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The chemotherapy for malignant brain tumors creates two major problems to be solved viz systemic toxicity and interference by the blood brain barrier. The interstitial chemotherapy with sustained release of anticancer drugs has been widely investigated to overcome these problems. The Mitomycin C (MMC) - contained fibrin glue might be a promising candidate for use in local chemotherapy of malignant brain tumors. We investigated pharmacokinetics of the MMC-contained fibrin clot in vitro, activity of the MMC for the cultured glioma cell line, and its effect on the normal mouse brain. The MMC concentration in saline was measured up to 96 hours after the placement of fibrin glue into 5, 10 and 15 ml of saline. Then we periodically replaced the saline to keep the concentration difference of the MMC between the saline and the fibrin clot and evaluated the dissolution of the MMC for 288 hours. The potency of the MMC to suppress the rat glioma cell line was measured after being dissolved from the MMC-contained fibrin clot. The effects of the MMC-contained fibrin clot were histologically evaluated. The MMC-contained fibrin glue, the MMC solution and the fibrin glue were separately injected into the mouse brains. Mice were sacrificed 24, 72, 168 and 336 hours after the injection and brains were examined with photomicroscopy. The MMC was released into the saline rapidly within 24 hours then gradually released until 96 hours had elapsed. Total amounts of the dissolved MMC were proportional to the amounts in the saline.(ABSTRACT TRUNCATED AT 250 WORDS)

The pathophysiology and treatment of malignant brain tumors (malignant glioma, metastatic brain tumor and malignant lymphoma) were discussed. In order to improve the prognosis of malignant brain tumor patients, many clinical trials have been conducted. The most acceptable treatment for malignant glioma is surgical resection plus radiochemotherapy with ACNU. A multidisciplinary approach to treatment is important for control of metastatic brain tumors. Treatment of malignant lymphoma includes radiotherapy and chemotherapy in combination. Combination chemotherapy with CHOP is more effective for malignant lymphoma.

✓ The question of whether unruptured intracranial vertebral artery dissections should be treated surgically or nonsurgically still remains unresolved. In this study, six consecutive patients with intracranial vertebral artery dissection presenting with brain-stem ischemia without subarachnoid hemorrhage (SAH) were treated nonsurgically with control of blood pressure and bed rest, and five received follow-up review with serial angiography. No further progression of dissection or associated SAH occurred in any of the cases, and all patients returned to their previous lifestyles. In the serial angiograms in five patients, the findings continued to change during the first few months after onset. Four cases ultimately showed “angiographic cure,” while fusiform aneurysmal dilatation of the affected vessel persisted in one case. In one patient, arterial dissection was visualized on the second angiogram despite negative initial angiographic findings. These results indicate that intracranial vertebral artery dissection presenting without SAH can be treated nonsurgically, with careful angiographic follow-up monitoring. Persistent aneurysmal dilatation as a sequela of arterial dissection seemed to form a subgroup of fusiform aneurysms of the posterior circulation. These aneurysms may be prone to late bleeding and may require surgical treatment.

Proliferation of LNCaP 104-S cells, a clonal subline of the human prostate cancer cell line, was very slow in androgen-depleted medium but increased 10-13-fold in the presence of 0.1 nM of a synthetic androgen, R1881. This induction of proliferation was diminished at higher concentrations of R1881, indicating the biphasic nature of the androgen effect. After 20-30 passages in androgen-depleted medium, these cells progressed to 104-I cells, which exhibited much lower proliferative sensitivity to 0.1 nM R1881. After another 20-30 passages, LNCaP 104-I cells gave rise to 104-R cells, which proliferated rapidly without additional androgen. Proliferation of 104-R cells was induced 2-fold by 0.01 nM R1881 but was repressed by 0.1 nM R1881 and above. Thus, androgen induction and repression of proliferation could be seen at lower concentrations of androgen as the cells progressed. During the transition of 104-S cells to 104-R cells, the androgen receptor mRNA level increased 2.5-fold whereas the androgen receptor protein level increased 15-fold in the absence of androgen. Androgen receptor transcriptional activity, measured by androgen induction of prostate-specific antigen mRNA and chloramphenicol acetyltransferase activity in transfected cells, increased up to 20-fold during the progression. LNCaP cells, therefore, appear to be able to adapt to reduced androgen availability by increasing their sensitivity to androgen, raising questions concerning the therapeutic strategies used against prostate cancer. Androgen induction of c-myc expression in 104-R cells occurred at a 10-fold lower concentration (0.01 nM) than in 104-S cells (0.1 nM). In all stages, cell proliferation and c-myc expression were repressed by androgen at a high concentration (20 nM), but the repression of cell proliferation was blocked by retroviral overexpression of c-myc.

