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Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 109 records · Page 6Linked to original sources

A dopamine-secreting pheochromocytoma.

We describe a patient with pheochromocytoma, which secretes dopamine. He was admitted to hospital because of chronic diarrhea. After surgical resection of the tumor, dramatic cessation of the diarrhea and blood pressure elevation were observed. Decreased expression of dopamine beta-hydroxylase in the tumor was considered a possible mechanism of producing a pathophysiological concentration of dopamine. This case shows that excessive excretion of dopamine, a vasodilative hormone, may affect blood pressure.

Adrenal Gland Neoplasms↗

Oxidized-LDL and atherosclerosis. Role of LOX-1.

The accumulation of substantial numbers of monocyte/macrophages and activated T lymphocytes in focal areas of the arterial intima appears to be a hallmark of atherosclerosis. Our report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherosclerotic lipoproteins, such as oxidized LDL and remnant lipoproteins in diabetic and Type 3 hyperlipidemia, can upregulate adhesion molecules for monocytes and T lymphocytes, and growth factors, such as heparin-binding epidermal growth factor-like growth factor and PDGF A and B chains. Recently, we identified the novel receptor for oxidized LDL, named LOX-1. We summarize the importance of the interaction between oxidized LDL and its receptor, LOX-1, in terms of early stage atherogenesis.

Animals↗

Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells.

Macrophages appear to take up oxidized low density lipoprotein (Ox-LDL) by multiple receptor-mediated pathways. This study, therefore, has been performed to determine if LOX-1, a novel receptor for Ox-LDL, which was identified in vascular endothelial cells, is also expressed in macrophages. Expression of LOX-1 can be induced after macrophage-like differentiation in human peripheral blood monocytes as well as THP-1 cells. Furthermore, expression of LOX-1 in macrophages is also upregulated by an inflammatory cytokine TNF-alpha, which was shown to be present in atherosclerotic arterial wall. Expression of this novel receptor LOX-1 may play an important role in Ox-LDL uptake and subsequent foam cell formation in macrophages.

Animals↗

Keratoacanthoma developing on a pigmented patch in incontinentia pigmenti.

Cutaneous manifestations of incontinentia pigmenti (IP) have classically been described as three sequential stages: an initial vesicobullous stage, a verrucous stage and a stage of swirled pigmentation. Verrucous lesions tend to last longer than vesicobullous eruptions, often persisting until 1 year of age. However, adult patients with verrucous lesions are rare. We report a case of keratoacanthoma with marked dyskeratosis on a pigmented patch in a 20-year-old woman. This tumor, like subungual keratotic tumors of IP, might have been developed as one of the late manifestations of the disease.

Adult↗

Identification of soluble forms of lectin-like oxidized LDL receptor-1.

Lectin-like oxidized LDL receptor-1 (LOX-1) is a type II membrane protein belonging to the C-type lectin family molecules, which can act as a cell-surface endocytosis receptor for atherogenic oxidized LDL. In this study, we show that soluble forms of LOX-1 are present in conditioned media of cultured bovine aortic endothelial cells (BAECs) and CHO-K1 cells stably transfected with LOX-1 cDNA. Immunoblot analysis of conditioned media from TNF-alpha-activated BAECs and CHO-K1 cells stably expressing LOX-1 revealed that soluble LOX-1 has an approximate molecular mass of 35 kDa. In TNF-alpha-activated BAECs, cell-surface expression of LOX-1 precedes soluble LOX-1 production. Cell-surface biotinylation followed by immunoprecipitation and immunoblotting showed that soluble LOX-1 in cell-conditioned media is derived from LOX-1 expressed on the cell surface. Production of soluble LOX-1 was inhibited by PMSF, suggesting that PMSF-sensitive proteases may be involved in this process. Purification of soluble LOX-1 by high-performance liquid chromatography and N-terminal amino acid sequencing of soluble LOX-1 identified the 2 cleavage sites between Arg(86)-Ser(87) and Lys(89)-Ser(90), which were located in the membrane proximal extracellular domain of LOX-1. The data demonstrate that cell-surface LOX-1 can be cleaved at 2 different sites and transformed into soluble forms. Further studies may explore therapeutic and diagnostic applications of soluble LOX-1 in atherosclerotic diseases.

