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Z-100, Mycobacterium tuberculosis strain Aoyama B, which suppresses the growth of various experimental tumor cell lines, was incorporated into biodegradable copoly( L -lactic acid/glycolic acid) (70:30 mol%) copolymer with a number-average molecular weight of 2900, in order to evaluate the controlled release function, prolongation of survival duration, and hematopoietic functions such as endogenous colony forming unit of spleen (endogenous CFU-S) and colony forming unit of culture (CFU-C) in mice irradiated with a lethal dose of 8.5 Gy (y-rays from a 6° Co source). In this study, the Z-100 formulation was implanted subcutaneously in the back of mice immediately after irradiation. All of the control mice without the use of the Z-100 formulation died within 19 days, as compared to only 30% mortality throughout the experimental period of 35 days for the experimental mice treated with the Z-100 formulation. Such prolongation of survival time in mice promoted recoveries of stem cells or granulocytic and macrophagic precursor cells.

To elucidate the influence of aging upon the improvement of symptoms and cardiac size associated with surgical repair of atrial septal defect, clinical symptoms, cardiothoracic ratio and hemodynamic variables in older patients (group A; age at operation > or = 50 years old, n = 11) were compared with those in younger patients (group B; age at operation < 50 years old, n = 8). There were no differences in hemodynamic variables, i.e., peak systolic pulmonary pressure, pulmonary to systolic flow ratio (Qp/Qs), pulmonary to systolic vascular resistance ratio (Rp/Rs) and left to right shunt ratio between the two groups. Symptomatic benefits occurred in all patients, although 3 patients in group A who had atrial fibrillation preoperatively still displayed symptoms such as exertional dyspnea. The postoperative (after 3 months) cardiothoracic ratio improved in all patients except for 3 patients in group A who were operated at over 60 years of age. Although there was no significant difference in preoperative cardiothoracic ratio between the two groups, the postoperative cardiothoracic ratio in group B was significantly smaller than that in group A. These results indicate that operative closure of atrial septal defect is recommended for all patients aged 50 years old or older, but early improvement of symptoms and cardiomegaly in older patients is lower than that in younger patients.

Between 1991 and 1993, 230 patients visited Wakkanai Municipal Hospital because of foreign bodies in the nasal cavity, external auditory canal or pharynx, and between 1984 and 1993, 35 patients because of foreign bodies in the esophagus or upper respiratory tract.Of the 265 patients, 110 had a foreign body in the pharynx, 73 in the external auditory canal, 47 in the nasal cavity, 24 in the esophagus, and 11 in the upper respiratory tract.The most common foreign bodies were fish bones in the pharynx or esophagus, cotton balls in the external auditory canal, and BB bullets in the nasal cavity.Two patients had accidentally inhaled pieces of crab shells into the trachea. Since they were hollow cylinders, they did not cause suffocation. They could not be removed in one piece because the spines of the shells were stuck in the lining of the trachea so they had to be crushed and the fragments removed.The incidence of foreign body cases in Soya was calculated to be 8 to 10 per ten thousand people per year.

Effect of cilnidipine, a new calcium antagonist, on autoregulation of cerebral blood flow was studied in spontaneously hypertensive rats. Cilnidipine, at doses of 1-100 micrograms/kg, i.v., showed a hypotensive effect in a dose-dependent manner without affecting regional cerebral blood flows (rCBF) in the cerebral cortex or nucleus caudatus. At intraduodenal doses of 1 or 10 mg/kg, cilnidipine also did not affect rCBFs, while it produced long-lasting hypotension with a slow onset, decreasing blood pressure by about 40% of the pre-administration value at 10 mg/kg. Cilnidipine at a dose of 10 mg/kg, i.d. significantly lowered the lower limit for autoregulation of cerebral blood flow. These findings suggest that autoregulation of cerebral blood flow remains intact even in the excessive hypotension induced with cilnidipine and that the drug shifts the lower limits for autoregulation of cerebral blood flow downward.

Purpose: To elucidate the role of partial splenic embolization (PSE) procedures, long-term outcome was assessed in terms of the recurrence of thrombocytopenia. Methods: A retrospective study was performed after 41 PSE procedures in 36 patients for hypersplenism owing to portal hypertension. The underlying disease was biliary atresia in 32 patients, extrahepatic portal obstruction in 3, and idiopathic cirrhosis in 1. Results: The average volume embolized was 70.1%. The patients were followed up from 20 days to 182 months (average, 70.8 months). Five patients subsequently died, and 6 underwent liver transplantation. The causes of death or the reasons for liver transplantation were not related to hypersplenism. Eleven patients (30.6%) had recurrence of thrombocytopenia ( 3 ). There was no significant difference in the volume embolized or platelet count before PSE between the patients with and without recurrence of thrombocytopenia. The peak value of platelet count after PSE was significantly lower in the patients with recurrence of thrombocytopenia ( P = .0091). In 17 of 24 survivors without liver transplantation, platelet counts remained normal throughout the follow-up period. Conclusions: PSE is a safe and effective procedure. Hematologic indices improved in all 36 patients after PSE, and its long-term efficacy was shown in 70% of the survivors.

Awake surgery for lesions in the non-dominant parietal lobe is rare. We report two cases of right parietal lobe glioma for which awake surgery was performed in order to avoid ataxie optique and hemispatial neglect due to injury in the superior and inferior parietal lobule, respectively. Among several tests to assess the dysfunction of spatial recognition, line bisection test was selected for the task during awake surgery because of its simplicity, easy repetition, and utility. The tumor was successfully removed without any neurological deficit in both the cases. The line bisection test is simple and useful for preserving spatial recognition during an awake surgery.

