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Biomedical subjects

Masaki Fujimura

Publications and source records attributed to Masaki Fujimura.

At least 91 records · Page 5Linked to original sources
PubMed2002

Isolated chronic cough with sputum eosinophilia caused by Humicola fuscoatra antigen: the importance of environmental survey for fungus as an etiologic agent.

We report here a 35-year-old man with isolated chronic cough associated with sputum eosinophilia in which Humicola fuscoatra (H. fuscoatra) antigen was an etiologic agent. He was admitted for the diagnosis and the treatment of his severe nonproductive cough. Although 80% of the nucleated cells in his induced sputum were eosinophils, he did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective against his coughing. His cough worsened on his return home, suggesting the existence of some etiologic agent in his house. H. fuscoatra was isolated from his house, and the bronchoprovocation test with H. fuscoatra antigen was positive: i.e., development of coughing and decrease in capsaicin cough threshold (capsaicin concentration causing five or more coughs) from the prechallenge value of 31.3 microM to 1.95 microM at 6 and 48 hr, respectively, after the challenge. In addition, repeated environmental survey for fungi was suggestive of the importance of H. fuscoatra in the sputum eosinophilia. This is the first report concerning chronic cough with sputum eosinophilia caused by allergic reaction to H. fuscoatra antigen.

Adult↗
PubMed2002

A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method.

PURPOSE: This phase I study was designed to determine the maximum tolerated dose of carboplatin combined with a fixed dose of docetaxel (60 mg/m(2)) and the safety and efficacy of this combination chemotherapy in unresectable non-small cell lung cancer. METHODS: Patients received a 60 min intravenous infusion of docetaxel followed by a 90 min infusion of carboplatin with dose escalation using the continual reassessment method. The starting dose of carboplatin was targeted to an area under the plasma concentration curve of 3 using Calvert's equation and dose escalation was based on course 1 toxicities. RESULTS: From January 1999 to February 2000, 16 patients entered this trial. The major dose-limiting toxicity was neutropenia. Thrombocytopenia was rare and major non-hematological toxicities included fever that was not associated with neutropenia and grade 2 nausea and vomiting. Objective responses were seen in five patients (response rate 31.3%). CONCLUSIONS: Based on this phase I clinical trial, the maximum tolerated dose of carboplatin combined with 60 mg/m(2) of docetaxel was a target area under the plasma concentration curve (tAUC) of 6 and the recommended tAUC for further trials is 5.5. This combination appeared to be effective for non-small cell lung cancer. A phase II clinical trial is recommended using 60 mg/m(2) of docetaxel and carboplatin with a tAUC of 5.5.

Aged↗
PubMed2002

Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D(2)-mediated manner.

T-helper (Th) 2-type cytokines predominate in decidua, plausibly accounting for protection of a semiallograft, the embryo and placenta, from attack by the maternal immune system. However, localization of Th2 and T-cytotoxic (Tc) 2 cells in decidua has not been reported, presumably because of the difficulty in detecting intracellular cytokines in tissues. Here, by staining tissues for a novel surface maker of Th2/Tc2, the chemoattractant receptor-homologous molecule CRTH2, which is expressed on Th2 cells, we show that CRTH2(+) Th2 cells and CRTH2(+) Tc2 cells are significantly increased at the materno-fetal interface (implantation site) in decidua. We also show that trophoblast, uterine epithelium and endometrial glands all express haematopoietic-type prostaglandin (PG) D(2) synthase (hPGDS). Since CRTH2 is a chemoattractant receptor for PGD(2) and mediates PGD(2)-dependent migration of blood Th2 cells, our findings suggest that Th2 and Tc2 cells may be recruited to the materno-fetal interface, at least in part in a PGD(2)-mediated manner.

Cell Separation↗
PubMed2002

HER2 is frequently over-expressed in ovarian clear cell adenocarcinoma: possible novel treatment modality using recombinant monoclonal antibody against HER2, trastuzumab.

