Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 145 records · Page 8Linked to original sources

PubMed1999

Antioxidative activity of indenestrol A, a diethylstilbestrol metabolite.

To elucidate the various activities of synthetic estrogens, the antioxidative activities of diethylstilbestrol (DES) and related metabolic analogs were examined. The antioxidative activities were assessed in terms of the inhibitory effect on Fe2+(-) and ascorbic acid-induced peroxidation of egg phosphatidylcholine (egg PC), and also superoxide scavenging ability using cyclic voltammetry. Moreover, after in vivo administration of the test compounds to mice, the animals were subjected to hyperoxia, and catalase, glutathione peroxidase and superoxide dismutase activities in the brain, lungs and liver were measured. The results indicated that indenestrol A, one of the metabolites of DES, had the strongest antioxidative activity among the test compounds under both in vivo and in vitro conditions.

Animals↗

PubMed1999

Studies on disease-modifying antirheumatic drugs. III. Bone resorption inhibitory effects of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl) quinoline-3-carboxylate (TAK-603) and related compounds.

In the course of our studies aimed at obtaining new drugs for treatment of bone and joint diseases, chemical modification of the potent bone resorption inhibitors justicidins, was performed and various naphthalene lactones, quinoline lactones and quinoline derivatives bearing an azole moiety at the side chain were prepared. Their inhibitory effects on bone resorption were evaluated by Raisz's method, and several compounds, including ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl)quinoline -3-carboxylate (6c, TAK-603), were found to have activities comparable with or superior to the justicidins. The 4-(3-isopropoxy-4-methoxy)-phenyl derivative (6d), in particular, displayed a marked increase in potency. TAK-603 and compound 6d were very effective in preventing osteoclast formation and bone resorption by mature osteoclasts. Further, TAK-603 was shown to be effective in preventing bone loss in ovariectomized mice.

Animals↗

PubMed1999

Involvement of N-acetylcysteine-sensitive pathways in ricin-induced apoptotic cell death in U937 cells.

We have found that the antioxidant N-acetylcysteine (NAC) strongly inhibited ricin-induced apoptotic cell death in U937 cells (human myeloid leukemia), as judged by cytotoxicity, nuclear morphological change, and DNA fragmentation. Consistent with these observations, a significant depletion of cellular glutathione was observed in ricin-treated cells, and NAC prevented the decrease in cellular glutathione. On the other hand, among the caspase inhibitors tested, Z-Asp-CH2-DCB, which inhibited ricin cytotoxicity, also suppressed ricin-mediated glutathione depletion, while NAC did not affect the generation of caspase-3 like activity in ricin-treated cells. These results suggest that glutathione loss takes place downstream from caspase activation during the ricin-induced apoptotic process. Treatment with a specific inhibitor of glutathione biosynthesis, buthionine sulfoximine (BSO) failed to induce apoptosis, and had no effect on the overall extent of ricin-induced apoptosis, even though the glutathione level was decreased to less than 5% of the control level. However, NAC still protected against ricin-induced apoptosis in the BSO-treated cells. We conclude that glutathione loss is one of several apoptotic changes caused by ricin, but is not a sufficient factor for the progress of apoptosis. NAC may prevent ricin-induced apoptosis through maintaining an intracellular reducing condition by acting as a thiol supplier.

Acetylcysteine↗

PubMed1999

An evaluation of left ventricular function after surgery for pure mitral regurgitation using dobutamine-stress echocardiography--should the mitral complex be preserved?

