Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 199 records · Page 11Linked to original sources

PubMed2000

Serum KL-6 in adult patients with polymyositis and dermatomyositis.

OBJECTIVE: To determine the serum levels of KL-6, a mucin-like high-molecular-weight glycoprotein, in polymyositis/dermatomyositis (PM/DM) patients. METHODS: Serum samples from 42 adult PM/DM patients and 38 healthy control subjects were examined using specific enzyme-linked immunosorbent assay (ELISA) systems. RESULTS: The serum levels of KL-6 in the PM/DM patients were significantly higher than those of the healthy controls. The elevated serum KL-6 levels correlated with the presence of interstitial lung disease (ILD) and decreased percentage diffusing capacity of carbon monoxide (%DLco) in the PM/DM patients. The serum KL-6 levels inversely correlated with %DLco and percentage vital capacity. Additionally, the serum KL-6 levels were elevated in five of the seven DM patients with malignant neoplasia. CONCLUSIONS: These results suggest that the serum KL-6 level might be a useful serum marker for ILD and internal malignancy in PM/DM.

Adult↗

PubMed2000

Maturation/M-phase promoting factor: a regulator of aging in porcine oocytes.

Deterioration in the quality of mammalian oocytes during the metaphase-II arrest period is well known as "oocyte aging." Oocytes in which aging has occurred are called aged oocytes, and these oocytes show enhanced activation and higher fragmentation rates after parthenogenetic activation. Previously we showed that porcine aged oocytes had low maturation/M-phase promoting factor (MPF) activity, and we suggested that this low MPF activity contributed at least in part to the aging phenomena. In the present study, we examined the relationship between MPF activity and these aging phenomena by artificially regulating MPF activity in porcine metaphase-II-arrested oocytes. Since we have shown recently that aged porcine oocytes contain abundant phosphorylated inactive MPF, so-called pre-MPF, we used vanadate and caffeine, which affect the phosphorylation status of MPF, to regulate MPF activity. Incubation of 48-h-matured oocytes with vanadate for 1 h increased the phosphorylation of MPF and decreased MPF activity. The parthenogenetic activation and fragmentation rates were significantly increased compared with those of control oocytes. Conversely, treatment of 72-h-cultured aged oocytes with caffeine (last 10 h of culture) decreased the level of pre-MPF and elevated MPF activity. These oocytes revealed significantly lower parthenogenetic activation rates and a lower percentage of fragmentation than did untreated aged oocytes. These results indicate that not only the increased ability for parthenogenetic activation but also the increased fragmentation rate observed in porcine aged oocytes may be attributable in part to the gradual decrease in MPF activity during prolonged culture. Control of MPF phosphorylation with these agents may allow for some degree of manipulation of oocyte aging.

Animals↗

PubMed2000

Glucose modifies the cross-talk between insulin and the beta-adrenergic signalling system in vascular smooth muscle cells.

BACKGROUND: Abnormalities in the vascular function of insulin are observed in insulin resistance, and hyperglycaemia is one of the important factors inducing insulin resistance. OBJECTIVE: To investigate the role of glucose in the interaction of insulin and beta-adrenergic signalling systems in vascular smooth muscle cells (VSMC). METHODS: After cells were treated with D-glucose (525 mmol/l) and insulin (100 nmol/l), adenylyl cyclase activity was measured in the presence of isoproterenol, forskolin, and cholera toxin. Assays for insulin-induced activities of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) were performed. RESULTS: In the presence of low glucose concentrations (5 mmol/l), insulin enhanced isoproterenol-, forskolin- and cholera toxin-stimulated adenylyl cyclase activities. This stimulatory effect was abolished by PI3-K inhibitors, wortmannin, or LY294002. In contrast, in the presence of high glucose concentrations (25 mmol/l), insulin attenuated isoproterenol-stimulated activity but not cholera toxin- or forskolin-stimulated activity. Insulin-stimulated activities of IRS-1 and PI3-K, but not MAPK activity, were also attenuated in the presence of high concentrations of glucose. The MAPK kinase inhibitor, PD98059, abolished the inhibitory effect of insulin on the beta-adrenergic signalling system. Troglitazone and pioglitazone prevented this inhibitory effect of insulin by restoring IRS-1 and PI3-K activities. CONCLUSIONS: In the presence of low glucose concentrations, insulin stimulates the beta-adrenergic signalling system through the IRS-1/PI3-K pathway. However, in the presence of high glucose concentrations, the effect of insulin is switched to an inhibitory one, through the MAPK pathway. Our finding suggests that high glucose concentrations modify the cross-talk between insulin and the beta-adrenergic signalling systems in VSMC.

