[Effect of macrolides on IL-8 gene expression by cultured airway epithelial cells].
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Biomedical subjects
H Tomoike
Publications and source records attributed to H Tomoike.
Serum levels of soluble form of Fas molecule in patients with congestive heart failure.
Compared with soluble Fas molecule (sFas, an inhibitor of Fas-mediated apoptosis) in normal volunteers, the serum level of sFas significantly increased by 41% in New York Heart Association (NYHA) class III (p <0.05) and by 97% in NYHA class IV patients with congestive heart failure (p <0.001). Furthermore, sFas showed correlations with soluble forms of TNF receptor-p55 (RI) and -p75 (RII) (r = 0.68 and r = 0.56) which inhibit activities of TNF alpha.
Adult↗
Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome.
BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.
Alleles↗
Elevated levels of type II soluble tumor necrosis factor receptors in the bronchoalveolar lavage fluids of patients with sarcoidosis.
Since tumor necrosis factor (TNF) is known to be involved in granuloma formation in sarcoidosis, and soluble TNF receptors (sTNF-Rs) inhibit TNF action in vivo, we evaluated the levels of sTNF-Rs in the bronchoalveolar lavage fluids (BALF) of 31 subjects using an enzyme-linked immunosorbent assay. Our group consisted of 13 patients with sarcoidosis (7 sarcoidosis patients who received no treatment and 6 who received corticosteroid therapy) and 18 control subjects (11 healthy nonsmokers and 7 asymptomatic smokers). Type II (75-kDa), but not type I (55 kDa) sTNF-R in BALF was elevated significantly in patients with sarcoidosis compared with the healthy nonsmokers (type I: 126.7 +/- 17.6 pg/ml BALF vs 79.4 +/- 16.5 pg/ml BALF, p > 0.05; type II: 98.3 +/- 27.8 pg/ml BALF vs 26.7 +/- 4.9 pg/ml BALF, p < 0.05). Although levels of type I sTNF-R in BALF from sarcoidosis patients were not correlated with any cellular profiles of BALF, concentrations of type II correlated significantly with the numbers of lymphocytes in BALF. We concluded that sTNF-R is a normal constituent of the epithelial lining fluids and that levels of type II sTNF-R are elevated significantly in the BALF from individuals with sarcoidosis. This suggests that sTNF-Rs may influence the local bioactivity of TNF and may also contribute to the pathogenesis of sarcoidosis.
Antigens, CD↗
Effects of activation sequence on monophasic action potential configuration in the dog.
The effects of altered activation sequence on the monophasic action potential (MAP) in in situ beating hearts are not known, although its effects on refractory periods are well documented. In nine anesthetized, open-chest dogs, complete atrioventricular block was produced, and the heart was driven by either right ventricular or left ventricular stimulation. The MAPs of the right and left ventricles were recorded by contact electrodes at cycle lengths of 1,000, 800, 600, and 400 ms. The MAP configuration was evaluated with regard to the difference between phase 1 and phase 2 MAP amplitudes and MAP duration at 50 and 90% repolarization. An MAP recorded from the ventricle that was being electrically stimulated was designated an ipsilateral ventricular stimulation, whereas the MAP recorded from the nonstimulated ventricle was termed a contralateral ventricular stimulation. The difference in amplitude and the 50% and 90% MAP durations for ipsilateral ventricular stimulation were consistently larger than for contralateral ventricular stimulation at all cycle lengths tested. Transient outward current did not appear to play a major role in producing such differences in MAP because intravenous treatment with 4-aminopyridine, a blocker of transient outward current, did not affect the configuration of the MAP. These findings provide an insight on the influence of ventricular activation sequence on the shape of the transmembrane action potential.
4-Aminopyridine↗
Electrophysiologic effects of sodium channel blockade on anisotropic conduction and conduction block in canine myocardium: preferential slowing of longitudinal conduction by flecainide versus disopyramide or lidocaine.
