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Biomedical subjects

Jun A Takahashi

Publications and source records attributed to Jun A Takahashi.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of pituitary macroadenomas with multidetector-row CT (MDCT): comparison with MR imaging.

INTRODUCTION: It is important to have information on cavernous sinus extension and bony destruction in pituitary macroadenomas before surgery, but magnetic resonance (MR) imaging cannot always depict them. In the present study we sought to determine whether multidetector-row computed tomography (MDCT) could provide preoperative information in addition to that provided by MR imaging in pituitary macroadenoma. METHODS: The subjects comprised 33 consecutive patients (15 women, 18 men; mean age 50 years) with surgically proven macroadenoma. For MDCT, using the soft-tissue window and bone window, three orthogonal multiplanar reconstruction images were generated from venous-phase contrast-enhanced 0.5-mm isotropic voxel data. MDCT and MR images were evaluated with regard to: (1) clarity of tumor margins; (2) identification of the normal pituitary gland; (3) identification of erosion or destruction of the sellar floor; and (4) visualization of the adjacent optic pathways. RESULTS: MDCT more clearly demonstrated the lateral tumor margin than MR imaging (P = 0.002). No significant differences in visualization of the normal pituitary gland were noted between MDCT and dynamic MR imaging (P = 0.7). MDCT more clearly demonstrated sellar floor erosion or destruction at the sphenoid sinus than MR imaging (P < 0.001). MR imaging was superior to MDCT for visualizing the adjacent optic pathways (P < 0.001). CONCLUSION: MDCT is superior to MR imaging for assessing lateral tumor margin and the sellar floor at the sphenoid sinus. MDCT offers useful preoperative information in addition to that obtained from MR imaging.

Adenoma↗
PubMed2006

Neuropoietin induces neuroepithelial cells to differentiate into astrocytes via activation of STAT3.

Neuropoietin (NP) is a recently identified member of the interleukin (IL)-6 family of cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, and is highly expressed in embryonic brain. In this study, we show that NP has the potential to induce neuroepithelial cells to differentiate into astrocytes. NP stimulation leads to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which is clearly inhibited by either expression of a dominant-negative form of a transcription factor, signal transducer and activator of transcription 3 (STAT3) or by a nucleotide-substitution in the STAT3-binding element within the gene promoter. We further show that NP induces binding of endogenous STAT3 to its cognate sequence within the gfap gene promoter in neuroepithelial cells. Moreover, like the other IL-6 cytokine family members, NP promotes astrocyte differentiation in a synergistic manner with bone-morphogenetic protein (BMP)-2. Taken together, our data indicate that NP can be considered as a new astrocyte-inducing cytokine in the developing brain.

Animals↗
PubMed2006

Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation.

Aquaporins (AQPs) is a water channel family which facilitates the passage of water across cell membranes. Recently, expression of aquapporin 1 (AQP1) was found to be involved in not only water transport but also tumorigenesis. In present study, we analyzed the expression of AQP1 in 26 consecutive cases of human hemangioblastomas. Significant upregulation of AQP1 expression was found in hemangioblastomas compared with control brain (P=0.002). In hemangioblastomas, expression of AQP1 was predominantly localized on membranes of stromal cells. The expression level of AQP1 in cystic group of hemangioblastomas is much higher than that of solid group (P=0.021). Most hemangioblastomas showed a negative expression of AQP1 on endothelial cells. These results imply that increased expression of AQP1 in stromal cells may play a role in cyst formation and tumorigenesis of heman-gioblastomas.

Adult↗
PubMed2006

A dyad symmetry element in the fibroblast growth factor-2 gene promoter with different levels of activity in astrocytoma and hepatocelluar carcinoma cell lines.

Fibroblast growth factor-2 (FGF-2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF-2 gene expression. Here, we report the characterization of a unique element in the FGF-2 gene promoter. We investigated the transcriptional regulation of the FGF-2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF-2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied. Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF-2 gene expression.

