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Biomedical subjects

Nobuhiro Yuki

Publications and source records attributed to Nobuhiro Yuki.

At least 37 records · Page 2Linked to original sources
PubMed2005

Electrophoresis-assisted open-tubular liquid chromatography/mass spectrometry for the analysis of lipooligosaccharide expressed by Campylobacter jejuni.

Lipooligosaccharide (LOS) is the major component of the external membrane of Campylobacter jejuni. LOS contains a hydrophobic moiety, lipid A, and a hydrophilic moiety, oligosaccharide. Due to the unique mimicry of human ganglioside structures and potential involvement in the induction of the autoimmune polyneuropathies, Guillain-Barré and Miller Fisher syndromes, the structural characterization of C. jejuni LOS has received much attention. We have been using capillary zone electrophoresis-mass spectrometry to analyze O-deacylated LOS from C. jejuni. In an attempt to optimize the separation conditions, the effect of methanol on the separation of LOS was investigated. It was found that methanol resulted in stronger adsorption of LOS onto the wall of fused-silica capillary. In this paper, we applied this adsorption to perform electrophoresis-assisted open-tubular liquid chromatography electrospray mass spectrometry for the analysis of O-deacylated LOS mixtures from C. jejuni. The analytical potential of the proposed strategy for the analysis of O-deacylated LOS glycoforms from five bacterial colonies is demonstrated. Online tandem mass spectrometry is shown to provide a powerful tool for characterization of variations in the hexosamine backbone, phosphorylation of the lipid A, and sialic acid sequence information.

Campylobacter jejuni↗
PubMed2005

Ganglioside mimicry as a cause of Guillain-Barré syndrome.

PURPOSE OF REVIEW: Campylobacter jejuni is the most frequent agent of antecedent infection in an axonal variant of Guillain-Barré syndrome, acute motor axonal neuropathy, and anti-GM1 or anti-GD1a IgG antibody is also associated with acute motor axonal neuropathy. Molecular mimicry has been found between human GM1 ganglioside and the lipo-oligosaccharide of C. jejuni isolated from an acute motor axonal neuropathy patient. Progress has been made in Guillain-Barré syndrome research, especially on acute motor axonal neuropathy subsequent to C. jejuni enteritis. RECENT FINDINGS: Sensitization of rabbits with C. jejuni lipo-oligosaccharide, as well as GM1, induced the production of anti-GM1 IgG antibody, and the subsequent development of acute flaccid paralysis. Pathological changes in rabbit peripheral nerves were identical to those seen in human acute motor axonal neuropathy. These findings provide conclusive evidence that molecular mimicry is a cause of human autoimmune disease. Ganglioside-like lipo-oligosaccharide is synthesized by sialyltransferase Cst-II, N-acetylgalactosaminyl-transferase CgtA, and galactosyltransferase CgtB. There is a strong association between the simultaneous presence of these genes and Guillain-Barré syndrome-associated C. jejuni strains. Knockout mutants of C. jejuni genes involved in lipo-oligosaccharide sialylation had reduced reactivity with anti-GM1 sera from Guillain-Barré syndrome patients, and did not induce an anti-GD1a IgG antibody response in mice. Lipo-oligosaccharide biosynthesis genes appear to be essential for the induction of anti-GM1 or anti-GD1a IgG antibody and the subsequent development of acute motor axonal neuropathy. SUMMARY: The concept that carbohydrate mimicry causes autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.

Animals↗
PubMed2005

Epidemiology of Campylobacter jejuni isolated from patients with Guillain-Barré and Fisher syndromes in Japan.

