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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 271 records · Page 15Linked to original sources
PubMed1994

DT-diaphorase as a determinant of sensitivity to adriamycin in non-small-cell lung-cancer cell lines.

We have reported the establishment of a mitomycin-C (MMC)-resistant non-small-cell lung-cancer cell line, PC-9/MC4. As determined by an MTT assay, this resistant cell line was found to be 4 times more sensitive to adriamycin (ADM) than was the parental PC-9. There were no significant differences in sensitivity to etoposide, mitoxantrone, daunomycin, epirubicin, pirarubicin, 9-aminoanthracycline or 3'-deamino-3'-morpholino-13-deoxo-10-hydroxy carminomycin. These data suggest that neither qualitative or quantitative changes in DNA topoisomerase II nor the enhanced repair of DNA can explain the differing sensitivity to ADM observed. No significant differences were found in the accumulation of ADM and glutathione (GSH) in these cell lines. Although total glutathione-S-transferase (GST) activity in PC-9/MC4 cells was lower than that observed in PC-9 cells and treatment with ethacrynic acid (EA) reduced sensitivity to ADM in both cell lines, relative resistance was unaffected. NADH-cytochrome b5 reductase (B5R) activity in PC-9/MC4 cells showed a 3-fold greater decrease than that in PC-9 cells, and DT-diaphorase (DTD) activity in PC-9/MC4 cells showed an approximately 200-fold greater decrease than that in PC-9 cells. Addition of dicumarol, an inhibitor of DTD, decreased the sensitivity of ADM of PC-9 but not of PC-9/MC4. DTD activity in the PC-9 cell line was inhibited by treatment with dicumarol while in PC-9/MC4 it remained unchanged. These data suggest that DT-diaphorase is a determinant of sensitivity to ADM in the 2 cell lines.

Adenocarcinoma↗
PubMed1994

Phylogenetic and ontogenetic study of neuropeptide Y-containing nerves in the liver.

The distribution of neuropeptide Y was investigated by light and electron microscopic immunohistochemistry in the liver of various vertebrates including the eel, carp, bullfrog, turtle, chicken, mouse, rat, guinea-pig, dog, monkey and human. The ontogenetic development of neuropeptide Y was also studied in the mouse liver. In all species examined except the eel, neuropeptide Y-like immunoreactivity was detected in nerve fibres. In the carp, bullfrog, turtle, chicken, mouse and rat, positive fibres were distributed around the wall of hepatic vessels and the bile duct of the Glisson's sheath. The density of the positive fibres increased with evolution. On the other hand, in the guinea-pig, dog monkey and human, numerous neuropeptide Y-positive fibres were observed not only in the Glisson's sheath but also in the liver parenchyma. Positive fibres formed a dense network to surround hepatocytes. The present immunoelectron microscopic study has confirmed that neuropeptide Y-positive terminals are closely apposing to hepatocytes. Ontogenetically, neuropeptide Y-positive fibres were first found in embryonic liver of 19-day-old mice. Positive fibres increased with age and the highest peak was seen one week after birth. This ontogenetic pattern has suggested that neuropeptide Y plays a certain role in developing liver.

Animals↗
PubMed1994

Amino-acid alterations in the beta-tubulin gene of Neurospora crassa that confer resistance to carbendazim and diethofencarb.

We have previously shown that increased sensitivity to diethofencarb in the carbendazim(MBC)-resistant F914 strain of Neurospora crassa is caused by a single amino-acid change in beta-tubulin, 198Glu to Gly. Three diethofencarb-resistant mutants that are also resistant to MBC were isolated from strain F914. They contained single base-pair-substitution mutations in the beta-tubulin gene. The amino acid changes in beta-tubulin, Phe from 250Leu, Val from 165Ala, and Ala from 237Thr, were responsible for diethofencarb-resistance in the mutant strains FR511, FR513, and FR421, respectively. The amino acid at position 198 of beta-tubulin in these mutants was Gly, which is the same as in strain F914. beta-tubulin genes with 198Glu were constructed by site-directed mutagenesis. The altered beta-tubulin genes derived from FR511 and FR421 transformed the wild-type strain to resistance to MBC, indicating that 250Phe and 237Ala in beta-tubulin are responsible for resistance not only to diethofencarb but also to MBC.