Ovarian clear cell adenocarcinoma (CCA) is generally chemo-resistant. Recently the poor prognosis and resistance to chemotherapeutic agents of HER2/neu over-expressing tumors have become clear. Thus, we investigated the expression level of HER2 in surgically resected CCA and ovarian serous adenocarcinoma, endometrioid adenocarcinoma, and mucinous adenocarcinoma specimens, as well as CCA cell lines, by an immunohistochemical method. HER2 was over-expressed in 42.9% of CCA (P=0.026, vs. ovarian serous adenocarcinoma), 20.8% of ovarian serous adenocarcinoma, 23.1% of ovarian endometrioid adenocarcinoma, and 30.0% of mucinous adenocarcinoma specimens. Three CCA cell lines, RMG-1, HAC-II and KK were also positively stained for HER2. A flow-cytometric study of HER2 revealed 7.2-, 6.4- and 4.5-fold greater expression of HER2 than that of normal mammary gland, respectively. Trastuzumab, a humanized recombinant monoclonal antibody against HER2 significantly and dose-dependently reduced the growth of CCA cell lines in vitro. The extent of the inhibitory effect of trastuzumab was dependent on the expression level of HER2. Trastuzumab also dose-dependently inhibited the growth of xenografted RMG-1 tumor. The survival period of trastuzumab-treated mice was longer than that of the control group. From these findings, trastuzumab appears to be a candidate as a treatment modality for HER2 over-expressing ovarian CCA.

Adenocarcinoma, Clear Cell↗
PubMed2002

Macrophage colony-stimulating factor (M-CSF) prevents infectious death induced by chemotherapy in mice, while granulocyte-CSF does not.

To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not improved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P < 0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P < 0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy.

Animals↗
PubMed2002

Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.

BACKGROUND: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known. OBJECTIVE: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs. METHODS: Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge. RESULTS: Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge. CONCLUSION: Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.

Administration, Inhalation↗
PubMed2002

Acute eosinophilic pneumonia following cigarette smoking: a case report including cigarette-smoking challenge test.

A 21-year-old woman presented with acute progressive dyspnea. Chest computed tomography (CT) revealed diffuse bilateral infiltrates. Based on the results of transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid (BALF) and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspected that the disease was related to smoking because she had started smoking ten days before the onset of symptoms. Therefore, a cigarette-smoking challenge test was done with the patient's informed consent. After the challenge, eosinophilic pneumonia was documented by BALF and TBLB findings, which were similar to those detected on admission, without significant radiographic findings.

Acute Disease↗
PubMed2002

Reasons for the delays in the definitive diagnosis of lung cancer for more than one year from the recognition of abnormal chest shadows.

OBJECTIVE: Primary lung cancer generally has a poor prognosis if not diagnosed at an early stage. But some lung cancers grow very slowly. In particular, adenocarcinoma is sometimes observed for years with no change of tumor size. In this study, we examined the reasons for the delays in reaching a definitive diagnosis of lung cancer. METHODS: We retrospectively reviewed primary lung cancer cases between January 1995 and December 1999 and examined those whose definitive diagnoses were delayed for more than a year. RESULTS: A total of 222 primary lung cancers were diagnosed. Of those, 19 patients (group A, 8.6%) were diagnosed after more than a year, and the other 203 (group B, 91.4%) were diagnosed within one year. The proportion of women in group A was significantly higher than that in group B (p<0.05). The mean age of group A was significantly younger than that of group B (p<0.05). The Brinkman Index of group A was significantly lower than that of group B (p<0.05). The histologic types were significantly different between the two groups (p<0.05). In group A, 18 patients (94.7%) had adenocarcinomas. Five primary reasons for the delays in group A were identified: 1) Four patients were tentatively diagnosed as inflammation or benign tumor on CT and were consequently not followed-up. 2) The chest CT shadows in 6 patients were suspected lung cancers but transbronchial lung biopsy findings did not show malignancy. 3) Four patients were tentatively diagnosed as inflammation or benign tumor on CT, but the tumors showed only very slow growth or no change at all. 4) The chest CT shadows of 2 patients were suspected lung cancer, but the patients refused to undergo video-assisted thoracic surgery (VATS) or closer examination. 5) Three patients did not consult medical facilities for a second examination. CONCLUSIONS: Many of the adenocarcinomas reviewed in our study grew slowly or remained unchanged for years. Doctors are mainly responsible for the delays in the definitive diagnosis and should aggressively perform VATS or closer examinations without hesitation.

Adenocarcinoma↗
PubMed2002

[Apoptosis as a measure of chemosensitivity to anti-cancer drugs in gynecological cancer].

OBJECTIVE: To examine apoptosis as a measure of chemosensitivity to anti-cancer drugs in gynecological cancer xenografted into nude mice. METHODS: The TUNEL method was used to investigate the induction of apoptosis after exposure to anti-cancer drugs in thirteen gynecological cancers xenografted into nude mice. Moreover, in vivo sensitivities of gynecologic cancer to anti-cancer drugs were determined according to the protocol developed by Battle Laboratories, Columbus, Ohio USA. Both methods were examined for correlation. RESULTS: The apoptosis index by the TUNEL method showed a correlation with the findings using the protocol developed by Battle Laboratories, Columbus, Ohio USA. CONCLUSIONS: Our findings indicate the ability to determine the measure of chemosensitivity by the apoptosis index.

