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S Kusunoki

Publications and source records attributed to S Kusunoki.

At least 19 recordsLinked to original sources

Anti-ganglioside complex antibodies associated with severe disability in GBS.

Ganglioside complexes (GSCs) are known as target antigens in Guillain-Barré syndrome (GBS). To elucidate the clinical importance of the anti-GSC antibodies in GBS, we investigated serum antibodies to GSCs containing two of the gangliosides, GM1, GD1a, GD1b and GT1b, and analyzed clinical features of anti-GSC-positive GBS patients. Thirty-nine (17%) of 234 GBS patients had IgG anti-GSC antibodies. Anti-GSC-positive GBS had antecedent gastrointestinal infection and lower cranial nerve deficits more frequently than control GBS. The presence of antibody specificity to GD1a/GD1b and/or GD1b/GT1b was significantly associated with severe disability and a requirement for mechanical ventilation.

Adult↗

Effect of the aldose reductase inhibitor fidarestat on experimental diabetic neuropathy in the rat.

AIMS/HYPOTHESIS: Fidarestat, an aldose reductase inhibitor (ARI), has been reported to improve clinical symptoms and nerve conduction deficits in human diabetic neuropathy. We evaluated the dose-dependency and some of the mechanisms of the drug action in experimental diabetic neuropathy (EDN). METHODS: Control rats and rats with EDN were fed on normal pellets or pellets containing 0.00066% (1 mg/kg) or 0.00263% (4 mg/kg) fidarestat for 10 weeks. We evaluated the effect of fidarestat on nerve blood flow (NBF), electrophysiology, and sorbitol and fructose content in sciatic nerve in control and diabetic rats. For detection of oxidative stress in peripheral nerve, we measured sciatic nerve reduced glutathione (GSH) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunolabelling of dorsal root ganglion (DRG) neurons. RESULTS: NBF, compound muscle action potential and amplitude of C-potential were significantly improved in diabetic rats fed on the diet supplemented with fidarestat. Fidarestat suppressed the increase in sorbitol and fructose, normalised GSH in sciatic nerve, and reduced the number of 8-OHdG-positive cells in DRG. CONCLUSIONS/INTERPRETATION: Fidarestat improves neuropathy, presumably via an improvement in oxidative stress. This study supports a role for fidarestat in the treatment of diabetic neuropathy.

8-Hydroxy-2'-Deoxyguanosine↗

CSF tau protein: a new prognostic marker for Guillain-Barré syndrome.

We measured the CSF tau protein levels in 26 patients with Guillain-Barré syndrome. The levels of the poor outcome group (Hughes grade at 6 months was between II and VI, n = 6) were higher than those of the good outcome group (0 or I, n = 20) (p < 0.0005). The higher levels of CSF tau may reflect axonal degeneration and could predict a poor clinical outcome in Guillain-Barré syndrome.

Adult↗

Activity-dependent conduction block in multifocal motor neuropathy: magnetic fatigue test.

BACKGROUND: Multifocal motor neuropathy (MMN) is often misdiagnosed as motor neuron disease, especially when overt evidence of conduction block (CB) is lacking. Activity-dependent CB (ADCB), defined as transient CB induced by brief exercise, has been recently found in MMN but not in ALS. METHODS: To test the diagnostic utility of ADCB for differentiating MMN from ALS, the authors recorded the compound muscle action potentials (CMAPs) from small hand muscles by magnetically stimulating nerve roots before and after 1 minute of maximal voluntary contraction (magnetic fatigue test). They examined nine patients with MMN with unequivocal clinical responses to IV immunoglobulins (IVIgs), yet lacked CB according to the conventional criteria. RESULTS: Six MMN patients had postexercise CB/temporal dispersion maximum in the immediate postexercise period. ADCB in an MMN patient improved after IVIg. Further analysis revealed that prolongation of the duration from the onset to the positive peak of the CMAP was the most sensitive indicator for MMN, presumably because the phase cancellation obscures the abnormalities of the other parameters. CONCLUSION: The magnetic fatigue test is useful in detecting mild conduction block presumably located in a proximal nerve segment in patients with multifocal motor neuropathy who do not fulfill its conventional electrodiagnostic criteria.

Adult↗

Anti-ganglioside complex antibodies in Miller Fisher syndrome.

BACKGROUND: Some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain-Barré syndrome (GBS). Anti-GSC antibodies may be associated with particular clinical features of GBS. OBJECTIVE: To investigate antibodies to GSCs in the sera of patients with Miller Fisher syndrome (MFS) characterised by elevation of the IgG anti-GQ1b antibody. RESULTS: In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b-GM1 complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without sensory symptoms had anti-GQ1b/GM1 antibodies. CONCLUSIONS: At least three different specificities in MFS-associated antibodies, GQ1b-specific, anti-GQ1b/GM1-positive and anti-GQ1b/GD1a-positive, were observed. In patients with MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may be considered to be prime target antigens for serum antibodies. A tendency to escape sensory disturbances is shown by anti-GQ1b/GM1-positive MFS.

