Gelatinase B deficiency does not protect against lipopolysaccharide-induced acute lung injury.
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Animals↗
Biomedical subjects
T Betsuyaku
Publications and source records attributed to T Betsuyaku.
Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema.
This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in comparison with neutrophil elastase (NE) complexed with alpha1-protease inhibitor (NE-alpha1-PI), which was previously demonstrated to be increased in bronchoalveolar lavage (BAL) fluid from subjects with subclinical emphysema. Eight nonsmokers and 31 current smokers with (n=17) and without (n=14) emphysema, as evidenced by lung computed tomographic scans, were studied. The concentrations of immunologically detected cathepsin L and cystatin C, but not cathepsin B, were significantly increased in BAL fluid from the smokers with emphysema compared with those without emphysema, although the activity of cathepsin L, measured using a synthetic substrate and cathepsin L, released from cultured alveolar macrophages at 24 h, did not show any significant difference between the two groups. When comparison was made only for the subjects aged <60 yrs, the difference between the two groups disappeared for cathepsin L, but remained for NE-alpha1-PI. There was no significant correlation between the level of cathepsin L and that of NE-alpha1-PI in BAL fluid from the subjects with emphysema. In conclusion, increased levels of cathepsin L and cystatin C were demonstrated in bronchoalveolar lavage fluid from subjects with subclinical emphysema. However, the roles of cathepsin L and neutrophil elastase in the development of emphysema may vary between subjects and between the young and the old.
Adult↗
Topoisomerase II alpha content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines.
PURPOSE: Topoisomerase II alpha content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. METHODS: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase II alpha levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. RESULTS: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase II alpha levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean +/- SD 0.89 +/- 0.54 and 5.3 +/- 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 +/- 0.56 and 4.0 +/- 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase II alpha levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. CONCLUSIONS: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase II alpha levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase II alpha levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.
Adenocarcinoma↗
The efficacy of radiofrequency catheter ablation for the treatment of ventricular tachycardia associated with cardiomyopathy.
We performed radiofrequency catheter ablation (RF ablation) for ventricular tachycardia (VT) in 2 patients with dilated cardiomyopathy (DCM) and 1 patient with arrhythmogenic right ventricular dysplasia (ARVD). Patient 1 had incessant VT associated with DCM. RF ablation was performed where diastolic potentials were recorded and concealed entrainment was demonstrated. VT was terminated by RF ablation. Patient 2 had drug-resistant VT associated with ARVD. RF ablation was performed where perfect pace-mapping was obtained during sinus rhythm, diastolic potentials were recorded and concealed entrainment was demonstrated. VT was terminated by RF ablation. Patient 3 had 2 morphologically distinct VTs associated with DCM. The target for RF ablation was 1 of the 2, which was a drug-resistant type. Perfect pace mapping was obtained where delayed potentials were recorded. As the current strength of pacing was reduced, the QRS complex configuration switched to the other type. This site was thought to be the common slow conduction zone for the re-entry circuit of the 2 types and RF ablation was performed at this site. In these 3 cases, VT did not recur after ablation. RF ablation is effective for the treatment of VT associated with cardiomyopathy.
Aged↗
Pulmonary function is diminished in older asymptomatic smokers and ex-smokers with low attenuation areas on high-resolution computed tomography.
OBJECTIVES: The relation between pulmonary function and low attenuation areas (LAAs) on high-resolution computed tomography (HRCT) is not clear in subclinical pulmonary emphysema. Accordingly we examined pulmonary function and HRCT in asymptomatic community-based volunteers. DESIGN: The existence of LAAs on CT was evaluated independently by three respiratory physicians who were blind to the pulmonary function test data and smoking histories of the subjects. The LAA grade was assessed by a visual scoring method from 0 to 5, and the individual LAA score and the values of pulmonary function tests were compared. PARTICIPANTS: 57 subjects aged from 32 to 82 years [mean 62 +/- (SD) 11] years were enrolled in the study. RESULTS: LAAs were found in 20 of the 49 subjects who were current or ex-smokers but in none of the 8 who never smoked. LAAs observed were mostly less than 25% of the total areas of the lungs. Although all mean values were within normal limits, the forced expiratory volume in 1 s (%pred), maximal expiratory flow at 50% of forced vital capacity (%pred), diffusing capacity of the lungs for carbon monoxide (DLCO; %pred) and diffusing capacity for carbon monoxide per unit alveolar volume (DLCO/VA; %pred) were all significantly less in those with LAAs than in those without LAAs. There was also a significant tendency for DLCO %pred and DLCO/VA %pred to decrease as the LAA scores increased. CONCLUSION: Those who have LAAs on CT have a small but significant deterioration in pulmonary function tests even if the LAAs observed are minimal or mild in degree. Longitudinal studies will be necessary to determine whether LAAs on CT identify the subjects who will develop airflow obstruction over time.
