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Object. The purpose of this study was the analysis of a large series of patients treated with gamma knife radiosurgery for pituitary adenoma in a single institution. Methods. One hundred eight patients with pituitary adenomas were treated over the last 7 years. Seventy-four patients have been followed for more than 6 months and form the basis of this report. Conclusions. Twenty-three patients harbored nonfunctioning adenomas, and 56 harbored functioning adenomas. The mean margin dose was 22.5 Gy (nonfunctioning adenomas, 19.5 Gy; functioning adenomas, 23.8 Gy). Control of tumor growth was achieved in 91%. A significant decrease of excessive hormone production was seen in 80% of patients, and the endocrinological normalization rate was 30.3%. Postradiosurgical complications were seen in 2.5%.

We previously reported that the coagulation system in cerebrospinal fluid (CSF) is strongly activated in the early stage of a subarachnoid haemorrhage (SAH). We evaluated the relationship among thrombin activity, degree of SAH, amount of clearance of SAH, and vasospasm. The CSF levels of fibrinopeptide A (FPA) were measured by radio-immunoassay in 36 SAH patients, who were diagnosed by computerized tomography (CT) within 12 hours and on whom surgery was performed within 48 hours. Clearance of SAH (%) was evaluated as the size of the clot in the basal cistern visualized between the initial and postoperative CT. The mean level of FPA in the patients of Group 3 (Fisher's CT classification) (182.2 ng/ml) was significantly higher than those in the patients of Group 2 (36.2 ng/ml). There was a significant difference in the mean level of FPA between patients with (47.6 ng/ml) and without infarction (408.3 ng/ml). In 18 of the 27 patients of Group 3 for whom the clearance of the SAH was determined, the patients showing a lower clearance rate (50%) of SAH demonstrated a significantly higher rate of infarction and a significantly higher level of FPA (466.6 ng/ml) than did the patients with a higher clearance rate (50%) of SAH (79.2 ng/ml). These results suggest that, the thrombin activity in CSF is correlated with the degree of SAH, the persistence of subarachnoid clot and the development of vasospasm.

Human decidua of early pregnancy contains considerable numbers of CD3-CD56+ natural killer (NK) cells. In this study, two major protein products of the decidua, placental protein 14 (PP14) and placental protein 12 (PP12), were tested for the ability to regulate human NK cell activity. In vitro overnight exposure to PP14 of blood lymphocytes or purified large granular lymphocytes (LGL) resulted in suppression of cytotoxicity against K562 target cells in a 4-h 51Cr release assay. The NK inhibition was dependent on concentrations of PP14, being detectable at 5 micrograms/ml and reaching maximum at 50 micrograms/ml. Manifestation of PP14-induced NK suppression required 18-h contact with NK cells. The suppression of NK activity by PP14 was not abolished by indomethacin. In a target binding assay the number of PP14-treated LGL binding to K562 was comparable to that of untreated ones. By contrast with PP14, PP12 produced no effects on NK cells. These results indicate that PP14 suppresses the function of NK cells, which might be involved in prevention of maternal immune rejection of fetus at the fetomaternal interface.

Although some studies have indicated that endometriosis may increase the risk of developing ovarian cancer, there are no data from epidemiologic studies in Japan. We prospectively analyzed all cases of ovarian endometrioma enrolled in the prefecture-wide Shizuoka Cohort Study on Endometriosis and Ovarian Cancer Programme, which was initiated in 1985. To evaluate the risk of ovarian cancer by time periods subsequent to ovarian endometrioma diagnosis, a cohort of 6,398 women with a clinically documented ovarian endometrioma in Shizuoka between 1985 and 1995 was identified from the Shizuoka Cancer Registry (SCR), with follow-up through 2002. Ovarian cancer incidence among cohort members was ascertained by linkage to the SCR using a unique person-identification number. Standardized incidence ratios (SIR) and their 95% confidence intervals (CI) were computed by a use of prefecture-wide rates of ovarian cancer, adjusted for age and calendar year. During follow-up of up to 17 years of the ovarian endometrioma cohort, 46 incident ovarian cancers were identified, yielding that the ovarian cancer risk was elevated significantly among patients with ovarian endometrioma (SIR = 8.95, 95% CI = 4.12–15.3). The SIR did not increase with increasing follow-up duration. The risk increased with increasing age at ovarian endometrioma diagnosis, with a SIR equal to 13.2 (95% CI = 6.90–20.9) in women above 50 years of age. Our findings for the first time support the hypothesis that ovarian endometrioma increases the subsequent risk of developing ovarian cancer in Shizuoka, Japan

Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome.From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality).Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%).Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Acute allograft rejection (AR) in solid organ transplantation is generally regarded to develop through cell-mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, humoral immunity may play some roles in AR. Although flow cytometry crossmatch (FCXM) is reported as a useful method for the detection of antibodies against donor antigen, specific role of T- or B-cell FCXM and its sensitivity for AR is controversial.T- and B-cell FCXM using fresh donor peripheral lymphocytes were performed before and after blood-type compatible living donor liver transplantation in 47 patients. IgM and IgG anti-donor antibodies were analyzed in relation to clinical AR.Positive pre-transplant T-cell FCXM was associated with a high incidence of positive post-transplant T-cell FCXM (p=0.017). Four of five cases (80%) with positive pre-transplant T-cell FCXM experienced earlier AR (day 8.0+/-4.4, mean+/-SD) than 16 of 42 cases (31%) with negative pre-transplant T-cell FCXM (17.3+/-6.8; p=0.016). In addition, higher dose of steroids was given to treat AR episodes in cases with positive pre-transplant T-cell FCXM (79.9+/-10.3 mg/kg/month) than in those with negative pre-transplant T-cell FCXM (47.1+/-26.6; p=0.039). In the first month after transplantation, 13 episodes of positive post-transplant T-cell FCXM were all concomitant with or preceded clinical AR compared with seven ARs in T-cell FCXM-negative cases (p0.0001). T-cell FCXM between positive sera and third parties revealed some crossreactions. In contrast, detection of antibodies by B-cell FCXM in pre- and post-transplant phases was scarcely associated with AR, and no correlation was found between T- and B-cell FCXM before and after transplantation.Positive T-cell FCXM is closely related with AR and that before transplantation is a predictor of early and refractory AR as well as post-transplant FCXM. In contrast, not a few detections of antibodies irrelevant to AR are observed in B-cell FCXM, suggesting its low specificity.

Cyclic neutropenia is characterized by regularly recurring episodes of neutropenia. It has been reported that pregnancy often has a mitigating effect on the symptoms. However, there have been no detailed studies on changes in the neutrophil count before, during and after pregnancy.A 24-year-old woman with cyclic neutropenia had a successful pregnancy, during which her symptoms improved spontaneously, with decreased severity. The disease recurred soon after pregnancy, and cyclic neutropenia was inherited by the child.Cyclic neutropenia may follow a favorable course during pregnancy, with decreased severity, but postpartum maternal and neonatal complications can occur.

Although decidualization of endometrial stromal cells (ESC) is crucial for blastocyst implantation and maintenance of pregnancy, its complex mechanism still remains largely unknown. It has long been believed that hCG can directly induce in vitro decidualization of ESC via cAMP signaling. Recently, however, it has been reported that the LH/CG receptor is not present in human endometrium, and the direct effect of hCG on decidualization has become controversial. To reevaluate the exact effect of hCG on decidualization, human ESC were isolated and cultured with hCG and/or ovarian steroids. ESC treated with 17beta-estradiol plus progesterone (E(2)/P) transformed morphologically and produced significant PRL, whereas ESC treated with hCG alone showed no significant increase in PRL in culture medium and exhibited no morphological changes. Moreover, hCG did not promote E(2)/P-induced PRL production or intracellular cAMP accumulation, and protein kinase A inhibitor failed to block E(2)/P-induced PRL production. These results suggest that hCG does not directly affect in vitro decidualization of human ESC and that the process of E(2)/P-induced in vitro decidualization might consist of several pathways, including the intracellular cAMP signaling cascade.

Indirect immunofluorescence staining revealed that endometrial stromal cells (ESC) in the ectopic endometrium of patients with endometriosis or adenomyosis expressed aminopeptidase N/cluster of differentiation (CD) 13 antigen and neutral endopeptidase/CD10 antigen, both of which are expressed on ESC in the normal endometrium throughout the menstrual cycle. Thus, ESC in the ectopic endometrium resembled ESC in the normal endometrium not only morphologically but also antigenically. Both peptidase antigens may be useful markers for the histological diagnosis of endometriosis and adenomyosis.

