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Biomedical subjects

Y Yamano

Publications and source records attributed to Y Yamano.

At least 109 records · Page 6Linked to original sources
PubMed1995

Disulfide bridges in extracellular domains of angiotensin II receptor type IA.

Angiotensin II receptor type IA (AT1A) has a cysteine (Cys) residue in each of four extracellular domains, and these Cys residues are believed to form two disulfide bridges. However, the question as to which pairs of Cys residues form disulfide bridges have not been experimentally determined. We constructed four mutants of rat AT1A, in which extracellular Cys residues were individually replaced by glycine (mutant C-1, C-2, C-3 and C-4). Further, we constructed two double mutants, in which two extracellular Cys residues were simultaneously substituted for by glycine. The binding affinity for angiotensin II in a double mutant C-1 + 4 (Cys18,274Gly) was similar to that in individually substituted mutants (C-1, C-2, C-3 and C-4) whereas the ligand binding of a double mutant C-2 + 4 (Cys101,274Gly) was completely abolished. The bindings of the non-peptide AT1A antagonist [125I]EXP-985 to mutants C-1, C-4 and C-1 + 4 were only slightly reduced whereas in mutant C-2, C-3 and C-2 + 4 the specific binding for [125I]EXP-985 was completely abolished. These results suggest that disulfide bridges in AT1A are formed between Cys18 and Cys274, and between Cys101 and Cys180, and the latter disulfide bond is essential for the binding of the non-peptidic antagonists [125I]EXP-985 or losartan.

Angiotensin II↗
PubMed1995

Oxidative DNA damage induced by silica in vivo.

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Cloning, expression and regulation of angiotensin II receptors.

Complementary DNAs for angiotensin II type 1 receptor isoforms AT1A and AT1B were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. The AT1 type receptor interacted with more than one type of G-proteins. The ligand binding site of AT1 involving Arg167, Lys199, and Asp263 has been identified by site directed mutagenesis. The regulation of the receptors occur at many stages. The isoform, AT2, was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by stable GTP analogs, it is a seven transmembrane domain receptor. It mediates the modulations of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A. The modulation was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms. AT1 mediates cellular growth. Interestingly, AT2 expression is inversely related to the mitogenic activity of cells.

Amino Acid Sequence↗
PubMed1995

Correction of dorsi-flexed intercalated segment instability after restoration of scaphoid height in a cadaver model of scaphoid non-union.

Models of scaphoid non-union with static dorsi-flexed intercalated segment instability were produced in five frozen arms from cadavers or subjects following accidents by repetitive mechanical loading of the wrist joints longitudinally after a bone defect has been made at the mid-portion of the scaphoid. We designed four models of reduction: anatomical reduction; reduction with a shortened scaphoid; anatomical reduction but with the radio-lunate ligament sectioned, and a shortened scaphoid with the radio-lunate ligament sectioned. Results suggested that anatomical reduction with rigid fixation with a Herbert screw was most effective for correction of malalignment with DISI. Preservation of the radio-lunate ligament during the palmar approach to the scaphoid seemed to be important to prevent ligamentous carpal instability.

Bone Screws↗
PubMed1995

Augmented lung adenocarcinoma cytotoxicity by the combination of a genetically modified anti-Lewis Y antibody and antibodies to complement regulatory proteins.

