Epidemiological study of acute encephalitis in Tottori Prefecture, Japan.

BACKGROUND AND PURPOSE: To conduct an epidemiological survey of acute encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in Tottori Prefecture, western area of Japan. METHODS: A questionnaire survey on the annual number of patients aged 16 years or more with acute encephalitis from 2001 to 2005 was undertaken in 2006. RESULTS: During the study period, 49 patients were diagnosed with acute encephalitis. The subtype of acute encephalitis was as follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis associated with collagen disease, one patient with viral encephalitis other than HSE, 20 patients with encephalitis with unknown causes. The service-based incidence rate of acute encephalitis was 19.0 per million person-years. The incidence rate of NHALE subtype was 4.7 per million person-years. CONCLUSIONS: Our epidemiological survey indicated an estimated 550 patients would develop NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.

The reduction of nonspecific binding in chemiluminescent sandwich enzyme immunoassays.

The reduction in nonspecific binding obtained in EIA procedures based on glucose oxidase (GO)-labelled antibody is determined by the origin of the antibodies used for both the solid phase and for GO labelling. We have examined the relationship between nonspecific binding and various antibody combinations for the purpose of establishing highly sensitive chemiluminescent sandwich enzyme immunoassays. It was shown that nonspecific binding could be reduced by the following combination of solid phase and GO labelled antibodies: (i) guinea pig IgG-guinea pig IgG, (ii) goat IgG-rabbit IgG, (iii) goat IgG-rabbit Fab'. On the basis of these results, we succeeded in establishing highly sensitive chemiluminescent sandwich enzyme immunoassays for human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP). The detection limit was 2.5 mIU/ml for hCG using combination (i), 1 ng/ml for AFP using combination (ii), and 0.05 ng/ml (70 amol/assay) for AFP using combination (iii).

Histochemical demonstration of Cl(-)-ATPase in rat spinal motoneurons.

Using an enzyme-histochemical technique, rat spinal cords were stained for Cl(-)-ATPase, Na+,K+-ATPase and anion-insensitive Mg2+-ATPase. Cl(-)-ATPase activity was demonstrated in plasma membranes of spinal motoneurons, Na+,K+-ATPase activity and anion-insensitive Mg2+-ATPase activity were detected in neuronal plasma membranes and blood vessels, respectively.

Spinocerebellar ataxia type 6: founder effect in Western Japan.

An accumulation of SCA6 cases has been observed in the Chugoku area of Western Japan. In the Tottori prefecture, located in the northeastern part of the Chugoku district, we observed a cluster of SCA6 families within the eastern area, suggesting that there may be a founder in the Japanese SCA6 population. Genotyping with DNA microsatellite markers linked to the CACNL1A4 gene on chromosome 19p13 demonstrated shared allelic characteristics and revealed a common haplotype in the majority of Japanese families. The common haplotype of the shared (CAG)(22) repeat found in this study may indicate the meiotic stability of CAG repeats in SCA6 patients.

Clinical usefulness of electrically elicited pain-related evoked potentials.

In 14 patients with sensory disturbance, the clinical usefulness of electrical pain-related evoked potentials (EPREPs) were studied. In four patients with deep sensation disturbance, conventional somatosensory evoked potentials (SEPs) were abnormal. However, EPREPs were abnormal only in one of the patients. In nine patients with pain-temperature sensation disturbance, SEPs were normal except for only one patient and EPREPs were abnormal in seven of the nine patients. In a patient with herpes zoster myelitis, EPREPs elicited by electrical stimulation below the disturbed spinal level were delayed. After symptomatic improvement, EPREPs recovered. EPREPs are useful in the clinical field.

[Prevalence and founder effect of Huntington's disease in the San-in area of Japan].

After the DNA diagnosis, we evaluated the prevalence of Huntington's disease (HD) in the San-in area of Japan, and confirmed the founder effect. The population of the area was 1,387,000 on October 1st, 1993. There were 10 patients with HD in the San-in area, who were diagnosed clinically. They all had involuntary movement, mental disturbance, changes of character and atrophy of the caudate nucleus. However, one of the patients showed no positive family history of HD. The other nine patients had members with HD in their families, although those family members of the patients had already died. The expansion of the CAG repeat was observed in nine of the patients. In the patient who had no positive family history, expansion of the CAG repeat was not seen. According to the nine patients with expansion of the CAG repeat, the prevalence was 0.65/100,000. Haplotypes using polymorphism markers of D4S111 and D4 S136 were studied. The haplotypes which were observed in only 2.7% of the normal population were shown in all nine HD patients. Thus, the obvious disequilibrium was seen. These results suggested a common ancestor of these HD patients.

