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Biomedical subjects

Hiroyuki Murai

Publications and source records attributed to Hiroyuki Murai.

At least 19 recordsLinked to original sources
PubMed2006

Myeloradiculitis caused by Cryptococcus neoformans infection in a patient with ulcerative colitis: a neuropathological study.

Meningitis is the most common feature of cryptococcal infection of the nervous system. We herein describe the case of a 48-year-old man with fulminant cryptococcal myeloradiculitis, whose initial symptoms were impotence, dysuria and weakness of the lower extremities. He had been administered prednisolone and azathioprine for 7years for ulcerative colitis before onset of myeloradiculitis. He finally developed meningoencephalitis and died 2 months after onset despite treatment with amphotericin B and flucytosine. Post-mortem examination revealed numerous infiltrations of cryptococci in the spinal roots as well as in the meninges and subarachnoid space. Inflammatory cells and cryptococci had infiltrated the vessel walls in the spinal cord, and this was accompanied by necrotizing myelopathy. Myeloradiculitis is rare in cryptococcal infection, and this is the first case report to demonstrate direct cryptococcal infection in the spinal roots. Cryptococcal infection should be considered while managing myeloradiculopathy of unknown etiology, especially in immunocompromised patients.

Colitis, Ulcerative↗
PubMed2006

Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis.

To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-beta), we measured the intracellular cytokine production patterns of IFN-gamma, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which previously displayed alterations during the early course of IFN-beta treatment, in 15 Japanese patients after long-term IFN-beta administration. The patients were treated with IFN-beta-1b 8 x 10(6) units given subcutaneously every other day for a mean period of 34.5 +/- 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p = 0.0231 and p = 0.0170, respectively) T cells while IFN-gamma, a representative type 1 cytokine, was significantly decreased in the absolute producing cell numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after approximately 3 years of IFN-beta administration; (2) the intracellular IFN-gamma / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p = 0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-gamma / IL-4 ratio in CD4+ T cells and increased percentage of CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-beta therapy (p = 0.0152 and p = 0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-beta, while a higher intracellular IFN-gamma / IL-4 ratio is associated with treatment failure.

Adult↗
PubMed2006

Character changes from idiopathic cranial pachymeningoencephalitis.

A 66-year-old man with idiopathic cranial pachymeningoencephalitis was described. He suffered from left orbital pain, and character changes. He became short tempered, and was very attached to trifles. Two years prior to these symptoms, he had developed transient left abducent nerve palsy. Head MRI showed a thickening and enhancement of the dura mater on gadolinium-enhanced T1-weighted images, and high signal intensity lesions at bilateral frontal lobes predominantly in the white matter on T2-weighted images. Biopsies revealed microglial proliferation in the cerebral parenchyma, and mild lymphocytic perivascular infiltration. No evidence of intracranial infection was detected. We therefore treated him with methylprednisolone pulse therapy followed by oral prednisolone. His character became gradually normalized, and bilateral frontal lobe lesions seen on MRI disappeared. This is the first case to describe recurrent pachymeningoencephalitis with character changes, and symptoms were probably due to frontal lobe dysfunction.

Abducens Nerve Diseases↗
PubMed2006

[Hashimoto's encephalopathy with bilateral pallidal lesions presenting memory disturbance and executive dysfunction].

A 76-year-old man began to mistake his family for another person, and fall asleep easily while watching TV. He was treated with donepezil but without any effect. He was referred to our hospital on June. On admission, his consciousness was alert. Cranial nerves and motor functions were normal, but pathological reflexes were positive bilaterally. Serological examinations revealed high titers of antibodies against thyroglobulin and TPO, and antibody against alpha-enolase was positive. Total protein level in CSF was 40 mg/dl and cell counts were normal. On MRI, localized symmetrical lesions were observed in bilateral pallidum to genu of internal capsule. SPECT revealed hypoperfusion areas in bilateral striate bodies and frontal lobes. Neuropsychological examinations indicated impairment of executive function and procedural memory. The diagnosis of Hashimoto's encephalopathy was made and we treated the patient with oral prednisolone 60 mg/day followed by gradual tapering. After the treatment, clinical symptom as well as neuropsychological function improved. Neuropsychological impairment in this case was probably due to the disconnection of the thalamo-frontal projection. This case provides interesting suggestions that Hashimoto's encephalopathy may present with vasculitic infarctions in bilateral MCA perforators, and that this disease should be included in one of the differential diagnoses of cerebral infarctions of unknown etiology.

