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We examined the cross-sectional relationship of soy product intake to serum concentrations of estradiol (E2) and sex hormone-binding globulin (SHBG) in 50 healthy premenopausal Japanese women. Intakes of soy products and various nutrients were estimated through a semiquantitative food-frequency questionnaire. Blood samples were drawn from each subject on Days 11 and 22 of her menstrual cycle. The intake of soy products was inversely correlated with E2 on Days 11 and 22 of the cycle after controlling for age, body mass index, cycle length, and intakes of total energy, fat, and crude fiber (r = -0.23, p = 0.08 and r = -0.32, p = 0.04, respectively). No significant correlation was observed between soy product intake and SHBG. There was a tendency for the intake of individual soy foods such as tofu and miso to be inversely correlated with E2 on Days 11 and 22 of the menstrual cycle. Miso intake was inversely significantly correlated with SHBG on Day 22 of the cycle (r = -0.36, p = 0.02). If the observed association is causal, our results suggest that the consumption of soy products lowers the risk of developing breast cancer risk modifying estrogen metabolism.

The objective of this study was to clarify whether pre-exposure to hypoxia influences neuronal death following transient cerebral ischaemia. Twenty gerbils were exposed to 10% oxygen in a chamber for 3 weeks. The other control gerbils (n = 20) were fed in normoxia for 3 weeks. Both carotid arteries in the neck were occluded with aneurysm clips for 5 minutes under halothane anaesthesia in 30 gerbils, recirculated and then fed in normoxia. Five animals in both groups were sacrificed before, and 2, 4, and 7 days after surgery. The animals were fixed with 4% paraformaldehyde and histological study was performed. Immunohistochemical study was also done with antibodies against basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The neuronal death in the hippocampus was more severe in the hypoxic group. Expression of both bFGF and VEGF was obvious in the cingulate cortex, corpus callosum and internal capsule before clipping in the hypoxic group, but not observed in the normoxic group before clipping. We observed the expression of both bFGF and VEGF widely in the brain at 2 and 4 days after recirculation in both groups. The expression in the hypoxic group was much more prominent than that in the normoxic group. These expressions were not observed at 7 days in both groups. Pre-exposure to hypoxia followed by transient cerebral ischaemia accelerated neuronal death in the hippocampus, and induced the more obvious expression of both VEGF and bFGF compared with those in the normoxic group.

It has been implied that fat and fiber intakes influence breast cancer risk. The effects of these dietary factors may be mediated by hormonal changes. We evaluated the relationships between fat or fiber intake and serum concentration of estradiol (E2) or sex hormone-binding globulin in premenopausal women. In 1994 blood samples were collected from each of 50 premenopausal healthy Japanese women on Days 11 and 22 of the menstrual cycle. Nutrient intakes were assessed by food frequency questionnaire in which the subjects were asked about their diets during one year before the study. Each nutrient intake was categorized into tertile after adjustment for total energy. Linear regression models, including age and cycle length as covariates, were utilized to evaluate the association between the nutrient intakes and the hormone concentrations. A statistically significant trend was observed between increasing fat intake and increasing E2 on Day 11 of the cycle (p = 0.05). The positive trend for increasing sex hormone-binding globulin on Day 22 with fat intake was of borderline significance (p = 0.06). There was a statistically significant inverse trend for E2 on Day 11 of the cycle with fiber intake (p = 0.05). It was suggested that fat as well as fiber intake should affect the hormone status.

Pituitary abscess is a rare disorder. However, preoperative diagnosis is important to prevent a cranial approach leading to severe meningitis. A case of a 55 year-old woman with pituitary abcess is reported. The patient was admitted with a several-week history of frontal headache and no signs of inflammation. Computed tomographic (CT) scan showed a slightly low-density suprasellar expanding mass lesion with an enhanced thin wall in the pituitary region. Magnetic resonance imaging showed a homogenous high-intensity signal relative to brain parenchyma on T1-weighted images with an enhanced thin wall and a homogenous low-intensity signal on T2-weighted images. This was histologically shown to be a pituitary abscess. Our case and review of the available literature suggest that pituitary abscess generally shows a homogenous low-density on CT scan and a homogenous low- to iso- and high-intensity signals or homogenous high- and low-intensity signals on T1- and T2-weighted images, respectively, with a cystic appearance and enhanced smooth wall.