Most of meningiomas belong to benign tumor. But inspite of Simpson grade I surgical resection, it had been reported that a part of these cases recurred after initial operation. In discussing tumor recurrence in meningioma, it is important to evaluate not only the extent of surgical resection and malignancy but also cell proliferative potential, which had been studied immunohistochemically by using BudR, PCNA and MIB-1. Recently, it is known that topoisomerase (Topo) II alpha expression becomes remarkable in tumorigenesis. The correlation with cell proliferative potential has been reported. In this paper we evaluated the relationship of cell proliferative potential and tumor recurrence immunohistochemically by using Topo II alpha and MIB-1 monoclonal antibody in the 21 recurrent cases of meningiomas and hemangiopericytomas. As a result, mean Topo II alpha staining index (SI) and MIB-1 SI initial surgical resection were 2.29% and 3.41%, respectively, at recurrence these SIs had risen at 4.3% and 6.25%, respectively. As to the interval from initial surgical resection to recurrence, in the cases which recurred under 3 years Topo II alpha SI and MIB-1 SI were 3.13% and 5.00%, on the other hand, in the cases which recurred later than 3 years were 1.16% and 1.30%, respectively. Topo II alpha SI and MIB-1 SI 1 of former cases were higher than latter cases. Furthermore good correlation between the Topo II alpha SI and MIB-1 SI was found. It is concluded that Topo II alpha expression was as well available for the marker of cell proliferative potential and for one of the predicting factors for tumor recurrence in meningioma and hemangiopericytoma as MIB-1 SI.

There are various classification systems for pituitary adenomas based on whether mammosomatotroph cells, which simultaneously express both prolactin (PRL) and growth hormone (GH), can be found. Until the present, the identification of such cells required special techniques and could not be performed in paraffin-embedded specimens. This hindered large-scale studies for detection of mammosomatotrophs in various pituitary adenomas and, as a result, such classification has remained controversial. To establish a methodology for the detection of mammosomatotrophs in paraffin-embedded specimens and to propose a more logical classification for pituitary adenomas, the authors conducted this retrospective study.We performed double immunofluorescence staining of PRL and GH in paraffin-embedded specimens of various pituitary adenomas with subsequent observation with a confocal laser-scanning microscope.Mammosomatotrophs were found in four of the 10 GH-secreting adenomas and one of the 10 clinically nonfunctioning adenomas. However, mammosomatotrophs were not identified in all 10 cases of prolactinoma.This is the first report in the literature that successfully demonstrates the presence of mammosomatotrophs in routine paraffin-embedded pituitary adenomas. The new methodology is important for future study of the function and role of these cells. A large-scale study for mammosomatotrophs in various pituitary adenomas with this method and a more logical classification of pituitary adenomas are proposed.

The effect of intraoviductal embryos on endometrial receptivity was studied by intraendometrial and intrauterine embryo transfer. Five-week-old female ICR mice were mated after superovulation; a vaginal plug confirmed day 1 of pregnancy. On day 4 (90 h after hCG injection), blastocysts were collected and transferred to pseudopregnant female mice and to recipient mice in which the uterotubal junction had been ligated bilaterally on day 1 of pregnancy. Three embryos per uterine horn, a total of six embryos per recipient mouse at days 1-6, were transferred to the endometrium or uterine cavity and implantation and pregnancy rates were calculated. The implantation rate for intraendometrial embryo transfer to recipients of days 3, 5 and 6 was significantly higher for uterotubal junction-ligated mice (72.2, 20.8 and 9.7%, respectively) than for pseudopregnant mice (55.0, 8.3 and 0.0%, respectively). The implantation rate for intrauterine embryo transfer to recipients at days 2, 5 and 6 was significantly higher for uterotubal junction-ligated mice (11.1, 25.0 and 8.3%, respectively) than for pseudopregnant mice (0.0, 3.3 and 0.0%, respectively). Uterotubal junction-ligated mice achieved implantation and bore neonates by intrauterine embryo transfer on days 2 and 6, whereas no implantation was achieved in pseudopregnant mice. The difference in implantation rate could not be explained by a difference in progesterone concentration between the groups. The distribution of proliferating cells in the endometrium was also studied immunohistochemically by use of anti-proliferating cell nuclear antigen (PCNA) antibody in the recipient mice. PCNA-positive cells were more abundant in uterotubal junction-ligated mice and demonstrated a marked extension from the epithelium to the stroma over time, in contrast to those in pseudopregnant mice. These findings indicate that an intraoviductal embryo exerts a biological effect by sending a signal to the endometrial epithelium and stroma, thus facilitating endometrial receptivity to the embryo and improving the rate of implantation.

