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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 19 recordsLinked to original sources
PubMed2006

Mitotic arrest caused by an X-ray microbeam in a single cell expressing EGFP-aurora kinase B.

Although the highest radiosensitivity of cells in the M phase among the other cell phases, such as the G(1), S and G(2) phases, has been known, the exact mechanism of radiosensitivity in mitotic cells remains unclear. Recently, mitotic arrest caused by DNA-damaging reagents has been shown, and the molecular mechanism in the arrest has been discussed in detail. In this study, abnormal cell-cycle progression in the M phase was investigated when a single mitotic cell in each mitotic stage was irradiated with a 5.35 keV X-ray microbeam focused on the cell nucleus. An X-ray microbeam irradiation system installed at BL-27 in Photon Factory, High Energy Accelerator Research Organization (HEARO, Tsukuba) was used. HeLa cells, genetically modified and expressing enhanced green fluorescent protein-tagged aurora kinase B, were used as irradiated samples in order to recognise the stage of each cell in the M phase. Thus, 10 Gy irradiation concentrated at the nucleus of a single cell elongated the cell-cycle progression in the M phase by delaying the metaphase/anaphase transition. The dose dependence of the elongation of the M phase was also examined. An irregular distribution of DNA in anaphase cells was observed after irradiation.

Aurora Kinase B↗
PubMed2006

Usefulness of intraoperative magnetic resonance imaging for glioma surgery.

BACKGROUND: Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome. METHODS: From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality). FINDINGS: Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P < 0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%). CONCLUSIONS: Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Adult↗
PubMed2006

Refractory hypotension during combined general and epidural anaesthesia in a patient on tricyclic antidepressants.

We report a case of refractory hypotension that occurred after epidural injection of local anaesthetic, in a patient who was receiving tricyclic antidepressant therapy and was under general anaesthesia. The patient failed to respond to repeated injections of appropriate doses of sympathomimetics, but did respond to high-dose catecholamine infusions. We suggest that epidural anaesthesia should be used with care when combined with general anaesthesia for patients on long-standing tricyclic antidepressant therapy. If refractory hypotension should occur in such patients, the use of direct-acting vasoconstrictors such as noradrenaline should be considered.

Aged↗
PubMed2005

Differentiation of the radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases: importance of multi-voxel proton MRS.

Comparative analysis of the diagnostic accuracy of FDG PET, single-voxel, and multi-voxel proton MRS for differentiation between radiation-induced necrosis and tumor recurrence was done in 9 patients with brain metastases treated by gamma knife radiosurgery. In all cases enlargement of the lesion and increase of the perilesional edema were demonstrated by MRI on average 10.6+/-2.6 months after initial treatment. Radiation-induced necrosis was identified in 5 patients (histologically in 2, clinically in 3). In one of these a false positive result of FDG PET was observed, whereas data of proton MRS were always correct. The diagnosis of tumor recurrence was established in 4 patients (histologically in 3, clinically in 1). Among these both FDG PET and single-voxel proton MRS showed false negative results (each method twice), whereas multi-voxel proton MRS always permitted us to establish the correct diagnosis. The present study demonstrates the higher diagnostic accuracy of multi-voxel proton MRS, in comparison with single-voxel proton MRS and FDG PET, for the differentiation of the radiation-induced necrosis and tumor recurrence. Its use is especially important in mixed lesions with co-existence of both post-irradiation changes and viable neoplasm. Monitoring of the treatment response by serial multi-voxel proton MRS seems to be reasonable during follow-up of patients with brain metastases after radiosurgery.

Abnormalities, Radiation-Induced↗
PubMed2005

Malignant progression of benign brain tumors after gamma knife radiosurgery: is it really caused by irradiation?

