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Summary Background & aims The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. Subjects/Methods We studied 85,293 Japanese subjects by questionnaire at baseline (age 45–74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. Results After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50–0.99) and 0.66 (0.44–0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39–0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Conclusions Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men.

A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population.A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998.Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72-1.00; P trend0.05), slightly more strongly with distal colon cancer (P trend0.05); but an increased risk of rectal cancer in women (P trend0.05). The westernized pattern showed a significant positive linear trend for colon (P trend0.05) and distal cancer (P trend0.05) in women. There was no apparent association of traditional Japanese dietary pattern on the overall or any specific sites risk of CRC.A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women.

Aims Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. Methods and results The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000–04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50–79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality. The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73–1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55–0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64–0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01–4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07–11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03–1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40–0.99), respectively. Conclusion An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Background and aims Higher intake of fish or n-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of coronary heart disease (CHD). However, it is unclear whether increased blood levels of n-3 PUFAs are associated with reduced risk of CHD in the Japanese population. Methods The relationship between circulating levels of n-3 PUFAs (eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid) and risk of CHD was examined in a nested case-control study among participants in the Japan Public Health Center (JPHC)-based Study Cohort. Plasma n-3 PUFA phospholipid levels were measured at baseline by gas chromatography in 209 cases with CHD and 418 controls matched for sex, age, date of blood draw, time elapsed since last meal before blood collection, and study location. The CHD cases (n = 209) comprised 168 cases of myocardial infarction and 41 of sudden cardiac death, otherwise classified as 157 non-fatal and 52 fatal coronary events, respectively. Mean duration of follow-up was 13.5 years. Results Multivariate conditional logistic analysis showed no significant association between n-3 PUFAs and risk of total CHD. The odds ratio (OR) for the highest versus lowest quartiles of plasma n-3 PUFAs was 0.79 (95% confidence interval [95% CI]: 0.41–1.51, p for trend = 0.51). Subtype analysis of CHD revealed that the multivariate ORs for the highest versus lowest quartiles for n-3 PUFAs were 0.91 (95% CI: 0.43–1.89, p for trend = 0.90) for myocardial infarction, 0.08 (95% CI: 0.01–0.88, p for trend = 0.04) for sudden cardiac death, 0.89 (95% CI: 0.42–1.89, p for trend = 0.97) for nonfatal coronary events, and 0.12 (95% CI: 0.02–0.75, p for trend = 0.03) for fatal coronary events. Conclusions Plasma n-3 PUFA levels were not associated with risk of total CHD but were inversely associated with risks of sudden cardiac death and fatal coronary events among middle-aged Japanese individuals.

Seafood/fish intake has been regarded as a protective factor for coronary heart disease (CHD), while smoking is a strong risk factor. To examine whether associations between smoking and risk of CHD are modified by seafood/fish intake, we studied 72,012 Japanese men and women aged 45-74 years who completed 2 food frequency questionnaires, 5 years apart, during the period 1995-2009. After 878,163 person-years of follow-up, 584 incident cases of CHD (101 fatal and 483 nonfatal), including 516 myocardial infarctions, were documented. There was a clear dose-response association between smoking and CHD risk among subjects with a low seafood/fish intake (

We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale population-based cohort study in Japan.We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders.Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup/day were 0.96 (0.89-1.03) for 1-2 cups/day, 0.88 (0.82-0.95) for 3-4 cups/day, and 0.87 (0.81-0.94) for more than 5 cups/day (P for trend.001). Corresponding hazard ratios for women were 0.90 (0.81-1.00), 0.87 (0.79-0.96), and 0.83 (0.75-0.91; P for trend.001). Green tea was inversely associated with mortality from heart disease in both men and women and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality.This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan.

Cell cultures are indispensable to the study of human pituitary adenomas Nevertheless, in vitro studies of human pituitary adenomas have been hindered by the small amount of tissue available and by difficulties in establishing monolayer cultures using standard culture techniques owing to poor cell attachment to ordinary plastic flasks It is well known that pituitary adenoma cells attach poorly to plastic culture flasks, form floating aggregations in the medium, and are easily washed out by medium change (1) Pituitary adenoma cells do not grow rapidly enough for subcultures, so the primary culture is maintained for a relatively long period However, such cells are occasionally overgrown by fibroblasts, which eventually become free floating in the medium (1, 2). Plastic dishes coated with extracellular matrix have been used recently for culturing of pituitary adenoma cells (3, 4), but good results are not necessarily obtained using this method in our experience. Therefore, in this chapter, I describe simple techniques for obtaining an in vitro model system of human hormoneproducing pituitary adenoma, which has relatively firm cell attachment and well-preserved hormonal function (5). In brief, human pituitary adenoma cells are cultured on a microporous membrane (6) coated with a basement membrane extract under the control of seeding medium volume (5).