Adult↗
Elastin-derived peptides and neutrophil elastase in bronchoalveolar lavage fluid.
To evaluate effects of current smoking on the breakdown of lung elastin, we measured levels of elastin-derived peptides (EDP) in unconcentrated bronchoalveolar lavage (BAL) fluid from 42 community-based older asymptomatic volunteers (60 +/- 11 yr [mean +/- SD]) and examined the relationships of the concentrations of EDP with immunologically detected neutrophil elastase (NE) bound with alpha(1)-proteinase inhibitor and with esterolytic activity against the NE-sensitive synthetic substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA). The measurement of EDP levels was carried out by an indirect, competitive ELISA, using a sheep IgG fraction generated against insoluble human lung elastin as a primary antibody. EDP concentrations were significantly elevated in current smokers (n = 24) compared with age-matched noncurrent smokers (n = 18) (29.9 +/- 3.5 [mean +/- SE] versus 17.0 +/- 1.8 ng/mg BAL fluid albumin, p < 0.01). We found weak but significant correlations of EDP levels with NE-alpha(1)-proteinase inhibitor complex (r = 0.38, p < 0.05) and with the esterolytic activity against the NE-sensitive synthetic substrate in BAL fluid (r = 0.65, p < 0.001). In addition, EDP levels in BAL fluid had a significant positive relationship with plasma cotinine concentrations (r = 0.53, p < 0.001), though not with pack-years of smoking (r = 0.1, NS). These data provide further evidence that the concentrations of EDP increase in BAL fluid from current smokers compared with noncurrent smokers and that enhanced breakdown of the lung elastin is associated with the increased load of NE in the lung.
Aged↗
A case of adenosine-sensitive ventricular tachycardia in a very elderly male.
The best-known type of adenosine-sensitive ventricular tachycardia is idiopathic and of right ventricular outflow origin; however, there is little information about other types of adenosine-sensitive ventricular tachycardia. Idiopathic adenosine-sensitive ventricular tachycardia is common in the young. An 87-year-old man with ventricular tachycardia was admitted to our hospital. His ventricular tachycardia was sensitive to adenosine triphosphate, edrophonium, verapamil, and Valsalva's maneuver. He had experienced no anginal episodes. His ventricular tachycardia was thought to be idiopathic. We report this very rare case of adenosine-sensitive ventricular tachycardia, which was not derived from the right ventricular outflow tract, in a very elderly male.
Adenosine↗
[Effect of aging on respiratory system].
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Adult↗
[Neutrophil elastase and elastin-derived peptides in BAL fluid and emphysematous changes on CT scans].
We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV1. We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not.
Aged↗
Neutrophil elastase associated with alveolar macrophages from older volunteers.
We focused on the role of neutrophil elastase (NE) in alveolar macrophages (AMs), and evaluated the esterolytic activity using an NE-sensitive substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA) in AMs from 36 older healthy volunteers (61 +/- 2 yr mean age +/- standard error) and examined the relationship to chronic effects of cigarette smoking and also to the presence of low attenuation areas (LAAs) on the computed tomographic (CT) scans. The AMs from the subjects with LAAs showed significantly higher activity than those from the current smokers without LAA (1.16 +/- 0.40 versus 0.34 +/- 0.07 nM, respectively, p < 0.05). Although the study of inhibitory profile revealed that the esterolytic activity could not be attributed to NE alone, the NE activity seemed to dominate in AMs at least from some who had higher esterolytic activity. We then examined the releasability of NE from cultured AMs in 10 subjects. The immunologic NE complex with alpha 1-protease inhibitor (alpha 1-PI) was released significantly higher in the LAA(+) group than in the LAA(-) group (17.4 +/- 6.5 versus 1.8 +/- 0.6 micrograms/L, respectively, p < 0.05). These data suggest that NE in AMs may play a role in the development of emphysematous changes in susceptible smokers.
Adult↗
Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema.
In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.
Aged↗
A case of familial ventricular tachycardia.