Animals↗

PubMed2000

Effect of inhaled nitric oxide on cardiovascular response to catecholamine in heart failure.

We examined the dose responses to continuous infusion of isoproterenol (ISO) and norepinephrine (NE) in normal (control) and procainamide-induced heart failure dogs with or without inhalation of 70 ppm nitric oxide (NO). Inhaled NO affected neither left ventricular (LV) function nor hemodynamics at baseline in both control and heart failure dogs. There were no significant differences in the responses to ISO and NE with or without inhaled NO in the control. The responses of LV dP/dt to ISO and NE were significantly enhanced in heart failure; however, they were not affected by inhaled NO. In contrast, LV pressure and dimension at end diastole were significantly increased, and pulmonary vascular resistance (PVR) was significantly decreased by inhaled NO during infusion of both ISO and NE in heart failure. In conclusion, the positive inotropic response to cathecholamine is not affected by inhaled NO even in heart failure. Inhaled NO decreases PVR, but potentially increases LV preload in the presence of additional stress of cathecholamine in heart failure.

Administration, Inhalation↗

PubMed2000

Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.

To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future.

Adolescent↗

PubMed2000

Periodicity manifestations in the turbulent regime of the globally coupled map lattice

We revisit the globally coupled map lattice. We show that in the so called turbulent regime various periodic cluster attractor states are formed, even though the coupling between the maps are very small relative to the nonlinearity in the element maps. Most outstanding is a maximally symmetric three cluster attractor in period-3 motion, due to the foliation of the period-3 window of the element logistic maps. An analytical approach is proposed which successfully explains the systematics of various periodicity manifestations in the turbulent regime. The linear stability of the period-3 cluster attractors is investigated.

Journal Article↗

PubMed2000

Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma.

Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few antigens have been identified in non-melanoma tumors. We recently purified a new natural antigenic peptide, designated F4. 2, by biochemical elution from a human gastric signet cell carcinoma cell line and showed that it is recognized by an autologous human histocompatibility antigen (HLA)-A31-restricted cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction of F4. 2-specific CTLs from peripheral blood T lymphocytes of HLA-A31( +) gastric cancer patients. The T cells of seven HLA-A31( +) patients with gastric cancers were stimulated in vitro by F4.2-pulsed autologous dendritic cells which had been induced from peripheral blood of each patient by incubation in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-4. We tested the cytotoxicity of the T cells against F4.2-loaded C1R-A*31012 by a 6-h (51)Cr release assay after 3 stimulations with F4.2-pulsed dendritic cells. F4.2-specific cytotoxicity was detectable in the stimulated T cells from two of the seven HLA-A31( +) patients. Further, both F4.2-specific CTLs also lysed the gastric cancer cell line, HST-2, from which F4.2 was derived. These results suggest that F4.2 peptide may be useful as an HLA-A31-restricted peptide vaccine in certain patients with gastric cancer.

Adjuvants, Immunologic↗

PubMed2000

Expression and comparative chromosomal mapping of MKP-5 genes DUSP10/Dusp10.

We have isolated a mouse cDNA for a novel MAPK phosphatase, designated as MKP-5. Two MKP-5 mRNA transcripts of 3.5 kb and 2.7 kb were detected. The 3.5-kb transcript was expressed in almost all the tissues examined, and was particularly abundant in cerebellum, skeletal muscle, and bone marrow. On the other hand, the 2.7-kb transcript was specifically and highly expressed in testis. The MKP-5 genes (DUSP10/Dusp10) were localized to chr 1q41, Chr 1H5 and chr 13q26 in human, mouse and rat, respectively. They were mapped in regions where conserved linkage homology has been identified among the three species.

Amino Acid Sequence↗

PubMed2000

Expressions of various growth factors and their receptors in tissues from neurofibroma.

BACKGROUND: Platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta are known to enhance the growth of neurofibroma-derived cells from neurofibromatosis type 1 (NF-1) patients. OBJECTIVE: This study aims to elucidate whether these growth factors and their receptors are up-regulated in NF-1 patients. METHODS: Tissues and culture cells from neurofibroma in NF-1 patients, nontumor lesions in NF-1 patients, and the skin of normal controls were collected. To evaluate the expressions of growth factors and their receptors, reverse-transcriptase polymerase chain reaction and immunohistochemistry were performed. RESULTS: PDGF-beta receptor subunit was expressed in the neurofibroma tissues from NF-1 patients, but not in the nontumorous tissues from NF-1 patients or skin from normal controls. As for the other factors, there were no significant differences among these tissues. Neurofibroma sections also stained positive for the PDGF-beta receptor subunit. CONCLUSIONS: The interaction of PDGF and PDGF-beta receptor subunit may be important in the tumorigenesis of NF-1.

