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M Niino

Publications and source records attributed to M Niino.

At least 19 recordsLinked to original sources
PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗
PubMed2003

HLA-related subpopulations of MS in Japanese with and without oligoclonal IgG bands. Human leukocyte antigen.

BACKGROUND: Oligoclonal IgG bands (OCB) are present in most patients with MS in Western countries; however, in Japanese MS patients, the OCB-positive rate is not as high. A relationship between immunogenetic backgrounds, namely, human leukocyte antigen (HLA) DR2 and DR4 positivity, and OCB production in MS patients from Hokkaido, the northernmost island of Japan, has been previously suggested by the authors. OBJECTIVES: To investigate the role of OCB in Japanese MS and to verify the interaction between immunogenetic backgrounds and OCB positivity. METHODS: OCB, DR2(15), and DR4 positivity were studied in 45 patients with newly diagnosed MS. In addition to confirming the authors' previous findings, the clinical and demographic features, MRI findings, OCB positivity, and DRB1*15 and DRB1*04 polymorphisms of an expanded data set of 99 MS patients were investigated by using multivariate analysis. Patients with opticospinal MS (OS-MS) were excluded from this study. RESULTS: A relatively low OCB-positive rate (53.3%), HLA-DR15 association with OCB-positive MS (p = 0.0044), and DR4 association with OCB-negative MS (p = 0.0410) were confirmed. DR15 was not associated with OCB-negative MS. Demographic features, disease course, and disability were similar in the OCB-negative and OCB-positive group, whereas there was a preponderance of women in the OCB-positive group. An independent negative association of DRB1*0405 (p = 0.0021, adjusted odds ratio = 0.21) with OCB positivity was found. CONCLUSIONS: MS is heterogeneous in its association with HLA alleles, and based on the immunogenetic differences, the MS patients in this population include at least two HLA-related subpopulations with and without OCB.

Adolescent↗
PubMed2003

Polymorphisms of apolipoprotein E and Japanese patients with multiple sclerosis.

The relation between apolipoprotein (APOE) gene polymorphisms and disease progression of multiple sclerosis (MS) is controversial. The present study was designed to investigate the relation between APOE gene polymorphisms and Japanese patients with MS. We analysed the frequencies of APOE gene polymorphisms in 135 MS patients and 134 healthy controls, using PCR-RFLP. The results showed no significant differences in the distribution of APOE gene polymorphisms between MS patients and controls. With regard to disease progression, there was no association between APOE gene polymorphisms and epsilon4 allele positivity and disease progression index (EDSS/ years). Furthermore, in patients with more than 10 years of disease onset, there were no significant differences between the frequencies of epsilon4 allele and patients with EDSS of more than 6. Although the low rate of epsilon4 allele in Japan should be taken into consideration, our results showed no relation between APOE gene polymorphisms and Japanese patients with MS.

Adult↗
PubMed2002

Prostaglandin E1 protects cultured spinal neurons against the effects of nitric oxide toxicity.

The effects of prostaglandin (PG) E(1) on NO neurotoxicity were examined using rat cultured spinal neurons. Rat cultured spinal neurons exposed to the NO donor, 2,2'-(hydroxynitrosohydrazono) bis-ethanamine (NOC18), showed neurotoxic effects that were accompanied by apoptotic nuclear change, free radical generation, a reduction in glutathione, and mitochondrial dysfunction. PGE(1), at concentrations of 1-100 nM, protected cultured spinal neurons from NO toxicity by reversing the oxidative and pro-apoptotic properties elicited by NOC18 exposure. The administration of PGE(1) increased the intracellular cyclic AMP (cAMP) levels in cultured spinal neurons. In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the existence of EP4, a cAMP-elevating PGE receptor, in cultured spinal neurons. The protective effects of PGE(1) against NO neurotoxicity was partially blocked by an inhibitor of MEK [the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase], suggesting that the MAPK/ERK pathway may play a significant role in the activity of PGE(1). PGE(1) up-regulated the expression of the anti-apoptotic protein, Bcl-2, as determined by Western blot analysis. PGE(1) also induced the expression of thioredoxin in cultured spinal neurons. Our data indicate that PGE(1) exerts a protective action against NO neurotoxicity in cultured spinal neurons, and suggests a therapeutic potential of PGE(1) against spinal cord disease, such as amyotrophic lateral sclerosis.

Alprostadil↗
PubMed2002

Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation.