Astrocytoma↗
PubMed2006

A step-by-step resection guided by electrocorticography for nonmalignant brain tumors associated with long-term intractable epilepsy.

To delineate a surgical strategy for long-term intractable epilepsy associated with nonmalignant brain tumor, we developed a protocol for 25 patients whereby removal of tumor alone and additional irritative peritumoral tissue between sulci (gyrectomy), as well as further resectioning, was performed based on intraoperative electrocorticogram results. In five patients, no irritative zones were observed that required resectioning following complete removal of tumors. Additional gyrectomy was indicated in 18 patients who demonstrated gliosis or cortical dysplasia in the peritumoral residual irritative zone. Remote irritative zone observed in two patients was correlated with long-term and frequent seizures. During a follow-up period of at least 5 years, seizure outcome was Engel category I in 92%, and all patients have remained tumor-free. Peritumoral gyrectomy as a means of removing likely epileptic tissue following tumor resection appears to be a useful method for treating long-term intractable tumoral epilepsy. Further resectioning of remote tissue should be considered in patients with severely intractable seizures.

Adolescent↗
PubMed2006

MR imaging of Liliequist's membrane.

Liliequist's membrane is an arachnoid structure well-known to neurosurgeons. However, the importance of this membrane had been lost until the development of endoscopic third ventriculostomy (ETV). ETV is superior in its minimal invasiveness, but in some subgroups of hydrocephalus, the effectiveness of ETV may be reduced. Liliequist's membrane may block the cerebrospinal fluid (CSF) flow from the defect of the third ventricle floor, which may cause failure of ETV. Liliequist's membrane can be visualized on magnetic resonance (MR) imaging in normal healthy individuals, however, its visibility is different among individuals. CSF artifacts exist to varying degrees, but do not impede visualization of Liliequist's membrane in most subjects. Since Liliequist's membrane is a cisternal structure, the three-dimensional (3D) constructive interference in steady state (CISS) sequence is useful. The outcome of ETV could be predicted with MR imaging findings of Liliequist's membrane in a patient with obstructive hydrocephalus. High-field (> or =3 Tesla) MR imaging of Liliequist's membrane also offers superior resolution and is expected to provide additional information about Liliequist's membrane.

Arachnoid↗
PubMed2006

Initial experiences of palliative stereotactic radiosurgery for recurrent brain lymphomas.

In Kyoto University Hospital, stereotactic radiosurgery (SRS) has been performed for its rapid palliative effect in patients with recurrent primary central nervous system lymphoma (PCNSL), often in combination with salvage chemotherapy. In the present study, the treatment outcome and toxicity of SRS for recurrent PCNSL was retrospectively evaluated. Between March 1998 and June 2004, 17 histologically proven recurrent PCNSLs in nine patients were treated with linac-based stereotactic radiosurgery. All patients had developed intracranial recurrences after initial treatment including external beam radiation therapy (EBRT). The prescribed dose was 10.0-16.0 (median 12.0) Gy. Seven of nine patients received systemic chemotherapy around the time of SRS. The target volume was 0.4-24.5 ml (median 3.5 ml). Initial tumor response could be evaluated in 15 of 17 lesions. Among them, radiological complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was observed in 3, 10, 2, and 0 lesions, respectively. One-year overall survival rate and relapse-free survival rate after first SRS was 58% and 22%, respectively. Improvement of symptoms was observed in six patients. The time from SRS to symptomatic relief was 1-57 days (median 3 days). No > or = grade 2 acute toxicities related to SRS were observed. In conclusion, linac-based SRS with a prescription dose of 10-12 Gy for recurrent PCNSL is useful for palliation, especially considering the short time, rapid tumor response, and low treatment toxicity.

Aged↗
PubMed2006

Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.