Animals↗
PubMed2002

[Comparison of reproducibility to measure cough sensitivity between our original and astograph methods].

BACKGROUND: We have established a 15-seconds tidal breathing method using our originally developed apparatus to measure cough sensitivity to capsaicin. Astograph, an apparatus to measure bronchial responsiveness to methacholine, has been widely used in clinical practice in Japan. If Astograph is available for measurement of cough sensitivity, it will contribute to promoting the spread of cough sensitivity test. METHODS: Fifteen-seconds tidal breathing methods using our original apparatus and Astograph were compared in 29 healthy subjects. To assess the agreement of the two methods, increasing concentrations of capsaicin solution were inhaled for 15 seconds until 5 or more cough were elicited and cough threshold, the lowest concentration of capsaicin eliciting 5 or more coughs, was determined by each method on 2 separate days at one week interval. On each day, the cough threshold measurement was repeated twice at one-hour interval to assess the repeatability. RESULTS: Difference and repeatability coefficient were 0.35 and 2.00 in our original method and 0.14 and 1.88 doubling concentration in Astograph method, respectively, indicating good repeatability of both methods. Difference and coefficient of agreement between the two methods was 0.30 and 2.44 doubling concentration, respectively. CONCLUSIONS: Astograph is suitable for measurement of cough sensitivity to capsaicin because of its good repeatability and agreement with our original method already established.

Adult↗
PubMed2002

Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells.

The mechanism that regulates the growth of ovarian clearcell adenocarcinoma (CCA) are not well understood. We investigated the role of several growth factors that bind to membrane tyrosine kinase receptors and added them to the ovarian CCA cell lines KK, RMG-1, and HAC-II to evaluate their effect on growth and cellular invasion. Epidermal growth factor and transforming growth factor-alpha significantly stimulated the growth and invasion of CCA cell lines in vitro. ZD1839, an epidermal growth factor receptor-tyrosine kinase inhibitor, decreased the growth and invasion of CCA cell lines in vitro and in vivo inhibited the growth of xenografts of the CCA cell line RMG-1. Severe combined immunodeficient mice bearing RMG-1 xenografts treated with ZD1839 survived for longer than the untreated control group. From these findings, we conclude that ZD1839 may offer a new and effective treatment for ovarian CCA.

Adenocarcinoma, Clear Cell↗
PubMed2002

[A case of infective endocarditis accompanied with pulmonary complications in a drug addict].

A 21-year-old man who had a history of intravenous drug addiction was admitted with complaints of high fever and a productive cough. Chest CT on admission showed multiple consolidations, and pneumonia was initially diagnosed and treated. Because echocardiography after admission showed vegetation, with no bacteriological findings, attached to the tricuspid valve, right-sided infective endocarditis was diagnosed. After antibiotic therapy was changed, his fever was reduced and the inflammatory findings were eliminated. In the western world, most cases of right-side infective endocarditis are caused by drug addicts, but in Japan, this disease is very rare. Right-side infective endocarditis in drug addicts causes a high rate of pulmonary complications, in particular, septic pulmonary embolism. Many drug addicts suffering from pulmonary complications may consult doctors, but if the latter are not well-informed about this disease, it may not be possible to give an accurate diagnosis or proper treatment.

Adult↗
PubMed2002

[A case of left diaphragmatic eventration treated by thoracoscopic plication].

A 59-year-old woman was admitted to our hospital because of left diaphragmatic eventration due to a left phrenic nerve injury following surgery for recurrent thyroid cancer. She underwent plication by thoracoscopic surgery followed by marked expansion of the left lung and improvement of pulmonary function and dyspnea on exercise. Thoracoscopic plication for diaphragmatic eventration is a useful minimally invasive surgical technique.

Diaphragmatic Eventration↗
PubMed2002

[A case of hemophagocytic syndrome caused by tuberculosis].

