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Biomedical subjects

M Munakata

Publications and source records attributed to M Munakata.

At least 37 records · Page 2Linked to original sources
PubMed2001

Improving glucose metabolism and/or sarcoplasmic reticulum Ca2+-ATPase function is warranted for immature pressure overload hypertrophied myocardium.

The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week-old pressure overload hypertrophied rabbit hearts in response to dobutamine by (1) serial echocardiograms in vivo and (2) isolated Langendorff perfusion. Cytosolic Ca2+([Ca2+]i) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose +/- pyruvate was also evaluated. Both systolic and diastolic [Ca2+]i tended to be higher and diastolic calcium removal (tauCa) significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved tauCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca2+]i as well as a slower tauCa. Pyruvate completely preserved myocardial function and [Ca2+]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca2+]i, slower tauCa and reduced sensitivity of the contractile proteins to Ca2+. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism.

Animals↗
PubMed2001

Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.

The effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14-carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely dissociated rat neocortical neurons by using a nystatin-perforated patch recording configuration. VA activated a steady-state outward current in a concentration-dependent manner, with an EC50 of 0.65 microM. The reversal potential for the current shifted 56.5 mV with tenfold changes in the extracellular K+ concentration, suggesting that the current was carried by K+. The VA-induced current was not suppressed by apamin (1 microM), charybdotoxin (1 microM), Cs+ (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10 microM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4 mM. These pharmacological properties of the VA-induced current were compatible with a slowly inactivating delayed rectifier current (I(K)). It was suggested that the current activated by VA was I(K). The VA-induced current was not affected by Ca2+ depletion or by staurosporine (0.1 microM), quinacrine (10 microM), wortmanin (1 microM) or genistein (1 microM). The intracellular perfusion of GDPbetaS (0.4 mM) also had no significant effect. Thus, VA may directly activate the K+ channels.

Animals↗
PubMed2001

Influence of night shift work on psychologic state and cardiovascular and neuroendocrine responses in healthy nurses.

Night shift work has often been associated with increasing degree and frequency of various psychologic complaints. The study examined whether psychologic states after night work are related to adaptive alterations of the cardiovascular and neuroendocrine systems. We studied 18 healthy nurses (age 29+/-2 years) engaged in a modified rapid shift rotation system (day work, 8:15-17:15; evening work, 16:00-22:00; night work, 21:30-8:30). Blood pressure, heart rate, RR interval variability (L/H and HF power spectrum for sympathetic and vagal activities), and physical activity were measured using a multibiomedical recorder for 24 h from the start of work during the night and day shifts. Plasma ACTH and cortisol concentrations were measured at the end of each shift and at 8:30 AM on a day of rest. Each subject's psychologic state was assessed using a validated questionnaire. Among the parameters measured, scores for confusion, depression, anger-hostility, fatigue and tension-anxiety were highest, and scores for vigor lowest, after a night shift. Systolic blood pressure and heart rate during work were lower during night shift than during day shift (119+/-2 vs. 123+/-1 mmHg, p<0.05 and 75+/-1 vs. 84+/-2 bpm, p<0.001, respectively). Both parameters were lower still (p<0.005 and p<0.05) when measured outside of the hospital under waking conditions following a night shift than following a day shift, even though the levels of physical activity were similar. The HF power spectrum of RR interval variability was greater not only during work (24.2+/-2.1 vs. 18.5+/-1.8 ms, p<0.005) but also during the awake period (29.1+/-2.5 vs. 24.4+/-2.6 ms, p<0.005) after the night shift compared with the day shift. Plasma ACTH and cortisol concentrations were lower after night work than in the day of rest (7.3+/-1.2 vs. 11.5+/-2.3 pg/ml, p<0.1 and 11.1+/-1.1 vs. 14.4+/-1.1 mg/dl, p< 0.05). Systolic and diastolic blood pressures during night shift work and the subsequent awake period correlated positively with scores for vigor and negatively with scores for confusion (p<0.05). Plasma ACTH and cortisol concentrations did not correlate with any psychologic scores. We conclude that psychologic disturbances after night work were associated with altered cardiovascular and endocrine responses in healthy nurses. Some of the psychologic complaints may be attributable to lower waking blood pressure.

