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Biomedical subjects

H Kowa

Publications and source records attributed to H Kowa.

At least 19 recordsLinked to original sources
PubMed2006

Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia.

Although it has been well documented that pre-eclampsia is caused by a combination of maternal and fetal susceptibility genes, little is known about the precise etiology of this complicated disorder. To investigate how the expression of fetal genes contributes to the mechanisms underlying the progression of this disease, we have analyzed differentially expressed genes using placentas from 13 normal pregnancies and 14 pregnancies with severe pre-eclampsia. We performed genome-wide expression profiling using high-density oligonucleotide microarrays, followed by validation using real-time PCR. Among the 47,000 genes that were screened in the microarray, 137 genes were found to be differentially expressed between normal and pre-eclamptic tissues. Among these candidates, 70 were up-regulated and 67 were down-regulated. The up-regulated genes included leptin and inhibin A, which are well-known biological markers for pre-eclampsia, as well as FLT1, which was recently proved to be tightly linked with the etiology of this disease. Gene ontology analysis further revealed several biological processes that could be associated with the development of pre-eclampsia, including response to stress, host-pathogen interactions, lipid metabolism, and carbohydrate metabolism. Analyses of biological mechanisms highlighted some important pathways that may be involved in this disorder, such as the TGF-beta and CEBPA-related pathways. Furthermore, when our present subjects were classified as either severe cases of early onset or late onset pre-eclampsia, the expression of 11 genes could be correlated with the severity of this disorder. These genes may therefore prove to be novel biological markers by which the severity of this condition could be predicted. Our data are likely to be a useful future resource in the elucidation of the disease-process and in the identification of novel markers for pre-eclampsia.

Adult↗
PubMed2004

Serotonin 2C receptor gene Cys23Ser polymorphism: a candidate genetic risk factor of migraine with aura in Japanese population.

OBJECTIVES: The goal of this study is to clarify the association between migraine and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. MATERIALS AND METHOD: This study included 37 individuals with migraine with aura (MWA), 80 with migraine without aura, 43 with tension type headache (TH) and 360 with controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS: The Ser allele frequency in control subjects is much less than that in Caucasian population. The Ser allele frequency in patients with MWA was higher than that in control subjects. CONCLUSION: The present study provides that 5HTR2c Cys23Ser polymorphism may be associated with MWA in Japanese population.

Adult↗
PubMed2003

Glutathione S-transferase polymorphisms: susceptibility to migraine without aura.

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. We investigated glutathione S-transferase (GST) P1 Ile(105)Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers and 372 Japanese controls. The headache group consisted of 38 cases of migraine with aura, 95 migraine without aura (MWOA) and 41 tension-type headache sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA (64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence interval: 1.32-3.61, adjusted for age and gender). In a comparison of the current smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one of the genetic risk factors for MWOA in the Japanese population.

Adult↗
PubMed2001

Amyloid beta protein deposition in patients with frontotemporal lobar degeneration: relationship to age and apolipoprotein E genotype.

Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of 54 autopsy cases of frontotemporal lobar degeneration (FTLD) using methenamine silver staining, and immunohistochemistry employing the monoclonal end-specific antibodies BC05 and BA27 to visualize deposits containing Abeta(42(43)) and Abeta(40), respectively. Abeta was detected in 14 (26%) patients, nearly always in the form of diffuse Abeta(42(43)) containing plaques though some cored, neuritic plaques with trace amounts of Abeta(40) were occasionally seen. The 14 patients showing Abeta deposits were significantly older at onset of illness than those 40 patients without Abeta. It was only possible to genotype 46/54 cases, 16 of whom bore at least one copy of the Apolipoprotein E (APOE) epsilon4 allele, giving an allele frequency of 20%. Possession of APOE epsilon4 allele was significantly associated with deposition of Abeta such that 10/16 epsilon4 allele bearers had Abeta deposits. Eight of these ten patients showed only mild to moderate amounts of Abeta, but in two patients, one homozygous and one heterozygous for epsilon4 allele, there was extensive neuritic plaque and neurofibrillary tangle formation. In contrast, only few non-epsilon4 allele bearers (4/30) showed minor Abeta deposits. When stratifying for APOE epsilon4 allele, both bearers and non-bearers of epsilon4 allele with Abeta deposits had a significantly later age at onset than their respective groups without Abeta deposits. We conclude that the likelihood of Abeta deposition, as a secondary and coincidental feature unrelated to the primary pathological process, within the brains of individuals with FTLD will be high if patients have a sufficiently late onset of illness or happen to be a bearer of the APOE epsilon4 allele. Indeed 9/14 patients with Abeta deposits studied here had an onset of illness after 55 years of age and bore APOE epsilon4 allele.