To evaluate the importance of preserving the mitral complex, clinical outcomes and postoperative left ventricular (LV) functions of 175 patients with pure mitral regurgitation (MR) were analyzed. They were divided into three groups; patients who had conventional mitral valve replacement (cMVR; n = 47), posterior mitral leaflet preserved MVR (pMVR; n = 66) or mitral valvuloplasty (MVP; n = 62). There was no operative death or hospital death in this study. The actuarial survival rate was 85.2% in cMVR, 78.5% in pMVR, and 84.7% in MVP at 10 years after operation. The actuarial freedom from reoperation 10 years postoperatively was 100% in cMVR, 97.9% in pMVR, 85.8% in MVP. The actuarial freedom from thromboembolism (TE) at 10 years was 92.2% in cMVR, 87.1% in pMVR, 93.5% in MVP. Freedom from all types of events including non-cardiac death was 78.3% in cMVR, 64.8% in pMVR, 65.3% in MVP at 10 years, respectively. Pre- and postoperative LV function was evaluated using echocardiography. Patients with MVP had better LV performance than those with MVR. However, there was no significant difference between the cMVR and pMVR groups. For further estimation of postoperative LV function, dobutamine-stress echocardiography (DSE) was performed. The results of DSE revealed that the LV contractility in MVP was obviously better than those in MVR groups especially in systole. The change in ejection fraction (EF) from baseline to peak dobutamine stress in the pMVR group was significantly greater than in cMVR. This study supports the concept that the preservation of continuity between the mitral annulus and papillary muscle plays an important role in clinical outcome and postoperative LV function. In conclusion, MVP should be a first choice as an operative method for pure MR when technically feasible. When it is impossible to perform MVP, pMVR, not cMVR, should be the next choice. This study suggests that preservation of papillary muscle-mitral annular continuity during mitral valve surgery for pure MR is beneficial to LV systolic function.

Adult↗

PubMed1999

CRKL binding to BCR-ABL and BCR-ABL transformation.

The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Alveolar ridge augmentation by distraction osteogenesis using titanium implants: an experimental study.

The left mandibular premolars were extracted from five adult dogs. After twelve weeks, a box-shaped osteotomy of the alveolar bone was carried out and two 10 mm implants were placed 5 mm into the transport alveolar segment, leaving 5 mm exposed. The alveolar bone was vertically augmented 5 mm by screwing the implants. After distraction, the implants were left to integrate into the bone. Histological and radiographical evaluations showed the lifting of the transport segment and the development of new bone in the distraction area. Although integration of implants within both the transport segment and the regenerated bone was observed, two of the ten implants failed and partial bone resorption of the transport segment was noted.

Alveolar Process↗

PubMed1999

[Unrelated bone marrow transplantation in two severe aplastic anemia patients preconditioned with a regimen of cyclophosphamide, antithymocyte globulin, and total body irradiation].

We report our experiences with HLA-matched unrelated bonemarrow transplantation combining a preconditioning regimen of cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation for two patients with severe aplastic anemia (SAA) who had already undergone repeated blood transfusions. Short-term methotrexate and cyclosporine were administered for graft-versus-host disease (GVHD) prophylaxis. Both patients achieved rapid engraftment within 3 weeks, furthermore, neither acute nor chronic GVHD developed. Our conditioning regimen appeared to be well-suited for unrelated bone marrow transplantation in heavily transfused SAA patients. However, both patients experienced bouts of fever about 20-30 and 40-50 days after transplantation, and it was difficult to differentiate whether they were affected by acute GVHD, cytomegalovirus (CMV) infections, or serum sickness. Because weakly positive CMV antigenemia was detected, both patients were given ganciclovir. Although their fever did not respond initially, it gradually subsided following the combined administration of prednisolone. These outcomes suggest it is essential that attention be devoted to the potential for serum sickness and the high risk of herpes virus infections, particularly by CMV, following the use of intensive preconditioning regimens that include ATG.

Adolescent↗

PubMed1999

Effects of high temperature on the emergence and survival of adult Culex pipiens molestus and Culex quinquefasciatus in Japan.

The emergence rate and adult survival (longevity) of Japanese strains of Culex pipiens molestus and Culex quinquefasciatus were compared at temperatures of 21, 25, and 30 degrees C. The pupation and emergence rates in both strains were higher at 21 and 25 degrees C than at 30 degrees C. The adult emergence rate, especially in females, was lower in Cx. p. molestus than in Cx. quinquefasciatus. Longevity of females and males was lower in Cx. p. molestus at 25 degrees C and above. The survival of Cx. p. molestus was adversely affected by temperatures of 28 degrees C and higher. High temperature may restrict the distribution of this species. Therefore, if Cx. p. molestus infests the Okinawa region, the likelihood that it will become established is minimal.

Animals↗

PubMed1999

Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778.