The effect of whole-body hyperthermia on the development of peritumoral brain oedema and intracranial pressure was studied in cats with intracerebral transplanted tumour. Whole-body hyperthermia was achieved by means of extracorporeal circulation. The temperature within the brain tumour tissue was increased to 41.8 +/- 0.15 degrees C (mean +/- SD) for 2 h. Measurements of brain water content revealed that hyperthermia worsened the degree of peritumoral brain oedema. Microscopical observation demonstrated that extravasation of horseradish peroxidase, indicating disruption of the blood-brain barrier in the oedematous region, was more severe in animals exposed to hyperthermia than in non-treated animals. Intracranial pressure significantly increased from 13.5 +/- 5.26 mmHg to 25.8 +/- 6.16 mmHg (p0.05) during hyperthermia, although it was controlled at 20.7 +/- 2.60 mmHg by continuous infusion of glycerol. The results suggest that whole-body hyperthermia acting on a brain-bearing tumour caused an increase in intracranial pressure due to worsening of the degree of peritumoral vasogenic type of brain oedema. We emphasize that whole-body hyperthermia may be performed with careful monitoring of intracranial pressure for patients who have brain tumour.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case- control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two- sided. Results: Breast cancer risk increased with increasing BMI (P-trend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m(2) increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin- bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

A displacement control system for an electrostatic drive cantilever beyond the pull-in limit is newly proposed using a feedback control. The electrostatic force is linearized around a target position for the purpose to obtain a linearized equation. Based on the equation of motion, the feedback control system is designed by the optimal regulator. The system performance is evaluated by a numerical simulation using a distributed parameter system for the electrostatic drive cantilever. The simulation results show divergent states by the 2nd. resonance mode of the cantilever. To overcome the unstable state, idealistic low-pass filter is added on the feedback loop to cut off higher resonance mode. The system shows stable operation for large displacement over the pull-in limitation.

The possible effects of repeated night-time exposure to an extremely low frequency magnetic field (ELF-MF) on melatonin were investigated in nine healthy male subjects aged 23-37 yr. The 16-week experiment consisted of 3 weeks of pre-exposure, 11 weeks of night-time exposure to MF generated from a nonheated electric sheet (ES), and 2 weeks of post-exposure recovery observation. The average MF intensity (rms, mainly 50 Hz AC) on the surface of the sheet was 0.7 microT at the head, 8.3 microT at the waist, and 3.5 microT at the feet of the subject. For each of the urine samples collected 5 times a day on scheduled sampling days, the urinary excretion rate (ng/h) of melatonin was determined, and 24 h rhythms were extracted for each subject and each experimental period (pre-exposure, first half and latter half exposure, and post-exposure periods) by the method of complex cosine curve fitting. Although estimates of the peak height, acrophase, and total daily amount of melatonin were characterized by significant variations among individual subjects, they did not reveal any statistically significant difference between exposure periods and nonexposure periods. Thus, the present study indicates that any profound effect of the MF originating from an ES on nocturnal melatonin production and its circadian rhythm is unlikely.

It has been reported that matrix metalloproteinases (MMPs) are highly expressed in malignant glioma cells and that this increased expression may facilitate the invasiveness of tumor cells. The authors investigated the expression and enzymatic activity of MMPs in rat brain during the growth of malignant gliomas at different time intervals. C6 rat glioma cells were unilaterally implanted into rat cerebral hemispheres. After 7 or 14 days, these brain tissues were prepared for SDS-PAGE zymography, Western blotting, immunohistochemistry, and in situ zymography. SDS-PAGE zymography and Western blotting revealed that the expression of proMMP-2 in rat brains with C6 glioma cells was significantly higher than that in normal or the sham-operated rat brains, and that the activated form of MMP-2 was detected only in the former but not in the latter. On immunohistochemistry, C6 glioma cells presenting invasive growth into the rat brain parenchyma and vessels demonstrated MMP-2 immunoreactivity. On in situ zymography, foci of invasive C6 glioma cells in rat brain tissue showed gelatinolytic activity. These results suggest that expression and activation of MMP-2 may be one of the crucial steps for glioma cell invasion into the brain parenchyma in vivo.

Few studies have prospectively examined endogenous hormone levels as risk factors for breast cancer. The present study compares prediagnostic hormone levels using stored serum from breast cancer cases and controls selected from the Life Span Study population of the Radiation Effects Research Foundation in Hiroshima and Nagasaki, Japan. Stored serum samples collected in 1968-1970 were assayed for 72 women subsequently diagnosed with breast cancer and 150 control subjects in 72 case-control sets matched on age, date of blood collection, exposure, radiation dose, and city. Serum levels were determined for sex hormone binding globulin, total estradiol (E2), bioavailable E2, dehydroepiandrosterone sulfate, and prolactin. Matched case-control comparisons of hormone levels were carried out by conditional logistic regression and were adjusted for menopausal status at the time of blood drawing. The odds ratio per unit log change in bioavailable E2 was 2.2 [95% confidence interval (CI), 1.02-5.31 for all subjects, and 2.3 (95% CI, 0.55-6.8) and 2.1 (95% CI, 0.55-9.7), respectively, based only on premenopausal or postmenopausal serum. The estimated odds ratios in each quintile of bioavailable E2 level, using the lowest quintile as referent, were 1.00, 1.89, 1.43, 3.45, and 3.37 (P for trend = 0.035). For sex hormone binding globulin, the overall odds ratio was 0.58 (95% CI, 0.14-2.26), and 1.00 (95% CI, 0.19-5.45) and 0.21 (95% CI, 0.02-1.88) based on premenopausal and postmenopausal serum, respectively. This study offers further prospective support for the hypothesis that a high level of biologically available E2 is a risk factor for the subsequent development of breast cancer.