Amino Acid Sequence↗

Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits.

A novel lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) was recently identified in bovine aortic endothelial cells. It is strongly suggested to have a potential role in the initiation and development of atherosclerosis. In this study, we have isolated cDNA clones encoding the rabbit homologue of LOX-1 by screening a rabbit placenta cDNA library. In amino acid sequence and domain structure organization, the rabbit LOX-1 is highly conserved with the human counterpart. Transfection of rabbit LOX-1 cDNA to HEK-293 cells confers on them the activity to bind and internalize oxidized low density lipoprotein. Rabbit LOX-1 was identified as a 45-kDa protein by Western blot analysis with a specific monoclonal antibody. Notably, analyses by reverse transcription-polymerase chain reaction and Western blot revealed that LOX-1 was accumulated in 8-week-old Watanabe heritable hyperlipidemic rabbit aortas compared with normal rabbit aortas. Immunostaining confirmed that the augmented expression of LOX-1 was primarily localized within the intima at the earliest stages of atherogenesis. The most prominent staining was in the endothelial cells of lesions. Furthermore, the distinctive staining of LOX-1 was identified in the endothelium of non-lesion areas of Watanabe heritable hyperlipidemic rabbit aortas. Taken together, these findings support the possibility that LOX-1 might be involved in the initiation of atherosclerosis.

Amino Acid Sequence↗

Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein- and lysophosphatidylcholine-induced human mesangial cell migration.

The objectives of the present study were (1) to determine whether oxidized LDL and lysophosphatidylcholine (lyso-PtdCho), a major phospholipid component of oxidized LDL, stimulate the migration of cultured human mesangial cells and (2) to investigate the possible effects on mesangial cell migration of the cardiac natriuretic peptides atrial and brain natriuretic peptide (ANP and BNP). Oxidized LDL (10 and 100 microg/mL) and lyso-PtdCho (10(-7) to 10(-5) mol/L) stimulated migration in a concentration-dependent manner. In contrast, the effects of native LDL and phosphatidylcholine were modest or nonexistent. Protein kinase C (PKC) inhibitor and downregulation of PKC activity by phorbol ester inhibited oxidized LDL- and lyso-PtdCho-induced migration. Human ANP(1-28) and human BNP-32 significantly inhibited oxidized LDL- and lyso-PtdCho-induced migration in a concentration-dependent manner. C-ANF (des-[Glu(18),Ser(19),Gly(20),Leu(21),Gly(22)]ANP(4-23)), a specific ligand for ANP clearance receptors, could not inhibit oxidized LDL- and lyso-PtdCho-induced migration. Inhibition by ANP and BNP of lyso-PtdCho-induced migration was paralleled by an increase in the cellular level of GMP. Oxidized LDL- and lyso-PtdCho-induced migrations were inhibited by 8-bromo-cGMP. The results suggest that oxidized LDL and lyso-PtdCho stimulate the migration of human mesangial cells, at least in part, through a PKC-dependent process and that ANP and BNP inhibit this stimulated migration, probably through a cGMP-dependent process.

Atrial Natriuretic Factor↗

Aldose reductase inhibitor improves insulin-mediated glucose uptake and prevents migration of human coronary artery smooth muscle cells induced by high glucose.

