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Biomedical subjects

M Koyanagi

Publications and source records attributed to M Koyanagi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ancient gene duplication and domain shuffling in the animal cyclic nucleotide phosphodiesterase family.

The animal cyclic nucleotide phosphodiesterases (PDEs) comprise at least seven subtypes, PDE1-7, which differ from each other in domain organization and primary function, and they diverged from an ancestral gene by gene duplication and domain shuffling during animal evolution. To obtain rough estimates for the divergence times of these subtypes, cloning of PDE cDNAs from Ephydatia fluviatilis (freshwater sponge) by RT-PCR was carried out. We obtained four cDNAs, EFPDE1, EFPDE2, EFPDE3, and EFPDE4, which are possibly homologs of the vertebrate PDE1, PDE2, PDE3, and PDE4, respectively, judging from the sequence similarity, domain organization, and branching pattern in the phylogenetic tree. The phylogenetic tree of the PDE family revealed that most gene duplications and domain shufflings that gave rise to different subtypes had been completed in the early evolution of animals before the separation of sponges and eumetazoans.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Angina pectoris caused by coronary microvascular spasm.

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.

Acetylcholine↗
PubMed1998

Sponge Pax cDNA related to Pax-2/5/8 and ancient gene duplications in the Pax family.

Members of the Pax gene family encode transcription factors containing a DNA-binding paired domain which is involved in developmental control and the formation of the central nervous system (CNS). The family members are classified into six classes or subfamilies, depending on the presence or absence of paired-type homeobox and octapeptide. To obtain rough estimates of times when the different classes of the Pax family diverged by gene duplication, we cloned and sequenced a Pax-related cDNA, sPax-2/5/8, from Ephydatia fluviatilis, a freshwater sponge, which encodes a paired-type homeobox and an octapeptide, in addition to a paired domain. A phylogenetic tree based on the paired domain sequences suggest that sPax-2/5/8 is a homologue of vertebrate Pax-2/5/8. It was also suggested that the majority of gene duplications that gave rise to distinct classes has been completed in the very early evolution of animals before the parazoan-eumetazoan split. Long after the ancient gene duplications, further gene duplications that gave rise to members in each subfamily occurred on the chordate lineages and completed before the fish-tetrapod split. This suggests that the major classes of the Pax genes involved in the formation of CNS characteristic of triploblasts had already existed long before the Cambrian explosion of triploblasts, and there is no direct link between the creation of new genes with novel functions and the Cambrian explosion. The pattern of gene diversification found in the Pax family is similar to those in five gene families involved in the signal transduction analyzed by us. Furthermore, the evolutionary rates of the Pax proteins have been shown to decrease with increasing organismal complexity during animal evolution.

Amino Acid Sequence↗
PubMed1998

Effect of PAF receptor antagonists on adrenocortical secretion induced by ACTH in normal and athymic nude mice.

The effect of SM12502 and CV6209, platelet-activating factor (PAF) receptor antagonists on corticosterone (B) secretion induced by ACTH was examined in the perfused adrenals of CD1 ICR (normal) and CD1 ICR nu/nu (athymic) mice. Bilateral adrenals were perfused in situ with an artificial medium equilibrated by 95% O2 + 5% CO2. Continuous infusion of 10 microM SM12502 or CV6209 inhibited the B response to 100 pg/ml ACTH markedly in normal mice but insignificantly in athymic mice. Infusion of PAF did not significantly affect B secretion in either normal or athymic mice. Administration of 0.1 microM of N-methylcarbamyl PAF, a nonmetabolizable PAF agonist, significantly increased B secretion in normal mice, but not in athymic mice. Infusion of SM12502 significantly depressed the B response to 10 microM forskolin or 1 mM dibutyryl cyclicAMP (cAMP) in normal mice, but not in athymic mice. The results indicate that endogenous PAF and its receptor may play a role in the ACTH-initiated signaling pathway at the phase after responsiveness to cAMP and its receptor may have little function in athymic mice.

