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Koji Inoue

Publications and source records attributed to Koji Inoue.

At least 37 records · Page 2Linked to original sources
PubMed2005

Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9.

The granuloma is a host defence response to persistent pathogenic irritants. In the process of granuloma formation, the activation, migration, and fusion of macrophages occur locally, but the mechanisms involved remain elusive. Tetraspanins regulate cell migration and fusion by organizing functional molecular complexes in membrane microdomains. Here we investigated the role of tetraspanin CD9 in hepatic granuloma formation. Immunostaining of the liver of untreated wild-type mice showed that CD9 was expressed by vascular endothelial cells and perivenular hepatocytes. When intrahepatic granulomas were induced by intravenous injection of Propionibacterium acnes, hepatocyte CD9 was extensively upregulated, while inflammatory cells constituting granulomas were mostly negative for CD9. Compared with wild-type littermates, CD9-knockout mice showed dissemination of Propionibacterium acnes and reduced number and size of granulomas after the injection. Moreover, production of granuloma-inducing cytokines, TNF-alpha and IFN-gamma, was delayed and chemotactic activity for macrophages was suppressed in the liver of mutant mice. These results suggest that CD9 is one of the proteins that promotes granuloma formation in the liver.

Animals↗
PubMed2005

Reversible ventricular dysfunction takotsubo cardiomyopathy.

BACKGROUND: Recently, many cardiologists have recognized the existence of a rapidly reversible form of heart failure of unknown origin characterized by a takotsubo-shaped, dyskinetic left ventricle on left ventriculography. AIM: To determine the detailed clinical features of takotsubo cardiomyopathy. METHODS: Thirteen elderly patients (11 women and 2 men with a mean age of 75.3 years) who had normal coronary arteries and takotsubo-like left ventricular dysfunction were prospectively enrolled in this study. RESULTS: Cardiac enzymes did not increase significantly, but the mean plasma norepinephrine level was very high on admission (0.98 microg/l). Coronary angiography revealed normal coronary arteries in all patients, but left ventriculography showed apical akinesis combined with basal hyperkinesis, i.e., a takotsubo (Japanese octopus fishing pot)-shaped ventricle. Left ventricular wall motion normalized within a mean of 16.9 hospital days in 12 patients, but 1 patient died of acute renal failure on hospital day 7. Cardiac events did not recur during a follow-up period of 0.5 to 5 years. CONCLUSION: Takotsubo cardiomyopathy seems to be a new type of acute heart failure, which generally has a good prognosis and does not recur. Myocardial damage by catecholamine overload, adrenoceptor hypersensitivity, and changes of catecholamine dynamics due to stress may cause this condition.

Aged↗
PubMed2005

Relationship between exercise intolerance and levels of neurohormonal factors and proinflammatory cytokines in patients with stable chronic heart failure.

We investigated the correlations between exercise intolerance and the plasma levels of neurohormonal factors and proinflammatory cytokines in chronic heart failure (CHF) patients. Sixty-two CHF patients who underwent cardiopulmonary exercise testing (CPX) were enrolled in this study. Peak oxygen uptake (peak VO2) and the plasma concentrations of noradrenaline (NA), brain natriuretic peptide (BNP), and soluble tumor necrosis factor receptors I and II (TNFR-I and -II) were all measured during the CPX. The patients were divided into three groups according to their peak VO2; a severe exercise intolerance group (severe group; peak VO2 < 18 mL/min/kg), moderate exercise intolerance group (moderate group; 18 24). There were no significant differences in left ventricular ejection fraction (EF) among the three groups. NA and BNP both increased gradually in parallel with the worsening of exercise intolerance (NA, 211.5 +/- 75.7 pg/mL, 331.8 +/- 163.7, 441.9 +/- 202.9, respectively; BNP, 37.9 +/- 25.4 pg/mL, 148.9 +/- 117.1, 247.9 +/- 150.0, respectively). TNFR-I and II were significantly higher in the severe group than in the moderate group (1746.1 +/- 950.7 versus 1085.2 +/- 370.5 pg/mL and 2855.3 +/- 1550.9 versus 2047.7 +/- 648.7 pg/mL, respectively), while the values in the moderate group were not significantly different from those in the mild group. EF showed no significant correlations with NA, BNP, TNFR-I, or TNFR-II, whereas peak VO2 exhibited significant negative correlations with NA (r = -0.50, P < 0.0001), BNP (r = -0.53, P < 0.0001), TNFR-I (r = -0.50, P < 0.0001), and TNFR-II (r = -0.45, P < 0.0001). It is concluded that NA and BNP rise in parallel with the degree of exercise intolerance, while TNFR-I and -II rise only when exercise intolerance reaches severe levels.

