Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 55 records · Page 3Linked to original sources

PubMed2001

Role of oxidized LDL in atherosclerosis.

A critical event in the early stages of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, localized attachment of circulating monocytes to arterial endothelial cells appeared to precede the formation of foam cells. It is suggested that monocyte recruitment into early lesions depends on the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1, and P-selectin, that can support the adhesion of monocytes and lymphocytes. Moreover, oxidized LDL, lysophosphatidyl-choline, and oxidized fatty acids induce the expression not only of these adhesion molecules but also of scavenger receptors, such as CD-36, SR-A, and LOX-1. Recently, we isolated and characterized the novel receptors for oxidized LDL, namely, LOX-1 and SR-PSOX. Expression of LOX-1 is found on endothelial cells, smooth muscle cells, and macrophages, whereas SR-PSOX is expressed on macrophages. In this paper the significance of oxidized LDL and its receptors, LOX-1 and SR-PSOX, in terms of atherogenesis is discussed.

Animals↗

PubMed2001

Peroxisome proliferator-activated receptor a ligands increase lectin-like oxidized low density lipoprotein receptor-1 expression in vascular endothelial cells.

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a receptor for atherogenic oxidized LDL expressed in vascular endothelial cells, smooth muscle cells, and macrophages. Peroxiosme proliferator-activated receptors (PPARs) include subfamilies PPARalpha and PPARgamma, which are expressed in endothelial cells and involved in transcriptional regulation of a large number of genes that affect lipoprotein and fatty acid metabolism as well as inflammation. We therefore explored the effects of PPARalpha and PPARgamma ligands on expression of LOX-1. Treatment of cultured bovine aortic endothelial cells (BAECs) with PPARalpha ligands (fenofibrate and WY14643) remarkably upregulated LOX-1 expression, which was detected by western and northern blot analyses. LOX-1 promoter-reporter gene assay showed that PPARalpha ligands activate transcription of the LOX-1 gene. PPARgamma ligands, in contrast, did not significantly affect LOX-1 expression in BAECs. PPARalpha appears to be a key regulator in promoting LOX-1 expression in BAECs. Upregulated expression of LOX-1 may modulate the catabolism of oxidized LDL and atherosclerotic progression.

Animals↗

PubMed2001

Expression of scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) in human atheroma.

Recently, we identified a novel macrophage cell-surface receptor for oxidized low-density lipoprotein (Ox-LDL), designated SR-PSOX (scavenger receptor for phosphatidylserine and oxidized lipoprotein). Here we examine SR-PSOX expression in human atherosclerotic lesions using carotid endarterectomy specimens from 21 patients, directional coronary atherectomy specimens from 11 patients, and normal aortas from 2 patients. RT-PCR analysis demonstrated that SR-PSOX expression was upregulated in atherosclerotic lesions, but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was abundantly expressed by macrophages in the intima of atherosclerotic lesions. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and therefore may play important roles in human atherosclerotic lesion formation.

Arteriosclerosis↗

PubMed2001

Immune response induced by airway sensitization after influenza A virus infection depends on timing of antigen exposure in mice.

To study which phase of viral infection promotes antigen sensitization via the airway and which type of antigen-presenting cells contributes to antigen sensitization, BALB/c mice were sensitized by inhalation of ovalbumin (OA) during the acute phase or the recovery phase of influenza A virus infection, and then 3 weeks later animals were challenged with OA. The numbers of eosinophils and lymphocytes, the amounts of interleukin-4 (IL-4) and IL-5 in the bronchoalveolar lavage fluid, and the serum levels of OA-specific immunoglobulin G1 (IgG1) and IgE increased in mice sensitized during the acute phase (acute phase group), while a high level of gamma interferon production was detected in those sensitized during the recovery phase (recovery phase group). In the acute phase group, both major histocompatibility complex class II molecules and CD11c were strongly stained on the bronchial epithelium; in the recovery phase group, however, neither molecule was detected. OA-capturing dendritic cells (DCs) migrated to the regional lymph nodes, and a small number of OA-capturing macrophages were also observed in the lymph nodes of the acute phase group. In the recovery group, however, no OA-capturing DCs were detected in either the lungs or the lymph nodes, while OA-capturing macrophages were observed in the lymph nodes. These results indicate that the timing of antigen sensitization after viral infection determines the type of immune response.

Animals↗

PubMed2001

Appropriate dosing of pilsicainide hydrochloride in patients on hemodialysis.

