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Biomedical subjects

Atsushi Kubo

Publications and source records attributed to Atsushi Kubo.

At least 19 recordsLinked to original sources
PubMed2006

Influence of ageing on perioperative cardiac risk in non-cardiac surgery.

BACKGROUND: ageing is known to augment perioperative cardiac risk in non-cardiac surgery. However, it remains unclear whether the increased risk is attributable to ageing itself or to the associated cardiac risk factors and coronary artery disease. METHODS: this retrospective study enrolled 1,351 patients who underwent non-cardiac surgery after dipyridamole stress myocardial perfusion scintigraphy. These patients were divided into the following four groups: Group 1-E (aged 75 or more, normal single photon emission computed tomography (SPECT)), Group 1-Y (aged less than 75, normal SPECT), Group 2-E (aged 75 or more, abnormal SPECT) and Group 2-Y (aged less than 75, abnormal SPECT). Clinical risk factors, scintigraphic findings and occurrence of perioperative cardiac events were analysed. RESULTS: the older cohorts had a significantly higher number of risk factors than their younger counterparts. No significant difference was observed in the degree of perfusion abnormality between Groups 2-E and 2-Y. Although the event rates were comparable in Groups 1-E and 1-Y, Group 2-E yielded a significantly higher rate than Group 2-Y. Ageing was an independent predictor of cardiac events in Group 2 in multivariate analysis. CONCLUSIONS: ageing has no influence on perioperative cardiac risk in patients without overt myocardial infarction or ischaemia. The likelihood of cardiac events is increased by ageing, independently of other variables, in patients with perfusion abnormality.

Aged↗
PubMed2006

Higher order structure contributes to specific differences in redox potential and electron transfer efficiency of root and leaf ferredoxins.

Plant type ferredoxin (Fd) is a small [2Fe-2S] cluster containing electron-transfer protein with a highly negative redox potential. Higher plants contain different iso-protein types of Fd in roots and leaves, reflecting the difference in redox cascades between these two tissues. We have combined subdomains of leaf and root Fds in recombinant chimeras, to examine structural effects and the relationship between groups of residues on redox potential, electron transfer, and protein-protein interactions. All chimeras had redox potentials that were intermediate to the wild type leaf and root Fds. Surprisingly, the largest differences resulted from exchange of the N-terminus, the region farthest from the redox center. Homology modeling and energy minimization calculations suggest that the N-terminal chimeras may indirectly influence redox potentials by structurally perturbing the active site. Measurements of electron transport and protein interaction indicate that synergistic interaction between the C- and N-terminal of root Fd bestows a specific high affinity for accepting electrons in the root type electron cascade, and that there is discrimination against photosynthetic electron donation to root Fd based on the C-terminus of the molecule. Taken together, the experimental and computational studies support a model in which higher order structure contributes to iso-protein specific interaction and electron-transfer properties.

Amino Acid Sequence↗
PubMed2006

Repair of potentially lethal damage in normal cells and ataxia telangiectasia cells; consideration of non-homologous end-joining.

When cell lines are held in a quiescent state after irradiation, survival rates are greater than those from cells that are stimulated to grow immediately after irradiation. These differences in survival rates correspond to rates of potentially lethal damage repair. The effects of confluent holding recovery after gamma-irradiation were investigated using normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052). Calyculin-A-induced premature chromosome condensation and fluorescent in situ hybridization were applied to study G2/M chromosomal aberrations. Survival results indicated normal capacity for PLDR in AG1522 cells but that PLDR was extremely compromised in GM02052 cells. The chromosomal aberration frequency decreased when AG1522 cells were allowed to repair for 24-h, whereas 24-hour incubation had little effect on the aberration frequency in GM02052 cells. Since the main mechanism for dsbs repair during G0/G1 phases of the cells cycle involve the non-homologous end-joining (NHEJ) process, our study indicates that for AG1522 cells the NHEJ repair process is more likely to induce accurate chromosome repair under quiescent G0 conditions than proliferating G1 phase, while in GM02052 cells the fidelity of NHEJ is similarly defective at either cell cycle phase. Reduced fidelity of NHEJ may be responsible for PLDR defect and its hyper-radiosensitivity in A-T cells.

Ataxia Telangiectasia↗
PubMed2006

BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm.