Adrenocorticotropic Hormone↗
PubMed2001

[Beta 2-Adrenergic receptor gene polymorphisms].

beta 2-adrenergic receptor gene is an intronless single gene coding 413 amino acid and is located on chromosome 5q31-33. This area is also noted as a candidate locus for asthma susceptibility genes. Up to now, 9 polymorphisms in the coding lesion and 10 polymorphisms in the 5' promotor lesion have been reported. Some of them have functional significance. In terms of both pathophysiological and pharmacogenetic view of asthma, these polymorphisms have been attracted an attention of many researchers. In this review, I will summarize the recent knowledge about this topic and discuss some future directions.

Amino Acid Sequence↗
PubMed2000

Bridged silver(I) complexes of the polycyclic aromatic compounds tetraphenylethylene and 1,1,4,4-tetraphenyl-1,3-butadiene.

For the purpose of investigating the coordination behavior of the sterically congested alkenes and exploring the possibility of cofacial complexation in the polycyclic aromatic system for formation of extended polymeric networks, tetraphenylethylene (tphe) and 1,1,4,4-tetraphenyl-1,3-butadiene (tphb) have been studied with regard to their complexation with a silver(I) ion. The crystal structures of [Ag(tphe)(ClO4)(p-xylene)], [Ag2(tphe)(ClO4)2], [Ag4(tphe)(CF3SO3)4], [Ag2(tphb)(ClO4)2], and [Ag2(tphb)(CF3SO3)2], together with the metal-free ligands tphe and tphb, have been determined by single-crystal X-ray diffraction. The pi-electron-rich cleft in organic components is found to offer a potential site for complexation, which can be utilized to generate an interesting array of organometallic compounds with one- and two-dimensional frameworks.

Journal Article↗
PubMed2000

Vesnarinone restores contractility and calcium handling in early endotoxemia.

BACKGROUND: Endotoxin (lipopolysaccharide, LPS) is a trigger of the systemic inflammatory response. We have previously found that vesnarinone and amrinone, when given before LPS, prevented cytokine production and LPS-related cardiac dysfunction. We tested the hypothesis that vesnarinone would improve intracellular Ca(2+) handling and calcium-activated contractile force after the onset of endotoxemia. METHODS AND RESULTS: Adult rabbits received a bolus injection of LPS or vehicle. Vesnarinone (3 mg/kg) was given intravenously 90 minutes later. Two hours after LPS administration, hearts were perfused in the isolated Langendorff mode. Peak left ventricular developed pressure, +/-dp/dt, oxygen consumption (MVO(2)), and ratexpressure product were evaluated in conjunction with fluorescent spectroscopic determinations of intracellular calcium concentrations (Ca(i)) and the rate of Ca(i) transient decline during diastole (tauCa). Peak left ventricular developed pressure and +/-dp/dt were significantly lower in the LPS group. These were completely restored by vesnarinone. There was significantly slower diastolic calcium removal (increased tauCa) in LPS hearts that was also corrected by vesnarinone; however, the cytosolic calcium overload characteristic of LPS hearts was only partially improved. Reduced mechanical inefficiency (the ratio of rate-pressure product to MVO(2)) and myofilament sensitivity to Ca(i) were also significantly improved by vesnarinone. CONCLUSIONS: Acute endotoxemia caused contractile protein calcium insensitivity, oxygen wastage, and abnormal calcium cycling. Vesnarinone, given in the rescue mode, normalized LPS-induced myocardial dysfunction and partially restored abnormal calcium cycling. Although the mechanisms responsible for these effects require further clarification, it appears that agents such as vesnarinone may be useful to treat inflammatory-induced myocardial dysfunction.

Animals↗
PubMed2000

Activation of coagulation in C57BL/6 mice given verotoxin 2 (VT2) and the effect of co-administration of LPS with VT2.