The production of amyloid beta protein precursor (APP), which is a potent inhibitor of matrix metalloproteinases and serine proteinases, in human astrocytic tumors (n = 17) and normal brain tissues (n = 3) was investigated. We found proteinase inhibitory activity at around 120 kD by trypsin reverse zymography in the culture media of explant cultures of anaplastic astrocytomas and glioblastomas, but not in those of astrocytomas and normal brain tissues. Immunohistochemistry using a monoclonal antibody against human APP demonstrated that APP was detectable mainly in tumor and endothelial cells. Semiquantative analysis of western blotting revealed that immunoreactivity for APP in the culture media of tumor explant cultures appeared to be increased associated with the malignancy of astrocytic tumors. These findings suggest that APP production may be related to the malignant progression of human astrocytic tumors.

This is a report on a patient with traumatic carotid-cavernous sinus fistula (CCF). She gradually noticed noise in her head and suffered from partial ophthalmoplegia. Angiography demonstrated a left high flow CCF. She underwent a direct surgical treatment with a detachable balloon because an endovascular balloon embolisation for the CCF had been unsuccessful. Immediate disappearance of the bruits after surgery was noted and the patient recovered progressively her ophthalmoplegia. Follow angiograms 3 months after surgery revealed the disappearance of the fistula and an appearance of a false aneurysm. She is asymptomatic and periodically monitored in the outpatient clinic.

Hyperthermia has been introduced as a new modality of treatment for glioma. In these experiments, the cytotoxicity of hyperthermia in C6 glioma cells was enhanced by increasing the intracellular acidity with amiloride and/or 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS). Intracellular pH (pHi) is regulated mainly by Na+/H+ and HCO3-/Cl- antiports through the cell membrane, and amiloride acts on the former, DIDS on the latter to lower pHi. The cellular thermosensitivity to clinically achievable brain hyperthermia at 42 degrees C was enhanced by 0.5 mM amiloride (Na+/H+ antiport inhibitor). T0 values (T0 = the heating period required to reduce experimental survival rate by 1/e) at 42 degrees C without and with amiloride was 192 and 81 min, respectively. The addition of DIDS (HCO3-/Cl- antiport inhibitor) further enhanced. T0 value was 25 min. Fluorophotometric measurement of pHi was employed using the pH sensitive dye, bis(carboxyethyl)carboxyfluorescein, which is trapped in viable cells. The average pHi in control C6 glioma cells in pH 7.2 media was 7.21. In the untreated cells heated at 42 degrees C for 1 hour, the pHi was 7.12. The pHi of the cells heated in the presence of amiloride was decreased to 6.83. The pHi was further lowered to 6.67 by the treatment with amiloride in combination with DIDS for 2 hours. Hyperthermia with amiloride and DIDS may be a more effective treatment for malignant gliomas.

The temporal increase of plasma corticosterone (CORT) levels at 3 or 4 days after a single oral administration of trimethyltin (TMT) was suppressed by intracerebroventricular administration of the interleukin-1 receptor antagonist (IL-1ra). On the other hand, glutamate receptor antagonist (MK801) did not affect the TMT-induced CORT level increase. These results indicate that this transient activation of the hypothalamo-pituitary-adrenocortical axis in TMT-treated rats may be in part attributable to the neuroendocrine effects of IL-1 produced by microglia.

Total resection is the optimal treatment for malignant gliomas. However, we sometimes find an unexpected residual tumor mass on magnetic resonance imaging performed after an operation because of a macroscopically unclear margin of the tumor during operation. This study was designed to evaluate the effect of fluorescein sodium on imaging of glioma in combination with a surgical microscope for detection of the tumor at surgery in a rat glioma model. For this study, we produced two filters for the excitation and emission of fluorescein that can be easily fitted to and removed from a surgical microscope manually during the operation. For the in vivo study, Wistar rat brains bearing C6 glioma were removed at appropriate intervals after the intravenous administration of 10-20 mg/kg body weight of fluorescein sodium, and their surface and coronal sections through the tumor were observed using a surgical microscope with the filters. For the in vitro study, the cultured C6 glioma cells were exposed to 5 micrograms/ml of fluorescein sodium for 2 hours and then observed by confocal laser scanning microscopy. In the in vivo study, the C6 glioma itself and the brain within 2-3 mm of the gross surface of the tumor (probably indicating part of the perifocal edema) were well stained a brilliant yellowish green for a few hours. The normal brain was not stained. The intensity of the fluorescence was dose-dependent and was stronger under the xenon than under the halogen lamp. The in vitro study demonstrated almost no uptake of fluorescein by the C6 glioma cells. This fact indicates that the fluorescein in the stained tumor exists in extracellular spaces due to the disruption of the blood-brain barrier. These results suggest that this staining technique using fluorescein sodium and a surgical microscope with special filters during the operation may be the intravenous administration of 10 useful for detection of gliomas and warrants evaluation of clinical application.

