangioscopy using EHL.However,the stones were too large and partly soft clay-like for lithotripsy.Next,we attempted lithotomy with ERC and cholangioscopy by the rendezvous technique using a nasal endoscope and achieved complete lithotomy.No complication was observed at the end of this procedure.CONCLUSION Cholangioscopy by rendezvous technique using a nasal endoscope is a feasible and safe endoscopic method for removing huge CBD stones.     

MELAS syndrome with m.4450 G > A mutation in mitochondrial tRNAMet gene

Mutations in the mitochondrial tRNA^Met gene have been reported in only five patients to date, all of whom presented with muscle weakness and exercise intolerance as signs of myopathy. We herein report the case of a 12-year-old girl with focal epilepsy since the age of eight years. At age 11, the patient developed sudden visual disturbances and headaches accompanied by recurrent, stroke-like episodes with lactic acidosis (pH 7.279, lactic acid 11.6?mmol/L). The patient frequently developed a delirious state, exhibited regression of intellectual ability. Brain magnetic resonance imaging revealed high-intensity signals on T2-weighted images of the left occipital lobe. Mitochondrial gene analysis revealed a heteroplasmic m.4450G?>?A mutation in the mitochondrial tRNA^Met. The heteroplasmic rate of the m.4450G?>?A mutation in blood, skin, urinary sediment, hair, saliva, and nail samples were 20, 38, 59, 41, 27, and 35%, respectively. The patient’s fibroblast showed an approximately 53% reduction in the oxygen consumption rate, compared to a control, and decreased complex I and IV activities. Stroke-like episodes, lactic acidosis, encephalopathy with brain magnetic resonance imaging findings, and declined mitochondrial function were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. To our knowledge, the findings associated with this first patient with MELAS syndrome harboring the m.4450G?>?A mutation in mitochondrial tRNA^Met expand the phenotypic spectrum of tRNA^Met gene.     

Thermolabile polymorphism of carnitine palmitoyltransferase 2: A genetic risk factor of overall acute encephalopathy

ObjectivesAcute encephalopathy is an acute brain dysfunction after preceding infection, consisting of multiple syndromes. Some syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), are severe with poor outcome, whereas others, such as clinically mild encephalitis/encephalopathy with reversible splenial lesion (MERS), are mild with favorable outcome. Previous study reported the association of the thermolabile polymorphism in Carnitine Palmitoyltransferase 2 (CPT2) gene and severe syndromes of acute encephalopathy. To further explore the pathogenetic role of CPT2 in acute encephalopathy, we conducted a case-control association study of a typical thermolabile CPT2 polymorphism, rs2229291, in 416 patients of acute encephalopathy, including both severe and mild syndromes.MethodsThe case cohort consisted of 416 patients, including AESD, MERS, and other syndromes. The control subjects were 100 healthy Japanese. rs2229291 was genotyped by Sanger sequencing. Genetic distribution was compared between the patients and controls using Cochran-Armitage trend test.ResultsMinor allele frequency of rs2229291 was significantly higher in AESD (p = 0.044), MERS (p = 0.015) and entire acute encephalopathy (p = 0.044) compared to the controls. The polymorphism showed no significant association with influenza virus, or with outcome.ConclusionsThis study provided evidence that CPT2 is a susceptibility gene for overall acute encephalopathy, including both severe and mild syndromes, and suggested that impairment of mitochondrial metabolism is common to various syndromes of acute encephalopathy.     

New era of research on cancer‐associated glycosphingolipids

Cancer‐associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors. Recent progress in the analysis of their implications in the malignant properties of cancer cells revealed that cancer‐associated glycosphingolipids are not only tumor markers, but also functional molecules regulating various signals introduced by membrane microdomains, lipid rafts. In particular, a novel approach, enzyme‐mediated activation of radical sources combined with mass spectrometry, has enabled us to clarify the mechanisms by which cancer‐associated glycosphingolipids regulate cell signals based on the interaction with membrane molecules and formation of molecular complexes on the cell surface. Novel findings obtained from these approaches are now providing us with insights into the development of new anticancer therapies targeting membrane molecular complexes consisting of cancer‐associated glycolipids and their associated membrane molecules. Thus, a new era of cancer‐associated glycosphingolipids has now begun.     

Clinical Outcomes of Transcatheter Arterial Embolization for Adhesive Capsulitis Resistant to Conservative Treatment

Purpose

To evaluate clinical outcomes of transcatheter arterial embolization (TAE) for adhesive capsulitis resistant to conservative treatments.