Tumescenamide C, a new cyclic lipodepsipeptide, was isolated from a culture broth of an actinomycete Streptomyces sp. KUSC_F05. Tumescenamide C was a congener of tumescenamides A and B, representing a sixteen-membered ring system, consisting of two proteinogenic and three non-proteinogenic amino acids, to which a methyl-branched fatty acid was attached. The planar structure was determined by spectroscopic analysis, while its absolute stereochemistry was determined by chemical degradation and asymmetric synthesis. Tumescenamide C exhibited antimicrobial activity with high selectivity against Streptomyces species.

Molecular targeted therapy can potentially provide more effective treatment for patients with high-grade gliomas. Notch and Akt are notable target molecules as they play important roles in a variety of cellular processes, such as regeneration, differentiation, proliferation, migration, and invasion. Here, we assessed the therapeutic possibility of inhibiting Notch and Akt in gliomas using the clinically available, selective small molecule inhibitors MRK003 and MK-2206. We evaluated their efficacy individually and as a combination therapy in U251 and U87 glioma cell lines. We confirmed that MK-2206 effectively inhibits Akt phosphorylation in a dose-dependent manner, whereas MRK003 inhibits Notch signaling and Akt phosphorylation. Both MRK003 and MK-2206 significantly inhibited cell growth, migration, and invasion in a dose-dependent manner. Akt dephosphorylation was enhanced by combination therapy with MRK003 and MK-2206. However, the effect of combination treatment did not exceed that of MK-2206 monotherapy in proliferation assay. Inhibition of invasion, further enhanced by combination therapy, correlated with increased Akt inactivation. In summary, combination therapy with MRK003 and MK-2206 may be effective for inhibiting invasion but not proliferation.

CONTEXT AND OBJECTIVE There are no reports on reintubation incidence and its causes and consequences during the postoperative period following elective intracranial surgery. The objective here was to evaluate the incidence of reintubation and its causes and complications in this situation. DESIGN AND SETTING Prospective cohort study, using data obtained at a tertiary university hospital between 2003 and 2006. METHODS 169 patients who underwent elective intracranial surgery were studied. Preoperative assessment was performed and the patients were followed up until hospital discharge or death. The rate of reintubation with its causes and complications was ascertained. RESULTS The incidence of reintubation was 12.4%, and the principal cause was lowered level of consciousness (71.5%). There was greater incidence of reintubation among females (P = 0.028), and greater occurrence of altered level of consciousness at the time of extubation (P < 0.0001). Reintubated patients presented longer duration of mechanical ventilation (P < 0.0001), longer stays in the intensive care unit (ICU) and in the hospital (P < 0.0001), greater incidence of pulmonary complications (P < 0.0001), greater need for reoperation and tracheostomy, and higher mortality (P < 0.0001). CONCLUSION The incidence of reintubation in these patients was 12.4%. The main cause was lowering of the level of consciousness. Female gender and altered level of consciousness at the time of extubation correlated with higher incidence of reintubation. Reintubation was associated with pulmonary complications, longer durations of mechanical ventilation, hospitalization and stay in the ICU, greater incidence of tracheostomy and mortality. CONTEXTO E OBJETIVO Não há relatos sobre incidência de reintubação, suas causas e consequências no pós-operatório de cirurgia intracraniana eletiva. O objetivo foi avaliar a incidência de reintubação, suas causas e complicações em pós-operatório de cirurgia intracraniana eletiva. TIPO DE ESTUDO E LOCAL Estudo de coorte prospectivo, com dados que foram obtidos de 2003 a 2006 em um hospital universitário terciário. MÉTODO 169 pacientes submetidos a cirurgia intracraniana eletiva foram estudados. Foi realizada avaliação pré-operatória e os pacientes foram acompanhados até a alta hospitalar ou óbito, verificando a taxa de reintubação, suas causas e complicações. RESULTADOS A incidência de reintubação foi de 12,4% sendo a principal causa o rebaixamento do nível de consciência (71,5%). Houve maior incidência de reintubação no sexo feminino (P = 0,028), bem como do nível de consciência alterado no momento da extubação (P < 0,0001). Pacientes reintubados apresentaram maior tempo de ventilação mecânica (P < 0,0001) e de internação em unidade de terapia intensiva (UTI) e hospitalar (P < 0,0001), maior incidência de complicações pulmonares (P < 0,0001), maior necessidade de reoperação e traqueostomia, além de aumento de mortalidade (P < 0,0001). CONCLUSÃO A incidência de reintubação nesses pacientes foi de 12,4%. A principal causa da reintubação foi o rebaixamento do nível de consciência. O sexo feminino e nível de consciência alterado no momento da extubação foram relacionados à maior incidência de reintubação. A reintubação foi associada a complicações pulmonares, maior tempo de ventilação mecânica, de internação e de permanência na UTI, maior incidência de traqueostomia e mortalidade.

Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language-processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery.Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB).After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039).The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.

Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an "on" or "off" switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.