Effects of treatment in vivo and in vitro with lipopolysaccharide (LPS) on the responsiveness of rat thoracic aorta were examined. The endothelium-denuded aortic strips isolated 6 hr after intraperitoneal (i.p.) administration of LPS (20 mg/kg), which could produce hemodynamic changes, relaxed in response to L-arginine. The same amplitude of relaxation was produced by L-arginine in the aortic strips incubated with a lower dose of LPS (1 microgram/ml) in vitro for 6 hr. Both relaxing responses were inhibited by NG-nitro-L-arginine (L-NOARG). The contractile responses to phenylephrine and KCl were reduced by LPS treatment in vivo or in vitro, but the extent of inhibition was greater in vivo than in vitro. Further, the attenuation of contractile responses was completely reversed by L-NOARG in the strips treated in vitro, whereas the reversal by L-NOARG was incomplete in the strips treated with LPS in vivo. Endothelium-dependent relaxation induced by acetylcholine was attenuated by LPS in vivo but not in vitro. These results suggest that the hyporesponsiveness of rat thoracic aorta after treatment in vitro with LPS, which can produce hemodynamic changes, may be related to an enhanced NO production in the smooth muscle cells, while not only the NO pathway but also additional factors may be involved in the vascular hyporesponsiveness of the sepsis rats.

For minimal invasive endoscopic neurosurgery, a mini-caliber endoscope equipped with a useful working channel and its guidance system is basically essential. We developed the device for ultrasound guided endoscopic neurosurgery. A minicaliber fiberscope with an outer diameter of 3.4 mm equipped with 2.5 mm of working channel for forceps, suction, and coagulation probe was developed. A 5 MHz phase arrayed 12 mm ultrasound probe was used as guidance system. A fixation device for the mini-caliber fiberscope and ultrasound probe was also constructed. The surgical procedure is very simple, and can be performed through a 2 cm burr hole. Real-time and a directly visualized image might provide more safety and reliability during brain surgery.

The authors report a case of an intracavernous internal carotid artery aneurysm associated with a persistent trigeminal artery variant (PTAV). A 47-year-old-woman developed a subarachnoid hemorrhage due to the rupture of aneurysm and underwent direct clipping operation. PTAV is basically an anomalous anastomosis between the internal carotid artery and the anterior inferior cerebellar artery. In this patient, the PTAV originated from the C4 portion of the right internal carotid artery and distributed in the territory of the hemispheric branch of the posterior inferior cerebellar artery. There have been only three reported cases of the internal carotid artery aneurysms arising from the crotch of PTAV. It is also unusual that rupture of such a small aneurysm in the cavernous sinus causes subarachnoid hemorrhage. Embryological development of PTAV and possible mechanism of subarachnoid hemorrhage from the intracavernous aneurysm are discussed.

Red blood cell (RBC) deformability is necessary for maintenance of normal oxygenation in microcirculation. To evaluate oxygen utilization in the early stage of endotoxin shock, we observed RBCs from a rheological point of view in mesenteric microcirculation in rats. Endotoxin shock was induced by Shwaltzman reaction. The velocity of RBC decreased from 1.33 mm.sec-1 to 0.55 mm.sec-1 at 60 min after the provoking injection. RBC could not change its shape in capillaries. In contrast, the mean blood pressure remained at 110 mmHg throughout this observation. In hemorrhagic shock the deformability of RBC in capillaries was not impaired even though mean blood pressure decreased to 43 mmHg. In vitro, we examined the index of RBC deformability with or without endotoxin by the modified Reid's method. The index was decreased significantly by endotoxin. We conclude that impaired deformability of RBC may be a factor of insufficient oxygen utilization in the early stage of endotoxin shock.

This report describes the clinico-pathological features of a group of 36 patients with malignant lymphoma of the central nervous system (CNS) who were treated at one institution between 1970 and 1993. All cases were B cell type lymphomas. The authors summarize the most salient findings with respect to clinical course, pathology, treatment and disease outcome, and emphasize the value of diagnostic and therapeutic modalities in the management of patients with primary CNS lymphoma.