When differentiated in the presence of activin A in serum-free conditions, mouse embryonic stem cells efficiently generate an endoderm progenitor population defined by the coexpression of either Brachyury, Foxa2 and c-Kit, or c-Kit and Cxcr4. Specification of these progenitors with bone morphogenetic protein-4 in combination with basic fibroblast growth factor and activin A results in the development of hepatic populations highly enriched (45-70%) for cells that express the alpha-fetoprotein and albumin proteins. These cells also express transcripts of Afp, Alb1, Tat, Cps1, Cyp7a1 and Cyp3a11; they secrete albumin, store glycogen, show ultrastructural characteristics of mature hepatocytes, and are able to integrate into and proliferate in injured livers in vivo and mature into hepatocytes expressing dipeptidyl peptidase IV or fumarylacetoacetate hydrolase. Together, these findings establish a developmental pathway in embryonic stem cell differentiation cultures that leads to efficient generation of cells with an immature hepatocytic phenotype.

Activins↗
PubMed2006

Unique treatment policy for well-differentiated thyroid cancer in Japan: results of a questionnaire distributed to members of the Japanese Society of Thyroid Surgery and the International Association of Endocrine Surgeons.

Although surgery has been the mainstay of treatment for patients with well-differentiated thyroid cancer, the extents of thyroid resection and lymph node dissection adopted in Japan differ from those in other countries. Furthermore, regarding the indications for postoperative radiation therapy and hormonal therapy, and treatment modalities for cancer recurrence, there are marked discrepancies between Japan and other countries. A questionnaire survey was thus conducted among domestic and overseas thyroid surgeons to ascertain the actual treatment policy for well-differentiated thyroid cancer in Japan and various foreign countries. For small papillary carcinomas of 2.0 cm or less (T1), thyroid resection was more extensive in foreign countries than in Japan, although the extent of lymph node dissection was limited in the former. For large papillary carcinomas exceeding 3.0 cm (T2), on the other hand, total thyroidectomy was the treatment of first choice for all overseas respondents, but of only 20% in Japan, despite lymph node dissection being more extensive in Japan than in other countries. Overseas surgeons were much more likely to favor postoperative TSH suppression therapy and high-dose (131)I therapy. For recurrence following surgery for papillary thyroid cancer, both domestic and overseas respondents indicated surgical resection to be the most common treatment option, and favored high-dose (131)I therapy as well. In Japan, however, high-dose (131)I therapy is available only in a few institutions. Such limited indications for high-dose (131)I therapy in Japan may reflect a discrepancy in the frequency of total thyroidectomy, a prerequisite for postoperative high-dose (131)I therapy, between Japan and other countries. This is the first questionnaire study conducted in both Japan and other countries in relation to treatment modalities for thyroid cancer. The results reveal that there is a clear disparity in treatment policies between Japan and foreign countries.

Americas↗
PubMed2006

Systematic analysis of embryonic expression profiles of zinc finger genes in Ciona intestinalis.

The recent decoding of a number of animal genomes has provided unprecedented information regarding evolution and gene structures, but this information must be supplemented with precise gene annotations and the temporal and spatial expression patterns of individual genes. In the present study, we systematically identified and characterized 566 zinc finger genes in the genome of Ciona intestinalis, an emerging model system for genome-wide studies of development and evolution. Of these genes, 356 genes encoded a potential transcription factor based on putative nucleic acid binding activity or domains of unknown function. We further examined the expression patterns of 225 genes during embryogenesis, and, when considered with a previous study [Imai, K.S., Hino, K., Yagi, K., Satoh, N., Satou, Y., 2004. Gene expression profiles of transcription factors and signaling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks. Development 131, 4047-4058], we have characterized the developmental expression patterns of nearly 85% of the potential zinc finger-containing transcription factors. Overall, zinc finger genes are preferentially maternally expressed with little larval expression during development. The present study provides a valuable reference for genome-wide studies in this species and for future studies wishing to examine zinc finger gene expression patterns in other animals.

Animals↗
PubMed2006

Directed differentiation of mouse embryonic stem cells into thyroid follicular cells.

