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Biomedical subjects

K Kuwano

Publications and source records attributed to K Kuwano.

At least 91 records · Page 5Linked to original sources

Soluble form of P-selectin in patients with acute myocardial infarction.

BACKGROUND: P-selectin, an integral membrane glycoprotein of platelets and endothelial cells, is rapidly redistributed to the cell surface after cellular activation. The soluble form of P-selectin has been shown to be present in people with normal circulation. The purpose of the present study was therefore to examine the soluble form of P-selectin in patients with acute myocardial infarction (AMI). METHODS: Whole blood was obtained from nine patients with AMI and from 10 volunteers who made up the control group. Plasma concentrations of the soluble form of P-selectin were examined with a monoclonal antibody-based enzyme immunoassay. RESULTS: Plasma P-selectin levels in control volunteers were 178 +/- 44 ng/ml. In patients with AMI, plasma P-selectin levels on days 1, 2 and 3 were 743 +/- 374, 627 +/- 267, and 588 +/- 223 ng/ml, respectively (P < 0.001)--significantly higher than the levels in the control volunteers. CONCLUSION: Plasma concentrations of the soluble form of P-selectin were markedly higher in patients with AMI, suggesting the activation of platelets, or endothelial cells, or both. Thus, quantitative measurements of plasma P-selectin concentrations may help to assess the pathophysiology of inflammatory reactions in patients with AMI.

Adult↗

Cyclic flow variations in a conscious dog model of coronary artery stenosis and endothelial injury correlate with acute ischemic heart disease syndromes in humans.

OBJECTIVES: The purpose of this study was to test the hypothesis that episodes of cyclic flow variations (CFVs) in conscious dogs with coronary stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans. BACKGROUND: Although the canine model with CFVs has proved to be a useful model of coronary thrombosis, whether CFVs progress to these syndromes has not been clearly described. METHODS: Cyclic flow variations were produced by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery and 24-h Holter electrocardiogram (ECG) were recorded during the 1st 5 postoperative days. RESULTS: Of 41 dogs that underwent the initial operative procedure successfully, 29 developed an episode of CFVs. In five dogs in which CFVs persisted throughout the monitoring period, the left anterior descending coronary artery flow decreased until day 3 and thereafter increased through day 5. Transient coronary occlusion during CFVs induced ST segment changes that returned to baseline after reflow. In 12 dogs, CFVs progressed to persistent coronary occlusion, and histologic examination revealed thrombus formation at the stenotic site and evidence of myocardial infarction. Four of these 12 dogs died suddenly of ventricular arrhythmias during persistent coronary occlusion; another 5 dogs died of reperfusion arrhythmias during CFVs with no evidence of myocardial infarction. CONCLUSIONS: Conscious dogs with CFVs closely correlated with clinical acute ischemic heart disease syndromes, suggesting them to be a useful model for investigating the complex mechanisms of cellular interactions in the pathogenesis of these syndromes.

Animals↗

Antiviral effect of TNF-alpha and IFN-gamma secreted from a CD8+ influenza virus-specific CTL clone.

We observed that an influenza-specific cytotoxic T lymphocyte (CTL) clone (B7B7) stimulated with peptide-antigen could produce TNF-alpha and IFN-gamma simultaneously. The culture supernatant containing both TNF-alpha and IFN-gamma of antigen-stimulated CTL clone B7B7 significantly enhanced the lysis of influenza A/PR/8 virus-infected L-M2d6 cells or Meth A cells. Enhanced lysis of influenza virus-infected cells by the supernatants was inhibited by pretreatment of the supernatant with antimurine TNF-alpha antibody and antimurine IFN-gamma antibody. In addition to a single CTL clone, we observed that bulk-cultured CTLs were able to produce TNF and IFN when incubated with target cells. These results suggest that the protective mechanism mediated by TNF-alpha and IFN-gamma secreted from CTL may be possible in the course of an influenza infection.

