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T Mizuno

Publications and source records attributed to T Mizuno.

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

The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin.

Many leukocyte functions depend on interactions between the leukocyte-specific beta2 integrins CD11/CD18 and their ligands, the intercellular adhesion molecules (ICAMs). Telencephalin (TLN) is a novel member of the Ig superfamily expressed in the central nervous system. The NH2-terminal five Ig-like domains of TLN show the highest homology with the Ig domains of ICAM-1, ICAM-2, ICAM-3, and LW (ICAM-4), the known cellular ligands for CD11a/CD18. Here, we demonstrate that TLN interacts with CD11a/CD18. Peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells bound to immunopurified recombinant human TLN proteins. This adhesion was through CD11a/CD18 and was significantly inhibited by an Ab to CD11a/CD18. Reciprocally, TLN-transfected L cells also bound to purified CD11a/CD18. Recombinant TLN proteins comprising either the first five Ig domains (TLN(1-5)) or the entire extracellular portion (TLN(1-9)) showed binding to CD11a/CD18. We conclude that TLN is a novel neuronal cell adhesion molecule that may be important in integrin-mediated cell-cell interactions in the central nervous system, and that the CD11a/CD18-dependent recognition site of human TLN is located within the NH2-terminal five domains of this molecule.

Amino Acid Sequence↗
PubMed1997

cDNA cloning and chromosomal localization of the human telencephalin and its distinctive interaction with lymphocyte function-associated antigen-1.

We have isolated cDNA encoding human telencephalin (TLN), a brain segment-specific neuronal adhesion molecule. Human TLN comprises an NH2-terminal signal peptide, an extracellular region with nine Ig-like domains, a single transmembrane region, and a COOH-terminal cytoplasmic tail. The NH2-terminal five Ig-like domains of TLN were closely related to those of intercellular adhesion molecules (ICAMs)-1 and -3. The TLN gene was mapped to the human chromosome 19p13.2, where the ICAM-1, -3, and -4 (LW) genes are located. Furthermore, we observed lymphocyte function-associated antigen-1 (LFA-1)-mediated adhesion of HL-60 cells on recombinant TLN protein, as well as on ICAM-1. However, the interaction of TLN with LFA-1 on HL-60 cells was divalent cation-independent and phorbol 12-myristate 13-acetate stimulation-independent. We conclude that TLN is a unique neuronal member of ICAM subgroup of the Ig superfamily and propose a novel type of interaction between the Ig superfamily molecule and integrin, which does not require the activation of integrin. TLN on the surface of telencephalic neurons may be a target molecule in the brain for LFA-1-expressing microglia and leukocytes in physiological or pathological conditions.

Amino Acid Sequence↗
PubMed1997

A Japanese family carrying a novel mutation in the Emery-Dreifuss muscular dystrophy gene.

We report on a Japanese family affected by Emery-Dreifuss muscular dystrophy carrying a novel mutation of the emerin (STA) gene. The cardinal clinical feature of the family was cardiac conduction block and mild myopathy. A deletion of 11 bp with a frameshift was identified in exon 6, causing truncation of the predicted protein. The relationship between mutation and phenotype is discussed.

Adolescent↗
PubMed1997

Downregulation of polo-like kinase correlates with loss of proliferative ability of cardiac myocytes.

Cardiac myocytes rapidly increase the cell number during the fetal and early neonatal period, but they lose their proliferative ability soon after birth. To understand the mechanism of how cardiac myocytes exit from the cell cycle, we examined the role of a newly identified serine/threonine kinase, polo-like kinase (Plk), in the process of proliferation of cardiac myocytes. Northern blot analysis revealed that Plk gene was abundantly expressed in cardiac myocytes and non-myocytes of fetal and neonatal rats but not in cardiocytes of adult rats. Western blot analysis showed that Plk protein was also detected only in fetal and neonatal hearts. During the early stage of cardiac differentiation. Plk expression was well correlated with the proliferative ability of cardiocytes. Plk mRNA was most abundant in undifferentiated embryonic stem (ES) cells and the mRNA levels decreased along with cardiac differentiation in the developing ES cell system. Once serum was deprived from the culture media, expression levels of Plk were markedly decreased and DNA was not synthesized in both cardiac myocytes and non-myocytes of neonatal rats. Re-addition of serum stimulated Plk gene expression and DNA synthesis in non-myocytes but not in cardiomyocytes. All these results taken together with the critical role of Plk in DNA synthesis in many cell types suggest that downregulation of Plk is important for the permanent withdrawal of cardiomyocytes from the cell cycle.

