Biomedical subjects

Manabu Osoegawa

Publications and source records attributed to Manabu Osoegawa.

31 records · Page 2Linked to original sources

PubMed2004

Presence of IgE antibodies to bacterial superantigens and increased IL-13-producing T cells in myelitic patients with atopic diathesis.

BACKGROUND: Superantigens are considered to exacerbate autoimmune inflammation through the expansion of autoreactive T cells; however, the immune response to bacterial superantigens has not been extensively studied in any type of myelitis. We recently reported the occurrence of a distinct type of myelitis in patients with atopic diathesis, which in a recent nationwide survey was reported to be widespread in Japan. The aim of this study was to investigate the presence of IgE antibodies to bacterial superantigens and the proportion of IL-13- or IL-5-producing CD4+ or CD8+ T cells in patients with myelitis and atopic diathesis. METHODS: Twenty-four myelitic patients with and 12 myelitic patients without hyperIgEemia, 28 patients with multiple sclerosis (MS) and 34 healthy controls were enrolled in this study. IgE antibodies to staphylococcal enterotoxins A (SEA) and B (SEB) in sera were measured using a liquid-phase enzyme immunoassay, and the intracellular production of IL-5 and IL-13 in peripheral blood CD4+ and CD8+ T cells was measured by flow cytometry. RESULTS: The myelitic patients with hyperIgEemia showed significantly higher positive rates of serum SEA/SEB-specific IgE antibodies (41.7 and 62.5%, respectively) than the healthy controls (5.9 and 8.8%), patients with MS (0 and 21.4%) and those with normoIgEemic myelitis (0 and 0%). Moreover, IL-13-producing CD4+ T cells and CD8+ T cells increased significantly in the myelitic patients with hyperIgEemia compared to the controls, while IL-5-producing CD4+ or CD8+ T cells did not. CONCLUSIONS: The IgE response to staphylococcal superantigens is heightened in myelitic patients with atopic diathesis, which might contribute to increases in IL-13-producing T cells and thus the development of myelitis.

Adult↗

PubMed2004

Therapeutic effects of normal cells on ABCD1 deficient cells in vitro and hematopoietic cell transplantation in the X-ALD mouse model.

Bone marrow transplantation (BMT) is accepted as an efficient therapy for X-linked adrenoleukodystrophy (ALD). To clarify the mechanisms of this treatment, we examined the effects of hematopoietic cell transplantation (HCT) in an ATP-binding cassette, subfamily D, member 1 (ABCD1) knock out mice and co-culture of ALD patient fibroblasts with normal cells. We treated ABCD1 knock out mice with HCT using lacZ-transgenic mice as donors, which enabled us to detect donor-derived cells. We also examined the effects of co-culturing a normal microglia cell line (N9) with ALD fibroblasts. beta-Galactosidase (beta-GAL) activity was higher in spleen, lung and kidney than in liver, brain and spinal cord of the recipient ABCD1 knock out mice. HCT reduced the accumulation of very long chain fatty acid (VLCFA) in those tissues. The reduction of the VLCFA ratio was significant in spleen and lung; tissues with higher beta-GAL activity. ABCD1 was detectable in spleen from HCT mice. Co-culture of ALD fibroblasts with normal fibroblast cells reduced VLCFA accumulation in ALD cells. This effect was not observed when the cells were co-cultured while separated by a filter membrane. Our data suggest that supplying normal cells for ABCD1 knockout mouse by HCT corrects metabolic abnormalities in ALD tissues through a cell-mediated process. The correction requires direct cell-to-cell contact for recovering normal cell function.

Adrenoleukodystrophy↗

PubMed2004

Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy.

Muscle biopsy specimens of two patients with fatal reducing body myopathy showed few necrotic or regenerating fibers. On the other hand, enlarged densely stained myonuclei, in addition to the presence of many reducing bodies, were striking on light microscopy, and chromatin condensation was seen on electron microscopy. To confirm the involvement of apoptosis, we performed the TUNEL method at the electron microscopic level on muscles of the two patients and five age-matched controls. The density of DNA fragments in myonuclei showing chromatin condensation was significantly higher in reducing body myopathy compared to that in control muscles. In addition, the myonuclei surrounded by many reducing bodies tended to show more intense chromatin condensation and a higher density of DNA fragments than those distant from the reducing bodies. These results suggest that apoptosis takes part in muscle fiber degeneration in fatal reducing body myopathy, although the precise relationship between reducing bodies and apoptosis is uncertain.