Purpose For the application of less invasive robotic neurosurgery to the resection of deep-seated tumors, a prototype system of a force-detecting gripper with a flexible micromanipulator and force feedback to the operating unit will be developed. Methods Gripping force applied on the gripper is detected by strain gauges attached to the gripper clip. The signal is transmitted to the amplifier by wires running through the inner tube of the manipulator. Proportional force is applied on the finger lever of the operating unit by the surgeon using a bilateral control program. A pulling force experienced by the gripper is also detected at the gripper clip. The signal for the pulling force is transmitted in a manner identical to that mentioned previously, and the proportional torque is applied on the touching roller of the finger lever of the operating unit. The surgeon can feel the gripping force as the resistance of the operating force of the finger and can feel the pulling force as the friction at the finger surface. Results A basic operation test showed that both the gripping force and pulling force were clearly detected in the gripping of soft material and that the operator could feel the gripping force and pulling force at the finger lever of the operating unit. Conclusions A prototype of the force feedback in the microgripping manipulator system has been developed. The system will be useful for removing deep-seated brain tumors in future master–slave-type robotic neurosurgery.

Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an “on” or “off” switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.

In this paper, three kinds of devices and applications of nano carbon materials, i.e., carbon nanotube and graphene are introduced. 1) Using the feature of the nanostructure of carbon nanotube, quantum nano memory which can store the single charge one by one at the interface of the all arounded double stacked gate insulator was realized. 2) Only by modulating the gate bias, the particle nature and the wave nature of electron can be controlled, and Kondo resonance state was realized. 3) First selective bio sensor was realized using the aptamer modified graphene FET with high sensitivity.

A combined therapy of the alkylating agent temozolomide (TMZ) and radiotherapy is standard treatment, and it improves the survival of patients with newly diagnosed glioblastoma (GBM). The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes the most cytotoxic lesions generated by TMZ, O(6)-methylguanine, establishing MGMT as one of the most important DNA repair mechanisms of TMZ-induced DNA damage. Thus, the expression of MGMT, its activity, and its promoter methylation status are associated with the response of GBM to TMZ, confirming that MGMT promotes clinical resistance to TMZ. Previous studies have shown that a variety of drugs such as interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increased the sensitivity of TMZ through MGMT-dependent or MGMT-independent mechanisms. In this review, we describe drugs and promising molecules that influence the responsiveness of GBM to TMZ and discuss their putative mechanism of action. In MGMT-positive GBMs, drugs that modulate MGMT activity could enhance the therapeutic activity of TMZ. Thus, administration of these drugs as an adjunct to TMZ chemotherapy may have clinical applications in patients with malignant gliomas to improve the outcome.

Pituitary apoplexy during pregnancy is so rare that only 15 cases (12 pituitary adenomas, 2 lymphocytic neurohypophysitis, and 1 normal pituitary gland) have been published to date. Here, we report the case of a pregnant woman presenting with pituitary apoplexy from a nonfunctioning pituitary adenoma and provide a possible mechanism and management option for postoperative diabetes insipidus (DI).A 26-year-old woman presented with sudden onset of headache and bitemporal hemianopsia in the 26th week of her first pregnancy. Magnetic resonance imaging clearly revealed an 18 mm pituitary mass with a fluid-fluid level component displacing the optic chiasma upward. Endonasal endoscopic transsphenoidal surgery was successfully carried out 7 days after the onset of symptoms. DI became apparent immediately after the operation and was not controllable by arginine vasopressin (AVP) but by 1-desamino-8-D-arginine vasopressin (DDAVP) instead. This finding suggests an association between DI and vasopressinase secretion from the placenta, because vasopressinase can degrade AVP but not DDAVP. DI had diminished by the time the patient delivered a healthy girl at the 40th week of gestation.Postoperative DI associated with pituitary apoplexy during pregnancy should be treated by DDAVP, which is not affected by placental vasopressinase secretion.

Recently, intraoperative mapping has disclosed that, in addition to the classic language centers (that is, the Broca and Wernicke centers), other cortical regions may also play an important role in language organization. In the prefrontal cortex, although the lateral superior frontal gyrus (LSFG) could have language-related functions, there are no detailed reports that demonstrate the anatomical connection between the LSFG and other well-known language cortices, such as the Broca center. To show the existence of the structural connection, white matter association fibers between the inferior frontal gyrus (IFG) and the LSFG were examined using fiber dissection (FD) and diffusion tensor (DT) imaging-based tractography.Eight cadaveric cerebral hemispheres were dissected to reveal the association fibers between the IFG and LSFG. The DT imaging-based tractography studies targeting the prefrontal cortex were obtained in 53 right-handed patients who had no organic cerebral lesions.The association fiber tract between Brodmann area 44/45 (the Broca center in the dominant hemisphere) and LSFG were detected in all specimens by FD. In the DT imaging-based tractography studies, the tract was identified in all patients bilaterally, except for the 4 in whom the tract was detected only in the left hemisphere. This tract was spread significantly wider in the left than in the right hemisphere, and left lateralization was evident in male patients.Based on its character, this tract was named the Broca-LSFG pathway. These findings suggest a close relationship between this pathway and language organization. The structural anatomy of the Broca-LSFG pathway may explain speech disturbances induced by LSFG stimulation that are sometimes observed during intraoperative language mapping.

