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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 595 records · Page 33Linked to original sources
PubMed1994

[MEP (methotrexate, etoposide and cisplatin) and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced uroepithelial cancer--a preliminary report of MEP as second line chemotherapy for recurrence after M-VAC].

Combination chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC regimen) or with methotrexate, etoposide and cisplatin (MEP regimen) was administered to 32 patients with advanced measurable uroepithelial cancers. Fifteen patients among them were adequately treated with M-VAC regimen, and 11 with MEP regimen. Complete remission was not achieved clinically in any patients. Partial remission occurred in 73.3% (11/15) of M-VAC patients and 72.7% (8/11) of MEP patients. Of eleven MEP patients, six were treated with MEP therapy as second line chemotherapy for the recurrence after other chemotherapy (5 cases after M-VAC, 1 case after intraarterial cisplatin). They showed a considerable response (4 patients, PR; 2 patients, MR) and an appreciable remission period, not inferior to those of first line chemotherapy with M-VAC regimen. The present study shows that MEP may be a promising regimen for advanced uroepithelial cancers, especially as a second line chemotherapy for relapsed cases after M-VAC therapy.

Adult↗
PubMed1993

A role of heat shock proteins for homologous recombination in Escherichia coli.

Effects of mutations in heat shock protein genes on homologous recombination in Escherichia coli were examined by measuring intra-molecular recombinations in the plasmid, pIK43. Recombination frequencies in the groES, groEL and dnaK mutants were decreased 6 to 21% of those of the isogenic wild type strain, at a sub-lethal temperature. Thus, the heat shock proteins GroES, GroEL and DnaK apparently participate in homologous recombination in Escherichia coli.

Bacterial Proteins↗
PubMed1993

3,4-Dihydroxychalcones as potent 5-lipoxygenase and cyclooxygenase inhibitors.

A novel series of 3,4-dihydroxychalcones was synthesized to evaluate their effects against 5-lipoxygenase and cyclooxygenase. Almost all compounds exhibited potent inhibitory effects on 5-lipoxygenase with antioxidative effects, and some also inhibited cyclooxygenase. The 2',5'-disubstituted 3,4-dihydroxychalcones with hydroxy or alkoxy groups exhibited optimal inhibition of cyclooxygenase. We found that 2',5'-dimethoxy-3,4-dihydroxychalcone (37; HX-0836) inhibited cyclooxygenase to the same degree as flufenamic acid and 5-lipoxygenase, more than quercetin. Finally, these active inhibitors of 5-lipoxygenase inhibited arachidonic acid-induced mouse ear edema more than phenidone.

Administration, Topical↗
PubMed1993

Absence of linkage disequilibrium at amyloid precursor protein gene locus in Japanese familial Alzheimer's disease with 717Val-->Ile mutation.

To date, eleven independent FAD pedigrees with the 717Val-->Ile mutation have been identified. Interestingly, five pedigrees were of Japanese origin and four were of British origin. The apparent ethnic prediction of this mutation raises the possibility that there is a founder effect in these two island nations. We did not observe any significant linkage disequilibrium in any locus of APP and GT12 loci in the five Japanese FAD pedigrees with the 717Val-->Ile mutation. A founder effect would probably not be present in Japanese FAD pedgrees with the 717Val-->Ile mutation.

Alleles↗
PubMed1993

Requirement of phosphatidylglycerol for flagellation of Escherichia coli.

We report that phosphatidylglycerol is required for flagellation of Escherichia coli. Cells carrying the pgsA3 mutation did not form swarm rings in semisolid agar. P1 transduction experiments revealed that the potential for phosphatidylglycerol synthesis and for the formation of swarm rings was co-transducible. The pgsA3 mutant transformed with the wild type pgsA+ gene cloned into the R-plasmid vector had the potential for both phosphatidylglycerol synthesis and cell motility. Electromicroscopic and SDS-PAGE analyses showed that the pgsA3 mutation causes the lack of flagellation.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat.

Recent advances in molecular biology have allowed the study of the candidate genes for essential hypertension. To identify the genes responsible for basal blood pressure in the spontaneously hypertensive rat strain, the rat model of genetic hypertension, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 progeny obtained from SHR and Wistar-Kyoto rats, a reference normotensive strain. Our investigation revealed that a locus on the chromosome 4 cosegregates with the blood pressure in SHR, especially at neuropeptide Y locus. The degree of cosegregation with all values of blood pressure without sodium loading was moderate but consistent. We propose that neuropeptide Y locus on chromosome 4 is a new candidate for the hypertensive effect in original SHR.

Animals↗
PubMed1993

Oncogene ect2 is related to regulators of small GTP-binding proteins.

We have developed an efficient expression cloning system that allows rapid isolation of complementary DNAs able to induce the transformed phenotype. We searched for molecules expressed in epithelial cells and possessing transforming potential to fibroblasts, and cloned a cDNA for the normal receptor of a growth factor secreted by NIH/3T3 cells. Here we report a second novel transforming gene, ect2. The isolated cDNA is activated by amino-terminal truncation of the normal product. The Ect2 protein has sequence similarity within a central core of 255 amino acids with the products of the breakpoint cluster gene, bcr (ref. 5), the yeast cell cycle gene, CDC24 (ref. 6), and the dbl oncogene. Each of these genes encodes regulatory molecules or effectors for Rho-like small GTP-binding proteins. The baculovirus-expressed Ect2 protein could bind highly specifically to Rho and Rac proteins, whereas the dbl product showed broader binding specificity to Rho family proteins. Thus ect2 is a new member of an expanding family, whose products have transforming properties and interact with Rho-like proteins of the Ras superfamily.

3T3 Cells↗
PubMed1993

Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population.

