Biomedical subjects

Taku Fukuda

Publications and source records attributed to Taku Fukuda.

6 recordsLinked to original sources

PubMed2006

[A case of Mycobacterium fortuitum meningitis following surgery for meningioma].

A 57-year-old woman had undergone surgery for meningioma. After the surgery, she suffered from repeated fever and headache. One year after surgery, she was admitted to our hospital for further examination. Cerebro-spinal fluid (CSF) findings indicated bacterial meningitis infection. Germ culture, acid-fast bacterium culture, PCR for mycobacteriosis and cryptococcus antigens as well as cytological examination of CSF were checked repeatedly. However, all examinations were negative and etiology was unknown. We treated with many anti-bacterial, anti-fungal and anti-tubercular drugs, but CSF findings were not improved. We repeated CSF examination and finally Mycobacterium fortuitum (M. fortuitum) was isolated. Clarithromycin (CAM) was started for M. fortuitum meningitis. After drug sensitivity testing, levofloxacin (LVFX), which was effective against M. fortuitum, was added to CAM, after which clinical and CSF findings improved dramatically. M. fortuitum rarely causes CNS infection. Several English literatures on M. fortuitum meningitis after traumatic injury and surgery have been published. Its CSF findings distinctly resemble those of bacterial meningitis, but are resistant to the usual antituberculosis drugs. We reported a case of M. fortuitum meningitis associated with surgery for meningioma.

Clarithromycin↗

PubMed2005

Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis.

Muscle-specific tyrosine kinase (MuSK) antibodies are found in some patients with "seronegative" myasthenia gravis (MG), but how they cause myasthenic symptoms is not clear. We visualized acetylcholine receptors (AChRs) and complement component 3 (C3) in muscle biopsies from 10 Japanese MG patients with MuSK antibodies, compared with 42 with AChR antibodies. The AChR density was not significantly decreased in MuSK antibody (Ab)-positive end-plates compared with AChR antibody-positive end-plates, and C3 was detected in only two of eight MuSK Ab-positive patients. MuSK antibodies do not appear to cause substantial AChR loss, complement deposition, or morphological damage. Effects on MuSK function need to be explored.

Adolescent↗

PubMed2004

Structural abnormalities at neuromuscular synapses lacking multiple syntrophin isoforms.

The syntrophins are modular adapter proteins that function by recruiting signaling molecules to the cytoskeleton via their direct association with proteins of the dystrophin protein family. We investigated the physiological function of beta2-syntrophin by generating a line of mice lacking this syntrophin isoform. The beta2-syntrophin null mice show no overt phenotype, or muscular dystrophy, and form structurally normal neuromuscular junctions (NMJs). To determine whether physiological consequences caused by the lack of beta2-syntrophin were masked by compensation from the alpha-syntrophin isoform, we crossed these mice with our previously described alpha-syntrophin null mice to produce mice lacking both isoforms. The alpha/beta2-syntrophin null mice have NMJs that are structurally more aberrant than those lacking only alpha-syntrophin. The NMJs of the alpha/beta2-syntrophin null mice have fewer junctional folds than either parent strain, and the remaining folds are abnormally shaped with few openings to the synaptic space. The levels of acetylcholine receptors are reduced to 23% of wild type in mice lacking both syntrophin isoforms. Furthermore, the alpha/beta2-syntrophin null mice ran significantly shorter distances on voluntary exercise wheels despite having normal neuromuscular junction transmission as determined by micro-electrode recording of endplate potentials. We conclude that both alpha-syntrophin and beta2-syntrophin play distinct roles in forming and maintaining NMJ structure and that each syntrophin can partially compensate for the loss of the other.

Animals↗

PubMed2004

Are MuSK antibodies the primary cause of myasthenic symptoms?

OBJECTIVE: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). BACKGROUND: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. METHODS: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MUSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. RESULTS: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MUSK reveals one rare and two common DNA polymorphisms. CONCLUSIONS: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.

Adult↗

PubMed2003

Myasthenic syndrome caused by mutation of the SCN4A sodium channel.

In a myasthenic syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, nerve stimulation at physiologic rates rapidly decremented the compound muscle action potential. Intercostal muscle studies revealed no abnormality of the resting membrane potential, evoked quantal release, synaptic potentials, acetylcholine receptor channel kinetics, or endplate ultrastructure, but endplate potentials depolarizing the resting potential to -40 mV failed to excite action potentials. Pursuing this clue, we sequenced SCN4A encoding the skeletal muscle sodium channel (Nav1.4) and detected two heteroallelic mutations involving conserved residues not present in 400 normal alleles: S246L in the S4/S5 cytoplasmic linker in domain I, and V1442E in the S3/S4 extracellular linker in domain IV. The genetically engineered V1442E-Na channel expressed in HEK cells shows marked enhancement of fast inactivation close to the resting potential, and enhanced use-dependent inactivation on high-frequency stimulation; S246L is likely a benign polymorphism. The V1442E mutation in SCN4A defines a novel disease mechanism and a novel phenotype with myasthenic features.

Adult↗

PubMed2003

Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome.

The aim of this study was to clarify whether autoimmunity against P/Q-type voltage-gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD-LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q-type VGCC in these patients and controls for the amount and ratio of autoantibody-channel complex using an 125I-omega-conotoxin MVIIC-binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q-type VGCC measured by Scatchard analysis were reduced in PCD-LEMS patients (63.0 +/- 7.0 fmol/mg, n = 3), compared with the controls (297.8 +/- 38.9 fmol/mg, n = 6). The ratio of autoantibody-VGCC complexes to total P/Q-type VGCCs measured by immunoprecipitation assay were increased in PCD-LEMS patients. We analysed cerebellar specimens by autoradiography using (125)I-omega-conotoxin MVIIC, which specifically binds to P/Q-type VGCCs. In PCD-LEMS cerebellum, the toxin binding sites of P/Q-type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q-type VGCCs in the normal cerebellum. This suggests that P/Q-type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD-LEMS.

Aged↗