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Biomedical subjects

Fumihiko Sakai

Publications and source records attributed to Fumihiko Sakai.

At least 19 recordsLinked to original sources
PubMed2006

The efficacy of goshuyuto, a typical Kampo (Japanese herbal medicine) formula, in preventing episodes of headache.

OBJECTIVE: The purpose of this clinical trial was to assess the efficacy of goshuyuto, a typical Kampo formula, in preventing episodes of headache in chronic headache patients. RESEARCH DESIGN AND METHODS: Because the treatment target of a Kampo formula is decided on a basis different to that of Western medicine, we first selected patients belonging to a subgroup that responded to goshuyuto before conducting the usual randomized controlled trial. During stage 1, the subjects were instructed to orally consume goshuyuto for 4 weeks. Only those subjects judged as responders advanced to stage 2, during which a double-blind, randomized, placebo-controlled study was conducted. The subjects consumed the same dose of goshuyuto or placebo for 12 weeks. RESULTS: Of the 91 subjects enrolled in stage 1, 60 were judged as responders. Of these, 53 advanced to stage 2; 28 were assigned to the goshuyuto group and 25 to the placebo group. The decrease in the number of days on which headache episodes occurred was greater in the goshuyuto group than in the placebo group (2.6 +/- 3.7 vs. 0.3 +/- 4.0 days, p = 0.034); no difference was observed with regard to the reduction in the frequency of consuming reliever medications (2.2 +/- 4.0 vs. 1.4 +/- 8.2, p = 0.672). Improvement in the associated symptoms was observed in more than 50% of the subjects in the goshuyuto group. CONCLUSION: Goshuyuto is useful in preventing episodes of headache in chronic headache patients. Responder-limited design is a candidate for evaluating Kampo medicine.

Adult↗
PubMed2005

The Global Campaign (GC) to Reduce the Burden of Headache Worldwide. The International Team for Specialist Education (ITSE).

The social perception of headache, everywhere at low levels in industrialised countries, becomes totally absent in developing ones. Headache disorders came into the World Health Organization's strategic priorities after publication of the 2001 World Health Report. Among the leading causes of disability, migraine was ranked 19th for adults of both sexes together and 12th for females. The Global Campaign (GC) to Reduce the Burden of Headache Worldwide was planned by the major international headache organizations together with WHO in order to identify and remove those cultural, social and educational barriers recognised as responsible factors for the inadequate treatment of headache disorders worldwide. Within the GC activities, the education of the medical body will represents a central pillar. An International Team for Specialist Education (ITSE) has been created to train physicians from all over the world through the acquisition of a university level Master Degree in Headache Medicine. Once trained as headache specialists, physicians will become trainers, offering education in this field to other health care providers in their own countries. In this way they will give life to a cultural chain raising awareness locally of headache, its burden and its medical control.

Education, Medical, Graduate↗
PubMed2005

Prevention of the cryptic epitope SLAYGLR within osteopontin does not influence susceptibility to Candida albicans infection.

The effect of an antiosteopontin antibody (M5 Ab) reacting with the SLAYGLR sequence within osteopontin on the host susceptibility to infection was investigated in a murine model of disseminated candidiasis. The treatment with anti-tumor necrosis factor alpha antibody enhanced fungal infection, while the treatment with M5 Ab did not affect the infection.

Animals↗
PubMed2005

Pathogenesis of stroke-like episodes in MELAS: analysis of neurovascular cellular mechanisms.

