[Suppressive effect of 14-cyclol linkage macrolides on bleomycin-induced pulmonary fibrosis].
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Animals↗
Biomedical subjects
A Azuma
Publications and source records attributed to A Azuma.
Cloning and expression of uridine/cytidine kinase cDNA from human fibrosarcoma cells.
Uridine/cytidine kinase which converts uridine and cytidine to their corresponding monophosphates is a rate-limiting enzyme involved in the salvage pathway of pyrimidine synthesis. We isolated cDNA encoding the enzyme from human fibrosarcoma cells, then determined its nucleotide sequence by the 5'-RACE method followed by confirmation employing the human genome DNA library. The isolated uridine/cytidine kinase cDNA (UCK cDNA) consisted of 786 nucleotides encoding 261 amino acids and was found to have approximately 70% homology with mouse UCK cDNA. Northern blot analysis of human leukemia RNAs with labeled UCK gene showed a single band at 1.6 kb to be UCK mRNA, and southern blot analysis of the UCK cDNA after digestion with BamHI, SacI and XbaI enzymes showed four band signals, suggesting the UCK gene to have at least 4 exons. A truncated form of UCK cDNA was expressed as the His-tag conjugated protein in Escherichia coli. The expressed and purified protein specifically converted uridine and cytidine to their corresponding monophosphates and also phosphorylated antitumor nucleosides such as 5-fluorouridine, cyclopentenyl-cytosine and 3'-C-ethynylcytidine. The present results suggest that our cloned human UCK cDNA encodes the correct amino acid sequence for UCK protein, showing high intracellular phosphorylation activity forward natural and synthetic pyrimidine nucleosides.
Amino Acid Sequence↗
[Genetic variation of NADPH/NADH oxidase and susceptibility to diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)].
Diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD) are both characterized by chronic airflow obstruction of unknown etiology. It is hypothesized that neutrophils play the major role in the pathogenesis of these diseases. Recent studies have suggested that genetic factors may be related to individual susceptibility to these diseases. We have investigated the association between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide-generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples obtained from both patients with DPB (n = 82), COPD (n = 53), and control subjects (n = 82) were used for this genotyping assay; and the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the DPB, COPD, and control groups, respectively. There were no differences in the distribution of the genotype of p 22 phox among these groups, either. We concluded that there is no association between the C 242 T polymorphism of p 22 phox, and susceptibility to DPB and COPD.
Bronchiolitis↗
[Assessment of myocardial damage and metabolic disorder in the left ventricle in patients with mitral stenosis using 201Tl and 123I-BMIPP myocardial SPECT].
This study was designed to evaluate the myocardial damage and metabolic disorder of the left ventricle in patients with mitral stenosis. We studied 15 patients with mitral stenosis. Their grade of chronic heart failure using New York Heart Association classification were class I: 5 patients, class II: 5, class III: 3, class IV: 2, respectively. The severely stenotic group (valve area < 1.5 cm2) included 6 patients, mildly stenotic group (1.5 cm2 < or = valve area < 2.5 cm2) included 9. A 111 MBq of 123I-BMIPP was intravenously injected at rest, SPECT images were obtained at 15 min and 3 hours after injection. A 111 MBq of 201Tl was intravenously injected at rest, and SPECT images were obtained at 15 min after injection. Washout rate (WR) of 123I-BMIPP from the whole left ventricle was obtained using polar maps. The concentration of norepinephrine (NE: pg/ml) in the blood at rest was measured. The mean values of pulmonary artery pressure was measured in ten patients using Swan-Ganz catheter. 123I-BMIPP myocardial SPECT and measurement of NE were reexamined in 5 patients after mitral valvuloplasty. NE values were 476 +/- 72 and 793 +/- 286 in classes I + II and III + IV, respectively. NE values was increased in the severe heart failure group (p < 0.05). NE values were 480 +/- 69 and 743 +/- 295 in the mildly and severely stenotic groups, respectively. NE value was increased in severely stenotic group (p < 0.05). Twelve patients showed normal uptake on both 201Tl and 123I-BMIPP myocardial SPECT. Three patients showed slightly reduced uptake on both 201Tl and 123I-BMIPP myocardial SPECT. WR was 27.2 +/- 4.8% and 44.3 +/- 6.7% in class I + II and class III + IV, respectively. WR was increased in severe heart failure group (p < 0.05). WR was 27.8 +/- 6.0% and 41.3 +/- 9.4% in the mildly and severely stenotic group, respectively. WR was increased in the severely stenotic group (p < 0.05). NE was correlated with WR (p < 0.001). In patients with mitral valvuloplasty, WR was 44.3 +/- 6.7% and 31.4 +/- 4.7% before and after mitral valvuloplasty, respectively. NE values were 857 +/- 266 and 574 +/- 165, respectively. Both WR and NE were decreased after mitral valvuloplasty (p < 0.01). In patients with mitral stenosis, WR was increased in the severe heart failure group and severely stenotic group without apparent myocardial damage. Myocardial metabolism in the left ventricle might be influenced by right heart failure through, for example, NE and neurohormonal factors.