We examined involvement of the polyol pathway in high glucose-induced human coronary artery smooth muscle cell (SMC) migration using Boyden's chamber method. Chronic glucose treatment for 72 hours potentiated, in a concentration-dependent manner (5.6 to 22.2 mol/L), platelet-derived growth factor (PDGF) BB-mediated SMC migration. This potentiation was accompanied by an increase in PDGF BB binding, because of an increased number of PDGF-beta receptors, and this potentiation was blocked by the aldose reductase inhibitor epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited high glucose-potentiated (22.2 mmol/L), PDGF BB-mediated migration. Epalrestat at 100 nmol/L inhibited a high glucose-induced increase in the reduced/oxidized nicotinamide adenine dinucleotide ratio and membrane-bound protein kinase C (PKC) activity in SMCs. PKC inhibitors calphostin C (100 nmol/L) and chelerythrine (1 micromol/L) each inhibited high glucose-induced, PDGF BB-mediated SMC migration. High glucose-induced suppression of insulin-mediated [(3)H]-deoxyglucose uptake, which was blocked by both calphostin C (100 nmol/L) and chelerythrine (1 micromol/L), was decreased by epalrestat (100 nmol/L). Chronic high glucose treatment for 72 hours increased intracellular oxidative stress, which was directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by epalrestat (100 nmol/L). Antisense oligonucleotide to PKC-beta isoform inhibited high glucose-mediated changes in SMC migration, insulin-mediated [(3)H]-deoxyglucose uptake, and oxidative stress. These findings suggest that high glucose concentrations potentiate SMC migration in coronary artery and that the aldose reductase inhibitor epalrestat inhibits high glucose-potentiated, PDGF BB-induced SMC migration, possibly through suppression of PKC (PKC-beta), impaired insulin-mediated glucose uptake, and oxidative stress.

Aldehyde Reductase↗

[Chemokines as mediators for intercellular communication in the brain].

Chemokines constitute a large and still growing family of structurally-related small (8-10 kDa) cytokines that have chemotactic activity for leukocytes. Recently, some receptors for chemokines were reported to be used as a co-receptor by HIV at infection. In addition to their well-established role in inflammatory response and recently-reported role as a co-receptor for HIV, recent data suggest that chemokines and their receptors physiologically and pathologically play crucial roles as the mediators for intercellular communication among the cells intrinsic to and recruited into the brain; i.e., neurons, astrocytes, microglia, endothelial cells and leukocytes. Some chemokines such as SDF-1 and fractalkine are constitutively produced in the brain, implicating that they have an important role in maintenance of CNS homeostasis or determination of the patterning of neurons and/or glial cells in developing brain and normal adult brain. Chemokines such as MCP-1, MIP-1 alpha and CINC were shown to be induced by various neuroinflammatory stimuli, suggesting that they are involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, stroke and AIDS dementia syndrome. Chemokines and their receptors are potential targets for therapeutic intervention in neurodegenerative diseases.

Animals↗

Endomorphin-1 discriminates the mu-opioid receptor from the delta- and kappa-opioid receptors by recognizing the difference in multiple regions.

Endomorphin-1 is a novel endogenous peptide that is highly selective for the mu-opioid receptor over the delta- and kappa-opioid receptors. The structural basis of high selectivity of endomorphin-1 to the mu-opioid receptor was examined using chimeric receptors between mu- and delta-opioid receptors and those between mu- and kappa-opioid receptors. The chimeric receptors were constructed by using restriction enzyme sites intrinsically possessed by or introduced to the mu-, delta- and kappa-opioid receptor cDNAs. The junctions for the construction were located at the first intracellular loop (Bbs I site), third transmembrane domain (Afl III site) and fifth transmembrane domain (Bgl II site). The competitive binding assay using chimeric receptors revealed that the region from the Bbs I site to the Afl III site, including the first extracellular loop, contributes to the discrimination between mu- and delta-opioid receptors by endomorphin-1 more than any other regions. However, the region from the Afl III site to the Bgl II site and that from the Bgl II site to the carboxy terminal also somewhat contribute to the discrimination between mu- and delta-opioid receptors. For the discrimination between mu- and kappa-opioid receptors, two regions, that is, the region from the Bbs I site to the Afl III site and that from the Bgl II site to the carboxy terminal, were shown to be important. The present results show that endomorphin-1 discriminates the mu-opioid receptor from the other two types of opioid receptors by recognizing the differences in several amino acid residues widely distributed through the receptor structure. We previously reported that DAMGO, a synthetic highly mu-selective peptide, discriminates between mu- and delta-opioid receptors by recognizing the difference in only one amino acid residue and discriminates between mu- and kappa-opioid receptors by recognizing the difference in four residues localized in the restricted region. Although both endomorphin-1 and DAMGO are mu-opioid receptor selective peptides, molecular mechanisms for mu-selectivity are different between these peptides.

