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Keiichiro Susuki

Publications and source records attributed to Keiichiro Susuki.

At least 19 recordsLinked to original sources
PubMed2006

Leukocyte and complement activation by GM1-specific antibodies is associated with acute motor axonal neuropathy in rabbits.

Acute motor axonal neuropathy (AMAN) in humans is associated with the presence of GM1-specific antibodies. Immunization of rabbits with GM1-containing ganglioside mixtures, purified GM1, or Campylobacter jejuni lipo-oligosaccharide exhibiting a GM1-like structure elicits GM1-specific antibodies, but axonal polyneuropathy only occurs in a subset of animals. This study aimed to dissect the molecular basis for the variable induction of AMAN in rabbits. Therefore, we analyzed the pro-inflammatory characteristics of GM1-specific antibodies in plasma samples from ganglioside-immunized rabbits with and without neurological deficits. GM1-specific plasma samples from all rabbits with AMAN were capable of activating both complement and leukocytes, in contrast to none of the plasma samples from rabbits without paralysis. Furthermore, GM1-specific IgG-mediated activation of leukocytes was detected before the onset of clinical signs. These data suggest that AMAN only occurs in rabbits that develop GM1-specific antibodies with pro-inflammatory properties.

Acute Disease↗
PubMed2006

Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barré syndrome.

The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain-Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity. Ganglioside-specific IgG antibodies generally induced leukocyte activation, irrespective of specificity. The magnitude of leukocyte degranulation correlated with GM1- and GQ1b-specific IgG titers, but not with disease severity. Finally, GM1-specific IgA activated leukocytes through the IgA receptor, FcalphaRI (CD89). Therefore, both ganglioside-specific IgG and IgA can recruit leukocyte effector functions, which may be relevant in the pathogenesis of GBS and MFS.

Adolescent↗
PubMed2006

Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy with anti-SGPG IgM antibody.

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was resistant to corticosteroids and immunosuppressants, but after administration of rituximab, clinical symptoms improved and the patient remained in a stable state for approximately 10 months. Rituximab may be a potent therapeutic option for refractory cases of CIDP irrespective of detectable M-protein in either serum or urine.

Adult↗
PubMed2006

Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton.

Paranodal junctions of myelinated nerve fibers are important for saltatory conduction and function as paracellular and membrane protein diffusion barriers flanking nodes of Ranvier. The formation of these specialized axoglial contacts depends on the presence of three cell adhesion molecules: neurofascin 155 on the glial membrane and a complex of Caspr and contactin on the axon. We isolated axonal and glial membranes highly enriched in these paranodal proteins and then used mass spectrometry to identify additional proteins associated with the paranodal axoglial junction. This strategy led to the identification of three novel components of the paranodal cytoskeleton: ankyrinB, alphaII spectrin, and betaII spectrin. Biochemical and immunohistochemical analyses revealed that these proteins associate with protein 4.1B in a macromolecular complex that is concentrated at central and peripheral paranodal junctions in the adult and during early myelination. Furthermore, we show that the paranodal localization of ankyrinB is disrupted in Caspr-null mice with aberrant paranodal junctions, demonstrating that paranodal neuron-glia interactions regulate the organization of the underlying cytoskeleton. In contrast, genetic disruption of the juxtaparanodal protein Caspr2 or the nodal cytoskeletal protein betaIV spectrin did not alter the paranodal cytoskeleton. Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes.

Animals↗
PubMed2006

Anti-GT1a IgG antibodies in a child with severe Guillain-Barré syndrome.

This report describes a male, age 8 years 10 months, with severe Guillain-Barré syndrome after Campylobacter jejuni infection. The patient developed fulminant muscle weakness, external ophthalmoplegia, bulbar palsy, and respiratory distress. A high level of serum monospecific anti-GT1a immunoglobulin G antibody was detected. He was treated with intravenous immunoglobulins and artificial ventilation. Two years after the onset, the patient still suffered from residual leg weakness and foot drop. After 3 years and clinical recovery, the antibody was no longer detectable. This report presents the first case in childhood suggesting an association between a severe Guillain-Barré syndrome after C. jejuni enteritis with monospecific anti-GT1a immunoglobulin G antibody.

Antibodies, Anti-Idiotypic↗
PubMed2006

[A case of acute oropharyngeal palsy with nasal voice as main symptom].