Production of tissue inhibitor of metalloproteinases-1 (TIMP-1), a specific inhibitor of matrix metalloproteinases, was investigated in human astrocytic tumors (n = 15) and normal brain tissues (n = 3). Enzyme immunoassay indicated that TIMP-1 levels in the culture media of tumor explants were significantly higher in glioblastomas as compared with anaplastic astrocytomas, astrocytomas, and normal brain tissues. Immunohistochemistry using a monoclonal antibody against TIMP-1 demonstrated that TIMP-1 was detectable mainly in tumor cells, especially in glioblastoma. These results suggest that increased expression of TIMP-1 is associated with the malignant progression of astrocytic tumors.

MX2, a new lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to adriamycin against murine and human tumor cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. Colony formation is inhibited even with only 2 hour treatment with MX2 in a dose-dependent manner. In this colony forming efficiency assay the drug concentration required for 50% inhibition of colony formation for C6 glioma cells was 24.0 +/- 4.5 ng/ml. Mild photocytotoxicity of MX2 against C6 glioma cells was observed at a high concentration (100 ng/ml) of MX2 following exposure to white light but not red light. In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) exhibited an additive cytotoxic effect against C6 glioma cells when the cells were treated with MX2 either immediately after red light illumination following incubation with HpD or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.

We investigated the effects of captopril on the activity of matrix metalloproteinases (MMPs) secreted by T98G glioma cells and their invasiveness in vitro. On gelatin zymography, captopril inhibited gelatinolytic activities in the culture media of T98G cells. This inhibitory effect was reversed by the presence of excess zinc. In an in vitro invasion assay, invasion into the reconstituted basement membrane (Matrigel) by T98G glioma cells was inhibited by captopril in a dose-dependent manner. This inhibitory effect was also reversed by the addition of zinc to the culture media. However, at the effective concentration of captopril for the prevention of tumor cell invasion it did not inhibit the motility, adhesion to Matrigel or proliferation of T98G cells. These findings suggest that captopril inhibits the invasiveness of T98G glioma cells due to its MMP inhibitory activity, chelating zinc ions at the active center of MMPs.

A 65-year-old male and an 80-year-old female presented with unusual simultaneous bilateral hypertensive intracerebral hemorrhages in the putamina and thalami, respectively. The hematomas were demonstrated by computed tomography performed within a few hours of onset. The patients underwent conservative therapy. The male patient died 4 days after the onset and the female finally became vegetative. The majority of patients with bilateral intracerebral hemorrhages generally have a poor outcome due to the development of severe disturbed consciousness, tetraparesis, and pseudobulbar palsy, even if the hematomas are not so large. The indication of surgery for this type of hemorrhage may be confined to patients with small hematomas who can be expected to have a good functional outcome after removal of the larger hematoma.

A detailed immunohistochemical and electron microscopic study of a case of clear cell (glycogen-rich) meningioma is presented. The neoplasm recurred three times and the patient died of the disease. The specimens obtained at all three operations showed similar basic histologic patterns. The tumor was comprised mainly of a syncytial, sheet-like proliferation of polygonal cells with clear cytoplasm containing abundant glycogen. The immunohistochemical features included epithelial membrane antigen- and vimentin-positive cytoplasm. The ultrastructural examination revealed distinctive meningocytic cells which contained large amounts of glycogen granules. In addition, the presence of numerous blocky, collagen conglomerations were a conspicuous feature of this tumor. The collagen deposits exhibited intensive immunopositivity for types I, III, IV and VI collagen, and their fine structure suggested the production of the extracellular matrix substance from the contiguous meningothelial cells with well developed Golgi complexes and frequent vesicles near the cell membrane. Proliferating cell nuclear antigen cell kinetics study revealed high labeling index of this neoplasm. The findings for this clear cell (glycogen-rich) meningioma may be useful in the differential diagnosis and treatment of this distinctive subtype of meningioma.

