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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 199 records · Page 11Linked to original sources

Chemokine receptors in human basophils: inducible expression of functional CXCR4.

We examined the expression profile of chemokine receptors in human basophils and their regulation by cytokines. Basophils expressed transcripts of CC chemokine receptors (CCR)1, CCR2, CCR3, and CCR5 and CXC chemokine receptors (CXCR)1, CXCR2, and CXCR4. In contrast to the other receptors, surface-CXCR4 expression was not detected in fresh- and whole-blood basophils, but it became apparent gradually during incubation. Among 16 chemokines tested, eotaxin induced the most potent basophil migration. SDF-1 also induced a strong, migratory response comparable with that induced by eotaxin in 24-h, cultured basophils, but it failed to induce degranulation. IL-3 abrogated CXCR4 expression completely, and it only down-regulated CCR2 and CCR3 expression slightly. IL-5, GM-CSF, and IL-4 also down-regulated CXCR4 expression. Thus, expression of CXCR4 was the most strongly affected by cytokines, and this may represent an alternative mechanism for control of cell-specific, biological responses to SDF-1.

Basophils↗

[Two elderly patients with advanced gastric cancer responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin followed by oral administration of S-1].

Recently, as society ages there have become more elderly gastric cancer patients with/without several complications(cerebrovascular diseases, cardiac diseases, atherosclerosis, DM, etc.), that were non-resected and require highly effective chemotherapy and good QOL. We report two elderly gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, S-1. The treatment protocol was tegafur 800 mg/body, days 1-7 (continuing 16 h, intravenously with 500 mg/body from 16 to 0 h, 300 mg/body from 0-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, (16 h), Isovorin 25 mg/body, days 1-5, (16 h, oneshot infusion, for 4 courses followed by a week rest. Next was S-1 120 mg/body x 2 times orally for 28 days, followed by 2 weeks rest, the administered for another 28 days. The first patient was 74 years of age, with advanced type 3 plus early type IIc gastric cancers with liver metastasis (H1). After chemotherapy the liver metastasis disappeared, there was a 70% reduction in the advanced cancer and the early cancer disappeared. The second patient was 84 years of age, with advanced type 3 gastric cancer invading the esophagus. After chemotherapy, the primary lesion was reduced 80% and the esophageal invasion mass shrunk. The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient.

Adenocarcinoma↗

[Reconstruction of the pulmonary outflow tract without external conduit].

Between October 1987 and December 2000, 50 patients underwent reconstruction of the pulmonary outflow tract without external conduit. The primary malformation was tetralogy of Fallot with pulmonary atresia in 37, double outlet of right ventricle in 4, corrected transposition of the great arteries in 4, transposition of the great arteries with ventricular septal defect and pulmonary stenosis in 4, and double outlet of left ventricle in 2. Mean age at operation was 7.2 years, and mean body weight was 18.3 kg. To reconstruct posterior wall of the pulmonary outflow tract, interposition of autologous pericardium was performed in 24, direct anastomosis between pulmonary trunk and ventriculotomy in 13, longitudinal incision from ventriculotomy through pulmonary trunk in 12, and interposition of left atrial appendage in 1. Anterior wall was reconstructed with monocusp valved outflow patch (MVOP). There was one hospital death and no late death. At 10 years, the freedom from reoperation for pulmonary outflow tract obstruction was 100%, and freedom from reoperation for any cause was 86.6%. Transcatheter stenting for peripheral pulmonary stenosis was performed in 6 patients 2 to 10 months after operation.

Adolescent↗

[Congenital aortic stenosis].

Recent advances in and controversies concerning the management of children with congenital valvular aortic stenosis are discussed. In neonates with critical aortic stenosis, improved survival has recently been reported after surgical open valvotomy and balloon valvuloplasty, although it is difficult at this point to compare the results of the two procedures and determine their differential indications. Good results have also been achieved after extended aortic valvuloplasty for recurrent aortic stenosis and/or insufficiency, but the length of follow-up in these patients is still short. The technique first reported in 1991 for bilateral enlargement fo a small annulus permits the insertion of an aortic valve 3-4 sizes larger than the native annulus. It entails no risk of distorting the mitral valve, damaging the conduction system or important branches of the coronary arteries, or resulting in left ventricular dysfunction. The Ross procedure is now widely applied in the West, with reports of early mortality rates of less than 5% and event-free survival rates of 80-90% during follow-up of 4-8 years. Longer follow-up and continued careful evaluation are required to resolve the issue of possible dilatation and subsequent neoaortic valve dysfunction and pulmonary stenosis due to allograft degeneration after pulmonary autograft root replacement in children.

