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T Tanaka

Publications and source records attributed to T Tanaka.

At least 55 records · Page 3Linked to original sources
PubMed2006

Disruption-induced mucus secretion: repair and protection.

When a cell suffers a plasma membrane disruption, extracellular Ca(2+) rapidly diffuses into its cytosol, triggering there local homotypic and exocytotic membrane fusion events. One role of this emergency exocytotic response is to promote cell survival: the internal membrane thus added to the plasma membrane acts as a reparative "patch." Another, unexplored consequence of disruption-induced exocytosis is secretion. Many of the cells lining the gastrointestinal tract secrete mucus via a compound exocytotic mechanism, and these and other epithelial cell types lining the digestive tract are normally subject to plasma membrane disruption injury in vivo. Here we show that plasma membrane disruption triggers a potent mucus secretory response from stomach mucous cells wounded in vitro by shear stress or by laser irradiation. This disruption-induced secretory response is Ca(2+) dependent, and coupled to cell resealing: disruption in the absence of Ca(2+) does not trigger mucus release, but results instead in cell death due to failure to reseal. Ca(2+)-dependent, disruption-induced mucus secretion and resealing were also demonstrable in segments of intact rat large intestine. We propose that, in addition to promoting cell survival of membrane disruptions, disruption-induced exocytosis serves also the important protective function of liberating lubricating mucus at sites of mechanical wear and tear. This mode of mechanotransduction can, we propose, explain how lubrication in the gastrointestinal tract is rapidly and precisely adjusted to widely fluctuating, diet-dependent levels of mechanical stress.

Animals↗
PubMed2006

Effective chemoradiotherapy protocol with 5-fluorouracil for cervical squamous cell carcinoma in vitro.

PURPOSE OF INVESTIGATION: 5-Fluorouracil (5FU) is frequently used in concurrent chemoradiotherapy for patients with advanced cervical cancer, although its optimal chemoradiotherapy protocol has not yet been established. In search of an optimal chemoradiotherapy protocol, some in vitro experiments were carried out. METHODS: The radiosensitive human cervical squamous cell carcinoma cell line ME180 was examined to investigate the effects of 5FU on radiosensitivity and the effects of irradiation on 5FU-sensitivity. RESULTS: 5FU dose-dependently enhanced cellular radiosensitivity at therapeutic concentrations. Although high doses of y-ray irradiation significantly reduced the 5FU-sensitivity, a low dose of irradiation at therapeutic doses (< 2.5 Gy) had no effect on 5FU-sensitivity of the irradiated cells. Cells pretreated with 5FU eight hours before irradiation showed significantly higher 5FU-sensitivity than cells concurrently treated with 5FU and irradiation. In contrast, cells treated with 5FU eight hours after irradiation showed significantly lower 5FU-sensitivity than cells concurrently treated with 5FU and irradiation. Moreover, all four post-irradiation surviving subclones obtained from repeatedly irradiated ME180 cells showed significantly lower 5FU-sensitivity than the non-irradiated parent cells. CONCLUSION: 5FU acts as a radiosensitizer for cervical squamous cell carcinoma and 5FU-sensitivity is reduced in irradiated cells. Therefore, 5FU administration immediately before irradiation may be a more effective treatment than concurrent chemoradiotherapy or post-irradiation chemotherapy with 5FU.

Antimetabolites, Antineoplastic↗
PubMed2005

Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

OBJECTIVE: To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS: 92 consecutive patients with DCM were enrolled and followed up for four years. MAIN OUTCOME MEASURES: Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate. RESULTS: 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (> or = 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (> or = 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations. CONCLUSIONS: The concentration of serum H-FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM.

Biomarkers↗
PubMed2005

Randomly diluted eg orbital-ordered systems.

Dilution effects on the long-range ordered state of the doubly degenerate e(g) orbital are investigated. Quenched impurities without the orbital degree of freedom are introduced in the orbital model where the long-range order is realized by the order-from-disorder mechanism. It is shown by Monte Carlo simulations and the cluster-expansion method that a decrease in the orbital-ordering temperature by dilution is substantially larger than that in the randomly diluted spin models. Tilting of orbital pseudospins around impurities is the essence of this dilution effect. The present theory provides a new viewpoint for the recent resonant x-ray scattering experiments in KCu(1-x)Zn(x)F(3).

Journal Article↗
PubMed2005

Symmetry-resolved absorption spectra of vibrationally excited CO2 molecules.

