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T Kanai

Publications and source records attributed to T Kanai.

At least 145 records · Page 8Linked to original sources
PubMed1995

Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470, and mitomycin C on the growth and liver metastasis of human colon cancer.

Angiogenesis inhibitors have attracted considerable interest. The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using a xenotransplanted human colon cancer, TK-4. Suturing of small pieces of TK-4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP-470 and a group receiving MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP-470 group and neither of these animals had numerous metastases.

Animals↗
PubMed1995

The upstream region of the isocitrate lyase gene (UPR-ICL) of Candida tropicalis induces gene expression in both Saccharomyces cerevisiae and Escherichia coli by acetate via two distinct promoters.

The upstream region of the isocitrate lyase gene (UPR-ICL, 1530bp) of an n-alkane-utilizable yeast, Candida tropicalis, induced gene expression in another yeast, Saccharomyces cerevisiae, when the yeasts were grown on acetate. Surprisingly, UPR-ICL displayed the same regulatory function in the bacterium Escherichia coli when grown on acetate. We determined the interesting nucleotide sequence of UPR-ICL. The deletion analysis of UPR-ICL in both cells revealed the presence of two distinct promoters: one was localized at -394 to -379 and regulated gene expression in S. cerevisiae; the other was located near the initiation codon and regulated gene expression in E. coli. The two promoter sequences were similar, but not identical to regulatory elements that have been previously reported in S. cerevisiae and E. coli, respectively. Accordingly, the possibility of novel regulatory mechanisms could not be excluded. This is an interesting example of the presence of distinct cis-acting regulatory elements responsible for the induction of gene expression in one gene by acetate in both S. cerevisiae and E. coli. Preservation of such promoters through evolution is also discussed.

Acetates↗
PubMed1995

Effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on the dopaminergic and cholinergic receptors as evaluated by positron emission tomography in the Rhesus monkey.

The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) on the central cholinergic and dopaminergic systems in the Rhesus monkey brain were investigated by positron emission tomography (PET) with the muscarinic cholinergic receptor ligands (N-[11C]methyl-benztropine) and dopaminergic receptor ligands selective for D1, D2, and D3 subtypes ([11C]SCH23390, N-[11C]methyl-spiperone, and (+)[11C]UH232, respectively). None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP used significantly affected the regional cerebral blood flow (rCBF as determined by Raichle's H(2)15O method), and 10 mg/kg of R-THBP had little effect on the regional cerebral metabolic rate of glucose (rCMRglc) in the Rhesus monkey brain, as assessed by the graphical [18F]fluoro-deoxyglucose method. The effect of R-THBP on the muscarinic cholinergic system was dose dependent; while 3 mg/kg of R-THBP did not significantly alter the uptake ratio of N-[11C]methylbenztropine in several brain regions to that in the cerebellum, 10 and 30 mg/kg of R-THBP significantly reduced the uptake ratio in the thalamus, as well as in the frontal and temporal cortices. None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP tested affected [11C]SCH23390 (dopamine D1 receptor) binding. However, the k3 value for N-[11C]methyl-spiperone (dopamine D2 receptor) binding, which represents the association rate X Bmax value, was significantly decreased in the striatum. The uptake ratio of (+)[11C]UH232 (dopamine D3 receptor) in the striatum to that in the cerebellum was also decreased by administration of R-THBP (3 and 30 mg/kg i.v.). These findings suggest that R-THBP acts on dopamine D2 and D3 receptors selectively without markedly affecting dopamine D1 receptor binding. Furthermore, the changes in cholinergic and dopamine D2 and D3 receptors in vivo can not be attributed to a change in rCBF but may depend on the action of R-THBP.

Animals↗
PubMed1995

Interleukin-1 receptor antagonist expression in epithelial cells of human endometrium.

OBJECTIVE: To examine the expression of interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) in the human endometrium in the follicular and luteal phases. METHODS: The concentrations of IL-1alpha and IL-1beta in the culture supernatants of endometrial cells were determined by enzyme-linked immunosorbent assay. Transcription of the IL-1ra gene in the endometrium was investigated by reverse polymerase chain reaction (PCR). Human endometrium was immunohistochemically stained using a monoclonal antibody specific to IL-1ra. RESULTS: The concentrations of IL-1alpha and IL-1beta in the culture supernatants were 11 and 55 pg/ml, respectively, in the follicular phase, and 10 and 40 pg/ml, respectively, in the luteal phase. The concentration of IL-1ra was 465 pg/ml in the follicular phase and 1710 pg/ml in the luteal phase. Densitometric analysis of the reverse PCR products showed that the expression of IL-1ra mRNA was increased in endometrial cells in the luteal phase. Immunohistochemical staining revealed that epithelial cells were the main source of IL-1ra in human endometrium. CONCLUSIONS: Human endometrial cells produce IL-1 (mainly IL-1beta) and IL-1ra. The level of IL-1ra production in human endometrial epithelial cells was greater in the luteal phase than in the follicular phase due to the increased transcription of the IL-1ra gene.