Effect of intermittent intrathecal injection of rtPA(TD-2061) on subarachnoid clot lysis and angiographic vasospasm was evaluated in canine double SAH model. Animals were divided into 5 groups; SAH control dogs, SAH dogs treated with physiological saline, SAH dogs treated with vehicle, SAH dogs treated with rtPA(5kIU/0.5 ml/kg), and SAH dogs treated with rtPA(25kIU/0.5m1/kg). Measurement of tPA activities in CSF following the intracisternal injection of rtPA revealed that thrombolytic activities of rtPA lasted for about 2 h after the injection. In SAH dogs treated with 25kIU/kg of rtPA, the amount or residual subarachnoid clot on Day 7 was significantly less than in SAH control dogs. Intracisternal injection of either 5kIU/kg or 25 kIU/kg of rtPA reduced the degree of vasospasm significantly. These results indicated that four times intermittent infusion of 5–25kIU/kg of rtPA into the cisterna magna was effective in reducing the severity of vasospasm.

The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with the dominant white-spotting (W) locus of the mouse. In this study we investigated the expression of human c-kit protein in various adult and fetal human tissues immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate c-kit+ cells from mast cells expressing c-kit, mast cells were identified by staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult uterus, c-kit+ cells were widely distributed in the basal layer of the endometrium, myometrium and cervix, the number and distribution being almost identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells clustered beneath the epithelium and a few mast cells were observed in the myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells were detected within smooth muscle layers of the intestine, colon and oesophagus, while mast cells were observed in the mucosal and submucosal layers of these organs. In contrast to mice, no expression of c-kit protein was detected in the human placenta and decidua. Thus, the distribution of c-kit+ cells in various tissues is similar but not identical between adult and fetus and between human and mouse.

We raised a murine monoclonal antibody, OG-3, which reacts with human granulosa cells. Immunohistologically, OG-3 antigen was weakly expressed on the granulosa cells of some growing and atretic follicles, but not on those of preovulatory follicles. After ovulation, the antigen expression rapidly increased on granulosa cells during corpus luteum formation. The antigen expression on granulosa/large luteal cells decreased in the mid-luteal phase, but increased again in the late luteal phase. In early pregnancy, OG-3 antigen expression on large luteal cells increased after 7 wk of gestation. The OG-3 antigen distribution in various organs resembled that of human leukocyte antigen (HLA) class II molecules. An HLA-class II-positive human B cell line (AKIBA) and a murine L-cell transfectant expressing HLA-DR antigen were positive for OG-3 antigen, whereas an HLA-class II-negative human T-cell line and L-cell transfectants expressing HLA-DP and DQ antigens were negative. The molecular mass of OG-3 antigen purified from AKIBA cells was 32-35 kDa. The staining profiles in ovaries with anti-HLA-DR or anti-HLA-class II antibodies were similar to that with OG-3. These results indicate that OG-3 antigen is identical to HLA-DR, and that HLA-DR is a differentiation antigen for human granulosa cells.

Giant aneurysm arising from the distal segment of the anterior cerebral circulation is extremely rare, and only 14 cases of anterior cerebral circulation aneurysms have been reported in the literature. This report describes two cases of giant intracranial aneurysms, one arising from the distal segment of the middle cerebral artery, and the other from the azygos anterior cerebral artery. Although both of the patients started with intracranial hemorrhage, their surgical outcomes were good. The growth mechanisms of each aneurysm are discussed based on the clinical and pathological findings. Since the wall of the middle cerebral artery aneurysm showed granulomatous changes with infiltration of many inflammatory cells, the aneurysmal enlargement is considered to have resulted from chronic inflammation of the wall. In the case of anterior cerebral artery aneurysm, hemodynamic stress through the azygos artery may have caused the giant aneurysm. Operative indication for giant intracranial aneurysm is controversial. Since the surgical outcomes of reported cases are definitely better than those of the patients with proximal giant aneurysm, we conclude that giant aneurysm arising from the distal segment of the cerebral artery should be treated surgically.

The reactions of the mesenteric microcirculation dynamics to prostaglandin E1(PGE1) and nicardipine were investigated under continuous biomicroscopy with a high speed video analyzer in septic shock models using rats. Both of the drugs induced similar reactions. In the hyperdynamic state, the vasodilation and increasing velocity of red blood cells (RBC) stimulated by both of these vasodilators were similar to those in normal control state. However, in the hypodynamic state the vasodilators especially PGE1 had little effect on increasing the velocity of RBC in spite of their vasodilating action. Therefore these vasodilators are useful in order to improve the microcirculatory blood flow in states such as early septic-shock state.

