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Gliomatosis cerebri is a rare tumor of the central nervous system, and here we report two cases of this tumor. Case 1: A 41-year-old female was admitted to our department for evaluation of activity loss and mental changes. MR imaging revealed a high intensity symmetrical lesion in the bilateral frontal and temporal regions, thalamus and midbrain on FLAIR images. The patient had no neurological deficits and no abnormal findings in clinical laboratory data, including data for the cerebral spinal fluid. A specimen obtained by open biopsy revealed widespread infiltration of neuronal structures by small astrocytic cells, although without destruction of the neuronal structures. The patient was diagnosed with gliomatosis cerebri, and surgery and whole brain radiation at 44Gy were performed. The MRI lesion showed some shrinkage 20 months after surgery, and the KPS score was 90, the same as that before admission. Case 2: A 56-year-old male was admitted for numbness of the face and extremities. MR imaging revealed a high intensity lesion in the bilateral thalamus and a ringed enhanced lesion in the right thalamus. A specimen obtained by open biopsy revealed anaplastic oligodendroglioma, which was diagnosed as gliomatosis cerebri. Radiation at 54Gy, chemotherapy (ACNU, vincristine) and gamma-knife surgery were performed, and two months later MR imaging showed that the tumor (including the ringed enhanced lesion) had shrunk markedly. His KPS was 90 at 13 months after onset. These cases suggest that radiation therapy is effective for gliomatosis cerebri.

A 41-year-old man developed hyperperfusion 24 hours after undergoing successful clipping surgery for an unruptured middle cerebral artery aneurysm with temporary occlusion for 7 minutes. The patient exhibited motor aphasia 24 hours after surgery. Single photon emission computed tomography revealed hyperperfusion. The patient was sedated for 72 hours using propofol, and his symptoms gradually resolved. He returned to his previous job 2 months after surgery. Hyperperfusion syndrome is possible following any aneurysm surgery, including surgery for unruptured aneurysms using the temporary occlusion technique.

Protein kinase Cdelta (PKCdelta) has an important role in radiation-induced apoptosis. The expression and function of PKCdelta in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCdelta-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCdelta activation correlated with the degradation of PKCdelta, indicating that PKCdelta activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCdelta activation was lower than that in radiosensitive 3SBH5. Cytosol PKCdelta levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCdelta levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCdelta activation compared to that of 3SBH5. On the other hand, Atm(-/-) mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm(-/-) cells, had decreased PKCdelta levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCdelta degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCdelta activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells.

Purpose: To investigate changes in radical scavenging ability and lipid peroxidation in liver microsomal membranes and cooperative suppression of lipid peroxidation by microsomal and cytosolic radical scavengers, 24 h after whole-body, low-dose X-irradiation of rats., Materials and Methods: Male Wistar rats were irradiated with 1-50 cGy of X-rays. Liver microsomal radical scavenging ability was determined using the trapping ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH), a stable free radical. Microsomal alpha-tocopherol (Vit.E) content was determined using an electrochemical detector. Microsomal glutathione peroxidase (GPx) activity was determined as the consuming rate of NADPH. Microsomal lipid peroxidation was determined by the thiobarbituric acid method., Results: Low molecular weight radical scavenging ability of rat liver microsomes increased 24 h after whole-body, low-dose X-irradiation when alpha-tocopherol was included, showing a maximum level at 5-10 cGy. Microsomal GPx activity also increased 24 h after 5 cGy irradiation. The lipid peroxidation level in microsomes decreased, showing a maximal suppression at 5 cGy. High-dose irradiation-induced microsomal lipid peroxidation was strongly suppressed cooperatively by microsomal and cytosolic antioxidants induced by low-dose irradiation., Conclusion: Low doses of radiation induce increases in liver microsomal antioxidants, which in turn result in enhanced suppression of microsomal lipid peroxidation cooperatively with cytosolic antioxidants induced by low-dose irradiation.