Symmetry-resolved x-ray absorption spectroscopy has been first carried out on high-temperature molecules. From the angle-resolved ion yield spectra of CO2 both at room temperature and at 430 degrees C, symmetry-resolved absorption profiles of the C 1s(-1) 2pi(u) and O 1s(-1) 2pi(u) resonances have been extracted for the vibrational ground state molecules and bending-vibration excited ones. The profiles change dramatically between them, and the Renner-Teller effect becomes more evident for the vibrationally excited molecules. The effects of the multimode vibronic coupling are suggested for the O 1s(-1) 2pi(u) and O 1s(-1) 3s sigma(g) resonances.

Journal Article↗
PubMed2005

Violation of the Franck-Condon principle due to recoil effects in high energy molecular core-level photoionization.

Carbon 1s photoelectron spectra of methane are measured over a photon energy range between 480 eV and 1200 eV. Additional components appear between the individual symmetric stretching vibrational components and are attributed to the excitations of asymmetric stretching and bending vibrations due to recoil of the high-energy photoelectron emission. This recoil effect is the evidence for the violation of the Franck-Condon principle which states that neither the positions nor the momenta of the nuclei change during the ionization event.

Journal Article↗
PubMed2005

Nature of phosphorus limitation in the ultraoligotrophic eastern Mediterranean.

Phosphate addition to surface waters of the ultraoligotrophic, phosphorus-starved eastern Mediterranean in a Lagrangian experiment caused unexpected ecosystem responses. The system exhibited a decline in chlorophyll and an increase in bacterial production and copepod egg abundance. Although nitrogen and phosphorus colimitation hindered phytoplankton growth, phosphorous may have been transferred through the microbial food web to copepods via two, not mutually exclusive, pathways: (i) bypass of the phytoplankton compartment by phosphorus uptake in heterotrophic bacteria and (ii) tunnelling, whereby phosphate luxury consumption rapidly shifts the stoichiometric composition of copepod prey. Copepods may thus be coupled to lower trophic levels through interactions not usually considered.

Animals↗
PubMed2005

Multiple intracranial subarachnoid osteomas.

OBJECTIVE AND IMPORTANCE: Intracranial osteomas, which have no connections with the dura or the skull, are very rare. Here we report one case of multiple intracranial subarachnoid osteomas. CLINICAL DESCRIPTION: A 24-year-old gentleman, who had no previous history of systemic disease, meningitis or head injury, presented with a 6-month history of non-specific intermittent headache over the whole head. Neuro-imaging showed multiple ossified lesions in the right frontal area, which were found to compress the underlying cerebral hemisphere. The patient underwent a right frontal craniotomy. The masses were dissected from the depressed brain along the intact pial planes, however, all of the white bone-hard masses tightly adhered to the superficial cortical veins. The masses were removed and the cortical veins were sacrificed. The patient had headaches and was nauseous for three days after the surgery due to venous congestion; however, the patient was neurologically intact on discharge. Pathological diagnosis was osteoma. CONCLUSION: To our knowledge, this is the first report of multiple intracranial subarachnoid osteomas. Surgical findings strongly support the hypothesis of the origin of the tumour that the primitive mesenchymal cells from the connective tissue might have migrated into the subarachnoid space accompanying the intracerebral blood vessels.

Adult↗
PubMed2005

Semiflexible polymers confined in soft tubes.

We discuss various conformations for a polymer (of persistent length l(p)) confined into a deformable tube (the wall being a lipid bilayer with a certain surface tension sigma and curvature energy K). Our study assumes that there is no adsorption of the chain on the wall. Three states are compared: (a) an unperturbed tube, plus a confined chain, (b) a tube swollen in all the region surrounding the chain (similar to a snake eating a sausage), (c) a globule, a roughly spherical coil surrounded by a strongly deformed tube. We construct a (qualitative) phase diagram for these systems with two variables: the surface tension sigma and the degree of polymerization N. Our main conclusion is that "globules" usually win over "snakes".

Adsorption↗
PubMed2005

Applicability of anti-neovascular therapy to drug-resistant tumor: suppression of drug-resistant P388 tumor growth with neovessel-targeted liposomal adriamycin.

