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Biomedical subjects

Y Tamura

Publications and source records attributed to Y Tamura.

At least 217 records · Page 12Linked to original sources
PubMed1997

Cell-transforming activity and genotoxicity of phenolphthalein in cultured Syrian hamster embryo cells.

Phenolphthalein is a cathartic agent widely used in non-prescription laxatives. For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phenolphthalein, the ability of this chemical to induce cell transformation and genetic effects was examined using the Syrian hamster embryo (SHE) cell model. Cell growth was reduced by treatment with phenolphthalein at 10-40 microM in a dose-related manner. Treatment with phenolphthalein for 48 hr induced a dose-dependent increase in morphological transformation of SHE cells. Over the dose range that resulted in cell transformation ( 10-40 microM), treatment of SHE cells with phenolphthalein induced gene mutations at the hprt locus but not at the Na+/K+ ATPase locus. A statistically significant level of chromosomal aberrations was elicited in SHE cells treated with phenolphthalein at the highest dose (40 microM). Meanwhile, neither numerical chromosomal changes nor DNA adduct formation, analyzed by the nuclease P1 enhancement version of 32P-post-labeling, were induced by treatment with phenolphthalein at any concentrations examined. We thus report cell-transforming activity and mutagenicity of phenolphthalein assessed with the same mammalian cells in culture. Our results provide evidence that phenolphthalein has cell-transforming and genotoxic activity in cultured mammalian cells. The mutagenic and clastogenic activities of phenolphthalein could be a causal mechanism for carcinogenicity in rodents.

Animals↗
PubMed1997

Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations.

Immunotherapy of mice with preexisting cancers with heat shock protein preparations derived from autologous cancer resulted in retarded progression of the primary cancer, a reduced metastatic load, and prolongation of life-span. Treatment with heat shock protein preparations derived from cancers other than the autologous cancer did not provide significant protection. Spontaneous cancers (lung cancer and melanoma), chemically induced cancers (fibrosarcoma and colon carcinoma), and an ultraviolet radiation-induced spindle cell carcinoma were tested, and the results support the efficacy of autologous cancer-derived heat shock protein-peptide complexes in immunotherapy of cancers without the need to identify specific tumor antigenic epitopes.

Animals↗
PubMed1997

Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to rheumatoid arthritis treatment.

An ongoing search for new antifolate drugs useful against rheumatoid arthritis (RA) led us to prepare new methotrexate (MTX) derivatives containing enantiomerically pure L-erythro- or L-threo-gamma-fluoroglutamic acid. The derivatives in which the phenyl ring was replaced by a 3'-substituted phenyl or methylthiophene ring showed potent immunosuppressive activities, including in vitro inhibition of mitogen responses to both T and B cells and in vivo inhibition of antibody production in mice. These compounds also exhibited inhibitory activity in adjuvant arthritis in rats. Their toxicity was lower than that of MTX, which was probably due to the strong electronegativity of fluorine, which increases the acidity of the gamma-carboxyl group and thereby decreases polyglutamylation in normal cells. These results revealed the potential of the fluorinated MTX derivatives as candidate drugs for the treatment of RA.

Animals↗
PubMed1997

Adiabatic compressibility of flagellin and flagellar filament of Salmonella typhimurium.

The partial specific volume and adiabatic compressibility of flagellin, its F40 fragment deprived of the disordered terminal regions, from Ala-1 to Arg-65 and from Ser-451 to Arg-494, and the flagellar filament of Salmonella typhimurium were determined from the density and the sound velocity measurements at 15 degrees C. The partial specific volumes were 0.728 cm3/g, 0.745 cm3/g, and 0.734 cm3/g, and the partial specific adiabatic compressibilities were 4.0 x 10(-12) cm2/dyn, 6.7 x 10(-12) cm2/dyn, and 4.7 x 10(-12) cm2/dyn, for flagellin, F40, and the filament, respectively. The smaller values of flagellin than those of F40 are reasonably explained by the presence of disordered terminal regions, which are supposed to be highly hydrated by water molecules. The volume increase upon polymerization of flagellin into the filament is also confirmed by depolymerization under a high pressure. The smaller volume and compressibility of the filament compared with those of F40 suggest an extensive hydration of the filament on its complex surface structure, which surpasses the effect on the volume and compressibility by a possible increase in the cavity volume at intersubunit interfaces upon polymerization.