Campylobacter jejuni isolation is the standard for the diagnosis of this type of bacterial infection, but there have been no epidemiological studies of a large number of C. jejuni isolates from patients with Guillain-Barre syndrome (GBS) and Fisher syndrome (FS). For 13 years, stool specimens from GBS/FS patients have been sent from 378 hospitals throughout Japan to the Tokyo Metropolitan Institute of Public Health. A total of 113 strains (11%) were isolated from the stool specimens from 1,049 patients. The isolation rate did not differ by region. The rates were 22% for 449 patients with a history of diarrhea and 2% for the others. An additional 18 isolates were provided by various hospitals. There was no noticeable seasonal distribution in the onset of C. jejuni isolated from patients with GBS/FS. The male/female ratios were 1.7:1 for GBS and 2.2:1 for FS. The patient age range showed a peak in 10- to 30-year-old subjects who had GBS and in 10- to 20-year-old subjects who had FS. The predominance of young adults and male patients who had C. jejuni-associated GBS/FS may be related to the preponderance of young adults and male patients who had C. jejuni enteritis. The median interval from diarrhea onset to neurologic symptom onset was 10 days for GBS/FS. Penner's C. jejuni serotype HS:19 was more frequently present in GBS (67%) than in enteritis (6%) patients. HS:2 was more frequent in FS (41%) than in enteritis (14%) patients. These findings suggest that certain C. jejuni strains specifically trigger GBS and that others specifically trigger FS.

Adolescent↗
PubMed2005

[Clinical features and treatment of Fisher syndrome].

To clarify the clinical features of patients with Fisher syndrome, we reviewed detailed clinical profiles and laboratory findings in 267 cases. The men:women ratio was about 3:2, median age at onset 42 years, and the two peaks were 30-39 and 50-59. Sixty two percent of the patients had an antecedent illness with upper respiratory infectious symptoms. As initial symptoms, 63% had diplopia, 33% ataxic gait, and 17% dysesthesia of the upper and/or lower limbs. Besides ophthalmoplegia, ataxia, and areflexia, blepharoptosis (42%), internal ophthalmoplegia (35%), facial palsy (25%), and bulbar palsy (16%) were present. Limb weakness was significant in 25% and sensory impairment in 52%. CSF albuminocytological dissociation was present in 80% after the second week. Most patients were given intravenous immunoglobulin (59%). None died, and almost all had a monophasic remitting course and a generally good outcome.

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

Clinical correlates of serum anti-GT1a IgG antibodies.

Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Fisher syndrome (FS) or Bickerstaff's brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The nosological relationship between these conditions has yet to be established. To investigate the relationships between each manifestation and between clinical features and the coexistence of anti-GQ1b IgG, we reviewed neurological signs present during illnesses of 140 patients who had anti-GT1a IgG. Based on our criteria, FS was diagnosed for 64 (46%) patients, GBS for 22 (16%), BBE for 14 (10%), and PCB for 6 (4%). Overlapping conditions were diagnosed for some patients: FS and GBS (5%), PCB and FS (5%), BBE and GBS (4%), and PCB and BBE (1%). Patients who initially had bulbar palsy developed not only PCB but FS or BBE. The population of anti-GT1a-positive patients frequently had ophthalmoplegia, ataxia, and areflexia, whereas the subpopulation who had anti-GT1a IgG without GQ1b reactivity frequently had preceding diarrhea as well as oropharyngeal, neck, and limb weakness. Patients with anti-GT1a IgG presented a variety of clinical conditions, indicative of a continuous clinical spectrum. A major part of this clinical variation was due to the coexistence of anti-GQ1b IgG. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to FS and BBE as well.

Adolescent↗
PubMed2004

Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and GalNAc-GD1a.

This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE) associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to Campylobacter jejuni enteritis, the patient rapidly developed consciousness disturbance and hyperreflexia in addition to external ophthalmoplegia and cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic theta activities, predominantly in the front-central area. He received high doses of immunoglobulin intravenously and had completely recovered 3 months later. High anti-GM1b and anti-GalNAc-GD1a IgM antibody titers present during the acute phase decreased with his clinical improvement. An absorption study showed the anti-GM1b and anti-GalNAc-GD1a IgM antibodies to be cross-reactive. Anti-GM1b and anti-GalNAc-GD1a antibodies have been detected in some patients who developed Guillain-Barré syndrome after C. jejuni enteritis, whereas the anti-GQ1b IgG antibody is associated with BBE. Infection by C. jejuni bearing a GM1b-like or GalNAc-GD1a-like lipooligosaccharide may trigger the production of anti-GalNAc-GD1a and anti-GM1b IgM antibodies. It is not clear why our patient developed BBE rather than Guillain-Barré syndrome. These antibodies may, however, prove useful serological markers for identifying BBE patients who do not have the anti-GQ1b IgG antibody.

