Biomedical subjects

M Hibi

Publications and source records attributed to M Hibi.

At least 91 records · Page 5Linked to original sources

PubMed1996

[Mediastinitis treated by an omental transfer following CABG using the right gastroepiploic arterial graft].

We treated four cases with mediastinitis after coronary artery bypass grafting using the right gastroepiploic artery. These four patients were treated with the pedicled omentum. Omental transfer was successful in three cases. After the harvest of the right gastroepiploic arterial graft, the residual omentum was viable. The residual omentum was applicable for the treatment of mediastinitis.

Aged↗

PubMed1995

Interaction of the protein nucleobindin with G alpha i2, as revealed by the yeast two-hybrid system.

The heterotrimeric G protein, G alpha i2, transduces signals from seven membrane spanning receptors to effectors such as adenylyl cyclase and ion channels. The purpose of this study was to identify these or other cellular proteins that interact with G alpha i2 by use of the yeast two-hybrid system. A human B cell cDNA library was screened by this system using full length G alpha i2. Four positive colonies were obtained. Two of the four were identified as nucleobindin, a calcium binding protein and a putative antigen to which anti-nuclear antibodies are generated in mice with a disorder that resembles systemic lupus erythematosus. Nucleobindin has a leucine zipper, EF hands, and a signal peptide sequence and is thought to localize to the nucleus as well as being secreted. The specificity of intehraction between G alpha i2 and nucleobindin was confirmed by an in vitro binding assay using recombinant proteins. Transfection of G alpha i2 and nucleobindin in COS cells increased G alpha i2 expression relative to cells transfected with G alpha i2 and mock vector. Our results indicate that the yeast two-hybrid system provides a means to identify novel proteins that interact with G alpha proteins. Nucleobindin appears to represent one of those proteins.

Animals↗

PubMed1995

Mitral valve replacement via right thoracotomy after coronary arterial grafting.

Mitral valve replacement was performed through a right thoracotomy using femorofemoral bypass under profound systemic hypothermia in a 62-year-old man who had undergone coronary artery bypass grafting using both internal thoracic arteries. The right thoracotomy approach minimizes the risk of injury to the arterial grafts, and deep hypothermia obviates the need to interrupt the grafts to administer cardioplegia. This technique provides excellent exposure of the mitral valve while minimizing the operative risk.

Bioprosthesis↗

PubMed1995

[A case of octogenarian left atrial myxoma].

We reported a case of left atrial myxoma in advanced age. The case was eighty years old man. He admitted with congestive heart failure. He was diagnosed as left atrial myxoma by echocardiography. The open heart surgery was done. The myxoma was 79 g in weight and 8.5x5x3 cm in size. Post operative course was uneventful. The echocardiography is useful for diagnosis of the left atrial myxoma. The left atrial myxoma should be operated when it is diagnosed how the patient is advanced age. The septal-superior exposure gives a good operative field.

Age of Onset↗

PubMed1995

[Cardiac operation of the cases associated with malignant tumor].

Twelve cases of malignant tumor (mean age 64 years) underwent the cardiac operation. The procedure of cardiac operations were 10 coronary artery bypass grafting and 2 mitral valve replacement. The detail of malignant tumors were 4 gastric cancer, 3 colon cancer, 3 lung cancer, 1 esophageal cancer and 1 lip cancer. The cardiac operations followed the operations of malignant tumor in 4 cases and the cardiac operations were followed by the operations of malignant tumor in 7 cases. The former cases did not recur the tumor from 10 to 30 months follow up period. The all latter cases survived except 1 case from 1 month to 21 months. Our management for the cases associated with malignant tumor and cardiac diseases as next. We perform the cardiac operation for the case whose life expectancy is longer than 1 year. We perform the cardiac operation before the operation of malignant tumor. We perform the operation for malignant tumor as soon as the patient had recovered from the cardiac operation. We would not perform any adjuvant therapy before completion of the operation for the heart and tumor.

Aged↗

PubMed1994

Altering the specificity of signal transduction cascades: positive regulation of c-Jun transcriptional activity by protein kinase A.

Protein phosphorylation is commonly used to modulate transcription factor activity. However, all existing genetic evidence for stimulation of transcription factor activity by phosphorylation rests on loss-of-function mutations. To demonstrate conclusively that phosphorylation of a transcription factor potentiates its transactivation potential in vivo, we constructed a c-Jun mutant that is phosphorylated by the cAMP-sensitive protein kinase A (PKA) instead of the UV- and Ras-responsive protein kinase JNK. The transcriptional activity of this mutant is enhanced by PKA, but not by JNK activation. These results provide a positive and conclusive proof that phosphorylation of c-Jun on a critical site (Ser73) located in its activation domain is directly responsible for enhancing its transactivation function.