A 62-year-old male presented with a rare brain metastasis from malignant mesothelioma manifesting as headache and progressive left hemiparesis. He had previously undergone pleurectomy for malignant mesothelioma. Chest x-ray films showed no recurrence of mesothelioma. Computed tomography and magnetic resonance imaging revealed a homogeneously enhanced nodular mass adjacent to the falx in the right frontal lobe. The tumor was totally removed and diagnosed histologically as brain metastasis from malignant mesothelioma. Following surgery, left hemiparesis improved gradually. Brain metastasis from malignant mesothelioma is usually discovered in the terminal stage or at autopsy. Surgical removal and radiotherapy should be considered for isolated lesions.

An 11-year-old boy was admitted with a painless lump in the right frontal area as his chief complaint. On admission, physical and neurological examinations were normal except for the localized lump constituting the frontal lesion. Skull roentgenogram showed an osteoblastic and osteolytic mass with radiating bony spicules "sunray appearance" around the coronal suture. CT scans demonstrated it more clearly. The initial surgery was performed in July 1993. Pathological specimen showed osteosarcoma of the skull. The patient was transferred to our hospital for chemotherapy. The regimen consisted of intravenous high dose methotrexate 9,000 mg given for 6 hours with leucovorin rescue in a single course. Following 4 courses of high dose methotrexate, he underwent residual tumor resection. Two courses of intraarterial carboplatin 150 mg and methotrexate 200 mg were also given. Histologically, the lesion showed complete remission of the tumor, and no viable tumor cells were seen. Two additional courses of high dose methotrexate were given. The patient is doing well without evidence of recurrence. This case indicates that the chemotherapy with systemic high dose methotrexate and intraarterial carboplatin and methotrexate is effective for skull osteosarcoma.

Seven Japanese monkeys were used in this study. Magnetic resonance angiography (MRA), using the time-of-flight (TOF) method, was obtained. After control studies of both MRA and conventional angiography, subarachnoid haemorrhage (SAH) was induced on day 0. Angiography was performed again on day 7 to observe the development of cerebral vasospasm. The reactivity of the vessels to acetazolamide was also observed. Spasm was detected on both MRA and conventional angiography on day 7. MRA after acetazolamide showed dramatic enhanced vasodilatation in both control and spastic arteries on day 7, whereas conventional angiography showed no change.

Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.

We have evaluated the effect of mannitol on focal cerebral ischemia using T2-weighted magnetic resonance (MR) imaging and intravoxel incoherent motion (IVIM) MR imaging. The left middle cerebral artery (MCA) was exposed via the transorbital approach in 20 adult cats and occluded just proximal to the origin of the perforating arteries. Seven cats in treatment group received mannitol (0.5 g/kg i.v.) at 0, 6, 12 and 18 hours after MCA occlusion. The other 13 cats received saline and served as controls. Sequential MR coronal images were obtained at 2, 4, 6, and 24 hours after MCA occlusion using a GE Signa (1.5 tesla) system. IVIM MR imaging demonstrated ischemic cerebral injury as a sharply demarcated area at 2 hours after MCA occlusion in control group, while T2-weighted MR imaging failed to show clear evidence of the injury until 2-6 hours. At 24 hours after MCA occlusion, the infarcted area in the mannitol treatment group was 36.9 +/- 7.7% (S.E.M) of the left hemisphere, as compared to 57.3 +/- 5.3% in control group (p0.05). Mannitol has beneficial effect on ischemic injury.

Eight chordomas were studied by using specific antibodies against cytokeratin, vimentin, desmin, type II collagen, S-100 protein, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). One chondrosarcoma was included as a representative of chondroid tumors. All chordomas were positively stained for epithelial markers (cytokeratin and EMA), whereas the chondrosarcoma was not. All chordomas and the chondrosarcoma expressed vimentin, type II collagen and S-100 protein. Oncofetal antigens (CEA and AFP) and desmin were found in five (63%) chordomas, whereas these antigens were not found in the chondrosarcoma. Ultrastructurally the chordoma cells showed junctional complexes, microvillous projections and basal lamina-like structures alongside the tumor cells, whereas the tumor cells of the chondrosarcoma had neither junctions and microvillous projections, nor basement membrane. The present study demonstrates the utility of these tumor markers and ultrastructural features in the differential diagnosis of chordomas and tumors with similar histologic patterns such as chondrosarcomas.

