Biomedical subjects

Jun-Ichi Kuratsu

Publications and source records attributed to Jun-Ichi Kuratsu.

At least 19 recordsLinked to original sources

PubMed2007

Glioblastoma with an intratumoral feeding-artery aneurysm.

We report a patient with recurrent glioblastoma, in whom serial magnetic resonance angiography (MRA) demonstrated gradual enlargement of an artery feeding the tumor and the development of an intratumoral aneurysm that led to intratumoral hemorrhage. The literature contains no previous reports that clinically document intratumoral aneurysms arising from these vessels. This is a rare case of glioblastoma in which the association of an intratumoral feeding-artery aneurysm, whose rupture led to intratumoral bleeding, was documented by serial MRA imaging and follow-up.

Adult↗

PubMed2006

Stereotactic surgery for subthalamic nucleus stimulation under general anesthesia: a retrospective evaluation of Japanese patients with Parkinson's disease.

We compared retrospectively the outcome of bilateral subthalamic nucleus (STN) stimulation in 15 patients with Parkinson's disease who underwent the procedure under general anesthesia (GA) with that achieved in 10 patients under local anesthesia (LA). At 3 months postoperatively, all cardinal parkinsonian motor symptoms, evaluated on Unified Parkinson's Disease Rating Scale were significantly improved compared to preoperative baselines in both groups. The administration of GA did not adversely affect postoperative improvements in motor and daily activity scores, except for off-medication bradykinesia. Our results suggest that GA compares favorably with LA in surgical procedure for bilateral STN stimulation.

Aged↗

PubMed2006

Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia.

We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.

Animals↗

PubMed2006

Therapeutic time window and dose dependence of neuroprotective effects of sodium orthovanadate following transient middle cerebral artery occlusion in rats.

Vanadium is widely distributed in the environment and exhibits various biological and physiological effects in the human body. We previously documented the neuroprotective effect of sodium orthovanadate (SOV) against in rodents i.v. injected with 2 ml/kg 50 mM SOV just after the induction of middle cerebral artery occlusion (MCAO; 0 min post-MCAO). To evaluate its potential clinical use, we determined here therapeutic time window (0, 45, and 90 min post-MCAO) and the neuroprotective dose (2 ml/kg, 12.5, 25, 37.5, and 50 mM) of SOV in rats. A single injection of 50 mM SOV at 0 or 45 min post-MCAO produced similar neuroprotective effects, and even 50 mM delivered 90 min post-MCAO exerted significant neuroprotection. Although the maximal neuroprotective effect was obtained at 50 mM SOV, 25 mM injected once and 12.5 mM delivered at 0 and 45 min post-MCAO significantly reduced the infarct volume. We also documented that SOV treatment ameliorates ischemic neuronal cell injury via the activation of both protein kinase B (Akt) and extracellular signal-regulated kinase (ERK), inhibits serum glucose, and elicits the gradual recovery of regional cerebral blood flow (rCBF) after transient MCAO in rats. To elucidate the important factor(s) involved in the neuronal protection afforded by SOV, we measured Akt and ERK activity, physiological parameters, blood glucose levels, and rCBF following various SOV treatments. In conclusion, Akt activation was the most important factor in SOV-induced neuroprotection; ERK activation, the gradual recovery of rCBF, and decreased blood glucose were weak contributors.

Animals↗

PubMed2006

Spontaneous arteriovenous fistula of the orbit: case report.

BACKGROUND: A spontaneous arteriovenous fistula of the orbit is exceedingly rare. We report the first case of such condition treated with direct surgical exposure of the superior ophthalmic vein (SOV) followed by embolization. CASE DESCRIPTION: A 55-year-old man presented with upper lid swelling, conjunctival chemosis, and proptosis of the right eye. Angiography revealed an intraorbital shunt supplied by the ophthalmic artery whose venous drainage curved anteriorly to the SOV. Because transarterial and transvenous endovascular approaches to treat the fistula were impossible, we performed direct surgical exposure of the SOV followed by the embolization of the fistula. Postoperative angiograms demonstrated complete closure of the fistula. All symptoms had disappeared by 2 months after surgery. CONCLUSIONS: For appropriate treatment planning, it is necessary to identify the location of the shunt. In cases where transarterial and transvenous endovascular approaches to treat the fistula are difficult or impossible, direct surgical exposure of the SOV followed by embolization may accomplish complete closure of the fistula without significant risk for iatrogenic injury.

Angiography↗

PubMed2006

A long-term ventricular drainage for patients with germ cell tumors or medulloblastoma.

