R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.

At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMNs revealed that a secreted activator of Wnt signaling, R-spondin 2 (Rspo2), is highly expressed in SMNs.

Reactions of community members regarding community health workers' activities as a measure of the impact of a training program in Amazonas, Brazil.

Objectives: The aim of this study was to evaluate the impact of community health worker (CHW) training on recognition and satisfaction regarding the performance of CHWs among members of the community in Amazonas, Brazil, which is a resource-poor area underserved with regard to medical health-care accessibility.

Methods: Baseline and endline surveys concerning recognition and satisfaction with respect to CHW performance among members of the community were conducted by interview using a questionnaire before and after implementation of a program to strengthen community health projects in Manicoré, Amazonas, Brazil. One of the components of the project was CHW refresher training, which focused on facilitating adequate use of health-care services and providing primary health care, including health guidance.

Effects of Vibration Therapy on Immobilization-Induced Hypersensitivity in Rats.

Background: Cast immobilization induces mechanical hypersensitivity, which disturbs rehabilitation. Although vibration therapy can reduce various types of pain, whether vibration reduces immobilization-induced hypersensitivity remains unclear.

Objective: The purpose of this study was to investigate the preventive and therapeutic effects of vibration therapy on immobilization-induced hypersensitivity.

Upregulation of interleukin-1β/transforming growth factor-β1 and hypoxia relate to molecular mechanisms underlying immobilization-induced muscle contracture.

Introduction: In this study we investigated the molecular mechanism underlying muscle contracture in rats.

Methods: The rats were divided into immobilization and control groups, and soleus muscles of the right and left sides were selected for analyses.

Results: The levels of CD11b and α-SMA protein, IL-1β, and TGF-β1 mRNA, and type I and III collagen protein and mRNA were significantly greater in the immobilization group than in the control group at all time-points.

Neuromuscular disease. DOK7 gene therapy benefits mouse models of diseases characterized by defects in the neuromuscular junction.

The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal muscle. Defects in NMJ transmission cause muscle weakness, termed myasthenia. The muscle protein Dok-7 is essential for activation of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb-girdle myasthenia (DOK7 myasthenia), a neuromuscular disease characterized by small NMJs.

[Increased rate of serum uric acid levels in Yusho sufferers].

We measured serum uric acid levels in Yusho sufferers annually from 2007 to 2012 in Nagasaki prefecture. We observed an increased rate of serum uric acid levels in 38.2% of the male and 5.

Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats.

This study examined mechanical and thermal hypersensitivity in the rat hind paw during cast immobilization of the hind limbs for 4 or 8 weeks and following cast removal. Blood flow, skin temperature, and volume of the rat hind paw were assessed in order to determine peripheral circulation of the hind limbs. Sensitization was analyzed by measuring the expression of the calcitonin gene-related peptide (CGRP) in the spinal dorsal horn following cast immobilization.

Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis.

Objective: We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG).

Methods: In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35.

A case of Japanese spotted fever complicated with central nervous system involvement and multiple organ failure.

Japanese spotted fever (JSF), first reported in 1984, is a rickettsial disease characterized by high fever, rash, and eschar formation. A 61-year-old man was admitted to a local hospital in Nagasaki City, Japan, after several days of high fever and generalized skin erythema. His condition deteriorated and laboratory findings indicated disseminated intravascular coagulation (DIC).

Protein-anchoring strategy for delivering acetylcholinesterase to the neuromuscular junction.

Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq(-/-) mice recovered motor functions, synaptic transmission, as well as the morphology of the NMJ.

[Histochemical findings of and fine structural changes in motor endplates in diseases with neuromuscular transmission abnormalities].

We herein review the histochemical findings and fine structural changes of motor endplates associated with diseases causing neuromuscular transmission abnormalities. In anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG), type 2 fiber atrophy is observed, and the motor endplates show a reduction in the nerve terminal area, simplification of the postsynaptic membrane, decreased number of acetylcholine receptors, and deposition of immune complexes. In anti-MuSK antibody-positive MG, the fine structure shows a decrease in the postsynaptic membrane length, but the secondary synaptic cleft is preserved.

[Differences in the bone mineral density in patients with Kanemi Yusho treated before and after the age of 18 years].

This study examined patients with Kanemi Yusho. The patients' height, weight, and bone mineral density were measured. The density of the distal end of the radius was measured using dual energy X-ray absorptiometry and the calcaneum was measured with ultrasound.

False-positive accumulation of metaiodobenzylguanidine in a case with acute intermittent porphyria.

