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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 19 recordsLinked to original sources

Genetic analysis to complement histopathological diagnosis of brain tumors.

Gliomas, the most frequent tumors originating in the human nervous system, are divided into various subtypes. Currently, microscopic examination alone is insufficient for classification and grading so that genetic profiles are increasingly being emphasized in recognition of the emerging role of molecular diagnostic approaches to glioma classification. Glioblastomas (WHO grade IV) may develop de novo (primary glioblastomas) or through progression from lower-grade astrocytomas (secondary glioblastomas), while both glioblastomas show similar histological features. In contrast, they do constitute distinct disease entities that evolve through different genetic pathways, and are likely to differ in prognosis and response to therapy. Oligodendrogliomas (WHO grade II) account for 2.7% of brain tumors and 5-18% of all gliomas. Since this tumor is recognized as a particular subtype of glioma that shows remarkable responses to chemotherapy, a correct diagnosis is of prime importance. The difficulty is that histological differentiation of oligodendrogliomas from diffuse astrocytomas is highly subjective in cases without typical morphological features and there is a lack of reliable immunohistochemical markers. While histological distinction of low-grade gliomas from reactive astrocytes is also often difficult, reactive astrocytes usually lack genetic alterations. More biological and molecular approaches to glioma classification thus appear warranted to provide improved means to achieve correct diagnoses.

Astrocytoma↗

Both host prion protein 131-188 subregion and prion strain characteristics regulate glycoform of PrP Sc.

Prion proteins (PrPs) contain 2 N-linked glycosylation sites and are present in cells in 3 different forms. An abnormal isoform of prion protein (PrP(Sc)) has different glycoform patterns for different prion strains. However, the molecular basis of the strain-specific glycoform variability in prions has remained elusive. To understand the molecular basis of these glycoform differences, we analyzed PrP(Sc) in 2 lines of transgenic mice (MHM2 and MH2M with PrP null background) that expressed a chimeric PrP. Our result indicated that PrP 131-188 (substitutions at I139M, Y155N, and S170N) contributed to both PrP(C) and PrP(Sc) glycoform ratios. Furthermore, the PrP(Sc) glycoform pattern within these transgenic mice showed a subtle difference depending on the inoculated prion. This study indicated that the PrP(Sc) glycoform ratio was influenced by both host PrP(C) and the prion strain.

Animals↗

Biomechanical testing of the fractured distal radius treated with a new bone cement--is it strong enough?

This study evaluates the in vitro ability of CAP, a bone graft substitute with osteointegration and osteoconductive properties, to restore the anatomy and strength of fractured distal radii. Ten pairs of cadaveric radii were imaged and tested to failure, simulating a fracture. The radii were reconstructed using CAP and were re-fractured and sequentially imaged. The deformities of the bones were determined through computerised evaluation of the radiographs. Radiographic analysis showed that CAP is capable of restoring the anatomy of the distal radius. The load and work required to fracture intact radii were compared to those required to fracture the reconstructed radii. The load to fracture was similar in the two situations. The work to fracture, however, was higher with reconstructed radii, suggesting that these are stronger than the original bones. Our study supports the hypothesis that CAP is capable of restoring the original anatomy and dimensions of the distal radius and re-establishing its mechanical strength.

Biomechanical Phenomena↗

Excimer fluorescence as a tool for monitoring protein domain dynamics applied to actin conformation changes based on circulary polarized fluorescence spectroscopy.

Fluorescence-detected circular dichroism (FDCD) was introduced into the study of protein conformation changes. Actin was used as a model protein which undergoes dynamic conformation changes as it polymerizes. Actin labeled with N-(1-pyrene)iodoacetamide (PIA) showed monomer fluorescence peak at 386 and 410 nm, and excimer fluorescence peak at around 480 nm. Excimer was formed by PIA-dimers labeled to different sites of amino acid residues. New information concerned with actin structural changes were monitored by fluorescence emission spectra excited with left- and right-circulary polarized light at 355 nm. FDCD intensities were shown as the difference in the fluorescence emission DeltaF, where DeltaF=(F (L)-F (R))/(F (L)+F (R)) denoting F (L) and F (R) as emissions obtained by excitation with left- and right-circulary polarized light. When solvent conditions of PIA-actin were changed by addition of NaCl, TFE, or ATP, DeltaF showed sensitive responses to these compounds. From the analysis of DeltaF (M) and DeltaF (E) which represent the peaks of DeltaF at the monomer- and excimer-emission band, the information concerned with the actin intrastructural changes were obtained. This method based on monitoring the excimer fluorescence with FDCD could be used for other proteins to extract finer structural changes that cannot be detected by the normal fluorescence spectroscopy.