To obtain better insight into the pathogenesis of verotoxin-producing Escherichia coli-associated diseases, in this study, we explored the effect of verotoxin 2 (VT2) on coagulation in an animal model. After being given VT2 (50 ng/kg, lethal dose), C57BL/6 mice showed progressively increasing expression of TF mRNA in the kidney and brain and elevated plasma levels of thrombin-antithrombin III complex (TAT), normotest, fibrinogen, and PAI-1 paralleling the disease course over 24 hours; platelet counts were decreased at 48 hours with hemorrhage in the kidney and brain. Co-administration of lipopolysaccharide (LPS, 0.5 mg/kg) with VT2 (50 ng/kg) exhibited more prominant and/or prolonged increase in not only expression of TF and PAI-1 mRNAs in the kidney and brain but also plasma levels of TAT, fibrinogen, and PAI-1 and was associated with more remarkable hemorrhage in the tissues. Although VT2 (5 ng/kg) was not a lethal dose, co-administration of LPS (0.5 mg/kg) with VT2 (5 ng/kg) enhanced the susceptibility to VT2, resulting in more prolonged elevation of TAT levels during the first 24 hours than that in the LPS group and a second elevation at 72 hours, followed by death. Plasma IL-1beta level reached a maximum at 24 hours after VT2 (50 ng/kg) injection prior to the increase in TAT levels, whereas the increase in TNFalpha level immediately after injection was associated with the increase in PAI-1 mRNA. These observations indicate that the activation of coagulation by VT2 may occur through a mechanism different from that used by LPS, since plasma TAT levels rose in the mice immediately after LPS injection and returned to normal over 36 hours.

Animals↗
PubMed2000

2-D interwoven and 3-D 5-fold interpenetrating silver(I) complexes of 1-(isocyanidomethyl)-1H-benzotriazole and 1,3-bis(dicyanomethylidene)indan.

This paper presents novel and distinctive organosilver polymers with intriguing structure motifs, constructed from iodoacetonitrile (L1), 1-(isocyanidomethyl)-1H-benzotriazole (L2), 1,3-bis(dicyanomethylidene)indan (L3), and silver(I) salts, respectively. Treatment of L1 with AgClO4 generated [Ag(L1)(ClO4)]n (1), whose X-ray determination revealed a 2-D wavy sheet structure with square grids. Reaction of L2 with AgPF6 gave rise to a novel 2-D wavy interwoven network, ([Ag(L2)(PO2F2)0.5])n (2). The complex [Ag2(L3)2]n (3) obtained by reaction of AgClO4 with L3 can be regarded as unprecedented 3-D 5-fold interpenetrating nets with columnar aromatic stacks and indicates semiconductive behavior. The IR, ESR spectroscopic results, conductivities, and structural features of the complexes are discussed, respectively. The present findings may provide insight into the coordination versatility of silver(I) and polynitrile ligands and an inspiration for the self-assembly of novel supramolecular networks with multifunctional ligands. Crystal data: 1, C2H2AgINClO4, orthorhombic, Pca2(1) (No. 29), a = 14.503(1) A, b = 5.104(2) A, c = 10.2019(9) A, Z = 4; 2, C8H6AgN4PF4O, orthorhombic, Pnna (No. 52), a = 12.2705(3) A, b = 21.150(1) A, c = 10.040(1) A, Z = 8; 3, C30H10Ag2N8, triclinic, P1 (No. 2), a = 14.920(2) A, b = 11.896(2) A, c = 7.400(4) A, alpha = 86.55(2) degrees, beta = 80.87(2) degrees, gamma = 74.47(1) degrees, Z = 2.

Journal Article↗
PubMed2000

Structural studies of silver(I) coordination polymers with aryl iodide derived ligands.