Aged↗
PubMed2004

Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide.

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6-/-) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6-/- slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.

Animals↗
PubMed2004

Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator.

We have identified cDNA encoding a new member of the adrenomedullin (AM) family, AM2, for the first time in mammals (mouse, rat and human). The predicted precursor carried mature AM2 in the C-terminus, which had an intramolecular ring formed by an S-S bond and a possibly amidated C-terminus. Phylogenetic analyses clustered AM2 and AM into two distinct but closely related groups. Similarity of exon-intron structure and synteny of neighboring genes showed that mammalian AM2 is an ortholog of pufferfish AM2 and a paralog of mammalian AM. AM2 mRNA was expressed in submaxillary gland, kidney, stomach, ovary, lymphoid tissues and pancreas of mice, but not in adrenal and testis. Intravenous injection of synthetic mature AM2 decreased arterial pressure more potently than AM, and induced antidiuresis and antinatriuresis in mice. These results show that at least two peptides, AM and AM2, comprise an adrenomedullin family in mammals, and that AM2 may play pivotal roles in cardiovascular and body fluid regulation.

Adrenomedullin↗
PubMed2004

[Testicular cancer with inferior vena caval embolus causing pulmonary embolism following chemotherapy: a case report].

A 21-year-old male presented with right scrotal discomfort. Right high orchiectomy revealed non-seminoma and he was diagnosed with stage I non-seminoma. Since acute myeloid leukemia (AML) was diagnosed incidentally, no adjuvant therapy was given and he received chemotherapy for AML. One year later, he complained of lumbago and general malaise. Complete remission of AML had been achieved and bone marrow puncture revealed no signs of recurrence. Computed tomography showed retroperitoneal lymph node swelling, inferior vena caval embolus distal to the hepatic vein, and multiple lung nodules. Metastasis of testicular neoplasm was suspected and chemotherapy with Bleomycin, Etoposide, and Cisplatin was started. On the fourth day of chemotherapy, the patient complained of sudden dyspnea and acutely went into shock. Pulmonary embolism was diagnosed and an inferior vena cava filter was placed. Chemotherapy was continued for four courses and the tumor showed complete remission. He has been free of disease for 24 months. In rare cases of testicular cancer with inferior vena caval embolus, the physician should be aware of the possibility of causing pulmonary embolism after chemotherapy.

Acute Disease↗
PubMed2003

Identification of a novel adrenomedullin gene family in teleost fish.

Adrenomedullin (AM) is a multifunctional peptide known to form a hormone family with calcitonin gene-related peptide (CGRP) and amylin. We have cloned five distinct AM cDNAs from the pufferfish, Takifugu rubripes, and named them TrAM-1, -2, -3, -4, and -5. Judging from the deduced precursor sequences and processing pattern of the C-terminal mature peptides, TrAMs may be divided into at least two groups; AM-2 and -3, and AM-1, -4, and possibly -5. Phylogenetic analysis of the mature peptides, exon-intron structure of their genes, and tissue distribution of their mRNA also support this classification. TrAM-1 and -4 were ubiquitously expressed in various tissues including the kidney and interrenal (adrenal homolog) as in the case of mammalian AM, while TrAM-2 and -3 were expressed most abundantly in the brain followed by the vascular tissues. Synteny of the genes around AM gene showed that TrAM-1 is the ortholog of mammalian AM. The presence of a PAMP-like sequence in the prosegment of TrAM-1 also supports this notion. Multiple AMs were also detected in another pufferfish, Tetraodon nigroviridis, and in zebrafish, Danio rerio. The present study shows for the first time the presence of a novel AM family in teleost fish that is independent from CGRP and amylin, which further suggests the possible existence of multiple AMs in mammals.