Ventricular tachycardia was noted in 4 members of the same family. One showed diffuse hypokinesis of the left ventricle by echocardiography and left ventriculography, 2 showed progressive left ventricular dysfunction and 1 showed regional perfusion defects of the left ventricle shown by thallium scintigraphy. One patient was diagnosed as dilated cardiomyopathy. Although no definitive cause of the left ventricular disturbance was identified in the 3 other patients, they may have all been dilated cardiomyopathy.
Cardiomyopathy, Dilated↗
Establishing diagnosis of pulmonary malignant lymphoma by gene rearrangement analysis of lymphocytes in bronchoalveolar lavage fluid.
We report the successful application of gene rearrangement analysis to the lymphocytes obtained by bronchoalveolar lavage (BAL) for the diagnosis of pulmonary malignant lymphoma. A 45-yr-old female patient who had been suffering from back pain was shown to have macroglobulinemia and pulmonary infiltrative shadow by chest radiography. Transbronchial lung biopsy revealed a small B-cell infiltrate with monotypic immunoglobulin expression (IgM/kappa light chain), and malignant lymphoma was highly suspected. BAL was performed to evaluate the cell profiles. The phenotyping of lavaged lymphocytes by flow cytometry revealed that the major component of the lymphocytes was CD3-positive T cells, and that CD21-positive B cells accounted for only 10% of all lymphocytes. This result was contradictory to the immunohistochemical population of lymphocytes in biopsied specimens. However, gene analysis of lavaged lymphocytes revealed positive immunoglobulin heavy chain rearrangement and negative immunoglobulin light chain and T-cell receptor rearrangement, suggesting that B cells making up a minor population of lavaged lymphocytes were proliferating monoclonally. Thus, in this case, gene analysis was an effective procedure for detecting the origin of tumor cells and distinguishing monoclonality from reactive accumulations. To our knowledge, this case represents the first reported application of gene rearrangement analysis to cells obtained by BAL. The sensitivity and usefulness of this analysis for the accurate evaluation of pulmonary lymphoproliferative lesions, when applied to BAL cells, should be emphasized.
Bronchoalveolar Lavage Fluid↗
[A study of microtubules in hypertrophied cardiomyocytes].
Microtubules, components of the cytoskeleton, play an important role in the maintenance of cellular shape, in intracellular transport of organelles and membrane vesicles, and in signal transduction in the cell. Studies on the role of microtubules in hypertrophied myocardial cells have been carried out using an acute pressure overloading model in which stenosis was produced in the aorta. Clinically, however cardiac hypertrophy is most frequently caused by a gradual increase in blood pressure due to essential hypertension. We evaluated the role of microtubulas by observing their serial changes in cells from spontaneously hypertensive rats (SHR), which are used as a model of essential hypertension. Blood pressure, body weight, left ventricular weight, and the cell cross-sectional area were measured in SHR and Wistar-Kyoto (WKY) rats aged 4, 6, 10, and 16 weeks (5 rats each). Microtubules in cardiocytes were observed using confocal laser scanning microscopy by the immunofluorescence method against beta-tubulin. Microtubules in cardiocytes run primarily in a longitudinal direction, thinly through the intermyofibrillar spaces and densely around the nuclei. The numbers of microtubules were measured separately in the perinuclear region and the nonperinuclear region, and their total was calculated. The cross-sectional area of a whole cell and nucleus was measured at the level of the nucleus, and microtubule density was calculated by the number of nonperinuclear microtubules in the cytosolic area. Five myocardial cells were randomly selected in each rat, and the mean density (/micron2) was observed. For comparison, similar analysis was done in an acute pressure loading model. This study showed that: 1) In the acute pressure overload model, hypertrophy was immediately observed, and microtubules were increased in 16% of cardiocytes. In SHR, an increase in blood pressure and hypertrophy of hearts were observed at the age of 6 weeks and after. The density of microtubules at the age of 4, 6, 10, and 16 weeks was 0.69 +/- 0.03 (/micron2), 0.73 +/- 0.05 (/micron2), 0.64 +/- 0.02 (/micron2), respectively, in WKY rats, and 0.54 +/- 0.03 (/micron2), 0.54 +/- 0.02 (/micron2), and 0.51 +/- 0.02 (/micron2), respectively, in the SHR, showing a relatively stability in the latter. This suggested that a gradual increase of blood pressure could not be a stimulus that changes the density and distribution of microtubules. 2) The immunofluorescence method against beta-tubulin using confocal laser scanning microscopy seems to be good method for quantitative analysis of microtubules in cardiocytes.
