Reduced expression of BTBD10 in anterior horn cells with Golgi fragmentation and pTDP‐43‐positive inclusions in patients with sporadic amyotrophic lateral sclerosis

Overexpression of BTBD10 (BTB/POZ domain‐containing protein 10) suppresses G93A‐superoxide dismutase 1 (SOD1)‐induced motor neuron death in a cell‐based amyotrophic lateral sclerosis (ALS) model. In the present study, paraffin sections of spinal cords from 13 patients with sporadic ALS and 10 with non‐ALS disorders were immunostained using a polyclonal anti‐BTBD10 antibody. Reduced BTBD10 expression in the anterior horn cells was more frequent in spinal cords from ALS patients than in cords from patients with non‐ALS disorders. We further investigated the relationship between the level of BTBD10 immunoreactivity and the morphology of the Golgi apparatus (GA) and the presence of phosphorylated TAR‐DNA‐binding protein 43 (pTDP‐43). Mirror sections of spinal cords from five sporadic ALS cases were immunostained with antibodies against BTBD10 and trans‐Golgi‐network (TGN)‐46 or pTDP‐43. Whereas 89.7–96.5% of the neurons with normal BTBD10 immunoreactivity showed normal GA morphology and no pTDP‐43 cytoplasmic aggregates, 86.2–94.3% of the neurons with reduced BTBD10 expression showed GA fragmentation and abnormal pTDP‐43 aggregates. These findings suggest that reduced BTBD10 expression is closely linked to the pathogenesis of sporadic ALS.     

The superior approach with the stomach roll-up technique improves intraoperative outcomes and facilitates learning laparoscopic distal pancreatectomy: a comparative study between the superior and inferior approach

Surgery Today - We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal...     

Characterization of early onset neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is an autosomal dominant multiple neoplasia syndrome of the central nervous system. The aim of the present study was to characterize the clinical course of early onset NF2. The specific Japanese disease registry for NF2 in 2010 was analyzed retrospectively. The male:female ratio for the 312 patients identified in the database was 1:1.29. The median age at onset was 25 years (range 2–76 years), with 31.3% of patients exhibiting symptoms at <20 years of age. Patients with an age at onset of <20 years were found to have more frequent spinal cord and extravestibular cranial nerve involvement, cutaneous signs, and convulsions than patients with a later age at onset. Of patients younger than 18 years of age, half did not exhibit hearing problems; in contrast, they frequently had other cranial nerve schwannomas, cranial meningioma, spinal cord tumors, and subcutaneous schwannoma. There were weak but significant positive correlations between symptomatic periods and disability scores in patients with an age of onset of ?20 years (R = 0.225; P < 0.01) and those with an earlier age of onset (R = 0.306; P < 0.01). Although there were no significant differences in disability scores between genders or patients with an age at onset of <20 versus ?20 years, patients with an earlier age at onset had significantly higher disability scores for spinal symptoms than patients with an age at onset of ?20 years. Atypical extravestibular presentation is common in early onset NF2, with more prominent spinal symptoms.     

Magnesium sulphate infusion suppresses the cardiac release of noradrenaline during a handgrip stress test

BACKGROUND: Magnesium has several important cardiovascular effects, but its effect on cardiac sympathetic efferent neuron activity has not been clarified. Objectives: To examine the effect of magnesium sulphate infusion on cardiac sympathetic efferent postganglionic neuronal liberation of noradrenaline. PATIENTS AND METHODS: Twenty-two patients who underwent cardiac catheterization were randomly allocated to the control group or the magnesium group. Plasma noradrenaline and adrenaline concentrations in the aorta and the coronary sinus were measured. Noradrenaline or adrenaline release from the heart was calculated by dividing the difference in noradrenaline or adrenaline concentration between the aorta and the coronary sinus by that of the aorta. After baseline blood sampling, the control patients and the patients in the magnesium group received intravenous infusion of saline or magnesium sulphate (10 mmol). All patients were then subjected to 3 min of handgrip exercise stress test to augment sympathetic efferent neuronal activity, and the blood sampling was repeated. RESULTS: Although blood pressure was increased by the handgrip stress test, there were no differences in heart rate and blood pressure between the two groups, both at baseline and during the handgrip stress test. The plasma noradrenaline and adrenaline concentrations and noradrenaline or adrenaline release from the heart did not differ between the two groups in the baseline condition. However, the handgrip stress increased plasma noradrenaline concentrations and the cardiac noradrenaline release was increased in the control group, whereas the cardiac noradrenaline release was not increased by the handgrip stress in the magnesium group (P<0.02). CONCLUSIONS: These data indicate that magnesium sulphate infusion suppresses the release of catecholamines by the heart, which is an indirect index of sympathetic efferent neuronal activity.     

Thromboembolism in lung cancer patients]

We reviewed 649 primary lung cancer patients with special reference to the occurrence of thromboembolism. Thirteen episodes of thromboembolism were detected in 12 (1.8%) of the 649. Eight of the 12 were men, and their mean age was 63. Adenocarcinoma was the predominant cell type. Most patients had an advanced stage of the disease, but in some in the cancer was at an early stage. In 5 cases, the finding of thromboembolisms led to diagnosis of the lung cancer (38.5%). Anticoagulant therapy was performed in 9 cases, of which 8 responded without serious complication. We emphasize the importance of anticoagulant therapy as a therapy indicated for thromboembolism in patients with lung cancer.     

CTLA-4 AT-repeat polymorphism reduces the inhibitory function of CTLA-4 in Graves' disease.

Graves' disease (GD) is thought to be an autoimmune disease with a strong genetic component. Candidate genes include human leukocyte antigen (HLA) class II genes and CTLA-4. The CTLA-4 gene has a variable length AT-repeat polymorphism in the 3'-untranslated region. We previously found that the AT-repeat of 104 bp or longer was associated with GD. In this study, we categorized patients with GD and normal controls (NC) by genotyping the CTLA-4 AT-repeat and investigated the function of CTLA-4. Peripheral blood mononuclear cells (PBMC) and DNA were prepared from adult Caucasians (NC = 34, GD = 37). Genotypes of the AT-repeat polymorphism were divided into three groups according to their alleles. We related the CTLA-4 polymorphism in each genotype to augmentation of T-cell proliferation induced by a soluble anti-CTLA-4 antibody during incubation with irradiated Epstein-Barr virus (EBV)-transformed B cells. Proliferation of T cells from subjects with the 86/86 bp (shorter) allele was less than T cells from patients with longer alleles. The length of the AT-repeat allele correlated inversely with augmentation of proliferation after CTLA-4 blockade in subjects with GD. The CTLA-4 AT-repeat polymorphism affects the inhibitory function of CTLA-4. The long AT-repeat allele is associated with reduced control of T-cell proliferation and thus contributes to the pathogenesis of GD.