Animals↗

[Trends in variation within the day and between days of subjective symptoms of fatigue in adolescent males].

The purpose of this study was to clarify the trends in the variation within the day, and between days, of subjective symptoms of fatigue (SSF) in the daily life of male students. A SSF questionnaire (54 items) with guaranteed validity and reliability was administered to 104, 15-16 year-old healthy students, 3 times a day, in the morning (about 08:50), mid-day (about 12:10) and afternoon (about 16:10) for 5 days from Monday to Friday. As the main statistical analysis, two-way (day and week) ANOVA and post-hoc t tests were used. The SSF questionnaire was considered to have very high reliability because Cronbach's alpha coefficients in each survey point of time were .967-.977. SSF complaints between days were low on the whole, but complaints of drowsiness were relatively high. The trends in variation of SSF between days were greater than those within the day. The trends in variation within the day were noticeable in complaints regarding drowsiness and loss of vigor. Complaints regarding languor became high from the middle of the week to the weekend. On the other hand, SSF complaints except for languor, were high at the beginning of the week, especially on Monday and became lower after Tuesday. There is a trend in variation within the day for symptoms regarding drowsiness and loss of vigor. The trend in variation between days was confirmed for many SSFs, and was noticeable as compared to those within the day. Complaints regarding languor were high on the weekend, and SSF complaints except for languor were high at the beginning of the week, especially on Monday.

Adolescent↗

[The proposal of the activities of daily living (ADL) index for institutionalized older adults].

The purpose of this study was to propose the ADL index constructed with a unidimensional scale based on item difficulty for institutionalized older adults. Six hundreds and three subjects (159 males and 444 females) were divided into the following four groups based on assisting devices for movement: G1 did not use assisting devices for movement; G2 used a stick or a walker; G3 used a wheelchair; G4 could not move. As the results of examinations from the points of the approximation of proportions, non-answer rates and agreement rates of each item according to 74 ADL items representing 9 ADL domains, the 27 ADL items were selected as utility items. The reliability and unidimensionality of the ADL index consisting of 27 items were considered to be high. As the results of examining the difficulty of items and ADL ability characteristics of each group, the ADL concerning movement and other lower limb activity in G1 and G2, and concerning changes of posture and manual activity in G3 and G4 were considered to reflect the individual differences of ADL ability, respectively. The numbers of ADL items which should first be assessed in each group were as follows: 20 items in G1; 21 items in G2; 21 items in G3; 11 items in G4.

Activities of Daily Living↗

[A study of metallic mercury polluting a room after being spilled from a sphygmomanometer].

Mercury spilled from a mercurial sphygmomanometer on a hot carpet can vaporize and pollute the environment. We observed the vaporization of mercury in model experiments. Mercury (0.15g) was heated on a hot carpet and the near-by air was sampled with a midget impinger. The evaporated mercury levels were 5.0, 6.3, 8.1 and 10.0mg/m(3) at 20, 40, 60 and 80 minutes, respectively at a height of 30cm from carpet. The result indicated that even if a small quantity of mercury remained on the hot carpet, it could evaporate and pollute the indoor air. Little is known about the influence on human health of low mercury exposure, especially on children. In order not to pollute the air, we need to pay attention to mercury.