Aged↗
Prolonged survival of a bare lymphocyte syndrome type I patient with diffuse panbronchiolitis treated with erythromycin.
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Adult↗
[Assessment of myocardial fatty acid metabolism in patients with angina pectoris and diabetes mellitus using 123I-BMIPP myocardial scintigraphy].
PURPOSE: We studied the effect of myocardial ischemia and diabetes mellitus (DM) on the myocardial fatty acid metabolism using 123I-BMIPP myocardial scintigraphy. METHODS: We performed 123I-BMIPP myocardial scintigraphy in 50 patients with myocardial ischemia and without DM (AP), in 30 patients with myocardial ischemia and DM (AP + DM), 12 patients with DM and without myocardial ischemia (DM), and in 10 normal subjects (N). Myocardial uptake rate of 123I-BMIPP was obtained using the time activity curve. Myocardial washout rate of 123I-BMIPP was calculated using the polar images of early and delayed SPECT images. RESULTS: Myocardial uptake rate of 123I-BMIPP (%) were AP: 4.9 +/- 0.6, AP + DM: 5.5 +/- 0.5, DM 5.7 +/- 0.5 and N: 5.0 +/- 0.4. 123I-BMIPP myocardial uptake rate was increased in AP + DM and DM. 123I-BMIPP myocardial washout rate (%) were AP: 30.2 +/- 4.3, AP + DM: 24.5 +/- 3.9, DM: 16.1 +/- 2.8 and N: 19.4 +/- 3.2. 123I-BMIPP myocardial washout rate was increased in AP and AP + DM. 123I-BMIPP myocardial washout rate was increased particularly in patients with multi-vessels disease. 123I-BMIPP myocardial washout rate was decreased in DM. CONCLUSION: The present study suggested that diabetes mellitus increased myocardial fatty acid uptake and decreased myocardial fatty acid washout, and that myocardial ischemia increased myocardial fatty acid washout.
Aged↗
[A case of congenital esophagobronchial fistula discovered incidentally on esophagography].
A 50-year-old man was admitted to our hospital because of an abnormal shadow, detected during an upper gastrointestinal examination. A chest radiograph showed an infiltrating shadow in the right middle lung field. A chest CT showed a fistula communicating between a bronchus (rt. B6) and the middle of the esophagus. Resection of the fistula was performed by video-assisted thoracoscopic surgery (VATS). Isolation of the fistula was straightforward, and there was no evidence of inflammation or adherent lymph nodes around it. Histologic examination of the resected specimen revealed that the fistula lumen was covered with squamous epithelium and muscularis mucosa. These findings suggested that this case could be categorized as Braimbridge type II. In this case, the chest CT showed the esophagobronchial fistula clearly, and was useful for the diagnosis.
Bronchial Fistula↗
Kinematic of animal locomotion under various gravitational fields.
A simple kinematic analysis of human locomotion under various gravitational fields is presented and a desirable way of locomotion is proposed. A comment on flight behaviors of insects in nongravity fields is also presented.
Animals↗
Uncommon and dynamic changes detected by 123I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography in a stunned myocardium induced by coronary microvascular spasm.