Apoptosis↗

PubMed2004

Platelet-activating factor acetylhydrolase gene polymorphism and its activity in Japanese patients with multiple sclerosis.

We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G(994)-->T) and PAF-AH activity with susceptibility and severity of multiple sclerosis (MS) in Japanese. DNA was collected from 216 patients with clinically definite MS (65 opticospinal MS (OS-MS) and 151 conventional MS (C-MS)) and from 213 healthy controls. The missense mutation G(994)-->T that disrupts the PAF-AH activity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No statistically significant difference in the frequency of genotypes and alleles of the plasma PAF-AH polymorphism was observed among OS-MS patients, C-MS patients and healthy controls. However, the missense mutation tended to be associated with the severity of OS-MS, especially in females (GT/TT genotypes; 51.7% in female rapidly progressive OS-MS vs. 26.6% in female controls, p=0.0870). Moreover, PAF-AH activities were significantly lower in MS than in controls, irrespective of clinical subtypes, among those carrying the identical polymorphism in terms of nucleotide position 994 of the PAF-AH gene. These findings suggest that the PAF-AH gene missense mutation has no relation to either susceptibility or severity of C-MS, yet its activity is down-regulated, and that the mutation has no relation with susceptibility of OS-MS, yet it may confer the severity of female OS-MS.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2004

Anterior horn cell involvement in myelitis with atopic diathesis (atopic myelitis).

To clarify the involvement of anterior horn cells in myelitis with atopic diathesis (atopic myelitis), 20 patients with atopic myelitis were subjected to neurological evaluation, concentric needle electromyography (EMG), spinal cord magnetic resonance imaging (MRI) and motor and somatosensory evoked potentials. Apparent muscle atrophy was present only 1 of 20 patients (5%) and the rests clinically showed no lower motor neuron sign. On needle EMG, 12 patients (60%) showed varying degrees of lower motor neuron involvement. On-going denervation potentials, such as fasciculation potentials, fibrillation potentials and positive sharp waves, were seen in 5 patients and chronic neurogenic patterns, such as giant and polyphasic motor unit potentials with reduced recruitment patterns, in 12 patients. In 4 patients, the segments of lower motor neuron involvement on needle EMG were beyond those of the spinal cord lesions shown by MRI. In 2 patients showing on-going denervation potentials, such immunotherapies as plasma exchange and intravenous immunoglobulins, were applied and effective clinically as well as electrophysiologically. Therefore, varying degrees of subclinical anterior horn cell involvement seems to be common in atopic myelitis and reversible by immunotherapy.

Adolescent↗

PubMed2004

[Diagnosis and treatment of CNS parasite infection with special reference to parasitic myelitis].

The occurrence of visceral larva migrans due to Ascaris suum (A. suum) and Toxocara canis (T. canis) has occasionally been reported in Japan, although parenchymatous involvement of the CNS is extremely rare in A. suum/T. canis visceral larvae migrans. Recently we experienced 7 cases with myelitis caused by visceral larva migrans due to A. suum/T. canis (parasite myelitis). The characteristics of this myelitis are: (1) sensory disturbances (Lhermitte's sign, paresthesia, and hypesthesia) are predominant symptoms, while severe motor weakness is rare, (2) spinal cord lesions on T2-weighted MRI show more extensive lesions compared with mild symptoms, (3) Gadolinium enhancement of spinal cord lesions are limited as compared with spinal cord lesions on T2-weighted MRI lesions, (4) Some cases show the presence of eosinophils in CSF, while others show Th2 deviation in CSF supernatant, and (5) Tests for anti-A. suum/T. canis IgG antibody are strongly positive in serum and CSF. Moreover, 6 percent of 108 consecutive cases with non-compression myelopathy presenting at the Department of Neurology at Kyushu University Hospital from January, 1998 to December, 2002 had parasitic myelitis. Myelitis from visceral larva migrans due to A. suum/T. canis might be overlooked because of its mild neurologic impairment without systemic symptoms, but should be considered as one of the differential diagnoses in non-compression myelopathy.

Adult↗

PubMed2003

Myelitis with atopic diathesis: a nationwide survey of 79 cases in Japan.

