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T Yamada

Publications and source records attributed to T Yamada.

At least 163 records · Page 9Linked to original sources
PubMed2001

Protective responses against experimental Mycobacterium leprae infection in mice induced by recombinant Bacillus Calmette-Guérin over-producing three putative protective antigen candidates.

The components of Ag85 (Ag85A, Ag85B, and Ag85C) are putative protective antigen candidates against mycobacterial infection. A recombinant Mycobacterium bovis Bacillus Calmette-Guérin (rBCG) over-producing Ag85A, Ag85B, and MPB51 (rBCG/BA51) was constructed. rBCG/BA51 could secrete these antigens at levels more than five times higher than parental BCG. Immunization of C57BL/6 and BALB/c mice with this rBCG reduced the multiplication of Mycobacterium leprae in the foot pads of both strains of mice. The inhibition by rBCG/BA51 was more evident than that by parental BCG.

Animals↗
PubMed2001

Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine released from T-cells and macrophages. Although a detailed understanding of the biological functions of MIF has not yet been clarified, it is known that MIF catalyzes the tautomerization of a nonphysiological molecule, D-dopachrome. Using a structure-based computer-assisted search of two databases of commercially available compounds, we have found 14 novel tautomerase inhibitors of MIF whose K(i) values are in the range of 0.038-7.4 microM. We also have determined the crystal structure of MIF complexed with the hit compound 1. It showed that the hit compound is located in the active site of MIF containing the N-terminal proline which plays an important role in the tautomerase reaction and forms several hydrogen bonds and undergoes hydrophobic interactions. A crystallographic study also revealed that there is a hydrophobic surface which consists of Pro-33, Tyr-36, Trp-108, and Phe-113 at the rim of the active site of MIF, and molecular modeling studies indicated that several more potent hit compounds have the aromatic rings which can interact with this hydrophobic surface. To our knowledge, our compounds are the most potent tautomerase inhibitors of MIF. One of these small, drug-like molecules has been cocrystallized with MIF and binds to the active site for tautomerase activity. Molecular modeling also suggests that the other hit compounds can bind in a similar fashion.

Binding Sites↗
PubMed2001

Prognostic significance of polysialic acid expression in resected non-small cell lung cancer.

Polysialic acid (PSA) is a carbohydrate attached mainly to the neural cell adhesion molecule. Because PSA is composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and has a large negative charge, the presence of PSA attenuates the adhesive property of neural cell adhesion molecule and increases cellular motility. In an earlier study, we demonstrated that PSA and STX, a polysialyltransferase, were associated with tumor progression in non-small cell lung cancer (NSCLC) (F. Tanaka et al., Cancer Res., 60: 3072-3080, 2000). Therefore, in the present study, to assess the prognostic significance of PSA in resected NSCLC, a total of 236 patients who underwent complete resection for pathological (p)-stage I-IIIa disease were reviewed retrospectively. PSA was expressed in 44 of 236 (18.6%) patients, and the expression was correlated with p-stage disease. For all p-stage patients, 5-year survival rates for those with PSA-positive and PSA-negative tumors were 52.1% and 71.3%, respectively, demonstrating a significantly worse prognosis for the PSA-positive patients (P = 0.012). Analysis for only p-stage I patients also demonstrated a significantly worse prognosis for the PSA-positive patients; 5-year survival rates of the PSA-positive and the PSA-negative patients were 45.1% and 83.5%, respectively, (P < 0.001). In addition, there proved to be no difference in the postoperative survival among p-stage I, II, and IIIa patients when PSA expression was positive. Multivariate analysis confirmed that PSA expression was an independent factor to predict poor prognosis in resected NSCLC. These results suggested that PSA could be an important clinical marker and that preoperative induction and/or postoperative adjuvant therapies should be performed for PSA-positive NSCLC, even if the disease is classified as p-stage I.

Biomarkers, Tumor↗
PubMed2001

Relationship between diurnal rhythm of cell cycle and interferon receptor expression in implanted-tumor cells.

Whether the diurnal rhythm of cell cycle is associated with that of interferon-alpha/beta receptor (IFNAR) expression was investigated in implanted-tumor cells. The expression of IFNAR mRNA significantly increased when the proportion of tumor cells in DNA synthesis (S) phase increased in vitro. A diurnal rhythm was observed for cell cycle distribution in implanted-tumor cells. The specific binding of interferon-alpha to receptor and IFNAR mRNA increased when the proportion of tumor cells in S phase increased in vivo. The time-dependent expression of IFNAR was supported by that of transcription factor level induced by interferon-beta. The present result suggests that the rhythm of IFNAR expression is closely related to that of cell cycle distribution in implanted-tumor cells.

Animals↗
PubMed2001

Overexpression of a slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish.

Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation.

