Sphingosylphosphorylcholine is a novel messenger for Rho-kinase-mediated Ca2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C

Although recent investigations have suggested that a Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase-mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 micromol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester-induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.     

Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy

Hepatic lipase (HL) is a lipolytic enzyme that catalyzes hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Recently, a -514C/T polymorphism in the promoter region of the HL gene was found to be associated with variations in hepatic lipase activity and serum high density lipoprotein cholesterol (HDL-C) levels. Postmenopausal hormone replacement therapy (HRT) has known favorable effects on serum lipid and lipoprotein levels. In this study, we examined the relation between the -514C/T polymorphism and serum lipid and lipoprotein levels in postmenopausal women prior to and after 3 months of HRT. Significant associations between the -514 C/T polymorphism and HDL-C, low density lipoprotein cholesterol (LDL-C) and apolipoprotein A-I (apo A-I) levels were observed before and/or after 3 months of HRT. With HRT, serum total cholesterol (TC), LDL-C and apolipoprotein B (apo B) levels were reduced significantly (P=0.0001), and HDL-C and apo A-I levels were increased significantly (P=0.0001). However, the degrees of change in lipid and lipoprotein levels due to HRT did not differ significantly between the HL genotypes.     

Social Integration and Healthy Aging in Japan: How Gender and Rurality Matter

The current study analyzed the 1999 and 2001 waves of the Nihon University Japanese Longitudinal Study of Aging. Two measures of social integration were associated with lower risks of being physically disabled or depressed at Wave 1 and with a lower risk of progressing into deeper levels of physical disability and depression by Wave 2. Ceteris paribus, compared to elderly urbanites, elderly ruralites had a much higher risk of being physically disabled but much lower odds of being depressed. And compared to elderly men, elderly women had similar risks of being physically disabled but much higher odds of being depressed. Suggestions are made on how future research on longevity in Japan, the world’s most longevous nation, can explore the links among social integration, place, gender, and the postponement of mortality.     

Endoscopic ventriculocystostomy through the septum pellucidum via the contralateral anterior horn--technical note

Paraventricular fluid cysts have recently been treated by endoscopic fenestration performed from the cysts to the ventricular system. However, correct orientation and safe navigation of the endoscope may be difficult in patients with abnormal anatomy. Endoscopic fenestration from the ventricular system to a cyst was performed through penetration of the septum pellucidum via the anterior horn of the contralateral lateral ventricle. The advantage of this approach is correct orientation and introduction of the endoscope to the periventricular lesion because the usual landmarks can be identified in the normal contralateral lateral ventricle.     

Associations between physical strength, cerebral function and mental health in independent-living elderly Japanese women

Objectives  To evaluate the physical strength, cerebral function, and mental health conditions in elderly persons, and to examine the correlation between these functions. Methods  The subjects were 151 independent-living elderly Japanese women, mean age 70 +/-5 years (+/-SD; range, 60 to 80 years), with normal abilities in daily life. The health check-up was conducted from April to May 1997. Physical strength was estimated by measuring seven activities. Cerebral functions were assessed by six sub-tests of the General Aptitude Test Battery (GATB). Their mental health status was measured by four sub-scales of the General Health Questionnaire (GHQ)-28. Results  The physical strenght and almost all of the cerebral functions decreased with age. Social dysfunction and severe depression on the GHQ sub-scales also worsened with age. Physical strength was strongly correlated with cerebral functions after adjusting for the confounding effect of aging. There were also interrelations between physical strength and mental health. Conclusions  This study provided important information on the correlation between physical and mental status in elderly women. Future longitudinal studies with the intervention of physical training are required to determine whether a causal relationship exists between these factors.     

A survey of utilization of and problems with the MSDS in chemical substances management at workplaces in Kanagawa Prefecture]

Kanagawa Occupational Health Promotion Center conducted a survey on how the MSDS is utilized at workplaces with more than 50 employees handling chemical substances, and what measures are taken to help employees to thoroughly understand information in the Material Safety Data Sheet (MSDS). Questionnaires were sent out to 265 enterprises in Kanagawa prefecture, putting questions to industrial physicians and industrial hygiene supervisors. The objective of the survey was to find out how MSDS is adopted in the system to manage occupational health, what improvements the survey respondents want in MSDS and what expectations the respondents have of our center. 193 enterprises (72.8%) returned answers to the questionnaire. The major findings are as follows. (1) In many companies, information on hazardous/toxic materials is "controlled by a division using such materials", and roughly half of the companies have compiled a common list shared throughout the company. (2) For the most part suppliers submit to the MSDS. Larger companies have a higher rate of posting up or filing the MSDS at their workplaces. Only 25.8% of the companies "rewrite the MSDS so that workers can understand it." (3) Companies that carry out a hazard/toxicity assessment before introducing a new chemical substance account for 72.1%, which is higher than we expected. It indicates that even though the companies don't manage the MSDS adequately, they are highly concerned about hazard control of chemical substances. (4) The rate of answering that "the current MSDS is not easy to understand" is higher among large-sized enterprises and lower among enterprises with fewer than 300 employees. (5) Asked what improvement needs to be made on the MSDS, the industrial physicians and industrial hygiene supervisors gave same answers such as "Workers find the terminology difficult to understand." and "Levels of toxicity can't be clearly identified." (6) The respondents expect our center to provide information for the MSDS. In conclusion, it is considered that in order to prepare understandable MSDSs to workers in enterprises, the role of our center to provide information and education on the MSDS to respondents was important.     