We report a case of pilocytic astrocytoma of the cerebrum presenting in an elderly patient. A 76-year-old man was admitted to our department due to the development of dysarthria. MRI showed a cystic mass with an enhanced small mural nodule in the left frontal lobe. At surgery, the cyst contents were aspirated, and the mural nodule was excised. Histological examination showed a pattern that is usually seen in pilocytic astrocytoma of the cerebellum, including loose and compact areas composed of pilocytic and stellate cells, a few eosinophilic granular bodies, but not Rosenthal fibers. Pilocytic astrocytoma is a common type of pediatric brain tumor that can arise within either the cerebellum or the hypothalamic/chiasmatic region, but rarely seen in the cerebral hemisphere at an advanced age. To our knowledge, only 45 cases of pilocytic astrocytoma of the cerebrum developing in an adult are reported. In those cases, the symptoms of the disease developed during the third decade of life. The onset at a most advanced age as in the present case is thought to be extremely rare.

High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor–brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor–brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.

A 62-year-old woman presented with an uncommon case of anaplastic meningioma manifesting as recent memory disturbance. Magnetic resonance imaging revealed a mass located in the right temporal lobe. She became unconscious because of uncal herniation and underwent urgent surgery. The tumor was completely resected, except for a lesion tightly attached to arteries. Histological examination indicated the presence of anaplastic meningioma with an extremely high MIB-1 labeling index (70%). After 43 days, the patient developed local recurrence and dissemination in the left temporal lobe. The exceptionally high MIB-1 labeling index corresponded with a short tumor doubling time (8.2 days). Whole-brain irradiation and linear accelerator surgery for disseminated lesions were performed, and the tumor growth halted. Although meningiomas rarely show malignant behavior, corresponding to World Health Organization grade III, it is necessary to consider malignant behavior when treating meningiomas.

Sweet’s syndrome (SS), an acute febrile neutrophilic dermatois, is characterized by fever, neutrophilia, tender erythematous kin lesions (papules, nodules, and plaques), and a diffuse infiltrate redominantly composed of mature neutrophils. Neuro-Sweet disase (NSD) is an extracutaneous manifestation of SS [1]. SS can lso present as a paraneoplastic syndrome, which is a malignancyssociated form of the condition that is most commonly related to cute myelogenous leukemia (AML) or myelodysplastic syndrome MDS). Therapy-related myelodysplastic syndrome (t-MDS) is rare but ne of the most lethal complications of alkylating agents such as emozolomide (TMZ) and ACNU [2], which are widely used for adjuant chemotherapy with or without radiotherapy for malignant lioma. In this study, we provide the first report of NSD mim

Gangliogliomas of the spinal cord are rare, and the conus medullaris is an extremely rare site for their occurrence. The authors present a case in which a ganglioglioma was found in the thoracolumbar spinal cord, including the conus medullaris, of a 5-year-old female patient with neurofibromatosis type 1 (NF1) who presented with paraparesis and urinary disturbance. MRI revealed an intramedullary lesion within the thoracolumbar spinal cord, including the conus medullaris, which was surgically removed. Pathological investigation showed a ganglioglioma consisting of glioneuronal tumor cells. This is the first report to provide a pathological description of a spinal cord ganglioglioma in a patient with NF1. Because gangliogliomas usually have a good prognosis following resection, it is important to clearly distinguish them from other NF1-associated lesions, even though ganglioglioma of the thoracolumbar spinal cord, including the conus medullaris, is an extremely rare condition.

[1] We report an uplift of 5 m with a horizontal displacement of more than 60 m due to the 2011 Tohoku-Oki earthquake. The uplift was measured by an ocean-bottom pressure gauge installed before the earthquake on a frontal wedge, which formed an uplift system near the Japan Trench. Horizontal displacements of the frontal wedge were measured using local benchmark displacements obtained by acoustic ranging before and after the earthquake. The average displacements at the frontal wedge were 58 m east and 74 m east-southeast. These results strongly suggest a huge coseismic slip beneath the frontal wedge on the plate boundary. The estimated magnitude of the slip along the main fault was 80 m near the trench. Our results suggest that the horizontal and vertical deformations of the frontal wedge due to the slip generated the tremendous tsunami that struck the coastal area of northeastern Japan.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a 38 amino acid peptide originally isolated from ovine hypothalamus. It has a potent stimulatory action on adenylate cyclase in the rat pituitary. The presence of PACAP was studied in the tumor tissues of ganglioneuroblastoma and neuroblastoma by radioimmunoassay and immunocytochemistry. Immunocytochemical studies showed positive immunostaining in 4 out of 7 ganglioneuroblastomas and 4 out of 6 neuroblastomas. Immunoreactive PACAP concentrations in tissues of 3 gangioneuroblastomas ranged from 14.5 to 27.8 pmol/g wet weight ( 20.0 ± 5.7 pmol/g wet weight, mean ± S.D.) and the concentration in one neuroblastoma tissue was 111.0 pmol/g wet weight. Reverse phase high performance liquid chromatography of the tumor tissue extract of ganglioneuroblastoma showed a peak eluting in the position of PACAP1–38 and smaller broad peaks eluting later. These results indicated that high concentrations of immunoreactive PACAP were present in the tumor tissues of ganglioneuroblastoma and neuroblastoma, and suggest the possibility that this peptide plays a pathophysiological role in some ganglioneuroblastomas and neuroblastomas.