Ataxia↗
PubMed2004

Ataxic Guillain-Barré syndrome associated with anti-GM1b and anti-GalNAc-GD1a antibodies.

Ataxic Guillain-Barré syndrome (GBS) associated with anti-GQ1b IgG antibody has been reported. We, however, have had a patient with ataxic GBS who had IgG antibodies to the minor gangliosides GM1b and GalNAc-GD1a, and we therefore retrospectively investigated the clinical features of patients who had antibodies to GM1b or GalNAc-GD1a, but not to GQ1b. Information on patients' antecedent illnesses, initial symptoms, neurological signs, and CSF findings was reviewed in those with ataxic GBS or Fisher syndrome (FS) with anti-GM1b or anti-GalNAc-GD1a IgG antibodies. We tested whether the anti-GM1b and anti-GalNAc-GD1a antibodies are cross-reactive and constructed three-dimensional structural models of GM1b and GalNAc-GD1a. Ataxic GBS was diagnosed in 1 of 65 patients who had both anti-GM1b and anti-GalNAc-GD1a antibodies and in 3 of 159 patients who had anti-GM1b antibody without anti-GalNAc-GD1a antibody: FS was diagnosed in 1 of the 159 patients and in 1 of 35 who had anti-GalNAc-GD1a antibody without anti-GM1b antibody. All the patients' antibodies to GM1b or GalNAc-GD1a were associated with the IgG isotype. The clinical features of patients with ataxic GBS associated with anti-GM1b or anti-GalNAc-GD1a IgG antibodies did not differ from those of patients who had anti-GQ1b IgG antibody. Absorption study findings for serum from the patient who had both anti-GM1b and anti-GalNAc-GD1a IgG antibodies showed significant absorbance of anti-GM1b IgG antibody by GalNAc-GD1a and of anti-GalNAc-GD1a IgG antibody by GM1b, indicating that these antibodies are cross-reactive. This is the first report of ataxic GBS or FS associated with anti-GM1b or anti-GalNAc-GD1a IgG antibodies. These autoantibodies, as well as anti-GQ1b IgG antibody, may function in the development of some patients with ataxic GBS and FS.

Adult↗
PubMed2004

The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome.

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.

Animals↗
PubMed2004

[Outcome after Guillain-Barré syndrome: comparison of motor function status and changes in social life].

Effects on the motor function and social life of the patients after Guillain-Barré syndrome (GBS) were studied. A letter of inquiry was sent to the patients in November 2001; 98 patients responded validly. The questionnaire had questions with 3 possible answers related to situations at work, at home, and about leisure activities. The Hughes functional grade, which evaluates physical conditions, and arm disability scale scores were assessed. Although the assessments showed good recovery in most patients who had had a job, 31% had to quit work, and 17% had to discontinue their leisure activities. These physical assessments accurately reflected the severity of the conditions of the patients given in-home care (8%) because daily life activities depend on muscle strength. Of the 75 patients who had no, or minimal, neurological symptoms or signs in both assessments, 53% reported one or more changes in their social lives. We conclude that the questionnaire answers show that GBS patients may have serious psychosocial outcomes that are not measurable by the usual physical assessments. These findings may be a help when considering the rehabilitation of GBS patients and their return to social life.

Activities of Daily Living↗
PubMed2004

[Clinical features of neuropathies in a group of patients associated with anti-GalNAc-GD1a antibody].

To clarify the clinical features of patients with anti-GalNAc-GD1a antibody, we retrospectively investigated which conditions were associated with anti-GalNAc-GD1a antibody in a large number of patients. Sixty-four out of 1,713 patients had anti-GalNAc-GD1a IgG antibody. Fifty-seven (89%) were diagnosed with Guillain-Barré syndrome (GBS) or atypical GBS with preserved deep tendon reflexes. These patients were characterized by young man, antecedent diarrhea, distal-dominant limb weakness, and absence of cranial nerve impairment and sensory disturbance. Some of sera from patients had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies associated with axonal GBS. Our study suggests that the anti-GalNAc-GD1a antibody testing is useful for supporting the diagnosis of GBS. In addition, fine specificity of the antibody also was clarified.