Malignant transformation of benign neoplasm after radiosurgery is usually diagnosed based on the initial presence of benign tumor, its exposure to ionizing radiation, elapsed time from radiation exposure to malignant progression, and different histological characteristics or growth rate of the regrowing tumor comparing with those originally treated. Three presented cases fulfilled these diagnostic criteria; however, it seems that progression of the tumors (schwannoma, meningioma, chordoma) resulted from the natural course of the disease, rather than represented side effects of gamma knife radiosurgery. Evaluation of the proliferative potential of the benign neoplasm before radiosurgical treatment either directly, if tumor sampling is available, or indirectly, by calculation of the tumor growth rate and/or analysis of the data of the metabolic imaging (PET, MRS) is important for identification of "aggressive" subtypes, precise prediction of prognosis, and confirmation of the radiation-induced malignant transformation in cases of tumor regrowth.

Adult↗
PubMed2005

Simple biodosimetry method for use in cases of high-dose radiation exposure that scores the chromosome number of Giemsa-stained drug-induced prematurely condensed chromosomes (PCC).

There is a need for quick dose estimation by a simple method in radiation accidents. This study develops a simple and rapid dose estimation protocol for victims of such accidents, in particular those involving high radiation doses. Human peripheral blood lymphocytes (PBL) were gamma-irradiated in vitro at several dose points up to 60 Gy, and were stimulated with phytohaemagglutinin-P (PHA-P) for 2 days to obtain dividing cells. PBL were then forced to condense prematurely, using 50 nM calyculin A, and the obtained chromosome spreads were Giemsa stained. The G2-PCC (prematurely condensed chromosomes) index and chromosome number for each radiation dose point were scored. G2-PCC were stably induced using calyculin A within 24 h delays in stimulation of PBL with PHA-P. The chromosome number of G2-PCC increased steeply with radiation doses up to 30 Gy at a rate of 0.31 Gy(-1) and then decreased at 0.30 Gy(-1) up to 40 Gy. More than 10% of G2-PCC index remained up to a 15 Gy dose. Even after 40 Gy irradiation, about 2% PCC index was obtained, and this value was enough to score a sufficient number of chromosome spreads for analysis. Therefore, the combined use of chromosome number and G2-PCC index allows biodosimetry to be done easily and rapidly. If PCC are not induced using calyculin A, it is strongly suggested that the radiation dose is over 50 Gy. A rapid and easy dose estimation for large dose exposure whole-body was realized by combined analysis of Giemsa-stained chromosome number of G2-PCC and PCC index using calyculin A. This simple method will be of use for rapid decision making of therapy for radiation accident victims. This method also has potential for use as a biodosimeter for partial-body exposure accidents.

Adult↗
PubMed2003

C-erbB-2 or mutant Ha-ras induced malignant transformation of immortalized human ovarian surface epithelial cells in vitro.

Ovarian cancer is believed to develop from the ovarian surface epithelium through the accumulation of aberrations of oncogenes and/or tumor suppressor genes. However, it is unclear how the gene abnormalities are involved in ovarian carcinogenesis. To elucidate the process, we transfected genes reported to show their abnormalities in human ovarian cancers into human ovarian surface epithelial cells. Immortalization of the cells was achieved by the transfection of SV40 large T antigen (LT) and human telomerase reverse transcriptase (hTERT); however, the resultant cells showed no tumorigenesis. Additional transfection of either c-erbB-2 or mutant Ha-ras into the immortalized cells showed the anchorage-independent growth and tumorigenesis in mice with the incidence of 50% and 40%, respectively. Histologically, all the tumours were undifferentiated. In association with the tumorigenesis, the cells expressing c-erbB-2 or mutant Ha-ras demonstrated increased vascular endothelial growth factor secretion under hypoxia and enhanced resistance to apoptosis compared with the immortalized cells. Collectively, the introduction of either c-erbB-2 or mutant Ha-ras in the cells, which were efficiently immortalized by the transfection of LT and hTERT, showed tumorigenicity, suggesting that c-erbB-2 or mutant Ha-ras genes might be involved in ovarian carcinogenesis.

Cell Transformation, Neoplastic↗
PubMed2002

Quantitative analysis of the energetics of DNA damage.

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

Biophysics↗
PubMed2002

Enhancement of X-ray-induced breaks in DNA bound to molecules containing platinum: a possible application to hadrontherapy.