Adult↗

Anti-GQ1b antibody as a factor predictive of mechanical ventilation in Guillain-Barré syndrome.

Compared with 87 unventilated patients with Guillain-Barré syndrome (GBS), 44 ventilated patients with GBS more frequently had multiple cranial nerve involvement (91 vs 50%; p < 0.001) and IgG anti-GQ1b antibody (27 vs 8%; p = 0.006). In GBS patients without ophthalmoparesis, the presence of IgG anti-GQ1b antibody was associated with respiratory failure (12 [3/25] vs 0% [0/67]; p = 0.04). The presence of the antibody may be a factor predictive of respiratory failure in GBS.

Adult↗

GalNAc-GD1a in human peripheral nerve: target sites of anti-ganglioside antibody.

BACKGROUND: The authors previously reported that immunoglobulin G (IgG) antibody to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) is associated with the pure motor variant of Guillain-Barré syndrome (GBS). Elucidation of the localization of GalNAc-GD1a in human peripheral nerve tissue may lead to understanding of the pathogenetic role of anti-GalNAc-GD1a antibody in GBS. METHODS: IgG anti-GalNAc-GD1a-monospecific antibody was purified from anti-GalNAc-GD1a antibody-positive rabbit sera through an affinity column. Anti-neurofilament-200 monoclonal and anti-HNK-1 monoclonal antibodies were used as the markers for axon and myelin. Immunohistochemical study using double fluorescence labeling technique was conducted in human ventral roots (VR), dorsal roots (DR), intramuscular nerves, and sural nerves. Human teased ventral fibers also were studied. RESULTS: Anti-GalNAc-GD1a antibody immunostained an inner part of compact myelin and additionally a periaxonal-axolemma-related portion in the VR, small-diameter DR fibers, and IM nerves. In sural nerves, small fibers were selectively stained. In VR, the staining was localized in the paranodal region. CONCLUSION: Anti-GalNAc-GD1a antibodies in patients' sera may bind to those regions in the VR and IM nerves where GalNAc-GD1a is localized, and may function in the pathogenesis of pure motor type GBS. Further investigation is needed to explain the discrepancy between the immunolocalization of GalNAc-GD1a in sensory nerves and the absence of sensory disturbance in patients with GBS with IgG anti-GalNAc-GD1a antibodies.

Animals↗

Stiff-person syndrome associated with invasive thymoma: a case report.

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

Adult↗

Anti-Gal-C antibodies in GBS subsequent to mycoplasma infection: evidence of molecular mimicry.

The authors previously reported the presence of antibody against galactocerebroside (Gal-C) in sera from patients with Guillain-Barré syndrome subsequent to Mycoplasma pneumoniae infection. Anti-Gal-C antibody activities in these sera were inhibited specifically by the M. pneumoniae reagent. A rabbit anti-Gal-C antibody recognized several glycolipids in M. pneumoniae. These data show that a Gal-C-like structure is present in M. pneumoniae, indicative of molecular mimicry between a major myelin glycolipid, Gal-C, and M. pneumoniae.

Animals↗

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3.

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

Aged↗

Variability in immunohistochemistries of IgM M-proteins binding to sulfated glucuronyl paragloboside.

Serum IgMs from 4 of 12 patients with polyneuropathy and IgM M-proteins that bind to sulfated glucuronyl paragloboside (SGPG) strongly immunostained the human peripheral nerve myelin (group A), whereas those from the other eight patients strongly immunostained the cytoplasm of the Schwann cells surrounding the myelin sheath with only weak staining of the myelin (group B). Strong immunostaining of peripheral myelin by IgMs from group A patients may be due to the strong cross-reactivities against P0 and peripheral myelin protein-22 (PMP-22), which are localized in compact myelin. Only three patients (all in group B) showed some response to the immunotherapies. Weak reactivities to P0 and and PMP-22 might indicate the possibility of improvement after the immunotherapies.

Aged↗

Guillain-Barré syndrome associated with IgG monospecific to ganglioside GD1b.

The authors examined serum antiglycolipid antibodies in 445 patients with Guillain-Barré syndrome (GBS). Among them, nine had anti-GD1b IgG antibodies with no reactivity to other glycolipids tested. All those patients had sensory disturbance, and none had the primary axonal form. Anti-GD1b IgG antibodies may bind to primary sensory neurons and paranodal myelin, where GD1b is localized, and be involved in the pathogenesis of sensory disturbance and demyelination. However, more study is needed to substantiate the roles of anti-GD1b IgG antibodies.