Adrenomedullin↗
PubMed2003

Four functionally distinct C-type natriuretic peptides found in fish reveal evolutionary history of the natriuretic peptide system.

Natriuretic peptides (NPs) are major cardiovascular and osmoregulatory hormones in vertebrates. Although tetrapods generally have three subtypes, atrial NP (ANP), B-type NP (BNP), and C-type NP (CNP), some teleosts lack BNP, and sharks and hagfish have only one NP. Thus, NPs have diverged during fish evolution, possibly reflecting changes in osmoregulatory systems. In this study, we found, by cDNA cloning, four distinct CNPs (1 through 4) in the medaka (Oryzias latipes) and puffer fish (Takifugu rubripes), although to our knowledge no more than two CNPs have been isolated from a vertebrate species. Predicted mature CNP-1 was most similar, and CNP-4 was most dissimilar, to mammalian CNPs. However, synthetic CNP-4 most potently activated OlGC1, a medaka CNP-specific receptor (NPR-B) expressed in cultured cells, whereas CNP-1 and CNP-3 most activated OlGC7 and OlGC2, two medaka homologues of the ANP/BNP receptor (NPR-A), respectively. Linkage mapping in medaka followed by comparative genomic analyses among fishes and humans located four CNP genes in separate medaka chromosomes corresponding to human chromosomes 1, 2, 12, and 17. From conserved synteny, the following evolutionary history of NPs was evoked: (i) four CNP genes were generated by chromosomal duplications before the divergence of elasmobranchs; (ii) the CNP-3 gene generated ANP and BNP genes through tandem duplication before the divergence of tetrapods and teleosts; (iii) CNP-1 and -2 genes were retained in the teleost lineage but not in the tetrapod lineage; (iv) the CNP-3 gene disappeared from the tetrapod lineage after divergence of amphibians; and (v) the CNP-4 gene is retained in humans as CNP.

Amino Acid Sequence↗
PubMed2003

A novel guanylin family (guanylin, uroguanylin, and renoguanylin) in eels: possible osmoregulatory hormones in intestine and kidney.

As the intestine is an essential organ for fish osmoregulation, the intestinal hormone guanylins may perform major functions, especially in euryhaline fish such as eels and salmonids. From the intestine of an eel, we identified cDNAs encoding three distinct guanylin-like peptides. Based on the sequence of mature peptide and sites of production, we named them guanylin, uroguanylin, and renoguanylin. Renoguanylin is a novel peptide that possesses the characteristics of both guanylin and uroguanylin and was abundantly expressed in the kidney. By immunohistochemistry, guanylin was localized exclusively in goblet cells, but not enterochromaffin cells, of the intestine. After transfer of eels from fresh water to seawater, mRNA expression of guanylin and uroguanylin did not change for 3 h, but it increased after 24 h. The increase was profound (2-6-fold) after adaptation to seawater. The expression of uroguanylin was also up-regulated in the kidney of seawater-adapted eels, but that of renoguanylin was not so prominent as other guanylins in both intestine and kidney. Collectively, the novel eel guanylin family appears to have important functions for seawater adaptation, particularly long-term adaptation. Eel guanylin may be secreted from goblet cells into the lumen with mucus in response to increased luminal osmolality and act on the epithelium to regulate water and salt absorption.

Amino Acid Sequence↗
PubMed2003

C-type natriuretic peptide of rainbow trout (Oncorhynchus mykiss): primary structure and vasorelaxant activities.