We report a patient with acute oropharyngeal palsy following enteritis. A 19-year-old woman developed increasing nasal voice over a few days. Neurological examination on day 7 of her course showed paretic dysarthria and mild weakness of neck flexion and quadriceps femoris muscle (Medical Research Council grade, 4+). Her palatal movement was diminished, whereas both palatal and pharyngeal reflex was normal. She could swallow water, although she had a slight amount of liquid reflux to her nose on swallowing. High titers of serum anti-Campylobacter jejuni, anti-GQ1b and anti-GT1a IgG antibodies were detected. Her symptoms improved gradually without any treatment, and disappeared by 40 days from neurological onset. Nasal voice with slight swallowing impairment as initial symptom has been rarely reported, but can occur in acute oropharyngeal palsy. Therefore, neurologists should take into account the possibility of Guillain-Barré syndrome and the regional variants in patients who show nasal voice during the initial stage.

Acute Disease↗
PubMed2005

Difference in neuropathogenetic mechanisms in human furious and paralytic rabies.

Whereas paralysis is the hallmark for paralytic rabies, the precise pathological basis of paralysis is not known. It is unclear whether weakness results from involvement of anterior horn cells or of motor nerve fibers. There is also no conclusive data on the cause of the neuropathic pain which occurs at the bitten region, although it has been presumed to be related to sensory ganglionopathy. In this study, six laboratory-proven rabies patients (three paralytic and three furious) were assessed clinically and electrophysiologically. Our data suggests that peripheral nerve dysfunction, most likely demyelination, contributes to the weakness in paralytic rabies. In furious rabies, progressive focal denervation, starting at the bitten segment, was evident even in the absence of demonstrable weakness and the electrophysiologic study suggested anterior horn cell dysfunction. In two paralytic and one furious rabies patients who had severe paresthesias as a prodrome, electrophysiologic studies suggested dorsal root ganglionopathy. Postmortem studies in two paralytic and one furious rabies patients, who had local neuropathic pain, showed severe dorsal root ganglionitis. Intense inflammation of the spinal nerve roots was observed more in paralytic rabies patients. Inflammation was mainly noted in the spinal cord segment corresponding to the bite in all cases; however, central chromatolysis of the anterior horn cells could be demonstrated only in furious rabies patient. We conclude that differential sites of neural involvement and possibly different neuropathogenetic mechanisms may explain the clinical diversity in human rabies.

Adult↗
PubMed2004

Various immunization protocols for an acute motor axonal neuropathy rabbit model compared.

Various ganglioside immunization protocols were examined to refine the procedure for establishing an animal model of acute motor axonal neuropathy. The most effective was subcutaneous injection of an emulsion of 2.5mg of bovine brain ganglioside mixtures, keyhole lympet hemocyanin, and complete Freund's adjuvant to Japanese white rabbits, repeated at 3-week intervals. Under that protocol, all the rabbits developed marked flaccid paralysis associated with plasma anti-GM1 IgG antibody. This acute motor axonal neuropathy rabbit model also could be reproduced by the use of incomplete Freund's adjuvant, methylated bovine serum albumin, and New Zealand white rabbits. These results provide useful information for the confirmation of and further research on the model.

Acute Disease↗
PubMed2004

Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome.

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1-2 wk after various infections, in particular, Campylobacter jejuni enteritis. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] between the bacterial lipooligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in Guillain-Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1 IgG from patients with Guillain-Barré syndrome did not induce paralysis but blocked muscle action potentials in a muscle-spinal cord coculture, indicating that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.

Animals↗
PubMed2004

Guillain-Barre syndrome with meningoencephalitis after Campylobacter jejuni infection.

A 14-year-old boy presented with progressive ascending muscle weakness, urinary retention and disturbed consciousness. Initially his cerebrospinal fluid showed pleocytosis, and protein-cellular dissociation developed later. Campylobacter jejuni was isolated from his stool and serum anti-ganglioside antibodies were positive. Our case suggests that coexistence of meningoencephalitis at an early stage of illness does not necessarily exclude the diagnosis of Guillain-Barre syndrome.

Adolescent↗
PubMed2004

[A variant of Guillain-Barré syndrome with prominent bilateral peripheral facial nerve palsy--facial diplegia and paresthesias].

A patient with Facial diplegia and paresthesias, a rare regional variant of Guillain-Barré syndrome (GBS), is described. A 37-year-old woman developed paresthesias in the distal limbs and subsequently bifacial weakness. She had had a preceding episode of laryngitis. Neurological examination showed severe facial diplegia with loss of taste sensation on the tip of the tongue. Limb muscle power was preserved. Deep tendon reflexes were generally absent. She complained of paresthesias in the distal limbs, but sensory examination was normal. Cerebrospinal fluid showed albuminocytological dissociation. Electrophysiological studies revealed severe facial nerve involvements and demyelinative findings in her limbs. Intravenous immunoglobulin rapidly improved the abnormal sensation in her limbs. Although facial diplegia gradually lessened after the therapy, mild residual weakness was noted 6 months after the neurological onset. To diagnose facial diplegia and paresthesias, it is important to clarify the findings common to typical GBS such as the antecedent illness, acute and monophasic course, distal paresthesias, areflexia, cerebrospinal fluid albuminocytological dissociation, and demyelinative conduction abnormalities in the limbs.