We describe a rare case of subarachnoid hemorrhage due to a ruputured iatrogenic traumatic aneurysm in the cavernous carotid artery, caused by injury during surgery for skull base meningioma that was performed 2 years ago. A 64-year-old woman underwent craniotomy for resection of meningioma of the right sphenoid ridge. During surgery, venous bleeding from the cavernous sinus was easily controlled by packing. Tumor infiltration into the artery had not occurred, and total resection was successfully performed. Two years later, the patient was admitted to our hospital for subarachnoid hemorrhage, without clinical signs of carotid cavernous fistula. Angiography displayed an aneurysm in the cavernous portion of the right carotid artery, which had not been detected on a previous angiogram. The aneurysm was successfully embolized with a GDC via an endovascular approach. Three months later, the residual aneurysm became enlarged and aneurysmal embolization was performed for a second time. Follow-up angiography was performed 7 months after initial embolization, and revealed complete packing.

Protein kinase C (PKC; also known as PRKC) is known to be an important participant in radiation-induced apoptosis. However, its role is not fully clarified. Using 3SBH5 cells, which are radiation-sensitive thymic lymphoma cells, the involvement and functions of PKC were assessed in radiation- induced apoptosis. PMA (phorbol 12-myristate 13-acetate), a PKC activator, inhibited the radiation-induced apoptosis in 3SBH5 cells. On the other hand, chelerythrine, a PKC inhibitor, potentiated apoptosis. In addition, Gö6976, a classical PKC (cPKC) inhibitor, which specifically inhibits PKC (alpha and betaI), also promoted apoptosis. Interestingly, post-treatment (20 min after irradiation) with Gö6976 had no effect on the radiation-induced apoptosis. These results suggest that cPKC is activated early after irradiation for anti-apoptosis signaling and contributes to the balance between cell survival and death. Indeed, an increase of cPKC activity involving PKC (alpha, betaI and betaII) was observed in the cytosolic fraction 3 min after irradiation with 0.5 Gy. However, no translocation of cPKC was observed in the cells after irradiation. Our findings indicate that activation of cPKC (alpha or beta) soon after irradiation is critical to the understanding of the regulation of radiation-induced apoptosis in radiation-sensitive cells.

We describe a case of a 34-year-old woman in whom delayed occult cerebrospinal fluid rhinorrhea presented as meningitis. Removal of an implanted shunt system and surgical repair of the fistula were required. The cerebrospinal fluid fistula was located in the left frontoethmoidal region. Fourteen years previously, the patient had been treated successfully for injury to the left internal carotid artery in a motor vehicle collision, by clipping and by implantation of ventriculoperitoneal and subduralperitoneal shunts to reverse the associated hydrocephalus. To prevent the spread of intracranial infection, we immediately removed the implanted shunt system and followed this by placement of lumbar drainage. After complete resolution of meningitis in response to antimicrobial agents, we performed surgical repair of the fistula. Shunt reconstruction was not required. The patient was discharged with good performance status. This case illustrates the point that effective treatment of meningitis is greatly facilitated by timely removal of associated foreign material.

The adaptive response is an important phenomenon in radiobiology. A study of the conditions essential for the induction of an adaptive response is of critical importance to understanding the novel biological defense mechanisms against the hazardous effects of radiation. In our previous studies, the specific dose and timing of radiation for induction of an adaptive response were studied in ICR mouse fetuses. We found that exposure of the fetuses on embryonic day 11 to a priming dose of 0.3 Gy significantly suppressed prenatal death and malformation induced by a challenging dose of radiation on embryonic day 12. Since a significant dose-rate effect has been observed in a variety of radiobiological phenomena, the effect of dose rate on the effectiveness of induction of an adaptive response by a priming dose of 0.3 Gy administered to fetuses on embryonic day 11 was investigated over the range from 0.06 to 5.0 Gy/min. The occurrence of apoptosis in limb buds, incidences of prenatal death and digital defects, and postnatal mortality induced by a challenging dose of 3.5 Gy given at 1.8 Gy/min to the fetuses on embryonic day 12 were the biological end points examined. Unexpectedly, effective induction of an adaptive response was observed within two dose-rate ranges for the same dose of priming radiation, from 0.18 to 0.98 Gy/ min and from 3.5 to 4.6 Gy/min, for reduction of the detrimental effect induced by a challenging dose of 3.5 Gy. In contrast, when the priming irradiation was delivered at a dose rate outside these two ranges, no protective effect was observed, and at some dose rates elevation of detrimental effects was observed. In general, neither a normal nor a reverse dose- rate effect was found in the dose-rate range tested. These results clearly indicated that the dose rate at which the priming irradiation was delivered played a crucial role in the induction of an adaptive response. This paper provides the first evidence for the existence of two dose-rate ranges for the same dose of priming radiation to successfully induce an adaptive response in mouse fetuses.