A 55-yr-old man underwent surgery. Soon after the procedure was finished, the patient complained of chest pain, and the electrocardiogram showed increase in the ST-segment in some leads. Emergency angiography showed normal coronary arteries, but there was asynergy in the left ventricle, and delayed filling of contrast medium was observed in the LCA. An intracoronary infusion of isosorbide dinitrate did not improve the delayed filling of contrast medium or ST segment increase in the electrocardiogram. Soon after nicorandil was injected into the LCA, the patient's symptoms, electrocardiogram, and delayed filling of contrast medium dramatically improved. On the second day, initial imaging by 123I-BMIPP myocardial SPECT showed a moderate increase in tracer uptake in the apico-anteroseptal region and a moderate decrease in tracer uptake in the lateral region, in which the first left ventriculography showed akinesis, and delayed imaging revealed a moderate increase in tracer uptake in the apical region and a high washout of 123I-BMIPP in the anteroseptal and lateral regions. On the sixth day, initial imaging by 123I-BMIPP myocardial SPECT showed a moderate decrease in tracer uptake in the apical and lateral regions and a mild decrease in tracer uptake in the anteroseptal region, and delayed imaging revealed a moderate increase in tracer uptake in the apical region and a high washout of 123I-BMIPP in the anteroseptal and lateral regions. By the 30th day, 123I-BMIPP myocardial SPECT had normalized. We consider that these dynamic changes in 123I-BMIPP myocardial SPECT imaging may reflect metabolic changes in fatty acids in the ischemic state, the size of the triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.
Coronary Vasospasm↗
Diesel exhaust particles up-regulate expression of intercellular adhesion molecule-1 (ICAM-1) in human bronchial epithelial cells.
Epidemiological and experimental studies suggest that diesel exhaust particles (DEP) may play an active role in the increased respiratory mortality and morbidity. We have shown that DEP augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. ICAM-1 has been shown to play an important role in the local accumulation of inflammatory cells. We studied the effect of DEP on ICAM-1 gene expression and surface expression in human bronchial epithelial cell line BEAS-2B. DEP (5-50 microg/ml) showed a stimulatory effect on ICAM-1 mRNA levels as evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometric analysis demonstrated an increased ICAM-1 expression on the epithelial cell surfaces. The soluble form of ICAM-1 molecules was also increased by the stimulation of DEP. In vitro neutrophil attachment onto DEP-stimulated epithelial cells was augmented, which was partially blocked by anti-ICAM-1 neutralizing antibody. Finally, these events were significantly inhibited by pretreatment with anti-oxidants pyrrolidine dithiocarbamate and N-acetyl cysteine, and p38 mitogen activated protein kinase (MAPK) inhibitor SB203580. These findings suggested that DEP induced up-regulation of ICAM-1 gene, and this process might be largely dependent on oxidant-mediated NF-kappaB activation and p38-MAPK pathways.
Bronchi↗
Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis.
Diffuse panbronchiolitis affecting East Asians is strongly associated with the class I human leukocyte antigen (HLA) alleles. Recent observations suggest that a major disease-susceptibility gene may be located between the HLA-B and HLA-A loci in the class I region of the major histocompatibility complex on chromosome 6. To test this possibility, we analyzed 14 polymorphic markers in 92 Japanese patients and 93 healthy controls. Of these, seven marker alleles, including HLA-B54 and HLA-A11, were significantly associated with the disease. Maximum-likelihood haplotype analysis and subsequent direct determination of individual haplotypes identified a group of disease-associated haplotypes, one of which contained all seven disease-associated marker alleles. Another haplotype, containing HLA-B*5504, was also associated with the disease. All these haplotypes seem to have diverged from a common ancestral haplotype in East Asians and share a specific segment containing three consecutive markers between the S and TFIIH loci in the class I region. Furthermore, one of the markers within the candidate region showed the highest delta value, indicating the strongest association. Of 20 Korean patients with diffuse panbronchiolitis, 17 also shared the combination of the disease-associated marker alleles within the candidate region. These results indicate that an HLA-associated major susceptibility gene for diffuse panbronchiolitis is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3.
Alleles↗
Role of E-selectin in bleomycin induced lung fibrosis in mice.