Appropriate dosing of pilsicainide hydrochloride, an anti-arrhythmic drug excreted via the kidney, was investigated in patients on dialysis. Ten chronic hemodialysis patients with coexisting severe palpitation of supraventricular premature contractions (SVPC) were treated with 25 mg of pilsicainide hydrochloride before dialysis. All of their plasma concentrations were maintained within the therapeutic range and their mean dialysis rate was 32%. After 2 weeks, 7 patients were followed with consecutive daily dose treatment. In 3 of them, the dosage was returned to the single pre-dialysis administration because of the elevated plasma concentration reaching the toxic range 1 month after the start of administration. The dose schedule was maintained, and plasma pilsicainide concentrations remained within the therapeutic range during the 6-month follow-up. No abnormal findings were found in any parameters of electrocardiography, echocardiography or biochemistry. The number of SVPC diminished > 90% compared to the pretreatment level.

Anti-Arrhythmia Agents↗

PubMed2001

Lysophosphatidylcholine induces early growth response factor-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells.

Lysophosphatidylcholine (lyso-PC), a polar phospholipid that is increased in atherogenic lipoproteins and atherosclerotic lesions, has been shown to transcriptionally induce the expression of endothelial genes relevant to atherogenesis. In cultured bovine aortic endothelial cells (BAECs), we show that lyso-PC induces the expression of early growth response factor (Egr)-1 and thereby activates the proximal promoter of the platelet-derived growth factor (PDGF)-A chain located 55 to 71 bp upstream from the transcription start site, which has been shown to be crucial for PDGF-A chain expression induced by fluid shear stress and fibroblast growth factor-1. Northern blot analyses showed that lyso-PC (10 to 20 micromol/L) transiently (30 minutes to 1 hour) induced expression of Egr-1 mRNA. Induced expression of Egr-1 mRNA, which was associated with increased amounts of Egr-1 protein in nuclei, preceded PDGF-A chain mRNA induction in lyso-PC-activated BAECS: Nuclear runoff assay revealed that lyso-PC stimulates transcription of the Egr-1 gene. Transient transfection of the oligonucleotide corresponding to the proximal promoter of the PDGF-A chain (oligo A) linked to the luciferase reporter gene revealed that lyso-PC can activate the core promoter of the PDGF-A chain by 5-fold. Insertion of a guanine at 3 sites in the oligo A abolished the lyso-PC-induced increases in luciferase activities. Electrophoretic mobility shift assay with use of radiolabeled oligo A showed a lyso-PC-inducible shift band, which was suppressed by excess amounts of unlabeled oligo A or an anti-Egr-1 antibody. In addition, lyso-PC-induced Egr-1 expression was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase-1 (MEK1), suggesting that lyso-PC-induced expression of Egr-1 depends on the MEK1/extracellular signal-regulated kinase pathway. Taken together, transcriptional activation of Egr-1-dependent genes by this atherogenic lipid may be a key regulator of atherogenesis.

Animals↗

PubMed2001

HMG-CoA reductase inhibitors prevent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress.

In vitro and in vivo evidence of a decrease in vascular smooth muscle cell (SMC) migration induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been reported. When added to SMC cultures for 6 hours, the HMG-CoA reductase inhibitors fluvastatin, simvastatin, and pravastatin at 1 micromol/L resulted in a 48%, 50%, and 16% suppression, respectively, of human coronary SMC migration; these reductions mirrored the suppression in oxidative stress induced by 1 micromol/L lysophosphatidylcholine (lyso-PC) of 50%, 53% and 19%, respectively. The hydroxylated metabolites of fluvastatin, M(2) and M(3), at 1 micromol/L also suppressed the enhancement of SMC migration by 58% and 45% and the increase in oxidative stress induced by lyso-PC of 58% and 49%, respectively. Lyso-PC activated phospholipase D and protein kinase C (PKC), and this activation was also suppressed by HMG-CoA reductase inhibitors. The inhibition of phospholipase D and PKC was reversed by 100 micromol/L mevalonate, its isoprenoid derivative, farnesol, and geranylgeraniol but not by 10 micromol/L squalene. Antisense oligodeoxynucleotides at 5 micromol/L to PKC-alpha, but not those to the PKC-beta isoform, suppressed the lyso-PC-mediated increases in SMC migration and oxidative stress. These findings suggest that HMG-CoA reductase inhibitors have direct antimigratory effects on the vascular wall beyond their effects on plasma lipids and that they might exert such antimigratory effects via suppression of the phospholipase D- and PKC (possibly PKC-alpha)-induced increase in oxidative stress, which might in turn prevent significant coronary artery disease.