The radioadaptive response and the bystander effect represent important phenomena in radiobiology that have an impact on novel biological response mechanisms and risk estimates. Micromass cultures of limb bud cells provide an in vitro cellular maturation system in which the progression of cell proliferation and differentiation parallels that in vivo. This paper presents for the first time evidence for the correlation and interaction in a micromass culture system between the radioadaptive response and the bystander effect. A radioadaptive response was induced in limb bud cells of embryonic day 11 ICR mice. Conditioning irradiation of the embryonic day 11 cells with 0.3 Gy resulted in a significant protective effect against the occurrence of apoptosis, inhibition of cell proliferation, and differentiation induced by a challenging dose of 5 Gy given the next day. Both protective and detrimental bystander effects were observed; namely, irradiating 50% of the embryonic day 11 cells with 0.3 Gy led to a successful induction of the protective effect, and irradiating 70% of the embryonic day 12 cells with 5 Gy produced a detrimental effect comparable to that seen when all the cells were irradiated. Further, the bystander effect was markedly decreased by pretreatment of the cells with an inhibitor to block the gap junction-mediated intercellular communication. These results indicate that the bystander effect plays an important role in both the induction of a protective effect by the conditioning dose and the detrimental effect of the challenge irradiation. Gap junction-mediated intercellular communication was suggested to be involved in the induction of the bystander effect.

There is continuing controversy about the benefits of decompressive craniectomy for the treatment of massive infarction of middle cerebral artery (MCA) territory. Under conservative therapy, the mortality rate for this stroke is reported to be up to 80%. So the authors have actively carried out decompressive craniectomy since 1997, and have compared the outcome with patients who were admitted before 1997 and, consequently treated with conservative therapy. Fifteen consecutive victims of massive infarction of MCA territory were studied. Seven patients (male: 1, female: 6, mean age: 79.8 years) were treated with conservative therapy, and 8 patients (male: 3, female: 5, mean age: 71.8 years) were treated with decompressive craniectomy. There were no significant differences in age and consciousness level distribution between the two groups. Mortality rate in the conservative therapy group was 85.7% against 12.5% in the surgery group (p < 0.05). Functional performance, which was evaluated by activity in daily life (ADL), was also better in the surgery group e.g. 3 patients in ADL 3, and 3 in ADL 4 (1 patient died from a non-neurological cause). Even among the patients with speech-dominant hemispheric stroke, all except one were able to communicate in some way and understand language. Even though patients in this study were elderly, decompressive craniectomy reduced mortality and improved functional performance, so it seems that this surgery should be aggressively considered for massive infarction of MCA territory.

Reactive oxygen species play a critical role in the onset of apoptosis induced by various extracellular stimuli, including ionizing radiation. Therefore active regulation of reactive oxygen species-metabolizing enzymes may be one response to an apoptotic stimulus. In this regard, HP100 cells, H(2)O(2)-resistant variants derived from human leukemia HL60 cells, display an interesting phenotype in which the activity of catalase is constitutively high, whereas its mRNA is reduced after X-ray irradiation. In the present study, we investigated the molecular mechanisms underlying this phenomenon. By combining analyses from nuclear run-on, reporter gene transient transfection, genomic footprinting, site-directed mutagenesis, electrophoretic mobility shift analysis, and Western blotting experiments, we found that constitutively elevated catalase expression is strongly regulated at the transcriptional level by both Sp1 and CCAAT-recognizing factors and that much higher levels of nuclear Sp1 and NF-Y are present in HP100 nuclei as compared with HL60 nuclei. In addition, we demonstrated an X-ray-inducible association of a WT1/Egr-related factor with an overlapping Sp1/Egr-1 recognition sequence located within the core promoter of the catalase gene. This association may lead to inactivation of the promoter by disturbing or competing with the transactivating ability of Sp1.