The role of humoral immunity in acute rejection in solid organ transplantation remains controversial, although it is known that the presence of antidonor antibodies may precipitate graft rejection. We investigated the clinical relevance of antidonor humoral immunity for living donor liver transplantation (LDLT) by means of flow cytometry crossmatch (FCXM).T cell FCXM using fresh donor peripheral lymphocytes was performed before and up to 1 month after LDLT in 58 patients. Ten patients received ABO-incompatible grafts. IgM and IgG antidonor antibodies were analyzed in relation to clinical acute rejection as defined by liver function tests with or without histological evidence.Pretransplantation FCXM was positive for five patients (8.6%), resulting in two cases of positive posttransplantation FCXM and two rejection episodes. Twelve patients (20.7%) showed positive posttransplantation FCXM. The incidence of acute rejection within 1 month was 100% in FCXM-positive patients and 17.4% in FCXM-negative patients (P0.001). Thirteen (76.5%) of 17 rejection episodes in ABO-compatible cases were associated with concomitant antidonor IgM antibody. IgG antibody was also identified in six of these episodes. Antidonor antibodies disappeared after rejection treatments in all cases, but with some delay in clinical improvement. On the other hand, no antidonor antibodies were detected in any of the four rejection episodes in ABO-incompatible cases.Early acute rejection in LDLT is significantly associated with antidonor T cell antibody formation in ABO-compatible cases. This suggests a definite role for donor-specific humoral immunity in acute rejection. Rejection episodes without antidonor antibodies may suggest graft injury by pure cellular immunity, or possibly the presence of humoral immunity triggered by antigens not present on donor T cells.

Patients with laterocollis or rotatory type torticollis tend to show abnormal contraction of the levator scapulae muscle and the scalene muscles. These muscles are innervated from the anterior branches of the cervical spinal nerves. Because of this, the traditional Bertrand operation dealing with posterior branches does not adequately affect the symptoms of laterocollis. The authors report selective denervation of the levator scapulae muscle in three patients and discuss its rationale. All the three patients underwent denervation of both the C1-C6 posterior spinal rami and the branches from the C3 and C4 anterior rami to the levator scapulae muscle. We added myotomy of the scalene muscle in one patient, and denervation of the omohyoid muscle which is innervated from the ansa cervicalis and the descending branch of the hypoglossal nerve. The pre/post-operative Tsui scores were 12/4, 15/1, and 14/3 respectively. There were no complications. We conclude that selective peripheral denervation of the levator scapulae muscle is safe and effective in the treatment of laterocollic type torticollis.

A 32-year-old female presented with about a week's history of dull pain in the head and neck pain. On the day of admission, she experienced a sudden onset of severe pain, extending from the occipital to the lower back region and hypesthesia and paresthesia of the right C8-Th3 dermatome. On admission, she was alert but there was a band of hypesthesia and paresthesia at the level of C8-Th3. Cervical X-ray, computed tomography scan (CT) and magnetic resonance images (MRI) of the head revealed no definite abnormalities. The peripheral blood picture was normal, and the bleeding and clotting times were in the normal range. The cerebrospinal fluid (CSF) was bloody and the CSF pressure was 220 mm H2O. An emergent 4-vessel intracranial angiography disclosed no abnormal findings. MRI and myelography revealed an intradural extramedullary lesion extending from the Th2 to the Th5 levels, ventral to the spinal cord. A T1-weighted MR image showed iso-low intensity and a T2-weighted MR image showed low intensity at these lesions. Spinal angiography revealed no abnormal vessels. In one month, spinal compression cleared gradually without surgery and her clinical symptoms disappeared about 40 days after admission. Spontaneous spinal subdural hematoma is uncommon and only 28 cases have been reported. 15 cases have been treated with surgical procedure, but spinal compression cleared spontaneously in this case. This spontaneous recovery is such a rare event that only 3 such cases have been reported in the literature. However, with the prevailing MRI, this disease will be detected more frequently in the future.

The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial.Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures.Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (P = .023, Wilcoxon rank sum test) but not at 3 months (P = .056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores.Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.

