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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 163 records · Page 9Linked to original sources

Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects.

The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P << 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P << 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.

Administration, Inhalation↗

Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum (Trichosporon asahii).

The case of a 46-year-old man with a chronic cough with sputum eosinophilia (atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii) is reported. The diagnosis was made with the inhalation challenge test with T. asahii antigen. He was admitted for the diagnosis and treatment of a severe nonproductive cough in the summer season. Although his sputum contained 13% eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not effective for his cough. His symptoms worsened on returning home, suggesting the existence of some etiologic agent in his house. A high titer of serum anti-Trichosporon antibody was detected and antigen provocation test with the Trichosporon extract was positive: the development of a cough 6 h later and a decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 microM from 31.3 microM prechallenge). This is the first report on a chronic cough with sputum eosinophilia induced by T. cutaneum (T. asahii).

Chronic Disease↗

Bronchoprotective effect of an intrabronchial administration of cilostazol powder and a nebulized PDE1 and PDE4 inhibitor KF19514 in guinea pigs.

BACKGROUND: Both oral and intravenous inhibitors of cyclic nucleotide phosphodiesterase (PDE) 3 and PDE4 have been shown to have bronchodilator and/or pulmonary antiallergic effects but their adverse effects limit the clinical use. The purpose of the present study was to assess the bronchoprotective effect of intrabronchial administration of a selective PDE3 inhibitor, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone (cilostazol), in dry power form which is proposed to be desirable rather than propellant-driven metered-dose inhalers. METHODS: Effect of an intrabronchial administration of cilostazol powder on aerosolized histamine- and antigen-induced leukotriene-mediated bronchoconstriction were examined in anesthetized and artificially ventilated guinea pigs, in comparison with the effects of ultrasonically nebulized 5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c] [1,8] naphthyridin-4(5H)-one (KF19514), a selective PDE1/4 inhibitor. RESULTS: Cilostazol powder and KF19514 solution inhibited histamine- and antigen-induced bronchoconstriction in a dose-dependent manner. When assessing the resulting ED50 values, the activity of cilostazol powder against antigen-induced broncho-constriction was weaker than its antagonism of histamine-induced bronchoconstriction (60.4 vs. 7.0 microg), while those of KF19514 were the opposite (0.40 vs. 2.81 microg/ml). CONCLUSION: These results suggest that intrabronchially administered cilostazol powder has a bronchodilator effect, and ensure that PDE4 inhibitors have an antiallergic activity in addition to their bronchodilator effect.

3',5'-Cyclic-AMP Phosphodiesterases↗

Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8.

Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5 microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3 weeks. One day after the last administration, animals were anaesthetized and artificially ventilated through tracheal cannulae, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[-1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057, but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil accumulation in guinea-pigs in vivo. In part this appears to be due to release of leukotriene B4, whereas it may not be mediated by neutrophil elastase.

Animals↗

Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females.

We have shown previously that female sex is a determinant of cough sensitivity to inhaled capsaicin, but the relationship between atopy and the cough sensitivity has not been examined. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, nonspecific bronchial responsiveness, defined as the provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20), total immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar, ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led questionnaire on allergic diseases revealed that one and six subjects had mild current and past asthma, respectively. These seven subjects were excluded from the data analysis. PC20 was significantly lower in 42 subjects showing a positive specific IgE than in 22 subjects showing a negative specific IgE to any of the eight allergens (p<0.05), while the capsaicin cough threshold was not significantly different between the subgroups. PC20 was significantly lower in subjects with positive specific IgE to Dermatophagoides and house dust, but not to the three kinds of pollen examined. It was confirmed that atopy indicated by specific immunoglobulin E to mite-related antigens, but not to pollen antigens, is associated with nonspecific bronchial responsiveness, and it is suggested that atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic subjects.

Adult↗

Chylothorax associated with inflammatory carcinoma.

We report a rare case of a woman with inflammatory carcinoma, an unusual type of cutaneous metastasis, arising from signet-ring cell carcinoma of the stomach, who developed chylothorax as the skin lesion progressed over the chest. No thoracoabdominal lymphadenopathy which can cause obstruction of the thoracic duct was shown by computed tomography. Although a very rare condition, inflammatory carcinoma could be a cause of non-traumatic chylothorax.

Adenocarcinoma↗

Primary prostatic lymphoma of mucosa-associated lymphoid tissue.

We present a case of primary prostatic lymphoma referring to a 57-year-old man, who was admitted with the symptom of bladder outlet obstruction, and had a history of urination difficulty for two years. The symptoms and signs were compatible with a diagnosis of benign prostatic hypertrophy (BPH). The pathology of the specimen obtained from transurethral prostatectomy showed B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The patient has been asymptomatic and under complete remission after completion of chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine and prednisone for 6 cycles.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of a new anti-cancer drug regimen for endometrial cancer].