Adrenal Cortex↗
PubMed1998

Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels.

We recently showed that chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (alpha-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP-1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later-stage structural changes observed in rat hearts.

Animals↗
PubMed1998

Early induction of transforming growth factor-beta via angiotensin II type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats.

We previously reported that the chronic inhibition of nitric oxide (NO) synthesis increases cardiac tissue angiotensin-converting enzyme expression and causes cardiac fibrosis in rats. However, the mechanisms are not known. Transforming growth factor-beta (TGF-beta) is a key molecule that is responsible for tissue fibrosis. The present study investigated the role of TGF-beta in the pathogenesis of cardiac fibrosis. The development of cardiac fibrosis by oral administration of the NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) to normal rats was preceded by increases in mRNA levels of cardiac TGF-beta1 and extracellular matrix (ECM) proteins. TGF-beta immunoreactivity was increased in the areas of fibrosis. Treatment with a specific angiotensin II type 1 receptor antagonist, but not with hydralazine, completely prevented the L-NAME-induced increases in the gene expression of TGF-beta1 and ECM proteins and also prevented cardiac fibrosis. Intraperitoneal injection of neutralizing antibody against TGF-beta did not affect the L-NAME-induced increase in TGF-beta1 mRNA levels but prevented an increase in the mRNA levels of ECM protein. These results suggest that the early induction of TGF-beta1 via the angiotensin II type 1 receptor plays a major role in the development of cardiac fibrosis in this model.

Administration, Oral↗
PubMed1998

[Eosinophilic meningoencephalitis in a case of rheumatoid arthritis].

A 56-year-old man was admitted to our hospital due to gradually developing consciousness disturbance. He had an 11-year history of sero-negative rheumatoid arthritis (Stage III) maintained by daily administration of 10 mg of prednisolone and 300 mg of actarit. On admission, he showed meningeal irritation and a marked increase in eosinophils in his cerebrospinal fulid (CSF) (457/microliter), while eosinophils in his peripheral blood were not increased (0/microliter). Shortly after admission he fell into a coma. Upon measurement in the coma state, his peripheral blood eosinophil count was found to be increased (max: 1742/microliter). Parasitic infection, Angiostrongylus cantonensis in particular, was excluded both by repeated microscopic examination of CSF and by immunological approaches for CSF and serum. Serum examinations showed broad cross-reaction between various parasitic antigens and positive myeloperoxdase-antineutrophil cytoplasmic antibody (18 EU/ml). Three pulses of methylprednisolone (500 mg/day) followed by conventional prednisolone therapy (60 mg/day) was effective for alleviating the signs and symptoms of eosinophilic meningoencephalitis. In this patient, it was considered that the cerebrospinal angiitis resulting in eosinophilic meningoencephalitis had been elicited by immunological abnormalities.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Intermittent divergence of the protein tyrosine kinase family during animal evolution.

The protein tyrosine kinases (PTKs) are a large protein family consisting of many subfamilies with a variety of domain structures. The basic functions are thought to differ for different subfamilies. To know the dates at which the subfamilies diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by comparing sequences from a wide range of species covering diploblasts and triploblasts. The PTK tree revealed that almost all of the gene duplications that gave rise to different subfamilies occurred rapidly before the diploblast-triploblast split, accompanying with rapid amino acid substitutions. This type of gene duplication was, however, rarely observed after that split. Long after the subfamily divergence, another type of gene duplication that gave rise to diverse tissue-specific genes occurred in each subfamily on the chordate lineage since the separation from arthropods. This type of gene duplication occurred frequently before the fish-tetrapod split, accompanying with rapid amino acid substitutions. In contrast, both the frequency of gene duplications and the rate of the amino acid substitutions were considerably reduced after that split. These results strongly suggest that the PTKs diverged intermittently, but not gradually, during animal evolution.

Amino Acids↗
PubMed1997

Cervical cord ependymoma with numerous microrosettes.