OBJECTIVES: The purpose of this study was to determine the effects of sodium channel blockade on anisotropic excitation propagation in the intact canine left ventricle. BACKGROUND: Anisotropic ventricular conduction- electric conductivity dependent on the myocardial fiber direction-is one of the important mechanisms of ventricular arrhythmia. However, the effects of sodium channel blockade, especially the differential effect of a subclass of this agent, on the anisotropic properties remain unknown. METHODS: In 28 anesthetized, open chest dogs, a small cannula was inserted into the left anterior descending coronary artery. Saline (control), disopyramide, lidocaine or flecainide was infused selectively into the cannula. An array of 64 epicardial electrodes was placed on the anterior surface of the ventricle. Activation time (AT) was measured along the longitudinal (L) and transverse (T) directions. RESULTS: High dose flecainide (100 microg/kg body weight per min) delayed the AT along the L direction markedly (mean [+/-SE] 227 +/- 38%, p < 0.02) and mildly (121 +/- 10%, p < 0.02) along the T direction in regular beats (p < 0.007, L vs. T). Lidocaine and disopyramide did not show direction-dependent prolongation of the AT on regular beats. When examined on premature beats, AT was delayed, depending on the coupling interval and the fiber direction when saline, flecainide or lidocaine was infused. The conduction blocks along the L direction were observed in three of seven dogs on regular beats after flecainide and ventricular fibrillation ensued in two of these three dogs. CONCLUSIONS: A peculiar slowing of L conduction by flecainide may relate to the character of proarrhythmia.
Animals↗
Visualisation of exercise-induced ischaemia of the right ventricle by thallium-201 single photon emission computed tomography.
OBJECTIVE: Exercise thallium-201 (201T1) single photon emission computed tomography (SPECT) has been used to detect potential ischaemia in the left ventricular myocardium but not in the right ventricle. The purpose of this study was to establish the clinical usefulness of a right ventricular polar map of 201T1 SPECT for visualisation of exercise-induced right ventricular ischaemia. METHODS: Myocardial 201T1 SPECT was obtained immediately after treadmill exercise in 97 patients with suspected coronary artery disease. A region of interest was placed over the right ventricle (RV) on post-stress transaxial images. Short axis images of this region were generated and reconstructed as a bull's eye polar map. Normal ranges of RV 201T1 uptake were determined in 12 patients with normal coronary arteries. Scintigraphic criteria for identifying RV perfusion abnormality were derived from 25 patients with right coronary artery (RCA) stenosis greater than 75%. These criteria were applied to 60 consecutive patients with suspected coronary artery disease. RESULTS: Perfusion defects in the RV were larger in patients with proximal RCA stenosis than in those with distal RCA stenosis (mean (SD) 28 (16)% v 6 (5)%, P < 0.001). The sensitivity and specificity of the RV polar map for the detection of proximal RCA stenosis were 67% (8/12) and 98% (47/48), respectively. RV perfusion defects became undetectable in 9 patients who had successful percutaneous transluminal coronary angioplasty to a proximal RCA lesion. CONCLUSIONS: A right ventricular polar map display was useful for visualising exercise-induced right ventricular ischaemia.
Adult↗
Inhibition of neutrophil elastase-induced interleukin-8 gene expression by urinary trypsin inhibitor in human bronchial epithelial cells.
BACKGROUND: Urinary trypsin inhibitor (UTI), a potential inhibitor for proteinases including neutrophil elastase (NE), trypsin, plasmin, cathepsin B and H has been used for the treatment of lung diseases with the absence of side effects in Japan. METHODS: In this study, we investigated the inhibitory effects of UTI on both purified NE and NE activities present in bronchoalveolar fluids from patients with chronic bronchitis. We also investigated the inhibitory capacity of UTI with regard to NE-induced interleukin-8 gene expression in human bronchial epithelial cells by Northern analyses. RESULTS: UTI inhibited NE activities in bronchoalveolar lavage fluid from patients with chronic bronchitis and of the purified enzyme. In addition, UTI inhibited NE-induced interleukin-8 gene expression and protein secretion in a human bronchial epithelial cell line. CONCLUSIONS: Our results suggest that UTI is applicable to patients with a variety inflammatory lung diseases in which NE plays a pivotal role.
Bronchi↗
Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury.
Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.
Adult↗
Roles of nitric oxide and adenosine in the regulation of coronary conductance in the basal state and during reactive hyperemia.