A 59-year-old woman was admitted to our hospital with a picture of high fever and dyspnea. Pneumonia was diagnosed by chest CT scan and was treated. Laboratory findings showed pancytopenia and examination of aspirated bone marrow showed mature histiocytes with marked hemophagocytosis. She was treated with prednisolone, but her respiratory condition worsened, so she was ventilated. An acid-fast bacterial smear of bronchoalveolar lavage fluid from the left lingula showed Gaffky's scale No. 5, and so tuberculosis was diagnosed. Though anti-tuberculosis therapy was started, she died after eight days of hospitalization. Infection-associated hemophagocytic syndrome is caused by various infections. Until now, 26 cases of tuberculosis-associated hemophagocytic syndrome have been reported, and many of these diseases were caused by severe tuberculosis. If a patient with severe tuberculosis presents with leucocytopenia or thrombocytopenia, investigations should serve a differential diagnosis that takes into account disseminated intravascular coagulation, tuberculous granuloma of the bone marrow, side effects of anti-tuberculous drugs, and hypersplenism from hemophagocytic syndrome.

Female↗
PubMed2002

[A case of post-traumatic bilateral eosinophilic pleural effusion].

A 58-year-old man was admitted to our hospital with chest pain caused by chest trauma. After admission, his chest pain decreased and he was discharged. Later, he was admitted again with a high fever and dyspnea. Laboratory findings on second admission showed a leukocyte count of 7,900/microliter (9% eosinophils) and a C-reactive protein of 17.0 mg/dl. Chest radiography and chest CT scanning on second admission showed moderate bilateral pleural effusion. Close examination showed an increase of eosinophils in the pleural effusion (14% of total cell counts on the right and 27% of total cell counts on the left) that was exudate. Post-traumatic bilateral eosinophilic pleural effusion was diagnosed. The patient was treated with antibiotic therapy and his condition improved. A chest CT scan afterwards showed improvement of the bilateral pleural effusion. The eosinophil count in the peripheral blood was 1% at chest trauma, 15% in the hospital to the max and decreased to 3% with the decrease of pleural effusion. Post-traumatic eosinophilic pleural effusion may be accompanied with inflammatory findings, and the mechanism is guessed by immunological reaction.

Eosinophilia↗
PubMedDate not supplied

Importance of the angiotensin type 1 receptor in angiotensin II-induced bronchoconstriction and bronchial hyperresponsiveness in the guinea pig.

Although angiotensin II (Ang II) causes bronchoconstriction and bronchial hyperresponsiveness to methacholine in mildly asthmatic patients, the responsible mechanisms for these reactions are unclear. The authors examined the effect of intravenous infusion of Ang II on airway constriction in guinea pigs. Furthermore, the effects of subthreshold concentrations of Ang II on bronchial responsiveness to methacholine were investigated. Airway opening pressure (Pao), an index of bronchoconstriction, increased dose dependently after intravenous infusion of 3 and 10 nmol/kg Ang II (72.2 and 236.5 increase above the baseline value, respectively). In another set of experiments, animals received a methacholine inhalation challenge under a constant intravenous infusion of a subthreshold dose of Ang II (2 nmol/kg/min). The Ang II infusion elicited bronchial hyperresponsiveness to methacholine. The provocative concentration of methacholine, which produced a 200% increase above the baseline Pao (PC200), decreased from 306.9 to 156.1 micrograms/mL upon Ang II infusion. Pretreatment with TCV-116, a type 1 Ang II (AT1) receptor antagonist, but not PD123319, a type 2 Ang II (AT2) receptor antagonist, dose dependently prevented both the Ang II-induced bronchoconstriction and bronchial hyperresponsiveness to methacholine. The authors conclude that Ang II caused bronchoconstriction and induced bronchial hyperresponsiveness to methacholine via the AT1 receptors and that this effect did not involve the release of other bronchoactive mediators.

Angiotensin II↗
PubMedDate not supplied

Longitudinal changes of pulmonary function and bronchial responsiveness in cough-variant asthma treated with bronchodilators alone.

Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as beta 2 adrenergic agonists. The aim of this study was to assess longitudinal changes of pulmonary function and bronchial responsiveness in CVA, which was treated with bronchodilators alone. Seventeen CVA patients recorded intensity and frequency of cough every day. Spirometry and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20) were measured in the run-in period and after cough almost completely relieved on therapy. Cough score had improved within 2 weeks after the initiation of bronchodilator therapy. Forced expiratory volume in one second (FEV1) was significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L after improvement of cough. However, the geometric mean (GSEM) PC20 value did not change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial responsiveness in CVA does not improve when only bronchodilator therapy is carried out. Because bronchial hyperresponsiveness has been shown to be a risk factor for typical asthma onset from CVA, the effect of inhaled corticosteroids on the longitudinal changes in bronchial responsiveness should be examined.

Asthma↗