The purpose of this study is to present the histological characteristics of tumor origin and proliferative characteristics of craniopharyngioma. In 25 craniopharyngiomas, the immunoperoxidase technique revealed strong positive reactions for keratin and cytokeratin in cytoplasm of tumor cells. But, immunostaining of keratin and cytokeratin differ from each of layer of craniopharyngioma. The ciliated epithelium in the craniopharyngioma was not stained by keratin, but ciliated epithelium of Rathke's cleft cyst was stained by cytokeratin.

We studied the protective effect of prostaglandin E1 (PGE1)-induced hypotensive anesthesia on gastric mucosa in 30 elective surgical patients. Three groups, each composed of 10 patients, received PGE1, nitroglycerin or none during general anesthesia. Then we measured the viscosity and pH of gastric fluid continuously in each group. In the PGE1 group the viscosity and pH increased significantly and rapidly (P less than 0.05) as compared with the other groups. This suggests that PGE1 offers prophylactic effect against postoperative acute gastric mucosal lesion (AGML).

A 42-year-old man suffered from numbness in his right leg in May, 1989, and was admitted to another hospital for examination. Computed tomography and magnetic resonance imaging revealed thoracic intramedullary tumor and multiple intracranial tumors in the right frontal convexity, the right lower surface of the tentorium and the right parietal parasagittal region. In December, he underwent craniotomy and the right frontal tumor was totally removed. It was diagnosed histologically as meningioma. Because of continuing numbness in his right leg, he visited a neurologist at our university and was referred to us for removal of the spinal tumor on April 25, 1990. Neurological examination on admission revealed mild weakness of his right leg and exaggerated right knee jerk. Though he complained of numbness in his right leg, no sensory disturbance was demonstrated objectively. His bladder-bowel function was normal. There were no café au lait spots or subcutaneous neurofibromas. He and his mother were positive for anti-HTLV-1 (human T-lymphotrophic virus type 1) antibody. On May 1, laminectomy was performed at Th-7 to Th-9, and a yellowish brown tumor was found occupying the right posterolateral portion of the cord and extending to the surface. The dorsal root of Th-9, which was involved in the tumor, was cut and the tumor was subtotally removed. Histological examination showed interlacing bundles of spindle cells and loose areolar region. Immunohistochemically, the tumor was positive for S-100 protein and negative for GFAP. From these findings, the tumor was diagnosed as neurinoma. The postoperative course was uneventful, numbness disappeared, and the patient was discharged without neurological deficits.

The effect of ulinastatin on postischemic brain edema was investigated in adult mongrel cats. Focal brain ischemia was produced by occlusion of the left middle cerebral artery (MCA) through the transorbital approach. Following two hours of occlusion, the brain was reperfused for two hours. In all seven animals of the ulinastatin-treated group, ulinastatin was administered intravenously at a dose of 50000 U/kg before and after occlusion. In the control group, six animals were given only vehicle. Measurements of regional cerebral blood flow (rCBF) were performed before MCA occlusion by the hydrogen clearance method, and then repeated every 30 minutes during and after occlusion. Following two-hour reperfusion, the animals were sacrificed by intravenous KCl injection. Specific gravity of the cortex, where rCBF was measured, was determined by microgravimetric method. In the analysis of specific gravity of the cortex, in which mean rCBF during ischemia was above 15ml/100g/min, no significant difference was found between the ulinastatin-treated and control groups. In the specimen with mean rCBF below 15ml/100g/min during ischemia, cortical specific gravity was reduced remarkably in the control group, while not decreased in the ulinastatin-treated group. The difference was statistically significant between two groups (p less than 0.001). These findings suggest antiedema effect of ulinastatin.

Chondroblastoma of the skull is a rare tumor and only 54 cases have been reported to date. A case of chondroblastoma arising from the squamous part of the left temporal bone is reported. A 34-year-old woman had 6-month history of left conductive hearing disturbance and tenderness in the left temporal region. Plain skull X-ray showed a well demarcated osteolytic lesion in the temporal bone. CT demonstrated a heterogeneously high density mass, with enhancement. T1-weighted MRI showed a low intensity mass while T2-weighted images showed no signal area. The left external carotid angiograms showed a marked staining supplied by the left middle meningeal artery. This tumor grew destroying the left temporal squama and pyramidal bone, and extended to the external auditory canal and the middle ear cavity. The tumor was subtotally resected. Histologically, this tumor consisted of clusters of round or polygonal chondroblasts with oval or grooved nuclei and well-defined cell border. Multinucleated giant cells were also observed. Chondroid matrix was found in some areas. Immunohistochemically, the tumor cells were positive for S-100 protein. These findings lead us to the diagnosis of chondroblastoma. The diagnosis, histology, therapy, and prognosis of chondroblastoma are discussed including the review of 54 cases in the literature.