Becaplermin↗

PubMed2000

Importance of interleukin-8 in the development of reexpansion lung injury in rabbits.

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.

Animals↗

PubMed2000

Pneumoconiosis-related lung cancers: preferential occurrence from diffuse interstitial fibrosis-type pneumoconiosis.

It has been reported that patients with pneumoconiosis occasionally have a diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but little is known about the relation between pneumoconiosis-associated DIF and the risk of lung cancer. In the present study, we evaluated the incidence of DIF by chest CT and its contribution to lung cancer in 563 patients with nonasbestos pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with DIF had an exceedingly high concurrence of lung cancers when compared with pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001). Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20 [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias from pneumoconiosis with DIF were significantly more frequently observed in peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11 [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by immunohistochemistry was frequently observed in dysplasias from pneumoconiosis with DIF, although it was not significantly different compared with that in dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32). Taken together, these results may suggest a positive causal relationship between pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a pivotal role of diffuse fibrosis for the excess incidence of lung cancers, especially peripheral-type SCCs, in DIF-type pneumoconiosis.

Aged↗

PubMed2000

Reduced nasal nitric oxide in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown origin with inflammation in the respiratory bronchioles, bronchiectasis, and recurrent sinusitis. Patients with DPB suffer from chronic airway infections resulting from mucociliary dysfunction. Whereas a high concentration of nasal nitric oxide (NO) has been documented in healthy subjects, only two diseases are known to reduce nasal NO: primary ciliary dyskinesia syndrome and cystic fibrosis. We hypothesized that patients with DPB have abnormal levels of nasal NO. To test our hypothesis, we measured NO with the chemiluminescence technique. Air was sampled directly from the nose in 15 healthy subjects and eight patients with DPB. Nasal NO was 88% lower in DPB patients than in the age-matched control subjects (69 +/- 70 versus 556 +/- 87 nl/min; p < 0.001). Treatment with erythromycin for 2 wk did not alter the nasal NO in four control subjects. DPB is the third pulmonary disease in which nasal NO is low. The reduced nasal NO may well be involved in the pathogenesis of DPB, and NO measurements may serve as a noninvasive test in the diagnosis of DPB.

Adult↗

PubMed2000

The effect of divalent cations on the membrane properties and pharmacokinetics in rat of the lipid A analogue E5531.

To obtain information on the effects of Ca2+ on the membrane properties of the lipid A analogue E5531, we have determined the aggregate size, zeta potential, membrane fluidity, micropolarity and permeability of the E5531 membrane as a function of Ca2+ levels. Within the molar ratios of [Ca2+]/[E5531] = 1 and 3, Ca2+ increased the zeta potential of the E5531 membrane but had no effect on aggregate size (approximately 20 nm). Within the above ratios, Ca2+ decreased the membrane fluidity, as measured by micropolarity of E5531 and increased the phase transition temperature. The pharmacokinetics in rats for these samples with different membrane fluidity, prepared by changing the pre-dose formulation concentration of Ca2+, was determined and a correlation between membrane fluidity and pharmacokinetics was clearly observed. It thus appears that Ca2+ effects the membrane fluidity of E5531 as well as its pharmacokinetics in rats.

Animals↗

PubMed2000

Superoxide dismutase activity of iron(II)TPEN complex and its derivatives.

Superoxide is involved in the pathogenesis of various diseases, such as inflammation, ischemia-reperfusion injury and carcinogenesis. Superoxide dismutases (SODs) catalyze the disproportionation reaction of superoxide to produce oxygen and hydrogen peroxide, and can protect living cells against the toxicity of free radicals derived from oxygen. Thus, SODs and their functional mimics have potential value as pharmaceuticals. We have previously reported that Fe(II)tetrakis-N,N,N',N'-(2-pyridylmethyl)ethylenediamine (Fe(II)TPEN) has an excellent SOD activity (IC50 = 0.5 microM) among many iron complexes examined (J. Biol. Chem., 264, 9243-9249 (1989)). Fe(II)TPEN can act like native SOD in living cells, and protect Escherichia coli cells from free radical toxicity caused by paraquat. In order to develop more effective SOD functional mimics, we synthesized Fe(II)TPEN derivatives with electron-donating or electron-withdrawing groups at the 4-position of all pyridines of TPEN, and measured the SOD activities and the redox potentials of these complexes. Fe(II) tetrakis-N,N,N',N'-(4-methoxy-2-pyridylmethyl)ethylenediamine (Fe(II)(4MeO)4TPEN) had the highest SOD activity (IC50 = 0.1 microM) among these iron-based SOD mimics. In addition, a good correlation was found between the redox potential and the SOD activity of 15 Fe(II) complexes, including iron-based SOD mimics reported in the previous paper (J. Organometal. Chem., in press). Iron-based SOD mimics may be clinically applicable, because these complexes are generally tissue-permeable and show low toxicity. Therefore our findings should be significant for the development of clinically useful SOD mimics.

