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Hisanori Kowa

Publications and source records attributed to Hisanori Kowa.

At least 19 recordsLinked to original sources

Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods.

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6+/-3.7 pg/ml; mean+/-SD) and MO (6.6+/-3.2 pg/ml) were significantly higher than in controls (4.8+/-2.4 pg/ml) (P<0.01). CGRP levels in MA (18.8+/-8.8 pg/ml) and MO (19.1+/-9.4 pg/ml) were also significantly higher than in controls (13.4+/-4.4 pg/ml) (P<0.01). ACE activities in MA (34.6+/-19.0 U/l) were significantly higher than in MO (25.3+/-13.2 U/l) and controls (27.0+/-20.4 U/l) (P<0.05). There was a significant correlation between SP and CGRP levels (P<0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities (P<0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.

Adult↗

Migraine and MTHFR C677T genotype in a population-based sample.

OBJECTIVE: Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status. METHODS: We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study. RESULTS: Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine. INTERPRETATION: Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.

Adult↗

[Anti-Yo antibody associated paraneoplastic cerebellar degeneration with gastric adenocarcinoma in a male patient: a case report].

We report a 71-year-old man presenting with paraneoplastic cerebellar degeneration (PCD) associated anti-Yo antibody after surgery for gastric adenocarcinoma. Seven months after partial gastrectomy, he deviated to the right on walking. Furthermore, a feeling of dysarthria appeared and he was unable to sit after 2 months. When he was hospitalized, he showed a disturbance of his eye movement on lower gaze, a nystagmus on lateral gaze, saccadic eye movement on smooth pursuit, cerebellar ataxia, and decreasing of muscle tonus in his extremities. However, no atrophic findings of the brainstem and cerebellum were revealed by brain MRI. He responded poorly to treatment with high-dose methylprednisolone, high-dose immunoglobulin, double filtration plasmapheresis and rehabilitation. There was a strong anti-Yo immunohistochemical staining of the cytoplasm in both the patient's tumor cells and normal cerebellar Purkinje cells. These findings suggest that PCD associated with anti-Yo antibody triggered by adenocarcinoma might occur in this male patient.

Adenocarcinoma↗

[A case of acute bromvalerylurea intoxication: clinical course and alteration in serum bromvalerylurea concentration].

Bromvalerylurea is one of the non-barbiturates products and has been used as analgesics and hypnotics in Japan. A 20-year-old woman was admitted to our hospital for loss of consciousness. She had a 6-month history of transient delirium and drunken gait. Physical examination revealed erythema less than thumb's head size at her face, shoulder and thigh. Neurologically, she had a state of coma and low muscle tonus. EEG showed the pattern of burst-suppression. The level of her serum chloride was not elevated. The erythema made us check up her state of acute bromvalerylurea intoxication. High blood concentration of bromvalerylurea led to diagnosis of the bromvalerylurea intoxication. The maximum value of her serum bromvalerylurea concentration was 107 microg/ml on the second hospital day, while the concentration in cerebrospinal fluid were also increased and remained for several days. She was treated with respiration control and drip infusions. She gradually improved and recovered to be alert. She was complicated severe liver dysfunction and disseminated intravascular coagulation resulting from bromvalerylurea intoxication, also treated with intensive care and gradually recovered. We should take notice to bromvalerylurea, easily available over the counter, as one of the drugs which may cause severe loss of consciousness or coma, and general complications. And if the bromvalerylurea intoxication is prospective, we should consider whether the option of gastric irrigation is available regardless of the elapsed time.

Adult↗

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura.

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.

Adult↗

[Migraine update].

Migraine is one of the common diseases suffering 8.4 million patients in Japan. The pathophysiology of migraine remains unclear. The genetic and basic studies of the familial hemiplegic migraine, a specific subtype of migraine with aura, have demonstrated the dysfunction of mutant brain-expressed calcium ion channel and/or the Na+/K+ ion transporter and suggested the association between cortical spreading depression (CSD) and migraine with aura. It is suggested that the CSD, neurogenic inflammation and vasodilatation caused by unknown triggers may activate the 'brainstem migraine generator' and amplified back way. In consequence, headache and/or aura will be appeared and strengthened. Our etiological data of headache in Daisen located in Western Japan clarified as follows; 1) Overall prevalence of migraine in Daisen was 6.0%. Women observed a 5.9-fold higher risk of migraine than men. 2) Fatigue, mental stress, and lack of sleep were the main headache triggers. 3) Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician. 4) Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. As a conclusion, only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. The Japanese guideline for chronic headache treatment has declared in 2002. The International Classification of headache disorders has reedited to the 2nd edition. Public education concerning headaches is one of the most urgent issues in Japan.

Adult↗

A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis.