The authors evaluated the results of selective peripheral denervation (SPD) of posterior rami of the cervical spinal nerves and/or the accessory nerve for spasmodic torticollis. Five patients underwent seven operations in total and the results were evaluated with the modified Tsui's score which was used in the clinical trial of botulinum toxin (BTX) for torticollis in Japan. The preoperative score was 10.8 +/- 2.2 (mean +/- S.D.) and the postoperative score was 1.4 +/- 1.7. The score changes indicated the effects of the operation as "excellent" in four cases and "good" in one case. These results indicate that SPD is superior to BTX in terms of control of symptoms in spasmodic torticollis. After the initial operation, however, two patients showed the so-called "mole-hitting game phenomenon" in which normal muscles develop abnormal contraction after denervation of abnormal muscles. This forced us to perform the second operations. Although this phenomenon was first described in botulinum toxin treatment, this is probably the first report in surgically denervated cases.

We retrospectively studied 21 cases of histologically proven acoustic shwannomas with an emphasis on the correlation of their magnetic resonance imaging (MRI) findings and histological features. All cases were of low signal intensity in the T1W MRI. In the T2W MRI, 9 of them were of homogeneous high signal intensity (Hom-HSI-T2) and 12 of them were of heterogeneous high signal intensity (Het-HSI-T2). The cases of Hom-HSI-T2 were generally associated with capsular enhancement, and were usually cystic tumors with high vascularities and mainly Antoni A tissues. On the contrary, the cases of Het-HSI-T2 were generally associated with homogeneous enhancement, and were usually solid tumors with low vascularities and various tissue components.

Determination of the cell proliferation activity of neoplasm is useful in making a prognosis. Immunohistochemical detection using MIB-1 monoclonal antibody has recently allowed us to assess tumor cell proliferation easily, because it can be performed on paraffin-embedded specimens and the results have been demonstrated to be positively correlated with the results of PCNA staining. In this study, surgical specimens of 63 pituitary adenomas were examined by immunohistochemical staining with MIB-1 monoclonal antibody. Twenty-nine cases were non-functioning pituitary adenomas, 20 were prolactin (PRL)-producing pituitary adenomas, and 14 were growth hormone (GH)-producing pituitary adenomas. The MIB-1 positive rates of the pituitary adenomas ranged from 0% to 6.46%. In the non-functioning pituitary adenomas, the MIB-1 positive rates ranged from 0% to 4.55% (mean : 0.76%), in the PRL-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 6.46% (mean : 0.91%), and in the GH-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 1.28% (mean: 0.58%). There were no significant differences between these values according to the results of the Wilcoxon signed-rank test. Although the size of the non-functioning pituitary adenomas was not correlated with their MIB-1 positive rate, tumor size was closely correlated with the interval between the onset of the initial symptoms and the date of surgery. In the PRL-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum PRL levels as an index of secretory activity, but was correlated with the PRL staining positive rate. Preoperative bromocriptine therapy proved effective in reducing tumor size and serum PRL levels, but had no effect on the MIB-1 positive rate. In the GH-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum GH levels as an index of secretory activity, but was closely correlated with the GH staining positive rate. All three groups included both invasive and noninvasive tumor types, but there were no close statistical correlations between the three tumor types.

We have reported 7 cases of giant cell glioblastoma. All cases died within 14 months despite aggressive treatment. By immunohistochemical staining, lymphocyte infiltration was found in 6 cases. GFAP and vimentin stained positive in all cases. The MIB-1 positive rate was 13.8-90% (average, 34.9%); small and mononucleated giant cells stained more than multinucleated and monstrous cells. It was concluded that this tumor can be highly malignant and its degree of malignancy is determined by the biological behavior of the mononucleated giant cells and small cells.

The authors report a case of pleomorphic xanthoastrocytoma (PXA) with neurofibromatosis type 1 (NF-1). A 21-year-old woman, noted to have had a number of café au lait spots since birth, presented with the chief complaint of headache. Neuroradiological studies revealed a cystic tumor of the left parietal lobe. Surgical treatment was performed. The tumor was located on the surface of the parietal lobe with the formation of cysts. Light, electron microscopic, and immunohistochemical examination showed the characteristics of typical PXA. This is the second reported case of NF-1 associated with PXA.