When an aqueous solution of plasmid DNA at a constant low concentration of 5 micrograms/cm3 was irradiated with 60Co gamma-rays, D37 dose of single-strand breaks was decreased from 18 Gy at a dose-rate of 6.77 Gy/h of acute irradiation to 2.3 Gy at a dose-rate of 0.00212 Gy/h. Or G value was increased from 0.0010 to 0.0081. Similar dose-rate dependency of D37 dose and G value were also found when the plasmid DNA solution was treated with various concentrations of tritiated water at various dose-rates, ranging from 5.13 Gy/h to 0.000118 Gy/h. RBE of tritium beta-rays for single-strand breaks was ranged from 0.3 to 0.5 in a wide range of dose-rates. When the DNA solution was saturated with argon to remove oxygen, the dose-rate dependency of gamma-rays was abolished and that of tritium beta-rays was significantly suppressed. When the DNA solution in air was kept at 4 degrees C for 50 h or 25 days after acute irradiation, the G value of DNA breaks was the same as that kept at -20 degrees C for the same period, but much lower than that of the solution irradiated for the same period at a lower dose-rate to give the same total doses. This shows that the inverse dose-rate effect could not be induced from the different exposure periods but from continuous irradiation of different dose-rates. The inverse dose-rate effect for inactivation of transforming activity of DNA irradiated with tritiated water was also observed in the range from 0.0588 Gy/h to 0.00118 Gy/h.

It has been proposed that angiogenesis inhibitors should be used for the treatment of diseases accompanied by an uncontrolled angiogenic response, particularly such disease occurring during progressive growth of solid tumors. In this study, the antiangiogenic effect of dexamethasone (DEX) was studied in a system using chorioallantoic membranes (CAM) of fertilized eggs and rabbit corneas. First, DEX was examined for its effect on embryonic angiogenesis using 4, 5 day old CAMs of chick embryos. After the shell and shell membrane was removed, an EV pellet with or without DEX was placed within a silicon ring. Two days later, the antiangiogenic response was evaluated by measuring the avascular zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm or more in diameter, the response was scored as positive. DEX showed potent antiangiogenic activity and produced an avascular zone in 100% of CAMs at the highest dose tested. (250 ng/egg). Next, inhibitory effect of vascularization and tumor growth by local implant of DEX was observed in a rabbit cornea assay. An intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1-mm3 piece of glioma. In the treatment group, DEX-containing EV pellet was inserted between the limbus and glioma. Ten days after the implantation of glioma and EV pellet, vascular response and tumor growth was evaluated. For morphologic studies, the excised corneas were fixed with formaldehyde fixative and sectioned for light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Tungsten local transport in the diverter region emitted from the outer divertor was studied in JT-60U. Tungsten-coated CFC tiles were installed in the outer divertor position, on which outer strike points did not normally sit. A neutron activation method to measure tungsten surface density was used for the first time. On the outer wing tile, W existed only in the top surface, while on the inner divertor tile W was embedded in the thick carbon deposition layer. Poloidal distribution in the same toroidal section as the tungsten tiles showed dense W deposition near the inner strike points, the dome top and outer wing of the dome. Carbon ions by puffing 13CH4 at the same toroidal position of the W-tiles were also deposited near the inner strike points. Toroidal distribution on the outer wing showed significant localization of W deposition near the W tile array. In addition, toroidal asymmetry of W deposition on the outer wing probably due to the plasma parallel flow was observed.

Interleukin-1 (IL-1), a critical cytokine for the initiation of the immune response to infection or antigenic challenge, is known to also possess a variety of biological functions outside the immune system. We examined whether IL-1 could affect the decidualization of human endometrial stromal cells (ESC), a conspicuous part in the process of implantation, by assessing PRL production and morphological transformation in an in vitro system. Purified human ESC were cultured in the presence of progesterone (P) with or without the addition of IL-1. IL-1 markedly suppressed the induction of PRL production by P in a dose-dependent manner. The morphological decidualization of ESC in response to P was also inhibited by IL-1. This report demonstrates for the first time the possibility that IL-1 blocks decidualization, the functional differentiation of human endometrial stromal cells in response to ovarian steroids.