Animals↗

Protective cross-reactive epitope on the nonstructural protein NS1 of influenza A virus.

We reported previously that adoptive immunization with an influenza A virus NS1-specific H-2Ld-restricted, cross-reactive, CTL clone A-11 established by stimulation with A/PR/8/34 virus (H1N1) reduced lung virus titers in mice challenged with virus in vivo (Virology 178:174-179, 1990). Using a set of recombinant vaccinia virus constructs containing truncated portions of the NS gene we have localized this cross-protective CTL epitope to the N-terminal region of the NS1 protein. This region of NS1 is active in inducing CD8+ CTL in vivo because virus-stimulated BALB/c immune spleen cells in bulk cultures also recognized the N-terminal region of the NS1 protein.

Animals↗

Effects of new quinolones on Mycoplasma pneumoniae-infected hamsters.

The efficacies of the new quinolones temafloxacin, ofloxacin, and ciprofloxacin were investigated against Mycoplasma pneumoniae in an experimental hamster pneumonia model. Hamsters were infected intratracheally with M. pneumoniae and sacrificed 18 h after the final medication, and their lungs were aseptically removed, homogenized, and cultured quantitatively. The efficacies of these drugs were determined by the CFU of M. pneumoniae in lungs. Temafloxacin and ofloxacin, but not ciprofloxacin, were active when the oral administration of 200 mg/kg of body weight per day (once per day) for 5 days was initiated 24 h after infection. Although no effect on the elimination of M. pneumoniae was observed after the administration of these drugs at 200 mg/kg/day at 5 days after infection, the continuous administration for 15 days of temafloxacin, but not ofloxacin or ciprofloxacin, significantly reduced viable M. pneumoniae in the lungs. These results suggest that temafloxacin and ofloxacin are effective in the acute phase of infection and, moreover, that temafloxacin is effective in the late stage of infection during which progressive lung alterations and continuous increases in mycoplasmal growth occurred. The peak levels of temafloxacin in sera and lungs after oral administration were similar to those of ofloxacin and higher than those of ciprofloxacin. The areas under the curve of temafloxacin in the lung tissue, however, were higher than those of ofloxacin and ciprofloxacin. On the basis of these results, temafloxacin and ofloxacin might be promising antimicrobial agents for the treatment of mycoplasmal infection.

Animals↗

In vitro and in vivo activities of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae.

The in vitro potency and in vivo efficacy of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae were investigated by pharmacokinetic studies with M. pneumoniae-infected hamsters. By using fluoroquinolones, macrolides, and tetracyclines as references, Q-35 was found to possess the greatest mycoplasmacidal activity. The MIC for 90% of strains tested (MIC90) and the MIC50 were 0.78 and 0.39 microgram/ml, respectively, and the MBC for 90% of strains tested (MBC90) and the MBC50 were 3.13 and 0.78 microgram/ml, respectively. The MBC50-to-MIC50 ratio for Q-35 was 2. Furthermore, only Q-35 continued to be effective against 19 strains of erythromycin-resistant mutants of M. pneumoniae. The efficacies of fluoroquinolones against M. pneumoniae were also investigated by using an experimental hamster pneumonia model to measure the CFU of M. pneumoniae in the lungs. Q-35 and ofloxacin were efficacious following oral administration of 200 mg/kg/day for 5 days, initiated 24 h after infection, while ciprofloxacin was not active. Continuous administration of Q-35 for 10 days significantly reduced numbers of viable M. pneumoniae in the lungs. These results suggest that both Q-35 and ofloxacin are effective in the early phase of infection and, moreover, that Q-35 is also effective in the middle stage of infection, when progressive lung alterations and continuous increases in mycoplasmal growth occur. Peak levels of Q-35 in sera and lungs after oral administration were higher than those of ciprofloxacin but lower than those of ofloxacin. On the basis of these results, Q-35 appears to be a promising antimicrobial agent in chemotherapy of mycoplasmal infection.