It is not rare for a spinal Schwannoma to have cystic formations, but there are various opinions about the mechanism. Since the installation of MRI in our institution in 1989, we have experienced 4 cases of cystic spinal Schwannoma. The diagnosis of such lesions was based on identifying cystic formations histopathologically. Among these cases, tiny hemorrhages were noted microscopically in three of them along with hemosiderin depositions and phagocytes containing hemosiderin. Besides, there are also a lot of sinusoidal vessels with thin endothelium. Perhaps in these three cases, it is the tiny hemorrhages that resulted in degenerative changes which in turn caused the formation of microcysts. But in addition to the above findings, a lot of hyalinized vessels were also demonstrated in the angiomatous components of two cases. Therefore, it is also possible that the microcyst formation is secondary to the degenerative changes caused by ischemia within the tumors. On the other hand, in the only case without hemorrhage, neither phagocytes containing hemosiderin nor abnormal sinusoidal vessels could be found. In stead, a lot of clear foamy cells with positive lipid staining were seen. There may be some factors underlying the xanthomatous change of these tumors that cause their vacuolar formation from degenerated of the foamy cells. It is possible that all three factors mentioned above may act alone or in combination to contribute to the formation of cysts. At its late stage, a spinal Schwannoma may have various findings which can not be classified into either Antoni A or Antoni B type. In conclusion, a spinal Schwannoma can occasionally have cystic formations. Its mechanisms can be a hemorrhagic or an ischemic process occurring within the tumor.

A 30-year-old female and a 38-year-old male developed "definite" moyamoya disease after presenting with "probable" moyamoya disease manifesting as ischemic stroke. Angiography at first presentation demonstrated unilateral involvement with normal contralateral findings. The cases were classified as adult type "probable" moyamoya disease according to the diagnostic criteria. Follow-up angiography demonstrated the occlusive lesions had become bilateral, satisfying the criteria for "definite" cases. Serial angiography is required in adults presenting with "probable" moyamoya disease manifesting as ischemic stroke.

Management of huge pituitary adenoma (more than 5 cm in diameter) is one of the most important issues on the treatment of pituitary tumors. We have analyzed the therapeutic modality and the result of our cases. From 1967 to 1983, 50 patients with huge adenoma (14.1%) out of a total 354 pituitary adenomas were surgically treated. The operative mortality was 25% for radical transcranial (TC) approach (10/40), 14% (1/7) for transsphenoidal (TS) approach and 0% (0/3) for combined two stage operations. From long-term follow-up, excellent prognoses were observed in only 44% of the patients treated by radical TC operation. After 1984, we have employed partial removal by TS surgery at the first stage, followed by reoperation by TS or TC surgery with or without radiotherapy or bromocriptine in case by case. Seventeen huge pituitary adenomas out of a total 700 pituitary adenomas were operated. There was no mortality nor major complications. The two stage operation with initial TS surgery is recommended for the management of huge pituitary adenomas.

A multicenter cooperative study was conducted to investigate factors influencing posttraumatic epilepsy (PTE) and to evaluate the prophylactic effect of anticonvulsants. A retrospective study of 102 PTE patients revealed the following typical clinical features: occurrence in young males, traffic accidents, contusion and/or cerebral hematoma. The latent period after the injury was longer in children. The percentage of EEG paroxysmal activity gradually increased as the generalized abnormality diminished. A retrospective-prospective study of 1998 patients who suffered a head injury between 1984 and 1988 was conducted till 1994. During the follow-up period, 62 patients (3.1%) developed PTE. The drop-out cases were excluded, and the 154 cases followed at least two years were analyzed. Statistical analysis of differences between patients with and without PTE suggested following factors: young, immediate early epilepsy (within 24 hours after injury; IMEE) and early epilepsy (within one week after injury). The risk with the highest relative risk rate was early epilepsy. Multiple regression analysis revealed that three factors, IMEE, early epilepsy and young age, contributed to the prediction of PTE. There was no significant difference in the percentage of patients having PTE in the group treated with anticonvulsants and the untreated group. Anticonvulsant treatment after head injury was unlikely to have a prophylactic effect on the development of PTE.