Nitric oxide (NO) and adenosine are important mediators in the regulation of coronary vascular tone and are released into the interstitium from the vascular endothelium and myocardium, respectively. The roles of these autacoids in the regulation of coronary flow in the basal and reactive hyperemic states were examined in Langendorff rabbit hearts perfused with oxygenated Krebs-Henseleit solution at 37 degrees C and 110 mmHg pressure. Instantaneous perfusion pressure-flow relationships were analyzed to derive coronary conductance both in the basal state and during the early phase of reperfusion (hyperemic state). N omega-nitro-L-arginine methyl ester (L-NAME) at increasing concentrations (10(-6) to 10(-4) mol/L) (n = 7) and 8-phenyltheophylline (8-PT) at increasing concentrations (10(-9) to 10(-6) mol/L) (n = 7) were applied to assess the role of NO and adenosine, respectively. L-NAME dose-dependently reduced the coronary conductance in both the basal and early hyperemic states, while 8-PT dose-dependently reduced conductance only in the hyperemic state. Changes in conductance during the early hyperemic phase correlated well with changes in the debt repayment ratio for either L-NAME (r = 0.94) or 8-PT (r = 0.99). These data suggest that a flow-related NO release mechanism regulates the coronary conductance in both the basal and hyperemic states while the metabolic regulation of adenosine release plays a role in the presence of ischemia.
Adenosine↗
Soluble tumor necrosis factor receptors are elevated in relation to severity of congestive heart failure.
The level of tumor necrosis factor alpha (TNF-alpha) is increased in patients with congestive heart failure and may play an important role in the development and progression of heart failure. Two types of TNF receptor (TNF-RI and TNF-RII) are expressed in virtually every cell and have different biologic roles. Soluble forms of the two receptors (sTNF-RI and sTNF-RII) have been identified as extracellular domain fragments. Serum levels of TNF-alpha, sTNF-RI and sTNF-RII were measured in 66 patients with heart failure and 27 control subjects using an enzyme-linked immunosorbent assay (ELISA). Hemodynamic variables, norepinephrine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were evaluated. TNF-alpha was significantly higher in patients with heart failure than in controls subjects (9.4 +/- 1.4 vs 4.8 +/- 0.8 pg/ml; p < 0.05). sTNF-RI and -RII were significantly increased in relation to the severity of heart failure (control subjects, 0.66 +/- 0.04 and 1.97 +/- 0.15 ng/ml; NYHA class II, 1.10 +/- 0.08 and 2.28 +/- 0.12 ng/ml; NYHA class III, 1.63 +/- 0.22 and 3.00 +/- 0.24 ng/ml; NYHA class IV, 2.78 +/- 0.46 and 4.52 +/- 0.62 ng/ml, respectively). In 9 patients whose clinical symptoms improved after treatment, the levels of sTNF-RI and -RII decreased by 17.3 +/- 5.7% (p < 0.05) and 22.1 +/- 6.9% (p < 0.05), respectively. There were significant positive correlations between sTNF-RI and -RII and mean pulmonary pressure (r = 0.69 and r = 0.61; p < 0.001) and mean capillary wedge pressure (r = 0.65 and r = 0.54; p < 0.001 and p < 0.01, respectively), but not with left ventricular end-diastolic volume or ejection fraction (NS). sTNF-RI and -RII were also significantly positively correlated with plasma levels of norepinephrine (r = 0.75 and r = 0.50; p < 0.001 and p < 0.05), ANP (r = 0.72 and r = 0.70; p < 0.001), and BNP (r = 0.60 and r = 0.60; p < 0.001). In conclusion, soluble TNF receptors are increased in proportion to the severity of congestive heart failure and may reflect the current status of congestive heart failure rather than the level of left ventricular dysfunction.
Adult↗
Effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats.
Whether or not theophylline inhibits hypoxic pulmonary vasoconstriction in vivo still remains uncertain. We therefore studied the effect of theophylline on hypoxic pulmonary vasoconstriction in awake rats. Two days before hemodynamic measurement, indwelling catheters were placed. Animals were divided into three groups; Group-H (20 mg/kg of theophylline), Group-L (8 mg/kg of theophylline), Group-S (saline). At the day of hemodynamic measurement, animals breathed 21% and 10% O2 gas. [{Pulmonary vascular resistance (PVR) during 10% O2-PVR during 21% O2}/PVR during 21% O2] x 100 was termed as hypoxic pulmonary vasoconstriction (HPV). The first HPV measurement was followed without drug administration and then the second HPV measurement was performed with theophylline or saline infusion. Post-theophylline HPV was divided by pre-theophylline HPV to normalize individual variation. Ratio of post-theophylline HPV to pre-theophylline HPV was 0.49 +/- 0.10, 0.77 +/- 0.23, 1.06 +/- 0.33 in Group -H, -L, -S, respectively (means +/- S.E.M). Ratio of post-theophylline HPV to pre-theophylline HPV was significantly less in Group-H than in Group-S. This result suggests that theophylline used in the present study (18.6-26.9 micrograms/ml) attenuates hypoxic pulmonary vasoconstriction in the unanesthetized rat.