Circular Dichroism↗
PubMed1997

Coronary artery perforation with subepicardial hematoma.

Coronary artery perforation is a relatively rare complication in coronary angioplasty. We report the case of a 71-year-old male, who was salvaged by emergency surgery, for cardiogenic shock due to subepicardial hematoma associated with balloon angioplasty. Such a case has not yet previously been reported.

Aged↗
PubMed1997

Detection of Mycoplasma in avian live virus vaccines by polymerase chain reaction.

The polymerase chain reaction (PCR) was evaluated to detect mycoplasma contamination of avian live virus vaccines. The specificity of the primers showed that 34 strains belonging to nine species of avian mycoplasma DNA could be detected. The sensitivity of PCR to detect mycoplasma DNA was 10(0.2) colony forming units (cfu) of Mycoplasma synoviae and 10(0.7) cfu of Mycoplasma gallisepticum. When M. synoviae and M. gallisepticum were spiked into several avian live virus vaccines, PCR gave a positive reaction except for the avian pox and the avian encephalomyelitis vaccines which were prepared from organ homogenates. Short-term incubation of avian encephalomyelitis vaccines improved the sensitivity of PCR to detect both M. synoviae and M. gallisepticum. Therefore, PCR, combined with the short-term incubation, were shown to be most effective in detecting mycoplasma contamination in all of avian live virus vaccines.

Animals↗
PubMed1997

Benign cervical teratoma in an adult: report of a case.

Cervical teratomas are rarely encountered in adults. We report herein the case of a 21-year-old woman who was admitted to our hospital for surgical treatment of a neck tumor, 7.5 x 4.5 x 2.7 cm in size, located in the left lower pole of the thyroid. Ultrasonography (US) and computed tomography (CT) revealed a multicystic tumor. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma-related antigen (SCC) in the cystic fluid were extremely elevated in contrast to the normal levels found in the serum. The tumor was completely excised and histological examination revealed it to be composed of elements derived from the three germ layers, confirming a diagnosis of benign cystic teratoma.

Adult↗
PubMed1997

Alpha-Interferon for the treatment of idiopathic sudden sensorineural hearing loss.

We have employed alpha-interferon (IFN-alpha), an anti-viral agent, in the treatment of severe idiopathic sudden sensorineural hearing loss (ISSHL). Forty-two patients were studied and had an average hearing ability of > or = 70 dB before treatment. We also examined 2'-5' oligoadenylate synthetase (2,5A-S) activity, one of the parameters indicating anti-viral activity of IFN, to investigate the relationship between the suppression of viral proliferation and prognosis and explain the pathogenesis of ISSHL. Complete recovery was found in 27 patients (64.3%) after IFN therapy. Increased 2,5A-S activity was observed on the 3rd day of IFN therapy in 24 of the 27 patients who completely recovered. No severe adverse events were reported after IFN therapy. Findings suggest that IFN therapy may be effective and safe in the treatment of ISSHL and calls for further investigation.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation.

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.

Aminobiphenyl Compounds↗
PubMed1997

Mechanisms of enhanced production of PGI2 in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid.

The present investigation was performed to clarify the effect of EPA on PGI2 production in vitro using cultured rat vascular smooth muscle cells (VSMC). To simulate in vivo conditions, a triacylglycerol (TG) emulsified form of EPA was used. An increase in EPA content was achieved without alteration of arachidonic acid concentration. These experiments clearly demonstrated that co-incubation of EPA-TG increased PGI2 production by cultured VSMC in a dose dependent fashion. Among polyunsaturated fatty acid TG examined (docosahexaenoic acid, linoleic acid, oleic acid and EPA), only EPA-TG was effective. Cyclooxygenase (COX) was activated, but neither phospholipase A2 nor PGI2 synthase activity was changed. EPA treatment did not alter the amount of COX-1 and COX-2 protein in VSMC. Addition of antioxidants, such as butylated hydroxytoluene or vitamin E, decreased MDA levels in the medium and cells and reversed the enhanced PGI2 production in EPA rich-VSMC. Therefore, the high polyunsaturation of EPA could generate low levels of lipid peroxides and thereby lead to activation of COX and an increased PGI2 production. Although EPA increased PGI2 production, only a negligible amount of PGI3 was produced by rat aortic tissues. Enhanced production of PGI2 might contribute to the anti-atherogenic effect of EPA.