PURPOSE OF THE REPORT: The purpose of this report was to investigate the potential of positron emission tomography using F-18 fluorodeoxythymidine (FLT-PET) in evaluating primary brain tumors. MATERIALS AND METHODS: FLT-PET was performed in 25 patients with primary brain tumors. FLT uptake in the lesion was semiquantitatively evaluated by measuring the maximal standardized uptake value (SUVmax) and the tumor-to-normal tissue ratio (TNR). SUVmax and TNR were compared with the histologic grade and the expression of the proliferation marker (Ki-67). RESULTS: FLT uptake in normal brain parenchyma was very low, resulting in the visualization of brain tumors with high contrast. Both SUVmax and TNR significantly correlated with the malignant grade of brain gliomas, in which high SUVmax/TNR was obtained for high-grade gliomas. Patients with primary lymphoma also showed SUVmax/TNR equivalent to glioblastoma. There was a positive correlation between SUVmax/TNR and the Ki-67 index. In contrast, spuriously high SUVmax and TNR were obtained in 3 of 6 patients with suspected recurrent tumors (2 patients with recurrent grade 2 glioma and one patient with postoperative granuloma), all of which showed lesion enhancement on MRI after Gd administration. CONCLUSIONS: FLT-PET can be used to evaluate the malignant grade and proliferation activity of primary brain tumors, especially malignant brain tumors. However, the presence of benign lesions showing blood-brain barrier disruption cannot be distinguished from malignant tumors and needs to be carefully evaluated.

Adolescent↗
PubMed2006

Absence of tight junctions between microvascular endothelial cells in human cerebellar hemangioblastomas.

OBJECTIVE: Endothelial tight junctions form the main barrier of the blood-brain barrier (BBB). In human hemangioblastomas, cyst formation is a common and important clinical manifestation. Although most researchers consider that the cyst formation in hemangioblastomas may be caused by the breakdown of the BBB, the underlying molecular mechanisms for cyst formation remain unknown. At present, there are few reports about the change of tight junctions in microvessel endothelium of human hemangioblastomas. The purpose of this research is to investigate the change of tight junction and its major molecular components in microvessel endothelium of human hemangioblastomas. METHODS: Twenty-four consecutive patients with cerebellar hemangioblastomas were studied. Tight junctions in the microvessels of hemangioblastomas and the control brain were examined by electron microscopy. Immunohistochemistry and double immunofluorescent microscopy were used to analyze the expression of CLN5 and its relationship with astrocytic endfeet in the control brain and hemangioblastomas. Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blots were used to investigate the expression level of CLN5 in hemangioblastomas. Triple immunofluorescent microscopy was used to analyze the coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor on microvessels of hemangioblastomas. Clinical and experimental data were correlated and analyzed by the one-way analysis of variance, Kruskal-Wallis test, and Spearman rank correlation test. RESULTS: In the control brain, the paracellular cleft between adjacent endothelial cells is sealed by continuous strands of tight junctions. In cystic hemangioblastomas, a significant paracellular cleft could be found between adjacent endothelial cells. Some endothelial cells were connected with adherens junction and no tight junction was found between them. Compared with the control brain, expression of CLN5 was decreased in cystic hemangioblastomas (P < 0.05). Phosphorylated CLN5 was detected in most hemangioblastomas, but not in the control brain. Microvessels in hemangioblastomas showed a significant absence of astrocytic endfeet. Coexpression of vascular endothelial growth factor, vascular endothelial growth factor-R1, and placenta growth factor was detected in the endothelial cells. The Spearman rank correlation test showed a significant correlation between a greater degree of CLN5 expression and less morphological cystic formation in these patients studied (correlation coefficient = -0.520; P = 0.009). CONCLUSION: The continuity of tight junctions of the BBB is interrupted in human cerebellar hemangioblastomas. Significant absence of astrocytic endfeet and tight junctions can be found in microvessels of hemangioblastomas, which may lead to the breakdown of the BBB in these tumors. These findings suggest that the absence of tight junctions might play a role in cyst formation of hemangioblastomas.