Amino Acid Sequence↗

PubMed1994

Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases.

c-Jun transcriptional activity is augmented by expression of oncogenic Ras and Raf proteins. This study demonstrates a direct correlation between Ras transforming activity and c-Jun activation, supporting an important role for c-Jun in transformation by Ras. Since we observed that Ras activated c-Jun transcriptional activity by increasing phosphorylation of the c-Jun activation domain at residues Ser-63/Ser-73 and that oncogenic Ras proteins activated extracellular signal-regulated protein kinases (ERK1 and ERK2) (also known as mitogen-activated protein kinases), we evaluated the possibility that ERKs were directly responsible for c-Jun activation. Coexpression of wild-type ERKs with oncogenic Ras proteins potentiated, while kinase-defective ERKs inhibited, Ras-induced transcriptional activation from the Ras-responsive element (Ets-1/AP-1) present in the NVL-3 enhancer and the serum-response element in the c-fos promoter. In contrast, coexpression of either wild-type or kinase-defective ERKs inhibited Ras and Raf activation of c-Jun transcriptional activity. Thus, although activation of both ERK and c-Jun are downstream consequences of activation of the Ras signal transduction pathway, our results suggest that Ras-induced c-Jun phosphorylation and transcriptional activation are not a direct consequence of ERK1 and ERK2 activation.

3T3 Cells↗

PubMed1994

JNK is involved in signal integration during costimulation of T lymphocytes.

T lymphocyte activation and interleukin-2 (IL-2) production require at least two signals, generated by phorbol ester (TPA) and Ca2+ ionophore or costimulation of the T cell receptor (TCR) and the CD28 auxiliary receptor. We investigated how these stimuli affect mitogen activated protein (MAP) kinases. Full activation of the MAP kinases that phosphorylate the Jun activation domain, JNK1 and JNK2, required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28. Alone, each stimulus resulted in little or no activation. Similar to its effect on IL-2 induction, cyclosporin A (CsA) inhibited the synergistic activation of JNK, and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation. By contrast, the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+, CD28, or CsA. Hence, integration of signals that lead to T cell activation occurs at the level of JNK activation.

Animals↗

PubMed1994

JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.

The ultraviolet (UV) response of mammalian cells is characterized by a rapid and selective increase in gene expression mediated by AP-1 and NF-kappa B. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. Here, we describe the molecular cloning and characterization of JNK1, a distant relative of the MAP kinase group that is activated by dual phosphorylation at Thr and Tyr during the UV response. Significantly, Ha-Ras partially activates JNK1 and potentiates the activation caused by UV. JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. Thus, JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation. These properties indicate that JNK1 activation may play an important role in tumor promotion.

Amino Acid Sequence↗

PubMed1994

The effects of calcium antagonists and prostaglandin E1 on isolated canine coronary arterial tension.

The effects of calcium antagonists (nifedipine, nicardipine, diltiazem, and verapamil) and prostaglandin E1 (PGE1) on the tension of isolated canine coronary arterial strips were studied. In a solution containing 20 mEq/L of K+, 127 mEq/L of Na+, the tension was increased by 500-1,000 mg with 4 mEq/L of Ca2+. This increase in tension was suppressed by Ca-antagonists and PGE1 dose-dependently. Nifedipine 10(-5) M, nicardipine 3 x 10(-7) M, diltiazem 3 x 10(-6) M, and verapamil 3 x 10(-6) M completely suppressed the increased tension. The maximal suppression of the tension produced by PGE1 was about 40% at 10(-10) M. In 20 mEq/L K+ solution (0 mEq/L Ca2+, 37 degrees C), the reduction of the Na+ concentrations from 127 mEq/L to 12 mEq/L increased the tension by 50 to 100 mg. This increase in tension was not suppressed by Ca-antagonists or PGE1. In conclusion, this study demonstrated that Ca-antagonists and PGE1 suppressed an increase in the tension caused by Ca2+ but did not suppress an increase in the tension caused by Na+ reduction.

Alprostadil↗

PubMed1994

Nafamostat mesilate reduces blood cell adhesion to cardiopulmonary bypass circuits: an in-vitro study.