TAK-778 [(2R,4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4, 5-tetrahydro-4-methyl-7, 8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; mw 505.53], a novel osteoblast differentiation promoting compound, was characterized in vitro and in vivo models. TAK-778 at doses of 10(-6) M and higher promoted potently bone-like nodule formation in the presence of dexamethasone in rat bone marrow stromal cell culture. This was accompanied by increases in cellular alkaline phosphatase activity, soluble collagen release, and osteocalcin secretion. Under the culture conditions, TAK-778 also stimulated the secretion of transforming growth factor-beta and insulin-like growth factor-I, indicating that TAK-778 may exert regulatory effects on osteoblast differentiation via autocrine/paracrine mechanisms. Furthermore, the in vivo osteogenic potential of TAK-778 was studied in bony defect and osteotomy animal models, using sustained release microcapsules consisted of a biodegradable polymer, poly (dl-lactic/glycolic) acid (PLGA). Single local injection of TAK-778/PLGA-microcapsules (PLGA-MC) (0.2-5 mg/site) to rat skull defects resulted in a dose-dependent increase in new bone area within the defects after 4 weeks. When the pellet containing TAK-778/PLGA-MC (4 mg/pellet) was packed into place to fill the tibial segmental defect in rabbit, this pellet induced osseous union within 2 months, whereas the placebo pellet did not. In addition, single local application of TAK-778/PLGA-MC (10 mg/site) to rabbit tibial osteotomy site enhanced callus formation accompanied by an increase in breaking force after 30 days. These results reveal for the first time that a nonendogenous chemical compound promotes potently osteogenesis in vitro and enhances new bone formation during skeletal regeneration and bone repair in vivo and should be useful for the stimulation of fracture healing.

Animals↗

PubMed1999

[Clinical studies of faropenem in the field of obstetrics and gynecology].

The clinical effect of faropenem was evaluated in 165 ambulatory patients with various infections in the field of obstetrics and gynecology at 10 institutions in Yamagata Prefecture. The results obtained are summarized below. 1. The rate of efficacy, as determined from the clinical effect following 3- to 7-day repeated administration at a dose of 600 mg/day, was 97.9% (46/47) for intrauterine infections, 92.0% (23/25) for adnexitis, 93.8% (15/16) for external genital infections, 88.9% (8/9) for mastitis, 94.0% (63/67) for cystitis, and 100% (1/1) for cervicitis. The overall efficacy rate was estimated to be 94.5% (156/165). 2. The rate of clinical efficacy, as classified by isolate, was high, 95.1% for Gram-positive bacteria, 100% for Gram-negative bacteria, and 100% for anaerobes. As for bacteriological response classified by isolate, the eradication rate was high, 91.4% (74/81) for Gram-positive bacteria, 98.4% (62/63) for Gram-negative bacteria, 89.5% (17/19) for anaerobes, and 93.9% (153/163) in all. 3. No adverse reactions or laboratory abnormalities were observed in any patient. The results presented suggest that faropenem is a highly safe and effective antibiotic for the treatment of obstetric or gynecological infections of various kinds in an ambulatory setting.

Adult↗

PubMed1999

[Influence of milrinone on internal mammary artery grafts].

To evaluate the effects of milrinone on blood flow in the left internal mammary artery (LIMA) grafts and hemodynamic variables, we conducted a prospective randomized study. Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive milrinone treatment (Milrinone; n = 12) or no milrinone treatment (Control; n = 12). Milrinone was given after induction of anesthesia at a speed of 0.5 microgram/kg/min for 24 hours. After start of cardiopulmonary bypass (CPB), CPB perfusion flow was adjusted to 2.4 l/m2 and LIMA blood flow was measured. Blood samples for determination of plasma cAMP levels were collected and hemodynamic measurements were also assessed perioperatively. LIMA blood flow was significantly greater in Milrinone than that in Control (40 +/- 4 vs 29 +/- 4 ml/min/m2, p < 0.05). Plasma levels of cAMP were significantly (p < 0.05) greater in Milrinone than those in Control at tha start of CPB (18 +/- 1 vs 13 +/- 1 pmol/ml) and at the end of CPB (24 +/- 2 vs 17 +/- 2 pmol/ml). Systemic vascular resistance was significantly (p < 0.05) lower and cardiac index was significantly (p < 0.05) greater in Milrinone than those in Control postoperatively. With its positive inotropic and systemic vasodilator activities, milrinone may have direct vasodilator effect on LIMA.

Aged↗

PubMed1998

Interactions of p62(dok) with p210(bcr-abl) and Bcr-Abl-associated proteins.