Adult↗
PubMed2003

Clinical deterioration in Bickerstaff's brainstem encephalitis caused by overlapping Guillain-Barré syndrome.

A 37-year-old man developed an acute encephalitic condition after respiratory infection. His condition rapidly deteriorated, and he experienced ophthalmoplegia, tetraplegia, loss of brainstem reflexes and deep tendon reflexes, and deep coma. Electrophysiological evaluations indicated involvement of the peripheral nerve as well as the brainstem. Follow-up studies found acute progression of peripheral nerve damage. Serum anti-GQ1b IgG antibody was present. The initial condition was diagnosed as Bickerstaff's brainstem encephalitis, and subsequent overlapping of Guillain-Barré syndrome probably was responsible for the clinical deterioration. When unusual worsening is observed in clinically suspected encephalitis, neurologists must take into account the possibility of associated Guillain-Barré syndrome and related disorders.

Adult↗
PubMed2003

Longitudinal changes of anti-ganglioside antibodies before and after Guillain-Barré syndrome onset subsequent to Campylobacter jejuni enteritis.

Anti-ganglioside antibodies frequently are present in sera from patients with Guillain-Barré syndrome (GBS) during the acute phase, but no patients in whom anti-ganglioside antibodies were tested before the onset of the syndrome have been reported. We describe the first case of GBS subsequent to Campylobacter jejuni infection, in which longitudinal changes in anti-ganglioside antibody titers were measured before and after the onset of limb weakness. Serum antibody titers against GM1 (IgM/IgG), GM1b (IgM/IgG), GalNAc-GD1a (IgM/IgG), and GD1b (IgG) were highest on the day of onset, but negative before onset. Anti-C. jejuni IgG and IgA antibody titers paralleled those of the anti-ganglioside antibodies, indicative that C. jejuni infection triggered anti-ganglioside antibody production. Press et al. [J. Neurol. Sci. 190 (2001) 41] reported that anti-ganglioside antibody titers peaked during the recovery phase, but our findings are counter to theirs. We speculate that anti-ganglioside antibodies are the primary effectors of nerve damage in GBS.

Antibodies↗
PubMed2003

Acute motor axonal neuropathy rabbit model: immune attack on nerve root axons.

Macrophages in the periaxonal space and surrounding intact myelin sheath are the most prominent pathological feature of acute motor axonal neuropathy (AMAN). We describe this characteristic in nerve roots from paralyzed rabbits immunized with bovine brain ganglioside or GM1. IgG was deposited on nerve root axons. Distal nerve conduction was preserved, and late F wave components were absent during the acute phase. Initial lesions were located mainly on nerve root axons, as in human AMAN. This study thus provides supportive evidence that the rabbits constitute a model of AMAN.

Action Potentials↗
PubMed2003

Axonal pharyngeal-cervical-brachial variant of Guillain-Barré syndrome without Anti-GT1a IgG antibody.

We report two cases of pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome (GBS). The patients developed dysphagia and weakness of the neck and arms subsequent to Campylobacter jejuni infection. Oropharyngeal palsy recovered poorly. Electrophysiological findings demonstrated axonal conduction failure. Anti-GD1a immunoglobulin G (IgG) antibody was detected in one case, and anti-GM1b IgG antibody in another. Anti-GT1a IgG and immunoglobulin M (IgM) antibodies were negative in both cases. The current cases suggest that the PCB and axonal variants of GBS form a continuous spectrum from the viewpoint of electrophysiological studies as well as antiganglioside serology.

Adult↗
PubMed2003

[Ataxic Guillain-Barré syndrome with delayed facial diplegia].

We described a patient with ataxic Guillain-Barré syndrome who subsequently developed facial diplegia. A 38-year-old man developed ataxia, distal limb paresthesias, mild dysphagia, urinary retention and orthostatic hypotension a week after an episode of laryngitis. He had high titers of serum anti-GQ1b, anti-GD1b, anti-GM1b, anti-GT1a, and anti-GD1a IgG antibodies during the acute phase. Although the initial symptoms markedly improved by intravenous immunoglobulin therapy, asymmetric facial diplegia subsequently occurred and remained longer than ataxia. Similar course of facial nerve palsy has been reported in patients with Fisher syndrome. Common pathophysiological mechanism may function in the development of delayed facial diplegia in Fisher syndrome and ataxic Guillain-Barre syndrome.

Adult↗