We recently reported the occurrence of myelitis in patients with atopic disorders and its pathology to be eosinophilic inflammation. Because similar cases have been reported, we conducted a nationwide epidemiological survey (NES) of myelitis with atopy in Japan. We compared the clinicolaboratory features of the 30 NES cases with the 49 cases at Kyushu University Hospital (KU). Although the NES cases were distributed throughout Japan, the NES and KU cases shared common characteristics. We therefore combined all of the cases identified. The average onset age was 35.8+/-13.4 years, and the male/female ratio was 1:0.65. The onset mode was subacute/chronic in half the patients, and stepwise progression or symptom fluctuation was frequent (69.6%). The most common lesion site was determined clinically and by MRI to be the cervical cord, and paresthesia and/or dysesthesia were the most common symptoms initially (74.7%) and throughout the entire course (83.5%). Cerebrospinal fluid (CSF) abnormalities were infrequent and mild. These findings suggest that myelitis associated with atopy has mild but prolonged symptoms and occurs throughout Japan.

Adolescent↗

PubMed2003

Dysferlin expression in tubular aggregates: their possible relationship to endoplasmic reticulum stress.

Dysferlin is a newly identified sarcolemmal protein related to Miyoshi myopathy and limb-girdle muscular dystrophy. Although its function is still unknown, it is inferred from the presence of C2 domains and a transmembrane domain in its sequence that dysferlin may be expressed or located not only at the sarcolemma but also in other membranous organelles to interact with Ca(2+). Tubular aggregates (TAs) are derived from sarcoplasmic reticulum (SR) and found in various myopathies, especially in those related to disturbed intra-sarcoplasmic Ca(2+) homeostasis. To clarify the expression of dysferlin in TAs and the relationship among TA formation, dysferlin expression, and endoplasmic reticulum (ER) stress, we examined the expression of dysferlin and other sarcolemmal proteins by immunohistochemistry in 12 muscle biopsy specimens with TAs from 11 cases of periodic paralysis and 1 case of myalgia/cramps syndrome. Moreover, the expression of glucose-regulated protein 78 (GRP78) and GRP94, which are up-regulated under ER stress, was also examined by immunohistochemistry and immunoblotting. TAs showed strong expression of dysferlin. GRP78 and GRP94 were also intensely expressed in TAs. Total amounts of GRP78 and GRP94 were significantly increased in muscles with TAs compared with normal controls. These results indicate that muscles with TAs seem to be under ER stress, probably resulting from disturbed intra-sarcoplasmic Ca(2+) homeostasis. Strong expression of dysferlin in TAs suggests the possibility that it is located not only at the sarcolemma but also in the SR, at least in the pathological conditions.

Adolescent↗

PubMed2003

Juvenile muscular atrophy of distal upper extremity associated with airway allergy: two cases successfully treated by plasma exchange.

Juvenile muscular atrophy of the distal upper extremity (JMADUE) is postulated to be a type of flexion myelopathy. However, patients with typical clinical features of JMADUE but without evidence of flexion myelopathy have been reported. We recently reported a significant association of JMADUE with airway allergy. Here we report the successful treatment by plasma exchange (PE) of two patients with both airway allergy and JMADUE without evidence of flexion myelopathy. Patient 1 had a 5-year history of allergic rhinitis and high titers of mite antigen-specific IgE, and patient 2 had an 8-year history of pollinosis and high titers of cedar pollen-specific IgE. Both patients noted progressive distal muscle atrophy and weakness of the upper extremities: patient 1 for 3 months and patient 2 for 3 years. Neurologically, both showed asymmetric intrinsic hand muscle atrophy, oblique atrophy of the forearm muscles, and weakness and contraction fasciculation (minipolymyoclonus) of these muscles without any sensory impairment. Neither had any evidence of flexion myelopathy on magnetic resonance imaging (MRI) in a flexed position. Both were subjected to PE three times. Soon after the PEs, both showed improvement of distal muscle weakness of the upper extremities and marked reduction of contraction fasciculation of the forearm muscles. Patient 1 showed marked reduction in ongoing denervation potentials in the distal muscles on needle electromyography, while patient 2 showed marked improvement of F wave persistence of bilateral median and ulnar nerves. Serum total and allergen-specific IgE decreased after PEs in both patients. PE was thus considered to be effective in these two patients having JMADUE without evidence of flexion myelopathy. These observations may suggest the involvement of an immune-mediated process in the neural damage of JMADUE without evidence of flexion myelopathy, especially in patients with atopic diathesis, and may support the notion that JMADUE is etiologically heterogeneous.

Adolescent↗

PubMed2002

Eosinophilic myelitis associated with atopic diathesis: a combined neuroimaging and histopathological study.

