[Decompressive craniectomy for massive infarction of middle cerebral artery territory].

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.

Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells.

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.

Rescue of lethally irradiated mice from hematopoietic death by pre-exposure to 0.5 Gy X rays without recovery from peripheral blood cell depletion and its modification by OK432.

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.

Improvement of phase-contrast flow measurements: opposite directional flow-encoding technique to eliminate the influence of the Maxwell term phase errors.

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.

Adaptive response in embryogenesis. III. Relationship to radiation-induced apoptosis and Trp53 gene status.

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.

The dependence of p53 on the radiation enhancement of thermosensitivity at different let.

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.

WAF1 accumulation by carbon-ion beam and alpha-particle irradiation in human glioblastoma cultured cells.

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.

Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma.

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.

Induction of radical scavenging ability and protection against radiation-induced damage to microsomal membranes following low-dose irradiation.

PURPOSE: To investigate changes in rat liver cytosolic radical scavenging ability and in microsomal membrane function following low doses of radiation. MATERIALS AND METHODS: Wistar rats were irradiated with 1-50 cGy of X-rays and liver cytosolic radical scavenging ability was determined using DPPH, a stable free radical. Liver microsomal drug metabolizing activity was determined using hexobarbital as a substrate. Cytosolic antioxidants and microsomal enzymes were spectrophotometrically determined. RESULTS: Irradiation of rats at around 5-10 cGy induced liver cytosolic radical scavenging ability and a considerable increase in this ability at 5 cGy was observed for 3 days after irradiation. Glutathione reductase was suggested as a candidate of cytosolic antioxidants. Radiation-induced damage to liver microsomal drug metabolizing enzyme activity was suppressed by preirradiation with 5 cGy, mainly by protecting cytochrome P-450. CONCLUSIONS: Low doses of radiation increased cytosolic radical scavenging ability and resulted in protection of microsomal membrane function which is easily damaged by radiation-induced free radicals.

Mechanism of radiation-induced diacylglycerol production in primary cultured rat hepatocytes.

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.

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

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.

Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction of prenatal death and congenital malformation during the late period of organogenesis.

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.

Hyperthermic enhancement of tumour growth inhibition by accelerated carbon-ions in transplantable human esophageal cancer.

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.

Effects of accelerated carbon-ions on growth inhibition of transplantable human esophageal cancer in nude mice.

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.

Radiation-induced translocation of protein kinase C through membrane lipid peroxidation in primary cultured rat hepatocytes.

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.

Surface anatomy scanning (SAS) in intracranial tumours: comparison with surgical findings.

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.

Intracerebral arteriovenous malformation fed by the anterior ethmoidal artery--case report.

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.

[A case of epidural hematoma occurring on the opposite site of craniotomy after clipping surgery performed on internal carotid giant aneurysm].

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.

[A case report of advanced malignant mixed germ cell tumor of parasellar origin indicating marked efficacy of a salvage combined chemotherapy of CDDP and etoposide and subsequent chemotherapy using oral etoposide].

A case of a 13-year-old boy with malignant mixed germ cell tumor of parasellar origin was reported. After partial removal of the tumor, combined chemotherapy (using cisplatin, vinblastine and bleomycin: PVB therapy) and irradiation were performed, and the tumor was reduced to under one tenth. In spite of PVB maintenance chemotherapy, it became refractory later. The patient was then treated with both CDDP 20 mg/m2 daily for 5 days and etoposide 100 mg/m2 for 1, 3, 5 days. After this one course, the tumor was diminished. Oral etoposide was administered at our outpatient department, and the boy was free of disease for six months.