BACKGROUND: Hydrocephalus associated with intracranial germ cell tumors or disseminated medulloblastoma has been treated with ventriculoperitoneal shunt. However, this procedure has a potential risk of intraperitoneal metastasis of these brain tumors. To prevent this potential risk and to minimize the risk of infection, we developed a percutaneous long-tunneled ventricular drainage (PLTVD). To confirm the effectiveness, we retrospectively analyzed the results of this procedure. METHODS: From 1979 to 2003, we have treated 96 patients with germ cell tumors and medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31; medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal fluid drainage to manage the obstructive hydrocephalus due to persistent tumor or communicating hydrocephalus due to dissemination. We performed PLTVD for these cases using a flow-controlled shunt device and percutaneous long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen and connecting to a closed drainage system. The occurrence of extraneural metastasis and the incidence of infection were evaluated. RESULTS: The average duration of drainage was 74 days (range, 34-115 days). All 13 cases received full-dose chemotherapy and radiotherapy without infectious complications or extraneural metastasis. CONCLUSIONS: Percutaneous long-tunneled ventricular drainage was an effective method to manage long-lasting obstructive or communicating hydrocephalus with germ cell tumors and medulloblastoma.

Adolescent↗

PubMed2006

Rising incidence of primary central nervous system lymphoma in Kumamoto, Japan.

BACKGROUND: Primary central nervous system lymphoma is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL is reportedly on the increase in some parts of the world in the last 2 decades. METHODS: We surveyed 4007 patients diagnosed with PIT between 1989 and 2004, with histologic diagnosis being obtained in 70% of the patients. Of these, the PCNSL cases were reviewed. RESULTS: Of 4007, 136 (3.4%) carried a diagnosis of PCNSL. At 0.41 per 100,000 per year, the age-adjusted incidence rate for that period was higher than that for the period from 1989 to 1998 (0.29 per 100,000 per year). Moreover, the number of patients with PCNSL doubled from 45 (1989-1996) to 91 (1997-2004). CONCLUSIONS: Our findings point to an increase in the incidence of PCNSL among immunocompetent individuals in Kumamoto Prefecture.

Age Distribution↗

PubMed2006

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Adolescent↗

PubMed2005

Functional proteins involved in regulation of intracellular Ca(2+) for drug development: role of calcium/calmodulin-dependent protein kinases in ischemic neuronal death.

Excessive elevation of intracellular calcium level seems to be a trigger of ischemic neuronal injury. Calcium/calmodulin (CaM)-dependent protein kinase kinase (CaM-KK) is an upstream kinase for CaM kinase IV (CaM-KIV) that was reported to prevent apoptosis through phosphorylation of CREB (cyclic AMP responsive element-binding protein). We here observed that CaM-KK could directly activate Akt, thereby preventing apoptosis in cultured cells. Then we examined changes in Akt and CaM-KIV activities in gerbil forebrain ischemia. In 5-min-ischemia-caused delayed neuronal death in hippocampal CA1 neurons, Akt and CaM-KIV activities were decreased after reperfusion. On the other hand, during induction of ischemic tolerance, Akt activity gradually and persistently increased in the CA1 neurons with transient increase in CREB phosphorylation. Inhibition of Akt activity with wortmannin or CREB-DNA binding with CRE-decoy injection resulted in failure of generation of ischemic tolerance. These results indicated activation of Akt and CaM-KIV play important roles in induction of the ischemic tolerance. Activation of CaM-KK may provide a new strategy for overcoming the ischemic stress.

Androstadienes↗

PubMed2005

A case of leptomeningeal carcinomatosis from esophageal basaloid carcinoma diagnosed by quantitative reverse transcription-polymerase chain reaction for carcinoembryonic antigen.

We describe herein the case of a 68-year-old man who experienced leptomeningitis after esophagectomy from an esophageal basaloid carcinoma. Although the patient had a good operative course for the first 10 days after surgery, he suddenly had general convulsions with unconsciousness. He was placed on mechanical ventilation in an intensive care unit. Computed tomography and magnetic imaging resonance did not reveal any abnormal findings. No abnormal data in the cerebrospinal fluid were found by biochemical, virological, and cytological examination. The positive expression of carcinoembryonic antigen messenger ribonucleic acid in cerebrospinal fluid was detected by a quantitative reverse transcription-polymerase chain reaction method. Immunohistochemical staining using an anticytokeratin antibody confirmed the presence of tumor cells in the cerebrospinal fluid. Spontaneous breathing was recovered after treatment with systemic chemotherapy. Six months after surgery, computed tomography revealed multiple brain metastases. This case demonstrates that the quantitative reverse transcription-polymerase chain reaction method of analyzing carcinoembryonic antigen messenger ribonucleic acid may be a sensitive and useful method for determining leptomeningeal metastasis before the detection of tumors by cytological and imaging examinations in patients with cancer.