Endometrium↗
PubMed1995

A protocol with FK 506 for inducing unresponsiveness to murine islet allografts.

BACKGROUND: The most favorable protocol for transplantation is inducing unresponsiveness before operation by means of nondangerous modalities. This would permit discontinuance of long-term use of immunosuppressants. In this study we developed a potential protocol for inducing unresponsiveness to islet allografts by preoperative donor spleen cell inoculation (DSI) and a single injection of FK 506. METHODS: BALB/c (H-2d) and C57BL/6 (H-2b) mice were used as islet donors and recipients, respectively. The streptozocin-induced diabetic mice that had been given DSI at a dose of 1 x 10(7) or 1 x 10(4) and a single injection of FK 506 (10 mg/kg intramuscularly) at different schedules (on day 1, 3, 5, or 7 relative to DSI on day 0) were subjected to islet allografting on day 10. RESULTS: All islet recipients returned to normoglycemia within a few days with no toxic effect of FK 506 treatment. DSI at a dose of 1 x 10(7) alone led to shortening of the mean survival time to 10.1 +/- 4.1 days, as compared with 13.5 +/- 6.3 days for the untreated animals. In contrast, marked prolongation of graft survival was induced when FK 506 was given on day 3 (> 84 +/- 27.3 days, p < 0.0001) or on day 5 after DSI (> 50.9 +/- 46.0 days, p < 0.05). Five of seven allografts given FK 506 on day 3 and three of seven allografts given FK 506 on day 5 survived indefinitely. Other time schedules of DSI and FK 506 treatment (on day 1 or 7 after DSI) or FK 506 treatment alone had no significant effect on mean survival time. With the same protocol, third-party islet allografts (C3H) were immediately rejected (10.6 +/- 2.6 days). CONCLUSIONS: Prolongation of islet allograft survival was induced by certain doses of DSI and preoperative FK 506 treatment. This modality prevents an adverse effect of FK 506 on grafted islets and can induce unresponsiveness to islet allografts, offering a protocol for successful clinical islet transplantation.

Animals↗
PubMed1995

The architecture of the atrioventricular conduction axis in dog compared to man: its significance to ablation of the atrioventricular nodal approaches.

UNLABELLED: AV Node in Dog and Man. INTRODUCTION: Advances in treating patients with dual atrioventricular nodal pathways have called for a better understanding of the morphology of the approaches to the atrioventricular node. In this respect, it has recently been suggested that, in dog, anatomically discrete muscle bundles originating from the sinus node represent the substrate of the dual pathways recognized electrophysiologically in patients with atrioventricular nodal reentrant tachycardia. This concept is at odds with most anatomic studies of the human specialized atrioventricular junctional area. In this study, therefore, we studied histologically the junctional area in dog hearts, comparing them with our own findings in human heart and the descriptions of the earliest investigators. METHODS AND RESULTS: Five dog and six human hearts were prepared for histology and sectioned serially in different planes. Reconstructions were then made from each of three dog and two human hearts sectioned in orthogonal planes. Gross differences in the anatomy of the atrioventricular junctional area and in the structure of the conduction system were obvious between dog and human hearts. The penetrating portion of the conduction axis was longer in the dog, being much more extensively embedded in the central fibrous body. The atrioventricular node, in both dog and man, was composed of a zone of transitional cells overlying a compact region. The zone of transitional cells in the dog was more extensive posteriorly than anteriorly. No bundles insulated anatomically by fibrous tissue were found either in the internodal atrial myocardium or in the approaches to the atrioventricular node. Our findings in both dog and man are comparable with the initial descriptions of the atrioventricular junctional area. CONCLUSION: Although the disposition of the conduction system in dog and man is basically similar, there are important differences which relate to the gross anatomy. The anatomic substrate for functional duality of the inputs to the atrioventricular node remains unclear, since our study confirms that the concept of insulated atrionodal tract has no morphologic basis.

Animals↗
PubMed1995

Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene.

To investigate the clonality of uterine leiomyomas, we developed a PCR-based method involving the differential inactivation of the X-chromosome-linked phosphoglycerokinase (PGK) gene. Small DNA samples of 22 leiomyomas from 9 Japanese patients, showing heterozygosity at the BstXI site of the PGK gene, were digested with the methylation-sensitive restriction enzyme HpaII. Only the inactive (methylated) PGK gene allele was selectively amplified by PCR followed by digestion with BstXI and electrophoresis. All leiomyoma samples consisted of a single type of inactive allele, even though alleles were detected that were specific to each nodule. The results indicated that all leiomyoma nodules were unicellular in origin but independently generated in the uterus.