Possible individual variations in the sympathetic nervous system response to sound stimuli were investigated using the auditory evoked plethysmogram response (AEPGR). This study consists of the following 3 experiments; (EXP1) the sound level-response relationships between white noise at 50, 70, and 90 dB (A) and AEPGRmax as defined below, (EXP2) individual variations of AEPGRmax to white noise at 90 dB (A), and (EXP3) the relationship between the AEPGR pattern and the urinary catecholamine (CA) excretion rate during sleep on the preceding night. The subjects were 35 young persons in (EXP1), and 79 young (18-28 yrs. old) and 35 old (60-83 yrs. old) persons in (EXP2) and (EXP3), respectively. The results were: (1) a good sound level-response relationship between the sound levels of 50, 70, and 90 dB (A) and AEPGRmax was obtained on average; (2) an AEPGRmax of more than 100% in response to the 90 dB (A) white noise was found in about 10% of the subjects, whereas it was below 100% in 90% of them. The time prior to the maximum response in the former case varied from 4.6 to 22.2 sec, which was quite a contrast to that of 3.0-9.0 sec in the latter case; (3) The NE (norepinephrine), E (epinephrine) and DA (dopamine) excretion rates were shown to be significantly higher in the former group in (2) than in the other groups, regardless of adjustment for age, blood pressure and/or ECG findings. Thus, it is suggested that the cardiac response to E secreted from the adrenals due to white noise stimuli was predominant in the former group in (2). Therefore, this response pattern was called the AEPGR "beta type", whereas the other group was designated the "alpha type", since its AEPGR appeared to reflect only vasoconstriction. The suggested individual differences in AEPGR associated with increased night-rest catecholamine secretion were also discussed in relation to their possible relevance to chronic stress, neuroticism and other conditions.

Cerebral metabolic alterations in an experimental study have been reported by many investigators. Recent advances in magnetic resonance spectroscopy (MRS) allow a non-invasive study of brain metabolism in vivo [1]. In this study, changes of intracranial pressure and P-31 MRS were observed after inflation and deflation of an epidural balloon in the cat.

Prostacyclin produced in endothelial cells has vasodilating and antiplatelet activities. The effects of prostacyclin have been reported in experimental ischemic studies and in patients with ischemic stroke [3, 5]. Prostacyclin is too unstable to serve as a drug. The purpose of this study was to evaluate the effects of a stable prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy-6,9alpha-nitrilo-prostaglandin Fl methylester), on acute focal cerebral ischemia in cats.

This study was designed to establish in vitro model systems in human hormone-producing pituitary adenomas that are analogous to the in vivo cellular environment. Mechanically dispersed cells composed of single cells and aggregates from 6 pituitary adenomas (3 GH producing adenomas and 3 prolactinomas) were cultured on microporous membrane cell culture inserts (Millicell-CM) coated with Basement Membrane Matrigel for up to 6 months. Growth hormone or prolactin in the medium was measured during the culture, and morphological feature in vitro was also compared with that of the original tumor at intervals. Not only single cells but also large aggregated cells which usually float in the medium when seeded on conventional plastic, were flattened and firmly attached to coated microporous membrane under the control of medium volume in culture. In both type adenomas, especially prolactinomas, surviving aggregated adenoma cells revealed preserved hormone activity and no dedifferentiation of cell characteristics after 6 months in culture. Particularly during the first 2 months in culture, close similarity existed between in vivo and in vitro conditions with regard to cell morphology and hormone release. These results indicate that this new culture method may further aid the investigation of in vitro cellular structure and function in human pituitary adenomas under conditions which closely mimic the in vivo cellular environment.

This study was designed to investigate the effect of calcium channel antagonist (nicardipine) on basal and bromocriptine-inhibited GH or PRL secretion in eight patients with pituitary adenomas (six GH producing adenomas and two prolactinomas). GH or PRL was measured in blood collected at intervals for 12 hours after oral administration of nicardipine (Nc) (40 mg) and/or bromocriptine (Br) (2.5 mg) in each case. In vitro, pituitary adenoma cells were incubated in media containing Nc (200 ng/ml) and/or Br (200 ng/ml) over a 72-h period, and then in drugs-free media for three days. Media were collected at 24-h intervals and assayed for GH or PRL. In three of six GH producing pituitary adenomas, GH secretion was inhibited by Nc both in vivo and in vitro. In prolactinomas, PRL secretion was inhibited by Nc in vitro, but in vivo, an increase of plasma PRL levels was observed after Nc administration in one of two cases. In two acromegalic patients and one patient with prolactinoma, Nc reduced the suppression of GH or PRL secretion induced by Br. These findings indicate that influx of extracellular calcium plays an important part in both GH and PRL secretion in functioning pituitary adenomas, and that Nc effects on GH and PRL secretion in pituitary adenomas by blocking of influx of calcium and/or antidopaminergic action. It is considered that the combined administration of calcium channel antagonist (Nc) and Br for acromegalic patients and administration of Nc for patients with prolactinomas should be avoided.