Animals↗
PubMed1997

Protein kinase A and protein kinase C synergistically activate the Raf-1 kinase/mitogen-activated protein kinase cascade in neonatal rat cardiomyocytes.

Adrenoceptor agonists play an important role in cardiac hypertrophy. In cardiomyocytes, activation of alpha- and beta-adrenoceptors induces a variety of hypertrophic responses via activation of protein kinase C (PKC) and protein kinase A (PKA), respectively. Although PKC evokes activation of the Raf-1 kinase (Raf-1)/mitogen-activated protein (MAP) kinase cascade, PKA has been shown to inhibit the activation of Raf-1 and MAP kinases induced by growth factors in various cell types. The present study was performed to elucidate the role of PKA and PKC in cardiomyocyte hypertrophy. PKA activators such as forskolin (FSK), isobutylmethylxanthine, dibutyryl cAMP and isoproterenol, significantly activated Raf-1 and MAP kinases with a peak at 2 and 8 min, respectively, followed by an increase in protein synthesis in cardiac myocytes. Similar responses were observed when cardiomyocytes were stimulated with PKC activators such as 12-O-tetradecanoylphorbol-13-acetate (TPA), angiotensin II, phenylephrine and mechanical stretch. After depleting extracellular Ca2+ with EGTA, FSK did not activate MAP kinases, while down-regulation of PKC by long exposure with TPA did not influence FSK-induced MAP kinase activation. Furthermore, FSK and TPA synergistically activated Raf-1. Similar synergistic activation of MAP kinases was observed when other PKC activators were added to cardiac myocytes with FSK at the same time. In conclusion, unlike other cell types, PKA activates Raf-1 and MAP kinases followed by an increase in protein synthesis in cardiac myocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Thymic follicular hyperplasia manifested as an anterior mediastinal mass.

A rare case of thymic follicular hyperplasia manifested as an asymptomatic anterior mediastinal mass in a 44-year-old man is herein reported. The resected thymus showed prominent medullary lymphoid follicles, an increased number of Hassall's corpuscles, and cysts of varying sizes. This paper discusses the histopathological condition of this lesion.

Adult↗
PubMed1997

Molecular characteristics of malignant lymphomas in cats naturally infected with feline immunodeficiency virus.

Neoplastic disease, especially malignant lymphomas, are often observed in cats infected with feline immunodeficiency virus (FIV). In order to clarify the characteristics of lymphoma cells and to investigate the pathogenesis in FIV-infected cats, we examined the lymphoma tissues developed in five cats naturally infected with FIV by Southern blot analyses using feline immunoglobulin (Ig), T-cell receptors (TCR) and FIV probes. All of the five cases were serologically positive for anti-FIV antibody and negative for feline leukemia virus antigen. Of these five lymphoma samples, two displayed rearrangement of the Ig heavy chain gene and deletion of the Ig light (kappa) chain gene, indicating that the tumor cells were committed to B-cell development. One tumor sample was identified as a T-cell lymphoma because of the presence of a rearranged TCR beta-chain gene. The other two cases were considered to be non-T non-B cell lymphoma because they did not show any rearrangement of the Ig and TCR genes. Therefore, no consistent tumor type was found in lymphoma cases infected with FIV. Clonal integration of FIV provirus was not detected in any of the five lymphoma samples obtained from FIV-infected cats using Southern blot analysis, although FIV proviral genome was detected in the genomic DNA of all the lymphoma samples by using a polymerase chain reaction (PCR). These results indicated that FIV might not play a direct role in tumorigenesis of lymphoma in cats.

Animals↗
PubMed1997

5-Hydroxytryptamine-induced Ca2+ -independent cGMP formation is mediated by nitric oxide in a nitric oxide synthase-independent manner in NG108-15 cells.