Hepatitis B virus (HBV) reactivation in patients previously positive for hepatitis B surface antibody (HBsAb), so-called reverse seroconversion, has been considered to be a rare complication after hematopoietic stem cell transplantation (HSCT). We experienced two patients who developed reverse seroconversion among nine who were HBsAb positive and Hepatitis B core antibody (HBcAb) positive before HSCT; one after autologous bone marrow transplantation (BMT) and another after allogeneic peripheral blood stem cell transplantation (PBSCT). We reviewed the literature and considered that reverse seroconversion of HBV after HSCT is not uncommon among HBsAb positive recipients. The use of corticosteroids, the lack of HBsAb in donor, and a decrease in serum HBsAb and HBcAb levels may predict reverse seroconversion after HSCT.

Adrenal Cortex Hormones↗
PubMed2002

An examination of the association between beta2 adrenergic receptor polymorphisms and multiple sclerosis.

In multiple sclerosis (MS), beta-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack beta2 adrenergic receptor (beta2AR) expression. This differentially altered expression suggests that beta2ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the beta2AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of beta2AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary-progressive MS, this result was not significantly different from that observed in relapsing-remitting MS patients or control subjects. Together, our findings suggest that the presence of beta2AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies.

Adult↗
PubMed2001

Genetic polymorphisms of IL-1beta and IL-1 receptor antagonist in association with multiple sclerosis in Japanese patients.

In the present study, we have investigated the association of specific polymorphisms of the interleukin (IL)-1beta and IL-1 receptor antagonist (ra) gene with both the susceptibility to and the clinical characteristics of multiple sclerosis (MS) in Japanese patients. We collected and analyzed DNA from 98 MS patients and 104 healthy controls for distribution of IL-1beta or IL-1ra polymorphisms. Our results show no significant differences in the distribution of the polymorphisms between MS patients and controls. Furthermore, no association was observed between IL-1beta or IL-1ra polymorphisms and clinical characteristics, such as age at disease onset, clinical course and severity. Together, our findings suggest that IL-1beta or IL-1ra gene polymorphisms may not be relevant in the susceptibility to MS or the clinical characteristics of Japanese patients with MS.

Adult↗
PubMed2001

Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-gamma.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, plays a critical role in adipocyte differentiation and glucose homeostasis. It has been implicated that PPAR-gamma functions as a regulator of cellular proliferation and inflammatory responses. In the present study, we examined whether troglitazone, a selective PPAR-gamma agonists, ameliorated experimental autoimmune encephalomyelitis (EAE) induced by administration of myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in C57BL/6 mice. We found that troglitazone attenuated the inflammation and decreased the clinical symptoms. It was suggested that the amelioration was attributed to the attenuation of pro-inflammatory cytokine gene expressions.

Animals↗
PubMed2001

Heat shock protein 70 gene polymorphism in Japanese patients with multiple sclerosis.

Despite the strength of the association of multiple sclerosis (MS) and human leukocyte antigen (HLA)-DR2, other genetic elements could have a role in the pathophysiology of MS. We investigated possible associations with polymorphic susceptibility genes located within the HLA complex, i.e., heat-shock protein (HSP)70-1, HSP70-2, and HSP70-hom in Japanese patients with MS. Furthermore, we analyzed the influence of HSP70 gene polymorphisms on the severity of the disease, clinical course, magnetic resonance imaging findings, and oligoclonal bands in the cerebrospinal fluid, and HLA in MS patients. The results of the present study indicated that there were no significant differences in the distribution of all HSP70 genotypes and allele frequencies between Japanese MS patients and controls. In MS patients, there were no associations between HSP70 gene polymorphisms and the clinical data. Moreover, there were no significant differences in HSP70 genotype or allele frequencies between MS patients positive for HLA-DRB1*1501 alleles and matched controls. Our data indicate that HSP70 gene polymorphisms are not relevant in the susceptibility to or the severity of Japanese MS patients.

Adult↗
PubMed2001

Long-term blood pressure variability and cerebrovascular changes on CT in a community-based elderly population.

The effects of long-term blood pressure (BP) levels on cerebrovascular changes were analyzed in a community-based healthy elderly population. Cranial computed tomography (CT) was performed for 300 residents aged 69 years and older. Long-term BP during the ten years prior to CT was assessed, and the cerebrovascular changes were compared among different patterns of long-term blood pressure variability. White matter lesions (WML) and/or silent infarctions (SI) were found in 73 subjects (23.6%). Multiple logistic regression analysis showed that subjects with long-term diastolic hypertension (DHT) had the highest risk of cerebrovascular changes (adjusted odds ratio (OR), 95% confidence interval (CI); 7.1, 2.4-21.6, for WML; 7.2, 2.7-19.4, for SI), and that long-term isolated systolic hypertension (ISHT) was significantly associated with SI (adjusted OR, 95%CI, 2.3, 1.1-4.9), but not with WML (adjusted OR, 95%CI, 1.3, 0.5-3.3). Efforts to prevent both DHT and ISHT would be beneficial, though different underlying mechanisms for WML and SI were suggested.