Aged↗
PubMed2005

A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene.

We report a case of a 46-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuations and dopa-responsive dystonia (HPD/DRD). She developed difficulty in walking at the age of 44 years due to bradykinesia as well as hand tremors, muscle rigidity, increased tendon reflexes and mild dystonia in the lower extremities, all of which responded remarkably to low doses of levodopa (150 mg/day). Biopterin and neopterin concentrations in the cerebrospinal fluid (CSF) were decreased. Analysis of the guanosine 5'-triphosphate cyclohydrolase I (GCH1) gene revealed a novel mutation (W53X) in one allele. The GCH1 activity that was expressed in mononuclear blood cells was almost half the normal value (usually 2-20% of the normal value (39.0+/-9.2 pmol/ml) in patients with HPD/DRD). The relatively conserved GCH1 activity that is expressed in stimulated peripheral blood mononuclear cells may be related to the late clinical symptoms in this patient.

Biopterins↗
PubMed2005

Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis.

There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS-multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple sclerosis, selective and severe involvement of the optic nerves and spinal cord is characteristic, though its mechanisms are unknown. The present study aimed to find out possible differences in the cytokine/chemokine profiles in CSF between OS-multiple sclerosis and C-multiple sclerosis and to delineate the relationships between these profiles and neuroimaging and pathological features. Sixteen cytokines/chemokines, namely interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta), were measured simultaneously in CSF supernatants from 40 patients with relapsing-remitting multiple sclerosis (20 OS-multiple sclerosis and 20 C-multiple sclerosis) at relapse and 19 control patients with spinocerebellar degeneration (SCD), together with intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, IL-17, MIP-1beta, IL-1beta and IL-13 were only significantly increased in OS-multiple sclerosis patients, while TNF-alpha was only significantly increased in C-multiple sclerosis patients, using a cut-off level of 1 pg/ml. IL-8 was significantly elevated in both OS-multiple sclerosis and C-multiple sclerosis patients. MCP-1 was significantly decreased in both OS-multiple sclerosis and C-multiple sclerosis patients, while IL-7 was only significantly decreased in C-multiple sclerosis patients. IL-17, IL-8 and IL-5 were significantly higher in OS-multiple sclerosis patients than in C-multiple sclerosis patients. The increases in IL-17 and IL-8 in OS-multiple sclerosis were still significant even after exclusion of the patients undergoing various immunomodulatory therapies. Assays of intracellular cytokine production revealed that both the IFN-gamma+IL-4- T-cell percentage and intracellular IFN-gamma/IL-4 ratio in CSF cells were significantly greater in C-multiple sclerosis patients than in controls. Contrarily, OS-multiple sclerosis patients showed not only a significantly greater percentage of IFN-gamma+IL-4- T cells than controls but also a significantly higher percentage of IFN-gamma-IL-4+ T cells than C-multiple sclerosis patients. Among the cytokines elevated in multiple sclerosis, only IL-8 showed a significant positive correlation with the Expanded Disability Status Scale of Kurtzke score. Both the length of the spinal cord lesions on MRI and the CSF/serum albumin ratio had a significant positive correlation with IL-8 and IL-17 in multiple sclerosis, in which the spinal cord lesions were significantly longer in OS-multiple sclerosis than in C-multiple sclerosis. Three of six spinal cord specimens from autopsied OS-multiple sclerosis cases demonstrated numerous myeloperoxidase-positive neutrophils infiltrating necrotic lesions. These findings strongly suggest that in OS-multiple sclerosis, in addition to the Th1 cell upregulation seen in C-multiple sclerosis, intrathecal activation of the IL-17/IL-8 axis inducing heavy neutrophil infiltration contributes to extensive spinal cord lesion formation.

Adult↗
PubMed2005

Platelet-activating factor receptor gene polymorphism in Japanese patients with multiple sclerosis.

We evaluated the association of the platelet-activating factor receptor (PAFR) gene polymorphism (A224D) with the susceptibility and severity of multiple sclerosis (MS) in a Japanese population. DNA was collected from 162 Japanese patients with clinically definite 'conventional' MS (MS) and 245 healthy controls. The missense mutation A224D that impairs PAF-PAFR signaling was determined by polymerase chain reaction restriction fragment length polymorphism. The frequency of the AD/DD genotypes was significantly higher in MS patients (21.0%) than in healthy controls (13.5%) (p=0.045; odds ratio (OR), 1.71; 95% confidence interval (CI), 1.01-2.89). Moreover, the frequency of D allele in MS patients (11.7%) was also significantly higher than those in healthy controls (6.9%) (p=0.019; OR, 1.78; 95% CI, 1.10-2.89). These findings suggest that the PAFR gene missense mutation has a relation to the susceptibility for MS.