Age of Onset↗
PubMed2001

Somatosensory evoked potential recovery in myotonic dystrophy.

OBJECTIVE: To evaluate recovery functions of the sensory cortex using somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median nerve in patients with myotonic dystrophy (MD). SUBJECTS/METHODS: Twelve MD patients were enrolled in the present investigation. Five patients with facioscapulohumeral muscular dystrophy (FSH) and 12 healthy volunteers were studied as control groups. SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single pulse or paired-pulse stimuli at various interstimulus intervals (ISIs) (10, 20, 40, 60, 80, 100, 150, 200 and 300 ms) were given. Recovery functions of N9, N20onset-N20peak, N20-P25 and P25-N33 components were studied. RESULTS: Conventional SEPs to a single stimulus were normal in the latency and amplitude in all the patients. Recovery functions of both N9 and N20o-N20p components were normal in the patients. In contrast, in MD patients, disinhibited or hyperexcitable recovery pattern was observed in recovery curves of the N20-P25 or P25-N33 components, whereas those were normal in FSH patients. CONCLUSIONS: Disinhibited cortical excitability (or hyperexcitability) is present in the sensory cortex in patients with myotonic dystrophy. This may reflect cortical pathology or functional alteration of the sensory cortex in MD.

Adult↗
PubMed2001

Leukocyte mitochondrial DNA A to G polymorphism at 11084 is not a risk factor for Japanese migraineurs.

Mitochondrial dysfunction has been reported in patients with migraine. We investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166 Japanese migraineurs and 483 Japanese controls. The migraine group consisted of 43 patients suffering from migraine with aura (MWA) and 123 from migraine without aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7% in MWA and 8.1% in MOA. There was no significant difference among the groups (chi-square test). The mitochondrial DNA 11084 A to G transition was more common in Japanese subjects than reported in Caucasians; however, this polymorphism is not a genetic risk factor for migraine in Japanese patients.

Adult↗
PubMed2001

Analysis of alpha-synuclein, parkin, tau, and UCH-L1 in a Japanese family with autosomal dominant parkinsonism.

We examined whether autosomal dominant parkinsonism of a Japanese family, Sagamihara family, was due to the mutations of alpha-synuclein, parkin, tau, and UCH-L1, which have been reported as the causal genes for parkinsonism in other families. Restriction-enzyme digestion of polymerase-chain reaction (PCR) amplified genomic DNA fragments of alpha-synuclein exons 3 and 4 detected no point mutation. PCR-amplification of parkin exons 3, 4, 5, 6 and 7 detected no exon deletion. Direct sequencing of PCR-amplified DNA fragments of tau exons 9, 10, 12, and 13 and intron 10, and of UCH-L1 exon 4 revealed that all these exons and intron were normal including a polymorphic nucleotide substitution. These results indicated that the parkinsonism of the Sagamihara family seems not to be due to previously identified point mutations of alpha-synuclein, tau, or UCH-L1, or to exon deletion of parkin.

Exons↗
PubMed2000

The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for migraine.

Increased homocysteine levels are associated with various pathological conditions in humans, including stroke and cardiovascular disorders. Homocysteine acts as an excitatory amino acid in vivo and may influence the threshold of migraine headache. Frosst et al. [1995] reported an association between the homozygous C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and serum homocysteine levels. This study was designed to determine the prevalence of the MTHFR mutation in Japanese patients with migraine and tension-type headache (TH). Seventy-four patients with migraine headaches (22 with aura and 52 without aura), 47 with THs, and 261 normal controls were recruited. Genotyping of MTHFR C677T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. We detected that the incidence of the homozygous transition (T/T) in migraine sufferers (20.3%) was significantly higher than that in controls (9.6%). Moreover, the frequency of the T/T genotype in individuals with migraine headaches with aura was remarkably high (40.9%). The MTHFR T allele was more frequent in the migraine group than in the control group. Our results support the conclusion that the MTHFR gene, causing mild hyperhomocysteinemia may be a genetic risk factor for migraine. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:762-764, 2000.