Adult↗
PubMed1995

Differences in heavy-ion-induced DNA double-strand breaks in a mouse DNA repair-deficient mutant cell line (SL3-147) before and after chromatin proteolysis.

DNA double-strand breaks induced by X- or neon beam-irradiation in a DNA double-strand break-repair-deficient mutant cell line (SL3-147) were examined. The increase in the number of DNA double-strand breaks was dose depend after irradiation with X-rays and neon beams and was enhanced by chromatin-proteolysis treatment before irradiation. These results suggest that the induction of DNA double-strand breaks by ionizing radiation, including heavy-ions, is influenced by the chromatin structure.

Animals↗
PubMed1995

[The efficacy of transarterial immuno-embolization therapy in patients with unresectable hepatocellular carcinoma].

We devised a new therapeutic modality for multiple hepatocellular carcinoma (HCC) consisting of transarterial immuno-embolization (TIE) using OK-432 and fibrinogen, and applied the treatment to 22 patients with advanced HCC who had been insensitive to TAE, and 21 patients who had no treatment. Nineteen patients had a high AFP level of more than 200 ng/ml. The serum AFP level decreased in 15 patients after TIE, and in 7 patients the AFP level decreased to less than 30%. Furthermore, a marked reduction in tumor size was observed in 69% after TIE. We report 61% 1-year, and 3-year survival rate for cases who had been insensitive to TAE, and 86% 2-year survival rate for those who selected TIE as the first choice. A high fever of more than 38 degrees C occurred in all cases, and hypotension less than 80 mmHg was observed in 42% patients. No deterioration of liver function and no disturbance of the coagulation-fibrinolysis system due to TIE except in one patient with liver failure after TIE.

Carcinoma, Hepatocellular↗
PubMed1995

A novel promoter, derived from the isocitrate lyase gene of Candida tropicalis, inducible with acetate in Saccharomyces cerevisiae.

When the isocitrate lyase gene, containing 5'-upstream and 3'-flanking regions, of an n-alkane-assimilating yeast Candida tropicalis was introduced into Saccharomyces cerevisiae, the enzyme was functionally overexpressed in the cells grown on acetate. The amount of the recombinant isocitrate lyase expressed in S. cerevisiae was as much as 30% of the total soluble proteins in the cells, being comparable to that with GAL7 functional under the control of galactose. The expression was also observed when the cells were grown on glycerol, lactate, ethanol or oleate. These facts indicate that the isocitrate lyase gene upstream region (UPR-ICL) contains a strong promoter functional in S. cerevisiae. UPR-ICL is active as a promoter on cheap carbon sources such as acetate and nonconventional carbon sources such as oleate, whereas many conventional strong promoters demand relatively expensive sugars or sugar derivatives. Therefore, it is promising to construct an economical recombinant protein production system by using UPR-ICL.

Acetates↗
PubMed1995

[Postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer with a long-term complete response to radiation and split CF therapy (CDDP and 5-FU)--a case report].

We experienced complete remission in a patient with postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer after treatment with radiation (60Co: 30 Gy) and split CF therapy (CDDP: 20 mg/day + 5-FU: 1 g/day for 5 days). Since then, this patient has remained in complete remission for 43 months with intermittent split CF therapy one or two times a year.

Abdomen↗
PubMed1995

[RBE of carbon beam on hematopoietic injury].

The inactivation of hematopoiesis and survival of mice have been used in determining the relative biological effectiveness (RBE) of heavy charged particles of carbon 12 generated by Riken ring-cyclotron. Whole bodies of anesthetized mice were exposed to accelerator-generated carbon 12 of 135 MeV/u or X-rays of 200 kVp in graded doses. At about 5 hours after exposure, exogenous spleen colonies (CFU-S), granulocyte-macrophage progenitor cells (GM-CFC) and megakaryocyte progenitor cells (Meg-CFC) were assayed to determine dose relationships, and then D0 doses were determined. The inactivation of blood cells and lethality of mice (LD50/30) were also monitored for 30 days after irradiation. The RBE values of the 135 MeV/u carbon beam in terms of CFU-S were 1.68 for marrow and 1.41 for spleen, for GM-CFC they were 1.56 for marrow and 3.29 for spleen, for Meg-CFC they were 1.25 for marrow and 3.73 for spleen, while they were about 1.0 for erythrocytes, leukocytes and thrombocytes in mice irradiated with 2 Gy. However, the RBE values of the carbon beam were 1.32 for LD50/30.

Animals↗