Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.     

Bloom''s syndrome with porokeratosis of Mibeili and multiple cancers of the skin, lung and colon

A 38-year-old Japanese male with Bloom's syndrome (BS) and porokeratosis of Mibelli (PM) developed multiple carcinomas of the skin and lung. There were multiple, spontaneous chromosomal aberrations and frequent sister chromatid exchanges (SCE). Cutaneous delayed-type hypersensitivity reactions were defective and serum IgM was decreased. The lung cancer was treated with radiation, which was effective but caused a severe pulmonary atelectasis and esophageal stricture. The patient expired one-and-a-half years later because of pneumonia. Autopsy disclosed an adenocarcinoma of the colon. The concurrent PM was considered responsible for the occurrence of multiple skin cancers.     

Pre-operative higher hematocrit and lower total protein levels are independent risk factors for cerebral hyperperfusion syndrome after superficial temporal artery–middle cerebral artery anastomosis with pial synangiosis in adult moyamoya disease patients—case-control study

Neurosurgical Review - Superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis is a standard treatment for adult moyamoya disease (MMD) patients. Cerebral hyperperfusion...     

Association between central sensitivity syndrome and psychological factors in people with presurgical low back pain: A cross-sectional study

BackgroundLow back pain (LBP) is a major problem; it causes significant burden, incurs considerable economic and human costs, and adversely affects the quality of life (QoL). Central sensitivity syndrome (CSS) is known as a group of overlapping conditions that share a common pathophysiological mechanism of central sensitization. Previous studies have shown that CSS is present in several disorders. However, it has been studied for people with presurgical LBP. The purpose of the study was to investigate the proportion of patients with CSS for presurgical LBP and to analyse the association of CSS with clinical symptoms and psychological factors.MethodsData of demographics, the central sensitization inventory (CSI), psychological measures, clinical symptoms of 238 patients with presurgical LBP were evaluated. The patients were divided into two groups depending on the CSI scores (≥40 and < 40). The two groups were compared, and the correlation between the CSI scores and other outcomes was analysed. Furthermore, multiple regression analysis was performed to identify factors contributing to the CSI scores.Results13.0% of participants were CSS. All outcomes were significantly different between the groups and significant associations were found between the CSI scores and all other outcomes. In addition, Pain Catastrophizing Scale (PCS) was most significant associated scale for the CSI scores.ConclusionWe found that certain patients had CSS with presurgical LBP. The CSI scores were significantly associated with the majority of the factors. The PCS was the factor with the most influence on the CSI scores.     

Skeletonization of the atrioventricular node for AV node reentrant tachycardia: experience with 32 patients

We describe our experience with operative therapy for atrioventricular (AV) node tachycardia using an anatomically guided procedure. The operative rationale was to dissect the AV node from most of its atrial inputs (AV node "skeletonization") with the intent of altering the perinodal substrate and preventing reentry. The anteroseptal and posteroseptal regions were initially approached epicardially to facilitate identification of anatomical structures. Under normothermic cardiopulmonary bypass, the right atrial septum was mobilized and the intermediate AV node was exposed anterior to the tendon of Todaro. Atrioventricular node conduction was monitored electrocardiographically throughout the procedure. Ablation of concomitant accessory pathways was done prior to AV node skeletonization. Thirty-two patients aged 9 to 67 years (mean age, 30 years) underwent operation. Five patients had concomitant accessory pathways in addition to AV node reentry. At electrophysiological study before discharge, no patient had AV block although anterograde and retrograde Wenckebach cycle lengths were significantly prolonged. Six patients had retrograde AV block. Twenty-nine patients are free from arrhythmia and require no antiarrhythmic medication after a follow-up of 1 month to 45 months (mean follow-up, 17 months). Three patients had recurrence of tachycardia ten days, 2 months, and 7 months postoperatively. All patients subsequently had a successful reoperation.     

Ribose-transfer activity from uridine to 5-fluorouracil in Ehrlich ascites tumor cells.

Anabolism of 5-fluorouracil (5-FU) in the presence of uracil was examined using the cell-free extract of Ehrlich ascites tumor cells. FU-nucleoside formation from 5-FU with ribose 1-phosphate (R-1-P) or 2'-deoxyribose 1-phosphate was not readily inhibited even by the addition of uracil at 100 times higher concentration than 5-FU. FU-nucleotide formation from 5-FU with R-1-P and adenosine 5'-triphosphate or with 5-phosphoribosyl 1-pyrophosphate was slightly reduced as the concentration of uracil was increased. It was also found that 5-fluorouridine (5-FUR) was produced by "nucleoside N-ribosyltransferase," transferring a ribose moiety from uridine (UR) to 5-FU directly. This activity might play a role in the preferential formation of 5-FUR. However, 5-fluoro-2'-deoxyuridine was not produced by directly transferring a deoxyribose moiety. On the basis of several column chromatographies and characterization of kinetics, pH dependency, and response to inhibitors, the enzyme protein of the ribosyltransferase could not be distinguished from that of the phosphorylase.     

Clinicopathological features of hereditary breast cancer

The possible role of germline mutations ofBRCA1 andBRCA2 as causative agents of familial breast cancer was assessed. Their possible involvement in the carcinogenesis of hereditary breast cancer was investigated using 63 clinically suspect families. Twenty-one lineages (33.3%) had mutations in one of the twoBRCA genes. This relatively low incidence suggested that germline mutations in unknown genes are involved in the carcinogenesis of hereditary breast cancer in the Japanese population. However, the clinicopathological features characteristic of hereditary breast cancer, such as early disease onset, a high incidence of bilateral breast cancer, and a high incidence of multiple primary carcinomas in other organs were confirmed in the present study.