We investigated the effects of hyaluronic acid (HA) on the invasiveness of three human glioma cell lines (A172, T98G and U251) and their secretion of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and hyaluronidase. The invasion of all three glioma cell lines was enhanced by the impregnation of Matrigel with HA in an in vitro invasion assay using 12 microns porosity polycarbonate filter transwells. The secretion of MMPs and PAs was not influenced by the presence of HA. Hyaluronidase activity was not detected in the culture media of any glioma cell line. HA also enhanced the motility of A172 and U251 glioma cells, but did not influence the motility of T98G glioma cells. The adhesion and spreading of all glioma cell lines were inhibited on HA-coated plates. HA, however, did not influence the proliferation of any of the glioma cell line. These results suggest that the presence of HA contributes to glioma cell invasion, which involves the stimulation of detachment and motility of glioma cells and the maintenance of proteinase secretion by glioma cells.

Extranodal sinus histiocytosis with massive lymphadenopathy involving the meninges is a rare clinical entity. The authors describe the unusual case of an occipital meningeal lesion in a 25-year-old man in whom they found inflammation of the occipital lobe mimicking lymphoplasmacyte-rich meningioma. The clinical similarities and differences are discussed.

Background: Cerebrospinal fluid (CSF) otorhinorrhea is one of the most common postoperative complications following the suboccipital approach to the cerebellopontine angle and the internal auditory canal. Accurate preoperative detection of the site of CSF leakage is important because inaccuracy may require a more extensive exploratory surgical procedure in the repair operation. There are few reports on evaluation of magnetic resonance (MR) imaging in diagnosing CSF leakage., Case Description: MR imaging of two cases of postoperative CSF rhinorrhea is reported. A 53-year-old woman and a 29-year-old man underwent suboccipital operations for microvascular decompression of the facial nerve in hemifacial spasm and for removal of an acoustic schwannoma, respectively. In both cases, MR findings were useful in preoperatively delineating the site of the CSF leakage, which was confirmed during the repair operation., Conclusion: MR imaging may be useful in identifying the site of CSF leakage following the suboccipital approach to the cerebellopontine angle.

Human glioma cells (T98G and A172 cell lines) were cultured on various extracellular matrix (ECM) components including type I, IV and V collagens, fibronectin, laminin, and reconstituted basement membrane (Matrigel), and the role of matrix metalloproteinases (MMPs) in their growth and invasion was examined. T98G glioma cells grew well on these ECM components and invaded the reconstituted basement membrane. In contrast, A172 glioma cells showed growth inhibition on collagen types IV and V and Matrigel without invasion of the Matrigel. Gelatin zymography and enzyme immunoassays demonstrated that T98G glioma cells, but not A172 cells, secrete a large amount of matrix metalloproteinase-2 (MMP-2, 72 kD gelatinase/type IV collagenase = gelatinase A), and this was confirmed by immunoblotting and immunohistochemistry. Of the two different tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), T98G cells produced only TIMP-1 during culture on Matrigel, whereas A172 cells secreted both. Although both human recombinant TIMP-1 and TIMP-2 stimulated T98G cell growth slightly on Matrigel, the in vitro invasiveness was significantly reduced by only recombinant TIMP-2. These results suggest that MMP-2 plays an important role in the ECM invasion of T98G human glioma cells in vitro.

This study in mongrel dogs was designed to observe the effects of ethanol on both endothelial cells of the basilar artery and brain function. By use of sterile surgical technique, a super-selective catheter was placed in the proximal portion of the basilar artery in the dogs. Five dogs received 3 ml of 25% ethanol and 5 dogs received 3 ml of 50% of ethanol through the catheter over 2 minutes. The remaining 5 dogs received 3 ml of saline as a control. Auditory brain stem response (ABR) was monitored for 2 hours after ethanol infusion, and then perfusion-fixation was performed from the heart with 4% paraformaldehyde. The basilar artery was observed with scanning electron microscopy after routine procedures. The endothelial cells were intact in the control group. The 50% group showed a higher level of injury to the endothelium as well as a higher degree of platelet adhesion and fibrin clot formation compared with the 25% group. The extensive endothelial-cell damage subsequently caused thrombus formation. The ABR disappeared immediately after ethanol infusion in both ethanol groups, and recovered gradually in the 25% group, but did not re-appear during the time course of 2 hours in the 50% group. The ethanol less than 25% in concentration near the endothelium is considered to be safe as a transcatheter embolic agent with the attention to the central toxicity.