Aortic Valve Stenosis↗

[Tissue platinum distribution and the effect following intra-arterial injection of cisplatin to metastatic liver cancer--a case report].

A 63-year-old male with advanced esophageal cancer was admitted to our hospital. He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil (5-FU), and underwent resection of the esophagus and placement of a gastric tube. Two months later, multiple metastases appeared in the right lobe of the liver. Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were performed. To selectively infuse the drugs into the right hepatic artery, the left hepatic artery was embolized. Treatment had a marked effect in the right lobe, but new lesions were subsequently discovered in the left lobe. The patient died of pleuritis 27 days after the end of cisplatin infusion and 12 months after surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered. At autopsy, tissue samples were collected to measure the platinum concentration. The result showed the highest value to be in the right lobe, 4.8 times as high as that in the left lobe. It is suggested that the concentration of platinum in tissue is correlated with the anticancer effect of cisplatin to the tissue, despite of the traditional view that the tissue concentration and the effect are not related.

Antineoplastic Agents↗

[Acute myelogenous leukemia associated with disseminated intravascular coagulation and acute myocardial infarction at relapse].

A 71-year-old man with acute myelogenous leukemia (AML, M2) developed signs of chest oppression, and was diagnosed as having acute myocardial infarction (AMI). At the same time, his leukemia relapsed in association with disseminated intravascular coagulation (DIC). The patient's risk factors for AMI were hyperlipidemia, hyperglycemia, and a history of smoking. Coronary angiography showed occlusion of the circumflex branch. Percutaneous transluminal angioplasty (PTCA) was performed successfully, followed by administration of heparin. After chemotherapy, the patient's DIC improved and a second remission was attained. When elderly patients with AML show evidence of DIC, we should be aware of AMI as a possible complication. PTCA is a safe operation for such patients.

Aged↗

Species-identification dots: a potent tool for developing genome microbiology.

Identification of species has long been done by phenotype-based methodologies. Recently, genotype-based species identification has been shown to be possible by way of Genome profiling, which is based on a temperature gradient gel electrophoresis (TGGE) analysis of random PCR products. However, the results, though sufficient in information, provided by genome profiling were complicated and difficult to deal with objectively. To cope with this, a technology of utilizing species identification dots (spiddos), which corresponds to structural transition points of DNAs, was introduced. Pattern similarity score (PaSS), derived from spiddos, was shown to be usable for quantitatively measuring the closeness between genomes. This was demonstrated with the experiments applied to the genomes of Escherichia coli O157:H7 (19 strains). The same genomes were also examined by sequencing and RFLP methods in order to compare the effectiveness of these three methods. As a result, the spiddos method was shown to give reasonable results and to be the most advantageous for measuring the closeness between species in general. This means that spiddos is pushing the heavy gate open for genome microbiology.

Base Sequence↗

Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF).

The transcription factor DREF regulates proliferation-related genes in Drosophila. With two-hybrid screening using DREF as a bait, we have obtained a clone encoding a protein homologous to human myelodysplasia/myeloid leukemia factor 1 (hMLF1). We termed the protein Drosophila MLF (dMLF); it consists of a polypeptide of 309 amino acid residues, whose sequence shares 23.1% identity with hMLF1. High conservation of 54.2% identity over 107 amino acids was found in the central region. The dMLF gene was mapped to 52D on the second chromosome by in situ hybridization. Interaction between dMLF and DREF in vitro could be confirmed by glutathione S-transferase pull-down assay, with the conserved central region appearing to play an important role in this. Northern blot hybridization analysis revealed dMLF mRNA levels to be high in unfertilized eggs, early embryos, pupae and adult males, and relatively low in adult females and larvae. This fluctuation of mRNA during Drosophila development is similar to that observed for DREF mRNA, except in the pupa and adult male. Using a specific antibody against the dMLF, we performed immunofluorescent staining of Drosophila Kc cells and showed a primarily cytoplasmic staining, whereas DREF localizes in the nucleus. However, dMLF protein contains a putative 14-3-3 binding motif involved in the subcellular localization of various regulatory molecules, and interaction with DREF could be regulated through this motif. The transgenic fly data suggesting the genetic interaction between DREF and dMLF support this possibility. Characterization of dMLF in the present study provides the molecular basis for analysis of its significance in Drosophila.