To clarify co-carcinogenic effects of chrysotile (Chry) and amosite (Amo) asbestos with benzo(a)pyrene (Bap), 0.2 mg UICC (International Union against Cancer) standard reference sample of asbestos and 0.4 mg Bap were applied intratracheally once a week for 6 weeks. Eighteen and 24 months after the last instillation the number of tumors was examined. The Chry + Bap group yielded 37 tumors including 16 carcinomas in 12 animals, and the Amo + Bap group yielded 30 tumors including 11 carcinomas in 12 animals. Tumor-bearing animals were 100% in the Chry + Bap group and 92% in the Amo + Bap group, and carcinoma-bearing animals were 83% and 67%, respectively. The animals injected with Chry, Amo, and Bap alone developed no tumors. The number of tumors and carcinomas and the frequency of the tumor- or carcinoma-bearing animals in Chry + Bap and Amo + Bap were significantly higher than those of the groups injected independently. The number of tumors or the frequency of tumor-bearing animals was higher in Chry + Bap than in Amo + Bap; however, these differences were not significant. These results indicate that both Chry and Amo play an important role in the genesis of bronchogenic carcinoma.

Minority carrier properties, i.e., the lifetime, τ, and the diffusion coefficient, D, of p-type electromagnetic cast polycrystalline silicon wafers, have successfully been evaluated from the measurement of the frequency-domain photocurrent by a novel dual mercury probe method. The difference of more than one order in τ has been observed at different portions on the same cast polycrystalline Si wafer, corresponding to the existence of grain boundaries. In addition, the deviation in D has been experimentally established to be small in spite of the large difference in τ.

肺癌原発巣の同一結節内における中心部と辺縁部との癌細胞の細胞活性を比較するために, 29例の原発性肺癌の手術材料を用いて, Ag NORs数の計測とPCNA陽性率とを算出した. 29例の原発性肺癌手術例のうち扁平上皮癌は9例, 乳頭型腺癌および腺管型腺癌はそれぞれ10例であった.その結果,(1) 組織型や分化度にかかわりなく, 中心部の癌細胞1個当たりのAg NORs数は辺縁部のそれよりも多く認められた. (2) 癌細胞1個当たりのAg NORs数は分化度が高くなるに従って減少した. (3) 低分化扁平上皮癌以外の症例では結節辺縁部に存在する癌細胞のPCNA陽性率は中心部のそれよりも高率であった. 以上の所見は, 癌細胞の平均AgNORs数とPCNA陽性率との間には明らかな関連性が認められないことを示し, またAg NORs数は癌細胞の分化に関与していることを示唆している.

Background The DNA repair protein O(6)-methylguanine-DNA methyltransferase is a drug-resistant protein, which protects the tumors from chemotherapeutic alkylating agents, such as temozolomide. The methylation status of O(6)-methylguanine-DNA methyltransferase promoter has been shown to be a major predictive factor for clinical outcome in glioma patients when treated by alkylating agents. Thereby, there were many reports on O(6)-methylguanine-DNA methyltransferase promoter methylation and mRNA expression in primary glioma, in contrast, there were only a few studies in recurrent glioma. Methods We evaluated the O(6)-methylguanine-DNA methyltransferase mRNA expression and promoter methylation status in glioma patients before and after recurrence by quantitative real-time PCR and methylation-specific PCR assay. Thirteen paired primary and recurrent glioma patients were analyzed, including four patients in whom malignant transformation occurred from Grade II to Grade III. Results Methylation-specific PCR assay demonstrated that the status of O(6)-methylguanine-DNA methyltransferase promoter changed from methylated to unmethylated in 10 of 13 samples when the tumor relapsed. Moreover, intra-individual O(6)-methylguanine-DNA methyltransferase mRNA level increased in recurrent gliomas than in primary ones (P = 0.016). O(6)-methylguanine-DNA methyltransferase mRNA level was correlated with the methylation status (P = 0.012). Conclusions Our results give the evidence that the increase of O(6)-methylguanine-DNA methyltransferase mRNA expression caused by methylation changes in recurrence may be associated with chemoresistance in the recurrent glioma.

Background The anterolateral approach is one of the main routes for accessing suprachiasmatic lesions involving the anterior communicating artery (AComA) complex. Pterional (PT) craniotomy and its alternatives, including orbitozygomatic, orbitopterional, and mini-supraorbital craniotomies, have been developed as tailored frontotemporal craniotomies. One of the main differences between PT craniotomy and its alternatives is the removal of the orbital bone along with the sphenoid wing. However, which bone part is the most important to remove has not been discussed in relation to frontal lobe retraction. We have evaluated how the removal of the supraorbital bar versus the removal of the lateral orbital wall along with the sphenoid wing affects the relationship between the levels of frontal lobe retraction and area of exposure (AOE) in the suprachiasmatic region. Methods We performed three types of craniotomies: PT craniotomy, PT craniotomy with the removal of the supraorbital bar (PT-SO craniotomy), and PT craniotomy with the removal of the lateral orbital wall along with the sphenoid wing, i.e., the frontal process of the zygomatic bone and the orbital and cerebral faces of the greater sphenoid wing (PT-LO-SW craniotomy). For each craniotomy, the AOE around the suprachiasmatic region was measured at four different levels of frontal lobe retraction, namely, 5, 10, 15, and 20 mm, from the cranial base. Results At 5-mm retraction, PT-LO-SW craniotomy was the only craniotomy in which the AComA complex was visible. At 10-mm retraction, PT-LO-SW craniotomy afforded the greatest AOE among the three craniotomies, and the AOE was significantly greater than that of PT craniotomy (P = 0.025). At 15- and 20-mm retraction, there were no significant differences among the three craniotomies. Conclusions Treatment of lesions in the suprachiasmatic region via an anterolateral route involving a frontotemporal craniotomy requires sufficient removal of the lateral orbital wall along with the greater sphenoid wing so that brain retraction is minimized.