Adult↗
PubMed2005

Exacerbation of chronic inflammatory demyelinating polyradiculoneuropathy during interferonbeta-1b therapy in a patient with childhood-onset multiple sclerosis.

Interferonbeta-1b (IFNbeta-1b) is commonly used for relapsing-remitting multiple sclerosis (MS). We report a 23-year-old woman with childhood onset relapsing-remitting MS treated with IFNbeta-1b who developed overt chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) immediately after therapy. A baseline conduction study before IFNbeta-1b therapy revealed decreased motor conduction velocities and prolonged F wave latencies in several nerves, but there was no neurological sign indicating neuropathy. The existence of subclinical demyelinating neuropathy before IFNbeta-1b treatment was suggested, although the clinical criteria for CIDP were unfulfilled. Following two months of IFNbeta-1b therapy, numbness of her right upper and lower limbs progressively worsened and all tendon reflexes were depressed. Electrophysiologically, F waves were not evoked in any limbs except for the left ulnar and tibial nerves, which showed marked prolongation of F wave latencies. Moreover, subclinical hyperthyroidism developed in association with high titers of anti-thyroglobulin and antithyroid peroxydase antibodies, which were negative before IFNbeta-1b therapy. These findings indicated that peripheral demyelination worsened at the nerve roots after IFNbeta-1b therapy. In addition to the development of autoimmune thyroid disease, the patient now fulfilled the criteria for probable CIDP. Along with the results of a previous report demonstrating IFNbeta-induced CIDP development in patients with childhood MS, this case underscores IFNbeta as a potential risk factor for CIDP in patients with childhood onset MS.

Adult↗
PubMed2005

Comparison of the clinical courses of the opticospinal and conventional forms of multiple sclerosis in Japan.

We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and higher Kurtzke's expanded disability status scale (EDSS) scores, the OS-MS patients showed a markedly lower frequency of secondary progressive MS than the C-MS patients (4.6% vs. 29.1%, p=0.0001). The EDSS scores of the C-MS patients were significantly correlated with the disease duration, while those of the OS-MS patients were not. Among the C-MS patients, the frequency of secondary progressive MS was significantly more common in patients with a disease duration of more than 10 years than in those with a shorter duration. These results suggest that the irreversible disability in OS-MS is determined by relapses, rather than by chronic progression, whereas C-MS has a similar clinical course to MS in Westerners.

Adult↗
PubMed2005

[A case of brachial amyotrophic diplegia accompanied with Sjögren's syndrome presenting good response to immunotherapies in the early course of the disease].

A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sjögren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sjögren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies.

Aged↗
PubMed2005

[A patient with paraneoplastic limbic encephalitis induced by breast cancer presenting with hypersomnia].

A 50-year-old woman developed gait disturbance and hypersomnia over a period of a month. General physical examination revealed axillary lymph node swelling. On neurological examinations she was fully orientated but hypersomnic; short term memory disturbance, horizontal gaze evoked nystagmus and ataxic gait were observed. Electroencephalography disclosed a tendency for easily decreasing vigilance with delta activities but normal dominant rhythm. Cerebrospinal fluid examinations showed increased protein amounts (109 mg/dl) without either pleocytosis or atypical cells. An echogram of the breasts revealed a tiny mass in the left side. Pathological studies on a biopsied lymph node and the mass in her left breast showed a mammillary duct carcinoma. Brain MRI was normal, and no anti-neuronal antibody was detected in sera by two dimensional immunoblotting using human brain crude antigens. She was diagnosed as having paraneoplastic limbic encephalitis (PLE) associated with breast cancer. Over 42 hours polysomnography showed long total sleep time (TST) with a high ratio of sleep stage 1/TST and no REM sleep abnormalities; this resembled a thalamic-hypothalamic damaged sleep pattern. At first she was treated with plasma exchanges, but no improvement was observed. Hormonal and chemotherapies produced partial resolution of her neurologic symptoms and there were signs of reduction of the breast mass. Most reported PLE cases with hypersomnia have been associated with testicular cancer and anti-Ma antibodies. The present case is an extremely rare example manifesting hypersomnia without either testicular cancer or anti-Ma antibody. Since anti-tumor therapy successfully ameliorated her neurologic symptoms, cell-mediated immunity against a common tumor and neuronal antigens rather than hormonal immunity may have played a role in the development of her PLE.