Natriuretic peptides (NPs) play important roles in osmoregulatory and cardiovascular systems of vertebrates. For functional studies of NPs, rainbow trout (Oncorhynchus mykiss), a euryhaline fish, is an interesting model. The information on homologous NPs of salmonid fish is, however, still incomplete with respect to C-type NP (CNP). In this study, we isolated cDNAs encoding the precursor of CNP from the brain of trout. Predicted mature CNP (CNP-22) sequence was identical to that of killifish Fundulus heteroclitus, and only one amino acid was different from that of the eel Anguilla japonica, demonstrating a greater conservation among different teleost species than is found with atrial NP (ANP) and ventricular NP (VNP). While the preprosegment of trout CNP retained 57% similarity to the eel sequence, similarities were low to those of sharks and tetrapods. The major site of expression identified by RT-PCR was the brain with minor expression in the atrium. The putative mature CNP-22 was synthesized and its biological activity was compared with other trout NPs (ANP and VNP) using trout ventral aorta, efferent branchial and celiacomesenteric arteries and anterior cardinal vein in vitro. Synthetic trout CNP-22 relaxed all pre-contracted vessels with potencies comparable to trout ANP and VNP.

Amino Acid Sequence↗
PubMed2003

Codon 64 of K-ras gene mutation pattern in hepatocellular carcinomas induced by bleomycin and 1-nitropyrene in A/J mice.

Bleomycin is a radiomimetic antitumor agent with unique genotoxic properties. 1-nitropyrene is an environmental mutagen and carcinogen that undergoes both oxidative and reductive metabolism. In the present study, hepatocellular carcinomas were induced in male A/J mice by the intraperitoneal injection of bleomycin (120 mg/kg) followed by the intraperitoneal administration of 1-nitropyrene (total dose: 1,575 mg/kg). In order to understand the mechanism by which these two compounds induce hepatocellular carcinomas, the incidence and spectrum of mutations in the K-ras proto-oncogene in these hepatocellular carcinomas were analyzed. The hepatocellular carcinomas were induced by the administration of bleomycin and 1-nitropyrene were evaluated for point mutations in exon 1 and exon 2 of the K-ras gene by the polymerase chain reaction and a sequencing analysis. No mutation was found in the hotspots regions of the K-ras gene codon 12, 13, or 61. However, the codon 64 of the K-ras gene mutation was identified in 10 of 10 (100%) hepatocellular carcinomas. All mutations showed the same pattern, which was TAC-CAC transition. Codon 64 of the K-ras gene mutation may thus play an important role in the induction of hepatocellular carcinomas by bleomycin in the existence of 1-nitropyrene. As far as we know, this is the first report of a codon 64 mutation in the K-ras gene in a chemically induced tumor.

Animals↗
PubMed2003

Growth hormone and insulin-like growth factor I of a Euryhaline fish Cottus kazika: cDNA cloning and expression after seawater acclimation.

The four-spine sculpin Cottus kazika is a euryhaline teleost, in which faster growth in seawater (SW) and freshwater (FW) has been reported. In this study, cDNA clones encoding growth hormone (GH) and insulin-like growth factor I (IGF-I) were isolated from this species to examine the involvement of the GH/IGF-I axis in osmotic adaptation. The amino acid sequence of GH predicted from cDNA was highly similar to those of other fish species, 92% to Sparus aurata, 67% to Paralichthys olivaceus, and 63% to Oncorhynchus keta. The predicted sequence of IGF-I was also exhibited high similarity to those of other fishes, 97% to Myxocephalus scorpius, 95% to P. olivaceus, and 81% to O. keta. Tissue distribution of GH and IGF-I mRNA in fish reared in FW and SW was examined by reverse transcription-polymerase chain reaction (RT-PCR). The GH mRNA was detected only in the pituitary gland. The major site of IGF-I mRNA expression was the liver while minor signals were detected in various tissues including the pituitary, gill, fin, heart, spleen, intestine, and kidney. The expression level of GH mRNA in the pituitary was not different between FW- and SW-reared fish. However, the level of IGF-I mRNA in the liver of SW-reared fish was significantly higher than that of FW-reared fish. These results suggest the possible involvement of hepatic IGF-I in SW adaptation of this species.

Adaptation, Physiological↗
PubMed2003

Asian medaka fishes offer new models for studying mechanisms of seawater adaptation.