The influence of total body hyperthermia (TBHT) on normal brain tissue was studied in 40 dogs. The dogs were anesthetized with sodium thiopental (10 mg/kg/hr) intravenously, and were ventilated by artificial respirator. The TBHT was induced by extracorporeal circuit in cooperating a heat exchanger. Rectal temperature was raised to 41.5 degrees C and maintained at 41. 5 -42.0 degrees C for 2 hr (HT period) and was then fallen to normothermia by cooling, Regional cerebral blood flow (CBF) was measured by hydrogen clearance method before heating, during and after TBHT treatment. Brain temperature, rectal temperature, intracranial pressure (ICP), brain tissue pH and electroencephalography (EEG) were monitored continuously during TBHT. Histopathological changes of the brain tissue were studied in dogs killed just after TBHT and 2 weeks after TBHT. Autoregulation of the CBF during HT period was assessed by measuring the regional CBF and the ICP at a state of induced hypo- or hypertension. The brain temperature (at the depth of 5mm under the brain surface) was usually 0.6 degrees C lower than the rectal temperature during HT period. The regional CBF increased from 38.1 +/- 6.5 (mean +/- SD) to 49.1 +/- 9.8ml/100 g/min by raising rectal temperature, and it recovered to a normal value after cooling. The ICP increased from 10.3 +/- 4.2 to 16.8 +/- 3.4 mmHg by raising rectal temperature, and it returned to a normal value after cooling. Brain tissue pH decreased from 7.33 +/- 0.02 to 7.17 +/- 0.09 rapidly when the rectal temperature reached 41.0 degrees C, and then returned to a normal value gradually after the start of cooling.(ABSTRACT TRUNCATED AT 250 WORDS)

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

Eight cases of central neurocytomas were studied by immunohistochemistry and electron microscopy. Seven tumors were located in the lateral ventricles and one in the subependymal region. All but one patient had a favorable postoperative course. The tumors were composed of small uniform cells possessing amitotic round nuclei with frequent perinuclear halos, a few Homer Wright rosettes and no ganglion cells; an appearance resembling that of oligodendroglioma. Immunohistochemical studies disclosed neuron-specific enolase and Leu-7 positivity in all tumors, S-100 protein-positive cells were found in six, while glial fibrillary acidic protein--and vimentin-positive cells were confined to the blood vessels. Myelin basic protein as well as neurofilament were not detected in the tumors. Synaptophysin-positive areas were seen in one tumor. Ultrastructural examination showed distinctive neuronal tumor cells which had a cytoplasm with sparse dense-core vesicles and thin cell processes containing parallel microtubules. They were classified into three different types of tumor cells according to the extent of differentiation. The most consistent finding for histological diagnosis was the presence of typical or abortive synapses with clear and dense-core vesicles. Additionally, synaptophysin may be a specific marker for some central neurocytomas.

Five male Wistar rats were treated with methyl-mercury chloride (MMC) and compared with five agematched control rats. A dose of 10 mg/kg was given three times. The chronic effects of the MMC administration on the urinary output of catecholamines [norepinephrine (NE), epinephrine (E) and dopamine (DA)] were measured for 50 days. On the 69th day after MMC administration, the rats were examined for insulin-induced hypoglycemic stress. On the 90th day, the animals were decapitated and various organs were weighed and serum thyroid hormones [thyroid stimulating hormone (TSH) and total and free thyroxine (T4)] were measured. Decreases in DA excretion and DA response to stress were observed in the MMC-treated group. Inflammation of the kidney was also found, suggesting MMC-induced damage to the renal tubular region, the apparent site of renal DA synthesis. The MMC group and the control group showed differential NE and E response patterns. The lowered baseline excretion of NE appeared to continue even 70 days after MMC administration, while the difference in E excretion between the two groups disappeared 1 month after MMC administration. Both NE and E showed normal responsiveness to hypoglycemic stress induced by insulin. All serum TSH and total and free T4 baseline levels showed slight increases, and the thyroid gland weights in the MMC group were slightly heavier. These findings suggest a rather hyperthyroid state after the initial acute phase suppression, as suggested by the previous examinations. Thus, these findings suggest long-lasting effects of methylmercury administration, especially on renal DA synthesis. Baseline urinary excretion of NE and thyroid function could also be affected for a long time.

In cases of herpes simplex encephalitis, a low density lesion in the temporal lobe is a common CT finding, whereas hemorrhagic lesion is rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. Two cases of hemorrhagic lesion observed on CT in herpes simplex encephalitis are reported, and atypical CT findings of herpes simplex encephalitis is discussed.

Recently suggestions have been advanced that alternative fuels including ethanol, methanol or methane instead of so called "fossil fuels" may help improve the current conditions of air pollution. According to results of general survey in Sao Paulo, since their introduction in 1978, ethanol-fueled cars have increased their share to almost 50% of all light vehicles in 1983. The current status of air pollution in Sao Paulo metropolitan area (SPMA) is described in relation to the use of such alternative fuel. The average concentrations in air of SO2 and lead have been decreasing drastically during the period of 1982-88, whereas non-methane hydrocarbon, NO2 and O3 levels have been increasing to attain the worst levels in the world as indicated in Fig. 2. The use of ethanol-fuel, which contains less sulphate and lead, is thought to have contributed more or less to the above reductions of SO2 and lead in the air. However, the pollutants that have increased may derive mainly from diesel and gasoline exhausts of heavy vehicles. The general state of air pollutions appears not to have been improved, suggesting the difficulty in resolving air pollution issues. On the other hand, a current problem specific to ethanol-fuel is the aldehydes or other carcinogenic components in exhaust. Peak formaldehyde concentration, for example, have been reported to have reached 159 ppb in SPMA, which may be one of the highest levels shown in ambient air.(ABSTRACT TRUNCATED AT 250 WORDS)