Aged↗
PubMed2000

Estrogen receptor gene polymorphism in Japanese patients with multiple sclerosis.

Estrogen has been reported to have immunosuppressive functions, and to inhibit the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Since estrogen shows its biological effects via estrogen receptors (ER), we investigate the possible role of ER genes (ERG) in the pathogenesis of MS. PvuII and XbaI polymorphisms in ERG were detected by PCR-RFLP from the DNA of 79 conventional MS patients and 73 healthy controls. The [P] allele in the profiles in PvuII was significantly more prevalent in MS patients than in the controls (P<0.0005). In the study of XbaI polymorphism, the onset age of MS patients with the Xx genotype was earlier than that of the xx genotype group (mean age+/-S.D.; 22.60+/-8.04, and 27.49+/-9.14, respectively) (P<0.05) by ANOVA followed by Fisher's PLSD. Although the Xx genotype group tended to earlier onset age than the XX genotype group (29.60+/-11.10), this difference did not reach. On the basis of these results, PvuII polymorphism might be associated with susceptibility to MS, and XbaI polymorphism with onset age of MS. ERG polymorphism should be further studied in other populations to improve strategies for treatment of MS.

Adult↗
PubMed2000

Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behçet's disease.

Macrophage migration inhibitory factor (MIF) is becoming increasingly recognized as an important regulator of immune and inflammatory responses. It is released by activated T lymphocytes and macrophages and up-regulates the proinflammatory activity of these cells. MIF is required for antigen- and mitogen-driven T cell activation, and stimulates macrophages to release cytokines and nitric oxide. On the basis of the recent suggestion that pharmacological modulation of MIF production and neutralization of its activity may have important implications for treatment of a variety of autoimmune or inflammatory conditions, we determined the level of MIF in the cerebrospinal fluid (CSF) of patients with conventional-form multiple sclerosis (C-MS) and optic-spinal form multiple sclerosis (OpS-MS), and neuro-Behçet's disease (NBD). As control, the CSF of patients with non-inflammatory neurological diseases (NIND) was used. The concentration of MIF in CSF samples was significantly elevated in relapsed cases of C-MS (4.13+/-1.07 ng/ml) (mean+/-S.D.) compared with control samples (2.38+/-0.60 ng/ml) (P<0.0001), whereas MIF in the CSF of C-MS patients in remission was not elevated (2.65+/-0.67 ng/ml). The concentration of MIF in the CSF of OpS-MS patients in relapse (5.53+/-1.74 ng/ml) was higher than that of patients with C-MS in relapse (P<0.05). In NBD patients, the concentration of MIF in CSF was significantly elevated (7.47+/-5.61 ng/ml) compared with control samples (P<0.01) and correlated well with cell count in these samples (r=0.910, P<0.005). These results suggest that MIF may play a pivotal role in immune-mediated diseases of the central nervous system, and that MIF may be useful in the study of differences between C-MS and OpS-MS.

Adolescent↗
PubMed2000

Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles.

We have previously reported that the association between Bsm I polymorphism, one of the vitamin D receptor genes (VDRG) polymorphism, and multiple sclerosis (MS). In this report, we investigated the further possible role or relevance of VDRG in the pathogenesis of MS. Apa I polymorphism was detected by PCR-RFLP from the DNA of 77 conventional MS patients and 95 healthy controls. The study of the Bsm I and Apa I haplotypes was carried out by employing previously reported Bsm I data. The AA genotype and the [A] allele in the profiles were significantly more prevalent in MS patients than in controls (P=0.0070 and P=0.0321, respectively). In the [A] allele-positive MS patients, the positive rate of DPB1*0501 in HLA was significantly higher than that of the [A] allele-positive controls and that of the [A] allele-negative MS patients even when the corrected P value (P(corr)) was applied (P(corr)=0.0220 and P(corr)=0.0077, respectively). The frequency of DRB1*1501 was higher in the [A] allele-positive patients than in the [A] allele-positive controls and the [A] allele-negative patients (P(uncorr)=0.0431 and P(uncorr)=0.0089, respectively), but the P values did not reach statistical significance after P corrections. The rate of Bsm I and Apa I haplotypes was much higher in bA/bA-positive MS patients than in the controls (P=0.0003), and in the bA positive MS patients, the positive rate of DPB1*0501 was higher than that of the bA-positive controls and that of the bA-negative MS patients (P(corr)=0.0308 and P(corr)=0.0033, respectively). These results indicate that VDRG polymorphism may be associated with susceptibility to MS, and HLA alleles may correlate with risk for MS together with VDRG.