Amino Acid Sequence↗
PubMed1994

The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B.

Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10(-18), 10(-16), 10(-14) M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.

Administration, Inhalation↗
PubMed1994

Aerosolized acetaldehyde, but not ethanol, induces histamine-mediated bronchoconstriction in guinea-pigs.

It was reported that ethanol-induced bronchoconstriction was associated with elevated serum levels of acetaldehyde and histamine in Japanese asthmatic patients, but there is no study to investigate the airway response to acetaldehyde. We performed this animal study to test the hypothesis that acetaldehyde has the bronchospastic action via histamine release. First, we investigated the airway response to ascending doses (31.3, 62.5, 125, and 250 mM) of inhaled ethanol or acetaldehyde in guinea-pigs. Secondly, guinea-pigs pretreated with intraperitoneal injection of saline or 20 mg/kg diphenhydramine inhaled acetaldehyde. Finally, guinea-pigs pretreated with intraperitoneal injection of saline or 0.5 mg/kg atropine sulfate inhaled acetaldehyde. Inhalation of acetaldehyde, but not ethanol, caused bronchoconstriction in a dose-dependent manner. The bronchoconstriction induced by inhaled acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, acetaldehyde has the bronchospastic action via histamine release in guinea-pigs. It is suggested that histamine H1-antagonists may be available for preventing alcohol-induced asthma.

Acetaldehyde↗
PubMed1994

Effects of aerosol administration of a thromboxane receptor antagonist (S-1452) on experimental asthma in guinea pigs.

The importance of thromboxane A2 (TXA2), one of the arachidonate metabolites, in the pathogenesis of bronchial asthma has been emphasized recently. Because aerosolized administration of antiasthmatic drugs is effective and safe, this study examined the effect of aerosolized TXA2 receptor antagonist (S-1452) on allergic bronchoconstriction in passively sensitized and mechanically ventilated guinea pigs. Under the cover of antihistamine, antigen-induced bronchoconstriction was markedly inhibited by pretreatment with aerosolized S-1452 inhalation in a dose-dependent manner. Although aerosolized S-1452 itself provoked weak bronchoconstriction for its partial agonist effect, bronchial responsiveness to inhaled histamine did not change 10 min after S-1452 inhalation. These results indicate that aerosolized S-1452 may be useful in treating bronchial asthma.

Aerosols↗
PubMed1994

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects.

BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.

Acetaldehyde↗
PubMed1994

Involvement of thromboxane A2 in propranolol-induced bronchoconstriction after allergic bronchoconstriction in guinea pigs.

Although it is well recognized that beta-blockers can induce bronchoconstriction only in patients with asthma, mechanisms of the bronchoconstriction are not well known. We hypothesize that bronchoconstriction induced by beta-blockers may result from inflammatory mediators released by allergic reactions. In this study, we developed a guinea pig model for propranolol-induced bronchoconstriction (PIB) after antigen inhalation and investigated the effect of specific thromboxane (TXA2) receptor antagonists, S-1452 and ONO NT-126, on PIB in passively sensitized and artificially ventilated guinea pigs to determine whether TXA2 is involved in PIB. Propranolol caused bronchoconstriction with 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. On the other hand, propranolol did not produce bronchoconstriction after antigen provocation in nonsensitized guinea pigs or after saline provocation in sensitized animals. Pretreatment of the animals with S-1452 in doses of 0.01 and 0.1 mg/kg and ONO NT-126 in doses of 1.0 and 10 micrograms/kg injected intravenously 15 min after antigen challenge as well as before antigen challenge reduced PIB in a dose-dependent manner. Bronchoconstriction caused by methacholine did not induce PIB. These results suggest that TXA2 has an important role in the pathophysiology of the PIB that develops after the allergic bronchoconstriction.