Small animal models such as the rat have serious limitations for multiple human scale instrumentation, surgical manipulations, and computerized tomographic (CT) evaluations, so that large animal models are required for the study using them. Although brain tumors induced with Rous sarcoma virus in neonatal beagle or adult monkey had been reported, these animals are very expensive ones for tumor research. A major drawback of virally induced brain tumor model is, moreover, the need for specialized viral facilities and safety precautions for laboratory personnel. In this paper, a cat glioma model implanted with C6 glioma cells derived from rats injected with N-nitrosomethylurea is reported. For an implantation dose of 5 x 10(5) cells/50 microliters, C6 glioma cells were suspended in modified Eagle medium supplemented with 10% fetal bovine serum and 0.5% agar. Twenty adult mongrel cats were injected with 5 x 10(5) C6 glioma cells intracerebrally. Implanted cats had brain tumors of about 10 mm in diameter with a yield of 80%. The mean survival was about 3 weeks after implantation. Tumors developed as spheroidal, hemorrhagic masses with central areas of necrosis and peripheral edema. They were located within the parenchyma of the implanted region. This tumor possessed many of the histological and radiological characteristics of human glioblastoma such as the following: Areas of hemorrhage and necrosis surrounded by pseudopallisading were observed within the tumor consisting of spindle-shaped cells with pleomorphic nuclei. A mass lesion with ring or garland-like enhancement surrounded by brain edema was shown on the CT scans.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty male Wistar rats, weighing 200 to 300 g, were used for this study. During a 3- to 4-min period, 300 micrograms of 6-OHDA was injected stereotactically into the right lateral ventricle. The same amount of saline was injected into the ventricle for the control group. Seven days after this procedure, the right common carotid was occluded with a clip and 4 to 6 ml of blood was removed from the external jugular vein to reduce the blood pressure. The clip was removed in 2 hr, and blood flow was maintained for 1 hr. The SG of cerebral tissue was measured according to the method of Marmarou et al. The disruption of BBB was examined by Evans blue injection, and the brain tissue was also examined by electron microscopy. Rats with 6-OHDA treatment had brain edema although the control group had no edema. We suggest that the depletion of brain NA could cause a disturbance in cerebral microvascular tone and could make cerebral blood vessels more vulnerable to the decreased CBF when followed by restoration of the blood flow.

Impairment of the cerebral autoregulation and its effects on the development of brain oedema during chronic cerebral vasospasm after subarachnoid haemorrhage (SAH) were studied in primates. The unilateral induction of SAH by clot placement around cerebral arteries produced a moderate degree of vasospasm (more than 40% reduction of vessel caliber on angiogram) seven days after SAH. Abolishment of autoregulation was observed in the territories of the cerebral hemisphere supplied by the vasospastic arteries. It was found that in this region an increase in cerebral perfusion pressure easily produced a marked elevation of the cerebral blood flow over the upper limit of autoregulation threshold resulting in disruption of the blood-brain barrier.

SummaryTwenty-four hour urines were obtained from groups of male and female volunteers recruited from urban populations in developed and developing countries (UK, USA, Japan and Nigeria) and from an agriculture-based Polynesian population (Tokelau Islands). The urines were collected on typical working days, with minimal disturbance to subjects' normal routines. High-performance liquid chromatography was used to determine catecholamine concentrations in each urine, providing a basis for calculation of total 24-hour excretion. Mean 24-hour excretion of noradrenaline and adrenaline was low in the Polynesians compared to the modern, urban groups, and low in women compared to men. Discussion of the results includes assessment of the possible influences of artefact, physical characteristics of the population samples, physical environment and social and psychological factors.

Cerebrospinal fluid flow (CSF) was studied using isotope cisternography in 52 patients with increased intracranial pressure (ICP), all of whom showed acute transient rises of ICP, i.e., plateau waves, in their continuous ICP recordings. The patients were assigned to two groups. Group I was comprised of 23 patients without hydrocephalus and high ICP resulting from brain tumors, benign intracranial hypertension, and superior sagittal sinus thrombosis. Group II included 29 patients with either communicating hydrocephalus or high ICP resulting from rupture of intracranial aneurysm. Plateau waves were frequently observed in patients with baseline pressures ranging from 21 to 40 mmHg in both groups. The isotope cisternographic pattern in the Group I patients showed a large accumulation of radioactivity over the cerebral convexities, while that in the Group II patients revealed a complete obstruction of the subarachnoid space over both cerebral convexities. The isotope clearance from the intracranial CSF showed a marked delay in both groups of patients with one exception. The results suggest that, in the limited range of increased ICP caused by delayed CSF absorption, plateau waves are most evident regardless of the isotope cisternographic pattern.