Adult↗
PubMed2006

Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group.

OBJECT: This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.

Adult↗
PubMed2005

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

Animals↗
PubMed2005

Quantitative analysis of topoisomerase IIalpha to rapidly evaluate cell proliferation in brain tumors.

Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase IIalpha (topo IIalpha), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo IIalpha mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo IIalpha mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo IIalpha mRNA was significantly correlated with its immuno-staining index (p<0.0001, r=0.9077). Furthermore, it sharply detected that topo IIalpha mRNA decreased in growth-inhibited glioma cell. These results support that topo IIalpha mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.

Antigens, Neoplasm↗
PubMed2005

Clinical and molecular features of a TSH-secreting pituitary microadenoma.

We describe a case of a thyroid stimulating hormone (TSH)-secreting pituitary microadenoma, and report the systematic gene expression profile of the surgically- removed tumor. A 50-year-old woman was referred to our hospital because she had high TSH, free-T4, and free-T3 levels, and a pituitary tumor that was visualized with magnetic resonance imaging. Her basal TSH level was high even after a high T3 loading dose, and increased following administration of thyroid releasing hormone (TRH) even after administration of a high dose of exogenous T3. Her clinical symptoms and peripheral markers for T3 were responsive to exogenous T3. There was no thyroid hormone receptor (TR) beta gene mutation. The patient was diagnosed with a TSH-secreting pituitary adenoma, and trans-sphenoid surgery was performed. The histologic features and immunophenotype were consistent with a TSH-secreting pituitary adenoma. Reverse transcription-polymerase chain reaction analysis of pituitary hormones, pituitary-specific transcription factors, receptors, and transcriptional cofactors of clinical significance was performed on the removed tumor. The tumor expressed TSH, growth hormone, prolactin, alpha-subunit, pituitary transcription factor-1 (pit-1) but not proopiomelanocortin (POMC), prophet of pit-1 (prop-1) and pituitary cell-restricted T box factor (Tpit). TRbeta and TRH-receptor gene expression was normal. Three steroid receptor coactivators (SRC)-1, SRC-2, and SRC-3 were expressed. Nuclear receptor corepressor (N-CoR)2 was absent in the tumor, whereas nuclear receptor corepressor (N-CoR1) was expressed. Somatostatin receptor type 1 expression was significantly decreased, whereas type 4 receptor was expressed, which are unusual characteristics for pituitary tumors. The gene expression pattern in the tumor might have a role in the clinical features of this case.

Adenoma↗
PubMed2005

Long-term outcome in patients harboring intracranial ependymoma.

OBJECT: The prognostic significance of tumor grade and resection and the efficacy of prophylactic radiation remain controversial in the management of intracranial ependymoma. The outcomes in patients with intracranial ependymoma treated at the Kyoto University Hospital were reviewed retrospectively, and prognostic significance was analyzed. METHODS: Between 1972 and 2002, 29 patients were seen at the authors' institution. Eighteen cases involved a Grade II lesion according to the World Health Organization classification of ependymoma and 11 involved a Grade III lesion. Postoperative radiation was applied in 24 cases and chemotherapy was administered in nine. Overall survival and progression-free survival rates were significantly higher in patients with Grade II ependymoma (p = 0.006 and 0.004, respectively) and in patients who had undergone gross-total resection of the tumor (p = 0.002 and 0.04, respectively). Fourteen patients relapsed from 10 to 120 months (median 39 months) after diagnosis. In nine patients the ependymoma recurred only at the original tumor site. Three patients experienced both local and distant relapse, whereas two others had only a distant relapse. All relapses of the Grade II ependymoma initially occurred at the primary tumor site. Histological grade and extent of resection were significantly associated with tumor dissemination (p = 0.0034 and 0.0011, respectively). The field of postoperative radiation had no impact on patient survival or lesion recurrence. CONCLUSIONS: Tumor grade and resection are the two important prognostic factors with respect to patient survival, tumor recurrence, and tumor dissemination. Considering that relapses were predominantly local and that there was no apparent benefit from prophylactic radiation, the authors concluded that postoperative radiation should be focused on local control, especially for Grade II ependymomas.