Animals↗
PubMed2001

Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes.

BACKGROUND: The measurement of serum concentrations of cardiac troponin T (TnT) is a simple, useful method to detect myocyte injury that may be repeated multiple times to follow patients without interobserver variability. METHODS AND RESULTS: Multiple measurements of TnT with a second-generation assay were performed in 60 patients with dilated cardiomyopathy confirmed by coronary angiography and endomyocardial biopsy between April 1996 and December 1999. Three evolutionary patterns of TnT concentrations were identified. Thirty-three patients had concentrations of TnT <0.02 ng/mL throughout the follow-up period (group 1). The remaining 27 patients had high initial serum concentrations of TnT (>/=0.02 ng/mL). In 10 of these 27 patients, TnT decreased to <0.02 ng/mL during follow-up (group 2), whereas 17 had persistently high serum TnT concentrations despite being conventionally treated for chronic congestive heart failure (group 3). Although the initial echocardiographic left ventricular diastolic dimension (LVDd) and left ventricular ejection fraction (LVEF) were not significantly different among the 3 groups, follow-up echocardiography showed significantly decreased LVDd and increased LVEF in group 1 (each P:<0.01) and group 2 (each P:<0.05) compared with increased LVDd and decreased LVEF in group 3 (each P:<0.05). The cardiac event-free rate was significantly lower in group 3 than in groups 1 and 2 (each P:<0.001), and the survival rate was lower in group 3 than in group 1 (P:<0.05). CONCLUSIONS: Persistently increased TnT concentrations in dilated cardiomyopathy suggest ongoing subclinical myocyte degeneration associated with deterioration of the patients' clinical status.

Biopsy↗
PubMed2001

Suppression of transthyretin expression by ribozymes: a possible therapy for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy type 1 (FAP) is an autosomal-dominantly inherited disorder with systemic deposition of a variant transthyretin (TTR). We attempted to suppress TTR production by ribozyme degradation of TTR mRNA. Hammerhead and hairpin ribozymes cleaved TTR mRNA at specific individual sites in vitro. A ribozyme targeting a variant TTR (E61K) degraded the variant mRNA, but not a wild-type mRNA. These ribozymes also reduced the amounts of TTR mRNA and protein in HepG2 cells and COS-1 cells transfected with TTR-E61K cDNA. Ribozymes might be studied further as a potential treatment for FAP.

Amyloid Neuropathies↗
PubMed2001

Spontaneous reconstruction of the canine hypogastric nerve over a long period after removing half of its length.

Spontaneous reconstruction of the sympathetic pathway projecting to the seminal tract after serious injury has not been well understood. Multiple cross-innervation mechanisms from the spinal cord via the hypogastric nerve to the seminal tract have been demonstrated currently. This study was undertaken to explore long-term spontaneous reconstruction of the canine hypogastric nerve (HGN), which controls ejaculation, after removing half of its length. Further, the study tried to identify the crossed-pathway(s) reconstructed. Responses of the vas deferens/epididymis and bladder neck to electrical stimulation of the lumbar splanchnic nerve (LSN) or the HGN were examined. In six dogs whose hypogastric nerve was injured bilaterally as described above 4 years before, corresponding to more than 20 years in human, nine (43%) and 13 (57%) of the 21 LSNs stimulated elicited elevation of vasal and bladder neck pressure, respectively. By combining re-transection of a HGN, the following pathways to the vas deferens/epididymis were identified to have been reconstructed: (1) to the ipsilateral was deferens/epididymis without crossing to the other side; (2) to the contralateral vas deferens/epididymis by crossing to the other side at the caudal mesenteric plexus (CMP); (3) to the contralateral vas deferens/epididymis by crossing to the other side from the ipsilateral HGN at the commissural branches between the right and left pelvic plexuses (CBPP); and (4) to the ipsilateral vas deferens/epididymis by crossing twice at the CMP to the other side and at the CBPP again from the contralateral HGN to the ipsilateral side. The similar patterns of reconstruction were also observed in the bladder neck. The above results indicate that the sympathetic pathways via the HGN to the canine seminal tract can be reconstructed spontaneously in a high rate over a long period after serious injuries and that their cross-innervation system can be repaired.

Animals↗
PubMed2001

Protein-tyrosine kinase Syk expressed in human nasal fibroblasts and its effect on RANTES production.

Fibroblasts, a rich source of chemokines, interact with eosinophils and play a key role in the pathogenesis of airway disease. RANTES is produced by fibroblasts to attract and activate eosinophils. LPS is known to induce RANTES and cause protein tyrosine phosphorylation. Nonreceptor protein tyrosine kinase Syk is widely expressed and an important role in intracellular signal transduction in hemopoietic cells. In the present study, we examined whether Syk was expressed in a number of primary human nasal polyp tissue-derived fibroblast lines and whether it played some role in cellular function. Syk proteins were expressed in human nasal fibroblasts, but the expression level varied. There were positive correlations between the level of Syk expression and RANTES production induced by LPS. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with LPS. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production. These results suggest that Syk expression affects RANTES production in fibroblasts of nasal polyps.