Exposing mice to 0.5 Gy X rays 2 weeks before lethal irradiation has been reported to induce marked radioresistance and to rescue them from hematopoietic death. Here we examined effects of the 0.5-Gy pre-exposure on hematological changes in C57BL mice that were lethally irradiated with 6.5 Gy X rays. Approximately 77% of pre-exposed mice survived 30 days after this irradiation, whereas 80% of mice that did not receive this pre-exposure died by day 20. However, regardless of the pre-exposure, peripheral blood cell counts decreased markedly by day 3 and reached a nadir at day 20. CFU-S in femur and CFU-GM in spleen had started to recover at day 10 and 14, respectively, but recovery of functional peripheral blood cells occurred later. The effect of pre-exposure on survival was altered by OK432, a bioresponse modifier; the effect depended on the timing of its administration. OK432 given 2 days before 0.5 Gy enhanced the protective effect of pre-exposure, resulting in the survival of 97% of the mice. In contrast, injection of OK432 1 day before or 2 days after pre-exposure led to 100% mortality. Thus the survival-promoting effect of 0.5 Gy could be altered by OK432. The OK432-induced changes in the survival of mice could not be attributed solely to hematological changes, as shown by blood cell counts and progenitor cell contents. These results suggest that radioresistance induced by pre-exposure to 0.5 Gy X rays is not stable, but rather varies with the physiological conditions, and can be modulated by factors such as OK432.

A new method termed the opposite directional flow-encoding (ODFE) technique is proposed to increase the accuracy and the reproducibility of phase-contrast flow measurements by correcting the non-linear background of velocity images induced by concomitant magnetic fields (Maxwell terms). In this technique, the volume flow rate is calculated from the difference of two region of interest (ROI) values derived from two velocity images obtained by reversing the flow-encoding direction. To evaluate the technique, various phantom experiments were carried out and volume blood flow rates of internal carotid arteries (ICAs) were measured in four volunteers. The technique could measure the volume flow rates of the phantom with higher accuracy (mean absolute percentage error = 1.04%) and reproducibility (coefficient of variation = 1.18%) than conventional methods. Flow measurements with the technique was not significantly affected by ROI size variation, measuring position, and flow obliquity not exceeding 30 degrees. The volume flow rates in the ICAs of a volunteer were measured with high reproducibility (coefficient of variation = 2.89% on the right, 1.48% on the left), and the flow measurement was not significantly affected by ROI size variation. The ODFE technique can minimize the effect of the non-linear background due to Maxwell terms. The technique allows use of ROIs of approximate size including the flow signal and provides accurate and objective phase-contrast flow measurements.

Purpose: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells., Materials and Methods: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed., Results: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium., Conclusions: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.

We reported previously that a radiation-induced adaptive response existed in the late period of embryogenesis, and that radiation-induced apoptosis in the predigital regions was responsible for digital defects in embryonic ICR mice. To investigate the possible involvement of the Trp53 gene and radiation-induced apoptosis in radiation-induced adaptive responses in embryogenesis, the present study was conducted using Trp53 wild-type (Trp53(+/+)) and Trp53 heterozygous (Trp53(+/-)) embryonic mice of the C57BL/6 strain. The existence of a radioadaptive response in the Trp53(+/+) embryonic mice was demonstrated by irradiating the embryos with 5 or 30 cGy on embryonic day 11 prior to a challenging irradiation at 3 Gy on embryonic day 12. The two conditioning doses at 5 and 30 cGy significantly suppressed the induction of apoptosis by the challenging dose in the predigital regions of limb buds in the Trp53(+/+) embryonic mice, while no such effect was found in the Trp53(+/-) embryonic mice. These findings indicate that induction of a radioadaptive response in embryogenesis is related to Trp53 gene status and the occurrence of radiation-induced apoptosis.

