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Application of Monte Carlo track structure has been very successful in the modelling and quantification of DNA damage, clustered-damage and spectrum of DNA damage for energetic electrons and ions. However, there are paradoxical axioms in quantitative assessment of the energetics of DNA damage at very low electron energy and in the vacuum UV region. This paper, after a brief review of the parameters used in modelling of DNA damage, presents an analysis of experimental data of strand breaks in aqueous solution in the vacuum UV. the region to which little attention has been paid in spite of its fundamental importance in providing reaction parameters for radiation actions.

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.

We determined the number of single and double strand breaks (ssb and dsb) in a DNA-chloroterpyridine platinum complex induced by resonant photoabsorption in the L(III) innershell of a platinum atom. The number of ssb and dsb were measured in supercoiled plasmids (AG30) versus the chloroterpyridine platinum concentration, i.e., the ratio of intercalated molecules to the number of phosphate sites in DNA. A significant increase in the number of ssb and dsb was observed when the DNA contained intercalated molecules. This technique is an efficient way to induce ssb and dsb triggered by the atomic Auger effect.

A 27-year-old male who had been diagnosed with Ebstein's anomaly was admitted with uncontrollable congestive heart failure. The echocardiogram revealed severe tricuspid valve incompetence and the electrocardiogram showed atrial fibrillation. He underwent Hetzer's repair procedure for tricuspid valve incompetence and Minzioni's right atrial isolation technique to restore sinus rhythm. His congestive heart failure quickly disappeared and sinus rhythm was restored after operation. He was discharged 3 weeks postoperatively and remains well 22 months after his operation. Hetzer's technique for tricuspid valve repair in Ebstein's anomaly restructures the valve mechanism at the level of the true tricuspid anulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We conclude that Hetzer's procedure is an effective operation for Ebstein's anomaly.

Surgical robots are useful for minimally invasive surgery, since it enables precise manipulation of surgical instruments beyond human ability in a small operation space. In this approach, we are developing a micro manipulator for minimally invasive neurosurgery. The micro manipulator consists of two micro grasping manipulators, a rigid neuroendoscope, a suction tube, and a perfusion tube. This paper reports on the micro grasping manipulator. It has two D.O.F for bending and one D.O.F for grasping. This prototype is 3.1 mm in diameter and can bend 30 degrees in any direction. Stainless steel wire was used to actuate the manipulator.

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.

The distal region of a short arm of chromosome 1p is frequently deleted in many human cancers including neuroblastoma (NBL), in which it has been narrowed down to the smallest region of overlap between D1S244 and D1S214 (approximately 7 cM). During the search for the candidate tumor suppressor genes mapped within the region, we found the KIAA0591 gene which encoded a new human kinesin-related protein with a homology to human axonal transporter of synaptic vesicles (ATSV). The kinesin is an intracellular motor protein and often associated with neuronal differentiation and survival. Here we identified a complete open reading frame of the KIAA0591 gene by screening a cDNA library derived from human substantia nigra. The KIAA0591 protein contains a possible pleckstrin homology (PH) domain at its carboxy-terminus. However, it did not possess a force-generating motor domain which is well conserved among kinesin superfamily members (KIFs). Northern blot analysis demonstrated that KIAA0591 mRNA was preferentially expressed in both adult and fetal brains, kidney, skeletal muscle and pancreas. KIAA0591 was expressed in favorable NBLs at higher levels than in unfavorable NBLs, although RT-PCR SSCP analysis showed no mutation within the coding region of the KIAA0591 gene, when 8 neuroblastoma tissues and 15 neuroblastoma-derived cell lines were examined. Thus, the full-length KIAA0591 gene may be a novel member of human KIF superfamily which lacks motor domain and might function as a tumor suppressor in an epigenetic but not a classic Knudson's manner.

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 outcome of brain tumor treatment has greatly improved through the development of imaging diagnosis techniques such as CT scan or MRI, and microsurgical techniques. During the past 25 years, an efficient therapeutic modality for benign brain tumors, which constitute approximately half of all brain tumors, has been well established through early diagnosis an precise surgical manipulation. The outcome of malignant brain tumors has also improved with radiotherapy together with chemotherapy or an adjuvant treatment with biological response modifiers such as interferon. Although a complete therapeutic strategy for medulloblastoma or germ cell tumors is expected in near future, the ideal therapeutic modalities for other malignant brain tumors remain further off. On the other hand, focal radiotherapeutic equipment such as the gamma knife or photonradiosurgical system have been introduced for the treatment of brain tumors and the efficacy has been clinically proved. Even though much progress in brain tumor treatment has been made, the prognosis of malignant brain tumors in general is still poor and the lives of those patients are quite limited. The development of gene therapy or immunotherapy for brain tumors is, thus, looked forward to in the 21 st century.