Anti-neovascular therapy, one of the effective anti-angiogenic chemotherapy, damages new blood vessels by cytotoxic agents delivered to angiogenic endothelial cells and results in indirect eradication of tumor cells. We previously reported that liposomes-modified with a pentapeptide, Ala-Pro-Arg-Pro-Gly (APRPG-Lip) homing to angiogenic site, highly accumulated in tumor tissue, and APRPG-Lip encapsulating adriamycin (APRPG-LipADM) effectively suppressed tumor growth in tumor-bearing mice. In the present study, we examined the topological distribution of fluorescence-labeled APRPG-LipADM as well as TUNEL-stained cells in an actual tumor specimen obtained from Colon 26 NL-17 carcinoma-bearing mice. The fluorescence-labeled APRPG-Lip dominantly localized to vessel-like structure: a part of which was also stained with anti-CD31 antibody. Furthermore, TUNEL-stained cells were co-localized to the same structure. These data indicated that APRPG-LipADM bound to angiogenic endothelial cells and induced apoptosis of them. We also investigated the applicability of anti-neovascular therapy using APRPG-LipADM to ADM-resistant P388 solid tumor. As a result, APRPG-LipADM significantly suppressed tumor growth in mice bearing the ADM-resistant tumor. These data suggest that APRPG-LipADM is applicable to various kinds of tumor including drug-resistant tumor since it targets angiogenic endothelial cells instead of tumor cells, and eradicates tumor cells through damaging the neovessels.

Angiogenesis Inhibitors↗
PubMed2005

Alpha-synuclein-positive structures induced in leupeptin-infused rats.

Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems.

Animals↗
PubMed2005

Characterization of hypervariable region in hepatitis C virus envelope protein during acute and chronic infection.

Hepatitis C virus (HCV) causes persistent infection in most patients. To clarify the mechanisms underlying establishment of this persistent infection, nucleotide sequences of the E1/E2 region were characterized in 5 patients with acute and chronic HCV infection. We used direct DNA sequencing methods to identify the major sequence of HCV in each patient. Each HCV genome displayed a high frequency of nucleotide sequence variation in the hypervariable region (HVR) of E2. However, patient-specific conserved nucleotide sequences were identified in the E1/E2 region during the course of infection and conserved the higher-order protein structure. In the acute phase HCV infection, amino acid substitution in HVR-1 as the monthly rate of amino acids substitution per site (%) between each point exceeded 10.2%. In the chronic phase HCV infection, a significantly lower rate of amino acid substitution was observed in patients. The host immune responses to HVR-1 of each HCV isolates from all clinical courses were characterized using synthetic peptides and ELISA. One chronic patient serum (genotype 1b) did not react at all to its own HVR-1 peptides, however another patient (genotype 2b) reacted to all clinical course. These results indicated that HVR-1 might not always exhibit neutralizing epitopes of HCV infection. The sequence variation in HVR-1 may instead indicate the existence of various clones in acute phase infection and the adaption of these clones is thought to have caused persistent and chronic infection in each patient.

Acute Disease↗
PubMed2005

Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19.

BACKGROUND: Endometriosis, an estrogen-dependent disease, is believed to be influenced by multiple genetic and environmental factors. Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19). METHODS: All participants underwent diagnostic laparoscopy, and the stage of endometriosis was determined according to the Revised American Fertility Society classification. Of the 138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had stage III and 25 had stage IV. SNPs were discriminated by allele-specific oligonucleotide hybridization. RESULTS: Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend < 0.01). No statistically significant association was found for the CYP19 polymorphism. CONCLUSIONS: Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Genome-wide association study to identify SNPs conferring risk of myocardial infarction and their functional analyses.

Myocardial infarction might result from the interactions of multiple genetic and environmental factors, none of which can cause disease solely by each of themselves. Although molecular biological studies revealed that a number of proteins are possibly involved in its pathogenesis, little, if any genetic findings have been reported so far. To reveal genetic backgrounds of myocardial infarction, we performed a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers. We have identified functional SNPs within the lymphotoxin-alpha gene (LTA) located on chromosome 6p21 that conferred susceptibility to myocardial infarction. Furthermore, we could identify galectin-2 protein as a binding partner of LTA protein. The association study further revealed that a functional SNP in LGALS2 encoding galectin-2, which led to altered secretion of LTA, also indicated a risk of myocardial infarction. A combined strategy of genetic and molecularcellular biological approaches may be useful in clarifying pathogenesis of common diseases.

Case-Control Studies↗
PubMed2005

Successful islet transplantation from a single pancreas harvested from a young, low-BMI, non-heart-beating cadaver.