Elucidating the molecular mechanisms leading to the induction and specification of thyroid follicular cells is important for our understanding of thyroid development. To characterize the key events in this process, we previously established an experimental embryonic stem (ES) cell model system, which shows that wild-type mouse CCE ES cells can give rise to thyrocyte-like cells in vitro. We extend our analysis in this report by using a genetically manipulated ES cell line in which green fluorescent protein (GFP) cDNA is targeted to the TSH receptor (TSHR) gene, linking GFP expression to the transcription of the endogenous TSHR gene. The appearance of GFP-positive cells was dependent on the formation of embryoid bodies from undifferentiated ES cells and was greatly enhanced by TSH treatment during the first 2-4 d of differentiation. With the support of Matrigel, highly enriched ES cell-derived GFP-positive cells formed thyroid follicle-like clusters in a serum-free medium supplemented with TSH. Importantly, these clusters display the characteristics of thyroid follicular cells. Immunofluorescent studies confirmed the colocalization of TSHR with the Na+/I- symporter in the clusters and indicated that Na+/I- symporter was expressed exclusively in the plasma membrane. In addition, I- uptake activity was observed in these cells. Our results indicate that ES cells can be induced to differentiate into thyroid follicular cells, providing a powerful tool to study embryonic thyroid development and function.

Animals↗
PubMed2006

Equation of state of the postperovskite phase synthesized from a natural (Mg,Fe)SiO3 orthopyroxene.

Using the laser-heated diamond anvil cell, we investigate the stability and equation of state of the postperovskite (ppv, CaIrO(3)-type) phase synthesized from a natural pyroxene composition with 9 mol.% FeSiO(3). Our measured pressure-volume data from 12-106 GPa for the ppv phase yield a bulk modulus of 219(5) GPa and a zero-pressure volume of 164.9(6) A(3) when K'(0) = 4. The bulk modulus of ppv is 575(15) GPa at a pressure of 100 GPa. The transition pressure is lowered by the presence of Fe. Our x-ray diffraction data indicate the ppv phase can be formed at P > 109(4) GPa and 2,400(400) K, corresponding to approximately 400-550 km above the core-mantle boundary. Direct comparison of volumes of coexisting perovskite and CaIrO(3)-type phases at 80-106 GPa demonstrates that the ppv phase has a smaller volume than perovskite by 1.1(2)%. Using measured volumes together with the bulk modulus calculated from equation of state fits, we find that the bulk sound velocity decreases by 2.3(2.1)% across this transition at 120 GPa. Upon decompression without further heating, it was found that the ppv phase could still be observed at pressures as low at 12 GPa, and evidence for at least partial persistence to ambient conditions is also reported.

Journal Article↗
PubMed2006

Plastic deformation of MgGeO3 post-perovskite at lower mantle pressures.

Polycrystalline MgGeO3 post-perovskite was plastically deformed in the diamond anvil cell between 104 and 130 gigapascals confining pressure and ambient temperature. In contrast with phenomenological considerations suggesting (010) as a slip plane, lattice planes near (100) became aligned perpendicular to the compression direction, suggesting that slip on (100) or (110) dominated plastic deformation. With the assumption that silicate post-perovskite behaves similarly at lower mantle conditions, a numerical model of seismic anisotropy in the D'' region implies a maximum contribution of post-perovskite to shear wave splitting of 3.7% with an oblique polarization.

Journal Article↗
PubMed2006

Formation of oriented polypeptides on Au(111) surface depends on the secondary structure controlled by peptide length.

We synthesized three different lengths of poly(L-lysine) containing an -SH group at the terminal (PLL(n)-SH, n (polymerization degree) = 4, 10, 30) and adsorbed them on an Au(111) surface. To analyze the formation process and the structure of self-assembled monolayers (SAMs), we used atomic force microscopy (AFM) and Fourier transform infrared reflection absorption spectra (FT-IR RAS). At the initial stage of SAM growth, formation of nanosize domains was confirmed by AFM imaging. The alpha-helical PLL(30)-SH exhibited a well-defined SAM structure after adsorption reached equilibrium. The alpha-helical PLL(30)-SH was almost perpendicular to the gold surface and exhibited interesting molecular packing due to the secondary structure of PLL(30)-SH and the underlying Au(111) array. The tilt angle of the helix axis from the substrate normal was estimated to be about 50 degrees (AFM) and 44 degrees (FT-IR RAS) respectively. On the other hand, PLL(4)-SH and PLL(10)-SH formed beta-sheet-type SAMs on the Au(111) surface based on the structure determined by FT-IR RAS spectrum.

Adsorption↗
PubMed2006

Interim results of sentinel node biopsy during laparoscopic gastrectomy: possible role in function-preserving surgery for early cancer.