Japanese medaka (Oryzias latipes) is a freshwater (FW) teleost that is popular throughout the world for laboratory use. In this paper, we discuss the utility of Japanese medaka and related species for studying mechanisms of seawater (SW) adaptation. In addition to general advantages as an experimental animal such as their daily spawning activity, transparency of embryos, short generation time and established transgenic techniques, Japanese medaka have some adaptability to SW unlike the strictly stenohaline zebrafish (Danio rerio). Since other species in the genus Oryzias exhibit different degrees of adaptability to SW, comparative studies between Japanese medaka, where molecular-biological and genetic information is abundant, and other Oryzias species are expected to present varying approaches to solving the problems of SW adaptation. We introduce some examples of interspecies comparison for SW adaptabilities both in adult fish and in embryos. Oryzias species are good models for evolutionary, ecological and zoogeographical studies and a relationship between SW adaptability and geographic distribution has been suggested. Medaka fishes may thus deliver new insights into our understanding of how fish have expanded their distribution to a wide variety of osmotic environments.

Adaptation, Physiological↗
PubMed2003

Steroidogenic acute regulatory protein in eels: cDNA cloning and effects of ACTH and seawater transfer on its mRNA expression.

Steroidogenic acute regulatory protein (StAR) is a key molecule for steroid production by translocating cholesterol from the outer to inner mitochondrial membrane. Two cDNAs of different length encoding StAR was cloned from the head kidney of the eel (Anguilla japonica). In the 3'-untranslated region (UTR) of the longer cDNA, two putative polyadenylation signals were found. The shorter one differed from the longer one solely by the lack of middle of 3'-UTR including the first polyadenylation signal. Reverse transcription-polymerase chain reaction (RT-PCR) that differentiates the two mRNAs showed that the ratio of the two was highly variable among individuals, and no preferential expression was detected between freshwater and seawater eels. The predicted protein consists of 285 amino acid residues with 64-83% identity to other StARs thus far obtained. RT-PCR analyses revealed that eel StAR mRNA was expressed abundantly in the head kidney and gonad, and faintly in the brain; but no expression was detected in the gill, heart, liver, intestine, kidney and skeletal muscle. Plasma cortisol concentration increased, but StAR mRNA content in the head kidney did not change, 3 and 24 h after transfer of freshwater eels to seawater, indicating that the transcriptional regulation of StAR may not be involved in cortisol production after seawater transfer. However, ACTH elevated both plasma cortisol and StAR mRNA levels in the head kidney 1.5 and 4.5 h after injection. Thus, the steroidogenic effect of ACTH is mediated by increased StAR production as observed in mammals.

Adaptation, Physiological↗
PubMed2003

A transgene and its expression profile are stably transmitted to offspring in transgenic medaka generated by the particle gun method.

A particle gun is used in a potential method for introducing foreign genes into fish. In this paper, we report on the stable transmission of a transgene and its expression profile of the F4 generation in the transgenic medaka (Oryzias latipes). We established four transgenic strains, which contained a green fluorescent protein (GFP) gene controlled by a medaka beta-actin promoter, using a particle gun. One more transgenic strain was also generated by microinjection for comparison. In all five strains, the founder was discovered to be mosaic for the transgene. However, from the F1 to F4 generations, transgenes and their expression profiles were stably inherited in the Mendelian manner. The expression profile was common among the five strains regardless of the method for gene transfer: GFP fluorescence became detectable at an early neurula stage. In this stage, the fluorescence was observed ubiquitously in most tissues. As somite developed, GFP fluorescence became intense only in the skeletal muscle and lens but it decreased in other tissues. In adult fish, an intense fluorescence was restricted in the skeletal muscle and lens, while a considerably weak fluorescence was observed in the brain, gill, heart, kidney, spleen, and ovary. From these results, it was concluded that the transgene and its expression profile were stably transmitted to offspring, and thus the particle gun is an effective method for transgenesis in spite of its easiness.

Actins↗
PubMed2002

Coordination-position isomeric M(II)Cu(II) and Cu(II)M(II) (M = Co, Ni, Zn) complexes derived from macrocyclic compartmental ligands.