A novel pathway of 5-hydroxytryptamine (5-HT)-induced cGMP formation, which does not require Ca2+ and is distinct from the 5-HT, receptor-mediated pathway, is reported to exist in NG108-15 cells. Although the possible involvement of undefined 5-HT receptors and membrane-bound guanylyl cyclase is suggested. the mechanism is not clarified in detail in this Ca2+ -independent cGMP formation. In the present study, we investigated the activation mechanism of guanylyl cyclase activity. 5-HT-induced Ca2+ -independent cGMP formation was not observed in the cell membrane preparation. In intact cells, the 5-HT-induced Ca2+ -independent cGMP formation was inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolin-1-oxyl 3-oxide (carboxyPTIO), a nitric oxide (NO)-specific trapper, and by 3,7-bis(dimethylamino)-phenothiazinium chloride (methylene blue), a cytosolic guanylyl cyclase-specific inhibitor, suggesting the involvement of NO and cytosolic guanylyl cyclase. Ca2+ -independent cGMP formation was not inhibited by 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and various arginine-derivative nitric oxide synthase (NOS) inhibitors. Our findings suggest that 5-HT stimulation results in the generation of NO followed by cGMP formation in an NOS-independent manner in NG108-15 cells.

Animals↗
PubMed1997

Inhibition of transpositional recombination by OrfA and OrfB proteins encoded by insertion sequence IS3.

BACKGROUND: An insertion element IS3 is flanked by terminal inverted repeat (IR) sequences. IS3 encodes two, out-of-phase, overlapping open reading frames, orfA and orfB, from which three proteins are produced. OrfAB is a transframe protein produced by -1 translational frameshifting between orfA and orfB, and it is known to be IS3 transposase. OrfA and OrfB are the proteins produced without frameshifting, but their functions have not been elucidated. RESULTS: A plasmid carrying an IS3 mutant that produces only transposase generates miniplasmids--which are the IS3-mediated intramolecular transposition products--as well as characteristic IS3 circles and linear IS3 molecules. OrfA inhibited the generation of these small molecules to a lesser degree, but OrfB did not. OrfB, together with OrfA, however, inhibited the generation more strongly than OrfA alone. OrfA also inhibited the intermolecular transposition of mini-IS3 with the chloramphenicol-resistance gene flanked by IRs to a reduced frequency, and OrfB together with OrfA inhibited it almost completely. OrfA and/or OrfB did not, however, repress transcription from the promoter in the left-terminal region preceding orfA. CONCLUSIONS: The results obtained above show that OrfA and OrfB are not repressors but are inhibitors of transpositional recombination promoted by transposase. OrfA with an alpha helix-turn-alpha helix DNA-binding motif may compete with transposase to bind to terminal IRs. OrfA, together with OrfB that has a DDE motif conserved in retroviral integrases, may inhibit the formation of an active transpososome consisting oftransposase, two terminal IRs and target DNA for the strand transfer reaction. IS3 with a limited size, 1258 bp in length, uses strategies of translational frameshifting and coupling to produce transposase as well as negative regulators to make its copies at a low level, which minimizes a deleterious effect of transposition on bacterial hosts.

Bacterial Proteins↗
PubMed1997

Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats.

Many lines of evidence have suggested that angiotensin II (Ang II)plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH2-terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10(-9) mol/L and maximal activation at 10(-6) mol/L. Ang II activated JNK through the AT1 receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca2+. Although the addition of either Ca2+ ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca2+ ionophore and phorbol ester markedly activated JNK. Slight expressions of the c-jun gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c-jun gene as well as the c-fos gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1997

Hesperidin as an inhibitor of lipases from porcine pancreas and Pseudomonas.

In the course of our screening work for new types of lipase inhibitors, hesperidin was identified as a simple and small molecular weight inhibitor in the peels of Citrus unshiu. Hesperidin inhibited lipase activity from porcine pancreas and that from Pseudomonas, and their IC50 was 32 and 132 micrograms/ml, respectively. Hesperidin, neohesperidin, narirutin, and naringin are known as the main flavonoids in Citrus unshiu. Neohesperidin also inhibited the lipase from procine pancreas, but did not have any effect on Pseudomonas. Narirutin and naringin did not show this effect on lipases from porcine pancreas and Pseudomonas. In animal experiments, the concentration of plasma triglyceride in rats fed a diet containing 10% hesperidin were significantly lower than that fed the control diet.

Animal Feed↗
PubMed1997

Polysaccharide from Aspalathus linearis with strong anti-HIV activity.