BACKGROUND: The purpose of this study was to describe a new anti-cancer drug regimen for endometrial cancer. METHODS: The cytotoxicities of some anti-cancer drugs regimens against human endometrial cancer xenografted into nude mice (TEI, TET, TEU, TEN) have been studied. The activities of ADM, CDDP, CPM, CPT-11, TXL, CDDP + ADM, CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + TXL were evaluated in comparison with a control group using saline. Three mice were used for each group, and when xenografted tumor reached 6 mm of its diameter, 1/5 LD50 of these drugs was administered into the periotoneal cavity mice once a week for three weeks. RESULTS: The effective regimens were CPT-11 + TXL, CDDP + CPT-11, CDDP + CPM, CDDP + TXL for the endometrial cancer. CONCLUSIONS: It is suggested that these new drugs regimens should be tested in clinical studies.

Animals↗

[Experience of weaning from left ventricular assist system in an acutely-ill patient with dilated cardiomyopathy and severe left ventricular dysfunction: a case report].

A 21-year-old man with dilated cardiomyopathy recovered from terminal heart failure with the long-term use of the left ventricular assist system (LVAS). His heart failure was refractory to maximum medical therapy including beta-blockade and intravenous catecholamines. Application of LVAS restored renal and hepatic function and even cardiac function. Left ventricular size decreased from 79 to 57 mm, and cardiac index increased from 1.6 to 2.2 l/min/m2. After 6 weeks of LVAS application, he could walk in the ward and could start exercise on a bicycle ergometer 3 months after. Ninety-five days after implantation, the LVAS could be removed. His general condition remained good and stable for more than a year after the removal of the LVAS. Timely application of LVAS seems to be one of the most important factors for successful circulatory support. Detailed criteria for LVAS application are not established yet.

Adult↗

[Evaluation of a new anti-cancer drug regimen for surface epithelial-stromal ovarian cancer].

BACKGROUND: The purpose of this study was to describe a new anti-cancer drug regimen for epithelial ovarian cancer. METHODS: The cytotoxicities of some anti-cancer drugs regimens against human epithelial ovarian cancer xenografted into nude mice (TOM, TOH, TON) have been studied. The activities of CDDP, CPT-11, TXL, CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + CPM, CPT-11 + TXL, and TXL + CPM were evaluated comparing with a control group using saline. Three mice were used for each group, and when the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs was administered into the peritoneal cavity of mice once a week for three weeks. RESULTS: The three most effective regimens were CPT-11 + TXL, CDDP + CPM, and CDDP + CPT-11 for epithelial ovarian cancer.

Adenoma↗

[A case of systemic lupus erythematodes with hemosputum and pneumothorax probably resulting from pulmonary infarction and pulmonary angitis].

A 23-year-old man was admitted with fever, bloodysputum and consolidation in the bilateral lower lobes. Pulmonary infarction in the potla lower lobes was suspected because a lung perfusion scan showed a blood flow defect in the same places. Transbronchial biopsy was performed, and pulmonary hemorrhage and pulmonary angitis were demonstrated in the left lower lobe. His fever and bloodsyputum improved after steroid therapy, suggesting that pulmonary angitis may have been responsible for the bloodysputum. Subsequently pneumothorax occurred. In this case pulmonary infarction associated with pulmonary angitis may have been responsible for the pneumothorax.

Adult↗

[Bronchial asthma due to Stronger Neo-Minophagen C].

A 24-year-old woman who visited our hospital because of urticaria had a bronchial asthma attack about 5 min. after receiving Stronger Neo-Minophagen C (SNMC) intravenously. A skin test for SNMC and its components (glycyrrhizin, L-cystein, aminoacetic acid, and sodium sulfite) was positive for SNMC and borderline for sodium sulfite after 15 min. A skin test for mixtures of L-cystein and sodium sulfite was also positive. Inhalation provocation tests for SNMC and mixtures of L-cystein and sodium sulfite were positive after 5 min. An inhalation provocation test for sulpyrin was also positive. The patient's bronchial asthma attack was ascribed to SNMC. Type I allergy to mixtures of L-cystein and sodium sulfite was the suspected cause.

Adult↗

[A case of mediastinal teratoma discovered availing of pneumonia].

A 42-year-old woman was admitted to our hospital with hemosputum and an abnormal shadow on chest X-ray. Although her hemosputum disappeared after the treatment of pneumonia, the abnormal shadow was not improved. Chest CT showed a mediastinal mass. She underwent thoracotomy and the tumor, measuring 6 x 5 x 5 cm in size, was resected. Pathological diagnosis was a mature type teratoma with direct invasion to the lung. We have to take mediastinal teratoma into consideration as one of the causes of pneumonia.

Adult↗

Attenuation of nitric oxide synthase induction in IRF-1-deficient glial cells.