Administration, Oral↗

Induction of macrophage-mediated production of tumor necrosis factor alpha by an L-form derived from Staphylococcus aureus.

We investigated the capability of an L-form derived from Staphylococcus aureus to induce tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal macrophages. The activity for TNF-alpha induction was found in the membrane fraction of the L-form but not in the cytoplasmal fraction purified by the sucrose step gradient centrifugation. TNF-alpha mRNA was also detected in macrophages stimulated with L-form membranes. L-form induced TNF-alpha production in macrophages from both lipopolysaccharide-responsive and -unresponsive mouse strains. Regardless of the presence of polymyxin B, the activity of TNF-alpha induction of L-form was mostly found in the phenol layer, but not in the aqueous layer, both of which were prepared by phenol extraction method. Fractions of L-form membranes representing molecular masses of approximately between 29 and 36 kDa were primarily responsible for inducing the production of TNF-alpha consistently. Moreover, this stimulatory effect was abolished by digestion with Streptomyces griseus protease. In Western blot (immunoblot) analysis with anti-lipoteichoic acid antibody, two bands (65 and 45 kDa) were observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the phenol layer, whereas one band (14 kDa) was observed in either the aqueous layer or lipoteichoic acid of S. aureus. These results suggest that the component in the membrane of the L-form, distinct from cell wall components such as teichoic acid or lipopolysaccharide, possesses the capability to stimulate TNF-alpha production by macrophages.

Animals↗

Functional significance of increased airway smooth muscle in asthma and COPD.

Using a computational model, we investigated the effect of the morphologically determined increased airway smooth muscle mass, adventitial mass, and submucosal mass observed in patients with asthma and chronic obstructive pulmonary disease (COPD) on the increase in airway resistance in response to a bronchoconstricting stimulus. The computational model of Wiggs et al. (J. Appl. Physiol. 69: 849-860, 1990) was modified in such a way that smooth muscle shortening was limited by the maximal stress that the muscle could develop at the constricted length. Increased adventitial thickness was found to increase constriction by reducing parenchymal interdependence. Increased submucosal thickness led to greater luminal occlusion for any degree of smooth muscle shortening. Increased muscle thickness allowed greater smooth muscle shortening against the elastic loads provided by parenchymal interdependence and airway wall stiffness. We found that for constant airway mechanics, as reflected by the passive area-pressure curves of the airways, the increased muscle mass is likely to be the most important abnormality responsible for the increased resistance observed in response to bronchoconstricting stimuli in asthma and COPD. For a given maximal muscle stress, greater muscle thickness allows the development of greater tension and thus more constriction of the lumen.

Adult↗

Small airways dimensions in asthma and in chronic obstructive pulmonary disease.

The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of spontaneous rupture of the ascending aorta].

We report a rare case of spontaneous rupture of the ascending aorta without any evidence of aneurysm formation or aortic dissection. A woman aged 64 was admitted to our cardiac care unit as an emergency patient with severe chest pain. Her face was pale and systolic blood pressure was 70 mmHg in spite of intravenous administration of dopamine (10 micrograms/kg/min). She had a history of hypertension for two years under good medical control. No trace of the chest trauma was noted before her admission. Physical examination revealed neck vein engorgement and distant heart sounds. Chest X-ray film showed enlargement of the cardiac silhouette. ECG showed no evidence of acute coronary syndrome. Pericardial effusion with a floating hematoma-like mass was detected by 2-dimensional echocardiogram. Pericardiocentesis revealed bloody pericardial fluid (Ht: 26%). Aortagraphy was performed resulting in a clinical diagnosis of acute aortic dissection, but there were no signs of a false lumen, aneurysm formation or extravasation of the contrast medium. Although continuous pericardial drainage was performed, she suddenly lost consciousness, collapsed and died. A longitudinal intimal laceration 5 cm long was observed in the ascending aorta. Pathological examination revealed cystic medial necrosis and irregularity of the elastic fibers in the media. No atheromatous plaque was noted in the intima. Spontaneous rupture of the aorta is a life-threatening condition that requires urgent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of adenocarcinoma presenting as a cavitary lesion with niveau formation].