We report the results of a clinical trial of Magnetoencephalography (MEG) on spike foci in patients with epilepsy, which was performed from December 1990 to June 1991 at The University of Tokyo Hospital. Fifty patients with focal epilepsy; 26 primary epilepsy, 24 secondary epilepsy (7 brain tumor, 4 arteriovenous malformation, 4 encephalitis, 3 porencephaly, 2 arachnoid cyst, 1 brain abscess, 1 hemimegaloencephaly, 1 Lance-Adams syndrome, 1 hygroma), and ten normal subjects were enrolled in this study. MEG data were recorded using a 37-channel biomagnetometer system SMI-1001 (BTi Magnes, Biomagnetic Technologies, Inc., San Diego). A simultaneous 19-channel EEG recording with linked-ear reference was also obtained. The overall study was completed safely and none of the normal subjects showed abnormal paroxysmal MEG activity. Two patients showed interictal EEG spikes which would not have been noticed without first noting the presence of corresponding prominent MEG spikes. On the whole, the MEG signal seemed to have a wider frequency bandwidth than EEG. In most cases, the source localization predicted by MEG corresponded well with the EEG findings. The relative accuracy of MEG spike source localization was estimated to be within a cubic centimeter from the cases which showed tightly clustered localization of individual spikes. High-pass filtering reduced interference by superimposed slow wave activity, thereby improving the localization of spike sources. These results demonstrate that 37-channel biomagnetometer system could be a useful tool for analyzing epileptic spike sources.

The magnetoencephalography (MEG) and electroencephalography (EEG) were recorded simultaneously from 10 normal subjects using a 37-channel biomagnetometer. No paroxysmal spikelike waveform was observed in MEG at rest with eyes closed. The MEG and EEG were recorded also from 16 patients with primary epilepsy and 24 patients with secondary epilepsy. The examination proved to be safe for both normal subjects and patients with epilepsy. Interictal spikes were observed in 27 cases during the examination. The percentage of spikes identified in MEG but not in EEG was found to be 2. 3% of all spikes. The foci of the spikes identified in MEG were localized and determined in 20 cases. In 10 patients with secondary epilepsy, the localization of the foci were compared with the lesion demonstrated by magnetic resonance imaging (MRI) or computerized tomography (CT) and with the findings of EEG. In 6 cases, the foci by MEG were consistent. In the 4 cases where the MEG foci did not correspond to the MRI or CT findings, MEG foci were supported by the findings of EEG. MEG allows three-dimensional localization and enables us to elucidate the propagation of paroxysms. MEG was very useful in diagnosing epilepsy.

Whole tissue grafts of day 1 neonatal or day 21 embryonic suprachiasmatic nuclei (SCN) in rats transplanted into host's third ventricle restored circadian rhythmicity in 8 cases out of 18 SCN-lesioned arrhythmic rats. Restored circadian rhythmicity had been observed for maximum 14 months after the transplantation. Immunohistochemical staining (Vasoactive intestinal polypeptide: VIP and vasopressin) confirmed the survival of the transplanted SCN tissues within the host's third ventricle. This may be the case of the longest-term survival of functioning SCN grafts which connected with the host's brain by neurites after transplantation. This finding may be a promising support for clinical application of neural tissue transplantation. In contrast, rhodamine-labeled SCN cell suspension transplanted into host's third ventricle did not restore circadian rhythmicity in 24 cases. Histological analysis revealed aggregated donor cells attached to the third ventricle and immunocytochemically stained with both VIP and vasopressin. Furthermore, rhodamine within the host brain suggested the fiber connections between the host and the donor cells. This result indicated that the circadian oscillator in SCN may function only based on the structural integrity of the SCN.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and was shown to be allelic with the white-spotting locus (W) of the mouse. Mutations at the W locus have pleiotropic effects on the development of hematopoietic stem cells, melanoblasts, and primordial germ cells. In order to elucidate the role of c-kit protein in gametogenesis and oocyte maturation, we have examined immunohistochemically the expression of c-kit in the ovaries of mice at late fetal and postnatal stages, and in early embryos. By the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody, the c-kit protein was detected in ovaries after the time of birth, but not before. The expression of c-kit was observed mainly on the surface of oocytes, but not in granulosa cells nor in interstitial regions. Oocytes of primordial to fully grown Graafian follicles showed the c-kit protein. When ovulation was induced by hCG, the expression of c-kit in ovulated unfertilized oocytes was weaker than in oocytes of Graafian follicles. In 1-cell embryos the c-kit protein was still observed, but with cell division its expression further decreased, and it was not detected in embryos of 4-cell, 8-cell, and morula stages. In summary, the highest expression of c-kit was observed on the surface of oocytes arrested in the diplotene stage of meiotic prophase. With ovulation and the resumption of meiotic maturation, its expression declined. These results suggest that the c-kit protein may play some role in meiotic arrest, oocyte growth, and oocyte maturation.