Amino Acid Sequence↗

Intracellular signaling factors--enhanced hepatic nuclear protein binding to TTGGC sequence in the rat regucalcin gene promoter: involvement of protein phosphorylation.

The transcriptional mechanism of regucalcin gene expression was determined using gel mobility shift assay with TTGGC oligonucleotide (II-b) which is located between position -523 and -506 in the promoter region, containing a nuclear factor I (NF1) consensus motif TTGGC(N)(6)CC. The mutation analysis in this motif showed that TTGGC sequence was a specific binding region of the nuclear protein in rat liver and the cloned rat hepatoma cells (H4-II-E). When liver nuclei were incubated with ATP (1 mM), the nuclear protein binding to TTGGC sequence was increased. This binding was also increased in the nuclei of H4-II-E cells cultured with 10% FBS. Such an increase was also seen by culture with vanadate (100 microM), a potent inhibitor of protein tyrosine phosphatase. Serum-enhanced nuclear protein binding to TTGGC sequence was decreased in the presence of TFP (10 microM), staurosporine (100 nM), genistein (10 microM), PD98059 (10 microM), or wortmannin (10 nM), which are inhibitors of various protein kinases. Treatment of a monoclonal phosphotyrosine antibody (4G10) caused an alteration in the TTGGC oligonucleotide-nuclear protein complex formation, indicating that tyrosine phosphorylation of nuclear protein is partly involved in the binding to TTGGC sequence. Moreover, when H4-II-E cells were cultured with FBS (10%), Bay K 8644 (5 microM), PMA (1 microM), or insulin (20 nM), the protein binding to TTGGC sequence in the nuclei was increased, while it was reduced in the cytoplasm, indicating a nuclear localization of the TTGGC sequence-binding protein. This study demonstrates that hepatic nuclear protein can specifically bind to the TTGGC sequence in rat regucalcin gene promoter region, and that this binding is enhanced by intracellular signaling factors which are partly mediated through protein phosphorylation.

Animals↗

5-Amino-4-sulfanylphthalhydrazide as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography.

5-Amino-4-sulfanylphthalhydrazide (ASPH) was synthesized as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography (LC). Benzaldehyde, 4-tolualdehyde, 4-chlorobenzaldehyde, 4-formylbenzoic acid, 4-hydroxybenzaldehyde and vanillin were used as model compounds to optimize the derivatization conditions. This reagent, ASPH, reacts selectively with aromatic aldehydes in the presence of sodium sulfite and disodium hydrogenphoshite in acidic medium at 100 degrees C to give the corresponding highly chemiluminescent 2-arylbenzothiazole derivatives. The resulting derivatives generated intense chemiluminescence by reaction with hydrogen peroxide and potassium hexacyanoferrate(III) in alkaline solution. The ASPH derivatives of aromatic aldehydes were separated by reversed-phase liquid chromatography with isocratic elution, and detected chemiluminometrically after mixing with oxidizing agents. The detection limits (signal-to-noise ratio = 3) for aromatic aldehydes are in the range 0.2-4.0 fmol for a 20-microl injection volume. Currently, the method is not effective for aliphatic aldehydes because of interfering LC peaks.

Aldehydes↗

Natural chaotic inflation in supergravity

We propose a chaotic inflation model in supergravity. In the model the Kahler potential has a Nambu-Goldstone-type shift symmetry of the inflaton chiral multiplet which ensures the flatness of the inflaton potential beyond the Planck scale. We show that chaotic inflation naturally takes place by introducing a small breaking term of the shift symmetry in the superpotential. This may open a new branch of model building for inflationary cosmology in the framework of supergravity.

Journal Article↗

Stimulatory effect of regucalcin on mitochondrial ATP-dependent calcium uptake activity in rat kidney cortex.