Actins↗

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan.

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.

Anti-Bacterial Agents↗

FADD phosphorylation is critical for cell cycle regulation in breast cancer cells.

Anti-oestrogen therapy is effective for control of hormone receptor-positive breast cancers, although the detailed molecular mechanisms, including signal transduction, remain unclear. We demonstrated here that long-term tamoxifen treatment causes G2/M cell cycle arrest through c-jun N-terminal kinase (JNK) activation, which is dependent on phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine in an oestrogen (ER) receptor-positive breast cancer cell line, MCF-7. Expression of a dominant negative mutant form of MKK7, a kinase upstream of JNK, or mutant FADD (S194A) in MCF-7 cells suppressed the cytotoxicity of long-term tamoxifen treatment. Of great interest, similar signallings could be evoked by paclitaxel, even in an ER-negative cell line, MDA-MB-231. In addition, immunohistochemical analysis using human breast cancer specimens showed a close correlation between phosphorylated JNK and FADD expression, both being significantly reduced in cases with metastatic potential. We conclude that JNK-mediated phosphorylation of FADD plays an important role in the negative regulation of cell growth and metastasis, independent of the ER status of a breast cancer, so that JNK/FADD signals might be promising targets for cancer therapy.

Adaptor Proteins, Signal Transducing↗

Bulk- and surface-sensitive high-resolution photoemission study of two mott-hubbard systems: SrVO3 and CaVO3.

We study the electronic structure of Mott-Hubbard systems SrVO3 and CaVO3 with bulk and surface-sensitive high-resolution photoemission spectroscopy, using a vacuum ultraviolet laser, synchrotron radiation, and a discharge lamp (hv = 7-21 eV). A systematic suppression of the density of states (DOS) within approximately 0.2 eV of the Fermi level (EF) is found on decreasing photon energy, i.e., on increasing bulk sensitivity. The coherent band in SrVO3 and CaVO3 is shown to consist of surface and bulk-derived features, separated in energy. The stronger distortion on surface of CaVO3 compared to SrVO3 leads to a higher surface metallicity in the coherent DOS at EF, consistent with recent theory.

Journal Article↗

Electronic structure of charge- and spin-controlled Sr(1-(x+y))La(x+y)Ti(1-x)Cr(x)O3.

We present the electronic structure of Sr(1-(x+y))La(x+y)Ti(1-x)Cr(x)O3 investigated by high-resolution photoemission spectroscopy. In the vicinity of the Fermi level, it was found that the electronic structure was composed of a Cr 3d local state with the t(2g)3 configuration and a Ti 3d itinerant state. The energy levels of these Cr and Ti 3d states are well interpreted by the difference of the charge-transfer energy of both ions. The spectral weight of the Cr 3d state is completely proportional to the spin concentration x irrespective of the carrier concentration y, indicating that the spin density can be controlled by x as desired. In contrast, the spectral weight of the Ti 3d state is not proportional to y, depending on the amount of Cr doping.

Journal Article↗

Randomized clinical trial of hepatectomy using intermittent pedicle occlusion with ischaemic intervals of 15 versus 30 minutes.

BACKGROUND: The optimal ischaemic interval during hepatectomy with intermittent pedicle occlusion (IPO) remains to be established. The aim of the present randomized clinical trial was to compare the short-term outcome of hepatectomy using IPO with an ischaemic interval of 15 versus 30 min. METHODS: Between October 2002 and September 2004, 108 consecutive patients scheduled to undergo hepatectomy without bilioenterostomy were enrolled. During liver transection, IPO was performed with an ischaemic interval of either 15 min with 5 min of reperfusion (standard group, SG) or 30 min with 5 min of reperfusion (prolonged group, PG). After randomization and subsequent exclusion of certain patients, 44 patients in the SG and 48 in the PG were analysed. RESULTS: The mean(s.d.) bilirubin ratio (serum total bilirubin level on day 2 after operation divided by the preoperative level) was 1.6(0.8) in the SG and 1.7(0.8) in the PG (P = 0.874). The transection area per unit transection time was significantly greater in the latter group (median (range) 1.0 (0.4-2.1) versus 0.8 (0.0-1.5) cm(2)/min; P = 0.046). CONCLUSION: There was no difference in the bilirubin ratio when IPO was carried out for 30 or 15 min. By extension of IPO to 30 min, a greater resection area per unit time was possible with preservation of remnant liver function.

