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Biomedical subjects

Takahiko Saida

Publications and source records attributed to Takahiko Saida.

16 recordsLinked to original sources
PubMed2005

Differences in systemic and central nervous system cellular immunity relevant to relapsing-remitting multiple sclerosis.

In order to elucidate the differences between systemic and central nervous system (CNS) immunity that are relevant to exacerbations of multiple sclerosis (MS), paired peripheral blood and cerebrospinal fluid (CSF) samples obtained from 36 non-treated patients with relapsing-remitting MS (RRMS) were simultaneously examined using flow cytometry to determine the percentages of functional lymphocyte subsets, as well as enzyme-linked immunosorbent assays for measuring soluble immune mediators. Active RRMS patients (n = 27) were characterized by an increase in CD4+ CXCR3+ Th1 cells in blood as compared with inactive patients (n = 9), and this parameter was inversely correlated with plasma levels of IL-10 and IL- 12p70. In contrast, an increase in the percentage of CD4+ CD25+ cells and a decrease in the percentage of CD8+ CD11a(high) cells were features of CSF samples from those with active RRMS. Further, CSF CD4+ CD25+ cells had a close association with leukocyte counts as well as albumin and CXCL10 levels in the CSF, and, thus, could be useful as a measure for inflammatory reactions in the CNS. On the other hand, CD8+ CD11a(high) cells may function as immunoregulatory cells, as their percentage in the CSF showed a positive correlation with CSF levels of the anti-inflammatory cytokine IL-4. These findings suggest that MS relapses occur in a combination with altered cell-mediated immunity that differs between the peripheral blood and CSF compartments, while measurement of lymphocyte subsets may be helpful for monitoring disease status.

Antigens, CD↗
PubMed2005

Clinical course and prognosis of 27 patients with childhood onset multiple sclerosis in Japan.

To investigate whether outcomes of childhood onset multiple sclerosis (MS) have changed or not, the clinical courses of childhood onset MS in 27 patients at our hospital and those reported by Fukuyama in 1991 were compared. The ratios of our patients with poor prognosis in walking and vision were decreased. Widespread use of high-dose corticosteroid therapy and interferon therapy may be one cause of the low frequency of severe sequelae in our study.

Adolescent↗
PubMed2004

Immunomonitoring measures in relapsing-remitting multiple sclerosis.

Forty-five patients with relapsing-remitting multiple sclerosis (MS) were examined to determine intracellular cytokine profiles and the surface phenotype of circulating lymphocytes during active, recovery, and stable stages. Active stage patients were characterized by decreases in CD4(+)IL-4(+) Th2 as well as CD4(+)IFN-gamma(+) Th1 cells, when compared with stable stage patients and 16 healthy controls. CCR4(+) Th2 cells were persistently decreased at every MS stage as compared to the controls. CD4(+)CD29(+) and CD4(+)CXCR3(+) cells were closely correlated with IFN-gamma-producing cells. These findings suggest that simultaneous flow cytometry for these two types of measurements can provide information concerning current immune status in MS.

Adolescent↗
PubMed2004

First Regional MS Forum Meeting raises MS awareness and highlights questions. The MS Forum Pan-Asian Conference, 912 October 2003, Bangkok, Thailand.

Multiple sclerosis (MS) in Asia and the Middle East was the subject of extensive discussion and debate at the first Pan-Asian MS Forum conference, entitled MS Across Continents: Insights from Asia and the Middle East. The first regional MS Forum activity, and the first major gathering of MS experts from these regions for over 30 years, it attracted over 100 specialists to share their experiences on the features, characteristics and management of the disease.

Asian People↗
PubMed2004

[A case of myeloradiculitis as a complication of visceral larva migrans due to Ascaris suum].

A 35-year-old man noticed a tingling sensation and subsequent slight weakness in the distal part of the left lower extremities, which extended to the left thigh over the following 8 months, when he developed a urinary disturbance. He was admitted to a local hospital and diagnosed as having myelitis, because of the presence of a gadolinium (Gd)-enhanced lesion in the lumbar spinal cord corresponding to the tenth thoracic vertebra (Th10) level. The symptoms disappeared along with some residual sensory disturbance following intravenous administration of 1 g of methylprednisolone (IVMP) for 3 days. However, 4 months later, the patient gradually developed gait disturbance, dysuria, impotence, and fecal incontinence, and was admitted to our hospital in May 2001. A neurological examination revealed the presence of myeloradiculopathy causing a slight weakness in the left hamstring muscles, with positive Babinski and Lasegue signs on the same side. In addition, deep tendon reflexes were absent in the 4 extremities and vibration sense was moderately decreased in the lower extremities, though the results of electrophysiological tests of motor and sensory nerves were normal. A magnetic resonance imaging (MRI) study showed a Gd-enhanced lesion in the spinal cord at the Th8-9 vertebrae level, which was 1 to 2 vertebrae above the initially detected lesion. A lumbar puncture yielded cerebrospinal fluid (CSF) containing mononuclear cells at 7/mm3 that were comprised of an increasd number of CD4+CD25+ activated helper T cells; however, no myelin basic protein or oligoclonal IgG band was present. Serological examinations were negative for the presence of collagen/vascular disorders as well as viral infection due to CMV, EBV, HSV, VZV, and HTLV-1, however, positive for specific antibodies against Ascaris suum in both serum and the CSF, confirming the diagnosis of chronic myeloradiculitis due to visceral larva migrans. The patient was first treated with a single course of a daily 600-mg dose of oral albendazole for 4 weeks, which was resulted in restoration of muscle weakness, as well as disappearance of the Lasègue sign. However, in contrast to the clinical improvement, the CSF sample obtained immediately after completing the treatment showed a worsening trend, as the CSF cell count had increased with a manifestation of marked eosinophilia and CD4+CD25+ cells were also increased. Thereafter, 3-day IVMP treatment was performed twice in cojunction with 3 courses of oral albendazole therapy for the subsequent 4 months, which resulted in normalization of all laboratory measurements concerning the CSF along with a decrement trend in serum and CSF antibody titers specific to Ascaris suum. Our results suggest that neurological involvement due to visceral larva migrans can be efficaciously treated with not only helminthic drugs but also intravenous corticosteroids.