The dinucleating macrocyclic ligands (L(2;2))(2-) and (L(2;3))(2-), comprised of two 2-[(N-methylamino)methyl]-6-(iminomethyl)-4-bromophenolate entities combined by the -(CH(2))(2)- chain between the two aminic nitrogen atoms and by the -(CH(2))(2)- or -(CH(2))(3)- chain between the two iminic nitrogen atoms, have afforded the following M(II)Cu(II) complexes: [CoCu(L(2;2))](ClO(4))(2).MeCN (1A), [NiCu(L(2;2))](ClO(4))(2) (2A), [ZnCu(L(2;2))](ClO(4))(2).0.5MeCN.EtOH (3A), [CoCu(L(2;3))(MeCN)(2-PrOH)](ClO(4))(2) (4A), [NiCu(L(2;3))](ClO(4))(2) (5A), and [ZnCu(L(2;3))](ClO(4))(2).1.5DMF (6A). [CoCu(L(2;2))(MeCN)(3)](ClO(4))(2) (1A') crystallizes in the monoclinic space group P2(1)/n, a = 11.691(2) A, b = 18.572(3) A, c = 17.058(3) A, beta= 91.18(2) degrees, V = 3703(1) A(3), and Z = 4. [NiCu(L(2;2))(DMF)(2)](ClO(4))(2) (2A') crystallizes in the triclinic space group P(-)1, a = 11.260(2) A, b = 16.359(6) A, c = 10.853(4) A, alpha= 96.98(3) degrees, beta= 91.18(2) degrees, gamma= 75.20(2) degrees, V = 1917(1) A(3), and Z = 2. 4A crystallizes in the monoclinic space group P2(1)/c, a = 15.064(8) A, b = 11.434(5) A, c = 21.352(5) A, beta= 95.83(2)degrees, V = 3659(2) A(3), and Z = 4. The X-ray crystallographic results demonstrate the M(II) to reside in the N(amine)(2)O(2) site and the Cu(II) in the N(imine)(2)O(2) site. The complexes 1-6 are regarded to be isomeric with [CuCo(L(2;2)))](ClO(4))(2).DMF (1B), [CuNi(L(2;2)))](ClO(4))(2).DMF.MeOH (2B), [CuZn(L(2;2)))](ClO(4))(2).H(2)O (3B)), [CuCo(L(2;3)))](ClO(4))(2).2H(2)O (4B), [CuNi(L(2;3)))](ClO(4))(2) (5B), and [CuZn(L(2;3)))](ClO(4))(2).H(2)O (6B) reported previously, when we ignore exogenous donating and solvating molecules. The isomeric M(II)Cu(II) and Cu(II)M(II) complexes are differentiated by X-ray structural, magnetic, visible spectroscopic, and electrochemical studies. The two isomeric forms are significantly stabilized by the "macrocyclic effect" of the ligands, but 1A is converted into 1B on an electrode, and 2A is converted into 2B at elevated temperature.

Journal Article↗
PubMed2002

Dilatation of cerebral parenchymal vessels mediated by angiotensin type 1 receptor in cats.

We report the effects of angiotensin II (ANG-II), as well as angiotensin II type 1 (AT1) and type 2 receptor antagonists (CV-11974 and PD-123319, respectively) on the cerebral parenchymal microvessels in cats using the photoelectric method. ANG-II continuously and dose-dependently increased the cerebral blood volume (CBV) for 15 min. Maximum CBV increases were +0.36+or-0.11 vol% for 0.01 nmol/kg (P<0.05), +0.51+or-0.24 vol% for 0.1 nmol/kg (P<0.05), +1.87+or-0.55 vol% for 1 nmol/kg (P<0.05), and +2.14+or-0.77 vol% for 10 nmol/kg (P<0.05). Systemic arterial blood pressure increased at only 1 min following ANG-II infusion (1 and 10 nmol/kg). CV-11974 and PD-123319 per se did not change the resting CBV. CV-11974 completely inhibited the vasodilatory action of ANG-II, however, PD-123319 did not block it. We conclude that ANG-II directly dilates the parenchymal vessels through the AT1 receptor without increasing systemic blood pressure, and that intrinsic ANG-II may not be associated with maintenance of resting vascular tone.

Angiotensin II↗