Blotting, Western↗
PubMed2001

Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall-cell lung cancer.

Caspase-3 is a cysteine protease that plays an important role in the process of apoptotic cell death. Whereas many studies on the clinical significance of apoptosis in the therapy of malignant tumors have been reported, little has been studied clinically on caspase-3. In the present study, the clinical significance of caspase-3 expression in resected nonsmall-cell lung cancer (NSCLC) and its correlation with incidence of apoptosis were examined. A total of 118 consecutive patients who had undergone complete resection for pathologic Stage I NSCLC were retrospectively reviewed. Caspase-3 expression was examined immunohistochemically using a polyclonal antibody that recognized uncleaved caspase-3. The 5-year survival rate for patients with strong expression of caspase-3 (66.6%) was significantly lower than that for patients with weak expression (82.1%, P = 0.021). Expression of caspase-3 was not correlated with incidence of apoptosis, proliferative activity, or p53 status. Multivariate analysis confirmed that strong expression of caspase-3 was a significant factor to predict poor prognosis. These results suggest that enhanced expression of "uncleaved" caspase-3, that is, inactivated caspase-3, was correlated with poor prognosis in resected NSCLC.

Aged↗
PubMed2001

Use of a new ICG-dye-enhanced diode laser for percutaneous laser disc decompression.

BACKGROUND AND OBJECTIVE: The lasers used today for Percutaneous Laser Disc Decompression (PLDD) can not selectively ablate the nucleus pulposus (NP). We hypothesized that if indocyanine green dye were injected into the NP, 805 nm diode laser irradiation would result in selective and safe removal of NP tissue without damaging nearby tissues. STUDY DESIGN/MATERIALS AND METHODS: Twelve beagle dogs were used for three experiments, i.e., determination of attenuation coefficients of NP and AF, determination of weight of NP before and after laser irradiation, and histopathological study. RESULTS: The attenuation coefficient at 805 nm of NP which had been homogenized in the presence of ICG was 2521.3/cm. Upon application of the diode laser at a power of 1, 3, or 5 W (the intensity of laser irradiation: 0.353, 1.061, or 1.768 x 10(3) W/cm(2)) to NPs into which ICG had been injected, the weight of the NPs decreased by a mean 20, 45, and 65%, respectively. Macroscopic and microscopic examination of the discs after PLDD showed that only the NP where the tissues were stained by ICG were removed. CONCLUSIONS: These results indicated that the combined use of ICG and diode laser irradiation effectively and selectively ablates the NP with low laser power.

Animals↗
PubMed2001

Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma.

Vascular endothelial growth factor receptor 3 (VEGFR-3) has been proposed as a marker for lymphatic endothelial cells. This study investigated the expression of VEGFR-3 in the tumour vessels of lung adenocarcinoma and evaluated whether VEGFR-3 staining was useful for identifying lymphatic vessels within the tumour stroma. It also explored whether active growth of lymphatic vessels occurred in lung adenocarcinoma. Formalin-fixed, paraffin-embedded specimens obtained from 60 cases of lung adenocarcinoma, including five cases of pure bronchiolo-alveolar carcinoma (BAC) without stromal, vascular, and pleural invasion, were examined. No VEGFR-3-positive vessels were observed in pure BAC, but varying numbers of VEGFR-3-positive vessels were found in 39 of 55 (70.9%) invasive adenocarcinomas. A comparison of serial sections stained for VEGFR-3, CD31, and laminin-1 showed that most of the VEGFR-3-positive vessels appeared to be blood vessels (CD31-positive, laminin-1-positive), but some had the characteristics of lymphatic vessels (variable staining for CD31, little or no staining for laminin-1). VEGFR-3 staining highlighted lymphatic invasion by cancer cells; this invasion could not be detected by CD31 or haematoxylin and eosin (H&E) staining. Active growth of lymphatic vessels (as indicated by nuclear Ki-67 labelling of the endothelium) was observed in five tumours, four of which showed a high level of lymphatic invasion by cancer cells. It was concluded that VEGFR-3 immunostaining did not discriminate clearly between vascular and lymphatic endothelial cells, since expression of VEGFR-3 can be up-regulated in tumour blood vessels. However, VEGFR-3 staining combined with laminin-1 and CD31 staining would be useful for identifying lymphatic vessels and their invasion by tumour cells in a more objective way. Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells.