Animals↗
PubMed1997

Effects of ischemia-reperfusion on individual cytochrome P450 isoforms in the rat kidney.

Ischemia-reperfusion of organs such as the kidney produces reactive oxygen and free radical species in tissues and leads to injury of intracellular molecules critical to cell homeostasis. Ischemia-reperfusion affects the NADPH-dependent monooxygenase system including P450 system, which is also a source of reactive oxygen species. In this study, the effects of ischemia-reperfusion on monooxygenase activity and levels of individual P450 isoforms including CYP2C23, 4A2, and 4A8 in the rat kidney were investigated. Ischemia of the rat kidney for 30 min had little effect on lauric acid hydroxylation activity and levels of P450 isoforms but ischemia for 60 min significantly decreased lauric acid omega- and (omega-1)-hydroxylation activities and also decreased the levels of CYP2C23, 4A2, and 4A8. Reperfusion for 60 min after 30-min ischemia decreased the levels of CYP2C23 and 4A2 in the rat kidney although 30-min ischemia did not. Reperfusion for 240 min after 30-min or 60-min ischemia recovered the decreased levels of lauric acid hydroxylation activity and the levels of CYP2C23 and 4A2. Changes in the levels of monooxygenase activity and the levels of P450 isoforms in kidneys by ischemia-reperfusion are faster than those in the liver; it takes several hours for ischemia-reperfusion to affect the levels of monooxygenase activity and the levels of P450 in the rat liver. Our findings suggest that damage of P450 isoforms in the kidney by ischemia-reperfusion occurs by a mechanism different from that in the liver and that active oxygen or free radical species directly attack proteins.

Animals↗
PubMed1997

Cochlear implant after reconstruction of the external bony canal wall and tympanic cavity in radically mastoidectomized patients with cholesteatoma.

One of the postoperative complications of cochlear implants in patients, who previously received radical mastoidectomy, is an exposure of electrode by breakdown of thin epithelium in the open mastoid cavity. To avoid such complications, in the first stage, radical mastoidectomy with the reconstruction of the posterior bony canal wall and mastoid obliteration with bone chips and plates and the creation of the new tympanic cavity, were performed. One or 3 years later, implantation of a 22-channel cochlear implant, as the second stage procedure, was successfully performed in three patients with profound sensorineural hearing loss, due to cholesteatoma in the side of the ear in which cochlear implantation was indicated. The advantages of this technique are as follows: (1) Electrode is protected from the cavity problems, such as chronic infection or erosion of the epithelium in the open mastoid cavity; and (2) reconstruction of the new tympanic cavity and tympanic membrane is beneficial for avoidance of electrode exposure in the mastoid and tympanic cavity.

Aged↗
PubMed1997

Evaluation of the thoracodorsal artery as an alternative conduit for coronary bypass.

Complete coronary revascularization using arterial grafts has been performed recently because of their improved patency rates. However, as the need to repeat coronary bypass surgery has become more frequent, it can be difficult to find adequate conduits for further bypass surgery. Therefore, we investigated the use of the left thoracodorsal artery (LTDA) as an alternative bypass conduit. The length from its origin, internal diameter, and number and location of branches were angiographically measured in 16 patients, and in situ blood flow volume and external diameter were intraoperatively measured in 8. Moreover, each specimen of the LTDA, the internal thoracic artery (ITA), and the inferior epigastric artery (IEA) were evaluated histologically. We found that the thoracodorsal artery has the same diameter as the ITA angiographically, and the same histological findings as the IEA. In conclusion, the thoracodorsal artery may be useful as a coronary arterial graft.

Coronary Angiography↗
PubMed1997

Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor.