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).

This study was designed to examine whether mammosomatotroph cells (MS cells) can be easily detected using confocal laser scanning microscopy (CLSM) and whether the coexistence of growth hormone (GH) and prolactin (PRL) within the same secretory granule can be identified in the MS cell using CLSM. Conventional epoxy resin-embedded tissues of mixed GH- and PRL-secreting human pituitary adenomas were used for this double-labelling immunofluorescent study by CLSM. A semithin section of the tissue after plastic removal and bleaching was immunohistochemically double-stained with primary antibodies against GH and PRL, followed by secondary antibodies conjugated with Rhodamine (GH) and FITC (PRL). MS cells simultaneously showing fluorescence of both Rhodamine and FITC were easily detected by CLSM at lower magnification. At higher magnification, the coexistence of Rhodamine and FITC on the same secretory granule was identified by using a superimposed display. This finding was confirmed by immunoelectron microscopy. The CLSM technique may be useful for the study of MS cells.

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.

The chemotherapeutic effect of MX2 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin), a new lipophilic morpholino anthracycline, against rat C6 and human T98G glioma cells, was examined in vitro and in vivo. The subcellular distribution of MX2 was also studied. The drug concentrations of MX2 required for the 50% inhibition of cell growth (IC50) for C6 and T98G cells were 25.5 +/- 1.3 ng/ml and 70.6 +/- 6.8 ng/ml, respectively, which were much lower than the IC50 values for nimustine (ACNU). A C6 subline resistant to ACNU, C6/ACNU, was established by continuous exposure to graded concentrations of ACNU. The IC50 of MX2 for C6/ACNU was 28.3 +/- 2.2 ng/ml, indicating no cross-resistance to MX2. In the rats bearing the intracerebral C6 tumors, the life span was increased by about 40 to 100% after intravenous administration of MX2 at doses ranging from 1 to 3 mg/kg of body weight. Confocal laser scanning microscopy demonstrated visually the good accumulation of MX2 in the implanted intracerebral C6 tumors, as well as its predominant distribution in the cytoplasm over the nucleus in both cell lines in vitro. Ultrastructural studies also demonstrated the cytotoxic effects of MX2 against glioma cells. Our results suggest that MX2 may be a useful chemotherapeutic agent in the treatment of malignant gliomas and that confocal laser scanning microscopy is useful for the study of the cellular pharmacokinetics of anthracycline derivatives, such as MX2.

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.

Background: Local control of the tumor bed after removal of a tumor is one of the most important points in the treatment of malignant gliomas. This study was designed to examine whether fibrin glue is useful as a vehicle for sustained release of intraoperative local chemotherapy with nitrosourea (ACNU)., Methods: The growth-inhibiting activity of ACNU on C6 glioma cells and ACNU released into 5-mL supernatant saline from fibrin glue containing 5 mg/mL (10 mg) of ACNU was measured in vitro. C6 tumor inoculated in rat brains was covered with fibrin glue containing either 2 mg/mL or 5 mg/mL of ACNU for 5 days, and the histologic changes were examined., Results: ACNU inhibited the growth of C6 glioma cells in a dose-dependent manner, and the drug concentration required for 50% inhibition of cell growth (IC50) was about 4 micrograms/mL with 1 hour of treatment. Although about 50% of all ACNU included in the fibrin glue was released in the first hour, an effective concentration over the value of IC50 was sustained even after 12 hours. A histologic examination showed tumor cells damaged within a depth of about 2-3 mm from the tumor surface covered with fibrin glue containing ACNU., Conclusions: Fibrin glue may be useful as a vehicle for sustained-release chemotherapy, and intraoperative local chemotherapy with fibrin glue containing anticancer agents such as nitrosourea may be helpful in the local control of malignant gliomas.

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.

