Identification of polycavernoside A as the causative agent of the fatal food poisoning resulting from ingestion of the red Alga Gracilaria edulis in the Philippines

Outbreaks of seaweed poisonings are widely spread over the pacific area. Fatal glycosidic macrolides, polycavernosides, and potent tumor promoters, aplysiatoxins, have been previously isolated from edible seaweed. During 2002-2003, three fatal poisoning incidents occurred resulting from ingestion of two edible red alga, Acanthophora specifera and Gracilaria edulis, in Philippines causing eight deaths among 36 patients. Analytical methods for polycavernosides and aplysiatoxins were first developed, and the causative toxin from G. edulis, collected during the second poisoning event on December 2, 2002, was then investigated. The semipurified toxic fraction obtained from this alga based on mouse bioassay was applied to LC-diode array detection (LC-DAD) and LC/electrospray-MS (LC/ESI-MS) analyses. Both LC-DAD and LC/MS chromatograms of this fraction suggested the presence of polycavernoside A (PA) by comparison with the authentic PA. The amount of PA in the alga was estimated as 84 and 72 nmol/kg, using the standard calibration curves for LC-DAD and for LC/ESI-MS in single ion monitoring (SIM) mode, respectively. Other polycavernoside congeners, A2, A3, and B2, and aplysiatoxin and debromoaplysiatoxin were less than the detection limit (2 nmol/kg alga, signal-to-noise ratio: 3) by LC/ESI-MS SIM analysis. In ESI-MS/MS, authentic polycavernosides showed the daughter ions corresponding to a sequential loss of fucosylxylose residues. These fragmentations were applied to LC/ESI-MS/MS for polycavernosides in selective reaction monitoring (SRM) mode. On SRM mass chromatograms, the toxic fraction from the alga showed the peaks corresponding to PA, supporting the identification of PA as the cause of poisoning of G. edulis in Philippines.     

Thyroid blockade during a radiation emergency in iodine-rich areas: effect of a stable-iodine dosage

We examined the effect of stable iodine on thyroid gland blockade in patients with hyperthyroidism in order to make a preliminary evaluation of the appropriate dose of iodine prophylaxis in the event of a radiation emergency in Japan in which radioiodine is released to the environment. Eight patients were orally given single doses of 50 mg or 100 mg of potassium iodide, which contained 38 mg and 76 mg of iodide, respectively. Both doses significantly suppressed a thyroid uptake of (123)I for 24 h (p = 0.03). The protective effects at 24 h were 73.3% and 79.5%, respectively. No side effects were observed during the trial. The present study demonstrates that a single oral administration of 38 mg of iodide produces a thyroid-blocking effect equivalent to that of 76 mg of iodide, suggesting that a reevaluation of the stable iodine dosage during radiation emergencies in iodine-rich areas such as Japan is warranted.     

Occupational class and exposure to job stressors among employed men and women in Japan

BACKGROUND: The relationship between occupational class and exposure to job stressors among employed men and women in Japan remains unclear. METHODS: Data of 16,444 men and 3,078 women were analyzed. The information was obtained from answers to a questionnaire distributed among employees of nine companies in Japan between 1996 and 1998 (average response rate, 85%). The International Standardized Classification of Occupations was used to classify respondents into eight occupational categories. The Job Content Questionnaire was used to measure job demands, job control, worksite support, and job insecurity. The associations between occupational class and job stressors, as well as job strain, were examined controlling for age, education, marital status, chronic medical condition, and personality traits, such as neuroticism and extraversion. RESULTS: Men and women in high-class occupations (e.g., managers and professionals) had significantly greater job control, while job demands and worksite social support were not greatly different among occupations. A clear occupational class gradient in job insecurity was observed in women. A greater prevalence of high job strain was observed in low-class occupations compared to high-class occupations in both men and women. The occupational class gradient in job strain was greater for women. These patterns did not change after controlling for other covariates. CONCLUSION: The present study suggests an occupational class gradient in job strain for employed men and women in Japan. Japanese women workers may have a greater occupational class gradient in job strain and job insecurity than men.     

Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.     

Centrifugation attenuates the fluid shear response of circulating leukocytes

Human leukocytes retract pseudopods in response to physiological fluid shear, a phenomenon that serves to keep circulating leukocytes in a spherical state. We show here that leukocyte fluid shear response is attenuated irreversibly by centrifugation. Inhibition of shear response depends on duration and magnitude of acceleration during centrifugation and time duration after centrifugation. Even after low-speed centrifugation, leukocytes no longer retract pseudopods during shear application. After centrifugation at higher acceleration, leukocytes project pseudopods instead of retracting during shear application, which can be suppressed by a calcium channel blocker. We examined the role of fluid shear response in vivo by reintroduction of centrifuged cells into the rat circulation. Centrifuged leukocytes have a significantly enhanced tendency to migrate into tissue. These observations indicate that centrifugation may irreversibly damage the fluid shear response of leukocytes. It causes an impaired leukocyte behavior after reintroduction into the circulation, suggesting that shear response is a requirement for normal passage of leukocytes through the microcirculation.     

Diagnostic implications of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary artery disease

OBJECTIVES: To examine the diagnostic performance of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary heart disease. DESIGN AND METHODS: 361 patients with coronary artery disease and 710 healthy volunteers as normal controls were examined. Receiver-operating characteristics curve analysis in addition to statistical analysis (univariate, multivariate) were done to determine the usefulness of the assay. RESULTS: Patients with coronary artery disease showed significantly elevated circulating oxidized low density lipoprotein levels. Males less than 70 years of age showed a significant association between oxidized low density lipoprotein levels and coronary artery disease. Receiver-operating characteristics curve analysis showed superior performance (e.g., sensitivity, specificity) of oxidized low density lipoprotein as a diagnostic marker of coronary artery disease as compared against other lipid markers (total cholesterol, triglyceride, high density lipoprotein, lipoprotein (a), and total cholesterol to high density lipoprotein ratio) with optimal performance in younger males. CONCLUSIONS: Oxidized low density lipoprotein levels may be a promising biochemical risk marker of atherosclerotic disease, especially in young males.     

Germinoma with syncytiotrophoblastic giant cells recurring 13 years after radiotherapy for a pineal germinoma--case report

A 28-year-old man presented with progressive mental deterioration. Thirteen years earlier he had undergone radiation therapy for a pineal germinoma. Neuroimaging showed a homogeneously enhanced mass lesion along the ventricular wall. The cerebrospinal fluid (CSF) level of human chorionic gonadotropin (HCG) was high. Endoscopic biopsy revealed that the tumor was a two-cell pattern germinoma. The diagnosis was germinoma with syncytiotrophoblastic giant cells (STGC). He first received three cycles of chemotherapy with carboplatin and etoposide and then two cycles with ifosfamide, cisplatin, and etoposide. Subsequently, the tumor size decreased markedly and the CSF level of HCG returned to normal. However, he died 22 months after the recurrence. Histological verification and measurement of tumor markers are necessary for the optimum treatment of germ cell tumors. Adequate initial chemotherapy and long-term follow up are essential for patients with germinoma with STGC.