Antioxidants↗

PubMed2001

Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells.

Oxidized low density lipoprotein (Ox-LDL) induces apoptosis in vascular smooth muscle cells (VSMCs), which may increase atherosclerotic plaque instability. In this study, we examined the molecular mechanisms causing the Ox-LDL-induced apoptosis in VSMCs, especially focusing on the involvement of Bax/Bcl-2 and the lectinlike Ox-LDL receptor-1 (LOX-1). In cultured bovine aortic smooth muscle cells (BASMCs), Ox-LDL at high concentrations (>60 microg/mL) induced cell death as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA fragmentation was increased in BASMCs treated with high concentrations of Ox-LDL, indicating that the Ox-LDL-induced cell death in VSMCs was apoptosis. Ox-LDL upregulated LOX-1 expression through phosphorylation of extracellular signal-regulated kinase in BASMCs, and a neutralizing anti-LOX-1 monoclonal antibody, which can block LOX-1-mediated cellular uptake of Ox-LDL, prevented the Ox-LDL-induced apoptosis in BASMCs. This antibody also suppressed the increase in the Bax to Bcl-2 ratio induced by Ox-LDL in BASMCs. Furthermore, LOX-1 expression was well colocalized with Bax expression in the rupture-prone shoulder areas of human atherosclerotic plaques in vivo. LOX-1 may play an important role in Ox-LDL-induced apoptosis in VSMCs by modulating the Bax to Bcl-2 ratio. These molecular mechanisms may be involved in destabilization and rupture of atherosclerotic plaques.

Animals↗

PubMed2001

Calbindin d28k overexpression protects striatal neurons from transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: Increased intracellular calcium accumulation is known to potentiate ischemic injury. Whether endogenous calcium-binding proteins can attenuate this injury has not been clearly established, and existing data are conflicting. Calbindin D28K (CaBP) is one such intracellular calcium buffer. We investigated whether CaBP overexpression is neuroprotective against transient focal cerebral ischemia. METHODS: Bipromoter, replication-incompetent herpes simplex virus vectors that encoded the genes for cabp and, as a reporter gene, lacZ were used. Sprague-Dawley rats received bilateral striatal injections of viral vector 12 to 15 hours before ischemia onset. With the use of an intraluminal occluding suture, animals were subjected to 1 hour of middle cerebral artery occlusion followed by 47 hours of reperfusion. Brains were harvested and stained with X-gal (to visualize beta-galactosidase, the gene product of lacZ). The number of remaining virally transfected, X-gal-stained neurons in both the ischemic and contralateral striata were counted and expressed as the percentage of surviving neurons in the ischemic striatum relative to the contralateral nonischemic striatum. RESULTS: Striatal neuron survivorship among cabp-injected animals was 53.5+/-4.1% (n=10) versus 26.8+/-5.4% among those receiving lacZ (n=9) (mean+/-SEM; P<0.001). CONCLUSIONS: We conclude that viral vector-mediated overexpression of CaBP leads to neuroprotection in this model of central nervous system injury. This is the first demonstration that CaBP overexpression protects neurons in a focal stroke model.

Animals↗

PubMed2001

Expression of SR-PSOX, a novel cell-surface scavenger receptor for phosphatidylserine and oxidized LDL in human atherosclerotic lesions.

Receptor-mediated endocytosis of oxidized low density lipoprotein (Ox-LDL) by macrophages and the subsequent foam cell transformation in the arterial intima are key events in early atherogenesis. Recently, we have identified a novel macrophage cell-surface receptor for Ox-LDL by expression cloning from a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, designated as the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). Here, we examined SR-PSOX expression in human atherosclerotic lesions. Total cellular RNA and fresh frozen sections were prepared from human carotid endarterectomy specimens (from 21 patients) and directional coronary atherectomy specimens (from 11 patients). Fragments of human aortas of 2 patients without visible atherosclerotic lesions served as negative controls. Quantitative reverse transcription-polymerase chain reaction demonstrated that SR-PSOX mRNA expression was prominent in atherosclerotic lesions but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was predominantly expressed by lipid-laden macrophages in the intima of atherosclerotic plaques in carotid endarterectomy and directional coronary atherectomy specimens, although its expression was not detectable in normal arterial wall. Double-labeled immunohistochemistry confirmed that SR-PSOX is expressed by intimal macrophages. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and thus may play important roles in human atherosclerotic lesion formation.