A 62-kDa Ras GTPase-activating protein (RasGAP)-associated protein is tyrosine-phosphorylated under a variety of circumstances including growth factor stimulation and in cells transformed by activated tyrosine kinases. A cDNA for p62(dok), reported to be the RasGAP-associated 62-kDa protein, was recently cloned from Abl-transformed cells. In this study, the interactions of p62(dok) with Bcr-Abl and associated proteins were examined. In 32D myeloid cells and Rat-1 fibroblasts transformed by p210(bcr-abl), p62(dok) is tyrosine-phosphorylated and co-immunoprecipitates with Bcr-Abl, RasGAP, and CrkL, a Src homology 2 (SH2) and SH3 domain-containing adaptor protein. Tyrosine-phosphorylated p62(dok) from cells expressing p210(bcr-abl) bound directly to the SH2 domains of Abl and CrkL in a gel overlay assay. Previous work has shown that an SH2 domain deletion mutant of Bcr-Abl is defective in transforming fibroblasts but remains capable of inducing myeloid growth factor independence. In both fibroblasts and myeloid cells expressing this mutant, p62(dok) is underphosphorylated as compared with cells expressing full-length p210(bcr-abl) but remains capable of associating with Bcr-Abl. However, in a gel overlay assay, p62(dok) from cells expressing the SH2 domain deletion was incapable of associating directly with SH2 domains of Abl and CrkL. Interestingly, no direct binding between Bcr-Abl and p62(dok) could be demonstrated in a yeast two-hybrid assay. These data suggest that indirect interactions mediate the interaction between Bcr-Abl and p62(dok) and that the SH2 domain of Bcr-Abl is required for hyperphosphorylation of p62(dok). Further, hyperphosphorylation of p62(dok) correlates with the ability of Bcr-Abl to transform fibroblasts but not with the induction of growth factor independence in myeloid cells.

Animals↗

PubMed1998

NOLP: identification of a novel human nucleolar protein and determination of sequence requirements for its nucleolar localization.

This study reports cDNA isolation and partial characterization of a novel human nucleolar protein isolated by "nuclear transportation trap" described previously. The cDNA encodes a putative polypeptide of 524 amino acids with a short Escherichia coli DNA helicase homologous region, an acid-rich domain, three potential base-rich nuclear localization signals (NLSs), a serine-rich domain, and a deduced coiled-coil domain. The protein has no known prominent similarities with any other protein in the protein databases. Tissue distribution analysis demonstrated a predominant expression in brain and testis. To determine the sequence requirements for nucleolar targeting, a set of deletion constructs with a fluorescent tag were transiently expressed in COS-7 cells. We revealed that a region of 30 amino acids (position 342-371), which overlaps the first and second NLS, is sufficient for nucleolar localization. Furthermore, the adjacent region of 30 amino acids (position 372-401), which contains the third NLS, is sufficient for nuclear localization. These results suggest that this novel nucleolar protein has at least two distinct domains for directing to different subnuclear destinations.

Amino Acid Sequence↗

PubMed1998

Survival by Mac-1-mediated adherence and anoikis in phorbol ester-treated HL-60 cells.

During the exposure of human myelocytic leukemia HL-60 cells to phorbol diester, nonadherent cells die by apoptosis, but adherent cells survive and growth-arrest at G1 phase of the cell cycle. Here we have shown that the adherent cells rapidly died by apoptosis after forced detachment (anoikis), indicating that phorbol diester induced apoptosis by default. Dimethylsphingosine induced apoptosis in the adherent cells, and sphingosine-1-phosphate rescued the detached cells from apoptosis. Sphingosine kinase activity in adherent cells was higher than that in nonadherent cells and was decreased by forced detachment. It is likely that the phorbol diester-induced apoptosis and the adhesion-mediated survival are modulated by sphingosine and sphingosine-1-phosphate, respectively. The adherent cells were reverted and reproliferated when allowed to spontaneously detach from plastic surfaces by removal of phorbol diester. This result suggests that after removal of phorbol diester, the commitment signal of apoptosis by default is lost faster than the survival signal by adherence.

Apoptosis↗

PubMed1998

Identification of D-aspartate in rat pheochromocytoma PC12 cells.