Primary pulmonary adenocarcinoma rarely shows cavitation with a fluid level on chest roentgenograms. Herein we describe such a case misdiagnosed as pulmonary tuberculosis. The patient was a 63-year-old, female who had never smoked. Chest roentgenograms revealed a cavitary lesion in the left lower lobe, possessing a prominent fluid level. Fiberoptic bronchoscopic aspirate was positive for acid-fast bacilli on stains. Since there was no improvement with antituberculous chemotherapy, a left lower lobectomy was performed. The present case is of interest in the light of cavity formation in pulmonary carcinoma. The diagnosis and roentgenographic features are discussed.

Adenocarcinoma↗

Functional relationships between cyclodextrin glucanotransferase from an alkalophilic Bacillus and alpha-amylases. Site-directed mutagenesis of the conserved two Asp and one Glu residues.

Comparison of the amino acid sequences of cyclodextrin glucanotransferases (CGTases) with those of alpha-amylases revealed that two Asp and one Glu residues, which are considered to be the catalytic residues in alpha-amylases, were also conserved in CGTases. To analyze the function of the three conserved amino acid residues in CGTases, site-directed mutagenesis was carried out. The three mutant CGTases, in which Asp229, Glu257 and Asp328 were individually replaced by Asn or Gln, completely lost both their starch-degrading and beta-cyclodextrin-forming activities, whereas another mutant CGTase, in which Glu264 was replaced by Gln, retained these activities. The three inactive enzymes retained the ability to be bound to starch. These results suggest that Asp229, Glu257 and Asp328 play an important role in the enzymatic reaction catalyzed by CGTase and that a similar catalytic mechanism is present in both CGTases and alpha-amylases.

Aspartic Acid↗

Bioavailabilities of calcium, phosphorus and magnesium from whey mineral complex in growing male rats.

The bioavailabilities of Ca, P and Mg from whey mineral complex (WMC) were studied from the viewpoint of the mineral balance and bone properties in growing male rats and compared with bovine bone ash (BBA) and CaCO3. Ca source showed no significant effect on feed intake, body weight gain or feed efficiency (p < 0.05). When the dietary Ca level was 0.3%, the dry weight of the femur in rats fed WMC was significantly higher than that in rats fed BBA. The femur P content of rats fed 0.3% Ca as WMC was significantly higher than that of rats fed BBA or CaCo3. The breaking energy of the femur from rats fed WMC was significantly higher than that from rats fed BBA at a Ca level of 0.2% or 0.3%. There was the same tendency in bone densities as was observed in breaking properties. There was no significant difference in quantitative values for Ca balance among three groups of rats, whereas those rats fed WMC had a significantly higher P retention than other groups. Ca bioavailability from WMC and the effect on the utilization of P and Mg were discussed.

Animals↗

A case of an undifferentiated small cell carcinoma of the esophagus with a primary abdominal mass.

This paper reports a case with an undifferentiated carcinoma of the esophagus which primarily developed symptoms due to metastatic lesions. The case was a 59-year-old woman with a primary manifestation of an abdominal mass and with subsequent dysphagia. A protruding lesion with ulceration was found at the lower third of the thoracic esophagus by endoscopic examination and was histologically proved to be an undifferentiated carcinoma by biopsy. The abdominal mass was initially thought to be due to metastasis to an abdominal lymph node based on the diagnosis image finding at admission, but it was consequently found by autopsy to be a metastatic tumor in the liver. Therefore, undifferentiated carcinoma of the esophagus should be take into account for differential diagnosis of an abdominal mass.

Abdominal Neoplasms↗

Antimycoplasmal activities of new quinolones, tetracyclines, and macrolides against Mycoplasma pneumoniae.

