Infantile onset myasthenia gravis with MuSK antibodies.
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Adult↗
Biomedical subjects
M Motomura
Publications and source records attributed to M Motomura.
Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.
In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.
Journal Article↗
A novel mutation (T61I) in the gene encoding tumour necrosis factor receptor superfamily 1A (TNFRSF1A) in a Japanese patient with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) associated with systemic lupus erythematosus.
OBJECTIVE: To identify potential mutations in the tumour necrosis factor receptor superfamily 1A gene (TNFRSF1A) in a Japanese female patient with recurrent fever complicated by systemic lupus erythematosus (SLE), and in her family members. METHODS: DNA sequencing of exons 1-10 of the TNFRSF1A gene was performed to determine mutations that might be associated with the tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Moreover, the TNFRSF1A gene was examined in Japanese patients with autoimmune diseases, including SLE, rheumatoid arthritis (RA), mixed connective tissue disease (MCTD) and Behçet's disease, and in healthy Japanese controls. Enzyme-amplified sensitivity immunoassay (EASIA) analysis was used to assess serum levels of TNF, the 55-kDa TNF receptor (TNFRSF1A) and the 75-kDa TNF receptor (TNFRSF1B). Membrane TNFRSF1A expression was analysed on the surface of peripheral blood mononuclear cells by flow cytometry. RESULTS: A novel mutation, a heterozygous C to T transition in exon 3 which substitutes an isoleucine for a threonine at position 61 (T61I) was detected in the TNFRSF1A gene derived from the genomic DNA of a Japanese female TRAPS patient. Two nieces and one nephew, all with a similar clinical phenotype, also possessed the same TNFRSF1A mutation. We further demonstrated the same mutation in five of 60 SLE patients (8.3%) and in five of 120 healthy individuals (4.2%), with no significant differences. Although high titres of serum TNF and soluble TNFRSF1B protein were observed in this patient, low titres of soluble TNFRSF1A protein were detected. However, a defect in TNFRSF1A shedding in vitro was not observed in monocytes derived from this patient. CONCLUSION: This is the first report of a TRAPS patient associated with SLE with a novel TNFRSF1A mutation (T61I).
Adolescent↗
Anti-ryanodine receptor antibodies and FK506 in myasthenia gravis.
Anti-ryanodine receptor (RyR) antibodies were measured in sera from 33 myasthenia gravis (MG) patients using three peptides from the human RyR1 sequence, two C-terminal peptides included in the functional calcium release channel, and an N-terminal peptide implicated in ion-conduction. Antibodies were more frequently positive against the two C-terminal peptides, particularly in thymoma-associated MG. In a preliminary open trial with FK506, immunosuppressant and enhancer of RyR-related sarcoplasmic calcium release, the authors observed the sustained benefits in anti-RyR-positive MG patients.
Adult↗
Seronegative Lambert-Eaton myasthenic syndrome: study of 110 Japanese patients.
The authors characterized the clinical and immunologic features of 110 patients with Lambert-Eaton myasthenic syndrome (LEMS). Anti-P/Q-type voltage-gated calcium channels (VGCC) antibodies were detected in 85% of the patients (seropositive) but not in the rest (seronegative). Except for the indication that small cell lung carcinoma is less common in seronegative patients, no significant differences were found in the clinical characteristics of patients who had or did not have anti-P/Q-type VGCC antibodies. The results of passive transfer experiments suggest that seronegative LEMS is also an autoantibody-mediated disorder.
Adolescent↗
Paraneoplastic striatal encephalitis.
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Brain↗
Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.
Autonomic dysfunction, as well as neuromuscular involvement, is a common manifestation of Lambert-Eaton myasthenic syndrome (LEMS). Dry mouth and impotence have been described as typical features of autonomic dysfunction, but neurogenic bladder is infrequent or subclinical in LEMS. We report a patient with neurogenic bladder secondary to LEMS whose condition responded to 3,4-diaminopyridine (3,4-DAP). In this patient's serum, results of repeated measurement with P/Q-type VGCC antibodies proved positive, but not with N-type VGCC and synaptotagmin antibodies. A review of the literature turned up a few patients with voiding dysfunction related to LEMS, but no urodynamic studies were done on these patients. Ours is the first case in which 3,4-DAP was efficacious in treating LEMS and neurogenic bladder. Responses of 3,4-DAP in urodynamic studies suggest that in this LEMS patient neurogenic bladder was caused by defective neurotransmission both in the autonomic detrusor and skeletal abdominal muscles.
4-Aminopyridine↗
Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria.
To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.
Albuminuria↗
Lambert-Eaton myasthenic syndrome associated with an anterior mediastinal small cell carcinoma.
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Carcinoma, Small Cell↗
Isolation of cortical MTs from tobacco BY-2 cells.