An association study of the insertion/deletion (I/D) polymorphism located in intron 16 of the ACE gene with essential hypertension in the Japanese population was performed. The 287 bp I/D polymorphism was detected by polymerase chain reaction. Derived allele frequencies for insertion and deletion were not significantly different between 133 hypertensive and 104 normotensive subjects. A significant relationship between I/D polymorphism and plasma ACE activity was observed in the normotensive group, but not in hypertensives. These results suggest that I/D polymorphism of the gene is not implicated in Japanese hypertensive subjects, and that studies involving various ethnic groups are important.

Adult↗
PubMed1993

Fibroblast growth factor receptor 4 is a high affinity receptor for both acidic and basic fibroblast growth factor but not for keratinocyte growth factor.

A cDNA predicted to encode a transmembrane tyrosine kinase receptor with sequence features characteristic of known fibroblast growth factor (FGF) receptors was isolated from an expression library constructed from the human mammary epithelial cell line B5/589. This cDNA, designated cl44, encodes a product of 803 amino acid residues and was readily distinguishable from known FGF receptors. During the course of our studies, Partanen et al. (Partanen, J., Makela, T. P., Eerola, E., Korhonen, J., Hirvonen, H., Claesson, W. L., and Alitalo, K. (1991) EMBO J. 10, 1347-1354) isolated a new FGF receptor, designated FGFR4, from the human leukemia cell line, K562. Its amino acid sequence is identical to that of cl44 with the exception of 1 residue. The 5'-untranslated sequences of the two cDNAs diverged far upstream of the initiation codon. A myoblast line, L6E9, which lacks FGF receptors, was utilized to express high levels of FGFR4. We found, in contrast to Partenen et al., who reported only binding of acidic FGF, that FGFR4 bound both acidic and basic FGF with dissociation constants of 10-15 and 120 pM, respectively. No detectable binding of keratinocyte growth factor was observed. In studies aimed to determine whether FGF receptors contribute to the development of human tumors, we screened RNAs prepared from cell lines derived from a variety of solid tumors. High levels of the cl44 transcript were detected in 8 of 14 and 6 of 9 human mammary and kidney carcinomas, respectively, but only infrequently in other types of tumors. In contrast, FGFR1 was found to be frequently expressed in kidney, but not in breast tumor cells, suggesting a possible role for FGFR4 in human mammary cancer.

Amino Acid Sequence↗
PubMed1993

Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals.

A method which allows direct cloning of intracellular substrates for receptor tyrosine kinases (RTKs) was developed. By applying this technique to the study of the epidermal growth factor receptor (EGFR) signaling pathway, we have isolated a cDNA, designated eps8, which predicts a approximately 92 kDa protein containing an SH3 domain. Eps8 also contains a putative nuclear targeting sequence. Antibodies specific to the eps8 gene product recognize a protein of M(r) 97 kDa and a minor 68 kDa component, which are closely related, as demonstrated by V8 proteolytic mapping. The product of the eps8 gene is tyrosine-phosphorylated in vivo following EGF stimulation of intact cells and associates with the EGFR, despite the lack of a functional SH2 domain. Several other RTKs are also able to phosphorylate p97eps8. Thus, the eps8 gene product represents a novel substrate for RTKs. Adoptive expression of the eps8 cDNA in fibroblastic or hematopoietic target cells expressing the EGFR resulted in increased mitogenic response to EGF, implicating the eps8 gene product in the control of mitogenic signals.

3T3 Cells↗
PubMed1993

Possible selective effects of interferon alpha-2b on a malignant clone in a case of polycythemia vera.

A patient with polycythemia vera associated with chromosomal translocation (6;8) (q27;p11) and IgA monoclonal gammopathy was treated with interferon alpha-2b. Interferon alpha-2b induced good hematological control and reduced only IgA levels, but not IgG and IgM levels. In addition, cytogenetic improvement was obtained, the abnormal cells with chromosomal translocation declining from 100% to 50%. Interferon alpha may have selective effects on a malignant clone in polycythemia vera.

Chromosome Banding↗
PubMed1993

Isolation and mapping of microsatellites from a library microdissected from the Werner syndrome region, 8p11.2-p22.

We have constructed a new genetic linkage map of the Werner syndrome (WRN) region, using microsatellites from a library which was developed by a chromosome microdissection and enzymatic amplification method. These microsatellites were used to genotype members of CEPH families using a simplified detection system of polymerase chain reaction (PCR) products. Two-point analysis was used to assign 4 microsatellite markers relative to each marker and other markers reported in the CEPH public data base. We confirmed that these 4 markers are located to the WRN region, 8p11.2-p22. Such microsatellites microdissected from the definite chromosome region may be useful for positional cloning.

Base Sequence↗
PubMed1993

Midbrain tegmentum as an intermediate relay station of the periaqueductal-facial pathway in the cat.

Iontophoretic injection of horseradish peroxidase (HRP) into the medial part of the facial nucleus resulted in retrograde labeling in the lateral midbrain tegmentum contralaterally which corresponded to the paralemniscal zone (PL). Further experiments in which HRP was injected iontophoretically into the PL revealed heavy retrograde labeling in the lateral portion of the ipsilateral periaqueductal gray (PAG). These light microscopic studies indicated the possibility of the pathway from the PAG to the facial nucleus via the midbrain PL. The electron microscopic observations were carried out on the lateral midbrain tegmentum containing the PL after kainic acid, and wheat germ agglutinin conjugated HRP injections were made into the PAG and the contralateral facial nucleus in the same animal, respectively. Although in the neuropil many degenerating PAG fibers and retrogradely labeled neurons were observed, it was of particular interest that the degenerating fibers made synaptic contacts with HRP-labeled somata and dendrites.

Animals↗