Twelve infants with choroid plexus tumors were reviewed retrospectively. Enlarging head circumference, bulging fontanelle, and vomiting were the major symptoms and signs appearing 2 to 5 weeks (mean = 3.7 weeks) before diagnosis. The average age at diagnosis was 7.7 months. Total removal was performed in 11 patients with choroid plexus papilloma, and partial removal was achieved in 1 patient with a choroid plexus carcinoma. A cerebrospinal fluid (CSF) diversionary shunt was placed temporarily in 6 infants and permanently in 4. Of the two patients not requiring CSF diversionary shunt, 1 needed a subdural-peritoneal shunt postoperatively. Histologically, 11 of 12 tumors were choroid plexus papillomas, and one was a choroid plexus carcinoma. All 12 patients were followed up for 4 months to 11 years (mean = 5.6 years). Eleven of 12 patients were alive at the time of their last check-up. All 11 survivors had normal psychomotor and neurological development. The treatment and outcome of choroid plexus tumors and management of associated hydrocephalus are discussed.

Pituitary microadenomas can be properly diagnosed by magnetic resonance imaging (MRI) and endocrinological examinations. MRI can well demonstrate the three-dimensional morphological structure of microadenomas. The resolution of MRI is much better than X-ray computed tomography (CT). In this study, MRI of surgically verified microadenomas is analyzed. The localization and size of the tumor upon MRI correlated well with surgical findings. Although gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA) enhances the tumor and demonstrates well the whole figure of the tumor, the fine intratumoral structures such as hemorrhage or necrosis can better be visualized by T1- and T2-weighted images without Gd-DTPA enhancement. The MRI of other lesions such as Rathke’s cyst or internal carotid artery aneurysm are presented for the differential diagnosis.

In a prospective, controlled, randomized trial measuring the gastric juice pH and viscosity, 30 patients under general anesthesia received M1-blocker; pirenzepine or H2-blocker; ranitidine. The gastric juice pH value was significantly higher (P less than 0.05) both in the pirenzepine and the ranitidine group than in the control group. While in the pirenzepine group the viscosity of gastric juice was unchanged, in the ranitidine group it was reduced. The results suggest that pirenzepine offers more effective prophylaxis against stress ulcer than ranitidine.

Effects of interleukin-1 (IL-1) on FSH-induced differentiation of immature porcine granulosa cells in vitro were examined in short-term (48-h) cultures. IL-1 inhibited FSH induction of aromatase activity and of LH-stimulated cAMP accumulation by granulosa cells. Both these inhibitory actions of IL-1 were concentration-dependent. Significant inhibitory effects were observed with as low as 0.05-0.25 ng/ml of IL-1, with maximal effects at 25 ng/ml. IL-1 also significantly inhibited increases in [125I]iodo-LH binding and progesterone secretion induced by FSH, as well as reducing basal levels of aromatase activity and LH-stimulated cAMP accumulation. Studies on the mechanisms of IL-1 actions on FSH-induced differentiation of immature porcine granulosa cells revealed that IL-1 reduced cAMP accumulation by the cells in response to FSH in a time- and concentration-dependent manner. IL-1 also inhibited induction of aromatase activity and LH-stimulated cAMP accumulation induced by dibutyryl cAMP, suggesting that IL-1 also affects the steps distal to cAMP generation. In contrast, IL-1 had no effect on progesterone secretion induced by dibutyryl cAMP, suggesting that post-cAMP steps of progesterone secretion were unaffected by IL-1.

The effects of dilazep dihydrochloride on angiographic vasospasm and regional cerebral blood flow after subarachnoid hemorrhage were evaluated in double hemorrhage canine model. Severe angiographic vasospasm of basilar artery (percent reduction of intra-luminal diameter; 52.4%) was shown in untreated dogs. Daily intra-venous administration of dilazep (0.3 mg/kg for one hour) significantly inhibited angiographic vasospasm (percent reduction of intra-luminal diameter; 33.2%, p less than 0.05). Dilazep had a marked vasodilatory effect even in severe vasospasm in untreated dogs, and had a tendency to increase cerebral blood flow of the cerebral cortex in spite of reduced blood pressure. From these characteristics of action, intra-venous administration of dilazep would be useful agent for the treatment of cerebral vasospasm after subarachnoid hemorrhage.