The pathogenesis of stroke-like episodes in mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) is not fully understood although two main theories have been proposed; ischemic vascular hypothesis caused by "mitochondrial angiopathy" and generalized cytopathic hypothesis caused by "mitochondrial cytopathy". Crucial molecular mechanism includes the lack of taurine modification at the wobble uridine of mutant transfer RNAsLeu(UUR) resulting in defective translation of cognate codons due to a defect in codon-anticodon interaction. Whereas recent clinical studies have shed light on the neuronal hyperexcitability, which may potentially initiate a cascade of stroke-like events. Stroke-like episodes are characterized by neuronal hyperexcitability, neuronal vulnerability, increased capillary permeability, and focal hyperaemia. It is recognized that stroke-like lesions not only evolve in the area incongruent to a vascular territory, but also potentially spread into the surrounding cortex with concomitant vasogenic edema presumably provoked by prolonged epileptic activities. Based on the clinical observations, we speculate that stroke-like episodes appear to be non-ischemic neurovascular events; once neuronal hyperexcitability developed in a localized brain region as a result from either mitochondrial dysfunction in the capillary endothelial cells, or in neurons or astrocytes, epileptic activities may depolarize the adjacent neurons leading to propagation of epileptic activities in the surrounding cortex. Increased capillary permeability provoked by epileptic activities in the presence of mitochondrial capillary angiopathy may cause unique edematous brain lesions predominantly involving the cortex. As a consequence, susceptible neuronal population in the cortex may result in neuronal loss with a laminar or pseudo-laminar distribution.

Blood Vessels↗
PubMed2005

[Prophylactic treatment with botulinum toxin type A].

Migraine is a common neurological disorder, characterized by recurrent attacks of severe headache. Its prevalence is estimated 8.4% of general population in Japan. Acute migraine treatment has dramatically improved with the development of a novel class of selective 5-HT1B/1D/1F receptor agonists, known as the triptans, but prophylactic treatment still remains limited. Botulinum toxin type A(BoNT-A) has recently been shown to be effective in randomized control trials, but no prospective study has been conducted yet in Japan. In this paper, we review the results of recently published controlled trials, touching on its methodology, optimal dose, patient selection, and possible mechanisms, as well as on going clinical trial in our university.

Botulinum Toxins, Type A↗
PubMed2004

Development and testing of the Japanese version of the migraine-specific quality of life instrument.

We developed and tested a version of the migraine-specific quality of life (MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese, evaluated by physicians and nurses who has experienced migraine headaches, 'backtranslated', approved by the author of the original version, and tested in 70 out-patients with migraine. There were no ceiling or floor effects. All three subscales were found to be internally consistent: alpha > or = 0.76. The patients' scores were similar to those reported in the user's manual, with the exception of a difference of about 11 points on the Avoidance Behaviors subscale. Some correlations between MSQOL scores and SF-36 scores were statistically significant, although none exceeded 0.52. Linear associations between some measures of symptoms and some MSQOL scales were statistically significant, but those associations were consistent neither for the two kinds of symptom reports (severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in early 1999 correlated with more return visits for medication and with greater amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we interpret these results as indicating that, while they cannot be used as substitutes for reports of symptoms, scores on the Japanese version of the MSQOL can be used to assess the impact of migraine headaches on patients' lives.

Adolescent↗
PubMed2004

Tryptophan-immobilized column-based immunoadsorption as the choice method for plasmapheresis in Guillain-Barré syndrome.

Plasmapheresis is widely performed as treatment for patients with Guillain-Barré syndrome (GBS) in the acute phase. As tryptophan-immobilized column-based immunoadsorption (Tr-IA) is a safer method than either double-filtration plasmapheresis (DFPP) or plasma exchange (PE), we investigated whether or not Tr-IA is as effective as other methods, and should be selected as the procedure of choice in patients with GBS. We retrospectively compared clinical outcomes, using Hughes grading, in GBS patients treated with Tr-IA, DFPP or PE. The outcome in the Tr-IA group was also compared historically with patients treated by PE in seven previous studies. We studied 34 patients with GBS: 20 were treated with Tr-IA, 11 with DFPP, and 3 with PE. The age, sex, duration from onset to initiation of treatment, and Hughes grade at entry did not differ among the Tr-IA, DFPP and PE groups. There was no significant difference in outcomes among these three groups, nor was there a significant difference between the outcomes in the Tr-IA and DFPP groups with respect to subgroups of Hughes grade at entry. Also, our Tr-IA group did not show a different outcome from the previously reported patients treated with PE. The frequency of complications in our Tr-IA group is significantly lower than that in both our DFPP group, and in the previously reported cases of patients treated with PE. Tr-IA, DFPP and PE have almost the same efficacy in patients with GBS, but Tr-IA is recommended as the plasmapheresis method of choice because of its safety.