Aged↗

PubMed2005

C-kit expression in germinoma: an immunohistochemistry-based study.

In our immunohistochemical study of 25 human primary intracranial germinomas and germinomas with syncytiotrophoblastic giant cells (STGC), we stained the same sections for c-kit and placental alkaline phosphatase (PLAP). Immunohistochemical expression was graded using a semi-quantitative scoring system where 3+ =51-75%, and 4+ =76-100%. Of the 25 cases, 7 (28%) were graded 3+ and 18 (72%) 4+ for c-kit; 8 (32%) were 3+ or 4+ for PLAP. All 3 cases negative for PLAP-staining were strongly positive and all embryonal carcinomas, immature teratomas, and yolk sac tumors were negative for c-kit staining. The soluble isoform of c-kit (s-kit) is reportedly detectable in cerebral spinal fluid of patients with germinomas and germinomas with STGC. C-kit and s-kit may be powerful tumor markers for germinomas with or without STGC.

Adolescent↗

PubMed2005

Comparative clinical study of the anti-emetic effects of oral ramosetron and injected granisetron in patients with malignant glioma undergoing ACNU chemotherapy.

The effectiveness of ramosetron tablets and granisetron injection was compared for reducing the frequency of nausea, vomiting, and anorexia in patients with malignant glioma undergoing ACNU chemotherapy. Patients with malignant glioma to be treated with ACNU chemotherapy were randomly assigned to receive oral ramosetron (20 patients) or intravenous granisetron (19 patients) prior to ACNU injection. Gastrointestinal toxicity within 48 hours of ACNU injection was compared to that in patients who had received ACNU chemotherapy with dopamine D2 receptor-blocker as a historical control group. Within 24 hours of the administration of ACNU, 15 of the 20 patients treated with ramosetron and 16 of the 19 treated with granisetron were nausea-free, and 14 of the former and 14 of the latter regained their normal appetite. There was no significant difference in the anti-emetic effects. Ten of the 17 controls experienced no vomiting within 6 hours of the injection of ACNU, five were nausea-free within 24 hours, and two retained their normal appetite within 24 hours. Oral ramosetron has the same anti-anorectic and anti-emetic effects as intravenous granisetron. Ramosetron tablets are less expensive and are easy to take, so should be on the list of first-choice anti-emetic drugs for patients treated with ACNU chemotherapy.

Adult↗

PubMed2005

Skull metastasis from clear cell chondrosarcoma.

A 67-year-old man presented with left lower cranial nerve paresis and dysfunction of the left cerebellar hemisphere 4 years after amputation of the left lower leg because of clear cell chondrosarcoma (CCC). Neuroimaging studies showed an osteolytic extradural mass with homogeneous enhancement in the left posterior fossa. Bone scintigraphy disclosed a single high-uptake lesion at the same site. The tumor was removed totally via a left suboccipital craniotomy. Histological examination found mainly clear cells arranged in a microlobular pattern separated by thin fibrovascular stroma. The nuclei were regular with few mitotic figures. Immunohistochemical staining showed the tumor cells reacted intensely for both S-100 protein and vimentin. Osteoclast-like multinucleated giant cells were found at the periphery of the lobules. The primary tumor showed the same findings and the metastatic tumor manifested no malignant change. The histological diagnosis was metastatic CCC. CCC is a very rare neoplasm with slow growth and low-grade malignancy. Distant metastasis is rare but can occur in the skull base bone despite radical resection of the primary tumor. Osteolytic findings of homogeneous enhancement on magnetic resonance imaging and a high uptake on bone scintigraphy are indicative of metastatic tumor from previous CCC.

Aged↗

PubMed2005

Beta-catenin cleavage in non-apoptotic cells with reduced cell adhesion activity.