We isolated the cortical microtubules (CMTs) from tobacco BY-2 cells to identify their components. By centrifugation of protoplasts homogenized in the presence of taxol, a MT-stabilizing reagent, in a density gradient of Percoll, we obtained membranous vesicles to which MTs forming a sheet-like bundle were attached. Rhodamine-conjugated Ricinus communis agglutinin I (RCA-I), a lectin that bound to the surface of protoplasts, stained these vesicles, indicating that they were plasma membrane (PM) vesicles that retained CMTs. CMTs were released by solubilization of PM vesicles with Triton X-100. A sheet-like array of CMTs was retained even after solubilization of PM vesicles. Immunoblot analysis of the isolated CMTs demonstrated the presence of tubulin, actin, the 65 kDa microtubule-associated protein (MAP) and a 130 kDa RCA-I binding protein. Purification of the isolated CMTs by the temperature dependent disassembly-reassembly cycling method revealed four polypeptides, 190, 120, 85 and 65 kDa, co-assembling with CMTs.
Cell Fractionation↗
Semiquantitative measurement of acetylcholine receptor at the motor end-plate in myasthenia gravis.
OBJECTIVE: The purpose of this study was to investigate whether this semiquantitative measurement of the motor end-plate acetylcholine receptors (AChRs) can be used to confirm the diagnosis of myasthenia gravis (MG), and in particular ocular MG. METHODS: Motor point biopsies were performed from the biceps brachii muscles. Measurement of AChRs was made in peroxidase-labeled alpha-bungarotoxin stained muscle specimens. PATIENTS: Twenty patients with ocular MG, 37 with generalized MG, 5 with Lambert-Eaton myasthenic syndrome, 3 with botulism, 8 with amyotrophic lateral sclerosis, and 8 controls were included in this study. RESULTS: AChRs were decreased in all patients with generalized MG and in 80% of ocular MG including patients without detectable circulating anti-AChR antibodies, as compared with the control subjects. CONCLUSION: This method is useful to confirm the diagnosis of MG, in particular ocular MG without detectable anti-AChR antibodies.
Adolescent↗
[Guillain-barré syndrome associated Campylobacter jejuni serotype Penner 2: a case report].
We described a 15-year-old male who had Guillain-Barré syndrome(GBS). Nine days after watery diarrhea, the patient developed pain and weakness of foot muscles. On admission, the nerve conduction studies revealed peripheral neuropathy with axonal degeneration and demyelination. Campylobacter jejuni(C. jejuni) with serotype of Lior 4, Penner 2 was isolated from his stool culture. IgM anti-GM 1 antibody and other various anti-ganglioside antibodies were detected in his serum. After receiving plasma exchange and intravenous immunoglobulin therapy, he was able to walk without assistance. In general, C. jejuni with the serotype Penner 19 has been isolated from many GBS patients. In this patient, C. jejuni with the serotype of Penner 2 was isolated. The serotype is detected commonly in Miller Fisher syndrome.
Adolescent↗
[Lambert-Eaton myasthenic syndrome].
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Adolescent↗
[Lambert-Eaton myasthenic syndrome: diagnosis and treatment].
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular and autonomic transmission in which IgG autoantibodies lead to presynaptic voltage-gated calcium channel (VGCC) loss, or as a paraneoplastic disorder in association with small cell lung carcinoma (SCLC). Recent results strongly suggest that the antibodies to P/Q-type VGCC are the principal pathogenic factors in LEMS. Here, we present diagnosis and treatment of LEMS patients. Proximal weakness, depressed tendon reflexes, autonomic symptoms, and electrical posttetanic potentiation together are essential to accurately diagnose LEMS. The diagnosis is established immunologically by the presence of anti-P/Q-type VGCC antibodies, detected using the (125)I-omega-conotoxin MVIIC radioimmunoassay, which will be present in 85% of LEMS patients. The drug 3,4-diaminopyridine with anti-cholinesterase inhibitor is most effective in LEMS patients with or without SCLC. In LEMS with SCLC, specific tumor therapy will often improve the neurological disorder. In some cases plasmapheresis or intravenous immunoglobulin may be indicated.
English Abstract↗
Apheresis treatment in Lambert-Eaton myasthenic syndrome.
The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q-type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti-P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibody. The first case, a 72-year-old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q-VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti-P/Q-VGCC antibody titers. The second case, a 73-year-old male presenting with leg weakness, was treated by PE and double-filtration plasmapheresis. The P/Q-VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q-VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.
Aged↗
QT dispersion is increased in diabetic patients with foot ulcer.