Alleles↗
PubMed2000

Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD.

Plasma homocysteine and cysteine levels were measured in 90 patients with PD with the MTHFR C677T (T/T) genotype. The authors found that the levels of homocysteine-a possible risk factor for vascular disease-were elevated by 60% in levodopa-treated patients with PD, with the most marked elevation occurring in patients with the T/T genotype. Cysteine levels in subjects with PD did not differ from levels in control subjects. In the T/T genotype patients, homocysteine and folate levels were inversely correlated. Increased homocysteine might be related to levodopa, MTHFR genotype, and folate in PD.

Aged↗
PubMed2000

Cosinor analysis of heart rate variability in ambulatory migraineurs.

OBJECTIVE: To clarify whether the circadian rhythm of heart rate variability parameters can be identified in patients with migraine during a headache-free period and to identify any specific pattern of the circadian rhythm of heart rate variability, using time-domain and spectral analysis and cosinor rhythm analysis of heart rate variability during normal daily activity. METHODS: Forty-eight-hour Holter electrocardiograms were recorded for 27 patients with migraine during headache-free periods and 24 healthy controls during free activity. The circadian rhythms of heart rate fluctuation parameters, that is, mean interval, standard deviation, root-mean-square successive differences (RMSSD), %RR50, and low (0. 020 to 0.150 Hz) and high frequency (0.150 to 0.400 Hz) heart rate fluctuations were analyzed with the group mean cosinor method. RESULTS: The group mean cosinor analysis and the acrophase-amplitude analysis demonstrated significant differences in circadian rhythm in SD, RMSSD, %RR50, and high frequency between the group with migraine and controls. The amplitudes of SD, RMSSD, %RR50, and high frequency in the group with migraine were smaller than those in controls, which implied parasympathetic hypofunction in migraineurs. There were no significant differences in the MESOR (midline estimating statistic of rhythms) of the analyzed heart rate parameters except for low frequency. The MESOR of low frequency in the migraineurs was significantly smaller than that in the controls. CONCLUSIONS: Patients with migraine have hypofunction in the parasympathetic nervous system during normal daily activity in the headache-free period.

Adolescent↗
PubMed2000

Effects of artefacts on scanning laser polarimetry of retinal nerve fibre layer thickness measurement.

AIMS: To investigate the effects of artefacts on scanning laser polarimetry of the retinal nerve fibre layer. METHODS: Six eyes of six normal volunteers and an artificial nerve fibre layer were examined using the nerve fibre analyser II. The retinal nerve fibre layer thickness (RNFLT) was measured in each of four 90 degree quadrants, superior (S), temporal (T), inferior (I), and nasal (N), at 1.5 disc diameters from the disc margin. Study 1: Measurement in normal eyes. The amount of maximum error in RNFLT measurements was investigated as follows: (1) the intensity setting of the laser beam was changed to be as weak as possible or to be as strong as possible; (2) the intentional offsets of the laser beam axis in relation to the pupil were made in four directions; (3) the eye was rotated by shifting the head 45 or 90 degrees; (4) the right eye was measured by moving it to the left eye position on the head rest. Study 2: Measurements on an artificial nerve fibre layer. The birefringence measurements were confirmed with a plastic disc, which has a radial arrangement of birefringence. The plastic disc with black paper was fixed at the right eye position or the left eye position on the head rest. The retardation of the laser beam by the plastic disc on the black paper was measured. The retardation of the plastic disc was checked by an automatic birefringence evaluation system (ABR-10A, Uniopt Co, Ltd, Shizuoka). RESULTS: Study 1: The effects of the rotated eye and the measurement of the opposite eye position were significant. The eyes rotated 90 degrees showed quite a different pattern in which the thicker and thinner locations of the RNFLT are switched. The nasal RNFLT of the baseline and the 90 degree rotated eye are 41.9 (SD 6.0) microm and 122.5 (11.2) microm, respectively (p<0.0001, Scheffe multiple comparison test). Study 2: The uniform retardation of the plastic disc was observed with the ABR-10A. The NFA detects the retardation of the plastic disc which the retardation map showed as a double humped pattern. CONCLUSIONS: Study 2 indicated that the amount of corneal compensation was not small. The cause of significant influences by the rotated eyes and right eyes measurement in left eye position were thought to be incorrect corneal compensation. To increase the diagnostic ability of SLP, an improved compensation of the cornea is thought to be important.