Breast Neoplasms↗
PubMed2004

Effect of immunotherapy in myelitis with atopic diathesis.

OBJECTIVE: A recent nationwide survey of myelitis with atopic diathesis in Japan disclosed that the disease frequently shows a chronic persistent course. A neuropathological study of the spinal cord also revealed chronic active inflammation. Since the effects of various immunotherapies have not been studied extensively in this condition, we evaluated the efficacies of various immunotherapies in patients with myelitis with atopic diathesis. PATIENTS AND METHODS: Forty-two treatments in 26 patients with myelitis with atopic diathesis were retrospectively analyzed. One of the following therapies was administered: (1) corticosteroids (CS) (pulse therapy followed by oral administration with gradual tapering); (2) intravenous immunoglobulin (IVIG) (400 mg/kg/day for 5 consecutive days); (3) plasma exchanges (PE); or (4) PE followed by IVIG or CS (PE+IVIG/CS). The therapeutic efficacies were evaluated by thorough neurological examination and laboratory tests including MRI, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). RESULTS: Objective neurological findings improved in 89% of the PE group and 90% of the PE+IVIG/CS group, compared with only 72% of the CS and 60% of the IVIG groups. Improvement determined by laboratory tests was seen in 57% of the PE and 57% of the PE+IVIG/CS groups, compared with only 15% of the CS and none of the IVIG groups. Thus, the improvement rate determined by laboratory tests was significantly greater for therapies including PE than for those without PE (p=0.0187). CONCLUSIONS: These data suggest that immunotherapy is effective in myelitis with atopic diathesis despite a chronic persistent course, and that PE is the most beneficial immunotherapy.

Adolescent↗
PubMed2004

Th2 shift in juvenile muscular atrophy of distal upper extremity: a combined allergological and flow cytometric analysis.

Juvenile muscular atrophy of the distal upper extremity (JMADUE) is considered to be a type of flexion myelopathy; however, we recently reported cases of JMADUE associated with airway allergy successfully treated by plasma exchange. To further characterize the allergo-immunological features of JMADUE, 11 consecutive JMADUE patients in the neurology clinic at Kyushu University Hospital were studied. Past and present together with family histories of common allergic disorders were investigated. Total serum IgE was measured by an enzyme linked immunosorbent assay (ELISA) and allergen-specific IgE by a liquid phase enzyme immunoassay. Intracellular interferon (IFN) gamma-, interleukin (IL)-4-, IL-5- and IL-13-producing T cells in peripheral blood were analyzed by flow cytometry. Data from 42 healthy subjects were used as controls for allergological studies. Flow cytometric data from 21 healthy subjects were also used for comparison. The patients exhibited significantly higher frequencies of coexisting airway allergies such as allergic rhinitis (p=0.0057) and pollinosis (p=0.0064), family histories of allergic disorders (p=0.0075), and mite antigen specific IgE (p=0.0361) compared with the healthy subjects. Patients with JMADUE had a significantly higher percentage of IFNgamma-IL-4+CD4+T cells (p=0.0017), but not IL-5- or IL-13-producing CD4+T cells, and a reduced intracellular IFNgamma/IL-4 ratio in CD4+T cells (p=0.002) compared to the controls. These findings suggest that JMADUE has a significant T helper 2 (Th2) shift, which may in part contribute to the development of spinal cord damage.

Adolescent↗
PubMed2004

Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer's disease.

The amyloid beta-protein (Abeta) ending at 42 plays a pivotal role in Alzheimer's disease (AD). We have reported previously that intracellular Abeta42 is associated with neuronal apoptosis in vitro and in vivo. Here, we show that intracellular Abeta42 directly activated the p53 promoter, resulting in p53-dependent apoptosis, and that intracellular Abeta40 had a similar but lesser effect. Moreover, oxidative DNA damage induced nuclear localization of Abeta42 with p53 mRNA elevation in guinea-pig primary neurons. Also, p53 expression was elevated in brain of sporadic AD and transgenic mice carrying mutant familial AD genes. Remarkably, accumulation of both Abeta42 and p53 was found in some degenerating-shape neurons in both transgenic mice and human AD cases. Thus, the intracellular Abeta42/p53 pathway may be directly relevant to neuronal loss in AD. Although neurotoxicity of extracellular Abeta is well known and synaptic/mitochondrial dysfunction by intracellular Abeta42 has recently been suggested, intracellular Abeta42 may cause p53-dependent neuronal apoptosis through activation of the p53 promoter; thus demonstrating an alternative pathogenesis in AD.