"Microrosette ependymoma," which is ependymoma with numerous microrosettes throughout the tumor, has rarely been reported. We describe an autopsy case of cervical cord ependymoma with two unusual features: the presence of numerous microrosettes and the formation of trabecular architecture. The tumor originated in the C2 segment of a man aged 23 years and gradually expanded over the following 15 years and 10 months until the entire cervical cord was involved. Beside the low grade of malignancy, the tumor cells exhibited a strong tendency to form microrosettes and trabecular architecture, which formed many perivascular pseudorosettes. The microrosettes mostly consisted of only two or a few more cells, in the absence of large rosettes. Thus the constituent cells were those forming perivascular pseudorosettes. Electron microscopy and immunohistochemistry characterized the ependymal properties of the microrosettes, whose lumina frequently contained fibril bundles similar to those of the Reissner's fiber fibrils, in addition to cilia and microvilli. The pathogenesis of the occurrence of numerous microrosettes is unknown; however, a defect in the mechanism of regulation of rosette formation and enlargement is the most likely explanation.

Adult↗
PubMed1996

[A case of inflammatory pseudotumor of the lung with suppressed immune response in the patient with renal cell carcinoma after nephrectomy and administration of interferon].

A 60-year-old man with renal cell carcinoma was treated of right nephrectomy and high dose administration of Interferon-alpha (IFN) in 1990. Three and half years after operation, he complained of cough and hemoptysis. Chest X-ray showed a abnormal shadow (5.5 x 3.5 cm) in the upper lung field. On chest CT, a tumor mass with small cavity was located at S2, attended with the speculation and pleural indentation. A rough nodule suspected daughter tumor was pointed out near the tumor mass. Laboratory investigation revealed mild leucocytosis, an elevated ESR and C reactive protein. On lymphocyte subset, CD 4/8 ratio was 0.8 and NK cell activity was 11%. Immunosuppressive acid protein (IAP) in serum was 1,137 ng/ml. No organisms or malignant cells could be demonstrated in the biopsy materials or sputum. Right thoracotomy and upper lobectomy was carried out. Postoperative pathological diagnosis was inflammatory pseudotumor. Namely, the lesion was occupied with variable admixture of lymphocytes, plasma cells, histiocytes, phagocytes included hemosiderin, foam cells and whorled fibrosis. Daughter tumor was scar tissue. Now, he is well without recurrence and his immune response is within normal level. Some discussion of the literature was mentioned.

Autoimmune Diseases↗
PubMed1995

Corticosterone secretion in response to serotonin and ACTH by perfused adrenal of normal and athymic nude mice.

Adrenocortical secretory responses to chemical mediators and ACTH in CD1 ICR nu/nu (athymic) mice were compared with those in CD1 ICR (normal) mice. The bilateral adrenals of normal or athymic mice were perfused in situ with artificial medium equilibrated by 95% O2 + 5% CO2. Infusion of serotonin induced the secretory response of corticosterone significantly at 10 nM and markedly at 100 nM and the response at 1000 or 10000 nM declined as compared with that at 100nM in normal mice. Total corticosterone secretion in response to 100 or 1000 nM serotonin in athymic mice was about one fourth that in normal mice, respectively. Corticosterone responses to ACTH at the range of 10 to 300 pg/ml in athymic mice were comparable to those in normal mice. Infusion of histamine, platelet activating factor(PAF), or compound 48/80 did not induce significant corticosterone response in both normal and athymic mice. The data suggest that the congenital defect of the thymus and/or hair causes the hyporesponsiveness of adrenocortical cells to serotonin although the adrenal cortex of athymic mice is able to perform its function in response to ACTH.

Adrenal Cortex↗
PubMed1994

Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity.