Animals↗
Fatty acid metabolic imaging with iodine-123-BMIPP for the diagnosis of coronary artery disease.
UNLABELLED: Iodine-123-BMIPP kinetics under high glucose levels were examined. The feasibility of 123I-BMIPP imaging after oral glucose loading for the detection of impaired fatty acid metabolism was tested in patients with coronary artery disease. METHODS: Fatty acid metabolic imaging with 123I-BMIPP was performed on 29 patients in the fasting state and repeated after oral glucose loading. Myocardial SPECT images were obtained 20 min and 4 hr after the injection of 123I-BMIPP. Myocardial uptake of 123I-BMIPP was calculated by a Ishii-Macintyre method and the clearance of 123I-BMIPP from the myocardium was determined as (early counts-delayed counts) x 100/early counts. Regional accumulation of 123I-BMIPP was scored semiquantitatively from 0 (normal) to 4 (no activity), and the sum of regional scores in each patient was defined as a total defect score (TDS). RESULTS: Total myocardial uptake of 123I-BMIPP was 1.7% +/- 0.4% in the fasting state and 1.6% +/- 0.3% after oral glucose loading (p < 0.05). Iodine-123-BMIPP clearance from the myocardium was faster after glucose loading than in the fasting state (27% +/- 8% versus 11% +/- 6%, p < 0.01). After glucose loading, 123I-BMIPP clearance was faster in the ischemic myocardium (defined as areas perfused by stenosed coronary artery exceeding 90%) than in the nonischemic myocardium (33% +/- 8% versus 25% +/- 9%, p < 0.05). TDS in the ischemic myocardium increased from 1.8 +/- 0.4 in the fasting state to 2.1 +/- 0.4 after glucose loading (p < 0.01). The sensitivity for detecting coronary stenosis exceeding 90% increased from 55% (11/20) in the fasting state to 75% (15/20) after glucose loading without a loss of specificity (78%, 7/9). CONCLUSION: Oral glucose loading enhanced the detection of areas with impaired fatty acid metabolism due to coronary artery narrowing. Iodine-123-BMIPP imaging with oral glucose loading may be a new approach for the noninvasive diagnosis of coronary artery disease.
Adult↗
ACE inhibition reduces cardiac iodine-123-MIBG release in heart failure.
UNLABELLED: Radioiodinated metaiodobenzylguanidine (123I-MIBG), an analog of norepinephrine, has been used to assess cardiac sympathetic nerve activity. Decreased myocardial accumulation and enhanced washout of 123I-MIBG have been reported in patients with congestive heart failure (CHF). The purpose of this study was to determine whether angiotensin converting enzyme (ACE) inhibition reduced 123I-MIBG release and improved cardiac 123I-MIBG accumulation in patients with CHF. METHODS: Twenty-nine patients receiving conventional treatment for CHF, New York Heart Association (NYHA) functional class 2-3, were studied. Nineteen patients received additional treatment with enalapril, an ACE inhibitor, and 10 patients who were treated with conventional therapy alone were defined as a control group. Iodine-123-MIBG imaging and echocardiography were performed on all patients before treatment and repeated after 9.1 +/- 3.0 mo of treatment. Images were obtained 30 min and 4 hr after injection of 123I-MIBG, and a heart to mediastinum (H/M) ratio was defined to quantify cardiac 123I-MIBG uptake as a fraction of the mean counts per pixel in the heart divided by those in the mediastinum. The washout rate of 123I-MIBG from the heart was calculated as follows: (early counts - delayed counts)/early counts x 100(%). RESULTS: In patients with enalapril group, the H/M ratio of 123I-MIBG was increased after treatment (early image: 1.60 +/- 0.22 vs. 1.73 +/- 0.28, p < 0.05, delayed image: 1.63 +/- 0.28 vs. 1.82 +/- 0.33, p < 0.01). The washout rate of 123I-MIBG was reduced from 38% +/- 11% to 30% +/- 12% after treatment (p < 0.01). However in the conventional therapy group, the H/M ratios in the early and delayed images (early image: 1.58 +/- 0.31 vs. 1.52 +/- 0.23, delayed image: 1.49 +/- 0.27 vs. 1.49 +/- 0.25) and the washout rate (34% +/- 8% vs. 33% +/- 7%) remained unchanged after treatment. In patients with an increased H/M ratio of enalapril group (n = 13), a left ventricular ejection fraction increased from 48% +/- 12% to 55% +/- 9% (p < 0.01) after treatment. CONCLUSION: ACE inhibition reduces cardiac 123I-MIBG release and thus lowers cardiac sympathetic nerve activity. Iodine-123-MIBG may be helpful in evaluating the therapeutic effects of ACE inhibition on the cardiac sympathetic nervous system in patients with CHF.