Adult↗
PubMed1999

Focal (segmental) dyshidrosis in syringomyelia.

The features or mechanisms of dyshidrosis have not been sufficiently clarified. Neither has the difference between hyperhidrosis and hypohidrosis. To clarify the features and mechanisms of dyshidrosis (hyperhidrosis and hypohidrosis) in syringomyelia, the clinical features focusing on hidrosis of 30 patients with syringomyelia and Chiari malformation located from a syringomyelia database were prospectively analysed. The patients were classified into three groups: eight patients (26.7%) had segmental hypohidrosis, 10 (33. 3%) had segmental hyperhidrosis, and 12 (40.0%) had normohidrosis. We found that the Karnofsky functional status for the hyperhydrosis and normohidrosis groups were significantly higher than for the hypohidrosis group (p=0.0012), with no significant differences between the hyperhidrosis and normohidrosis groups. The duration from the onset of syringomyelia to the current dyshidrosis was significantly longer in the hypohidrosis group than in the hyperhidrosis group (p=0.0027). A significant correlation was identified between the duration from the onset of syringomyelia to the time at study and the performance score (r=-0.599, p=0.0003). The results substantiate previous hypotheses that in its early stage syringomyelia causes segmental hyperactivity of the sympathetic preganglionic neurons, and hyperactivity of these gradually subsides as tissue damage progresses. Focal hyperhidrosis may be regarded as a hallmark of a relatively intact spinal cord, as well as normohidrosis.

Adolescent↗
PubMed1999

Chronic inflammatory demyelinating polyneuropathy with multiple hypertrophic nerves in intracranial, and intra- and extra-spinal segments.

Hypertrophic nerves have occasionally been seen in chronic inflammatory demyelinating polyneuropathy (CIDP), but most are in the cauda equina. We report a case with CIDP in whom magnetic resonance imaging (MRI) with gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) enhancement demonstrated hypertrophy of various peripheral nerves including multiple cranial nerves. Interestingly, none showed neurological signs corresponding to the lesions, except for clinical signs consistent with CIDP. MRI can be useful for the detection of silent, but abnormal nerve involvement in CIDP.

Adult↗
PubMed1998

Prognostic value of dipyridamole-thallium myocardial scintigraphy in patients with Kawasaki disease.

BACKGROUND: Although coronary artery lesions are critical complications of Kawasaki disease, their long-term outcome is still unclear. It is sometimes difficult to monitor progressive changes from aneurysms to stenotic lesions because coronary angiography (CAG) cannot be repeated very often, especially in infants. Our prospective study was designed to evaluate the prognostic value of dipyridamole-thallium single-photon-emission CT (SPECT) in the long-term follow-up of patients with Kawasaki disease. METHODS AND RESULTS: Of 459 consecutive patients with Kawasaki disease, coronary aneurysms were detected in 90 cases by echocardiography during the acute stage. After paired studies of selective CAG and SPECT were conducted, all patients were followed up and monitored for the occurrence of any cardiac events for > or =8 years. During the follow-up interval, there were 15 cardiac events (1 death, 5 infarctions, 2 coronary artery bypass graft operations, and 7 occurrences of unstable angina). Of patients who had some event, thallium redistribution was found on SPECT in 14 (93%, P<0.001). Of the various clinical and scintigraphic image variables, the presence of thallium redistribution was the best multivariate independent predictor of a late cardiac event (chi2=57.8, P<0.0001). The number of aneurysms detected on CAG added minimal statistical improvement to the model (chi2=1.9, P=0.0009). CONCLUSIONS: Dipyridamole-thallium SPECT is safely performed and is useful and important for risk stratification in the long-term follow-up of patients with Kawasaki disease.

Age of Onset↗
PubMed1995

Hypoplastic left heart syndrome with a single coronary artery originating from the pulmonary artery.

A newborn male infant with hypoplastic left heart syndrome due to mitral and aortic atresia died on the third day of life. Autopsy revealed a single coronary artery originating from the pulmonary artery, reversed coarctation of the aorta, a coronary sinus type atrial septal defect and stenosis of the left subclavian artery. To our knowledge, hypoplastic left heart syndrome associated with a single coronary artery originating from the pulmonary artery has never been reported in the English or Japanese literature. This may be the first such case.

Coronary Vessel Anomalies↗