Accidents, Home↗

Effects of valsartan on angiotensin II-induced migration of human coronary artery smooth muscle cells.

The migration as well as proliferation of coronary artery medial smooth muscle cells (SMC) into the intima is proposed to be an important process of intimal thickening in coronary atherosclerosis. In the current study, we examined the effects of the angiotensin type 1 receptor antagonist valsartan on angiotensin II (Ang II)-induced migration of cultured human coronary artery SMC using Boyden's chamber methods. Ang II significantly stimulated human coronary artery SMC migration in a concentration-dependent manner between 10(-6) and 10(-8) mol/l when cells of passage 4 to 6 were used. However, the migration response to Ang II was moderately decreased in cells of passage 10 to 12, and was markedly decreased in cells of passage 15 to 17, compared to that of passage 4 to 6. Ang II-induced migration was blocked by the Ang II type 1 (AT1) receptor antagonist valsartan in a concentration-dependent manner. By contrast, the Ang II type 2 (AT2) receptor antagonist PD 123319 did not affect Ang II-induced migration. Ang II modestly increased the cell number of human coronary artery SMC after a 24-h incubation. This increase in cell numbers was also clearly blocked by valsartan, but not by PD 123319. These results indicate that Ang II stimulates migration as well as proliferation via AT1 receptors in human coronary artery SMC when cells of passage 4 to 6 are used. Valsartan may prevent the progression of coronary atherosclerosis through an inhibition of Ang II-induced migration and proliferation in these cells, although in vivo evidence is lacking.

Angiotensin II↗

Use of subjective estimation in motor skill tests of young children: judgment based on observation of behavior in daily life.

This study assessed what motor skill tests were appropriate by observing 636 young children's behavior in daily life (low-aged classes, M = 3.7 yr.; middle-aged classes, M = 4.7 yr.; high-aged classes, M = 5.7 yr.). A homeroom teacher and an assistant teacher estimated motor achievement as pass-or-fail, and then judged pass-or-fail based on practical testing. Estimate-re-estimate agreement, interrater agreement, and agreement between estimated values and measured values were examined for 27 items, e.g., skipping, bouncing a ball, and turning on one leg. Estimate-re-estimate agreement was high on the whole. Interrater agreement ranged from 34% to 100% for 3-yr.-olds, 21% to 100% for 4-yr.-olds, and 89% to 100% for 5-yr.-olds. Agreement between estimated values and measured values greater than 80% was found in most items for 5-yr.olds (14 items). After examining the above-mentioned agreements, 26 items were selected as possible tests to judge motor development, using a pass-or-fail, from the observation of young children's behavior in daily life.

Achievement↗

Examination of force-production properties during static explosive grip based on force-time curve parameters.

The present study attempts to clarify the properties of force-time curves in the force-development phase during static explosive grip exertion and to determine force-time parameters in relation to static explosive strength. 80 healthy young males (age 17.8 +/- 2.5 yr.) exerted maximal isometric force as fast and forcefully as possible. In total, 21 variables, e.g., time to fixed level, integrated area, average force, integrated area to fixed time, force at the maximal rate of force development, and maximal rate of force development, were selected as force-time parameters. Good reliability was obtained for average force in force levels above 90% of maximal strength (.64-.93), integrated area to a fixed time of 1.0-2.0 sec. (.86-.93), force at the maximal rate of force development (.67), and maximal rate of force development (.73). In addition, these values correlated closely with maximal grip strength (r= .65-.93). Further, significant differences in maximal grip strength, average force in force levels above 90% of maximal strength, integrated area to fixed time, and force at the maximal rate of force development were found among three groups categorized by average force in force levels of maximal strength. These results suggested that individual differences were present in the force-time curve patterns during the force-development phase of static explosive grip exertion and that the average force in force levels of maximal strength might be a valuable tool for evaluating static explosive strength.

Adolescent↗

[Opioid receptors].

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Analgesics, Opioid↗