Complement-dependent cytotoxicity (CDC) mediated by a chimeric anti-Lewis Y monoclonal antibody (cH18A; human IgG1) was investigated in this study. Human lung adenocarcinoma cell lines (PC7, PC9, and PC14) were used as the target cells. PC7 and PC9 cells, expressed Lewis Y antigen and were lysed by cH18A as effectively as by the parent mouse anti-Lewis Y antibodies (mH18A) in a concentration-dependent manner. PC14 cells did not express Lewis Y antigen and were not lysed by either cH18A or mH18A. cH18A mediated CDC activity against PC7 and PC9 cells was enhanced by the combined use of monoclonal antibodies directed against CD46(MCP), CD55(DAF), and CD59. These molecules are complement-regulatory proteins which protect host cells from CDC. PC7 and PC9 cells, showed high levels of surface expression of these proteins, PC7 cells were more susceptible to cH18A-mediated CDC than PC9 cells. Use of multiple blocking antibodies to the complement-regulatory proteins produced more enhancement of cH18A-mediated CDC than a single antibody. Moreover, expression of CD55 and CD59 by PC7 and PC9 cells was decreased after treatment with PI-PLC, resulting in increased susceptibility to cH18A-mediated CDC. Although the reason is unknown, PC7 cells became more susceptible to CDC than PC9 cells after PI-PLC treatment even in the absence of cH18A. These data suggest that chimeric monoclonal antibodies can be used to induce CDC against lung adenocarcinoma, and that such CDC is potentiated by a variety of antibodies blocking compliment-regulatory proteins on the tumour cell surface.

Adenocarcinoma↗
PubMed1995

Tissue- and development-specific expression of goat insulin-like growth factor-I (IGF-I) mRNAs.

We cloned four kinds of goat insulin-like growth factor-I (IGF-I) cDNAs. Each of them encodes the same mature IGF-I and different signal peptides. In this study, we analyzed expression of the four kinds of mRNAs in tissues in various developmental stages by a reverse transcriptase-polymerase chain reaction assay. The results suggest that their expression may be controlled by different promoters, the activities of which are tissue- and development-specific.

Animals↗
PubMed1995

Dynamic aspects in the expression of the goat insulin-like growth factor-I (IGF-I) gene: diversity in transcription and post-transcription.

Goat IGF-I (gIGF-I) cDNA was cloned using the reverse transcriptase-polymerase chain reaction (RT-PCR). The cDNA, which was homologous to rat class 1 IGF-I cDNA, was 969 bp long. From the open reading frame found in it, we predicted a 154 amino acid protein consisting of a 49 amino acid signal peptide, a 70 amino acid mature IGF-I peptide, and a 35 amino acid E domain (the COOH-terminal peptide). From the gIGF-I gene, we isolated and sequenced some segments containing four exons that encompassed the entire gIGF-I cDNA sequence. Goat liver RNA was analyzed by RT-PCR, and the nucleotides of the RT-PCR products were sequenced and checked with the nucleotide sequences of the segments from the gIGF-I gene. The gene had three leader exons (1W, 1, and 2, from upstream to downstream) and was transcribed into three kinds of mRNAs (classes 1W, 1, and 2). Another RNA species was detected by RT-PCR analysis of exon 1W. We sequenced it and found that in this transcript, the 3'-portion of exon 1 was inserted between exons 1W and 3, resulting in class 1W-1 del. mRNA. That is to say, the gIGF-I gene had three leader exons and four kinds of mature mRNA.

Amino Acid Sequence↗
PubMed1995

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) determined by a highly-sensitive chemiluminescent immunoassay during the clinical course of subacute thyroiditis.

Granulocyte colony-stimulating factor (G-CSF) concentrations in serum were determined for the first time by a newly developed and highly sensitive chemiluminescent immunoassay (the limitation of detection, 0.5 pg/ml) in ten patients with subacute thyroiditis, during treatment with glucocorticoid or indomethacin. Before therapy, circulating neurophil counts significantly increased to 5.15 +/- 2.07 x 10(3)/microliters compared with the convalescent phase (2.94 +/- 1.07 x 10(3)/microliters), and the data were correlated with individual serum G-CSF levels (r = 0.854, P < 0.01). Serum concentrations of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were less than the detectable threshold of ELISA. During two weeks of glucocorticoid therapy, although the circulating neutrophil counts increased from 5.15 +/- 2.46 x 10(3)/microliters to 7.73 +/- 1.64 x 10(3)/microliters (P < 0.01), serum G-CSF levels were depressed from 25.1 +/- 15.3 pg/ml to 13.8 +/- 13.9 pg/ml (P < 0.01). These data indicate that G-CSF is one of the mediators of the increase of neutrophils in subacute thyroiditis, while it does not contribute to steroid-induced neutrophilia.