Adult↗
PubMed2000

[Manifestation of primary biliary cirrhosis and Basedow's disease caused by exposure to carbon monoxide in a patient with HTLV-1 associated myelopathy].

A 55-year-old woman with HTLV-1 associated myelopathy (HAM) was discovered in a rentan kotatsu (Japanese foot warmer with a frame and a coverlet by burning briquet) with conscious disorder and admitted to an emergency hospital. Her conscious disturbance waned the 3rd day after admission with gradual improvement of communication and food intake. However, on the 18th day after admission, her orientation was poor again and she was unable to take food for herself and keep sitting. She was diagnosed as suffering from an interval form of acute carbon monoxide (CMO) poisoning and transferred to our hospital for the purpose of hyperbaric oxygen therapy on the 20th day after exposure to CMO. In the course of treatment she recovered but showed jaundice, pruritus, liver dysfunction and elevation of antimitochondrial antibody. She received liver biopsy and was found to have primary biliary cirrhosis (PBC). On the 150th day, she manifested perspiration and hypertension. The clinical and immunological feature revealed her Basedow's disease. The relationship between HAM and PBC due to the autoimmune process has been predicted by investigators. The implication of autoimmune disease and HLA haplotype is a main focus of attention. Our case supports their hypothesis, and suggested that the complication occurred with immunological and genetic correlation. Anti-HTLV-1 antibody was positive at a titer of 1:8192 before exposure to CMO. On transferring to us, it was negative and revealed excessive positive at a titer of 1:20,480 on the 80th day. Immunoglobulin analysis was normal on admission and increased during hospitalization. It was reported that prenatal exposure to relatively mild concentrations of CMO in rats reduces splenic macrophage phagocytosis and killing ability as well as macrophage respiratory burst. These data suggested that PBC and Basedow's disease were manifested by exposure to carbon monoxide.

Acute Disease↗
PubMed1999

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females with a mean age of 67.9+/-5.8 years), 12 patients with PSP (eight males and four females with a mean age of 62.6+/-5.8 years) and 36 control subjects (CTL) (16 males and 20 females with a mean age of 65.8+/-9.9 years). The CBD group included patients with probable CBD, while all the patients in the PSP group satisfied the diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP). CSF tau proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). The CSF tau protein level was 320.1+/-86.5 pg/ml in the CBD group, 151.5+/-52.7 pg/ml in the PSP group and 128.7+/-91.7 pg/ml in the CTL group. Significant differences were noted in tau protein levels between the CBD group and both the PSP group (P<0.001) and the CTL group (P<0.005). We suggested that the measurement of CSF tau proteins may be useful for the differentiation between CBD and PSP.

Aged↗
PubMed1999

[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].

To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.

Adolescent↗
PubMed1998

Kinesin and cytoplasmic dynein in spinal spheroids with motor neuron disease.

Kinesin and cytoplasmic dynein are two major molecular motors responsible for fast axonal transport. As visualized by immunohistochemistry with monoclonal antibodies, both motors were found to be distributed throughout the cell bodies, dendrites and axons of motor neurons in normal human spinal cords. Large axonal swellings, spheroids, in the spinal cords of patients with motor neuron disease showed massive accumulation of kinesin co-localized with highly phosphorylated neurofilaments. Of 114 spheroids in five spinal cords, 87% were stained heavily with the three anti-kinesin antibodies used in this study. Cytoplasmic dynein was scarce or absent in most of the spheroids. These findings suggest that kinesin selectively accumulates in the spheroids of motor neuron axons, causing disturbance of the machinery for anterograde fast axonal transport in motor neuron disease.

Aged↗