Autoantibodies↗
PubMed2004

[Details about the first medical examinations of patients with Guillain-Barré or Fisher syndromes].

Randomized controlled trials have shown beneficial responses to plasma exchange and intravenous immunoglobulin in Guillain-Barré syndrome (GBS), but details about the first medical examination of patients with GBS and Fisher syndrome (FS) have not been reported. We investigated the period from first consultations to treatment after the onset of patients with GBS and FS. A questionnaire was used to collect informations on 247 patients with GBS and 125 with FS, all of whom had been referred to our neuroimmunological laboratory informations between January 2001 and October 2001 for serum anti-ganglioside antibody tests. A letter of inquiry was sent to the primary physicians; 150 (61%) patients with GBS and 72 (58%) with FS responded validly. Patients with GBS generally consulted an internist [58%, neurologist (21%)] or orthopedist (17%), those with FS an internist [52%, neurologist (26%)] or ophthalmologist (25%). Consultation with a neurologist usually came after one with a physician. We conclude that physicians should be aware that patients may have GBS or FS, and that such recognition is useful for early diagnosis and treatment of these syndromes.

Guillain-Barre Syndrome↗
PubMed2004

[Intravenous immunoglobulin therapy for Guillain-Barré syndrome in Japan: changes in treatment after its inclusion in health insurance coverage].

In December 2000, health insurance in Japan was instituted for the use of intravenous immunoglobulin (IVIg) therapy for the acute phase of Guillain-Barré syndrome (GBS) that required aid to walk or worse. A nation-wide questionnaire survey was made to investigate the changes in treatment. In September 2002, a letter of inquiry was sent to experienced physicians in 620 teaching hospitals associated with the Societas Neurologica Japonica and 417 associated with the Societas Paediatrica Japonica. Totally, 356 neurologists (57%) and 223 pediatricians (53%) responded. After the introduction of IVIg health insurance coverage, more than 90% thought that GBS patients should be hospitalized and given treatment. The frequency of hospitals with an intensive care unit, however, was 70%. Before IVIg therapy's inclusion in health insurance coverage, many neurologists selected plasmapheresis (88%) rather than IVIg (4%) therapy, whereas pediatricians preferred IVIg (49%) to plasmapheresis (12%). After its inclusion, 75% of neurologists selected IVIg rather than plasmapheresis (21%), whereas pediatricians selected IVIg (86%) over plasmapheresis (5%). In March 2003, new payment system based on Diagnosis Procedure Combination was introduced into 82 large hospitals, and leads to difficulties to select IVIg in the hospitals. The payment system should be revised.

Guillain-Barre Syndrome↗
PubMed2004

[Bickerstaff's brainstem encephalitis and Fisher syndrome: their relationship and treatment].

The nosological position of Bickerstaff's brainstem encephalitis (BBE) was not eatablished, and its etiology was not clear until 1993. Because anti-GQ1b IgG antibody frequently occurs in patients with Fisher syndrome (FS) and there are clinical similarities between FS and BBE, we investigated anti-ganglioside antibodies in sera from three patients with BBE. High anti-GQ1b IgG antibody titers were present in their sera, but decreased with the clinical course of the illness. The findings that BBE and FS shared common autoantibody suggest that autoimmune mechanism common to FS is likely in BBE, and that both conditions form a continuous spectrum. To clarify the clinical features of BBE, we reviewed detailed clinical profiles and laboratory findings for 62 cases of BBE diagnosed by the strict criteria of progressive, relatively symmetric external ophthalmoplegia and ataxia by 4 weeks, and disturbance of consciousness or hyperreflexia. A striking feature was the association with flaccid symmetric tetraparesis seen in 60%. Limb weakness in the BBE cases studied was considered the result of overlap by the axonal subtype of Guillain-Barré syndrome. These indicates that the two disorders are closely related and form a continuous spectrum, and that treatment for Guillain-Barré syndrome should be applied for BBE.

Aged↗