A 69-year-old woman developed hydrocephalus after the embolization of an incidentally detected unruptured large internal carotid artery aneurysm with bare platinum coils. Endovascular embolization resulted in near-total aneurysm occlusion. She complained of mild headache 18 hours after the procedure and magnetic resonance (MR) imaging performed on the 6(th) post-treatment day revealed wall enhancement and perianeurysmal brain edema. Follow-up MR imaging showed recanalization of the aneurysm and gradual ventricular enlargement. She presented with typical symptoms of hydrocephalus including disorientation, gait disturbance, and urine incontinence at 7 months post-embolization. We removed 30 ml of cerebrospinal fluid by lumbar tap, which improved her condition without symptom recurrence for 2 months. She did not require shunt placement. Post-interventional hydrocephalus is known in patients with unruptured aneurysms embolized with bioactive second-generation coils. This case shows that hydrocephalus can occur after aneurysm embolization with bare platinum coils without intracranial hemorrhage.

A 55-year-old man was admitted to our hospital complaining of left hemiparesis. Magnetic resonance imaging (MRI) showed a smooth ring-like enhanced cystic tumor in the right parietal lobe. He underwent gross total resection of the tumor under neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence guiding method. Histopathological examination of the tumor showed small cells formed epithelioid solid nests with some focus of duct-like structure. On the basis of the MRI and operative and histological findings, this tumor was diagnosed as a metastatic poorly differentiated carcinoma, although the primary cancer could not be detected by metastatic work-ups. Afterward, this tumor recurred repeatedly. Histopathological examination of specimen from the fourth surgery indicated that the tumor was a glioblastoma (GBM). In the review of the histology and immunohistochemistry of the first tumor, atypical fibrillary cells were seen between solid nests and positive for glial fibrillary acidic protein, therefore the tumor was retrospectively diagnosed as epithelioid GBM. We assessed whether the changes in histopathology were accompanied by changes in the methylation status of O6-methylguanine methyltransferase (MGMT) promoter and the status of 5-ALA fluorescence. The methylation status of the MGMT promoter was found to have changed from methylated to unmethylated and 5-ALA fluorescence became positive along with the histological change.

Four patients presented with intracerebral hemorrhage secondary to ventriculoperitoneal (VP) shunt insertion. VP shunt insertion was performed for idiopathic normal-pressure hydrocephalus (Case 1), hydrocephalus after cerebellar hemorrhage (Case 2), and subarachnoid hemorrhage followed by meningitis (Cases 3 and 4). Cerebral hemorrhage was confirmed 4 hours (Case 1), 2 days (Case 2), 7 days (Case 3), and 13 days (Case 4) after the operation. Cases 1 and 2 required intraoperative hemostasis for bleeding from the cortical vein. The 7 previous and our 4 patients were divided according to early (within 2 days after shunt placement, n = 6, Group 1) and delayed (5-13 days post-shunting, n = 5, Group 2) hemorrhage. Bleeding was attributable to venous occlusion due to intraoperative manipulation in Group 1, and to the vulnerability of brain tissue induced by a primary brain disease in Group 2.

Here, we report the case of a patient with cerebellar high-grade glioma that developed after the patient underwent treatment for medulloblastoma. A 34-year-old man visited our hospital with complaints of dizziness and truncal ataxia. Magnetic resonance image showed a cerebellar tumor with multiple cavernomas and two lesions that were suspected to be meningiomas. The cerebellar tumor was surgically removed. According to pathological examination, the tumor was a high-grade glioma that was positive for methylated O-6-methylguanine-DNA methyltransferase promoter. In the past, he had received radiotherapy at the age of 5, after which he was operated for desmoplastic medulloblastoma in his right cerebellar hemisphere. Seven years after the initial therapy, cavernoma-induced intracerebral hemorrhage of the right temporal lobe was noted. To our knowledge, this is the first case of radiation-induced double intracranial tumors accompanied by symptomatic cavernoma.

Gliomas are the most frequent malignant intracranial tumors arising from the brain or spinal cord tissue. The most malignant among them is glioblastoma multiforme (GBM), which constitutes approximately 20–25% of all primary intracranial neoplasms with an incidence of 3–4/100,000. This type of tumor is characterized by progressive overgrowth of neoplastic glial cells with widespread and relentless invasion, resulting in acquisition of resistance to treatment and a poor prognosis due to recurrence. These features hamper efficient surgical intervention of the disease. Current chemo/radiotherapy conditions act sublethally but cannot effectively suppress the proliferation of glioma cells. Despite some progress, the therapeutic options are yet limited, and novel therapeutic strategies are clearly needed. Targeting of disease-specific molecules involved in the proliferation, apoptosis, and invasion of the tumor cells as well as in tumor angiogenesis may offer a high potential for the development of more effective therapies for GBM. RNA interference (RNAi) has been emerging not only for in vitro target validation, but also for a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. Indeed, RNAi has shown to act against GBM efficiently in numerous preclinical studies. Many efforts have been devoted to overcome the three major obstacles in use of RNAi in vivo; their specificity, instability, and poor cellular delivery of bioactive small interfering RNA (siRNA) across the blood–brain barrier. The identification of effective target and the establishment of novel siRNA delivery systems are needed for the clinical applications of RNAi for treatment of GBM.