Early onset familial Alzheimer's disease with spastic paraparesis (FAD-SP) has been associated with mutations of the presenilin 1 gene (PSEN1). We report a pedigree of FAD-SP due to a novel missense mutation of PSEN1 (Y154N). The symptoms of the proband were characterized by presenile dementia in her 40s, preceded by spastic paraparesis in her 30s, whereas the mother of the proband presented with spastic paraparesis in her 40s, followed by symptoms of dementia in her mid 60s. The mutation was found only in the proband, and not in a normal family member, normal Japanese control subjects, patients with sporadic Alzheimer's disease or patients with familial spastic paraparesis without dementia. Thus, Y154N is a novel PSEN1 mutation responsible for FAD-SP of Japanese origin.

Alzheimer Disease↗

Myasthenia gravis with thymus hyperplasia and pure red cell aplasia.

A case of myasthenia gravis (MG) with thymus hyperplasia and pure red cell aplasia (PRCA) is reported. A 57-year-old woman was diagnosed as having MG and was treated with thymectomy 26 years ago. The histology of the resected thymus was thymic lymphoid follicular hyperplasia. She developed rapidly progressive anemia and a bone marrow examination revealed PRCA. Her hematological results improved with oral administration of cyclosporine A. Cases of MG, thymoma and PRCA have been reported in the literature. We report the first case of MG without thymoma and PRCA.

Cyclosporine↗

Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.

Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation. The activity of mutant enzymes containing the 428C>T, [458G>T+459C>T] and 677C>T mutations was 12.7+/-4.7%, 48.1+/-18.8%, and 43.6+/-14.4%, respectively, of that of the wild type enzyme. Our results suggest that these two variants each result in a severe MTHFR deficiency, which causes a developmental delay and cerebral vascular disease.

Adolescent↗

The regulatory region polymorphisms of the MTHFR gene are not associated with Alzheimer's disease.

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer's disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist. Here, we have analyzed the 5'-upstream region of the MTHFR gene and examined AD patients (n = 223) and nondemented individuals (n = 323) for polymorphisms in the 5'-upstream region of the MTHFR gene. We identified two polymorphisms (-713G/A and -393C/A, upstream of the start codon). We found no significant relationship between AD and the 5'-upstream region polymorphisms of the MTHFR gene. Thus, our study does not reinforce the hypothesis of an independent involvement of the MTHFR gene upstream region polymorphisms in AD risk.

Aged↗

A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer's disease.

Epidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD). In our study, the MTHFR gene had four major regional haplotypes: Haplotype A (677C-1298A-1793G), Haplotype B (677T-1298A-1793G), Haplotype C (677C-1298C-1793G), and Haplotype D (677C-1298C-1793A). The frequency of Haplotype C in LOAD was significantly lower than that in control group. Furthermore, the benefit conferred by the presence of at least one Haplotype C was stronger in LOAD patients who lacked the ApoE 4 allele (OR=0.293; 95% CI=0.115-0.744; P=0.010). The results indicate that Haplotype C of the MTHFR gene is protective against the development of LOAD.

Aged↗

Population-based door-to-door survey of migraine in Japan: the Daisen study.

OBJECTIVES: To determine prevalence and characteristics of migraine in Japan, and to investigate use of medical care and whether food preference is associated with risk of migraine. METHODS: Structured questionnaires were given to all adult residents (N = 5758; 2681 men and 3077 women) in Daisen, a rural community in western Japan. Second questionnaires, specific to headache, were given to 1628 residents with headache. A telephone survey was also carried out. Statistical Packages for the Social Sciences analyzed the data. RESULTS: The 1-year prevalence of migraine was 2.3% (migraine with aura, 0.4% and without aura, 1.9%) in men and 9.1% (migraine with aura, 1.0% and migraine without aura, 8.1%) in women. Overall prevalence of migraine in Daisen was 6.0% (95% confidence interval [CI], 5.4% to 6.6%). Women observed a 5.9-fold higher risk of migraine than men (odds ratio, 5.9; 95% CI, 4.5 to 8.0; P <.0001, after age adjustment, by logistic analysis). Fatigue and loss of vigor were predominant premonitory symptoms of migraine. Fatigue, mental stress, and lack of sleep were the main headache triggers. Over a 3-month period, 20.3% of migraineurs experienced time or days off work due to headache. Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician, and of those with migraine, 61.0% with aura and 71.8% without aura had never visited a medical doctor for their headache. Consumption of alcohol and cigarette smoking did not influence the risk for migraine or tension-type headache, after age and gender adjustment (logistic analysis). Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. CONCLUSIONS: Only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. Public education concerning headaches is one of the most urgent issues in Japan.

Adult↗

Stroke recurrence within the first year following cerebral infarction--Tottori University Lacunar Infarction Prognosis Study (TULIPS).