Nafamostat mesilate (FUT-175) is a protease inhibitor, working as an inactivator of coagulation, fibrinolysis and platelet aggregation. Although FUT-175 directly blocks contact factors in coagulation, it also may decrease activation of humoral cascade systems when used in cardiopulmonary bypass circuits. We performed an in vitro study using fresh human blood in the following cardiopulmonary bypass circuits: standard circuit (C), biosurfaced circuit (B) and standard circuit containing FUT-175 (F). Each circuit was primed with 500 ml of electrolyte solution and 500 ml of fresh blood. Cardiopulmonary bypass was performed using a roller pump for four hours in two sets of each circuit configuration. Platelet factors (platelet count and beta-thromboglobulin), coagulation factors (thrombin-antithrombin III complex and fibrinopeptide A), fibrinolysis factors (alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor), complement factors (C3a, C4a), free hemoglobin, and granulocyte elastase were measured at the beginning and end of the study. Hemocytograms were measured concurrently. The FUT-175 group showed significantly lower levels of the measured indices than the biosurfaced group in thrombin-antithrombin III complex (7.4 +/- 2.1 vs. 54.9 +/- 38.1 ng/ml), fibrinopeptide A (7.2 +/- 2.0 vs. 20.2 +/- 14.6 ng/ml), beta-thromboglobulin (1940 +/- 250 vs. 2438 +/- 314 ng/ml) and free hemoglobin (25.2 +/- 14.3 vs. 73.8 +/- 18.4 mg/dl). There were no significant differences between Group F and Group B in platelet count, C3a, C4a and granulocyte elastase, although these indices were significantly lower in Groups F and B when compared to Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzamidines↗

PubMed1993

IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.

The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. The IL-6-induced gp130 homodimer appears to be similar in function to the heterodimer formed between the leukemia inhibitory factor (LIF) receptor (LIFR) and gp130 in response to the LIF or ciliary neurotrophic factor (CNTF). Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal-transducing molecules and activation of associated tyrosine kinases.

Antigens, CD↗

PubMed1993

Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130.

Here, we report the analysis of the structure-function relationship of the extracellular region of human interleukin 6 receptor (IL-6R). Upon binding of IL-6, IL-6R becomes associated extracellularly with a non-IL-6-binding but signal transducing molecule, gp130, and the IL-6 signal is generated. In this region, the cytokine receptor family domain, but not the immunoglobulin-like domain, was responsible both for IL-6 binding and for signal transduction through gp130. Because a soluble, extracellular portion of IL-6R (sIL-6R) could bind IL-6 and mediate IL-6 functions through gp130, amino acid substitutions were introduced into sIL-6R by site-directed mutagenesis. The results, together with the previously proposed tertiary structure model, suggested that the amino acid residues critical for IL-6 binding have a tendency to be distributed to the hinge region between the two 'barrel'-like fibronectin type III modules and to the same side of these two 'barrels'. Amino acid residues, of which substitutions barely affected the IL-6-binding but did abolish the IL-6 signalling capability of sIL-6R, were identified and found to be located mainly in the membrane proximal half of the second barrel. sIL-6R mutants carrying such substitutions lacked the capacity to associate with gp130 in the presence of IL-6.

Amino Acid Sequence↗

PubMed1993

Effects of magnesium on isolated canine coronary arterial tension.

The effects of magnesium on the tension of isolated canine coronary arterial strips were studied. In the solution containing K+ of 20 mEq.l(-1), Ca2+ of 4 mEq.l(-1), and Na+ of 127 mEq.l(-1), the tension was 811 +/- 111 mg with Mg2+ of 1 mEq.l(-1), 494 +/- 135 mg with Mg2+ of 10 mEq.l(-1), 272 +/- 126 mg with Mg2+ of 20 mEq.l(-1), -52 +/- 63 mg with Mg2+ of 30 mEq.l(-1), -69 +/- 80 mg with Mg2+ of 40 mEq.l(-1). In the solution containing K+ of 20 mEq.l(-1), Na+ of 12 mEq.l(-1) and Ca2+ of 0 mEq.l(-1), the tension was 102 +/- 22 mg with Mg2+ of 1 mEq.l(-1), 3 +/- 35 mg with Mg2+ of 10 mEq.l(-1), -49 +/- 33 mg with Mg2+ of 20 mEq.l(-1), -59 +/- 49 mg with Mg2+ of 30 mEq.l(-1), -65 +/- 54 mg with Mg2+ of 40 mEq.l(-1). The data demonstrated that Mg2+ above 30 mEq.l(-1) inhibited the increase in tension caused by Ca2+ and Mg2+ above 20 mEq.l(-1) inhibited the increase in tension caused by low Na+ concentration.