QT dispersion, a measure of inhomogenous ventricular repolarization, was measured in diabetic patients with foot ulcer. We recruited 75 patients with non insulin-dependent diabetes mellitus: patients with neuropathic ulcer (n=15, NU group), with ischemic ulcer (n=20, IU group), with previous myocardial infarction (n=20, MI group) and without any diabetic microangiopathies (n=20, DC group). We also studied normal control subjects (n=15, NC group). The interlead variability of rate corrected QT interval (QTc dispersion) was calculated. QTc interval in the MI group was significantly higher than that in the NC or DC but showed no difference in the NU and IU groups. QTc dispersion in the IU (54+/-15 msec) as well as MI (60+/-21 msec) group were significantly higher than the NC (36+/-18 msec) or DC group (39+/-14 msec). This may be due to complicated coronary artery disease in the IU group. Furthermore, QTc dispersion was also increased (49+/-14 msec) in the NU group in which cardiac autonomic nervous dysfunction was suggested. Patients with both types of diabetic ulcer demonstrated increased QT dispersion due to atherosclerosis or neurological disorder.
Aged↗
[Juvenile cerebral infarction associated with heparin cofactor II abnormality. A case report].
A 15-year-old woman with a history of transient dysarthria two years before, suddenly developed weakness of right upper extremity, right facial palsy, and dysarthria. She was admitted to our hospital on the third day. She had no hypertension, heart murmur and oedema. On neurological examination, she had mild right hemiparesis including face muscles and mild dysarthria. The right knee jerk was brisk with no Babinski's sign. Ataxia and sensory disturbance were not present. T2-weighted MRI showed a hyperintensity at the posterior limb of the left internal capsule. Cerebral angiography was unremarkable. Ultracardiography and 24-hour electrocardiography were normal. Laboratory data revealed no inflammatory findings, liver dysfunction, hyperglycemia and hyperlipidemia. Antinuclear and anticardiolipin antibodies were negative. Prothrombin time was normal, but activated partial thromboplastin time was slightly prolonged (35.4 sec, normal 25.2-34.4). Protein C, protein S and antithrombin III were normal. Heparin cofactor II (HC II) activity was decreased (44%) with normal HC II antigen (79%) and so she was diagnosed as heparin cofactor II deficiency type II (heparin cofactor II abnormality). Her father manifesting thromboangitis obliterans also had low HC II activity with normal HC II antigen. However, on her genetic analysis, we didn't detect any mutations in the coding region of HC II gene. Until now she has no recurrence of cerebrovascular attacks. On the basis of these results, we suspect that HC II deficiency was a possible risk factor of cerebral infarction in this case because she was so young and had no general risk factors except for HC II. No stroke associated with HC II deficiency type II has been reported up to date. This case is worth considering etiologies of juvenile cerebral infarction.
Adolescent↗
[Response to immunoadsorption and steroid therapies in a patient with carcinomatous Lambert-Eaton myasthenia syndrome accompanied by disturbed consciousness].
A 75 year-old man developed gait disturbance and somnolence over a period of three months. Electroencephalography indicated theta slowing and cerebrospinal fluid (CSF) examination showed an increased cell count of 23/microliter and IgG of 7.2 mg/dl. He showed fatigue-inducing muscle weakness and the Harvey-Masland test demonstrated a low M-wave amplitude of 0.6 mV which increased to 3 mV with 50 Hz high-frequency stimulations. The serum titer of P/Q type anti-voltage-gated calcium channel (VGCC) antibody was quite high at 11,901 pmol/L (< 20 pmol/L). The patient was diagnosed as Lambert-Eaton myasthenia syndrome (LEMS) although at first no carcinoma was detected. Immunoadsorption therapy with a phenilalanine absorber column resulted in a reduction in the titer of anti-VGCC antibody to half of the initial concentration, but it increased again within several days. Six repeats of immunoadsorption and concomitant administration of prednisolone at a dose of 40 mg daily succeeded in reducing the anti-VGCC antibody titer of to below 390 pmol/L. The patient's consciousness disturbance and muscle weakness improved simultaneously over the next month and the lumbar puncture and electroencephalography showed normal results. Prednisolone administration was maintained at a dose of 30 mg daily and one year after occurrence of the first symptoms, a small cell lung carcinoma was detected. There was no evidence of limbic encephalitis such as an elevation of anti-Hu antibody in his CSF and serum or abnormal signal intensities in the hippocampal formations on MR imaging. The etiology of his disturbed consciousness remained unclear, but, in the case of LEMS, it could be a manifestation of a paraneoplastic syndrome associated with small-cell lung carcinoma. It is noteworthy that the anti-VGCC antibody titer rose to 1,262 pmol/L 2 months before his tumor was detected and decreased to 286 pmol/L after chemotherapy. P/Q type anti-VGCC antibody could therefore be a useful tumor marker reflecting activity of small-cell carcinoma.
Aged↗