Ionic mechanisms play an important role in the regulation of hormone secretion. The GHRH-induced GH release by human GH-secreting cells is transmitted through protein kinase A (PKA), which activates nonselective cation current (NSCC) and induces membrane depolarization, intracellular Ca2+ increase, and GH secretion. To evaluate whether ionic mechanisms have pathophysiological significance in GH oversecretion of GH-secreting pituitary adenomas, we examined four adenomas with constitutively active Gs alpha mutation (gsp mutation) and compared with three gsp-negative adenomas. In primary-cultured cells of gsp-positive adenomas, GHRH did not increase the NSCC under voltage-clamp experiments. Detailed examination showed that NSCC was maximally activated at the basal level and application of GHRH did not increase the current in these adenomas. Furthermore, by using single-cell RT-PCR method, we demonstrated for the first time at the single cell level that gsp mutation is heterozygous in GH-secreting pituitary adenomas. These indicate that heterozygous gsp mutation fully activates NSCC at the basal level, which may account for the GH oversecretion in gsp-positive GH-secreting pituitary adenomas.

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 photon radiosurgery system is a miniature X-ray generator that can be placed stereotactically and intraoperatively into intracranial tumors to deliver a single fraction of high-dose interstitial irradiation. This battery-powered device produces low energy X-ray photons in a spherical and symmetrical pattern at the probe tip. Dose rates of up to 200 cGy/Mim are possible, allowing for the administration of 15 Gy to a lesion 3 cm in diameter in less than 1 hr. Background exposure is minimal, and no special shielding of the patient or health care personnel is required. Thirty-nine patients with brain tumor were treated in this method. There were no adverse effects. During the follow-up period of 1-30 months, 3 cases with 5 metastatic brain tumors died about 8 months after this treatment. Five recurrent cases of 21 malignant gliomas died about 4 months after treatment. Interstitial radiotherapy using photon the radiosurgery system promises to be a useful treatment for brain tumors.

We report a patient with intractable left facial pain and severe hyperkinesia of the left arm who was successfully treated with deep brain stimulation. The stimulation lead was positioned to pierce both the sensory relay nucleus and the nucleus ventrointermedius of the thalamus in a single stereotactic trajectory through an occipital burr hole.

The ischemic area surrounding the cerebral infarction in the eloquent area was salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by positron emission tomography (PET) using the [15O] gas inhalation steady-state method and clinical symptoms improved within a year after surgery. To confirm the ischemic area and select the suitable recipient artery was important for successful bypass surgery, because only an artery covering the ischemic area is expected to have low resistance. In this case a large ischemic area with disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET clearly exposed the localized misery perfusion area in the overestimated ischemic area by SPECT. We describe our experience and discuss the technique and efficacy of PET for STA-MCA anastomosis surgery.

A drug delivery system using copoly (lactic/glycolic acid) was developed for the intrathecal administration of nicardipine. This system was tested to determine its efficacy in preventing cerebral vasospasm in dogs. A rod-shaped implant (1-mm diameter, 10-mm long and which contained approximately 10% of nicardipine) was prepared by a heat compression method. In in vitro studies, 8% of the actual nicardipine loaded was released during day 1, 17% within day 2, 62% within day 4, and 96% within day 10. In in vivo studies, 12 dogs were assigned to two groups: the placebo group and the group treated with nicardipine. Angiography before the experiment was performed followed by right craniectomy and induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Eight pellets, either containing 8 mg of nicardipine or without nicardipine were placed in the cistern. On day 7, the angiography was repeated and cerebrospinal fluid was removed from the cisterna magna. The animals were then sacrificed, and the brain and blood clot were taken out. Cerebral vessels were measured three times with a calibrated optical micrometer, and the mean value was obtained. Average reduction of vessel diameters on the clot side in the placebo and nicardipine groups were -37% and -10% on the internal carotid (IC), -48% and -3% on the middle cerebral (MC), and -28% and -1% on the anterior cerebral artery (AC), respectively. There were significant differences in vessel diameters of IC (p0.05), MC (p0.005), and AC (p0.05) between these groups. No vasospasm was found in the left side. The nicardipine concentration in the clot was determined by high performance liquid chromatography. The mean concentration of nicardipine in the clot was 1.5 x 10(-4)M, at which concentration sufficient relaxation is evoked in vitro. The pellets did not last beyond day 7. Regarding the histological findings, there was a marked difference in vessel diameters between the placebo and the nicardipine treated groups. The arteries were surrounded with red blood cells and inflammatory cells. There were no specific changes related to the pellets and no sign of meningoencephalitis. A prolonged-release preparation of nicardipine that can be implanted intracranially at the time of surgery prevented vasospasm significantly in dogs. These results suggest that this new drug delivery system might be put into effect favorably in patients suffering from vasospasm due to subarachnoid hemorrhage.