INTRODUCTION: Intraoperative detection of sentinel nodes (SNs) has been used clinically to predict regional lymph node (LN) metastasis in patients with breast cancer and malignant melanoma. Intraoperative lymphatic mapping and SN biopsy can potentially be combined with minimally invasive surgery. However, few reports have demonstrated the validity of SN biopsy during laparoscopic gastrectomy. The aim of this study was to investigate the feasibility and accuracy of laparoscopic lymphatic mapping in predicting LN status in patients with gastric cancer. METHODS: A total of 35 patients with gastric cancer diagnosed preoperatively as T1, N0 were enrolled. Endoscopic injection of technetium-99m-radiolabeled tin colloid was completed 16 hours before surgery, and radioactive SNs were identified with a gamma probe intraoperatively. Isosulfan blue dye was injected endoscopically during the operation. Laparoscopy-assisted gastrectomy with LN dissection was performed. All resected LNs were evaluated by routine pathology examination. RESULTS: SNs were detected in 33 (94.3%) of 35 patients. The mean number of SNs was 3.9, and the diagnostic accuracy according to SN status was 97.0% (32/33), as one patient with a false-negative result was observed. The patient with the false-negative specimen was finally diagnosed as having advanced gastric cancer with invasion into the proper muscular layer and severe lymphatic vessel invasion, causing destruction of normal lymphatic flow by the tumor. CONCLUSIONS: Radio-guided SN mapping during laparoscopic gastrectomy is an accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer. Validation of this method requires further studies on technical issues, including indications, tracers, methods of lymph node retrieval, and diagnostic modalities of metastasis.

Adult↗
PubMed2006

Tamoxifen for recurrent desmoid tumor of the chest wall.

We report a case of a young woman with recurrent desmoid tumor. Computed tomography (CT) scans of the chest showed a large mass in the left chest wall. The tumor was unresectable because of the involvement of adjacent structures. Tamoxifen therapy led to marked tumor regression within 3 months. She had preserved her fertility, and thereafter she conceived a baby. In young women with recurrent desmoid tumor, tamoxifen should be considered as the first choice of treatment.

Adult↗
PubMed2006

Radiation therapy after breast-conserving surgery.

The authors critically reviewed previous articles concerning the significance of breast irradiation following breast-conserving surgery in terms of the following subject items: indications for breast-conserving therapy, the significance and complications of breast irradiation, the timing of the start of breast irradiation, the significance of boost irradiation, the potential improvement of survival with systemic therapy plus breast irradiation, the significance of axillary dissection, indications and the significance of regional nodal irradiation, accelerated hypofractionated radiotherapy, omission of breast irradiation in low-risk patients, and future directions. In addition, our previously reported results of breast irradiation following breast-conserving surgery at the Keio University Hospital are outlined. Our newly developed tangential irradiation technique directed to the axilla and a recently introduced three-dimensional simulation technique for radiotherapy treatment planning are also presented.

Breast↗
PubMed2006

Rotational and translational reproducibility of newly developed Leksell frame-based relocatable fixation system.

PURPOSE: The aim of this study was to evaluate three-dimensional movement of the cranium in a relocatable frame using positions of anatomical landmarks obtained from repeated quality-assurance (QA) computed tomography (CT) studies. MATERIALS AND METHODS: We analyzed 17 series of QA-CT data representing five patients who underwent stereotactic radiotherapy for treatment of acoustic neurinoma. Helical-CT scans with 1-mm collimation were obtained at the time of treatment planning and during the course of treatment. The right and left short processes of the incus and the top of the crista galli were used as the three anatomical reference points. RESULTS: Fluctuations in distance among the reference points were all <1 mm. The translational displacements for these points were <2 mm, with standard deviations (SD) of <2 mm. A plane that included all three reference points was defined as the reference plane. To investigate the direction of cranial rotation for each QA-CT scan, unit normal vectors of the reference plane were obtained. Three-dimensional analyses indicated that cranial rotation was greatest along the X-axis, followed by the Y-axis, with the least rotation along the Z-axis. CONCLUSION: The result suggested that movement of the craniocaudal axis in the sagittal plane was a major factor behind displacement of the cranium.

Adult↗
PubMed2006

Value of CT thallium-201 SPECT fusion imaging over SPECT alone for detection and localization of nasopharyngeal and maxillary cancers.