BACKGROUND: Young donors, donors with low body mass index (BMI), and non-heart-beating (NHB) donors are considered nonideal for islet transplantation. In this report, we successfully used a pancreas from a young, low-BMI, NHB donor for islet transplantation. METHODS: The donor was a 15-year-old adolescent boy whose cause of death was rupture of a primary brain tumor. According to Japanese regulations, his pancreas was procured after cardiac arrest. Warm ischemic time was 3 minutes and cold ischemic time was 300 minutes. The pancreas was digested by the automated method of Ricordi, followed by purification using continuous Euro-Ficoll gradients on a Cobe 2991 device. The recipient was a 35-year-old woman with unstable type 1 diabetes mellitus. Her pretransplant C-peptide level was null. She suffered frequent hypoglycemic unawareness. Her pretransplant M value, which is a good marker for glucose instability, was 125. Islet yield was 252,816 IEQ. There were no signs of contamination. Viability of islets assessed by FDA/PI staining was 83%. Stimulation index was 2.7. RESULTS: The patient received 5160 IEQ/kg of islets via the portal vein under local anesthesia. There were no transplant-related complications. Although she required minimal exogenous insulin, her C-peptide level increased to 0.7 ng/mL at postoperative day (POD) 14. Her M value at POD 15 to 19 decreased dramatically to 23.6, indicating good glycemic control. At 3 months posttransplant, episodes of hypoglycemia disappeared. CONCLUSIONS: Although an additional transplant is mandatory to wean patients from insulin, this case shows the possibility of using marginal donors, such as a young, low-BMI, NHB donor, for pancreas islet transplantation.

Adolescent↗
PubMed2005

Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD/SCID/beta2-microglobulin(null) mice.

Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe-combined immunodeficiency (SCID)/beta2-microglobulin(null) (NOD/SCID/beta2m(null)) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV-I integration identical to those of donors by Southern blot analysis. These cells infiltrated into recipients' liver, and formed nodular lesions, recapitulating the clinical feature of each patient. In contrast, in smoldering-type ATL cases, multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta2m(null) mice. When smoldering-type ATL cells were retransplanted into secondary NOD/SCID/beta2m(null) recipients, single HTLV-I-infected clones became predominant, suggesting that clones with dominant proliferative activity can be competitively selected in this xenogeneic system. Taken together, the NOD/SCID/beta2m(null) newborn system is useful to understand kinetics, metastasis, and disease progression of ATL in vivo.

Anemia, Refractory, with Excess of Blasts↗
PubMed2005

Five-year survival of patients with hepatocellular carcinoma treated with laparoscopic microwave coagulation therapy.

BACKGROUND AND STUDY AIM: Hepatocellular carcinomas (HCCs) that are located near the liver surface are difficult to treat with percutaneous locoregional therapies, so we have performed laparoscopic microwave coagulation therapy (LMCT) for these HCCs. We assessed the long-term survival of patients with HCCs treated with LMCT, the factors related to their survival, and the rates and causes of local and distant recurrences. PATIENTS AND METHODS: Participants were 68 patients with HCC treated in the past 8 years with LMCT under local or general anesthesia. LMCT was done using microwave electrodes with tips ranging from 15 to 45 mm in length; the effectiveness of LMCT was confirmed using contrast-enhanced computed tomography (CT) within 2 weeks of the LMCT procedure while patients were still in hospital, and within 1-3 months after the procedure in an outpatient setting; and the follow-up study was performed periodically by CT, ultrasonography, or magnetic resonance imaging (MRI) in addition to estimation of alpha fetoprotein. Factors contributing to survival were analyzed statistically. RESULTS: The mean lengths of the major and minor axes of the 71 HCC nodules in 68 patients were 20 mm and 18 mm, respectively, and the mean lengths of the major and minor axes of the coagulated areas were 43 mm and 29 mm, respectively. At dynamic CT after the LMCT procedure, treatment in 62 of the 68 patients (91%) was judged to have been completely effective; the remaining six patients underwent additional therapy while still in hospital. Eight of the 68 patients (12%) had local recurrences, 39 of them (57%) had distant recurrences, and 21 of them (31%) had no recurrence up to December 31, 2003. A total of 14 patients (21%) died during the 16-56 months after LMCT. When the survival rate was assessed for all patients treated with LMCT, 1-year survival was 97 %, 3-year survival was 81%, and 5-year survival was 43%. Whether the therapy was for primary or secondary HCC strongly influenced survival. CONCLUSIONS: LMCT is a useful modality in clinical practice for treatment of HCC nodules located near the liver surface, and it can be safely performed, in its entirety, under direct visual guidance.

Aged↗