[Two cases of multiple evanescent white dot syndrome examined with indocyanine green angiography].

Two cases of multiple evanescent white dot syndrome (MEWDS) were examined using indocyanine green angiography. Patients were 32 and 45 years old. Both were female. Fluorescein angiography demonstrated early hyperfluorescence corresponding to the white dots. The early phase of indocyanine green angiography showed no abnormal signs, but the late phase disclosed hypofluorescent lesions corresponding to the white dots and even other areas. Each hypofluorescent lesion was punctate and patchy in some areas. The white dots began to fade and returned to the normal color of the fundus from the center to the edge of the lesion. In indocyanine green angiography, the hypofluorescent lesions began to show a normal appearance at the center of the lesion. The indocyanine green angiogram was normal after the white dots had disappeared. The origin of hypofluorescence in indocyanine green angiography was unknown. However, the findings suggest that MEWDS may affect the choroid as well as the retinal pigment epithelium and photoreceptors.

[Quality of life in Parkinson's disease].

Parkinson's disease(PD) is a slowly progressive neurodegenerative disease. QOL improvement could be the main endpoint in some clinical trials, such as in those carried out in palliative care or incurable disease. Several instruments that assess to QOL of PD(PDQOL) have been established such as SF36, PDQ39 and PDQL. This article is reviewed about the importance for the improvement of PDQOL and the influence to PDQOL from the point of view from the epidemiological studies in Japanese population. The various approaches to the patients are necessary for the improvement of PDQOL.

Serum proteomic profiling of dementia with Lewy bodies: diagnostic potential of SELDI-TOF MS analysis.

Dementia with Lewy bodies (DLB) is the second most common senile degenerative dementia after Alzheimer's disease (AD). The presentation of overlapping symptoms between these two disorders leads to difficulties in the determination of clinical entities. Serum samples were subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis in order to identify a diagnostic marker for DLB. Four putative protein peaks (m/z 3,883, 4,964, 7,761 and 10,534) were differentially expressed in DLB patients compared to AD patients and control subjects. Receiver operating characteristics (ROC) analysis of a multivariate logistic model of the combination of three peaks (m/z 3,883, 7,761 and 10,534) exhibited the highest discriminatory ability of DLB subjects from non-DLB subjects with a sensitivity of 83.3%, a specificity of 95.8%, a positive predictive value of 90.9% and a negative predictive value of 92.0%. SELDI-TOF MS profiling, therefore, has revealed a serum signature with high diagnostic potential for DLB.

Rerupture of cerebral aneurysms during angiography--a retrospective study of 13 patients with subarachnoid hemorrhage.

UNLABELLED: OBJECTIVE, BACKGROUND: Cerebral angiography, performed within 24 hr of aneurysmal rupture, carries an increased risk of rebleeding. We have investigated the rerupture rate during angiography procedures under deep general anesthesia and the factors that contribute to rebleeding. METHODS: We divided 69 patients who had experienced aneurysmal rerupture into 2 groups. Group I (n = 13) suffered rebleeding during cerebral angiography and group II (n = 56) who rebled at a different time. We assessed the effects on rebleeding of the (1) time between the first insult and angiography, (2) WFNS clinical grade on admission, (3) blood pressure during angiography, (4) age and sex, (5) Fisher classification on admission, (6) aneurysmal site, and (7) Glasgow outcome score (GOS). RESULTS: Factors that had a statistically relevant effect on rebleeding during cerebral angiography (Group I) were the performance of angiography within 3 hr of the initial insult, the admission grade, and the aneurysmal site. Especially, the rerupture events during cerebral angiography were concentrated within 3 hr of the initial insult; the rate was 23.9% when angiograms were obtained within 3 hr of onset. Group I patients manifested a worse clinical grade and middle cerebral artery (MCA) aneurysms were prevalent in this group. However, there was no significant difference between the 2 groups with respect to blood pressure, age, sex, Fisher classification, and GOS. CONCLUSIONS: Cerebral angiography at ultra-early timing (within 3 hr of the insult) carries a high risk of aneurysmal rerupture, even if the procedure is performed under deep anesthesia and normotensive blood pressure. Cerebral angiography during that period should be avoided.