Administration, Inhalation↗
PubMed1994

Pulmonary plasma cell granuloma improves with corticosteroid therapy.

Two cases of pulmonary plasma cell granuloma that progressed after respiratory infectious disease are described. The men, 48 and 32 years old, were admitted to the hospital with blood-streaked sputum and mass or nodular shadow on chest radiograph. Close examination revealed that these tumors were plasma cell granulomas, which are known as postinflammatory pseudotumors. Biopsy specimens, obtained by way of transbronchial biopsy, demonstrated proliferation of mature plasma cells and infiltration of lymphocytes supported by granulation tissue, and there was no evidence of malignancy or tuberculosis. Although surgery is common in the treatment of pulmonary plasma cell granuloma, some cases relapse or invade the mediastinum. Therefore, we decided to treat these patients with prednisolone, 30 mg/d, an anti-inflammatory and immunosuppressive agent. Two or 4 weeks later, these tumors disappeared completely and they have never recurred. As middle-dosage corticosteroid therapy is not cytotoxic, it is useful for the treatment of pulmonary plasma cell granuloma, especially in multifocal, unresectable, and/or relapsing cases.

Adult↗
PubMed1994

Inhibitory effect of a selective thromboxane synthetase inhibitor, OKY-046, on acetaldehyde-induced bronchoconstriction in asthmatic patients.

We recently reported that inhaled acetaldehyde causes bronchoconstriction indirectly via histamine release in patients with asthma. The purpose of this study was to investigate a role of thromboxane A2 in acetaldehyde-induced bronchoconstriction in asthmatic airways. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects who were treated with placebo or OKY-046, a selective thromboxane A2 synthetase inhibitor, of 200 mg twice a day for 3 days, and 200 mg on the fourth day (test day) in a double-blind, randomized, placebo-controlled, crossover fashion. Percentage decreases in FEV1 caused by 20 and 40 mg/ml of acetaldehyde inhalation were significantly (p < 0.05 and p < 0.01, respectively) prevented by the pretreatment with OKY-046. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV1 (PC20-Ac-CHO) was significantly (p < 0.01) greater with the OKY-046 pretreatment (72.2 [1.1] mg/ml) than with the placebo pretreatment (19.8 [1.2] mg/ml). We conclude that thromboxane A2 is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A2 may play an important role in endogenous histamine-induced bronchoconstriction caused by acetaldehyde in asthmatic airways. We believe that this is a first report on the interaction between endogenous histamine and thromboxane A2 in asthmatic subjects.

Acetaldehyde↗
PubMed1994

Minocycline-induced pneumonitis with bilateral hilar lymphadenopathy and pleural effusion.

A 65-year-old man developed respiratory failure with diffuse interstitial shadow, bilateral pleural effusion, and bilateral hilar lymphadenopathy on chest X-ray and CT, after intravenous administration of minocycline. Corticosteroid therapy was effective. The findings from bronchoalveolar lavage (BAL) and transbronchial lung biopsy were compatible with eosinophilic pneumonia. Provocation test supported this diagnosis, but the lymphocyte stimulation test was negative. A review of the literature and the diagnoses of drug-induced pulmonary diseases are discussed.

Aged↗
PubMed1994

Rhabdomyolysis associated with bacteremic pneumonia due to Staphylococcus aureus.

A case of rhabdomyolysis associated with bacteremic pneumonia due to Staphylococcus aureus is reported. A 58-year-old man was admitted because of severe left lobar pneumonia, and presented myoglobinuria on admission. The serum creatine phosphokinase level was transiently elevated and myoglobinuria were disclosed. Sputum and venous blood cultures grew Staphylococcus aureus. Rhabdomyolysis has rarely been reported in cases of bacterial infection, especially those due to Staphylococcus aureus. This case might be an extremely rare case of rhabdomyolysis complicating Staphylococcus aureus bacteremia following severe left upper lobar pneumonia.