Adolescent↗
PubMed2004

[Mechanism based prevention and treatment of migraine].

Triptan therapy results in good relief of headache in 68% of the patients. For many of the patients with migraine, triptan provides complete pain relief in some attacks but not in others. A recent theory proposes that allodynia (pain sensitization) develops in the brain during migraine to increase the intensity of headache significantly. The presence of cutaneous allodynia, an exaggerated painful sensation resulting from a no noxious stimulus to normal skin, is reported in more than 70% of the patients. In our prospective study with 41 patients with migraine, 54.2% presented with skin allodynia. Triptan was effective in 77% of the patients without allodynia which was higher than the base line efficacy rate of 68% in all the patients. Our data support the hypothesis that the development and maintenance of cutaneous allodynia is propelled by sensitization of central trigeminal nucleus. It is suggested that the pain-free outcome increases drastically if triptan therapy is given before the phenomenon of allodynia develops during the attacks of migraine.

Humans↗
PubMed2003

Slowly progressive spread of the stroke-like lesions in MELAS.

BACKGROUND: Little is known about temporal and spatial progression of the stroke-like lesion during the acute stage of the stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). METHODS: In four stroke-like episodes of MELAS observed in three patients, MRI, EEG, and SPECT were studied consecutively within the first month of the onset. RESULTS: The first presenting symptoms were headache in all four stroke-like episodes, followed by hemianopsia, psychosis, and aphasia. In three episodes, epileptic seizure developed subsequently in close association with a progression of stroke-like lesion. In all four episodes, serial MRI showed a slowly progressive spread of the stroke-like lesion evolving from the temporal cortex to the surrounding parietal or occipital cortex over a few weeks following the onset of initial symptoms. Apparent diffusion coefficient (ADC) maps showed slightly decreased ADC values in the actively evolving brain lesions compared with those in nonaffected regions of the brain. EEG showed a pattern of focal periodic epileptiform discharges in three episodes. SPECT showed a focal hyperemia in all four stroke-like lesions, in two of which focal hyperemia persisted for the first month. A T1-weighted hyperintense cortical signal on MRI compatible with cortical laminar necrosis was seen during the subacute stage of all stroke-like lesions. CONCLUSION: Slowly and progressively spreading stroke-like lesions on MRI may reflect ongoing neuronal metabolic derangement associated with concomitant vasogenic edema provoked by prolonged epileptic seizure activities.

Adult↗
PubMed2003

Reliability and validity of the Japanese Migraine Disability Assessment (MIDAS) Questionnaire.

OBJECTIVE: This study was designed to assess the test-retest reliability, internal consistency, and validity of a Japanese translation of the Migraine Disability Assessment (MIDAS) Questionnaire in a sample of Japanese patients with headache. BACKGROUND: Previous studies have demonstrated that the English-language version of the MIDAS Questionnaire is a reliable and valid instrument for the assessment of migraine-related disability. Any translations of the MIDAS Questionnaire must also be assessed for reliability and validity. METHODS: Study participants were recruited from the patient population attending either the Neurology Department of Kitasato University or an affiliated clinic. Participants were eligible for study entry if they had 6 or more primary headaches per year. For reliability testing, participants completed the MIDAS Questionnaire on 2 occasions, exactly 2 weeks apart. To assess validity, patients were also invited to participate in a 90-day daily diary study. Composite measures from the 90-day diaries were compared to equivalent MIDAS measures (ie, 5 questions on headache-related disability and 1 question each on average pain intensity and headache frequency in the last 3 months) and to the total MIDAS score obtained from a third MIDAS Questionnaire completed at the end of this 90-day period. RESULTS: One hundred one patients between the ages of 21 and 77 years were recruited (81 women and 20 men). Ninety-nine patients (80 women and 19 men) participated in the diary study. At baseline, 46.5% of patients were MIDAS grade I or II (minimal, mild, or infrequent disability), 22.2% were MIDAS grade III (moderate disability), and 31.3% were MIDAS grade IV (severe disability). Test-retest Spearman correlations for the 5 disability questions and the questions on average pain intensity and headache frequency ranged from 0.59 to 0.80 (P<.0001). The test-retest Spearman correlation coefficient for the total MIDAS score was 0.83 (P<.0001). The degree to which individual MIDAS questions correlated with the diary-based measures ranged from 0.36 to 0.88. The correlation between the total MIDAS score and the equivalent diary-based measure was 0.66. In general, the mean and median values for the MIDAS items and total MIDAS score were similar to the means and medians for the diary-based measures. However, the mean MIDAS scores for the number of days on which headache was experienced and the number of missed workdays were significantly different compared to the diary-based estimates for these items (P<.05). In addition, the mean MIDAS score for the number of days of missed housework was significantly higher than the corresponding diary-based estimate (P<.01). CONCLUSIONS: The results from this study show that the Japanese translation of the MIDAS Questionnaire is comparable with the English-language version in terms of reliability and validity.