Complexes made of DNA and chloroterpyridine platinum (PtTC) bound to plasmid DNA were placed in aqueous solution and irradiated with monochromatic X rays tuned to the resonant photoabsorption energy of the L(III) shell of the platinum atom. The number of single- and double-strand breaks (SSBs and DSBs) induced by irradiation on a supercoiled DNA plasmid was measured by the production of the circular-nicked and linear forms. To distinguish the contribution of the direct effects of ionization from the indirect effects due to a free radical attack, experiments were also performed in the presence of a hydroxyl free radical scavenger, dimethyl sulfoxide (DMSO). An enhancement of the number of SSBs and DSBs was observed when the plasmids contained the platinum intercalating molecules. A quantitative analysis was made to evaluate the respective contributions of the direct effects (Auger effect) and the indirect effects (free radical attack) to the number of DNA strand breaks. Even when off-resonant X rays were used, the strand break efficiency remained higher than expected based upon the absorption cross section, suggesting that the platinum bound to DNA might be increasing the yield of strand breaks. A mechanism is suggested that involves photoelectrons generated from the ionization of water which efficiently ionize platinum atoms. If this mechanism is correct, then heavy atoms, with a large cross section for ionization by electrons that are bound to the DNA, should behave as a radiosensitizer. This observation may provide insight into understanding the effects of new radiotherapy protocols, related chemotherapeutic agents such as cisplatin, and conventional radiotherapy for the treatment of tumors. A possible way to deliver the dose selectively in a well-defined volume, which uses the properties of the linear energy transfer of atomic ions interacting with matter, is suggested.

Chromosome Breakage↗
PubMed2001

Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11.

Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7.

3' Untranslated Regions↗
PubMed2001

Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome.

OBJECTIVE: To determine whether the known inactivating FSH receptor gene mutations are present in Japanese women with secondary amenorrhea because of premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). DESIGN: Clinical and molecular studies. SETTING: An outpatient clinic in a university hospital. PATIENT(S): Fifteen women with idiopathic POF, 38 women with PCOS, and three normal controls. INTERVENTION(S): Extraction of DNA from blood samples for subsequent polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): PCR fragments digested with MunI, BsmI, and HhaI were compared in patients and controls. PCR fragments were also analyzed by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. RESULT(S): No inactivating mutations reported thus far in exons 6, 7, 9, and 10 of the FSH receptor gene were identified in Japanese women with POF and PCOS. DGGE analysis of PCR fragments of exon 10 also revealed no FSH receptor gene mutations in this region. CONCLUSION(S): Although we cannot exclude the presence of point mutations in other regions of the FSH receptor gene, the described FSH receptor mutations may be uncommon in Japanese patients with POF and PCOS.

Adult↗
PubMed2001

Active Crohn disease with maternal vitamin K deficiency and fetal subdural hematoma.

BACKGROUND: Fetal subdural hematoma is a rare condition not considered a complication of Crohn disease in pregnancy. CASE: A young woman with a diagnosis of Crohn disease presented at 22 weeks' gestation with diarrhea and melena for 3 weeks. Dietary and medicinal therapies were begun. At 28 weeks' gestation, fetal ultrasonography showed an intracranial mass, which was seen to expand on serial ultrasound and magnetic resonance imaging studies. A hematoma was suspected, and, although the mother had no overt hemorrhagic manifestations, maternal vitamin K deficiency was diagnosed by enzyme immunoassay and corrected. After cesarean delivery at 36 weeks' gestation, the newborn was normal, but magnetic resonance imaging showed a chronic subdural hematoma. CONCLUSION: Maternal vitamin K deficiency in active Crohn disease might cause fetal hemorrhage. Monitoring of vitamin K status during pregnancy with Crohn disease seems warranted.

Adult↗
PubMed2001

Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation.