OBJECTIVES: To identify determinants of recurrence after ischemic stroke in the Japanese population. MATERIALS AND METHODS: We enrolled 885 patients with acute ischemic stroke that had been admitted to our community hospitals. A total of 831 cases were followed for 1 year after the index stroke. Patients were assigned to one of the ischemic stroke subtype groups based on the NINDS Stroke Data Bank criteria. RESULTS: Rates of stroke recurrence were significantly different among stroke subtype groups: 14.4% in cardioembolic infarction, 7.3% in atherothrombotic infarction (ATI), 6.2% in lacunar infarction (LI) and 7.8% in infarction of uncertain cause. Previous history of stroke was the predictor of stroke recurrence for the groups of ATI and LI patients, and diabetes mellitus was the predictor of recurrence for the group of LI patients. CONCLUSION: The rate of recurrence and risk factors for stroke recurrence are different by stroke subtypes.

Aged↗

[A case of malignant fibrous histiocytoma with metastatic brain tumors after tumorgenic embolism].

A 61-year-old man had been treated for malignant fibrous histiocytoma with the pulmonary and the lymph node metastasis in the department of orthopedics in our hospital. He was admitted to our department because of an acute onset of conscious disturbance and non-fluent aphasia. Diffusion-weighted imaging (DWI) showed high signal intensity areas in the bilateral cerebella, thalami and posterior lobes. T2WI did not show any mass effects. Enhanced CT did not reveal any enhanced lesion. He was diagnosed as having cerebral embolism, and his conscious disturbance was improved after medication. Eight weeks later, he presented dysphagia, dysarthria, and ataxia in his extremities. DWI showed multiple lesions of low signal intensity located at the identical place where had showed high signal intensity in the initial DWI. T2WI showed high signal intensity area with mass effect. It was indicated that cerebral metastasis might grow after tumorgenic embolism. This is a rare case that tumor emboluses were developed to the metastatic brain tumors.

Brain Neoplasms↗

[An update on the familial headache syndromes].

Migraine is a common form of the chronic headache syndromes. Although the pathogenesis of migraine still remains enigmatic, there have been remarkable progress in headache research. Point mutations of P/Q-type Ca2+ channel alpha 1 subunit (CACNA1A) gene have been identified in familial hemiplegic migraine (FHM), which linked to chromosome 19 (FHM-1, OMIM 141500). Na-K ATPase alpha2 gene has been identified as the causative gene for FHM linked to 1q21-23 (FHM-2, OMIM 602481). Common forms of migraine (i.e. migraine with and without aura) seems to be caused from multifactorial genetic factors and environmental factors. An association study of allelic variation at Codon 23 (Cys or Ser) of 5HT2C-R gene in Japanese samples revealed that the Ser allele frequency in migraine with aura was significantly higher than that in the non-headache controls. However, negative association of this polymorphism have been reported in Caucasian migrainures. The C677T allelic variation of 5,10-methylenetetrahydrofolate reductase (MTHFR) are focused on in association with the coronary heart diseases and the cerebrovascular diseases. The T allelic frequency in migraine sufferers was significantly higher than that in controls. The C677T mutation of MTHFR is one of the genetic risk factors for migraine. These observations are confirmed in Turkish, Australian and Spanish samples. Positive associations of angiotensin converting enzyme (ACE) gene, endotheline receptor-A (ET-A) gene, and insulin receptor gene have been reported. Using the genomewide screen technology, significant linkage between the migraine with aura and a marker on 4q24 has been reported in Finnish families. The genome wide screen analysis will be one of the powerful strategies on exploring migraine gene. Genetic study of migraine headache is a promised and fruitful field and will provide deep understanding to migraine headache. Discovery of new responsible or susceptible genes to migraine will also open an avenue to develop new therapeutic strategy of migraine.

Headache Disorders↗

Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype.

In recent years, an intense interest has developed in the association between Parkinson's disease (PD) and hyperhomocysteinemia. Homocysteine (Hcy) is a neuronal excitotoxic amino acid, and is well known as a risk factor for vascular diseases. Some reports suggest that the administration of L-DOPA may promote hyperhomocysteinemia and idiopathic atherosclerosis. In this study, we report that a mild hypertrophy of the intima-media complex (IMC) of the carotid artery, which has been established as a marker for systemic atherosclerosis, is observed in PD patients compared with normal subjects. PD patients that were treated with L-DOPA for long durations showed a hypertrophic IMC, while the patients that were not treated with L-DOPA did not show any hypertrophic changes in the IMC. These hypertrophic changes were observed primarily in patients with a Hoehn-Yahr stage of 3-5. PD patients with hypertrophic IMC of the carotid artery also exhibited elevated plasma levels of Hcy associated with the C677T genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). Moreover, a prolonged duration of treatment with L-DOPA in patients with MTHFR T/T genotype enhanced the hypertrophy of IMC, compared with patients with the C/C or C/T genotype. These results suggest that hyperhomocysteinemia promoted by the C677T genotype of MTHFR and prolonged treatment with L-DOPA enhances atherosclerosis in PD patients and affects their general condition.

Aged↗