The majority (97%) of functional epitopes for stimulating thyrotropin receptor (TSHR) antibodies (stimulating TSHRAbs) in a large cohort (n = 59) of Japanese Graves' patients exists on the N-terminal region of the extracellular domain of TSHR, between residues 25 and 165 numbering from the methionine start site. This was determined by measuring the loss of stimulating activity in the Cos-7 cells transfected with TSHR/lutropin-choriogonadotropin receptor (LH-CGR) chimeras wherein TSHR residues 89-165 (Mc2) or 8-165 (Mc1 + 2) are replaced by comparable LH-CGR residues. There is no comparable loss when stimulating TSHRAb activity is measured in an Mc4 chimera, wherein TSHR residues 261 to 370 are replaced. In contrast, immunoglobulin (IgG) preparations from 35 patients with Hashimoto's disease or idiopathic myxedema, who have blocking TSHRAbs causing hypothyroidism, loose blocking TSHRAb activity in the Mc4 chimera, but not the Mc2 or Mc1 + 2 chimeras. Thus, in a large population of Japanese patients with autoimmune thyroid disease caused by TSHR autoantibodies, the major functional epitope for stimulating TSHRAbs is on the N-terminal portion of the TSHR extracellular domain, whereas that for blocking TSHRAbs is on the C-terminal portion of the extracellular domain. To further evaluate the nature of the critical functional epitope between residues 90 to 165, we divided this region approximately in half, creating chimeras Mc2a and Mc2b with, respectively, residues 90-124 or 125-165 replaced by comparable LH-CGR residues. IgGs from all patients tested lost significant stimulating activity using the Mc2a and Mc2b chimeras; however, when present, residual stimulating TSHRAb activity was evident on one or the other half of the region or on both halves, indicating that both segments are required for expression of the stimulating TSHRAb epitope within residues 90-165. Finally, we have identified a complex epitope involving both the N- and C-terminal portion of the extracellular domain that appears to account for the small fraction of stimulating TSHRAbs whose activity is not solely dependent on residues 25 to 165. Thus, using chimeras Mc1 + 2 + 4, with TSHR residues 8-165 and 261-370 substituted, or chimera Mc1 + 2 + 3 + 4, with residues 8-370 substituted, as well as Mc2, Mc1 + 2, and Mc4, we show that the Graves' IgGs which maintain stimulating TSHRAb activity when residues 8-165 of the TSHR are replaced by LH-CGR residues have an epitope involving residues 90-165 and the immunogenic 15mer peptide (YYVFFEEQEDEIIGF), residues, 352-366. Because that peptide can decrease the stimulating TSHRAb activity of these Graves IgGs in assays with the Mc2 chimera alone, we speculate that this complex epitope may be important in an epitope spreading process involved in the formation of stimulating TSHRAbs.

Amino Acid Sequence↗
PubMed1997

Increasing vasoconstrictor response to ergonovine with oxidative injury in canine coronary artery.

BACKGROUND: The effects of oxygen free radicals on coronary vasoreactivity remain unknown. OBJECTIVE: To examine whether oxygen free radicals increase coronary arterial tone and sensitivity to vasoconstrictor stimulation in closed-chest dogs. METHODS: Oxygen radicals were generated by the reaction of xanthine plus xanthine oxidase (XXO) and effects of these substances on the left coronary artery (the percentage diameter change) and on the constrictor effect of ergonovine were examined in vivo in 19 anesthetized, closed-chest dogs by selective coronary angiography. The effects of XXO solution and ergonovine were assessed in a cumulative fashion using 100, 200, and 300 ml XXO and 50, 100, 150, and 200 micrograms ergonovine, in 5 (group I) and 6 dogs (group II), respectively. The effects of XXO on the constrictor responses elicited by 50 micrograms ergonovine were examined in eight dogs (group III). Changes in the vascular endothelium were examined by postmortem electron microscopic examination. RESULTS: Oxidative injury alone produced slight constriction of the coronary artery, but the change was not significant. However, ergonovine-induced vasoconstriction was enhanced after administration of 100 and 200 ml (cumulative amount) XXO solution (P < 0.05, group II versus group III). The enhancement was no longer observed after administration of 300 ml (cumulative amount) XXO solution. Scanning and transmission electron microscopies revealed the formation of blebs and ulceration in the coronary endothelium after administration of XXO solution. CONCLUSION: These results suggest that oxygen radicals can enhance the ergonovine-induced coronary vasoconstriction in a concentration-dependent manner. There seems to be a critical level of oxygen radicals for the production of the effect.

Animals↗