Fifty strains of Mycoplasma pneumoniae were tested for susceptibility to new quinolones, tetracyclines, and macrolides. Temafloxacin, ofloxacin, and ciprofloxacin possessed the most mycoplasmacidal activity against these organisms. The MBC for 50% of the strains (MBC50)-to-MIC50 ratio for each of these drugs was 4. The MBC50-to-MIC50 ratios for the tetracyclines and macrolides were markedly higher, within a range of 32 to 2,000. On the basis of these results, temafloxacin and ofloxacin might be promising antimicrobial agents for the treatment of mycoplasmal infection.

4-Quinolones↗

Latent adenoviral infection in the pathogenesis of chronic airways obstruction.

Childhood infection of the respiratory tract has been proposed as an independent risk factor in the pathogenesis of the chronic obstructive pulmonary disease (COPD) that develops in cigarette smokers. The present study examines adult lung tissue for latent adenoviral DNA because many of its 41 serotypes cause childhood respiratory disease and the virus is known to persist in other tissues in a latent form. Lung tissue resected for solitary nodules from 20 patients with airways obstruction and 20 patients without airways obstruction, matched for age, sex, and smoking history, were compared to determine whether adenoviral DNA is more commonly found in patients with COPD. The polymerase chain reaction (PCR) was used to examine two widely separated segments of the adenoviral genome. In situ hybridization (ISH) was performed using a probe covering the entire viral genome to determine the types of cell infected by the virus. The PCR analysis showed that a 675 base pair target sequence of the E1A region of the adenovirus was present in most of the lungs studied with greater copy numbers in the smokers with airways obstruction in both paraffin-embedded (p less than 0.002) and frozen lung tissue (p less than 0.016), whereas the E3/19K region showed no difference between the groups. When sufficient copy numbers were present to localize the DNA by ISH it was found in epithelial cells of the smokers who had airways obstruction. These data are consistent with a current model of adenoviral integration into host DNA and suggest that the E1A region of the adenovirus may contribute to the pathogenesis of COPD.

Adenovirus Infections, Human↗

[In vitro antimicrobial activities of new quinolone antibiotics against Mycoplasma pneumoniae].

The antimicrobial activities against Mycoplasma pneumoniae of new quinolones (temafloxacin, ofloxacin, ciprofloxacin, enoxacin, and norfloxacin) and of tetracyclines and macrolides as controls were compared. Among new quinolones, temafloxacin, ofloxacin, and ciprofloxacin were more active than enoxacin and norfloxacin against fifty strains of Mycoplasma pneumoniae, giving MIC50 and MIC90 significantly lower than those of the latter two, by the agar-dilution method. The three more active antibiotics in the above assay were then determined for MICs and MBCs by the broth-dilution method. The MICs of every antibiotic except erythromycin determined by both the methods were very similar each other. The MICs of erythromycin determined by the broth-dilution method were ten-times higher than those determined by the agar-dilution method. Temafloxacin and ofloxacin gave MBCs only about four-times higher than MICs, whereas ciprofloxacin, minocycline, erythromycin and josamycin gave MBCs as much as 15 to 1,000-times higher than MICs. From the MICs and MBCs determined by the two assay methods, it is apparent that temafloxacin and ofloxacin, and to a less extent ciprofloxacin, have more potent mycoplasmacidal activities than do macrolides and tetracyclines.

Anti-Bacterial Agents↗

A case of malignant fibrous histiocytoma in the lung--resembling recurrent pulmonary thromboembolism.

Malignant fibrous histiocytoma (MFH) can be classified as a pleomorphic mesenchymal sarcoma which occurs most commonly in the extremities and retroperitoneum. We report a very rare case of MFH presumably originating in the pulmonary artery and resembling recurrent pulmonary thromboembolism. MFH was suggested by transbronchial biopsy and confirmed by open lung biopsy. Obstruction of the right main pulmonary artery and stenosis of the left main pulmonary artery was confirmed by pulmonary angiography.

Adult↗