Adenocarcinoma↗
PubMed2001

Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, induced xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in liver of mice. When TCDD was given to mice as a single oral dose of 40 microg/kg, the activities of XO and XDH increased about threefold within 3 days and the increased levels were maintained for 4 weeks. The treatment of mice with 3-methylcholanthrene also induced XO/XDH activities, but phenobarbital and dexamethasone had no effect. The level of aldehyde oxidase, a molybdenum flavoenzyme related to XO/XDH, in mouse liver was also enhanced about 1.5-fold by TCDD treatment. The inducing effect of TCDD and 3-methylcholanthrene was not observed in null mice (AhR(-/-)), which lack the AhR gene. XO and XDH activities were induced by TCDD in heterozygous mice (AhR(+/-)). The lipid peroxidation in liver was stimulated by TCDD. The induction of XO and XDH, which produces reactive oxygen species, may contribute to the various toxicities of TCDD.

Animals↗
PubMed2001

Identification of the mycobacterial DNA-binding protein 1 region which suppresses transcription in vitro.

We recently identified a novel DNA-binding protein from Mycobacterium bovis bacillus Calmette-Guérin (BCG), termed mycobacterial DNA-binding protein 1 (MDP1). MDP1 inhibited the in vitro syntheses of DNA, RNA and protein, and reduced growth rates of bacteria transformed with MDP1 genes. In this study, we examined the DNA binding regions of MDP1 by using a set of synthetic peptides. One dominant region was determined on peptide 4 composed of amino acids, at positions 31-50. The peptide 4 inhibited syntheses of both DNA and RNA in vitro. The critical amino acids residues for these functions were analysed utilizing synthetic peptides substituted with Ala. This domain was perfectly conserved in MDP1 homologues in mycobacteria, but not observed in other known DNA binding proteins. These results indicate mycobacteria possess a unique nuclear protein, which might be involved in growth regulation of these organisms.

Amino Acid Sequence↗
PubMed2001

Graft failure due to hemophagocytic syndrome after autologous peripheral blood stem cell transplantation.

Hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation can occasionally cause graft failure. We describe a female patient with B-cell non-Hodgkin's lymphoma (NHL) with graft failure due to HPS 12 days after autologous peripheral blood stem cell transplantation (PBSCT). Autologous PBSCT was carried out during unconfirmed/uncertain complete remission according to the Cotswolds classification after 6 cycles of biweekly (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and 3 courses of salvage chemotherapy including etoposide. The patient developed a high fever on day 2 post-PBSCT. Her white blood cell count rose to 0.9 x 10(9)/L on day 10 post-PBSCT, but then began to decrease. A bone marrow aspirate on day 12 post-PBSCT revealed an increase in the number of benign histiocytes with hemophagocytosis, and the patient was diagnosed with HPS. Although high-dose methylprednisolone therapy was continued, her white blood cell count further decreased to 0.3 x 10(9)/L, and the patient died of multiple organ failure on day 29 post-PBSCT. A computed tomography scan did not identify recurrent NHL, and necropsy specimens from the bone marrow, liver, and kidney revealed no neoplastic infiltration. Bone marrow necropsy showed marked hypocellularity with active histiocytic hemophagocytosis. HPS may have been induced by infection with methicillin-resistant Staphylococcus aureus rather than by lymphoma-associated HPS.

Aged↗
PubMed2001

A variant form of acute promyelocytic leukemia with marked myelofibrosis.

We describe a variant form, French-American-British (FAB) M3v, of acute promyelocytic leukemia (APL; FAB M3) with atypical morphocytochemical features, immature antigens (CD34 and HLA-DR) and marked myelofibrosis (MF). Usual APL cells do not express CD34 or HLA-DR antigens. MF may be more frequently observed in patients with M3v expressing CD34 and HLA-DR antigens than in patients with M3 lacking these antigens. Despite marked MF, recovery from the hypoplastic phase in the case we described was not delayed after remission induction chemotherapy consisting of enocitabine, 200 mg/mi2 intravenously; 6-mercaptopurine, 70 mg/m2 orally for 10 days; daunorubicin 40 mg/m2 intravenously for 4 days; and all-trans retinoic acid 45 mg/M2 orally between days 20 and 33. The promyelocytic leukemia-retinoic-acid receptor (PML-RAR) alpha fusion transcript, according to reverse transcriptase-polymerase chain reaction (RT-PCR), became negative in the bone marrow after the first course of consolidation chemotherapy. Autologous peripheral blood stem cell transplantation (autoPBSCT) was carried out after 3 courses of consolidation chemotherapy. There were no specific complications based on MF throughout the clinical course, including engraftment in autoPBSCT. The patient has been without MF and in molecular remission, defined as disappearance of the PML-RAR alpha fusion transcript according to RT-PCR, for 21 months. Longer follow-up will clarify the effects of autoPBSCT on prognosis in APL with MF.

Adolescent↗