Histologically proven eosinophilic myelitis has rarely been reported except in connection with parasitism. To clarify its clinicopathological features, we conducted a nationwide survey of biopsy-proven eosinophilic myelitis of unknown cause throughout Japan. Six such cases were collected and studied immunologically and pathologically. All were young to middle-aged men. All showed a protracted and fluctuating course with mild disability for 3-25 (mean 12.5) months before biopsy. Magnetic resonance imaging revealed localized lesions of T2-high and T1-iso signal intensity with a partial gadolinium enhancement in all cases. Cerebrospinal fluid (CSF) examinations were completely normal except for modest pleocytosis in two cases. Eosinophilia was present in the peripheral blood in two cases but was absent from the CSF of all cases. In spite of the chronic nature of the disease, spinal cord pathology revealed very active lesions with marked cell infiltration consisting mainly of CD8(+) T cells and varying numbers of eosinophils in the perivascular areas and the parenchyma. Both the myelin and axons were severely disrupted in all cases. Moreover, eosinophil cationic protein (ECP), an activated eosinophil product, was heavily deposited in the tissues. All but one case had hyperIgEemia and mite antigen-specific IgE in the sera, and two had accompanying atopic disorders. The present study thus revealed idiopathic eosinophilic myelitis to be a localized and persistent inflammation of the spinal cord, with distinct clinicopathological features, that has a possible link to atopic diathesis.

Adult↗

PubMed2002

Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy.

Hashimoto's encephalopathy (HE) is a rare autoimmune disease associated with Hashimoto's thyroiditis (HT). To identify the HE-related autoantigens, we developed a human brain proteome map using two-dimensional electrophoresis and applied it to the immuno-screening of brain proteins that react with autoantibodies in HE patients. After sequential MALDI-TOF-MASS analysis, immuno-positive spots of 48 kDa (pI 7.3-7.8) detected from HE patient sera were identified as a novel autoimmuno-antigen, alpha-enolase, harboring several modifications. Specific high reactivities against human alpha-enolase were significant in HE patients with excellent corticosteroid sensitivity, whereas the patients with fair or poor sensitivity to the corticosteroid treatment showed less reactivities than cut-off level. Although a few HT patients showed faint reactions to alpha-enolase, 95% of HT patients, patients with other neurological disorders, and healthy subjects tested were all negative. These results suggest that the detection of anti-alpha-enolase antibody is useful for defining HE-related pathology, and this proteomic strategy is a powerful method for identifying autoantigens of various central nervous system diseases with unknown autoimmune etiologies.

Amino Acid Sequence↗

PubMed2002

Increased IL-13 but not IL-5 production by CD4-positive T cells and CD8-positive T cells in multiple sclerosis during relapse phase.

In the present study, we flow cytometrically analyzed the intracellular production of interleukin (IL)-5 and IL-13 in peripheral blood CD4(+) and CD8(+) T cells from patients with multiple sclerosis (MS), human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and healthy controls. IL-13-producing T cells were significantly increased in both T cell subsets in MS at relapse, markedly in the conventional form of MS and modestly in the optocospinal form of MS, and returned to normal at remission. However, IL-5-producing T cells did not vary regardless of clinical phase or type. HAM/TSP showed no significant change in the number of IL-5- and IL-13-producing cells. A distinct profile of IL-13 and IL-5 production by disease and by phase of MS suggests an active involvement of these type 2 cytokines in central nervous system (CNS) inflammation.

Adult↗

PubMed2002

High incidence of subclinical peripheral neuropathy in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis): an electrophysiological study.

OBJECTIVE: To study subclinical involvement of the peripheral nerves in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis: AM). MATERIAL AND METHODS: We carried out a nerve conduction study of the median, ulnar, tibial, and sural nerves in 21 patients with AM and in 28 patients with clinically definite or laboratory-supported definite multiple sclerosis (MS). RESULTS: The patients with AM showed a significantly higher frequency of abnormal records than the MS patients in the sensory nerve conduction study (52.4% vs. 14.3%, p = 0.0106). The frequency of abnormal records in the motor nerve conduction study in AM patients was twice as high as in MS patients (38.1% vs. 17.9%), but the difference was not statistically significant. Abnormality in the F-wave-evoked frequency in the median nerve was also significantly more common in AM patients than in MS patients (57.9% vs. 10.7%, p = 0.0016). CONCLUSIONS: These findings suggest that subclinical peripheral neuropathy is frequent in patients with AM.

Adult↗