Background: Mannitol has been used in routine neurosurgical practice for the control of increased intracranial pressure. The effect of mannitol on focal cerebral ischemia was evaluated by somatosensory-evoked potentials (SEP) and magnetic resonance imaging (MRI)., Methods: The left middle cerebral artery (MCA) was exposed via the superomedial transorbital approach and occluded proximal to the origin of the perforating arteries. Ten cats received mannitol (0.5 g/kg IV) immediately, 6, 12, and 18 hours after MCA occlusion. The other 10 cats received saline solution and served as control. The animals were initially prepared to measure SEP before and 15, 30, and 60 minutes after MCA occlusion. Following SEP measurement, all cats were prepared for MRI. Sequential MRI of both intravoxel incoherent motion (IVIM) and T2-weighted spin echo techniques were obtained at 2, 4, 6, and 24 hours after MCA occlusion. The animals were sacrificed after the last MRIs for histologic study., Results: The SEP amplitude decreased to about 10% at 15 minutes after MCA occlusion and then gradually recovered to 38% at 60 minutes in the mannitol group, and 21% in the control group. In MRI study, IVIM imaging demonstrated ischemic cerebral injury as a sharply demarcated area at 2 hours after MCA occlusion, while T-2 weighted imaging failed to show clear evidence of injury until 2-6 hours. High-signal intensity areas on both IVIM and T2-weighted images were smaller in the mannitol group than those in the control group. Histologic study demonstrated that infarction size was 36.9% +/- 7.7% of the left hemisphere in the mannitol group and 57.3% +/- 5.3% in the control group (p < 0.05)., Conclusions: Mannitol is effective for acute cerebral ischemia, and SEP and MRI are useful for monitoring it.

Six patients with hypertensive intracerebral haemorrhage (HIH) were evaluated by both computed tomography (CT)and magnetic resonance (MR) angiography. The patients underwent MR angiography based on both time-of-flight (TOF) and phase-contrast (PC) methods. The CT scans showed putamenal haemorrhage in all patients. Early operations were performed and the haematoma was removed by stereotactic aspiration or a transsylvian approach in all cases. MR angiography offers great promise to distinguish HIH from other cerebrovascular diseases. The TOF method is very convenient for simultaneously observing both the intracerebral haematoma and the cerebral vasculature.

A serial measurement of endothelin-1(ET-1) levels in plasma, cisternal and ventricular cerebrospinal fluid(CSF) was performed in 16 patients with subarachnoid haemorrhage (SAH). The patients were classified as grade III or IV according to the clinical grade of Hunt and Hess, and computerised tomography(CT) was classified as Fisher's CT group 3. Cisternal and ventricular CSF and plasma were obtained from the patients on the day of operation days 0-3, days 5-8 and days 14-18 after SAH. ET-I concentration in each sample was quantified by sandwich-enzyme immunoassay. ET-I levels in plasma and CSF were the highest between days 0-3 and then decreased. The ET-I levels in the cisternal CSF were significantly higher during days 0-3(p<0. 01) and days 5-8(p<0. 01) than those in the ventricular CSF It is suggested that ET-I could play an important role in the early stages of the cerebral vasospasm.

Selenium (Se) levels in blood (whole blood, erythrocytes and serum) and blood glutathione peroxidase (GSH-Px) activity were investigated in people living at high altitude in Bolivia (4,000 m above sea level). These parameters were compared to those of people living at low altitude (300 m above sea level). The Se levels in whole blood of the high-altitude subjects did not differ significantly from those of the low-altitude subjects. However, the Se levels in erythrocytes were significantly lower in the high-altitude subjects than in the low-altitude subjects, whereas serum Se levels were higher in the high-altitude subjects than in the low-altitude subjects. GSH-Px activity (Unit/g Hb) was significantly lower in the high-altitude subjects than in the low-altitude subjects. The mean corpuscular Hb concentration (MCHC), an indicator of the age of erythrocytes, in the high-altitude subjects was significantly higher than in the low-altitude subjects. These results show that the GSH-Px activity in the blood of the high-altitude subjects is relatively low. This may be due to their aged erythrocytes and/or to relatively low Se intake in the high-altitude population compared with low-altitude population.

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.

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.

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.