Ethylenediamines↗

PubMed2000

Clinical surveillance of a thin bipolar pacing lead.

A total number of 415 co-radial, bipolar pacing leads (189 atrial leads; 226 ventricular leads) were implanted in 228 patients between November 1994 and July 1999. Mean pacing thresholds at the implantation were normal at 0.6 V in the atrium and at 0.4 V in the ventricle with a pulse duration of 0.4-0.5 ms. Lead impedance was relatively low (337-447 ohms for atrial leads; 369-459 ohms for ventricular leads) at the implantation and during the follow-up periods. No definite failure in lead materials was observed in either atrial or ventricular leads (mean follow-up of 19.7 and 19.2 months, respectively: up to 52.9 months for both leads). Predicted clinical surveillance up to 10 years calculated statistically showed that the upper 95% confidence limit was a constant of 100%. The lower 95% confidence limits at 5, 7, and 10 years were estimated to be 98.0%, 97.2%, and 96.0%, respectively. From the present study, the ThinLine lead is reliable for both sensing and pacing thresholds, and has excellent predicted lead longevity. Nevertheless, further observation is required regarding cost performance, such as early replacement of the pacemaker generator, because of the lower pacing lead impedance.

Aged↗

PubMed2000

Characterization and affinity purification of juvenile hormone esterase from Bombyx mori.

Juvenile hormone esterase (JHE) from hemolymph of the silkworm moth Bombyx mori was characterized for substrate specificity and inhibitor sensitivity. B. mori JHE hydrolyzed the juvenile hormone surrogate substrate methyl n-heptylthioacetothioate (HEPTAT) more efficiently than p-nitrophenyl acetate and 1-naphthyl acetate substrates widely used to assay total carboxylesterase activity. B. mori JHE was sensitive to 3-octylthio-1,1,1-trifluoro-2-propanone (OTFP), which was developed as a selective inhibitor for lepidopteran JHE, and relatively insensitive to diisopropyl fluorophosphate (DFP), an inhibitor of serine esterases but not of all JHEs. Affinity purification with a trifluoromethyl ketone ligand was more efficient for purification of B. mori JHE than DEAE ion exchange chromatography.

Acetates↗

PubMed2000

Effect of celiprolol on cardiac hypertrophy in hypertension.

The present study was undertaken to clarify whether celiprolol and atenolol, beta1-selective beta blockers with and without intrinsic sympathomimetic activity (ISA), respectively, might improve ischemic damage in the isolated perfused hearts of spontaneously hypertensive rats (SHR), and whether long-term treatment with celiprolol may reduce left ventricular hypertrophy (LVH) in patients with essential hypertension. Atenolol (50 mg/kg/day) or celiprolol (300 mg/kg/day) for 7 weeks significantly reduced the blood pressure in SHR to the same degree, and both drugs decreased the heart rate, but the magnitude of the fall in heart rate was significantly higher with atenolol treatment than with celiprolol treatment. Both treatments significantly reduced the ratio of LV weight to body weight in SHR and significantly improved the coronary reserve in SHR to the same extent. Both treatments significantly improved the extent of recovery of the pressure-rate product and the extent of percent recovery of the coronary flow after reperfusion following 30 min of ischemia in SHR. Celiprolol treatment in patients with essential hypertension for 12 months significantly decreased interventricular septal thickness (IVST)+LV posterior wall thickness (PWT) and LV mass index (LVMI), but there was no significant correlation between IVST+PWT or LVMI and blood pressure before and after treatment. IVST+PWT and LVMI were significantly decreased after 3 months of treatment and these LVH indices were significantly smaller after 6 and 12 months of treatment than after 3 months of treatment. In conclusion, both celiprolol and atenolol treatment reduced LVH and improved the ischemic damage in SHR. In essential hypertensive patients with LVH, celiprolol treatment effectively reduced blood pressure and achieved LVH regression.

Adrenergic beta-Antagonists↗

PubMed2000

Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.

The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.

Albuminuria↗