The effect of regucalcin, which is a regulatory protein of Ca(2+) signaling, on Ca(2+)-ATPase activity in isolated rat renal cortex mitochondria was investigated. The presence of regucalcin (50, 100, and 250 nM) in the enzyme reaction mixture led to a significant increase in Ca(2+)-ATPase activity. Regucalcin significantly stimulated ATP-dependent (45)Ca(2+) uptake by the mitochondria. Ruthenium red (10(-6) M) or lanthunum chloride (10(-6) M), an inhibitor of mitochondrial Ca(2+) uptake, markedly inhibited regucalcin (100 nM)-increased mitochondrial Ca(2+)-ATPase activity and (45)Ca(2+) uptake. The effect of regucalcin (100 nM) in elevating Ca(2+)-ATPase activity was completely prevented by the presence of digitonin (10(-2)%), a solubilizing reagent of membranous lipids, vanadate, an inhibitor of phosphorylation of ATPase, or dithiothreitol (50 mM), a protecting reagent of the sulfhydryl (SH) group of the enzyme. The activating effect of regucalcin (100 nM) on Ca(2+)-ATPase activity was not further enhanced by calmodulin (0.30 microM) or dibutyryl cyclic AMP (10(-4) M), which could increase Ca(2+)-ATPase activity. Trifluoperazine (TFP; 50 microM), an antagonist of calmodulin, significantly decreased Ca(2+)-ATPase activity. The activating effect of regucalcin on the enzyme was also seen in the presence of TFP, indicating that regucalcin's effect is not involved in mitochondrial calmodulin. The present study demonstrates that regucalcin can stimulate Ca(2+)-pump activity in rat renal cortex mitochondria, and that the protein may act on an active site (SH group) related to phosphorylation of mitochondrial Ca(2+)-ATPase.

Adenosine Triphosphate↗

Molecular cloning and expression during development of the Drosophila gene for the catalytic subunit of DNA polymerase epsilon.

We have cloned the genomic DNA and cDNA of Drosophila DNA polymerase epsilon (pol-epsilon) catalytic subunit (GenBank No. AB035512). The gene is separated into four exons by three short introns, and the open reading frame consists of 6660 base pairs (bp) capable of encoding a polypeptide of 2220 amino acid residues. The calculated molecular mass is 255018, similar to that of mammalian and yeast homologues. The deduced amino acid sequence of the pol-epsilon catalytic subunit shares approximately 41% identity with human and mouse homologues as well as significant homology those of C. elegans, S. cerevisiae and S. pombe. Similar to the pol-epsilon catalytic subunits from other species, the pol-epsilon catalytic subunit contains domains for DNA polymerization and 3'-5' exonuclease in the N-terminal region, and two potential zinc-finger domains in the C-terminal regions. Interestingly, a 38 amino acid sequence in the C-terminal region from amino acid positions 1823 to 1861 is similar to the site for Mycoplasma ATP binding and/or ATPase domain (GenBank No. P47365). Northern hybridization analysis indicated that the gene is expressed at the highest levels in unfertilized eggs, followed by zero to 4h embryos and adult females, and then embryos at other embryonic stages, instar larva stages and adult males. Low levels of the mRNA were also detected at the pupa stage. This pattern of expression is similar to those of DNA replication-related enzymes such as DNA polymerase alpha and delta except for the high level of expression in adult males.

Amino Acid Sequence↗

Sound velocity measurements of nuclear-ordered solid 3He along the melting curve.

We have measured the temperature dependence of the 10.98 MHz longitudinal sound velocity of solid 3He in the nuclear-ordered U2D2 phase and in the paramagnetic phase along the melting curve. The temperature dependence of the sound was attributed to the contributions from the nuclear spin system and the molar volume change along the melting curve. The sound velocity increased with temperature as T4 in the U2D2 phase and the sound anisotropy due to the exchange interaction was found to be about 10% among single-domain crystals investigated. The average value of the Gruneisen constant of the spin wave velocity in the ordered phase was gamma(c) = 16 and is compared to the calculated value of the multiple-exchange model.

Journal Article↗

Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells.

To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte-colony-stimulating factor-mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m(2), significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P <.0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12. 6%; n = 10) was significant (P <.0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34(+) cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.

Annexin A5↗

Time-course effects of a single administration of cocaine on receptor binding and subunit mRNAs of GABA(A) receptors.

We investigated the time-course effects of a single administration of cocaine (20 mg/kg) on GABA(A) receptor binding labeled by t-[(35)S]butylbicyclophophorothionate (TBPS) and on several types of GABA(A) receptor subunit mRNAs in the rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. The levels of alpha 1, beta 2, and beta 3 subunit mRNAs in several brain regions such as the cortex, cerebellum, and striatum were significantly decreased within 1 h, while beta 3 subunit mRNA was increased in the dentate gyrus. All of these changes were transient, occurring within 1 h after the injection of cocaine. In the cortex and cerebellum, the reduction in alpha1 subunit mRNA was followed by a significant decrease in [(35)S]TBPS receptor binding, which occurred 4 h after cocaine injection. These findings suggest that acute cocaine administration discretely regulates GABA(A) receptor subunit mRNA levels in several brain regions through a change in transcription or turnover rates of subunit mRNAs, which may be closely related to cocaine-induced behavioral abnormalities.

Animals↗