Indocyanine green angiographic aspects of multiple evanescent white dot syndrome.

PURPOSE: The authors investigated the indocyanine green angiography findings of multiple evanescent white dot syndrome (MEWDS). METHODS: Four patients with MEWDS underwent examination by indocyanine green angiography, conventional ophthalmoscopy, and fluorescein angiography. RESULTS: Fundus examination showed multiple white dots in the retinal pigment epithelium of the unilateral eye of each patient. Fluorescein angiography demonstrated early hyperfluorescence corresponding to the white dots. In the early phase, indocyanine green angiography showed no abnormal signs in the large choroidal vessels, but in the late phase, hypofluorescent lesions appeared, corresponding to the white dots. The hypofluorescent dots were clustered in the posterior pole and sporadic in the peripheral region, appearing to radiate away from the optic disc or fovea. The hypofluorescent dots disappeared at the recovery stage. CONCLUSIONS: Previous fluorescein angiographic and electrophysiologic studies have demonstrated the involvement of the retinal pigment epithelium (RPE) and photoreceptors in MEWDS: The current findings on indocyanine green angiography suggest that MEWDS affects the choriocapillaris or precapillary arterioles as well as the RPE and photoreceptors, and that the lesions spread to the midperipheral region, centering on the optic disc or fovea.

Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis.

Familial hypokalemic periodic paralysis is an autosomal dominant disorder. Recently, three predominant mutations were found in the muscle dihydropyridine-sensitive calcium channel alpha 1-subunit gene. We present a Japanese family that displays one of these, the Arg1239His mutation. All the affected individuals of this family displayed this mutation. Two cases had a history of recurrent episodes of muscle weakness and difficulty in running before their first paralytic attack. It is suggested that there are no racial differences with this mutation, and that mild muscle weakness occurs not only after but also preceding the first attack.

A genetic epidemiological study of spinocerebellar ataxias in Tottori prefecture, Japan.

We investigated the genotype frequencies of patients with spinocerebellar ataxias (SCA), using a community-based prevalence study among 613,349 inhabitants in Tottori prefecture, Japan. Prevalence date was April 1, 1998. On this date, 109 SCA patients were identified in this community. The prevalence of SCA was 17.8 per 100,000 individuals. The most common cause of inherited SCA was a mutation at the SCA6 locus (25%), followed by mutation at the SCA1 locus (15%), SCA3 locus (5%) and dentatorubral-pallidoluysian atrophy locus (5%). None of the expanded alleles was found in SCA2, SCA7 or Friedreich's ataxia. Mutation at SCA6 was also the most common form of sporadic SCA at 11%. Prevalences per 100,000 individuals were as follows: SCA6, 2.40; SCA1, 0.48; DRPLA, 0.32, and SCA3, 0.16.

Prevalence of focal dystonias in the western area of Tottori Prefecture in Japan.

We evaluated the prevalence of focal dystonias in the western area of Tottori Prefecture in Japan. The population of the area was 244,935 on October 1, 1992. Because four patients with blepharospasm and three patients with writer's cramp did not visit any hospitals or clinics in 1993 and did not reply to our question letter, we could not confirm their present condition: with or without focal dystonia in 1993. Four patients with facial dystonia including blepharospasm and oromandibular dystonia, seven with spasmodic torticollis, and four with writer's cramp were observed. The prevalence of focal dystonias was 6.12 per 100,000 persons, which may be lower than that in western countries. Although the reasons for this difference are still unclear, a genetic factor may be one implication.

Epidemiology of inflammatory neurological and inflammatory neuromuscular diseases in Tottori Prefecture, Japan.

We investigated the incidence of the following conditions: inflammatory neurological and neuromuscular diseases, adult meningitis and adult encephalitis in Yonago City, and Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), polymyositis/dermatomyositis (PM/DM), periarteritis nodosa (PN) and HTLV-1 associated myelopathy (HAM) during the period 1988-1992 in Tottori Prefecture, Japan. The annual incidence per 100,000 population was as follows: meningitis, 4.38; encephalitis, 0.90; GBS, 1.14; PM/DM, 1.01; and PN, 0.32. The prevalence per 100,000 population CIDP, 0.81; PM/DM, 9.92; PN, 2.59; and HAM, 1.30. There were marked localization of HAM in western Tottori, and there was seasonal variation in the prevalence of meningitis, encephalitis and GBS. The mean age at onset of meningitis was lower than that for encephalitis. Comparison with reported data revealed interracial differences in the epidemiology of PM/DM and PN.