Adult↗

Adenoviral-mediated overexpression of membrane-bound human FasL and human decoy Fas protect pig islets against human CD8+ CTL-mediated cytotoxicity.

Pig islets are considered to be most suitable source of islets for xenotransplantation into patients with type 1 diabetes mellitus. However, cellular rejection, especially CD8+ CTL-mediated cytotoxicity, remains a formidable barrier preventing long-term xenograft survival. Our previous study demonstrated that human CD8+ CTLs were highly detrimental to xenograft cells and that this strong cytotoxicity of human CTLs was mediated mainly by the Fas/FasL apoptotic pathway. Furthermore, we exploited novel methods for inhibiting human CD8+ CTL-mediated xenocytotoxicity with overexpression of membrane-bound human FasL and human decoy Fas antigen in xenografted cells. In the present study, we assessed the cytoprotective effects of these novel inhibitory molecules overexpressed by an adenoviral-mediated system in pig islets. Isolated pig islets were transfected with adenovirus vector encoding either human decoy Fas or membrane-bound human FasL genes. Thirty percent to 60% of transfected pig islets expressed these molecules producing 60% to 88% suppression of CTL killing compared with parental pig islets. These data indicated that pig islet grafts isolated from transgenic pigs with either membrane-bound human FasL or human decoy Fas antigen genes may control the innate cellular response to xenografts, and creating a window of opportunity to facilitate xenograft survival.

Adenoviridae↗

An unusual renal vascular anomaly: common origin of arteries to the lower poles demonstrated by a computed tomography angiography using 16-slice multidetector computed tomography.

Arterial connection between the left and right kidneys is extremely rare. Only eight cases of such anomalous conditions have been reported in the world literature and all were confirmed by invasive angiography or dissection. We report a patient with this vascular anomaly clearly demonstrated by 16-slice multidetector computed tomography.

Angiography↗

Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer.

Mitogen activated protein (MAP) kinases are well known serine threonine kinases that modulate gene expression, mitosis, cell proliferation and programmed cell death or 'apoptosis' in response to various stresses. Extracellular stress regulated kinase (ERK), c-jun NH2 terminal kinase and p38 are major members of the MAP kinases, and there is now a body of evidence of their involvement in genesis or sensitivity to chemotherapy of human prostate cancers. In this review, we focus on the molecular roles of MAP kinases and their pathological correlations, with particular attention to novel downstream signals through phosphorylation of the Fas-associated death domain protein that effectively regulates not only apoptosis but also the cell cycle in prostate neoplastic cells.

Adaptor Proteins, Signal Transducing↗

[Extracardiac rupture of aneurysm of the noncoronary sinus of valsalva: report of a case].

A 78-year-old female was admitted to our hospital because of sudden onset of chest pain and general fatigue. A chest X-ray showed marked cardiomegaly and computed tomography (CT) revealed pericardial effusion with left pleural effusion. Upon admission to CCU, she suddenly lost consciousness and was intubated. Echocardiography confirmed increase in the amount of the pericardial effusion, which was drained at CCU. By an emergent operation, ruptured aneurysm of the noncoronary sinus of Valsalva to the pericardial space was confirmed upon opening the chest and patch plasty of the sinus of Valsalva was performed. The postoperative course was uneventful, and she was discharged on the 24th postoperative day. Extracardiac rupture of aneurysm of the sinus of Valsalva is extremely rare, and the emergent operation is indispensable.

Aged↗

Spontaneous regression of hepatocellular carcinoma with complete necrosis: case report.

Spontaneous regression of hepatocellular carcinoma is rare phenomenon. A 74-year-old man was found to have a hepatocellular carcinoma with intrahepatic metastases in the lateral segment of the liver. Before surgery, he developed severe cholangitis due to choledocholithiasis and was treated endoscopically. The tumor marker level decreased markedly, and hepatectomy was performed. The resected tumor demonstrated complete necrosis.

Aged↗