Tetsuo Nomiyama

Prognostic Significance of the Immunohistochemical Staining of Cleaved Caspase-3, an Activated Form of Caspase-3, in Gliomas

Purpose: Gliomas are common tumors of the central nervous system, and the majority of patients with gliomas have a poor prognosis. The prediction of prognosis is very important in selecting treatment. In the present study, we retrospectively examined the immunohistochemical staining of cleaved caspase-3 (CC3), an activated form of caspase-3 that acts as a lethal protease at the most distal stage of the apoptosis pathway, in gliomas, and the correlation between the prognosis of patients and caspase-3 activation to find useful prognostic indicators. Experimental Design: Immunohistochemical staining of CC3 was done in 65 patients with gliomas. The percentage of CC3 staining-positive cells was defined as the CC3 immunoreactivity score (IRS). Survival analysis between CC3 IRS of glioma patients and survival time was carried out using the Kaplan-Meier method with the log-rank test and the Cox proportional hazards regression model. Results: CC3 IRS was statistically analyzed to designate the best provisional cutoff point, and when detected in >10% of glioma cells, it was considered positive. The Kaplan-Meier method with the log-rank test revealed that patients with CC3 IRS-positive tumors had significantly greater survival than those with CC3 IRS-negative tumors among three grades, 2, 3, and 4 (P = 0.0061), and within grade 3 of anaplastic astrocytoma (P = 0.0458). After adjustment for known clinical prognostic factors, such as age, WHO grade, and performance status, the hazard ratio for CC3 IRS-positive was 0.39 with 95% confidence interval between 0.19 and 0.85 (P = 0.0187). Within high grades, including grades 3 and 4, the hazard ratio was 0.40 with 95% confidence interval between 0.20 and 0.86 (P = 0.0192). Conclusions: CC3 IRS could be useful as a good prognostic indicator for glioma patients.

Uptake of cadmium in meals from the digestive tract of young non-smoking Japanese female volunteers.

Uptake of Cadmium in Meals from the Digestive Tract of Young Non‐smoking Japanese Female Volunteers: Yuriko Kikuchi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University

Cadmium concentration in current Japanese foods and beverages

Cadmium Concentration in Current Japanese Foods and Beverages: Yuriko Kikuchi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—

Screening for obstructive sleep apnea by cyclic variation of heart rate.

Background—Despite the adverse cardiovascular consequences of obstructive sleep apnea, the majority of patients remain undiagnosed. To explore an efficient ECG-based screening tool for obstructive sleep apnea, we examined the usefulness of automated detection of cyclic variation of heart rate (CVHR) in a large-scale controlled clinical setting. Methods and Results—We developed an algorithm of autocorrelated wave detection with adaptive threshold (ACAT). The algorithm was optimized with 63 sleep studies in a training cohort, and its performance was confirmed with 70 sleep studies of the Physionet Apnea-ECG database. We then applied the algorithm to ECGs extracted from all-night polysomnograms in 862 consecutive subjects referred for diagnostic sleep study. The number of CVHR per hour (the CVHR index) closely correlated (r=0.84) with the apnea-hypopnea index, although the absolute agreement with the apnea-hypopnea index was modest (the upper and lower limits of agreement, 21 per hour and −19 per hour) with periodic leg movement causing most of the disagreement (P<0.001). The CVHR index showed a good performance in identifying the patients with an apnea-hypopnea index ≥15 per hour (area under the receiver-operating characteristic curve, 0.913; 83% sensitivity and 88% specificity, with the predetermined cutoff threshold of CVHR index ≥15 per hour). The classification performance was unaffected by older age (≥65 years) or cardiac autonomic dysfunction (SD of normal-to-normal R-R intervals over the entire length of recording <65 ms; area under the receiver-operating characteristic curve, 0.915 and 0.911, respectively). Conclusions—The automated detection of CVHR with the ACAT algorithm provides a powerful ECG-based screening tool for moderate-to-severe obstructive sleep apnea, even in older subjects and in those with cardiac autonomic dysfunction.

Effects of weather variability and air pollutants on emergency admissions for cardiovascular and cerebrovascular diseases

We examined the effect of ambient temperature, air pressure and air pollutants on daily emergency admissions by identifying the cause of admission for each type of stroke and cardiovascular disease using generalized linear Poisson regression models allowing for overdispersion, and controlling for seasonal and inter-annual variations, days of the week and public holidays, levels of influenza and respiratory syncytial viruses. Every 1°C decrease in mean temperature was associated with an increase in the daily number of emergency admissions by 7.83% (95% CI 2.06–13.25) for acute coronary syndrome (ACS) and heart failure, by 35.57% (95% CI 15.59–59.02) for intracerebral haemorrhage (ICH) and by 11.71% (95% CI 4.1–19.89) for cerebral infarction. An increase of emergency admissions due to ICH (3.25% (95% CI 0.94–5.51)), heart failure (3.56% (95% CI 1.09–5.96)) was observed at every 1 hPa decrease in air pressure from the previous days. We found stronger detrimental effect of cold on stroke than cardiovascular disease.

Cross sectional observation of the effects of carbon disulphide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

OBJECTIVES: A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS2) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS2 on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. METHODS: The effects were evaluated of CS2 on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS2 and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS2 was either dichotomised or categorised into three groups by job type. RESULTS: Reductions were observed in motor (-1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS2 at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS2. Of 54 subjective symptoms many were increased--namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullness, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator--the concentration of glycosylated haemoglobin--was also increased in the workers exposed to CS2. CONCLUSIONS: Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS2. One interpretation is that relatively higher exposure to CS2 in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS2. Another possibility is that the current exposure to CS2 may cause these positive findings. A follow up observation is necessary to clarify these questions.

Evidence on n -acetyltransferase Allele-associated Metabolism of Hydrazine in Japanese Workers

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

A novel device (SD-101) with high accuracy for screening sleep apnoea-hypopnoea syndrome

Background and objective:  The SD‐101 is a non‐restrictive, sheet‐like medical device with an array of pressure sensors, to detect sleep‐disordered breathing by sensing gravitational alterations in the body corresponding to respiratory movements. This study evaluated the accuracy of the SD‐101 for screening sleep apnoea‐hypopnoea syndrome (SAHS) by comparison with polysomnography.

Lead induced increase of blood pressure in female lead workers.

Aims: Although lead exposure has, in the absence of mathematical modelling, been believed to elevate blood pressure in females, it is necessary to clarify the relation between lead and blood pressure by eliminating confounding factors in the analysis. Methods: Blood lead was measured in 193 female workers, including 123 lead exposed workers. Possible confounding factors were controlled by multiple regression analyses. Results and Conclusion: Blood lead above 40 μg/dl was found to be the most potent factor for elevating systolic/diastolic blood pressure. Aging, urine protein, and plasma triglyceride also contributed to systolic/diastolic/pulse pressure increase, but hypertensive heredity did not. Data suggested that lead induced changes in lipoprotein metabolism may play an important role in the lead induced blood pressure increase in female workers.

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers.

OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Roses questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.