Adult↗
PubMed1995

Radiological evaluation of disease progression in rheumatoid arthritis.

X-ray photographs of the wrist joints in 210 cases of Rheumatoid Arthritis (RA), who visited an outpatient clinic for RA in Orthopedic Department of the Osaka City Medical School were investigated using Carpo-Metacarpal Ratio (CMR) and Shinomiya's criteria, more detailed classification system based on the staging criteria of Steinbrocker. Radiological staging of the wrist joints revealed a correlation with the duration of RA and was considered to be a useful parameter in disease assessment. Radiological alterations in the wrist joints were progressive, but with great individual differences.

Arthritis, Rheumatoid↗
PubMed1995

Clinical effect of etidronate disodium (EHDP) on heterotopic ossification following total hip arthroplasty.

We investigated the status of the development of heterotopic ossification and compared the frequency of heterotopic ossification in the EHDP group with that in the untreated (control) group to evaluate the efficacy and safety of EHDP. Seventy-seven patients who had undergone total hip arthroplasty or femoral head prosthesis for the treatment of osteoarthritis and femoral neck fracture were enrolled in the study. Heterotopic ossification surrounding the hip joint was evaluated according to the roentgenographic classification. In the control group, heterotopic ossification was found in 10 patients (20%) during the period, while in the EHDP group, it was found in one patient (3.7%) during the treatment period after the operation. Gastrointestinal disorder, in one case only was a side effect observed during EHDP treatment. It was revealed that EHDP inhibits heterotopic ossification following total hip replacement in patients with osteoarthritis.

Adult↗
PubMed1995

A rare case of sarcoidosis with rheumatoid arthritis.

Sarcoidosis shows many of the clinical and immunological abnormalities and is a multi-organ granulomatous disease of unknown cause which has histological features of non-caseous epithelioid granuloma formation. Sarcoidosis is rarely coexisted rheumatoid arthritis. Although such arthropathy if occur is thought to manifest rheumatoid changes, the current presence of sarcoidosis and rheumatoid arthropathy has been reported by very few histological studies. We experienced a case of combination of sarcoidosis and rheumatoid arthritis both of which were histologically confirmed. This patient initially developed small papules on the face and was diagnosed as having sarcoidosis after one year. Later, she showed symptoms and signs of polyarthritis and was confirmed to have sarcoidosis and rheumatoid arthritis in combination by histological analysis. We present this case with some reference to literatures.

Arthritis, Rheumatoid↗
PubMed1994

Role of carboxyl tail of the rat angiotensin II type 1A receptor in agonist-induced internalization of the receptor.

Binding of angiotensin II (Ang II) to its receptor type 1A (AT1A) is known to trigger its internalization. We studied the role of cytosolic segments of AT1A in the internalization, and obtained results indicating a functional role of the cytosolic carboxyl terminal tail of AT1A in the internalization. Deletion of 50 amino acids from the carboxyl terminus abolished the receptor internalization. Deletion mutants lacking 13 and 32 amino acid residues in the carboxyl terminal cytosolic region were internalized to the same extent as wild type AT1A; however, internalization of a mutant lacking the last 42 residues was partially suppressed. Thus, residues 310 through 327 were shown to be essential for the internalization. We propose that a short domain in the cytoplasmic tail (residues 310 to 327) may play a dominant role in the agonist-induced receptor internalization of AT1A. Our results also suggest that the molecular determinants of the AT1A receptor involved in receptor internalization are distinct from those participating in the desensitization process.

Amino Acid Sequence↗
PubMed1994

Cloning, expression and regulation of angiotensin II receptors.