BACKGROUND: Bleomycin (BLM), a well known anti-cancer drug, often causes acute lung injury and fibrosis by mechanisms that are not well understood. It is suspected that some proteases and active oxygen species generated from inflammatory cells cause the lung injury and subsequent lung fibrosis. It was therefore hypothesised that inhibition of adhesion of inflammatory cells to the endothelium might prevent these developments. METHODS: BLM (100 mg/kg) was injected into the tail veins of ICR mice to evaluate the induction of E-selectin, an adhesion molecule known to induce neutrophil attachment on endothelial cells. E-selectin mRNA induction was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The myeloperoxidase (MPO) activities in the lung tissues of BLM treated and control mice were compared to evaluate neutrophil infiltration. Pathological changes in the lungs of soluble E-selectin transgenic mice (TG) and their TG negative (non-TG) littermates after BLM treatment were also compared. Serum samples of TG mice and non-TG mice were tested for their ability to block the binding of sialyl Lewis(x) to recombinant E-selectin in vitro. RESULTS: E-selectin mRNA was maximally induced at six hours after BLM treatment in the ICR mice. The soluble form of E-selectin which can competitively inhibit the binding of sialylated antigens on inflammatory cells to E- and P-selectins on the endothelium was detected in the serum of TG mice. BLM induced lung fibrosis occurred in non-TG mice but not in TG mice. This result confirms the finding that the serum of TG mice inhibits the binding of sialyl Lewis(x) to E-selectin in vitro. CONCLUSION: E-selectin plays an essential role in BLM induced lung fibrosis through the induction of neutrophil and other inflammatory cell accumulation, and soluble E-selectin may be of use in the prophylactic treatment of lung fibrosis.
Animals↗
Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation.
BACKGROUND: Activated T lymphocytes are one of the characteristic features of sarcoidosis. The mechanism of T cell activation, expressing various activation markers including interleukin 2 receptor (IL-2R), has been extensively investigated but the precise mechanism remains unknown. Although thioredoxin (TRX) displays a number of biological activities including IL-2R inducing activity, its role in the induction of IL-2R expression on T cells in sarcoidosis has not been determined. The expression of TRX and IL-2R in granulomas of patients with sarcoidosis has been studied to clarify a possible role for TRX in the induction of IL-2R expression. METHODS: Granulomas in specimens of lung tissue and lymph nodes from five patients with sarcoidosis were immunohistochemically stained with anti-TRX antibody and anti-IL-2Ralpha chain antibody and the concentration of TRX in the bronchoalveolar lavage (BAL) fluid from 20 patients with pulmonary sarcoidosis was measured. RESULTS: Granulomas in lung and lymph node tissue from patients with sarcoidosis showed strong reactivity with anti-TRX antibody. Positive staining was present in the macrophages, epithelioid cells, and Langhans' type giant cells but not in lymphocytes. IL-2R was expressed on lymphocytes in the same granulomas. By contrast, positive immunoreactivity was not found in lung tissue specimens from 12 control subjects. Concentrations of TRX in BAL fluid were higher in patients with pulmonary sarcoidosis (median (range) 122.6 (20.9-303.3) ng/ml) than in control subjects (32.9 (16.8-52.8) ng/ml, p<0.05). CONCLUSIONS: TRX is highly expressed and is locally produced by granulomas in patients with sarcoidosis. The coexistence of immunoreactive TRX and IL-2R in the same granulomas suggests that TRX might act as a local inducing factor for IL-2R expression on T cells.
Adult↗
Can serum carnitine levels distinguish hypertrophic cardiomyopathy from hypertensive hearts?