Brominated labdane-type diterpenoids from an Okinawan Laurencia sp

From an unidentified species of Laurencia collected from Okinawan waters two novel brominated metabolites, 1 and 2, along with known halogenated compounds, 2,10-dibromo-3-chloro-alpha-chamigrene (3) and microcladallene A (4), were isolated and identified. The structures of these new compounds were established as ent-labdane-type bromoditerpenes, (1S,3R,5S,6S,8S,9S,10R,13R)-1-acetoxy-3-bromo-6-hydroxy-8,13-epoxy-labd-14-ene (1) and (3R,5S,6S,8S,9S,10R,13R)-3-bromo-6-hydroxy-8,13-epoxylabd-14-en-1-one (2), by interpretation of their spectroscopic data as well as by X-ray crystallographic analysis.     

A case of acute encephalitis with refractory,repetitive partial seizures (AERRPS) showing transient disappearance of the seizure with occurrence of choreo-ballistic movement

We present here a 5-year-old girl with acute encephalities with refractory, repetitive partial seizures (AERRPS), a new clinical entity defined by the following five criteria: 1. acute encephalitis with a prolonged acute phase of more than 2 weeks, 2. persistent partial seizures with identical phenotype both in the acute and recovery phase, 3. seizures frequently evolving into convulsive status especially during the acute phase, 4. extremely intractable, and 5. no causative lesion or agent is identified. Interestingly, her seizures had completely diminished from the fifty-sixth day of her illness with concomitant appearance of choreo-ballistic involuntary movements. After the 120th day of the illness, seizures evolved again, though the involuntary movements persisted. This transient disappearance of intractable seizures might provide a clue to the pathophysiology of seizures in AERRPS.     

Interobserver discrepancy using the 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms: practical choices for patient care

PURPOSE: Morphological classifications designed by experts to stratify neoplasms according to biological potential must define categories that are reproducible among practitioners or the schemes actually create the heterogeneous populations that they seek to avoid. The application of the 1998 World Health Organization/International Society of Urologic Pathology scheme for urothelial neoplasms was studied in a community practice setting. We documented interpretive discrepancies for each category of neoplasm and determined whether a period of pathologist education may have a positive effect on the frequency of discrepant interpretations. The results suggest that patients may benefit from modifying the classification system. MATERIALS AND METHODS: A consecutive series of specimens was divided into learning and study sets that were each independently examined by 3 pathologists. Specimens in the learning set were interpreted without previous structured education, while those in the study set were interpreted immediately after intensive education. Interpretations for each specimen were compared and interpretive discrepancies were analyzed. RESULTS: Case distribution after education was similar among the pathologists but interpretations for any particular specimen often differed. The level of interpretive discrepancies varied according to the morphological similarity among categories in the classification scheme and was not necessarily decreased by education. When pathologists were required to discriminate between papillary urothelial neoplasm of low malignant potential and low grade carcinoma, the discrepancies were 50% after education compared with 39% before education. In contrast, there were no discrepancies when the discrimination was between papillary urothelial neoplasm of low malignant potential and high grade carcinoma or carcinoma in situ. Eliminating categories with poor reproducibility markedly improved the likelihood of unanimous agreement among practitioners but a probably irreducible level of 10% discrepancies remained. CONCLUSIONS: The 1998 World Health Organization/International Society of Urologic Pathology classification of urothelial neoplasms requires certain discriminations that cannot be reliably made by practitioners. Modifying the scheme to create categories of low grade neoplasm and high grade carcinoma would markedly increase its practical value to patients without significantly altering patient care.     

Oxidative stress and disturbed glutamate transport in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a hereditary motor neuron disease, and three clinical subtypes of autosomal recessive SMA, including Werdnig Hoffmann disease (type 1), have been shown to be induced by deletion within the same genes. In order to clarify the pathogenesis of motor neuron degeneration in SMA, we immunohistochemically examine the expressions of oxidative stress-related materials (oxidative products) and glutamate transporters, which can prevent glutamate neurotoxicity, in five autopsy cases of SMA type 1. Age-matched controls did not show any deposition of oxidative products in the brain. In contrast, the abnormal deposition of 4-hydroxy-2-nonenal-modified protein, a product of membrane lipid oxidation, was observed in the spinal motor neurons in three cases, although the motor neurons did not show an increase of nitrotyrosine, which was observed in adult-onset amyotrophic lateral sclerosis. In addition, the nuclei of neurons and glial cells in the precentral gyrus, thalamus or cerebellar cortex were immunoreactive for 8-hydroxy-2′-deoxyguanosine in two cases, which was one of the most commonly used markers for oxidative DNA damage. Regarding glial glutamate transporters, three of five cases of SMA type 1 showed a reduction in immunoreactivity for excitatory amino acid transporter-1 (GLAST) in the ventrolateral nucleus of the thalamus, in which there was neither neuronal loss nor gliosis in routine histochemistry. One case, having mechanical ventilation, demonstrated a reduced expression of another glial glutamate transporter (GLT-1) throughout the central nervous system. These data suggest that oxidative stress and disturbed glutamate transport can partly be involved in the motor neuron devastation and/or latent thalamic degeneration in SMA type 1.