金沢大学医薬保健研究域医学系, The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p< 0.040) and rs3796863 (p< 0.005) showed significant associations with a subset of ASD (IQ > 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society.

To clarify whether serpentine and amphibole asbestos have different effects on the lung, UICC chrysotile and amosite asbestos were injected intratracheally into hamster lung, and the lungs were examined at 30 min, 1,4,8, and 24 h, and 2 and 4 days after asbestos application by light and scanning electron microscopy. A leukocyte and macrophage reaction appeared at 4 h and increased up to 2 days, and the cell reaction was stronger and more prolonged after application of chrysotile than after application of amosite asbestos. Furthermore, chrysotile induced more prominent cell (leukocytes or/and macrophages) necrosis and alveolar wall thickening. These findings indicate that chrysotile asbestos induces more stronger cell reactions in the alveolar wall, and is more noxious than amosite. Acta Pathol Jpn 42: 707–711, 1992.

A 39-year-old male was admitted complaining of nonproductive cough and dyspnea on exertion. Death occurred eight months after onset of the symptoms. Autopsy examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by a tumor. The tumor had infiltrated into the left upper lobe and mediastinal lymph nodes, and metastatic nodules were found in both lungs and in the left adrenal gland. Small foci of infarction were noted in the lower lobes of both lungs. The tumor cells were of two types; pleomorphic spindle cells and bizarre multinucleated giant cells. Immunohistochemically, they were positive for vimentin, myosin, and lysozyme, but negative for desmin and muscle-specific actin. The cytoplasm of the tumor cells was showed by electron microscopy to contain microfilaments, dense bodies, and pinocytotic vesicles. We diagnosed this case as undifferentiated sarcoma of the pulmonary artery. Approximately 100 cases of pulmonary artery sarcoma have been reported. Histopathologically, almost all of the reported cases showed both spindle cells and pleomorphic giant cells, indicating a biologically anaplastic neoplasm.

Minority carrier recombination lifetime, τ, and diffusion coefficient, D, in the bulk, and surface recombination velocity, s, of silicon wafers are evaluated from the measurement of the frequency-domain photocurrent by a novel dual mercury probe method. The detailed experimental and analytical procedures to determine τ, D, and s are described and discussed from several points of view. From investigations of the influence of the absorption coefficient, α, and intensity of a probing intensity-modulated laser diode (LD) beam and of a lateral diffusion effect of minority carriers, it is shown that, for strong surface absorption of the LD beam, a one-dimensional, approximate analysis can be used to determine τ, D, and s. Applications to Si wafers, including electromagnetic cast polycrystalline Si and oxidized Si, are demonstrated

肺の腺癌, 扁平上皮癌, 小細胞癌を伴った広範囲な肺線維化を示す10例, および癌を伴わない広範囲な肺線維化を示す15例の剖検肺を用い, 線維化巣を病理組織学的に間質性, および肺胞内線維化巣とに二大別し, 線維化の形態と上皮細胞増生巣の発生頻度との関連を検討した.さらに (異型) 腺様増生,(異型) 扁平上皮化生を示す細胞の核小体形成領域数を計測した.その結果, 上皮細胞増生巣は左下葉に高頻度に見られ, 全肺葉で中枢側よりも末梢側に多発する傾向が見られた.広範囲な線維化を伴った腺癌例においては, 肺胞内線維化を示した例に比べて, 間質性線維化を示した例に上皮細胞増生巣および異型腺様増生巣がより高頻度に認められた.核小体形成領域数は腺様増生巣, 異型腺様増生巣, 腺癌細胞の順に増加した.異型扁平上皮化生巣でも扁平上皮化生巣よりも核小体形成領域数は多く認められた.

TAZAWA, Y., NISHINOMIYA, F., NOGUCHI, H., TSUCHIYA, S., HAYASHI, Y., ABUKAWA, D., WATABE, M., NAKAGAWA, M., IMAIZUMI, M., OHI, R., TADA, K. and KONNO, T. Hepatocellular Carcinoma in Children with Hepatitis B Surface Antigen. Tohoku J. Exp. Med., 1992, 167 (1), 47-55-This study discusses four children of hepatocellular carcinoma (HCC) who were asymptomatic HBsAg carriers or had HBsAg-positive chronic hepatitis for 3 to 11 years before the occurrence of the carcinoma. Three of these four patients were positive for anti-HBe at 3 to 5 years before the diagnosis of hepatocellular carcinoma. Autopsy findings disclosed liver cirrhosis in all the four patients. To the best of our knowledge few reports have documented children in HBsAg carrier status or with HBsAg-positive hepatitis prior to the development of hepatocellular carcinoma. It is emphasized that HBsAg-positive children, with or without detectable hepatic lesions in routine examinations, have a possibility of developing HCC, and should be carefully monitored for long periods.