Journal Article↗

PubMed1993

Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.

The activity of c-Jun is regulated by phosphorylation. Various stimuli including transforming oncogenes and UV light, induce phosphorylation of serines 63 and 73 in the amino-terminal activation domain of c-Jun and thereby potentiate its trans-activation function. We identified a serine/threonine kinase whose activity is stimulated by the same signals that stimulate the amino-terminal phosphorylation of c-Jun. This novel c-Jun amino-terminal kinase (JNK), whose major form is 46 kD, binds to a specific region within the c-Jun trans-activation domain and phosphorylates serines 63 and 73. Phosphorylation results in dissociation of the c-Jun-JNK complex. Mutations that disrupt the kinase-binding site attenuate the response of c-Jun to Ha-Ras and UV. Therefore the binding of JNK to c-Jun is of regulatory importance and suggests a mechanism through which protein kinase cascades can specifically modulate the activity of distinct nuclear targets.

3T3 Cells↗

PubMed1992

Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo.

The IL-6R system comprises two functionally different chains: a ligand binding-chain (IL-6R) and a non-ligand-binding but signal-transducing chain (gp130). gp130 associates with the IL-6-IL-6R complex, resulting in the formation of high-affinity IL-6 binding sites, and transduces the signal. A cDNA for murine gp130 has been cloned from the cDNA library of murine macrophages by using a human gp130 cDNA as a probe. The overall homology with human gp130 was 76.8% at the protein level. The extracellular region of murine gp130, as observed in human gp130, comprises 6 U of a fibronectin type III module and part of this region of approximately 200 amino acids has typical features of a cytokine receptor family. Cloned murine gp130 could transduce the growth signal in a murine IL-3-dependent cell line in response to a complex of IL-6 and soluble IL-6R. Two species of murine gp130 mRNA (7 and 10 kb) were expressed in almost all the cell lines. These transcripts were also ubiquitously expressed in murine tissues, embryonic stem cells, and embryos as early as day 6 of gestation. Administration of IL-6 in mouse caused up-regulation of the gp130 mRNA levels in several tissues. Both gp130 and IL-6R mRNA in liver were up-regulated in vivo by IL-6.

Amino Acid Sequence↗

PubMed1992

The molecular biology of interleukin 6 and its receptor.

Functional pleiotropy and redundancy are characteristic features of cytokines. Interleukin 6 (IL-6) is a typical example: IL-6 induces cellular differentiation or expression of tissue-specific genes; it is involved in processes such as antibody production in B cells, acute-phase protein synthesis in hepatocytes, megakaryocyte maturation, cytotoxic T cell differentiation, and neural differentiation of PC12 (pheochromocytoma) cells. It promotes growth of myeloma/plasmacytoma cells, T cells, keratinocytes and renal mesangial cells, and it inhibits growth of myeloid leukaemic cell lines and certain carcinoma cell lines. The IL-6 receptor consists of two polypeptide chains, a ligand-binding chain (IL-6R) and a non-ligand-binding, signal-transducing chain (gp130). Interaction of IL-6 with IL-6R triggers the association of gp130 and IL-6R, and the signal can be transduced through gp130. Association of gp130 with IL-6R is involved in the formation of high affinity binding sites. This two-chain model has been shown to be applicable to receptor systems for several other cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, IL-5 and nerve growth factor (NGF). The pleiotropy and redundancy of cytokines may be explained on the basis of this unique receptor system.

Animals↗

PubMed1992

Regulation of IL-6 receptor and gp130 expression on human cell lines of lymphoid and myeloid origin.

The expression of 80 kDa interleukin-6 receptor (IL-6R) and the associated molecule gp130 has been studied on human cell lines by FACS- and Northern blot analysis. The effects of dexamethasone, dibutyric-(DB)-cAMP and phorbol-12-myristate-13-acetate (TPA) have been studied on plasmacytoma cell line U266, B cell line BMNH and monocytoid cell line U937. Our data show a definite downregulation of IL-6R and gp130 expression by TPA in U266 and BMNH at both mRNA and cell surface protein levels. In U937 TPA inhibits only the IL-6R expression, without affecting that of gp130. DB-cAMP decreases the expression of both proteins in U937, slightly inhibits the IL-6R expression in U266, but is uneffective in BMNH. Dexamethasone induces considerable upregulation of gp130 only in U266. Our findings suggest separate regulation of IL-6R and gp130 on U266, BMNH and U937 cell lines.

Antigens, CD↗