Animals↗

PubMed2001

mtv shapes the activity gradient of the Dpp morphogen through regulation of thickveins.

Drosophila wings are patterned by a morphogen, Decapentaplegic (Dpp), a member of the TGFbeta superfamily, which is expressed along the anterior and posterior compartment boundary. The distribution and activity of Dpp signaling is controlled in part by the level of expression of its major type I receptor, thickveins (tkv). The level of tkv is dynamically regulated by En and Hh. We have identified a novel gene, master of thickveins (mtv), which downregulates expression of tkv in response to Hh and En. mtv expression is controlled by En and Hh, and is complementary to tkv expression. In this report, we demonstrate that mtv integrates the activities of En and Hh that shape tkv expression pattern. Thus, mtv plays a key part of regulatory mechanism that makes the activity gradient of the Dpp morphogen.

Animals↗

PubMed2001

[Cytokines and chemokines: mediators for intercellular communication in the brain].

The brain includes glial cells (astrocytes, microglia and oligodendrocytes) and endothelial cells in addition to neurons. Under some pathological conditions, it is invaded by leukocytes such as neutrophils, monocytes/macrophages and lymphocytes. Intercellular communication across these cell species is supposed to play crucial roles both in the brain functions and dysfunctions. However, the molecular basis of such intercellular communication remains unclear. We have studied the roles of cytokines and chemokines, which have been investigated as essential mediators in the immune and inflammatory systems, in intercellular communication across neurons, glial cells, endothelial cells and leukocytes. Messenger RNA expression of cytokines such as interleukin-1 beta was induced in brain microglia by i.p. injection of excitotoxin and neurostimulant, at least, partly via catecholaminergic systems. Messenger RNA of other cytokines such as leukemia inhibitory factor was induced in astrocytes. This cytokine specifically induced nociceptin mRNA in the cultured cortical neurons. Constitutive expression of some chemokines such as fractalkine and stromal cell derived factor-1 alpha was observed in the brain, suggesting that they play important roles in maintenance of brain homeostasis or determination of the patterning of neurons and/or glial cells in the developing and adult brains. Cytokines such as interleukin-1 beta and chemokines such as monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha were produced in ischemic brain and implicated in ischemic brain injury. In addition to ischemia, cytokines, chemokines and their receptors have been shown to be involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease and AIDS dementia syndrome. They are potential targets for therapeutic intervention for neurodegenerative diseases.

Animals↗

PubMed2001

Involvement of beta2-adrenergic and mu-opioid receptors in antinociception produced by intracerebroventricular administration of alpha,beta-methylene-ATP.

The present study examined what kind of receptors are involved in the antinociception produced by intracerebroventricular (i.c.v.) administration of a,beta-methylene-ATP using antagonists at adrenergic, serotonin or opioid receptors. Antinociceptive effect of alpha,beta-methylene-ATP (10 nmol/rat) was significantly attenuated by subcutaneous pretreatment with propranolol and naloxone, but not phentolamine or methysergide, at a dose of 10 mg/kg. I.c.v. pretreatment with propranolol (100 nmol/rat), butoxamine (100 nmol/rat), ICI-I 18,551 (100 nmol/rat) and naloxone (30 nmol/rat) significantly attenuated the antinociceptive effect of alpha,beta-methylene-ATP. However, i.c.v. pretreatment with atenolol (100 nmol/rat), naltrindole (30 nmol/rat) or nor-binaltorphimine (30 nmol/rat) did not show any significant effects. These results suggest that supraspinal beta2-adrenergic and mu-opioid receptors are involved in the antinociceptive effect of i.c.v. administered alpha,beta-methylene-ATP.

Adenosine Triphosphate↗

PubMed2001

Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.

Adult↗

PubMed2001

Intraductal papillary-mucinous tumor and mucinous cystic neoplasm: CT and MR findings.

Cystic lesions of the pancreas are increasingly detected by imaging at daily clinical practice. Among them mucinous cystic tumor and intradcutal papillary-mucinous tumor of the pancreas are clinically important since they are latently or overtly malignant and still have potentially good prognosis after resection. In this review article we describe history, clinicopathology and differential diagnosis of two entities, and findings and role of CT and MR imaging as well as MR cholangiopancreatography in the diagnosis and evaluation of intraductal papillary-mucinous tumor.

Adenocarcinoma, Mucinous↗

PubMed2001

Utility of ADL index for partially dependent older people: discriminating the functional level of an older population.