Object Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been broadly recognized as a beneficial tool for the resection of glioblastoma multiforme (GBM). Fluorescence in the ventricular walls, which were apparently free of macroscopic tumor or MR imaging enhancement indicative of CSF dissemination, was detected during surgery for GBM. To evaluate the clinical significance of the 5-ALA fluorescence, the authors resected ventricle wall tissue together with the adjacent tumors for pathological examination and then followed up the clinical courses of the patients. Methods Seven consecutive GBMs located near the lateral ventricle were surgically treated using a fluorescence-guided technique with 5-ALA at the authors' hospital since acquiring instrumentation for the detection of 5-ALA fluorescence in 2007. All of the procedures were performed using a ventricular entry, and 5-ALA fluorescence of the ventricular wall was detected despite the absence of macroscopic tumor invasion of the wall. Results A pathological examination of the resected ventricular wall tissues revealed tumor cells in 6 of the 7 cases and disruption of the ependymal cell layer in all 7 cases. Delayed communicating hydrocephalus followed surgery in all 7 patients, and ventricular wall enhancements on MR imaging were demonstrated after hydrocephalus in 2 of the patients. Conclusions Data in this study suggest that 5-ALA fluorescence of the ventricular wall may be predictive of postoperative hydrocephalus associated with CSF dissemination even in cases without evidence of CSF dissemination on MR imaging studies before surgery. The authors also speculate that postoperative radiotherapy covering the whole ventricular system may be a better therapeutic option for these patients.

Immune thrombocytopenic purpura (ITP) has been associated with several hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas and chronic lymphocytic leukemia, but it is rare in children with acute lymphoblastic leukemia (ALL). Here, we report a 7-year-old girl with chronic ITP during early intensive phase of chemotherapy for ALL. She underwent splenectomy because thrombocytopenia had persisted even after treatment with intravenous immunoglobulin (IVIG), steroids, vincristine, rituximab, and anti-D antibody. After splenectomy, her platelet count had recovered, and maintenance therapy could be resumed with a support of IVIG. To our knowledge, this is the first child case of chronic ITP during chemotherapy for ALL and splenectomy was effective in this patient.

Purpose: Glioblastoma represents the malignant brain tumor that is most refractory to treatment and in which the identification of molecular target(s) is urgently required. We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3β (GSK3β), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma. Experimental Design: The active fraction of GSK3β that is phosphorylated at the tyrosine 216 residue (pGSK3βY216) was identified in glioblastoma cell lines. GSK3β activity for phosphorylating its substrate was detected in these cells by nonradioisotopic in vitro kinase assay. Results: Higher expression levels of GSK3β and pGSK3βY216 were frequently detected in glioblastomas compared with nonneoplastic brain tissues. Inhibition of GSK3β activity by escalating doses of a small-molecule inhibitor (AR-A014418) or inhibition of its expression by RNA interference induced the apoptosis and attenuated the survival and proliferation of glioblastoma cells in vitro. Inhibition of GSK3β was associated with increased expression of p53 and p21 in glioblastoma cells with wild-type p53 and with decreased Rb phosphorylation and expression of cyclin-dependent kinase 6 in all glioblastoma cell lines. Administration of AR-A014418 at a low dose significantly sensitized glioblastoma cells to temozolomide and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, chemotherapeutic agents used in the clinical setting, as well as to ionizing radiation. Conclusion: These results indicate that GSK3β exerts a pathologic role by promoting the survival and proliferation of glioblastoma cells and by protecting them from apoptosis via the inactivation of p53- and/or Rb-mediated pathways. Consequently, we propose that GSK3β provides a potential therapeutic target in glioblastoma.

Adrenocortical carcinoma (ACC) is a rare neoplasm but some of the cases are highly malignant. Clinical outcome of the patients with advanced ACC still remained poor or dismal despite recent development of aggressive antitumor therapies. Target-specific therapies have been developed in a number of human malignancies and resulted in therapeutic benefits in some cancer patients. However, these therapies are only effective in the cases in which corresponding targets are expressed in tumor tissues. Therefore, we evaluated expression of potential surrogate markers using immunohistochemistry in archival materials of adrenocortical carcinoma in order to explore the potential application of target specific therapies in ACC in this study. We immunolocalized ten established or potential surrogate markers of target-specific therapies, located in the Ras/extracellular signal-regulated kinase and phosphatidylinositol-3 kinase/Akt pathways, in 41 ACC cases, 54 adrenocortical adenoma (ACA) cases, and five nonpathological adrenal glands and correlated the findings with clinicopathological factors of the patients. Among these markers examined, only epidermal growth factor receptor (EGFR) was significantly more abundant in ACC than in ACA (P < 0.01). These findings suggest that the agents which specifically inhibit signal transductions through EGFR such as monoclonal antibodies against EGFR are considered to be worthwhile to be attempted in future clinical studies.

Background: Intracranial germ cell tumors (GCTs) are rare neoplasms. Little is known about the pathogenesis of these tumors. The BCL10 gene, a proapoptotic signaling molecule involved in the Apaf-1/caspase-9 cell death pathway, may act as a tumor suppressor gene in multiple types of tumors including testicular GCTs. Methods: To evaluate whether alterations in the BCL10 gene play a role in the genesis of intracranial GCTs, we analyzed the BCL10 gene in 10 pure germinomas (PGs) and 10 nongerminomatous GCTs. Results: We found no inactivating mutations; however, 5 of 10 PGs and 1 of 10 nongerminomatous GCTs manifested specific single nucleotide polymorphisms (SNPs) that carried an amino acid substitution at codon 5 in exon 1 or codon 162 in exon 3. This SNP occurs at higher frequency in patients with PGs than healthy individuals (p = 0.07). CSF dissemination occurred in 4 of our 6 patients manifesting SNP (p = 0.037). Conclusions: Our data suggest that this specific SNP in the BCL10 gene may be partly responsible for the tumorigenesis of PG in Japanese individuals, and may be associated with the aggressive nature of these tumors.