In treating brain tumors with chemotherapy, the choice of drug is most important since human tumors have different drug sensitivities and growth rates. We have been studying the therapeutic effect of anticancer drugs against malignant brain tumors in the following in vivo models. 1) Human glioma-bearing nude mice. 2) Methylcholantrene-induced 203Gl mouse glioma-bearing immunocompetent C57BL/6 mice. 3) Human gliomas transplanted into the chorioallantoic membrane of chick embryos. We evaluated the advantages of each model for anti-cancer drug sensitivity tests. 1) Human glioma-bearing nude mice were found to be most useful in predicting the direct effects of anticancer drugs. We evaluated the effects of several drugs such as ACNU or interferons in six glioma strains transplanted into nude mice. 2) Immunocompetent C57BL/6 mice models were found useful in predicting the therapeutic effects of biological response modifiers. In this model, we can also evaluate changes in immunological parameters such as NK activities or T cell subsets. 3) In the drug sensitivity test using the CAM of chick embryos, various kinds of gliomas could be grafted with a high rate of success. The tumor reduction rate of the sensitivity test using this system tended to agree with that using nude mice. This test was found to be useful in predicting the effect of drugs against gliomas directly resected from individual patients.

The authors report a case of partially thrombosed giant aneurysm which was secondarily infected with purulent meningitis. The relationship between the infection of the aneurysm, the rapid growth of the aneurysm and the development of severe cerebral edema was discussed. A 53 year-old man was admitted on September 1, 1986, with a diagnosis of bacterial meningitis. On his admission, his body temperature was 39 degrees C, and he showed mental confusion but no neurological deficits. Laboratory data revealed signs of infection in white blood cell count, CRP, and erythrocyte sedimentation rate. Computerized tomographic (CT) scan and magnetic resonance (MR) imaging showed a massive round mass with perifocal edema measuring 40mm in the maximum diameter in the left paramedian frontal region. T1 weighted MR image also showed the presence of pus accumulation in the left ventricle. Cerebral angiography demonstrated a giant aneurysm at the distal portion of the azygos anterior cerebral artery, and irregular narrowing of both the supraclinoid segment of the carotid artery and its main branches indicating arteritis due to purulent meningitis. The patient was treated with ventricular drainage and administration of antibiotics. Culture of the purulent CSF was negative. The patient's lab data, CSF finding and neurological status improved progressively. However, follow-up CT scan and angiogram a month later showed enlargement of the aneurysm, dilatation of the patent lumen and perifocal edema. On October 8, the patient suddenly became comatose with anisocoria. A CT scan showed massive edema with marked midline shift. Emergency bifrontal craniotomy was carried out, and clipping was completed after removal of the thrombosed portion of the aneurysm, and thromboendarterectomy of the aneurysmal neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical localization of prostaglandin (PG) F2 alpha synthesized during recirculation following experimental forebrain ischemia was studied in Mongolian gerbils. The bilateral carotid arteries were clamped for 5 minutes, and the brains were frozen in situ after 5 minutes of recirculation. Sham-operated gerbils not subjected to arterial occlusion served as controls. Cryostat sections containing dorsal hippocampus 10 microns in thickness were incubated in rabbit anti-PGF2 alpha serum and stained with avidin-biotin-peroxidase complex after fixation in carbodi-imide and Zamboni's solution. In specimens from control animals, blood vessels were faintly stained with anti-PGF2 alpha serum, while neurons and glial cells were less intensely stained or unstained. Specimens from reperfused gerbils demonstrated strongly positive staining for PGF2 alpha in blood vessels, neurons (especially hippocampal pyramidal neurons), and glial cells. Staining for PGF2 alpha in the reperfused animals was substantially diminished by pretreatment with indomethacin (10 mg/kg, i.p.). The results indicate that recirculation after forebrain ischemia results in an increase in PGF2 alpha in neurons, glial cells, and blood vessels.

Using a transorbital middle cerebral artery (MCA) occlusion model in cats, we evaluated the anti-oedema effects of a new anti-inflammatory agent, ebselen (PZ51), on ischaemic cortical oedema caused by prolonged ischaemia and recirculation. Local cerebral blood flow was measured by the hydrogen clearance method in the MCA territory and the corresponding cortical specific gravity was assessed by a microgravimetric technique. Ebselen had no significant effect on normal and ischaemic lCBF, while it significantly ameliorated post-ischaemic hypoperfusion following recirculation. In the severely ischaemic regions, microgravimetry showed the beneficial effects on the ischaemic oedema caused by prolonged ischaemia and recirculation as well. Although the exact site of action is undetermined in this study, the observed effects of ebselen may be ascribed to this agent's broad-spectrum of anti-inflammatory activities.