To search for new molecules relating to the mechanism(s) of follicular differentiation, we raised a new monoclonal antibody (mAb), POG-2, which reacted with the surface of porcine ovarian granulosa cells. An immunohistological study revealed that the antigen appeared initially on the primary follicles. The antigen expression increased during follicular development, reached the highest level in small follicles 1-2 mm in diameter, and then decreased in the preovulatory follicles. The antigen was not detected on luteal cells in the CL. SDS-PAGE profiles of POG-2 antigen purified from isolated porcine granulosa cells by immunoaffinity chromatography indicated that it consisted of two proteins (120 and 130 kDa) and that the antigenic epitope of POG-2 was on the 120-kDa protein. We next purified a large amount of POG-2 antigen from the homogenate of porcine ovaries by immunoaffinity chromatography. Analysis of the partial amino acid sequence of the 120-kDa protein showed that 16 amino acids from the amino terminus were very similar to those of both human and murine mature integrin alpha 6, with 88% homology. SDS-PAGE profiles revealed that the 120-kDa protein was bound to a 28-30-kDa protein by a disulfide bond; this was compatible with the reported characteristics of human integrin alpha 6. We then examined the immunoreactive distribution of integrin alpha 6 using anti-integrin alpha 6 mAb GoH3. The staining profiles obtained with GoH3 were very similar to those obtained with POG-2. These findings showed that the molecule detected by POG-2 was a porcine homolog of human integrin alpha 6 and that integrin alpha 6 was a differentiation antigen of porcine granulosa cells, suggesting an involvement of integrins in follicular differentiation.

Six cases of subependymal giant cell astrocytoma (SGCA), five associated with tuberous sclerosis (TS), were reviewed by light microscopy, electron microscopy and immunohistochemistry. Histologically, all cases showed features typical of SGCA. GFAP and neurofilament expression were found in all cases. Synaptophysin and myelin basic protein were positive in single different cases. The MIB-1 positive rate was 0% in 4 cases, 3% in a case with recurrence after a partial resection, and 6.4% in another case with a rapid growing tumor. By electron microscope, glial filament was identified in the tumor cells of all cases, whereas none of them showed any ultrastructural evidence of a neuronal origin. We therefore suggest that SGCA is a glial origin tumor, arising from the astrocytic part of a subependymal nodule--the most common cerebral lesion of tuberous sclerosis caused by distorted migration of the germinal mantle-the neuronal part of which remains as entrapped remnants of dysgenetic, incompletely expressed neuronal cells.

We investigated the short-term effects of an intrathecal bolus injection of baclofen on central pain due to stroke or spinal cord injury. Pain relief was obtained in 64% of the patients. The effects developed 1-2 hours after the injection and continued for 10-24 hours. Both spinal segmental and supraspinal mechanisms may be involved in the production of baclofen-analgesia.

✓ 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.

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.

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.

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 c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and is shown to be allelic with the white-spotting locus (W) of the mouse. In order to elucidate the role of c-kit protein during placental development, we have examined the expression of c-kit protein in the uterus and placenta of mice at pre- and post-implantation stages by the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody. At Days 3 and 5 of pregnancy and pseudo-pregnancy, c-kit protein was detected in the glandular epithelium, but little expression was observed in the luminal epithelium. At Day 7 of pregnancy, expression was detected in the stromal cells around the uterine crypts of the mesometrial portion, but not in the vigorously proliferating decidual cells around the developing embryo. At Days 9 and 10 of pregnancy, the decidua basalis facing invading trophoblasts gradually expressed c-kit protein. In the mature placenta, c-kit protein was detected in the labyrinthine and decidual layers, but in neither the giant trophoblastic nor the spongiotrophoblastic layer. By Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), c-kit mRNA was detected at the stages of periimplantation and placental development. These results suggested that the c-kit protein might be involved in the proliferation and differentiation of placenta.

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).

With specific monoclonal antibodies, we found that human endometrial stromal cells and decidual cells express two function-related surface antigens. Indirect immunofluorescence staining revealed that both endometrial stromal cells and decidual cells during the first trimester of pregnancy expressed cluster of differentiation (CD) 13 antigen and CD10 antigen, which are identical to aminopeptidase N and neutral endopeptidase, respectively. By flow cytometric analysis, CD13 antigen was detected on 82-93% of the examined cells, and CD10 antigen was detected on 75-93% of the examined cells in endometrial stromal cell-enriched preparations. Furthermore, peptidase activity was detected in these cell preparations by an assay based on the hydrolysis of alanine-p-nitroanilide into p-nitroaniline and alanine.

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.

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.

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.