Beta-catenin functions both as a regulator of cadherin-mediated cell-cell adhesion and a mediator of Wnt signaling. Recently, caspase-3-dependent cleavage of beta-catenin was demonstrated to occur during apoptosis. Here, we show that beta-catenin is proteolytically cleaved in G401 Wilms' tumor cells that were detached from the culture dish. Beta-catenin cleavage products of the same electrophoretic mobility were detected in G401 cells after induction of apoptosis with staurosporine and cell cycle arrest by aphidicolin. The detached cells show no sign of anoikis and approximately 90% of the floating cells were able to reattach to new dishes. Furthermore, beta-catenin was not cleaved in cells cultured on dishes coated with poly(2-hydroxyethylmethacrylate), which inhibits cellular attachment on the dishes, with approximately 90% of cells viable under these conditions. All beta-catenin cleavage products lost N-terminal and C-terminal regions and were unable to associate with alpha-catenin, which is responsible for actin filament binding and organization. However, they were still able to associate with E-cadherin. Aggregation assays revealed that the floating cells had weak aggregation compared with the attached cells. These results suggest that the cleavage of beta-catenin during cell detachment functions at least in part to remove the alpha-catenin-binding domain, thereby reducing cell adhesion activity.

Amino Acid Sequence↗

PubMed2005

The environment of increased concentration of docosahexaenoic acid in glioblastoma may suppress the anti-tumor effect of macrophages.

Regarding glioblastoma, there has been controversy over whether a large number of infiltrating macrophages act as anti-tumor effectors or not. It has been exhibited that intratumoral lipid environments have a possible influence on anti-tumor immunity. Necrosis of glioblastoma and non-necrotic tissues of astrocytic tumors were analyzed to compare the amount of free docosahexaenoic acid (DHA) content. The apoptosis inducible effects of DHA on macrophages derived from peripheral blood monocytes and cultured glioma cells were evaluated by flow cytometry. The influence of DHA on the anti-tumor effects of macrophages was assessed at 0, 30, 60, and 90 mM of DHA by (51)Cr releasing assay and MTT assay. The mean concentration of free DHA in necrotic tissues (757.6 mmol/kg) was 5 times higher than that in non-necrotic tissues (147.2 mmol/kg). The DHA concentration of 30 mM induced apoptosis in macrophages, however, glioma cells were not affected even at a DHA concentration of 60 mM. Macrophages pre-exposed to DHA for 24 h decreased the cytotoxicity to U251MG cells as shown by (51)Cr releasing assay. Total viability of co-cultured macrophages and U251MG cells showed an increase at high concentrations of DHA (60 and 90 mM) according to 24 h MTT assay, although each separate culture did not. The DHA concentration in necrosis of glioblastoma was sufficient for macrophages to cause apoptosis and suppress their anti-tumor effects. The results suggest that liberated DHA in necrosis can induce apoptosis in macrophages and inhibit their functions.

Apoptosis↗

PubMed2004

Integrin-linked kinase (ILK) regulation of the cell viability in PTEN mutant glioblastoma and in vitro inhibition by the specific COX-2 inhibitor NS-398.

We report the increased activity and expression of the ILK protein in human glioblastomas and demonstrate that ILK activity is regulated by PTEN. The transfection of wild type-PTEN into the glioblastoma cell line U-251 MG altered the localization of ILK in the cell membrane; transfection with PTEN down-regulated PKB/Akt-Ser-473 phosphorylation via the inhibition of ILK-signaling. Our results suggest that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The selective COX-2 inhibitor NS-398 was found capable of down-regulating ILK and PKB/Akt phosphorylation. Our data indicate that inhibition of ILK signaling may be beneficial in the treatment of PTEN-deficient glioblastoma.

Brain↗

PubMed2003

Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.

Adolescent↗

PubMed2003

Novel Guglielmi detachable coils (GDCs) for the treatment of brain aneurysms. In vitro study of hydroxyapatite coating on Pt plate as GDCs model.

With the use of an alternate soaking process a thin layer of hydroxyapatite (HAp) was formed on a platinum plate (Pt plate) which was used as a model for Guglielmi detachable coils (GDCs). The in vitro coagulant activity of the HAp-coated Pt plate was evaluated for the purpose of brain aneurysm treatment. In order to fix and to form the apatite layer homogeneously, beta-mercaptopropionic acid was immobilized onto the Pt surface prior to use. The HAp layer was formed on the beta-mercaptopropionic acid-fixed Pt plate surface, and quantitative control of apatite formation was achieved by controlling the number of alternate soaking process cycles. The HAp formed on the Pt plate surface was confirmed by X-ray diffraction and X-ray photoelectron spectroscopy studies. Blood interaction with the Pt plate was altered from nonthrombotic to highly thrombotic by forming a HAp layer on the surface. The alternate soaking process is an appropriate method to modify the GDCs. Complete treatment of brain aneurysms is expected with the use of HAp-coated GDCs, which would allow formation of a stable blood clot.

3-Mercaptopropionic Acid↗