To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the involvement of apoptosis-inducing Fas molecule on the target cells and its ligand on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a CD4+ T-cell clone, BK1, could lyse the target cells expressing wild-type Fas molecule but not those expressing death signaling-deficient mutants. This indicates the involvement of Fas-mediated signal transduction in the target cell lysis by BK1. Anti-CD3-activated but not resting BK1 expressed Fas ligand as detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas ligand in the BK1 cytotoxicity. Ability to exert the Fas-mediated cytotoxicity was not confined to BK1, but splenic CD4+ T cells and, to a lesser extent, CD8+ T cells could also exert the Fas-dependent target cell lysis. This indicates that the Fas-mediated target cell lytic pathway can be generally involved in the T-cell-mediated cytotoxicity. Interestingly, CD4+ T cells prepared from gld/gld mice did not mediate the Fas-mediated cytotoxicity, indicating defective expression of functional Fas ligand in gld mice.

Animals↗
PubMed1993

The psychological and cosmetic aspects of breast conserving therapy compared with radical mastectomy.

An evaluation of the psychological and cosmetic morbidity of 31 patients who had undergone breast conserving treatment (BCT group) and 71 patients who had undergone radical mastectomy (RM group) revealed that 85% and 73%, respectively, were satisfied with their operative results. BCT appeared superior to RM in relation to body image, with 93% of the BCT group indicating BCT as a future choice of treatment, whereas only 35% of the RM group indicated RM as a future choice of treatment. For 59% of the BCT patients, the results were considered excellent or good by a physician, but fear of recurrence was frequently expressed by both groups even though an early stage of breast cancer had been significantly more common in the BCT group than the RM group. Sexual adjustment was the same in both groups. Body image was thus concluded to have been improved by BCT rather than RM, but psychological morbidity was essentially the same in both groups.

Adaptation, Psychological↗
PubMed1993

[A case report of combined aortic and mitral regurgitation associated with ankylosing spondylitis].

We reported a case of ankylosing spondylitis which successfully underwent aortic valve replacement for combined aortic and mitral regurgitation. A 42-year-old man was admitted with symptoms of shortness of breath and anginal pain. He was previously diagnosed ankylosing spondylitis by an orthopedician A grade III/VI to and fro murmur was audible at the left sternal border. Retrograde aortography revealed severe aortic regurgitation and mild mitral regurgitation. Cardiac catheterization showed moderately pulmonary hypertension and high pulmonary artery wedge pressure. He underwent aortic valve replacement with SJM prosthetic valve. His postoperative course was uneventful. In Japan, ankylosing spondylitis is rare disease, and cardiac lesions associated with these conditions is seldom met to us. The surgical problems and management of these lesions are discussed.

Adult↗
PubMed1992

CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation.

CD2 is an intercellular adhesion molecule that has been implicated in T cell activation and differentiation both in humans and mice. Although the ligand for human CD2 has been defined as LFA-3, that for murine CD2 has not been identified yet. To identify the ligand for mouse CD2, we generated a chimeric molecule consisting of the extracellular domain of mouse CD2 and human immunoglobulin (Ig)G1 Fc (mCD2Rg). A hamster monoclonal antibody (mAb), HM48-1, was established by screening mAbs that could block the binding of mCD2Rg to T cell lines at the ligand site. The putative mouse CD2 ligand recognized by this mAb was a glycosyl phosphatidylinositol-anchored glycoprotein with an apparent molecular mass of 45 kD, which were shared characteristics with human LFA-3. However, its expression was predominantly restricted to hematopoietic cells, unlike human LFA-3. Protein microsequencing analysis for the NH2-terminal 18 amino acid residues of the affinity-purified HM48-1 antigen revealed that it is almost identical with mouse CD48. This identity was further confirmed by the reactivity of HM48-1 with a soluble recombinant CD48 (sCD48) protein and the molecule recognized by a rat mAb raised against sCD48. A rat anti-CD48 mAb blocked the mCD2Rg binding as well as HM48-1. Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand. Finally, like anti-CD2 mAb, HM48-1 inhibited the phytohemagglutinin response and, when crosslinked, augmented the anti-CD3 response of splenic T cells. These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation.

Animals↗