Animals↗
A phase II study of combination therapy with 5'-deoxy-5-fluorouridine and cisplatin in the treatment of advanced gastric cancer with primary foci.
BACKGROUND: 5'-Deoxy-5-fluorouridine (5'-DFUR, doxifluridine) is a recently developed prodrug of oral 5-fluorouracil (5-FU), which is used clinically in Japan for the treatment of gastric, colorectal, and breast cancer. 5-FU has been reported to act synergistically with cisplatin (CDDP) in experimental and clinical studies. The authors conducted a multicenter Phase II study of combination therapy with 5'-DFUR and CDDP to evaluate the therapeutic usefulness of this regimen in the treatment of unresectable and advanced gastric cancers with primary foci. None of the patients had previously undergone chemotherapy. Their ages ranged from 27 to 75 years and performance status was grade 0 to 3. METHODS: 5'-DFUR (1400 mg/m2/d) was administered orally on days 1 through 4 and 15 through 18, and CDDP (80 mg/m2/d) was injected intravenously on day 5. This treatment cycle was repeated every 4 weeks. An independent panel of specialists evaluated the clinical response. RESULTS: Fifty-one patients were studied. Clinical evaluation of response was possible in 43 patients who met the protocol requirements. The overall response rate was 50.0% (14 of 28, 95% confidence limits, 30.7%-69.4%) for patients with measurable lesions. The median duration of response was 5.2 months (156 days). The overall median survival time was 8.9 months (268 days) for evaluated patients. Therapeutic toxicity of World Health Organization (WHO) grade > or = 3 was manifested as anorexia and nausea or vomiting in 20.9% and 18.6% of the patients, respectively. However myelotoxicity and nephrotoxicity of WHO grades 3 and 4 occurred in less than 10% of the patient group. No drug-related mortality occurred. CONCLUSIONS: Combined therapy with 5'-DFUR and CDDP is a safe and effective treatment regimen for advanced gastric cancers with primary foci which stresses the patient's quality of life, especially when used in an outpatient setting.
Adenocarcinoma↗
A secondary amyloidosis associated with systemic lupus erythematosus.
Secondary amyloidosis associated with systemic lupus erythematosus has rarely been reported. A 57-year-old female had been diagnosed as having possible systemic lupus erythematosus, although her clinical course was not typical. About one year after the diagnosis, treatment was begun with prednisolone because of progressive renal dysfunction, thrombocytopenia and low serum levels of complements. Recurrent diarrhea and gastrointestinal bleeding soon developed, then amyloidosis was revealed in the stomach and duodenum. Postmortem examination confirmed systemic amyloidosis. We discuss the significance of this rare association of systemic lupus erythematosus and secondary amyloidosis.
Amyloidosis↗
[A case of hypersensitivity pneumonitis caused by a humidifier].
A 58-year-old woman was admitted complaining of dry cough and exertional dyspnea. Physical findings, chest X-ray films, chest CT scan and respiratory function tests were suggestive of interstitial pneumonia. Transbronchial lung biopsy showed specific findings of hypersensitivity pneumonitis. As a result of positive provocation test using her home humidifier, a diagnosis of humidifier lung was made. Many microorganisms including Flavobacterium meningosepticum were cultured from the water left in the humidifier for one week. As both complement fixation test and precipitation test were positive to humidifier water and to extract of Flavobacterium meningosepticum, the humidifier and Flavobacterium meningosepticum were suggested to be causative in this case.
Alveolitis, Extrinsic Allergic↗
[A case of vasovagal syncope associated with venipuncture].
A 33 year-old-man presented recurrent syncopal episodes after venipuncture. This was sometimes associated with seizure. It was also noted that the syncope was aroused by mental stress. The patient was admitted to the department of neurological medicine because of epilepsy. Cardiac arrest of more than 15 seconds was detected during the venipuncture-prooshed syncope test. He had normal routine testing, holter monitoring, head CT scan, carotid sinus massage, valsalva maneuver etc. The syncope was similar to a malignant vasovagal one which has no typical warning signs. He had recurrent syncopal episodes without typical prodrome. Therefore a DDD pacemaker was implanted. It has not been completely established as effective in the treatment of vasovagal syncope, but for the treatment of syncope involving cardioinhibitory action, dual chamber pacing in considered as the main treatment available.
Adult↗