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.

Metastatic brain tumors generally accompany huge peripheral edema, and half of the cases have multiple lesions. Thus, one must manage the increased intracranial pressure (IICP). Ideally, local control of the tumor progression by surgical removal with radiation or radiosurgery is the best method to reduce IICP. We usually use a glyceol or steroids as medical treatment. Steroids are effective for peripheral edema, and we have used them for inoperable patients over the long term. One should estimate the condition of the primary lesion, systemic metastasis, and intracranial lesion in order to determine the therapy to assure patients the best quality of life.

We have developed an overlaid three-dimensional image (Volumegraph)-guided navigation system that allows navigation during operative procedures. The three-dimensional image is superimposed on the patient's head and body via a semi-transparent mirror. The Volumegraph can display three-dimensional images in the air by a light beam which is based on CT/MRI.The system consists of a Volumegraph (thin plate of three-dimensional recorded medium), a Volumegraphscope and an original designed triangular-shaped marker system for registration. The three-dimensional data obtained from CT and MRI before the operation were processed by a computer. Such image data are applied for preoperative investigation to recognize the three-dimensional structure of organs and tumor. These reconstructed three-dimensional images were superimposed and registered at the patient's head according to a fiducial marker (registration). Then the operator can operate with this three-dimensional-image-guided navigation system.Based on clinical application in 7 cases, the system was found to be advantageous because the surgical procedures could be navigated easily by augmented reality in the surgical field. Invisible parts of the surgical field were supplemented with the overlaid three-dimensional images (Volumegraph) as if it were the virtual operative field. At another time, spatial positioning and overlaid visualization by the Volumegraph was useful for identifying anatomical structures and functional location in the image.This preliminary study of overlaid three-dimensional-image-guided navigation demonstrated its clinical usefulness. The application of augmented reality in the surgical field makes it possible to do a neurosurgical intervention easily and accurately.

In 1995 we had about 6,500 neurosurgeons for a population of 125 million in Japan. The number of neurosurgeons per population is currently the largest of all countries in the world. In order to raise the clinical standard of neurosurgery for the benefit of the patients, it is necessary to make several actions to stabilize urgently the appropriate numbers of neurosurgeons in our country. It is considered to be worthwhile to present to the neurosurgeons in many countries the statistical data of the manpower and activities of neurosurgeons and problems regarding the medical and health care systems in Japan, which have a different medical, social and economical environment. In this paper, I would like to present the statistical data of neurosurgeons, the background of the current medical and health care problems and a proposal for solving the current situation in our country.

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.

Inhibin alpha and beta A subunit messenger ribonucleic acid (mRNA) levels were measured quantitatively by reverse transcription-polymerase chain reaction (RT-PCR) in human pituitary adenomas. The inhibin alpha subunit mRNA levels were undetectably low in cultured adenoma tissues, but beta A mRNA were 0.383 +/- 0.074 in 3 GH adenomas, 0.672 +/- 0.140 in 3 prolactinomas and 0.957 +/- 0.414 molecules/cell in 3 non-functioning adenomas. The addition of 10(-8) M activin A decreased the beta A mRNA levels within 4 h in 1 of 3 GH adenomas, 2 of 3 prolactinomas and 2 of 3 non-functioning adenomas, though the decreases were not statistically significant. The results showed an abundance of beta A subunit mRNA compared with alpha subunit mRNA in all human pituitary adenomas and a local role for activin in its own production through inhibin beta A mRNA subunit expression.

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.