Adult↗

Guillain-Barré syndrome with IgM antibody to the ganglioside GalNAc-GD1a.

We analyzed the characteristics of 29 Guillain-Barré syndrome (GBS) patients with IgM anti-GalNAc-GD1a antibodies. Fourteen of them had had an antecedent cytomegalovirus infection (CMV group) and 12 gastrointestinal infection (G-I group). Most of the G-I group patients (nine of 12) were subsequent to Campylobacter jejuni infection. Electrophysiological results in both groups patients predominantly indicated demyelinating neuropathy. The CMV group patients were characterized by slow progression and frequent facial and sensory deficits. IgM antibodies in their sera recognized an epitope shared by GalNAc-GD1a and GM2. The G-I group patients frequently showed motor type of GBS with cranial nerves spared. IgM antibodies specific to GalNAc-GD1a were present in their sera.

Adult↗

Characterization of a phospholipid antigen reacting with serum antibody in patients with peripheral neuropathies and paraproteinemia.

A phospholipid antigen that reacted with the serum antibody from a patient with peripheral neuropathy and paraproteinemia with both impaired sensory and motor functions, but not with sera from patients with only impaired sensory functions and healthy controls, was purified from bovine cauda equina as a minor component with a concentration of about 0.6 microg per gram wet-weight tissue. The structure of the phospholipid was characterized as lysophosphatidylinositol by means of thin-layer chromatography, gas-liquid chromatography, and negative-ion fast-atom-bombardment mass spectrometry. The major fatty acid component of this phospholipid was stearic acid (> 81%). Our data suggest the possible involvement of a lysophospholipid antigen in the immunopathogenesis of peripheral neuropathies with severe motor and sensory dysfunctions. There is an intriguing possibility that the difference in immunoreactivity of serum antibodies may underlie the differential clinical manifestations in patients with peripheral neuropathy and paraproteinemia.

Animals↗

Glucose loading during primary culture has opposite effects on the viability of hepatocytes exposed to potassium cyanide and to iodoacetic acid.

Whether or not to apply nutritional pretreatment and how to do so are controversial issues with respect to the liver about to undergo aggressive intervention. We studied the effects of glucose loading on the viability of hepatocytes that were subsequently exposed to the inhibitors of carbohydrate metabolism, potassium cyanide (KCN) and iodoacetic acid (IAA). After rat hepatocytes were cultured for 24 hours in Leibovitz's L-15 medium containing 0, 10, 20, and 30 mmol/L glucose, the medium was replaced with modified Hanks-HEPES buffer with or without 2.5 mmol/L KCN or 0.5 mmol/L IAA. Lactate dehydrogenase (LDH) activity, lactate concentration, and pH of the supernatant were measured after 0, 2, 4, and 6 hours of exposure to KCN and after 0, 20, 40, and 60 minutes of exposure to IAA. Glycogen and adenosine triphosphate (ATP) contents in the hepatocytes were measured simultaneously. Hepatocytes cultured with various concentrations of glucose for 24 hours stored levels of glycogen in proportion to the glucose concentration in the culture medium without any significant difference in viability. The hepatocytes cultured with higher glucose concentrations maintained a higher ATP content and released less LDH and more lactate, and the pH decreased in the supernatant during exposure to KCN. Conversely, hepatocytes cultured with lower glucose concentrations maintained a higher ATP content and released less LDH during exposure to IAA. In conclusion, prior glucose loading appears to be beneficial for hepatocytes if oxidative phosphorylation is to be inhibited, whereas withholding glucose appears to be beneficial if glycolysis is to be inhibited.

Adenosine Triphosphate↗

[A case of Miller Fisher syndrome with pharyngeal palsy as an initial symptom].

We report herein a rare case of Miller Fisher syndrome with pharyngeal palsy as an initial symptom. A 68-year-old man admitted to our hospital with pharyngeal palsy two weeks after a respiratory infection. He subsequently developed ataxic gait, paresthesia in the upper limbs and ophthalmoplegia. Double-filtrated-plasmapheresis had been performed four times and all the symptoms subsided within two months. In the acute phase of the disease, the titers of anti-GQ1b and GT1a antibodies were elevated. The titer of anti-GT1a antibody was higher than that of anti-GQ1b antibody. Recently, the activity of serum anti-GT1a antibody has been supposed to be associated with pharyngeal palsy. In the present case, higher titer of anti-GT1a antibody compared with that of anti-GQ1b antibody could possibly cause pharyngeal palsy as an initial symptom of Miller Fisher syndrome.

Aged↗