In the present study, the ADL index for the partially dependent older people (Demura et al., 1999) was applied to 218 bedridden (BED), 466 partially dependent (PD) and 245 independent living (IL) people in older groups. The purposes of this study were to clarify the meaning of the evaluation of this index and to examine how ADL items are useful in determining each older group. It is suggested that a perfect score with our ADL index means independent living level, and a score of zero means bedridden level. The results of discriminant analysis indicated that four items with low-difficulty, such as "eating," "going to the toilet," "tossing about in bed" and "writing," are useful in determining if the PD is becoming bedridden. While five items with high-difficulty, such as "putting on slacks," "putting on trousers," "standing up from a sitting posture," "going up stairs" and "washing the whole body," are useful in determining if the PD is becoming independent living. Furthermore, it is inferred that the possibility of falling into a bedridden situation increases when the total score is 5 or less, while the functional level is close to independent living when the total score is 13 or more. These findings make clear the meaning of the evaluation of our ADL index. Furthermore, the functional level of older population may be screened using evaluation of total and item scores of this ADL index.

Activities of Daily Living↗

PubMed2001

Spondyloarthropathies in Japan: nationwide questionnaire survey performed by the Japan Ankylosing Spondylitis Society.

OBJECTIVE: The Japan Ankylosing Spondylitis Society conducted a nationwide questionnaire survey of spondyloarthropathies (SpA) in 1990 and 1997, (1) to estimate the prevalence and incidence, and (2) to validate the criteria of Amor and the European Spondylarthropathy Study Group (ESSG) in Japan. METHODS: Japan was divided into 9 districts, to each of which a survey supervisor was assigned. According to unified criteria, each supervisor selected all the clinics and hospitals with potential for SpA patients in the district. The study population consisted of all patients with SpA seen at these institutes during a 5 year period (1985-89) for the 1st survey and a 7 year period (1990-96) for the 2nd survey. RESULTS: The 1st survey recruited 426 and the 2nd survey 638 cases, 74 of which were registered in both studies. The total number of patients with SpA identified 1985-96 was 990 (760 men, 227 women). They consisted of patients with ankylosing spondylitis (68.3%), psoriatic arthritis (12.7%), reactive arthritis (4.0%), undifferentiated SpA (5.4%), inflammatory bowel disease (2.2%), pustulosis palmaris et plantaris (4.7%), and others (polyenthesitis, etc.) (0.8%). The maximum onset number per year was 49. With the assumption that at least one-tenth of the Japanese population with SpA was recruited, incidence and prevalence were estimated not to exceed 0.48/100,000 and 9.5/100,000 person-years, respectively. The sensitivity was 84.0% for Amor criteria and 84.6 for ESSG criteria. CONCLUSION: The incidence and prevalence of SpA in Japanese were estimated to be less than 1/10 and 1/200, respectively, of those among Caucasians. The adaptability of the Amor and ESSG criteria was validated for the Japanese population.

Adult↗

PubMed2001

Heterogeneous expression of nonmuscle myosin heavy chain-B in mesangial cells of patients with Gitelman's syndrome.

AIMS: It has been suggested that angiotensin II (Ang II) promotes hypertrophy and hyperplasia of mesangial cells. Nonmuscle myosin heavy chain-B (NMHC-B) and alpha-smooth muscle (SM) actin are considered to be molecular markers for phenotypic change ofproliferative mesangial cells. One of the clinical characteristics in Gitelman's syndrome (GS) is the elevation of plasma Ang II. However, little is known about the relation between Ang II and phenotypic change of mesangial cells in patients with GS. In this report, we examined the expression of NMHC-B and alpha-SM actin in mesangial cells of two GS patients. MATERIALS AND METHODS: Plasma renin activity, and the concentrations of Ang II, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), urinary kallikrein, and 6-keto-PGF1alpha were measured. Immunohistochemical staining of NMHC-B and alpha-SM actin in mesangial cells of GS patients was also performed. RESULTS: Both cases of GS showed normal glomerular function, few histological abnormalities, and higher than normal plasma concentrations of renin and Ang II. Furthermore, one case showed a high urinary concentration of kallikrein and the expression of both NMHC-B and alpha-SM actin in mesangial cells. The other case showed a high urinary concentration of 6-keto-PGF1alpha but not kallikrein and without the expression of NMHC-B and alpha-SM actin. CONCLUSION: Not only plasma kinin-kallikrein and prostaglandins, but the renal expression of NMHC-B and alpha-SM actin may be variable in different patients with GS.

Actins↗