This paper reports novel silver polymers, built with iodine--silver interactions, with interesting structural motifs. Four silver(I) coordination polymers of the aryl iodide derived ligands, triiodobenzoic acid (HL1), tris(4-iodophenyl)amine (L2), and 5,7-diiodo-8-hydroxyquinoline (HL3), have been synthesized and characterized by X-ray crystallography. Treatment of Ag(CH3COO) with HL1 yielded [Ag(L1)] (1), whose structural analysis revealed 2D layers of ladders connected through weak Ag...I interaction. Reactions of AgClO4 and L2 in benzene and nitrobenzene afforded, respectively, two different products, [Ag(L2)(H2O)]ClO4.C6H6(2) and [Ag(L2)(ClO4)](3). While the structure of 2 could be described as a 2D layer of square and octagons perpendicular to [100], complex 3 is formed by 2D layers of the same topology of 2 (8(2).4), alternating as ABAB. In contrast, complex 4, [Ag2(H2L3)(CF3SO3)3], obtained by reaction of Ag(CF3SO3) and HL3, was found to consist of a 2D layer based on columnar arrays AgH2L3-Ag(triflate). The solid-state FT-IR and 109Ag NMR spectra of theses complexes are discussed on the basis of their crystal structures.

Journal Article↗
PubMed2000

Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure.

OBJECTIVE: The enhanced generation of various chemical mediators is regarded as one of the mechanisms by which severe heart failure progresses to multiple organ failure. Platelet-activating factor is a phospholipid mediator which plays an important role in inflammatory reactions and circulatory shock. We studied the changes in platelet-activating factor levels in a canine heart failure model treated with a left ventricular assist device and hemofiltration, and assessed the effect of a protease inhibitor, nafamostat mesilate. METHODS: Twenty dogs underwent multiple coronary ligations, and at 2 hours after the ligations they were maintained on left ventricular assist device support with continuous hemofiltration. The animals were divided into two groups: a nafamostat group (n = 10) that received nafamostat mesilate (2 mg/kg/hr), and a control group (n = 10) that received vehicle only. RESULTS: The blood platelet-activating factor level, before coronary ligations, in the control and nafamostat groups was 2.3 +/- 0.4 and 2.0 +/- 0.7 ng/ml, respectively, and the coronary ligations had little effect on the platelet-activating factor. However, after the initiation of left ventricular assist device, the platelet-activating factor in the control group (5.6 +/- 2.2) was significantly higher (p < 0.05) than that in the nafamostat group (1.1 +/- 0.3). Nafamostat administration was also effective in controlling the increase in the blood lactate level. Hemofiltration did not change the platelet-activating factor. CONCLUSIONS: We concluded that platelet-activating factor may play a critical role in the development of severe heart failure with left ventricular assistance, and nafamostat administration is likely to be beneficial in such a critical condition by suppressing the platelet-activating factor level.

Animals↗
PubMed2000

Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy.

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.

Amantadine↗
PubMed2000

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Cerebral Cortex↗
PubMed2000

Whole blood prothrombin time using diluted tissue factor is shortened in spontaneous hypertensive rats.

Clinical screening tests for blood coagulation that use plasma as samples cannot estimate the participation of platelets, leukocytes, and erythrocytes in blood coagulation system. We developed an assay to evaluate the total coagulation ability of blood and whole blood prothrombin time (WPT) using the principle of prothrombin time with the diluted-tissue factor as a trigger and a newly developed apparatus, STA, viscosity change detection system (electromagnetic clot detection). The activation of platelets by Ca ionophore shortened WPT and increased the expression of CD62P on the platelet surface. WPTs in citrated blood of spontaneous hypertensive rats (SHR) were significantly shorter than those of controls, Wistar Kyoto rats (WKY). Plasma levels of thrombin-antithrombin III (TAT) in SHR were significantly higher than those of WKY. Moreover, WPT and TAT levels were significantly correlated. Based on these results, WPT was found to be useful to estimate the activation of blood coagulation in whole blood.

Animals↗
PubMed2000

Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma?

BACKGROUND: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. OBJECTIVE: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. METHODS: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. RESULTS: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0. 7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). CONCLUSIONS: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients.

Adrenal Cortex Hormones↗
PubMed2000

Serum KL-6 concentrations in dairy farmers.

STUDY OBJECTIVES: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease (FLD). DESIGN: A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. SETTING: University hospital screening project for FLD within a dairy-farming community in Japan. PARTICIPANTS: Four hundred seventy-two dairy farmers were invited to attend a local clinic. MEASUREMENTS AND RESULTS: We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/- 57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 +/- 288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab(+) group were significantly higher than those of the Ab(-) group (p < 0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. CONCLUSION: Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease.

Actinomycetales↗