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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 199 records · Page 11Linked to original sources
PubMed1997

[Evaluation of a new anti-cancer drug regimen against uterine cervical cancer in nude mice].

The purpose of this study was to describe a new anti-cancer drug regimen for uterine cervical cancer. The cytotoxicities of some anti-cancer drugs regimens against the human uterine cervical cancer xenografted into nude mice have been studied. The activities of CDDP, CPT-11, TXL, CDDP + BLM, CDDP + MMC, CPT-11 + BLM, CPT-11 + CDDP, CDDP + 5-FU, CPT-11 + MMC, CPT-11 + TXL and CDDP + TXL for squamous cell carcinoma (TCR, TCK, TCG), and CDDP, MMC, TXL, CDDP + TXL, CDDP + MMC and MMC + TXL for adenocarcinoma (TCO, TCM, TCY), were evaluated comparing with a control group using saline. Five mice were used for each groups. When the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs were administered into the peritoneal cavity of the mice once a week for three weeks. The effective regimens were CDDP + MMC, CDDP + BLM, CDDP + CPT-11 and CPT-11 + MMC for squamous cell carcinoma of the uterine cervix. CDDP + MMC, CDDP + TXL, MMC + TXL and CDDP were effective for endocervical adenocarcinoma. It was suggested that these new drug regimens should be used in clinical studies.

Adenocarcinoma↗
PubMed1997

[Successful use of fluconazole against semi-invasive--pulmonary aspergillosis].

A 53-year-old man was admitted to the hospital because of productive coughing general malaise, and right-sided chest pain. At 41 years of age he was given a diagnosis of gastric cancer, underwent a and gastrectomy, was treated with anti-cancer drugs. At 49 years of age he suffered from atypical mycobacteriosis and received anti-tuberculosis drugs for 1 year. A chest X-ray film showed infiltrative shadows with a cavity in the right upper lung field. Semi-invasive aspergillosis was diagnosed on the basis of the clinical and radiographic findings, positive sputum cultures, and positive serologic tests. After 8 months of therapy with intravenous and oral fluconazole, no pulmonary aspergillosis was evident. Treatment with fluconazole was effective in this case of semi-invasive aspergillosis.

Antifungal Agents↗
PubMed1997

Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea-pigs.

BACKGROUND: Administration of propranolol can provoke bronchoconstriction only in asthmatic patients. Recently we developed an animal model for propranolol-induced bronchoconstriction (PIB). Our working hypothesis is that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. OBJECTIVES: Our goal in this study was to determine which products of arachidonate 5-lipoxygenase pathway are involved in the PIB. METHODS: Propranolol at a concentration of 10 mg/mL was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. Two different sulfidopeptide leukotriene (s-LT) antagonists, ICI198 615 in the doses of 0.03 and 0.3 mg/kg and vehicle and KCA757 in the doses of 1 and 5 mg/kg and vehicle, and a LTB4 antagonist ONO4057 in the doses of 1 and 10 mg/kg and vehicle were injected intravenously 15 min after antigen challenge. Effects of an anticholinergic agent atropine sulphate (5mg/kg) and an alpha-adrenergic blocker phentolamine (0.3 and 3 mg/kg) were examined in the same way. RESULTS: Bronchoconstriction occurred when 10 mg/mL of propranolol was inhaled 20 min after antigen challenge. Both ICI198 615 and KCA757 administered intravenously 15 min after antigen challenge reduced the PIB in a dose-dependent manner while ONO4057 did not alter the PIB. Atropine or phentolamine did not change the PIB. CONCLUSIONS: These results suggest that mediator mechanism, but not cholinergic or alpha-adrenergic nerve, is important in the PIB which developed after the allergic bronchoconstriction in our guinea-pig model and that s-LTs but not LTB4 have an important role in the pathophysiology of the PIB.

Adrenergic alpha-Antagonists↗
PubMed1997

[Effects of a thromboxane-synthetase inhibitor in patients with chronic persistent coughing and no airwayhyperresponsiveness].

We studied the effects of the thromboxane-synthetase inhibitor ozagrel in 22 patients with chronic persistent coughing who did not have airwayhyperresponsiveness. Treatment with ozagrel (400 mg/day for 2 weeks) reduced coughing in 12 patients. Sputum from the patients in whom ozagrel was effective had a higher percentage of lymphocytes and a lower percentage of neutrophils than did sputum from those in whom ozagrel was not effective. Furthermore, in the former group the capsaicin cough threshold increased but in the latter it did not change consistently. These data indicate that thromboxane A2 may contribute to coughing associated with lymphocytic airway inflammation.

Adult↗
PubMed1997

Characterization of a newly established human tumor cell line (TEN) from a patient with clear cell carcinoma of the uterine body and its sensitivity to anti-cancer agents.

A cell line derived from human endometrial clear cell adenocarcinoma was newly established and named TEN. The tumor cells were obtained from uterine body of a 74-year-old who had been undergone an abdominal simple hysterectomy. The histologic features of the tumor cells showed abundant clear cytoplasm with diastase digested glycogen granule growing in solid nest and tubular pattern. The TEN cells were continuously propagated in vitro during the past 45 months and they were at 75th passage. They grew in a monolayered sheet with a doubling time of about 53 hours. The TEN cells resembled the structure of the original tumor and had abundant glycogen granules, lipid droplets in the cytoplasm. The histopathology of the transplanted tumor in SCID mice resembled that of the original tumors. The TEN cells secreted a high content of CA125. Immunohistochemically, the TEN cells had c-erbB-2 and Cathepsin D immunoreactivity in some parts of the cell population. But they did not have estrogen, progesterone and EGF receptor. Sensitivities of the TEN cells to a variety of anti-cancer drugs were examined. In in-vitro tests, MTT assays employed. The results suggested that the TEN cells were not sensitive to any of 13 agents. On the other hand, in-vivo sensitivity test of transplanted tumor in SCID mice, the tumors were sensitive to CPT-11 and paclitaxel. We conclude that the TEN cell line will be effective material for chemosensitivities against the endometrial clear cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗
PubMed1997

Effect of beclomethasone dipropionate inhalation on eosinophilic bronchitis in patients with silicosis.