3-Iodobenzylguanidine↗
Iodine-123-BMIPP imaging in unstable angina: a guide for interventional strategy.
UNLABELLED: The aim of this study was to clarify the clinical implications of decreased myocardial uptakes of 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) in patients with unstable angina. METHODS: Fatty acid metabolic imaging with 123I-BMIPP was performed in 20 patients with unstable angina during the pain-free state. Regional uptakes of 123I-BMIPP were scored semiquantitatively, and clinical characteristics and angiographic findings were compared between the patients with the normal and abnormal 123I-BMIPP images. RESULTS: There were 9 patients with normal and 11 patients with abnormal 123I-BMIPP images. Severe coronary stenosis exceeding 90% (91% compared with 44%, p < 0.05) and 99% (82% compared with 0%, p < 0.01) and collateral opacification (36% compared with 0%, p < 0.05) were more frequently observed in patients with abnormal 123I-BMIPP images than in those with normal images. Percutaneous transluminal coronary angioplasty or coronary artery bypass grafting was performed in 22% of patients with normal 123I-BMIPP images and in 82% of patients with abnormal 123I-BMIPP images (p < 0.01). CONCLUSION: Fatty acid metabolic imaging with 123I-BMIPP can determine the functional severity of coronary artery disease and is helpful for a clinical judgment in interventional treatment.
Aged↗
[A patient with allergic bronchopulmonary candidiasis showing a high serum level of soluble interleukin 2 receptors].
An 84-year-old man was admitted to Yonezawa City Hospital with fever, cough, hemoptysis and progressive dyspnea. He had complained of wheezing asthmatoid and exertional dyspnea for the previous 10 years, regardless of the season. On admission, chest radiographs revealed a diffuse ground-glass shadow, fibrotic change, and volume reduction. Arterial blood gas analysis showed extreme hypoxemia. A computed tomographic (CT) scan of the chest showed not only faint ground-glass opacities and dense patches in the whole lung field, but also central bronchiectasis. Laboratory tests revealed that both total serum levels of IgE and specific IgE for Candida albicans were elevated. In the bronchoalveolar lavage fluid, lymphocyte, neutrophil and eosinophil percentages were high, and the CD4/CD8 ratio was low. We diagnosed the fibrotic stage of allergic bronchopulmonary candidiasis. During treatment with hydrocortisone and fluconazole, eosinophilia in the peripheral blood was observed, and serum candida antigen was positive. In addition, high serum levels of soluble interleukin 2 receptors were observed in this patient.
Aged↗
[Macrolide antibiotic actions on bacteria and cultured airway cells].
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Immunolocalization of an inwardly rectifying K+ channel, K(AB)-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia.
Immunolocalization of K(AB)-2 (Kir4.1), an inwardly rectifying K+ channel with a putative ATP-binding domain, was examined in rat kidney where expression of K(AB)-2 mRNA was previously shown. Anti-K(AB)-2 antibody was raised in rabbit and then affinity-purified. An immunohistochemical study revealed that K(AB)-2 immunoreactivity was detected specifically in the basolateral membrane of distal tubular epithelia. Therefore, K(AB)-2 is the first K+ channel shown to be localized in the basolateral membrane of renal epithelia. The finding suggests that K(AB)-2 may contribute to supplying K+ to the Na(+)-K+ pump, which is abundant in the basolateral membrane of distal tubular epithelia, as well as to maintenance of the deep negative membrane potential of these cells.
Amino Acid Sequence↗