A 23-year-old male with splenius type torticollis underwent selective denervation of C1 and C2 roots and C3-C6 spinal posterior rami, with excellent results. Based on this experience, we stress the importance of dynamic EMG and thorough review of video recording for identifying the involved neck muscles. In the operative procedures, the nerve rami are identified under the semispinalis muscle. To dissect the correct plane under the semispinalis muscle, the key point to keep in mind is to follow the great occipital nerve to the proximal part. An ultrasonic blood flow meter is useful to locate the vertebral artery in the spaces between the occiput and the C1 lamina and between C1-C2 laminae. Because fine nerve branches run in the soft tissues over the laminae, to avoid transient neuroapraxia, dissection around the C1, C2 arches should not be carried out under the periosteum, as is usually done in case of laminectomy. Dissection of C1 and C2 rami as far as the very medial part is rather difficult because of bleeding from the venous plexus and the presence of the vertebral artery. Therefore, the intradural approach might be easier for sectioning the C1 and C2 roots. We would like to add these points to the original description by Bertrand.

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.

Effects of treatment with lipopolysaccharide (LPS) both in vivo (intraperitoneal administration of 20 mg.kg-1 LPS for 6 hours) and in vitro (incubation with 1 microgram.kg-1 LPS for 6 hours) on the responsiveness of the rat thoracic aorta, carotid, renal, femoral, mesenteric, pulmonary arteries, and the femoral and mesenteric veins were examined. Intraperitoneal administration of LPS did not change the blood pressure of rats, but increased the heart rate significantly. The same amplitude of relaxation was produced by L-arginine in the aortic strips treated by LPS in vivo and in vitro, and the responses were inhibited by NG-nitro-L-arginine (L-NOARG). The contractile responses to phenylephrine in the aortic strips 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 to phenylephrine was completely reversed by L-NOARG in the strips treated with LPS in vitro, whereas the reversal by L-NOARG was incomplete in the strips treated with LPS in vivo. Different amplitudes of relaxations were also produced by L-arginine or SNP in the blood vessels treated by LPS in vivo or in vitro. However, the tail artery treated with LPS in vivo or in vitro did not relax in response to L-arginine but did produce a relaxation to SNP. These results suggest that the hyporesponsiveness of rat blood vessels after treatment with LPS in vivo or in vitro may be related to an enhanced NO production in the smooth muscle cells and that there is a possible heterogeneity of regional induction or activation of L-arginine/NO pathway by LPS in rat blood vessels.

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.

The nidal haemodynamics of cerebral arteriovenous malformations (AVMs) are unclear. We studied them by dynamic CT. Using dynamic CT and gammavariate curve fitting, appearance times (AT), mean transit times (MTT; first moment transit times) and peak times (PT) were determined for the nidus of an AVM in 3: patients, including 14 patients with haemorrhagic and 19 with epileptic episodes. The nidus of patients with haemorrhagic episodes demonstrated statistically delayed PT (P

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.

In the previous report, we demonstrated that bovine germinal vesicle (GV) stage oocytes vitrified using a nylon mesh holder showed an in vitro maturation rate to the metaphase II (MII) stage similar to that of fresh ones. However, cleavage and developmental rates of vitrified oocytes were low. Because mitochondria and the cytoskeleton are thought to have a central role in energy supply and cellular division in mammalian embryogenesis, it seems possible that alternation in their function in vitrified GV oocytes may contribute to subsequent lower cleavage and developmental rates. The oxygen consumption rate reflects the mitochondrial activity and its measurement may be an effective way for non-invasive evaluation of oocyte quality. In this study, to ascertain that altered mitochondrial functions and cytoskeleton may contribute to reduce the quality of oocytes after vitrification, we evaluated the distribution of active mitochondria and the cytoskeleton in vitrified oocytes. We also examined the relationship between oxygen consumption rate and the distribution of active mitochondria in vitrified oocytes. Bovine GV oocytes connected with cumulus cells were exposed to the cryoprotectant (EFS40) in a stepwise way and transferred onto a nylon mesh holder, followed by plunging them directly into liquid nitrogen. After warming, vitrified oocytes were allowed in vitro maturation. After denuding, matured oocytes were stained with a mitochondria-specific probe, rhodamine-123 and then oxygen consumption rate using an embryo respirometer (HV-403; Research Institute for Functional Peptides, Yamagata, Japan) was measured in each oocyte. According to morphological distribution of mitochondria, oocytes were classified as follows: type 1, uniform distribution; type 2, spotted distribution; and type 3, a weak fluorescence. The oxygen consumption rate of the fresh oocytes at the MII stage was significantly (P