Adolescent↗
PubMed2004

Ectopic posterior pituitary high signal in preoperative and postoperative macroadenomas: dynamic MR imaging.

BACKGROUND AND PURPOSE: In patients with macroadenoma, posterior pituitary high signal (PPHS) on T1-weighted magnetic resonance (MR) imaging is sometimes observed in an ectopic location. The present study compared incidences of ectopic PPHS before and after macroadenoma surgery using MR imaging, including dynamic MR imaging to ascertain whether this ectopic change is irreversible. MATERIALS AND METHODS: MR imaging was performed preoperatively in 111 cases of macroadenoma, and then repeated more than 1-year postoperatively in 47 patients. Enhancement of PPHS was assessed using dynamic MR imaging. Areas of enhanced hyperintensity were considered true PPHS, and the relationship between presence and location of true PPHS and adenoma volume was analyzed. Moreover, changes in the presence and location of true PPHS were ascertained among the patients who underwent postoperative follow-up MR imaging. RESULTS: Preoperatively, PPHS was seen only in the normal location in 29 patients (Group A: 26.1%). High signal was detected only in an ectopic location in 58 patients, and early enhancement of this ectopic high signal was confirmed by dynamic MR imaging in 56 patients (Group B: 50.5%). No PPHS was observed in 24 patients (Group C: 21.6%). Adenoma volume was significantly greater for Group B than for Group A (p<0.001). Among the Group B patients who underwent MR imaging postoperatively (n=31), the location of PPHS was not changed, except for two patients in whom PPHS was absent. Postoperatively, PPHS was not observed in the normal location in any patient in the Group B. CONCLUSIONS: Greater volume of adenoma is associated with a higher incidence of ectopic PPHS, and the ectopic change is irreversible.

Adenoma↗
PubMed2004

Overexpression of RFT induces G1-S arrest and apoptosis via p53/p21(Waf1) pathway in glioma cell.

The regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) has been reported to be a transcriptional repressor of FGF-2 and induce glioma cell death by its overexpression. Here we report that RFT regulates cell cycle as well as apoptosis by a novel mechanism. RFT expressed in some glioma cell lines, U138MG and T98G, but neither in U87MG nor U251MG. Overexpressed RFT-induced apoptosis in U87MG and U138MG with functioning-type p53 but neither in U251MG nor T98G with non-functioning-type p53. Administration of FGF-2 failed to prevent RFT-induced apoptosis. Overexpression of RFT caused G1-S arrest and upregulated both the phosphorylation of p53 at Ser-15 and the expression level of p21(Waf1). Furthermore, RNAi knockdown of p53 abolished RFT-induced apoptosis in U87MG. Taken together, our results support that RFT regulates G1-S transition and apoptosis via p53/p21(Waf1) pathway.

Apoptosis↗
PubMed2004

Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF: case report.

BACKGROUND: Intracranial varices are rare and most are associated with vein of Galen arteriovenous malformations (AVM) or fistulas (AVF). DESCRIPTION: A 43-year-old left-handed man presented with right hemihypesthesia and spastic gait. Neuroradiological examination revealed a spinal AVF and a giant intracerebral varix associated with a high-flow pial AVF. He had recurrent episodes of nasal bleeding, which were also confirmed in his mother's medical history, and telangiectases in the tip of his tongue and fingers. He was diagnosed with Rendu-Osler-Weber disease. After resection of the spinal AVF that produced his symptoms, we surgically exposed and obliterated the giant varix and AVF under intra- and postoperative hypotension and mild barbiturate therapy. The arteriovenous shunt was completely obliterated without hyperperfusion of the surrounding brain. CONCLUSION: This is an extremely rare case of Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF that did not involve the vein of Galen.

Adult↗