We report a 36-year-old woman presenting with hypertensive encephalopathy followed by bulbar palsy and quadriplegia. After an extensive screening for secondary causes of hypertension, the patient was suspected of having pheochromocytoma due to increased levels of catecholamines in the plasma and the urine, and positive (131)I-metaiodobenzylguanidine (MIBG) accumulation in the gallbladder. However, MIBG accumulation was not reproducible without any tumors accompanying this accumulation in the gallbladder.

Rheumatoid vasculitis of crural muscles confirmed by muscle biopsy in the absence of inflammatory myopathy: histologic and MRI study.

A 60-year-old man who had been diagnosed as rheumatoid arthritis admitted to our hospital by dysesthesia on his legs with edema. Nerve conduction velocity test led to diagnosis of mononeuritis multiplex. Magnetic resonance imaging (MRI) of lower legs showed high intensity in slow tau inversion recovery.

[Bone mineral density, PCB, PCQ and PCDF in Yusho].

We measured bone mineral density of the distal end of radius with dual energy X-ray absorptiometry, serum cross-linked N-telopeptides of type I collagen, serum bone-specific alkaline phosphatase, serum Ca, serum P, blood PCB level, blood PCQ level and blood PCDF level in Yusho. As a result, the osteoporosis group (< 70% of the young adult mean [YAM] bone mineral density [BMD]) was observed in 7.1% of the studied male subjects.

Low-level laser irradiation promotes the recovery of atrophied gastrocnemius skeletal muscle in rats.

Low-level laser (LLL) irradiation promotes proliferation of muscle satellite cells, angiogenesis and expression of growth factors. Satellite cells, angiogenesis and growth factors play important roles in the regeneration of muscle. The objective of this study was to examine the effect of LLL irradiation on rat gastrocnemius muscle recovering from disuse muscle atrophy.

Immobilization-induced cartilage degeneration mediated through expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and chondromodulin-I.

Immobilization results in thinning of the articular cartilage and cartilage degeneration, although the exact mechanisms are not clear yet. Hypoxia is thought to contribute to the degeneration of articular cartilage. We investigated the roles of hypoxia inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), and the newly cloned antiangiogenic factor, chondromodulin-I (ChM-1), in cartilage degeneration in immobilized joints.

Effects of therapeutic ultrasound on joint mobility and collagen fibril arrangement in the endomysium of immobilized rat soleus muscle.

This study examined effects of therapeutic ultrasound on joint mobility and collagen fibril arrangement in the endomysium of immobilized rat soleus muscle. Twenty-two male Wistar rats were divided randomly into control (n = 5) and experimental groups (n = 17). In the experimental group, bilateral ankle joints of each rat were fixed in full plantar flexion with a plaster cast over a 4-wk period.

[Overview: MuSK/Dok-7].

MuSK/Dok-7 mediate the clustering of acetylcholine receptor (AChR) during synapse formation and are expressed at the mature neuromuscular junction. These proteins are deeply associated with myasthenia gravis (MG) and congenital myasthenic syndrome (CMS). Compared with MG patients with AChR antibodies, those with muscle-specific tyrosine kinase (MuSK) antibodies are more likely to present oculobulbar than limb weakness, myasthenic crisis and muscle wasting.

[Decreased serum aldolase levels in Yusho].

We measured serum aldolase levels in Yusho sufferers annually between the years 2000 and 2005. We observed a decrease in serum aldolase levels in 47.7% of the patients studied.

Vasculitic neuropathy in a patient with hereditary C1 inhibitor deficiency.

Objective: To report the clinical, pathological, and mutational features of hereditary C1 inhibitor (C1INH) deficiency as a cause of isolated vasculitic neuropathy.

Patient: A 35-year-old woman with sensorimotor mononeuritis multiplex and facial palsy.

Results: The sural nerve biopsy results showed a decrease of myelinated fibers with axonal degeneration and severe hypersensitivity vasculitis, with deposition of C1q on vessel walls.

Laminin-induced autoimmune myositis in rats.

The present study aimed to examine if immunization with laminin causes myositis in rats and whether the pathologic findings mirror human polymyositis and dermatomyositis. Rats were immunized with an emulsion of laminin and complete Freund's adjuvant. As a result, muscle fiber necrosis with infiltrating macrophages was frequently observed and mononuclear cells were observed in the endomysium.

[A case of myasthenia gravis with anti-MuSK antibodies showing a dramatic improvement with plasma exchange].

A 49-year-old woman with seronegative myasthenia gravis (SNMG) was admitted to our hospital with severe respiratory failure, proximal muscle weakness and bulbar palsy. Permanent tracheostomy and continuous mechanical ventilation were performed. At a previous hospital, she was diagnosed as SNMG on the basis of the positive waning during 3 Hz repetitive stimulation of the ulnar nerve, although no acetylcholine receptor antibodies (Ab) were detected by serological examination.