This study was designed to examine the influence of total body hyperthermia (TBHT) using an extracorporeal circuit with a heat exchanger on the cerebral blood flow (CBF), intracranial pressure (ICP), brain tissue pH, cerebral autoregulation and blood-brain barrier (BBB) permeability in dogs. The rectal temperature of the dow was raised to 41.5 degrees C, maintained at 41.5-42.0 degrees C for 2 hours (HT period) and then reduced to normothermia by cooling. Regional CBF was measured by the hydrogen clearance method before heating, during the HT period and after cooling. ICP and brain tissue pH were monitored during the TBHT treatment. Autoregulation of the CBF during the HT period was assessed by measuring the regional CBF and the ICP in a state of induced hypo- or hypertension. The influence of TBHT on BBB permeability was examined using an immunohistochemical technique. The regional CBF increased from 38.1 +/- 6.5 (mean +/- SD) to 49.1 +/- 9.8 ml/100 g/min and the ICP from 10.3 +/- 4.2 to 16.8 +/- 3.4 mmHg when TBHT was raised. These returned to normal values after cooling. The regional CBF and the ICP changed in parallel with drug-induced changes of mean arterial blood pressure during the HT period. These changes suggest that autoregulation of the CBF is paralysed during the HT period. Brain tissue pH decreased rapidly when the rectal temperature exceeded 41.0 degrees C. The pH was 7.18 +/- 0.05 during the HT period and was relatively stable. The pH returned to a normal value after cooling. Immunopositive stain for albumin was not observed in heated brain tissue except for the normally leaky pineal gland and the choroid plexus, indicating preservation of BBB during TBHT. These results suggest that brain oedema may occur easily due to paralysed cerebral autoregulation when the arterial blood pressure fluctuates excessively, so arterial blood pressure must be controlled strictly during TBHT.

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.

The cellular uptake, subcellular distribution and retention of MX2, a new morpholino anthracycline, were compared with those of adriamycin (ADM) using confocal laser scanning microscopy (CLSM) in rat C6 and human T98G glioma cell lines. The tumor cells were exposed to 1-30 micrograms ml-1 of MX2 and ADM for 120 min and further incubated without drugs for 120 min after washing twice with medium. During incubation, real-time subcellular distribution of MX2 and ADM in living tumour cells were observed at various intervals using CLSM. For analysis of the in vivo uptake. Wistar rats bearing the C6 glioma were intravenously administered MX2 at a dose of 5 mg per kg body weight 60 min before sacrifice. The fluorescence of MX2 was predominantly seen in the cytoplasm in both C6 cells and T98G cells, although it was also present in the nucleus. In contrast, that of ADM was mainly confined to the nucleus in both cell lines. The fluorescent intensity of ADM in the nucleus after 120 min of exposure was approximately 1.5-fold higher than that of MX2 at the same dose exposure, probably indicating a greater amount of ADM accumulated in the nucleus than MX2. The influx and efflux of MX2 were much more rapid and greater than those of ADM in both cell lines. There was almost no difference in subcellular distribution among the doses tested in this study. The subcellular distribution of MX2 in vivo was almost similar to that of MX2 in vitro. These results suggest other mechanisms by which MX2 exerts its cytotoxic effects on tumour cells together with the inhibition of DNA topoisomerase II, which has been reported previously. It is considered that the CLSM technique is useful for the study of the cellular pharmacokinetics of antitumour agents such as anthracycline derivatives.

The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP-9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells.

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 (p < 0.05). 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.

MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether 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.

Electroencephalogram (EEG) power spectrum changes induced by pleasant music (2-min. fractions of 6 samples of music [famous classical and commercially available "alpha music" at 10-sec. intervals]) were investigated in relation to changes in 16 kinds of psychosomatic feelings. Subjects were 42 healthy young people aged 18-25 yrs. Two major components, "pleasant & relaxed" and "calm", were extracted through principal component analysis of the feeling changes, both of which were related to the "relaxation effects" of the music. These component scores were not related to the changes of EEG powers in the delta, theta, alpha and beta frequency components in 6 regions (frontal, parietal and occipital regions of the left and right hemispheres), when examined separately. However, the change of the total delta power for all the regions was significantly associated with both the "pleasant & relaxed" and "calm" component scores. The association between the total theta power change and "calm" score was found to be insignificant if the type-A personality variable was added to their regression model. On the other hand, the alpha-peak frequency was inversely related to the decrease of the "calm" score in the left occipital region (LO). The reduction of the alpha-peak power in the LO was also significant, and was associated not with the alpha-peak frequency changes but inversely with the "calm" score, although these alpha-component changes were not shown to be modified by the personality. Thus, the present study suggests, as a preliminary finding, that the "relaxation effects" of pleasant music can be associated with the EEG power spectrum component changes, especially with the change in the total theta power and possibly with that in the alpha power in the occipital, and the frequency shift of the peak in the alpha-range. Some of the associations were also shown to vary for the type-A personality, suggesting a clue to relating the personality to a differential stress-related psychosomatic trait, although the physiological significance of the changes in the low-frequency component range as well as those in the alpha-frequency component, which are obtained through FFT, should be further clarified.