Bacteremia↗
PubMed1994

Peripheral neuroectodermal tumor presenting pleural effusion.

Pleural effusion is a common finding of peripheral neuroectodermal tumor (PNET) of the chest wall (Askin's tumor), but little is known about the characteristics. A case of Askin's tumor with pleural effusion is reported. Repeated cytologies were negative for malignancy, but levels of lactic dehydrogenase (LDH) and neuron-specific enolase (NSE) in the pleural effusion were increased. Surgical biopsy was performed and immunohistochemical study of the tumor revealed the diagnosis.

Adult↗
PubMed1994

Cough receptor sensitivity and bronchial responsiveness in patients with only chronic nonproductive cough: in view of effect of bronchodilator therapy.

Twenty-two patients with only chronic nonproductive cough lasting for more than 2 months were prospectively examined to determine whether airway cough receptor sensitivity and bronchial responsiveness relate to the efficacy of bronchodilator therapy on the cough. Clenbuterol (10 micrograms, 4 times a day for 1 week) was effective on the cough in 10 patients (group 2) but not in the other 12 patients (group 1). Cough threshold to inhaled capsaicin was significantly less in group 1 than in group 2 at the first visit but not after the therapy when the cough stopped. Bronchial responsiveness to methacholine (PC20-FEV1) was not heightened in group 1, while that in group 2 was hyperreactive. These findings suggest that nonproductive cough is elicited based on two different mechanisms: (1) heightened airway cough receptor sensitivity in bronchodilator-resistant cough and (2) bronchoconstriction in bronchodilator-responsive cough such as cough-variant asthma.

Adult↗
PubMed1994

[A study of biological characteristics of large bowel adenocarcinomas showing mucin production; examination of histological differentiation and cell kinetics].

In order to clarify the biological behavior of mucin producing cancers of colon, we analyzed 32 cases showing histological heterogeneity in the tumors, by mucin histochemistry. 28 cases were mucinous adenocarcinoma, forming with tubular structures, and the remaining 4 cases were signet-ring cell carcinomas. HID-AB stain demonstrated that the mucin component was almost similar to that of normal mucosa around the cancer. In the tubular forming portions, in which polyploid or aneuploid cells were often detected, the growth fraction of cancers was significantly higher than in that of the other portions.

Adenocarcinoma, Mucinous↗
PubMed1994

[Argyrophilic proteins of nucleolar organizer regions of macrophages and lymphocytes in bronchoalveolar lavage fluid from patients with diffuse lung diseases].

Alveolar macrophages and T-lymphocytes in bronchoalveolar lavage fluid from patients with diffuse lung diseases have been shown to be activated. The object of this study was to investigate whether the numbers of nucleolar organizer regions (NORs) in alveolar macrophages and lymphocytes were abnormally high in these patients or not. Alveolar macrophages and lymphocytes were collected by bronchoalveolar lavage from 7 control subjects, 36 patients with pulmonary sarcoidosis, 10 patients with hypersensitivity pneumonitis, 6 patients with measles pneumonia, 6 patients with mycoplasma pneumonia, and 6 patients with progressive systemic sclerosis related to interstitial pneumonitis. These cells were cytocentrifuged and stained by one-step silver staining. Argyrophilic proteins of the nucleolar organizer regions (Ag-NORs) were counted in 300 alveolar macrophages and lymphocytes. The numbers found in control subjects were compared to those found in patients with diffuse lung diseases. In the patients with sarcoidosis, these numbers were also compared among subgroups divided according to staging, involvement of other organs, administration of steroids, and differences in deposition of 67Ga. We also examined correlations between Ag--NORs and known markers of activation in sarcoidosis. The numbers of Ag-NORs were significantly greater in patients with diffuse lung diseases than in control subjects. There were no significant differences in the numbers of Ag-NORs among subgroups of patients with sarcoidosis. No correlations were seen between the Ag-NORs and the markers of activation of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