Purpose: The aim of this study is to investigate the dependence of p53-gene status on the radiation enhancement of thermosensitivity at different levels of linear energy transfer (LET)., Methods and Materials: We used two kinds of human glioblastoma transfectants of A-172 cells bearing the wild-type p53 gene, A-172/neo cells with control vector containing the neo gene and A-172/mp53 cells with both the dominant negative mutated p53 gene and neo gene. We exposed these cells to X-rays and accelerated carbon-ion (C-) beams (13-200 KeV/microm) followed by heating at 44 degrees C. Cellular sensitivities were determined using clonogenic assay., Results: The radiation enhancement of thermosensitivity was LET-dependent for the A-172/neo cells, but this was not clearly demonstrated in the A-172/mp53 cells. The supraadditive radiation enhancement of thermosensitivity was observed in A-172/neo cells at the LET range of 13 to 70 KeV/microm, though only an additive effect was observed at higher LET. In A-172/mp53 cells, only an additive effect was observed through all the LET examined., Conclusion: These results indicate that the radiation enhancement of thermosensitivity is p53- and LET-dependent. Our results suggest that the combined use of high-LET radiation and hyperthermia brings useful application for cancer therapeutic purposes.

Purpose: There have been no reports about the effects of heavy-ion beams on the expression of the WAF1 gene, although ionizing radiation such as y-rays and X-rays is well known to induce WAF1 (p21/CIP1/sdi1) gene expression in a p53-dependent manner. In the present study, it was examined whether WAF1 accumulation was induced after carbon-ion (C-) beam or alpha-particle irradiation in four glioblastoma cell lines., Materials and Methods: A colony assay for radiosensitivity and Western blot analysis of WAF1 were applied to two human glioblastoma cell lines, A-172 bearing wild-type p53 (wtp53) and T98G bearing mutated p53 (mp53). A-172/neo and A-172/mp53 were transfected with a control vector (containing only a neo selection marker) and a mp53 expression vector respectively., Results: The amount of WAF1 increased markedly after X-ray irradiation in A-172 and A-172/neo cells but not in T98G and A-172/mp53 cells. The level of WAF1 reached a plateau at 3-10 h after X-ray irradiation at 5 Gy in A-172 and A-172/neo cells. Likewise, the levels of WAF1 in A-172 and A-172/neo cells reached a plateau at 3-10 h and 6-24 h after C-beam (3.0 Gy) and alpha-particle (4.5 Gy) irradiation respectively. The amount of WAF1 increased markedly in a dose-dependent manner 10 h after X-ray, C-beam or alpha-particle irradiation in A-172 and A-172/neo cells but not in T98G or A-172/mp53 cells. In addition, cell survival assay showed that these cell lines were most sensitive to C-beams, less sensitive to alpha-particles and least sensitive to X-rays at 10% survival. There was no difference in sensitivity among these cell lines against C-beam and alpha-particle irradiation whereas wtp53 cells (A-172 and A-172/neo) were more sensitive to X-rays than mp53 cells (A-172/mp53 and T98G)., Conclusions: These results indicate that C-beams and alpha-particles induce p53-dependent WAF1 accumulation as well as is the case with X-rays, suggesting that WAF1 protein accumulation may not contribute to cell killing.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.

Protein kinase C (PKC) is known to be a key enzyme in radiation-induced signal transduction pathways. We have previously demonstrated that gamma-irradiation induces PKC activation and translocation from cytosol to membranes as a consequence of membrane lipid peroxidation in cultured rat hepatocytes (Int. J. Radiat. Biol. 70, 473-480, 1996). The present study was undertaken to investigate production of diacylglycerol, an endogenous activator of PKC, following gamma-irradiation of hepatocytes. Diacylglycerol content increased 3 min after irradiation, then decreased at 15 min and increased again at 30 min, indicating a biphasic pattern. This result implies participation of diacylglycerol in the radiation-induced activation of PKC in hepatocytes. In order to clarify the mechanism of the initial process of radiation-induced diacylglycerol production, the effects of reactive oxygens were investigated. Treatment of cells with hydroxyl radical, a major oxygen radical produced by radiation, induced diacylglycerol production without any change in the content of phosphatidylcholine, showing a peak at 1 min after treatment. No change in the diacylglycerol content was observed at that time by hydrogen peroxide treatment. Furthermore, the diacylglycerol production by hydroxyl radical was inhibited by pretreatment with neomycin sulfate, a phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor. These results suggest that radiation exerts PI-PLC activation through hydroxyl radical generation, followed by diacylglycerol production and PKC activation.