This study was designed to establish an in vitro model system in human hormone-producing pituitary adenoma which is analogous to the in vivo cellular environment. Mechanically dispersed cells composed of single cells and aggregated cells from 9 pituitary adenomas (5 GH-producing adenomas and 4 prolactinomas) were cultured on microporous membrane coated with basement membrane extract. Not only single cells but also large aggregated cells which usually float in the medium when seeded on ordinary plastic flasks were morphologically flattened and firmly attached to coated microporous membrane within a few days under the control of seeding medium volume. In both types of adenoma, surviving aggregated adenoma cells revealed well-preserved hormonal activity with regard to both cell morphology and hormone release after 6 m in culture and no undifferentiation of cell characteristics was observed. It is concluded that this culture method may further aid the investigation of in vitro cellular structure and function in human pituitary adenoma under conditions which closely mimic the in vivo cellular environment.

With respect to the inverse association of serum ferritin level (SFL) with the risk of gastric cancer (GC) observed in some recent epidemiologic studies, possible mediation by achlorhydria as well as atrophic gastritis (AG), both of which are strongly associated with GC risk at not only the individual but also the population level, was examined in a cross-sectional study of 634 men aged 40 to 49 years randomly selected from 5 populations in Okinawa, Iwate, Nagano, Akita and Tokyo. AG and achlorhydria were serologically diagnosed based on the criteria of pepsinogen (Pep) I level < 70 ng/ml and Pep I/Pep II ratio < 3.0, as described previously, and a serum gastrin level of over 140 pg/ml, respectively. In the results, while the mean SFL for all the subjects differed significantly by area, similar areal differences in SFL were also found even when only the non-AG cases were considered. However, both of the above differences were eliminated with the exception of those between Okinawa and each of the other 4 areas, when adjustments were made for medical histories of diabetes mellitus, ulcers and liver disease, body mass index and gamma-glutamyltranspeptidase level. Therefore, no correlation among the 5 areas was observed between the adjusted areal mean SFLs and GC mortality in either case.(ABSTRACT TRUNCATED AT 250 WORDS)

A 24-year-old man sought treatment of a long-standing olfactory delusion (Eigengeruchs erlebnis) and associated psychotic symptoms, which disappeared after the removal of a suprasellar dermoid cyst. The pathophysiology of the phenomenon is discussed.

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I < 70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio < 3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR] = 1.9, 95 percent confidence interval [CI] = 1.1-3.3). As the level of plasma beta-carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI = 0.2-0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, beta-carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma beta-carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A mammosomatotroph cell was identified in two consecutive semithin sections of conventional epoxy-embedded tissue for light microscopy and an adjacent ultrathin section for electron microscopy cut from a mixed growth hormone (GH)- and prolactin (PRL)- secreting human pituitary adenoma in a 51-year-old female. The same mammosomatotroph cell demonstrated immunostaining for both GH and PRL simultaneously by light microscopy, and was morphologically evaluated by electron microscopy. The ultrastructural features of this cell resembled densely granulated GH-secreting adenoma cells, but also contained characteristics of PRL-secreting adenoma cells.

When the nutritional status of minerals and essential trace elements is assessed by their levels in plasma, intra-individual variation in the measured values, particularly diurnal variation, must be considered. In this paper, concentrations of nine elements (Na, Mg, P, K, Ca, Fe, Cu, Zn, and Se) in plasma collected 7 times in a 24-h period from 10 healthy Japanese adults were measured with hemoglobin and plasma concentrations of proteins (total protein, albumin, retinol binding protein (RBP), ceruloplasmin, and transferrin), total cholesterol, and cortisol. Then the pattern of diurnal variation in, and the interrelationships among, these parameters were clarified in subjects who consumed an ordinary meal. Significant diurnal variation examined by two-way analysis of variance (variations due to subject and sampling time) was found for Zn, RBP, and cortisol. Plasma Zn level was higher in the forenoon samples than in those taken in the afternoon. The pattern of diurnal variation found for cortisol was similar to, but slightly different from, that for Zn. The correlation coefficient between Zn and cortisol was significant (r = 0.555) using the standardized values for individuals, and in the result of multiple regression analysis, cortisol level was selected as the significant explanatory factor for Zn variation; however, the sampling time was the most significant factor. For other elements besides Zn, no significant diurnal variation was found. Moreover, no meaningful factors were selected for variations of those elements in the result of multiple regression analysis. These results indicate that, in assessing Zn nutriture with its plasma levels, it is necessary to unify the sampling time.