Aged↗
PubMed2004

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF.

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.

Adult↗
PubMed2004

High frequency of allergic conjunctivitis in myasthenia gravis without thymoma.

OBJECTIVES: To investigate the frequency of allergic disorders in myasthenia gravis (MG) patients and characterize the features of MG associated with allergic disorders. METHODS: Frequencies of past and present common allergic disorders in 160 MG patients who visited the Department of Neurology, Kyushu University Hospital from April 2000 to July 2003 and in 81 neurological normal controls were studied. RESULTS: Among various allergic disorders, the frequency of allergic conjunctivitis (AC) was significantly higher in MG patients (39/160, 24.4%, p(corr)=0.0112), especially with MG without thymoma (36/123, 29.3%, p(corr)=0.0016), in comparison to the controls (6/81, 7.4%). MG patients with AC showed a significantly higher rate of seronegative MG (43.6% vs. 17.4%, p=0.008) and a higher tendency of ocular MG (43.6% vs. 28.1%, p=0.071). Moreover, MG with AC had significantly lower anti-acetylcholine receptor antibody titers (median 6.8 nmol/l vs. median 23.6 nmol/l, p=0.0359) as well as a lower rate of coexisting thymoma (7.7% vs. 17.4%, p=0.016). The incidence of myasthenic crisis was also lower in MG with AC than without AC, yet the difference was not significant (7.7% vs. 15.7%). CONCLUSION: There was a significant association of AC with MG especially for ocular or seronegative MG in cases without thymoma.

Adult↗
PubMed2004

Time-dependent cytokine deviation toward the Th2 side in Japanese multiple sclerosis patients with interferon beta-1b.

To address the immune mechanism sustaining interferon beta (IFNbeta) efficacy in multiple sclerosis (MS), we longitudinally analyzed expressions of IFN-gamma, IL-4, IL-5 and IL-13 in CD4+ T cells and CD8+ T cells in 22 Japanese MS patients (16 patients with conventional MS and 6 with opticospinal MS) undergoing IFNbeta using flow cytometry. During the 48-week observation period, five opticospinal MS patients (83%) relapsed compared to only four conventional MS patients (25%); the frequency of relapsed patients was significantly higher in the former (p=0.046). The effects of IFNbeta on individual cytokines were time-dependent and altered cytokine productions were particularly evident in CD4+ rather than CD8+ T cells. A decreased intracellular IFN-gamma/IL-4 ratio in CD4+ T cells was thus evident soon after the initiation of therapy, and persisted for the entire 1 year follow-up period, regardless of whether or not the patient relapsed (p<0.01). IFNbeta treatment resulted in a rapid increase in the percentage of IFN-gamma- IL-4+ and IL-13+ CD4+ T cells 1 week after the initiation of therapy and high values were sustained for 6 months but declined to the baseline over 1 year. Later, the percentage of IFN-gamma+ IL-4- CD4+ T cells decreased significantly from weeks 24 through 48 of therapy (p<0.01). When comparisons with the pretreatment values were made for each subtype of MS, a significant reduction of IFN-gamma+ IL-4- CD4+ T cell percentages was shown in conventional MS (p<0.0001), but not in opticospinal MS. Moreover, when such a comparison was made by the presence or absence of relapse during therapy, a significant reduction of IFN-gamma+ IL-4- CD4+ T cell percentages was observed in MS patients without relapse (p<0.01). Thus, a reduction of IFN-gamma+ IL-4- CD4+ T cell percentages in the late phase of therapy is considered important for reducing relapse in conventional MS. When the expression patterns of IFN-gamma, IL-4, IL-5 and IL-13 in CD4+ T cells and CD8+ T cells were compared between patients with and without relapse during therapy, the only significant difference was an increase in the IL-13+ CD4+ T cell percentages in patients with relapse compared to those without (p<0.05). The results indicate that in CD4+ T cells IL-4 was preferentially up-regulated in the early course and IFN-gamma was down-regulated in the late phase of IFNbeta therapy. The net effect of IFNbeta on the immune balance was entirely toward type 2 immune deviation, possibly contributing to its beneficial effects on MS.

Adult↗