OBJECTIVE: The purpose of this study was to investigate the incremental clinical utility of CT and high-resolution SPECT fusion imaging. MATERIALS AND METHODS: Eighteen patients with nasopharyngeal cancer or cancers around the maxilla were scanned with high-resolution SPECT at the time of initial diagnosis (18 studies) and during follow-up after chemoradiotherapy (23 studies). SPECT results were compared with histologic findings or the findings of other imaging techniques. In addition, automatic image registration without fiducial markers was performed from CT and SPECT data, and the effect of fusion imaging on the localization of abnormalities was evaluated. RESULTS: All of the original 18 untreated lesions showed high uptake. Recurrent tumors had a tendency to show high uptake (seven of nine patients), whereas little or no uptake generally represented no recurrence (12 of 14 patients) (chi-square test with Yates correction: chi2 = 6.80, p < 0.01). In two patients, physiologic uptake in the unilateral prevertebral muscle was revealed on image fusion. In four of the nine recurrent nasopharyngeal cancers (44%), SPECT alone could not determine abnormalities in uptake sites, whereas CT/SPECT fusion imaging clearly localized the sites and was helpful for treatment strategy. CONCLUSION: High-resolution thallium-201 (201Tl) SPECT has a very high detection rate in patients with nasopharyngeal cancer and cancers around the maxilla. However, the anatomic identification or localization of the uptake sites is sometimes difficult without CT/SPECT fusion imaging. This technique without external markers is practically feasible to generate clinically valid fusion images.

Adult↗
PubMed2006

Initial mechanistic studies of antisense targeting in cells.

UNLABELLED: The continued development of antisense targeting will require a better understanding of the mechanism. METHODS: We performed initial studies of the mechanism of intracellular antisense targeting through measurements of in situ transcription, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), 32P-labeled uridine-5'-triphosphate (alpha-32P-UTP) incorporation, nuclear accumulations of 99mTc-labeled DNAs, and messenger RNA (mRNA) transcription rate. As reported earlier, an antisense DNA against the mdr1 mRNA coding for P-glycoprotein (Pgp) and its sense DNA control were used in KB-G2 (Pgp++) cells. RESULTS: Definitive evidence for antisense targeting was obtained by in situ transcription showing complementary DNA elongation in cells exposed to antisense DNA, acting therefore as an intracellular PCR primer of mdr1 mRNA, but not in cells exposed to sense DNA. Immunofluorescence staining showed higher accumulations of antisense versus sense DNAs in KB-G2 cells. Transnuclear migration was confirmed by higher accumulations in the nucleus compared with the cytoplasm in cells incubated with 99mTc-labeled antisense DNA. However, the observed specific accumulations of antisense DNAs of about 10(6) per cell over 10 h could not be explained by a feedback mechanism upregulating transcription in cells exposed to antisense DNA as no increase in mRNA levels was detected by both RT-PCR and 32P-UTP in these cells. To explore an alternative hypothesis, a novel approach using 99mTc-labeled antisense DNA as a probe of total mRNA from cells previously saturated with unlabeled antisense DNA was used to estimate the transcription rate. Compared with controls, mdr1 mRNA levels were found to be initially low after saturation and to recover at about 2,000 copies per minute per cell. If persistent, this transcription rate would provide 10(6) mRNAs in 10 h. CONCLUSION: The results of all studies are consistent with antisense as the mechanism of targeting. Though a feedback mechanism leading to upregulation of mRNA transcription is an unlikely explanation for the high specific accumulations, our results may be explained if antisense DNAs are targeting mdr1 mRNAs produced at high transcription rates. If the target is primarily pre-mRNA in the nucleus rather than mature mRNA in the cytoplasm, this would provide as well an explanation for the observed migration of 99mTc-labeled antisense DNA into the nucleus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

[Usefulness of 18F-FDG PET in the diagnosis for breast cancer patients].

Whole-body 18F-FDG PET is useful for qualitative diagnosis of breast mass and for preoperative staging, evaluation of therapeutic effect, prediction of prognosis, and detection of recurrence or metastasis in case of breast cancer. In addition, 18F-FDG PET is being actively used for cancer screening in Japan. 18F-FDG PET has almost equal or higher. capacity in detecting recurrence or metastasis of breast cancer as compared with conventional morphological study such as CT or MRI. However it should be noticed of the existence of false-negative and false-positive findings in some cases. In this paper we refer to the advantages and disadvantages of 18F-FDG PET in managing patients with breast cancer.

Breast Neoplasms↗