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 (p < 0.05) 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.

An artificial blood vessel with an endothelial-cell monolayer was used as an arterial substitute in rats. Endothelial cells were isolated from the aorta of a Wistar rat by the digestion method. The cell identification was established by the cobblestone appearance of a confluent cell monolayer, by an expression of factor VIII-related antigen, and by the presence of Weibel-Palade bodies. The luminal surface of the thin-walled polytetrafluoroethylene (PTFE) graft (4 mm in diameter and 10 mm in length) was coated with an endothelial-cell monolayer for 7 days in vitro. An interpositional graft was placed using the endothelial cell-coated PTFE prosthesis on the right common carotid artery in seven rats. A total of 10 rats received an interpositional graft with the noncoated PTFE prosthesis as a control. The patency rate at 1 month after implantation was significantly higher in the coated group than in the control group. The vascular prosthesis with an endothelial-cell monolayer is a promising technique to inhibit the development of thrombosis.

A woman with Addison disease developed hyperpigmentation, headache, and nausea despite conventional replacement therapy with cortisone. Excessively elevated plasma adrenocorticotropic hormone (ACTH) with absence of response to administration of corticotropin-releasing factor (CRF), and roentgenological evidence of enlargement of the sella turcica, as well as detection of enlarged pituitary gland on magnetic resonance images, led to a diagnosis of ACTH-producing microadenoma, which was removed by transsphenoidal microsurgery. The specimen obtained at surgery evidenced corticotroph hyperplasia, as demonstrated by immunohistochemical staining for ACTH. Fine structure exhibited densely granulated cells with a few bundles of microfilaments and an abundance of large lysosomal bodies. Surgical removal of the hyperplasia alleviated the patient's symptoms, and hyperpigmentation faded remarkably. Her plasma ACTH level returned to normal, has remained normal for more than 3 years, and responds adequately to CRF administration.

MR was useful in verifying CSF rhinorrhea following removal of an intracanalicular acoustic neurinoma via the occipital route in a 29-year-old man. MR accurately identified the location of the CSF leak.

Thirty male Wistar rats, weighing 350 to 400 gm each, received stereotactic injections of 6-hydroxydopamine (300 micrograms/kg) into the left lateral ventricle. The same amount of saline was injected into a control group of 15 rats. Seven days after this procedure, cerebral blood flow (CBF) was measured by the hydrogen clearance method. A hypertensive condition at a mean arterial pressure of about 160 mm Hg was maintained for 1 hour by intravenous infusion of phenylephrine. In the 6-hydroxydopamine-treated group, CBF increased significantly after the elevation of systemic blood pressure compared with that in the control group, and cerebral autoregulation was impaired. After a 1-hour study, the specific gravity of the cerebral tissue in the treated group significantly decreased; electron microscopic studies at that time revealed brain edema. It is suggested that depletion of brain noradrenaline levels causes a disturbance in cerebral microvascular tone and renders the cerebral blood vessels more vulnerable to hypertension.

Our operative experience of reconstruction of the skull base using a silicone plate during rhinoseptoplastic transsphenoidal surgery is described. A suitably shaped plate can be easily and quickly made from a large silicone block of the type that is widely used in cosmetic surgery. The plates can be distinguished on magnetic resonance images postoperatively. We consider that this technique is of use not only for repairing the sellar floor, but also for closing a wide defect of the skull base.

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.

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.

Changes in brain high energy phosphate metabolite and pH levels were studied using serial phosphorus (P)-31 magnetic resonance spectroscopy (MRS) in an epidural balloon cat model. The balloon was inflated with 1, 2, 3, or 4 ml of water at 1 ml/sec and deflated after obtaining a spectrum 4 minutes later. Serial spectra, intracranial pressure (ICP), physiological parameters, and the pupil sizes were observed for 1 hour. The mean ICP after balloon inflation increased to between 36 +/- 3 and 130 +/- 6 mmHg. Some animals showed oculomotor paralyses. Phosphocreatine, adenosine triphosphate, phosphodiester, and phosphomonoester levels suddenly decreased after inflation and gradually recovered after balloon deflation. Acidosis progressed with cerebral compression for 4 minutes and gradually recovered. All changes and recovery were volume related. This study demonstrates the potential of P-31 MRS for noninvasive, serial, in vivo measurements of critical high energy phosphate metabolites and intracellular pH after head injury.

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)