Site-directed mutagenesis of the putative active site residues of 3C proteinase of coxsackievirus B3: evidence of a functional relationship with trypsin-like serine proteinases.

Picornavirus 3C proteinases (3Cpro) are cysteine proteinases but recent sequence analyses have shown that they are related to trypsin-like serine proteinases. Two models of 3Cpro structure have been presented. Both models indicate that residues His40 and Cys147 are members of the catalytic triad but the models differ in the designation of the third member of the catalytic triad, which is assigned as either Glu71 or Asp85. To test the importance of these four residues in the catalytic activity of 3Cpro of coxsackievirus B3, a member of the enterovirus subgroup of the picornavirus family, single amino acid substitutions were introduced at each of the four sites. All of these mutations resulted in the reduction or inactivation of autocatalytic cleavage of the 3C precursor protein expressed in Escherichia coli, suggesting that all of these residues are essential for the proteolytic reaction. The substitution of Cys147 with Ala abolished 3Cpro activity while the mutant in which Cys147 was replaced with Ser retained reduced proteolytic activity both in cis and in trans. Our results strongly support the proposal that Cys147 of 3Cpro functions as a nucleophile analogous to Ser195 of trypsin-like serine proteinases.

Epidemiology of Parkinson's disease in Yonago City, Japan: comparison with a study carried out 12 years ago.

A study of the prevalence of Parkinson's disease (PD) was conducted in a Japanese city in 1992, and the data compared with those of a similar study performed in 1980. On the prevalence day, April 1, 1992, a total of 156 patients (46 males and 110 females) were found to be living in the investigated area, which had a population of 132,315. The prevalence per 100,000 population was 117.9 (72.8 in males and 159.1 in females), and the incidence during the period 1989 through 1992 was 15.0 per 100,000 population per year. The age- and sex-adjusted prevalence per 100,000 population was 99.5 in 1992 and 103.9 in 1980, as calculated using the 1990 Japanese population as the standard. The age-adjusted prevalence in the population under 60 years of age and the incidence in those under 55 years of age in 1992 were lower than in those under 55 in 1980. These results revealed that changes in the age structure of the population were the main contributors to the increased incidence of PD.

Expression and purification of recombinant 3C proteinase of Coxsackievirus B3.

We have cloned various lengths of coxsackievirus B3 cDNA encompassing the region encoding the 3C proteinase, which is essential to the viral replication cycle. Such viral cDNAs were fused in frame to the 5'terminal portion of the lacZ' gene carried on the vector pUC118 to express mature 3C proteinase in Escherichia coli. In the E. coli cells containing pCXB108 or pCXB117, constructed for this study, a large amount of 23-kDa protein was synthesized in the presence of IPTG. This protein was purified and was shown to be intact 3C proteinase. These data suggest that 3C proteinase, expressed as a part of a fusion protein, was active in E. coli and released itself from the precursor fusion protein by autocatalytic cleavage.

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.

Roles of hydrophobicity, protein binding and the probenecid-sensitive transport system in the cerebrospinal fluid delivery of nucleoside analogues with anti-viral activity.

Ten nucleoside analogues with anti-herpes or anti-HIV activity were investigated for their transport into the cerebrospinal fluid (CSF) following intravenous administration in rats. The novel anti-herpes agent 1-beta-D-arabinofuranosyl-2-thio-5-fluorocytosine (5F-araSC) showed the highest CSF/plasma concentration ratio (>20%), while that of acyclovir (ACV) was very low (<5%). A linear relationship was observed between the partition coefficient (chloroform/water) and CSF/unbound plasma concentration in 6 of 9 agents. The exceptions were DDI, AZT and ACV, which showed much lower concentrations in the CSF than expected from their hydrophobicity and protein binding activities. The effects of probenecid treatment on the CSF and plasma concentrations were measured with continuous intravenous administration of ACV, AZT, araC and 5F-araSC. Probenecid markedly increased the CSF concentrations of ACV and AZT, although the effect was minimal in araC and 5F-araSC. These results may provide useful information for molecular design of nucleoside analogues with better transport to the brain.