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of iNOS, is thought to facilitate neuronal damage during cerebral ischemia. Recently, interferon regulatory factor-1 (IRF-1) has been reported to be an essential transcription factor for iNOS mRNA induction in murine macrophages. However, expression of IRF-1 and its role in the central nervous system have not been examined. In the present study, by using primary glial cell cultures from mice with targeted disruption of the IRF-1 gene, we investigated whether IRF-1 is involved in iNOS mRNA induction in glial cells. After stimulation with lipopolysaccharide and interferon-gamma, IRF-1 mRNA was strongly induced in wild-type (IRF-1 +/+) glial cells. iNOS mRNA induction and nitrite production in IRF-1 -/- glial cells were reduced as compared with those observed in IRF-1 +/+ glial cells. Diethyldithiocarbamate, a selective inhibitor of nuclear transcription factor kappa B (NF-kappa B), completely inhibited iNOS mRNA induction. These results suggest that not only NF-kappa B but also IRF-1 play important roles in iNOS mRNA induction in the central nervous system.

Animals↗

Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells.

Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction.

Animals↗

Bronchoprotective effects of KF-19514 and cilostazol in guinea pigs in vivo.

It has been shown that inhibitors of cyclic nucleotide phosphodiesterase III and IV have a bronchodilator effect. We compared the effects of a selective phosphodiesterase III inhibitor, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone (cilostazol) and a phosphodiesterase I/IV inhibitor, 5-phenyl-3-(3-pyridil) methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (KF-19514) on antigen- and histamine-induced bronchoconstriction in guinea pigs in vivo. Intravenous administration of cilostazol and KF-19514 inhibited histamine- and antigen-induced bronchoconstriction in a dose-dependent manner. When assessing the resulting ED50 values, the activity of KF-19514 against antigen-induced bronchoconstriction was stronger than its antagonism of histamine-induced bronchoconstriction (0.004 vs. 0.056 mg/kg). while those of cilostazol were contrary (0.835 vs. 0.031 mg/kg). These results suggest that although both inhibitors of phosphodiesterase III and phosphodiesterase IV have a bronchodilator or bronchoprotective effect, phosphodiesterase IV inhibitors such as KF-19514 may be more useful for asthma treatment because KF-19514 had an anti-allergic effect in addition to the functional bronchodilator activity.

Animals↗

A ruptured aneurysm at the distal end of the basilar artery fenestration associated with multiple fenestrations of the vertebrobasilar system: case report.

BACKGROUND: An aneurysm at the fenestrated basilar artery usually arises at the proximal end of the fenestration, with few exceptions. We failed to reveal any case of aneurysm at this site associated with multiple fenestrations of the vertebrobasilar system. CASE REPORT: This 62-year-old male was admitted to our hospital 1 day after a sudden onset of headache. CT scan showed subarachnoid hemorrhage, and angiogram revealed an aneurysm at the distal end of the fenestrated basilar artery in association with two other fenestrations of the vertebrobasilar system. The limb of the basilar artery fenestration was trapped tightly with one clip through the transcondylar approach. Postoperative course was uneventful, and postoperative angiogram showed complete disappearance of the aneurysm. CONCLUSION: An extremely rare case of an aneurysm at the distal end of the fenestrated basilar artery in association with multiple fenestrations of the vertebrobasilar system is reported. The coexistence of vertebral artery fenestration and the fenestration of the vertebrobasilar junction may give a clue to the mechanism of occurrence of basilar artery fenestration.

Aneurysm, Ruptured↗

Inhibitory effect of indomethacin on tachyphylaxis in response to acetaldehyde-induced bronchoconstriction in patients with asthma.

BACKGROUND: Acetaldehyde, a main factor in alcohol-induced asthma, causes bronchoconstriction indirectly through histamine release; and tachyphylaxis in response to repeated inhalation of acetaldehyde is observed in patients with asthma. OBJECTIVE: The study was designed to clarify the mechanism of tachyphylaxis in response to acetaldehyde-induced bronchoconstriction. METHODS: We investigated the bronchial response to inhaled acetaldehyde in 10 patients with asthma who were treated with indomethacin in a double-blind, randomized, placebo-controlled, crossover fashion. RESULTS: The mean acetaldehyde concentration causing a 20% fall in FEV1 with placebo increased significantly from 13.0 mg/ml (geometric SEM = 0.115) to 31.1 mg/ml (geometric SEM = 0.069) over a period of 1 hour (p < 0.01), whereas there was a slight but not significant tachyphylaxis during indomethacin treatment. The tachyphylactic effect, expressed as logarithmic value of the second PC20 minus logarithmic value of the first PC20, was significantly (p < 0.05) reduced from 0.380 (0.066) with placebo treatment to 0.148 (0.094) with indomethacin treatment. CONCLUSION: These results suggest an important role of cyclooxygenase pathway products in decreased response to repeated inhalation of acetaldehyde in patients with asthma.

Acetaldehyde↗