Adult↗
PubMed2004

[Multiple sclerosis: treatment and prevention of relapses and progression in multiple sclerosis].

The benefit of interferon beta-1a and 1b treatment on relapsing remitting multiple sclerosis (MS) is now firmly established. IFN beta-1b, the only disease modifying drug approved in Japan, was comparably effective in OS-MS and C-MS in a Japanese treatment trial. Although the effect of Copaxone is less conclusive, superior safety profiles make this treatment an important alternative choice. Mitoxantrone has been approved by FDA for rapidly progressing patients. The usage should be restricted for two or three years to avoid cardiac side effects. Antegren, which is an anti-cell adhesion molecule monoclonal antibody and has been shown to be very effective for relapsing MS patients, now awaits approval by FDA. Many combination therapies are currently under systematic survey and hoped to provide superior efficacy.

Disease Progression↗
PubMed2003

Immune parameters associated with early treatment effects of high-dose intravenous methylprednisolone in multiple sclerosis.

To determine the immunological effects of high-dose intravenous methylprednisolone (IVMP) and elucidate immune measurements used for evaluation of its therapeutic effect, we analyzed lymphocyte subsets and humoral immune parameters in peripheral blood and cerebrospinal fluid (CSF) samples, before and within 2 weeks of treatment during 19 acute exacerbations in 16 relapsing-remitting multiple sclerosis (MS) patients. In addition to decreases in CSF albumin and IgG levels, treatment resulted in an increase of CD8(+)CXCR3(+) cells as well as a decrease in CD4(+) subsets expressing CD25, CD29, and CCR4 in the CSF. Further, the percentage of circulating CD4(+)CXCR3(+) Th1 cells also decreased. Clinical improvement was achieved following 15 of the 19 treatment occasions. Early (<2 weeks of treatment) clinical improvement was significantly associated with a decrease in CSF CD4(+)CD29(+) helper inducer T cells, whereas they were nearly unchanged in four patients who showed no improvement. Changes in other parameters following IVMP treatment were not different between the responder and non-responder groups.

Adult↗
PubMed2003

Clinical study of FK506 in patients with myasthenia gravis.

To investigate the usefulness of low-dose FK506 for the treatment of myasthenia gravis (MG), we treated 19 patients with generalized MG in a 16-week open clinical trial of FK506 (3-5 mg/day). At the end of the trial, total MG scores (range: 0-27 points) improved by 3 points or more in 7 of 19 patients (37%), and activities of daily living (ADL) scores (range: 0-6 points) also improved by 1 point or more in 8 of 19 patients (42%). Nine of 19 patients (47%) showed improvement in either MG or ADL scores. Significant reduction of anti-acetylcholine receptor antibody titers and interleukin 2 production were observed at the end of this study. Minor but commonly observed side effects were an increase in neutrophil count and a decrease in lymphocyte count. No serious adverse events such as renal toxicity or diabetes mellitus were observed during the 16-week treatment period. FK506 could safely serve as an adjunct to steroid therapy for MG at low dosage.

Adolescent↗
PubMed2003

Frequency of anti-AChR epsilon subunit-specific antibodies in MG.

A definite diagnosis of myasthenia gravis (MG) relies heavily on acetylcholine receptor (AChR) antibody testing. The relatively high number of antibody-negative patients therefore, causes frequent uncertainty in confirming the diagnosis. We evaluated the sensitivity and specificity of a new, commercially available AChR antibody test that uses an approximately equal mixture of AChR from TE671-epsilon (adult type) and TE671-gamma (fetal type) cells. This assay was used to re-examine 365 seronegative MG sera in which AChR antibody had not been detected by the standard assay that uses fetal type AChR. The new assay detected anti-AChR antibodies in 17 (15.5%) of 110 patients with ocular type and in 33 (12.9%) of 255 patients with generalized type MG. Anti-AChR epsilon subunit-specific antibodies were present in 13.7% of the patients in whom no AChR antibody had been detected by the standard assay, showing an increase from 79 to 82% in overall diagnostic sensitivity.