An adaptive response was demonstrated during embryogenesis in mice. Whole-body irradiation at a dose of 0-50 cGy was given to condition pregnant ICR mice on day 9 to day 11 of gestation. Then their whole bodies were exposed to a challenging dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths and living fetuses with external gross malformations were determined on day 19. A conditioning dose of 30 cGy on day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations induced by a 5-Gy dose on day 12. This indicates the existence of a critical dose and timing for administering a conditioning dose for radioadaptation during the late period of organogenesis in mice. The possible mechanisms involved are discussed.

The study examined the effects of combination of hyperthermia (42 degrees C) and 290 MeV/u carbon-ion (C-) beams or 200 kVp X-rays on tumour regrowth delay of transplantable human esophageal cancer as an in vivo model for radiotherapy of cancer. The C-beams were more effective in the tumour growth inhibition than X-rays. The relative biological effectiveness (RBE) of C-beams against X-rays was 2.00. It was observed that the interactive hyperthermic (42 degrees C, for 30 min) enhancement of tumour regrowth delay by high-linear energy transfer (LET) C-beams was similar to that of combination of low-LET X-rays with hyperthermia. The thermal enhancement ratios (TER) were 6.10 and 5.57 for X-rays and C-beams, respectively. These results suggest that hyperthermic treatment is effective in radiotherapy not only by low-LET radiation but also by high-LET radiation such as C-beams. In conclusion, the depression of the tumour growth by the combined treatment of hyperthermia (42 degrees C) and the C-beams strongly suggests the available possible application of interdisciplinary cancer therapy for refractory tumours.

We have studied the effectiveness of 290 MeV/u carbon-ion (C-) beams (linear energy transfer (LET) of 70 keV/mm) and 200 kVp X-rays on tumor growth inhibition as an in vivo model for radiotherapy of cancer. We measured the size of tumor growth of transplantable human esophageal cancer in nude mice after radiation with C-beams and compared this with X-rays as the control. A significant inhibition of tumor growth was observed by C-beams as compared with X-rays. The relative biological effectiveness (RBE) of C-beams against X-rays was 2.02. Histopathological studies showed that C-beams at 20 Gy induced prominent necrosis in the central region and multinucleate giant cells and inflammatory cells in peripheral regions of the tumor, whereas X-rays at 20 Gy induced only mild necrosis. The high RBE of C-beams obtained in this study provides in vivo evidence that C-beams are more effective than conventional X-rays for radiotherapy of cancer.

A mechanism of radiation-induced activation of protein kinase C was investigated in primary cultured rat hepatocytes. Irradiation of hepatocytes with 5 Gy or 50 Gy of gamma-rays caused an immediate and transient increase in the activity of protein kinase C in the membrane fraction, and a decrease in this activity in the cytosol fraction. A ligand binding procedure for protein kinase C using [3H]PDBu demonstrated that PDBu binding content increased in the membrane fraction and decreased in the cytosol fraction following irradiation. These results suggest that protein kinase C molecules were translocated from cytosol to the membrane after irradiation of the hepatocytes. Irradiation also induced lipid peroxidation of hepatocytes in the range from 0 to 50 Gy in a radiation dose-dependent fashion. This induction of lipid peroxidation was markedly suppressed by the addition of Trolox, a radical scavenger. Treatment of hepatocytes with Trolox also caused simultaneous inhibition of the radiation-induced increase in the PDBu binding content of the membrane fraction. We conclude that radiation-induced activation of protein kinase C results from the translocation of protein kinase C from cytosol to membrane due to membrane lipid peroxidation through reactive oxygen species produced by radiation.

We evaluated the usefulness of surface anatomy scanning (SAS) in intracranial tumours, comparing it with surgical findings. We examined 31 patients with brain tumours preoperatively. The tumours included 16 meningiomas, 8 gliomas, 4 metastases and 3 others. SAS clearly demonstrated the tumours, allowing them to be distinguished from the structures of the brain surface, including oedema, except in cases of metastasis. SAS clearly demonstrated large cortical veins. SAS is useful for three-dimensional delineation of the brain surface before surgery.