BACKGROUND: Acute allograft rejection (AR) in solid organ transplantation is generally regarded to develop through cell-mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, humoral immunity may play some roles in AR. Although flow cytometry crossmatch (FCXM) is reported as a useful method for the detection of antibodies against donor antigen, specific role of T- or B-cell FCXM and its sensitivity for AR is controversial. METHODS: T- and B-cell FCXM using fresh donor peripheral lymphocytes were performed before and after blood-type compatible living donor liver transplantation in 47 patients. IgM and IgG anti-donor antibodies were analyzed in relation to clinical AR. RESULTS: Positive pre-transplant T-cell FCXM was associated with a high incidence of positive post-transplant T-cell FCXM (p=0.017). Four of five cases (80%) with positive pre-transplant T-cell FCXM experienced earlier AR (day 8.0+/-4.4, mean+/-SD) than 16 of 42 cases (31%) with negative pre-transplant T-cell FCXM (17.3+/-6.8; p=0.016). In addition, higher dose of steroids was given to treat AR episodes in cases with positive pre-transplant T-cell FCXM (79.9+/-10.3 mg/kg/month) than in those with negative pre-transplant T-cell FCXM (47.1+/-26.6; p=0.039). In the first month after transplantation, 13 episodes of positive post-transplant T-cell FCXM were all concomitant with or preceded clinical AR compared with seven ARs in T-cell FCXM-negative cases (p<0.0001). T-cell FCXM between positive sera and third parties revealed some crossreactions. In contrast, detection of antibodies by B-cell FCXM in pre- and post-transplant phases was scarcely associated with AR, and no correlation was found between T- and B-cell FCXM before and after transplantation. CONCLUSIONS: Positive T-cell FCXM is closely related with AR and that before transplantation is a predictor of early and refractory AR as well as post-transplant FCXM. In contrast, not a few detections of antibodies irrelevant to AR are observed in B-cell FCXM, suggesting its low specificity.

Adolescent↗
PubMed2001

Surgical treatment of falcotentorial meningioma.

Meningiomas arising from the falcotentorial junction are rare. Among our surgical experience of 375 meningiomas, only 4 cases of so-called falcotentorial meningiomas were encountered. We present these four surgical cases. An occipital transtentorial approach was used in three cases, and a combined midline occipital and suboccipital approach in one case. Total tumour excision was impossible in two cases because of engulfing deep venous structures including the great vein of Galen. Postoperative Gamma knife radiosurgery was performed in these two cases. On the other hand, a posteriorly located tumour was relatively easy to remove, and macroscopic total removal was accomplished. In conclusion, precise microvascular anatomical knowledge is indispensable to satisfactorily excise meningiomas in the falcotentorial area without significant morbidity.

Craniotomy↗
PubMed2001

Messenger ribonucleic acid for the mouse decidual prolactin is present and induced during in vitro decidualization of endometrial stromal cells.

Although decidualization of endometrial stromal cells is crucial for blastocyst implantation and maintenance of pregnancy, its complex mechanism still remains largely unknown. To explore the mechanisms of decidualization, we have established an in vitro decidualization model in mice. Through extraction of mRNA from endometrial stromal cells for subsequent reverse transcriptase polymerase chain reaction analysis, we found that two ovarian hormones, 17 beta-estradiol and progesterone, induced morphological changes and expression of mRNA for prolactin (PRL) and the decidual/trophoblastic PRL-related protein (d/tPRP) in cultured mouse endometrial stromal cells. The expression of mRNA for the decidual PRL was also detected in the mouse decidua in vitro. In conclusion, mouse mRNA for decidual PRL is present and induced by estradiol and progesterone through in vitro decidualization of endometrial stromal cells.

Animals↗
PubMed2001

New possibilities for stereotaxis. Information-guided stereotaxis.

Information-guided stereotaxis, assisted by visualization of medical information, will become the next generation of neurosurgical systems. We performed 76 open MRI surgeries at Tokyo Women's Medical University between March 3, 2000 and April 12, 2001. Of them, comparisons of pre- and post-operative MR images for malignant gliomas in 21 cases revealed an average resection rate of 90.3% (the maximum 100%, the minimum 55%). In this article we describe real time updated navigation, augmented reality navigation, three-dimensional navigation, chemical navigation, information-guided navigation system (High definition visual Computer Aided Surgery System: HivisCAS), and open MRI-guided surgery that we are developing.

Humans↗