Antibodies↗
PubMed2003

[Multiple sclerosis: disease entity, subtypes and variants, and diagnostic criteria].

Multiple sclerosis (MS) is the prototypic inflammatory demyelinating disorder of the central nervous system (CNS). The increasing application of new powerful technologies during recent years has yielded new concepts and opened a new horizon. The prototype MS is called classical MS or Charcot variant and is characterized by the presence of the lesions in all parts of the CNS, consistently including cerebrum and/or cerebellum. It takes a relapsing-remitting course initially but, in most of the Caucasian cases, eventually turns into the chronic progressive stage (secondary chronic progressive form). Primary progressive MS takes slowly progressive course from the beginning. Both types of chronic forms are relatively rare in Japanese. Morphologically, the MS lesion is characterized by the key features: perivenular demyelination, inflammation gliosis, and axonal damage. The heterogeneity of MS lesions has been clearly established. Both T-cell and B-cell (antibody) mediated mechanisms are working and the primary target for the autoimmune damage could be myelin and/or oligodendroglia. Axonal damage could be most extensive within the first year after the disease onset. The list of candidate antigens includes myelin basic protein, proteolipid protein, and myelinoligodendroglialglycoprotein, but other non-myelin/oligodendroglial antigens such as S-100 protein also could induce CNS inflammation. Viral and microbial proteins are shown to share epitopes with those candidate antigens and, hypothetically, could induce CNS inflammation when infected to humans. New diagnostic criteria(McDonald et al, 2001) had been proposed and now include MRI criteria for morphological diagnosis and temporal activities. A Criterion for primary chronic progressive form is also included. The MS working group of Japanese MHL is now preparing for a new criteria for Japanese MS patients.

Animals↗
PubMed2002

Immunological disturbances in the central nervous system linked to MRI findings in multiple sclerosis.

To clarify immunological disturbances in the central nervous system (CNS) in multiple sclerosis (MS) by linking to magnetic resonance imaging (MRI) findings, 22 patients with relapsing remitting MS were studied. Cerebrospinal fluid (CSF) samples were analyzed during a total of 27 independent MS stages (20 active, 7 inactive) on 25 occasions during which gadolinium (Gd)-enhanced MRI scans were performed. The number of Gd-enhanced lesions was significantly correlated with CSF cell counts, as well as the number of CD4(+)CD29(+) helper inducer and IL-2 receptor (CD25)-positive activated helper T cells. In contrast, T(2) lesion load in the brain showed a trend of association with elevated IgG index.

Adolescent↗
PubMed2002

Chemokine receptors associated with immunity within and outside the central nervous system in early relapsing-remitting multiple sclerosis.

Thirty-four patients with early relapsing-remitting multiple sclerosis (RRMS) were studied to clarify the differences in chemokine receptor usage by blood and cerebrospinal fluid (CSF) lymphocytes relevant to the pathogenesis of MS. A total of 45 examinations (33 active and 12 inactive stages) revealed that circulating CD4+CXCR3+ T helper 1 (Th1) cells were increased in active MS patients and correlated with the number of gadolinium-enhanced lesions on magnetic resonance (MR) images. In contrast, CSF samples obtained during active stages were characterized by a decrease in the percentage of CD8+CXCR3+ T cells, which was inversely correlated with CSF cell count and intra-blood-brain barrier (BBB) IgG production.

Adolescent↗
PubMed2002

Detection of myelin basic protein in cerebrospinal fluid and serum from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) is a chronic inflammatory disease that primarily affects the spinal cord and may be a neurological syndrome that is clinically similar to multiple sclerosis (MS). Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of MS patents is generally measured by radioimmunoassay. We have recently established a sensitive enzyme-linked immunosorbent assay (ELISA) and measured the MBP concentrations in CSF and serum of HAM/TSP patients. METHODS: A sensitive two-site ELISA capable of measuring MBP at a concentration as low as 30 pg/mL in serum and CSF samples was used. RESULTS: Significantly higher CSF MBP concentrations were detected in 61% of HAM/TSP patients than in patients with non-neurological diseases. Serum MBP concentrations were also higher in 9% of HAM/TSP patients compared with patients with non-neurological diseases or healthy controls. CONCLUSIONS: Using our ELISA system, we detected MBP in CSF and serum not only in patients with central active demyelination as in MS, but also in patients with spinal cord demyelination as in HAM/TSP.

Adult↗
PubMed2002

[Determination of medullasin levels for the diagnosis of multiple sclerosis].

Medullasin levels in granulocytes of patients with neurological diseases and healthy volunteers were determined by the enzyme immunoassay using mouse monoclonal antibodies against human medullasin and o-phenylenediamine-H2O2 as the detection system of the enzyme activity. One hundred twenty-one out of 159 patients with multiple sclerosis (76.1%) showed positive results (above means of normals + 2SD) in this test, while only 16.9% (24/142) of patients with non-inflammatory neurological diseases had positive results. This enzyme immunoassay method for medullasin is considered to be an useful paraclinical test for the diagnosis of multiple sclerosis.

Adolescent↗