A 66-year-old male presented with a left frontal intracerebral arteriovenous malformation (AVM) fed by the anterior ethmoidal artery. The nidus was located intracerebrally, although the feeder was a dural artery, and was drained by the ascending frontal vein which showed varicose dilatation. The AVM was associated with an unruptured right anterior choroidal artery aneurysm. The AVM was removed and the aneurysm was clipped in a two-stage operation. The etiology of AVMs fed by the ethmoidal artery is still uncertain, but is probably due to a disturbance in normal embryonic development. The association with aneurysm seemed to be incidental.

Postoperative epidural hematomas remote from the operating field are sometimes seen as a complication after ventricle drainage, ventricle-peritoneal shunt or suboccipital craniotomy. Reported here is a very rare case of epidural hematoma which occurred on the opposite site of craniotomy after clipping surgery performed on internal carotid giant aneurysm. A 43-year-old woman was admitted to our hospital because of progressive visual disturbance in her right eye for twelve months. Precise examinations of her right eye revealed deterioration of visual acuity (0.02) right temporal-hemianopsia and an optic disc atrophy. A computed tomography scan (CT) showed a suprasellar round mass which was homogeneously well enhanced. Right carotid angiogram disclosed a large internal carotid artery aneurysm directed supramedially. The aneurysm was explored in June 1988. The neck was clipped with Sugita's ring clips through right frontotemporal craniotomy. The patient recovered fully and extubation was performed soon after the operation. Neurological examinations revealed no abnormal findings. Two days after the operation, she gradually developed impairment of consciousness and nausea. CT scan showed mass effect caused by epidural hematoma over the left temporoparietal region contralateral to the craniotomy site. Evacuation of the hematoma was carried out urgently. She had a good clinical course and postoperative angiogram demonstrated disappearance of the giant aneurysm. She was discharged and returned home without new neurological deficits. We review literature, and discuss presumptive pathogenesis responsible for such unexpected postoperative epidural hematomas.

The effect of radiation on the drug-metabolizing enzyme system of microsomes, reconstituted with liposomes of microsomal phospholipids, NADPH-cytochrome P-450 reductase and cytochrome P-450, was examined to elucidate the role of lipid peroxidation of membranes in radiation-induced damage to membrane-bound enzymes. The reconstituted system of non-irradiated enzymes with irradiated liposomes showed a low activity of hexobarbital hydroxylation, whereas irradiated enzymes combined with non-irradiated liposomes exhibited an activity equal to that of unirradiated controls. Irradiation of liposomes caused a decrease in cytochrome P-450 content by destruction of the haem of cytochrome P-450 and also inhibited the binding capacity of cytochrome P-450 for hexobarbital. The relationship between radiation-induced lipid peroxidation and membrane-bound enzymes is discussed.

Radiation-induced damage to the reconstituted system of membrane-bound enzyme, D-beta-hydroxybutyrate dehydrogenase obtained from rat liver mitochondria, was investigated in relation to the lipid peroxidation of membranes. The activity of D-beta-hydroxybutyrate dehydrogenase in fresh mitochondria was very low in general and was not affected by irradiation because of little incorporation of substrates into mitochondria. However, the enzyme activity in one-day-aged mitochondria or submitochondrial particles was five times higher than that of fresh mitochondria and decreased with increasing radiation dose accompanying the increase in peroxidation of membrane lipids. The activity of D-beta-hydroxybutyrate dehydrogenase in the reconstituted system of the purified enzyme with irradiated liver microsomes or irradiated liposomes was decreased considerably in comparison with either unirradiated control or irradiated enzyme. Therefore, the radiation-induced decrease in the enzyme activity was thought to be caused mainly by peroxidation of membrane lipids and not to be due to direct damage by radiation to the enzyme molecule itself. Irradiation of microsomes, a component of the reconstituted system, caused decreases in phosphatidylcholine and phosphatidylethanolamine content and an increase in lysophosphatidylcholine content. In addition, arachidonic acid contents in phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine were also markedly decreased with increasing radiation dose. These results are discussed in terms of a mechanism involving radiation-induced damage to membrane function and structures.