D-Aspartate is now known to be present in mammalian neuronal and endocrine cells in vivo, and may play some role(s) in neurocrine and endocrine functions. However, origin of D-aspartate is unknown. Here, we report that free D-aspartate (108 pmoles/3 x 10(7) cells) is present in the cultured PC12 cells, a rat pheochromocytoma cell line, as determined with immunohistochemical techniques as well as high performance liquid chromatography (HPLC) on a Pirkle-type chiral column. The amount of D-aspartate does not change with the passage. The culture medium does not contain D-aspartate. These results strongly suggest the presence of a de novo biosynthetic pathway for D-aspartate in the endocrine cells.

Animals↗

PubMed1998

Pancreatic carcinoma: correlation between E-cadherin and alpha-catenin expression status and liver metastasis.

BACKGROUND: Dysfunction of the E-cadherin/catenin-mediated cell-cell adhesion system has been associated with invasiveness and poor differentiation of human carcinomas. However, its importance in the genesis of liver metastasis has not been examined sufficiently. METHODS: A series of 26 primary pancreatic carcinomas and the concomitant liver metastases from 15 of them, obtained at autopsy, were analyzed for E-cadherin and alpha-catenin protein expression by immunohistochemistry. RESULTS: Both E-cadherin and alpha-catenin expression were preserved in 15 (58%) and reduced in 11 (32%) of the 26 primary pancreatic carcinomas. In the former 15 primaries, carcinoma cells were attached to each other tightly, whereas the latter 11 primaries showed isolated or loosely connected attachments. The metastatic ratio was higher in tumors exhibiting tight adhesion than in those with loose adhesion: 73% and 36%, respectively (P = 0.059). E-cadherin and alpha-catenin expression patterns in liver metastases basically followed those in the corresponding primaries (P < 0.01). CONCLUSIONS: Reduced E-cadherin and alpha-catenin expression in primary pancreatic carcinoma has no significant predictive value regarding the presence of liver metastasis. Rather, there is a greater tendency for liver metastasis in cases in which the integrity of the E-cadherin/catenin-mediated cell-cell adhesion system is intact.

Adult↗

PubMed1998

Involvement of Mac-1-mediated adherence and sphingosine 1-phosphate in survival of phorbol ester-treated U937 cells.

Phorbol esters exert a dual function in human leukemia cells, induction of differentiation and activation of integrin-mediated functions. Here we have shown that the plastic adherence of phorbol ester-treated U937 cells is mediated by expression of integrin Mac-1 (CD11b/CD18) on the cell surface and that these adherent cells exhibit anoikis (apoptosis when adherent cells are detached or adherence is inhibited). We used U937-derived clones overexpressing either antisense RNAs antisense to CD11b and CD18 mRNAs or mRNA from a truncated mutant CD11b gene. We have also shown that apoptosis in non-adherent cells or anoikis was mediated by sphingosine and that survival of adherent cells was achieved by a shift of the dynamic balance between sphingosine and sphingosine 1-phosphate toward the latter by adherence-activated sphingosine 1-kinase.

Apoptosis↗

PubMed1998

Favorable strategy for the ostial lesion of the left anterior descending coronary artery: influence on narrowing of circumflex coronary artery.

We examined the effectiveness of Palmaz-Schatz (P-S) stent and directional coronary atherectomy (DCA) in ostial lesions of left anterior descending arteries (LAD). The P-S stent was implanted in 11 cases at LAD ostial lesions, and DCA was performed in 13 cases. Percent stenosis and vessel diameter at the target site and the ostium of the circumflex coronary artery (LCX) were measured before and after the procedure. The initial success rate was 100% in both groups. No major complication occurred. LAD ostial lesions were improved from 81.3+/-3.4% to -8.1+/-5.7% by P-S stent and from 82.8+/-2.6% to -2.7+/-3.9% by DCA. LCX ostial vessel diameter was not changed by DCA (from 3.0+/-0.2 mm to 3.1+/-0.3 mm); however, it was significantly decreased by P-S stent (from 2.9+/-0.2 mm to 2.6+/-0.2 mm, P < 0.01). When the angle of LAD and LCX was < or = 80 degrees from the view of RAO 30 degrees and Caudal 30 degrees, the LCX ostium was significantly narrowed by stenting at LAD ostium (P < 0.01). These findings indicate that both the P-S stent and DCA are effective and safe therapies for LAD ostial lesions in cases with LAD-LCX angle > 80 degrees. In cases with LAD-LCX angle < or = 80 degrees, however, DCA is a favored therapy rather than P-S stenting to avoid narrowing of the LCX ostium.

Atherectomy, Coronary↗