Although echocardiography is a useful diagnostic tool in hypertrophic cardiomyopathy (HCM), it is sometimes difficult to differentiate it from hypertensive heart disease (HHD): some patients with HCM show symmetrical hypertrophy, whereas patients with HHD sometimes show asymmetrical septal hypertrophy. We used a radioiodinated long-chain fatty acid tracer to visualize the altered myocardial fatty acid metabolism of HCM and HHD. Carnitine is the essential substance for the beta-oxidation of long-chain fatty acids. We recently reported that serum free carnitine levels in HCM were elevated and that they were significantly correlated with the severity of myocardial fatty acid metabolic disorder. Therefore, we investigated serum carnitine levels in patients with HCM and HHD, which can contribute to the differentiation of each other. We studied 56 patients with HCM and 20 patients with essential hypertension. Serum free carnitine levels were significantly higher in patients with HCM than those with HHD (HCM 52.5+/-9.5 nmol/mL, HHD 46.6+/-6.4 nmol/mL, P<0.01), but they showed no statistical difference between patients with HHD and normal subjects. Serum acylcarnitine levels were significantly lower in patients with HCM than those with HHD (HCM 10.1+/-4.0 nmol/mL, HHD 14.5+/-4.9 nmol/mL, P<0.0005), although they did not differ between patients with HHD and normal subjects. Scintigraphic analyses with a long-chain fatty acid analog revealed that myocardial tracer uptake was much reduced in patients with HCM compared with that in patients with HHD (quantitative analysis: HCM 2.11+/-0.12, HHD 2.22+/-0.17, P<0.05; semiquantitative analysis: HCM 13.6+/-6.3, HHD 2.0+/-1.5, P<0.0001). In conclusion, the differences in serum carnitine levels between HCM and HHD reflect altered myocardial fatty acid metabolic impairment, and the levels can help to distinguish these 2 diseases.
Adult↗
Serological diagnosis of idiopathic pulmonary alveolar proteinosis.
Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).
Adult↗
Identification of protein disulfide isomerase as a phorbol ester-binding protein.
A specific binding protein for 12-O-tetradecanoylphorbol 13-acetate (TPA), different from protein kinase C (PKC) and histone H1, was purified from HeLa cell extract by the use of affinity gel pendanted with phorbol ester (TPA-GEL). The purified binding protein was identified as protein disulfide isomerase (PDI, EC 5.4.3.1) by peptide sequence analysis. The dissociation constants (Kd's) of TPA to PDI, histone H1 and PKCalpha were determined to be 1.03 x 10(-6) M, 5.70 x 10(-7) M, and 4.00 x 10(-7) m, respectively, by the surface plasmon resonance (SPR) method. TPA moderately inhibited PDI activity assessed in terms of reactivation of denatured RNase A.
Amino Acid Sequence↗
Interstitial pneumonia complicated by Sjögren's syndrome, Hashimoto's disease, rheumatoid arthritis and primary biliary cirrhosis.
A 66-year-old woman diagnosed as having Hashimoto's disease and rheumatoid arthritis manifested interstitial pneumonia. We diagnosed Sjögren's syndrome and primary biliary cirrhosis as complications in this case. Steroid therapy was relatively effective for the interstitial pneumonia which was in an active state; however, during tapering of the steroid, there was a relapse and also severe dry throat. Cyclophosphamide was added and was effective in the prevention of recurrence. Even after discontinuation of steroid therapy, her general condition is stabilized. It is very important to carefully investigate other organ involvement as a prognostic factor in cases in which there are multiple autoimmune diseases.
Aged↗
[Two cases of microvascular vasospastic angina usefulness of 99mTc-tetrofosmin myocardial SPECT in clinical diagnosis].
Case 1 involved a 52-year-old man with angina chest pain at rest and case 2 involved a 63-year-old woman with chest oppression at rest. An electrocardiogram (ECG) showed negative T wave in III and aVF leads in case 1, and complete atrioventricular block and ST segment depression in II, III, aVF, and V5-6 leads in case 2. In both cases, 99mTc-tetrofosmin myocardial SPECT showed reduced uptake in the inferior and posterior wall. Although bath patients' left coronary arteriographies were normal, right coronary arteriographies revealed severely delayed filling of contrast medium without significant narrowing of epicardial coronary arteries, suggesting microembolism or microvascular vasospasm. An intracoronary infusion of isosorbide dinitrate did not improve the delayed filling of contrast medium or ST segment depression on ECG. Soon after intracoronary infusion of diltiazem in case 1 and nicorandil in case 2, coronary arterial flows were normalized, chest symptoms disappeared, and ECG findings were normalized. The next day, both patients' 99mTc-tetrofosmin myocardial SPECT showed normal uptake. These findings suggest that myocardial ischemia in these cases might be explained as having been caused by microvascular spasm.
Calcium Channel Blockers↗