Hiroyuki Ishihara

A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot-Marie-Tooth disease type 1

A novel mutation (Arg381Cys) in the second zinc-finger domain of early growth response 2 (EGR2) was identified in a late-onset Charcot--Marie--Tooth disease type 1 (CMT1) patient. This patient had initial symptoms of numbness and weakness in the leg at age 59, and a median nerve motor conduction velocity of 27 m/s. A sural nerve biopsy showed a severe loss of myelinated fibers with numerous onion bulbs. This is the first report of the EGR2 mutation presenting a late onset of CMT1 phenotype. Its mutation was a different amino acid substitution at codon 381 (Arg381His) which demonstrated congenital hypomyelinating neuropathy or early-onset CMT1. This report suggests that the EGR2 mutation represents divergent phenotypes at codon 381, which may be a mutation hotspot.

Clinical features and skewed X-chromosome inactivation in female carriers of X-linked recessive spinal and bulbar muscular atrophy.

Abstract In X-linked recessive disorders, a few female gene carriers become symptomatic. Recent evidence implicates skewed X-chromosome inactivation in such female carriers. We studied the clinical features of eight female gene carriers of X-linked recessive spinal and bulbar muscular atrophy (SBMA), and evaluated the relationship between phenotype and genotype from the viewpoint of X-chromosome inactivation. Seven of eight cases were symptomatic, showing mild muscle weakness, frequent muscle cramps, slight elevation of the serum creatinine kinase level, or neurogenic changes on the electromyogram. Only one carrier was asymptomatic clinically. For the estimation of X-chromosome inactivation, the methylation status of the androgen receptor (AR) gene was determined by polymerase chain reaction-based assay. Highly skewed inactivation of the affected AR gene was found in the asymptomatic carrier, while symptomatic carriers had a random or lower inactivation pattern of the affected AR gene. These findings suggest that most female carriers of SBMA show some clinical abnormalities, and highly skewed inactivation of the affected X-chromosome seems to closely relate with escape of the manifestation in female carriers of SBMA.

White muscle disease in humans: myopathy caused by selenium deficiency in anorexia nervosa under long term total parenteral nutrition

Selenium is an essential trace element that is known to be a component of glutathione peroxidase, a scavenger of hydroperoxides.1 Its deficiency causes a decrease in glutathione peroxidase function, thereby resulting in oxidative damage to many organs. The two major clinical signs in patients with selenium deficiency are skeletal myopathy and cardiomyopathy. White muscle disease, named because of its characteristic acolouration of the muscle is a myopathy caused by selenium deficiency in animals in the areas where the soil is low in selenium.2 In humans, it was demonstrated that Keshan disease, dilated cardiomyopathy in the Keshan area in China, was caused by selenium deficiency.3 In addition, there are reports that selenium deficiency occurs in patients who are nourished by total parenteral nutrition alone for a long time because of inflammatory bowel disease or resection of the intestine due to various intestinal diseases.4 5 We experienced a case of anorexia nervosa with skeletal myopathy caused by selenium deficiency under long term parenteral nutrition. A 28 year old woman was admitted to our hospital with a 7 year history of anorexia nervosa receiving parenteral nutrition intermittently. At admission, she complained …

Transforming growth factor-β enhances connective tissue growth factor expression in L6 rat skeletal myotubes

Transforming growth factor (TGF)-beta plays an important role in fibrosis of various organs and tissues. TGF-beta1 stimulates fibroblastic cells to form extracellular matrix (ECM), and regulates all critical events in wound healing. Connective tissue growth factor (CTGF), a TGF-beta-inducible molecule, has recently been reported to promote fibroblast proliferation, migration, adhesion and extracellular matrix formation, both in vivo and in vitro. In this study, we demonstrated that TGF-beta1 enhances CTGF mRNA and protein levels in L6 rat skeletal muscle myotubes. TGF-beta might, therefore, play a role in fibrosis of skeletal muscle by stimulating CTGF expression in the muscle tissue itself.

Reduced Fractional Anisotropy in Early-Stage Cerebellar Variant of Multiple System Atrophy

In patients with the cerebellar variant of multiple system atrophy (MSA‐C), reduced fractional anisotropy (FA) has been reported in several brain areas. However, since previous studies have employed predetermined regions of interest (ROI), the brain areas showing the earliest alterations in FA are unknown. The sensitivity of detecting early‐stage MSA‐C and the time course of the FA reduction are also unknown. The purpose was to address these issues to determine the diagnostic value of FA for early diagnosis.

HLA typing in focal myositis

It is still controversial if idiopathic focal myositis is a part of systemic polymyositis. We present here four patients, including identical twins, with focal myositis accompanied by the same HLA typings. Gradually developing unilateral calf muscle pain was an initial symptom in all patients. Neither muscular weakness nor creatine kinase (CK) elevation was observed, while minimal inflammatory findings such as erythrocyte sedimentation rate (ESR) increase appeared in serum. Magnetic resonance imaging (MRI) revealed localized abnormalities of calf muscles. Biopsy specimen was characterized by perimysial and endomysial inflammatory infiltration consisted of T cells and macrophages and rare necrotic fibers. Corticosteroid administrations ameliorated their symptoms and signs, though recurrence occurred along with decreasing doses. HLA typings common to all patients were A2, B62, Cw3, and DQ3, whereas HLA-D DNA typings were DQB1 *0303 for two patients, and DQB1*0302 for three patients. These findings suggest that at least some focal myositis may be a new disease unit, with a common genetic background but not a part of systemic polymyositis.

A 51-year-old man with intramedullary spinal cord abscess having a patent foramen ovale

The authors report a case of a 51-year-old man with intramedullary spinal cord abscess (ISCA) having a patent foramen ovale (PFO). He developed fever and tetraplegia after a recent dental treatment. MRI showed ISCA with longitudinal swelling from the upper cervical to the lumbar spinal cord. Cerebrospinal fluid (CSF) analysis indicated bacterial meningitis, and the culture of CSF revealed Streptococcus viridans. Transoesophageal echocardiography revealed the existence of a PFO. We suspected another possibility other than systemic bacteraemia, that paradoxical bacteric embolisation through PFO after the dental treatment caused ISCA. While several reports of brain abscess with PFO are available, this is the first report of ISCA with PFO.

Total Clinical Course and Autopsy Findings of Left Ventricular Outflow Tract Obstruction Due to Sigmoid Septum: Histologically Proven Isolated Basal Septal Hypertrophy

We herein report the total course and autopsy findings of a woman who complained of chest discomfort and had plasma B-type natriuretic peptide 43 pg/mL and left ventricular outflow tract obstruction (with a resting pressure gradient of 181 mmHg) due to sigmoid septum at 73 years of age. Betaxolol and verapamil decreased her pressure gradient to 14 mmHg, but the pressure gradient (101 mmHg) again worsened. The betaxolol dose was increased and cibenzoline was added, resulting in a pressure gradient ≤21 mmHg. An autopsy was performed after death from a urinary tract infection at 80 years of age. The absence of any disarray of cardiac myocytes was confirmed.

Bone metabolism in epilepsy patients: An analysis of 30 cases taking classic anti‐epileptic drugs

The majority of classic anti‐epileptic drugs can decrease bone mineral density through the acceleration of vitamin D metabolism by cytochrome P450.