Polysaccharide that has been extracted with 1% sodium carbonate from Rooibos leaves (Aspalathus linearis) showed strong anti-HIV activity. Du-Zhong leaves also showed anti-HIV activity, although lower than the extract of Aspalathus linearis, but Japanese tea leaves and a hot water extract of Aspalathus linearis did not. The anti-HIV activity of the alkaline extract from Aspalathus linearis was recovered mainly in the 25-75% ethanol-precipitated fraction. The polysaccharide almost completely inhibited the binding of HIV-1 to MT-4 cells. It is inferred from these results that the polysaccharide from Aspalathus linearis is involved in the mechanism for virus binding to T cells.

Anti-HIV Agents↗
PubMed1997

Clarification of the promoter structure of the osmoregulated gpd1+ gene encoding an isozyme of NADH-dependent glycerol-3-phosphate dehydrogenase in fission yeast.

The gpd1+ gene of Schizosaccharomyces pombe, encoding an isozyme of NADH-dependent glycerol-3-phosphate dehydrogenase, is responsible for an osmoinducible glycerol production in response to external high osmotic stimuli, and its expression is osmoregulated at the level of transcription. In this study, the structure of the osmoinducible promoter of gpd1+ is described. Not only the core promoter elements including the putative TATA-box and transcription start site, but also a short upstream activation sequence (UAS) was identified, which are involved in the osmotic induction of the gpd1+ gene through the Wis1 MAP (mitogen activated protein) kinase pathway.

Base Sequence↗
PubMed1997

Apoptosis enhanced by soluble factor produced in feline immunodeficiency virus infection.

Feline immunodeficiency virus (FIV)-infected cells have been shown to undergo apoptosis by treatment with tumor necrosis factor alpha (TNF-alpha). This study detected a soluble factor which enhanced the apoptosis induced by TNF-alpha treatment. The sensitivity to TNF-alpha in the induction of apoptosis in a feline fibroblastoid cell line (CRFK) cells was significantly enhanced when the culture supernatant of FIV-infected CRFK cells or plasma samples from FIV-infected cats was added to the culture. These findings suggested that FIV infection induces production of a soluble factor which enhances CRFK cells sensitivity to TNF-alpha induction of apoptosis both in vitro and in vivo. This factor may contribute to the loss of lymphocytes in cats infected with FIV.

Animals↗
PubMed1997

Amyotrophic lateral sclerosis with anti-acetylcholine receptor antibody.

We report a case of amyotrophic lateral sclerosis (ALS) with anti-acetylcholine receptor (AChR) antibody in a 73-year-old female patient. She showed the typical course of ALS. She had no clinical findings of myasthenia gravis and had never undergone neurotoxin therapy using snake venom. Anti-AChR antibody was positive with a titer of 0.50 nmol/l on admission. We traced the titers during the progression of ALS; the titer was positive when muscle weakness worsened, and it became negative when the general condition became stable. We suppose that the occurrence of anti-AChR antibody may be partially relevant with abnormalities at the neuromuscular junction during the progression of ALS.

Aged↗
PubMed1997

[Surgical treatment of T4 primary lung cancer].

We investigated 257 T4 primary lung cancer patients who received operation in 30 hospitals of a lung cancer surgical therapy group of Chubu and present the results of questionnaires on the outcomes of surgical treatment for the T4 cases. T4 cases were classified as follows; 147 resections (57.4%); 110 exploratory thoracotomies (42.8%) ; 90 pleural dissemination and pleural effusions; 33 aorta; 30 left atrium and 17 superior vena cava. Survival rate of the T4 lung cancer patients in resection group and exploratory thoracotomy group were respectively 49.1% and 37.8% for one-year survival rate, and 15.1% and 4.7% for three-year survival rate. P of these two groups was 0.06 from Logrank test. Thirty three patients (21 resection and 12 exploratory thoracotomies) survived for two years and more. The number of cases by invasive organ was 17 pleural disseminations and effusion, 4 aorta, 4 left atrium and 3 mediastinum. We questionnaire on surgical operation for T4 cases with poor prognosis and obtained the result that half of the hospitals were positively performing surgery and the other half revealed a policy avoiding surgery.

Carcinoma, Non-Small-Cell Lung↗