Angiotensin II isoform 1 (AT1) receptor cDNAs were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. A single type of receptor seems to interact with more than one type of G-protein. AT1 consists of subtypes AT1A and AT1B, and the regulation of the receptors occurs at many stages. The isoform AT2 was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by GTP analogs, it is a seven transmembrane domain receptor. It mediates the inhibition of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A; the inhibition was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms.

Amino Acid Sequence↗
PubMed1994

Cloning of cDNAs for cecropins A and B, and expression of the genes in the silkworm, Bombyx mori.

cDNA clones coding cecropins A and B were isolated from a cDNA library constructed from the fat body of immunized Bombyx mori larvae. The cloned cDNAs had an open reading frame of 63 amino acids, indicating the primary translated peptides were processed to form mature cecropins of 35 amino acid residues. The homology in the coding regions of cecropins A and B was 73%. In immunized fat body, the expression of both cecropin A and B genes reached the maximal level 5 h after the injection of soluble peptidoglycan, and the high level was maintained until 9 h after immunization. The cecropin A and B genes were expressed at high levels in fat body and hemocytes, at lower but significant levels in malpighian tube, slightly in midgut, and none in silk gland.

Amino Acid Sequence↗
PubMed1994

Angiotensin II receptors: cloning and expression.

To identify the mechanisms of action of isoforms angiotensin II receptors (AT1A, AT1B, and AT2) and to overcome the difficulties encountered in attempts to purify the receptors, we have expression-cloned their cDNAs from bovine and rat sources and isolated human cDNA and rat and human genomic DNA. The AT1A and AT1B cDNAs were found to encode respective receptor proteins with 359 amino acid residues, whereas, AT2 encodes a 363 amino acid residue receptor protein. Both AT1 and AT2 were found to conform with the seven transmembrane receptor structural motif, but showed only 32% amino acid residue identity to each other. The AT1 receptor was shown to be coupled to, at least, three different G proteins activating phospholipase C, inhibiting adenylyl cyclase and opening an L-type Ca(2+)-channel, whereas, AT2 was found to inhibit a phosphotyrosine phosphatase activity without affecting guanylyl cyclase by a pertussis-toxin-sensitive, presumably G-protein-mediated mechanism.

Amino Acid Sequence↗
PubMed1994

Alteration of cartilage specific proteoglycan with non-weight bearing articular cartilage.

The cartilage composed of chondrocytes and their surrounding extracellular matrix, and mechanical motion of joint may influence on the metabolism of cartilage. In order to determine whether non-weight bearing status alter the metabolism of cartilage, we made histological and biochemical analysis with incorporation of 35S and the distribution of the molecular size of proteoglycans produced in the case of disused cartilage. Histologically, there were seen no disorder in cell arrangement, but poorer in cellularity and thinner in cartilage width as compared with normal one. Biochemical analysis, however demonstrate that incorporation of 35S in newly synthesized glycosaminoglycan (GAG) was lower and the molecular size also smaller than that of control suggesting that mechanical stress is an important environmental factor in maintaining the differential function of the cartilage.

Cartilage, Articular↗
PubMed1994

Jaw reconstruction using vascularized fibular grafts.

The mandible was reconstructed using 12 and 13-cm-long vascularized fibular grafts in 2 cases of extensive defects due to resection of the anterolateral portion of the mandible for the removal of bone Tumors. The straightness and hardness of the fibula allowed it to be given a two-dimensional curvature. The reconstructed mandibles were satisfactory both aesthetically and functionally. Large defects of the mandible cause distortion of the face and trouble with mastication. Treatment of massive mandibular defects by conventional bone grafting often ends in failure because of bone resorption, and for this reason, vascularized bone grafts are appropriate. We report here in 4 cases of the reconstruction of the jaw (Table 1) and the detail of the reconstruction with the use of vascularized fibular grafts is presented for the 2 cases of extensive anterolateral mandibular defects.

Adult↗