Adult↗
PubMed2003

Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis.

It has been shown that osteopontin (OPN) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). However, the molecular mechanism of OPN action is yet to be elucidated. Splenic monocytes obtained from arthritic mice exhibited a significant capacity for cell migration toward thrombin-cleaved OPN but not toward full-length OPN. Migratory monocytes expressed alpha9 and alpha4 integrins. Since cleavage of OPN by thrombin exposes the cryptic epitope recognized by alpha9 and alpha4 integrins, we investigated the role of the cryptic epitope SLAYGLR in a murine RA model by using a specific antibody (M5) reacting to SLAYGLR sequence. The M5 antibody could abrogate monocyte migration toward the thrombin-cleaved form of OPN. Importantly, M5 antibody could inhibit the proliferation of synovium, bone erosion, and inflammatory cell infiltration in arthritic joints. Thus, we demonstrated that a cryptic epitope, the SLAYGLR sequence of murine OPN, is critically involved in the pathogenesis of a murine model of RA.

Animals↗
PubMed2003

Detection of serum anti-ganglioside antibodies by latex agglutination assay in Guillain-Barré syndrome: comparison with ELISA.

OBJECTIVE: Rapid detection of serum anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) could facilitate early diagnosis and early initiation of treatment, which might shorten the term of illness and reduce sequelae. We examined serum anti-ganglioside antibodies in patients with GBS using the latex agglutination assay developed by Alaedini and Latov (J Immunoassay 21: 377-386, 2000) with some modifications. MATERIALS AND METHODS: We used 75 sera from GBS patients, which exhibited IgG anti-GM1, GD1b, or GQ1b, or IgM anti-GM2 antibodies on previous enzyme-linked immunosorbent assay (ELISA). Blue latex beads (2.5% solution of 0.3 microm) were coated with 1 mg/ml of GM1, GD1b, GQ1b or GM2. Aliquots (4 microl) of serum and the ganglioside-coated particles were mixed and rocked on a glass slide for 30 to 40 seconds. The reaction was observed under a microscope and compared with the antiganglioside antibody titers determined with ELISA. RESULTS: Agglutination was strong in sera of which the IgM or IgG titers of anti-GM1, GD1b, GQ1b or GM2 antibodies were found to be more than 1:6,400 on ELISA except for 2 samples, but weak or absent in sera with titers of 1:3,200. Agglutination was absent in sera of which the antibody titers were less than 1:3,200 on ELISA. CONCLUSION: We could rapidly detect serum IgM and IgG anti-GM1, GD1b, GQ1b and GM2 antibodies in patients with GBS by means of the latex agglutination assay when sera exhibited high titers of the respective antibodies on ELISA. The sensitivity of our agglutination assay was much lower than that of ELISA.

Antibodies, Anti-Idiotypic↗
PubMed2003

FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC) II. Biological activities in animal models.

FR235222, a novel immunosuppressant which possesses potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs), has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 exhibited marked immunosuppressive effects on mouse ex vivo splenic T-lymphocyte proliferation, mouse delayed type hypersensitivity (DTH) response, rat adjuvant-induced arthritis (AA) and rat heterotopic cardiac transplantation. These results showed potential clinical use of this compound as a new type immunosuppressant in the fields of autoimmune diseases and organ transplantations.

Acremonium↗