The efficacy of beclomethasone dipropionate (CAS 5534-09-8, BDP, beclomethasone) inhalation therapy over the course of 12 months were evaluated in 42 patients with established chronic silicosis. Their pulmonary functions were monitored every 3 months and volume of sputum production was established daily. Subjects were divided randomly into two groups; 21 patients (BDP group) were treated with BDP (400 micrograms/day) by way of a metered-dose inhaler, while the 21 controls did not receive the BDP inhalation therapy. Although FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 s), MMEF (maximal mean expiratory flow) and arterial blood oxygen tension did not improve significantly, sputum production significantly decreased in the BDP group. The patients who responded most dramatically to the treatment presented with sputum eosinophilia and elevated serum IgE levels prior to therapy. Pulmonary tuberculosis or exacerbation of chronic airway infection was not observed in any of the patients. These results suggest that corticosteroid inhalation therapy is helpful in the management of chronic silicosis, especially in patients with sputum eosinophilia. Positive atopic factors may be related to the pathogenesis of eosinophilic bronchitis, a complication of chronic silicosis.

Aged↗
PubMed1996

Inducible nitric oxide synthase following hypoxia in rat cultured glial cells.

Nitric oxide (NO) produced by inducible nitric oxide (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measuring nitrite. The levels of nitrite produced in the cultured media of glial cells significantly increased after 12-h hypoxia but not after 0- and 6-h hypoxia. The NOS inhibitor, NG-monomethyl-L-arginine, decreased hypoxia-induced nitrite formation. In glial cells after hypoxia/reoxygenation, the iNOS and mRNA and protein expressions were detected by reverse-transcription polymerase chain reaction and by immunocytochemical analysis, respectively. The present study provides the first evidence that hypoxia induces NO production from glial cells. This hypoxia-induced, glial cell-derived NO may play a critical role in the pathogenesis of cerebral ischemia in vivo.

Animals↗
PubMed1996

Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis.

A human CAD cDNA encoding a trifunctional enzyme of carbamoylphosphate synthetase-aspartate transcarbamoylase-dihydroorotase, which catalyzes the first three steps of de novo pyrimidine nucleotide biosynthesis, was cloned from a human fibroblast cell line of TIG-1-20 by polymerase chain reaction (PCR). The predicted open reading frame encodes a protein of 2,225 amino acids with a deduced molecular weight (Mr) OF 242,913. The deduced amino acid sequence exhibits 95.3 and 76.1% identity with the CAD sequences of hamster and Squalus acanthias. The DNA fragment of 6,679 bp containing the full-length coding sequence was amplified by nested PCR using the first-strand cDNA of human cell lines of TIG-1-20 and COLO205 as a template. Southern blot analysis suggested that the CAD gene exists as a single copy in the human genome.

Amino Acid Sequence↗
PubMed1996

Increase of chemokine levels in sputum precedes exacerbation of acute asthma attacks.

Basophils and eosinophils can be activated in vitro by several chemokines such as RANTES, monocyte chemotactic and activating factor (MCAF/MCP-1), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), and interleukin-8 (IL-8). To explore the clinical relevance of the in vitro observations, we measured here the concentrations of these chemokines in sputa from asthmatic patients during acute attacks. Before the onset of a late-phase exacerbation, sputum MCAF/MCP-1, MIP-1 alpha, and IL-8 levels transiently but markedly increased from the basal levels in all of the patients with exacerbation, whereas the sputum levels of these chemokines remained unchanged during the course in the patients without a late-phase exacerbation. These results suggest the involvement of these chemokines in the late-phase exacerbation of asthma.

Acute Disease↗
PubMed1996

Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non-small-cell lung cancer cell lines under hypoxia.

We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and a newly developed MMC analogue: 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC-9/MC4) that had been established in our laboratory from the parent PC-9 cell line by continuous exposure to MMC. We previously reported that the MMC-resistant cell line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9, the parent cell line, under aerobic conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one-electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under hypoxic conditions, but the impairment was not evident under aerobic conditions. KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC-9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by exposure to hypoxic conditions or by coincubation with tempol. There were no significant differences in the intracellular uptake of MMC and the activities of cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These results support the hypothesis that the one-electron reduction pathway plays a partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is excellent at circumventing resistance to MMC in NSCLC.

Antineoplastic Agents↗
PubMed1996

Analysis of thrombocytopenia due to carboplatin combined with etoposide in elderly patients with lung cancer.

Thrombocytopenia induced by carboplatin combined with etoposide for elderly lung cancer patients was analyzed in relation to the predicted thrombocytopenia by the equations advocated by Egorin et al. and Taguchi et al. The thrombocytopenia actually observed was strongly correlated with and significantly more severe than that predicted if carboplatin had been administered as a single agent. The AUC (area under the curve) of carboplatin predicted by Calvert's equation significantly affected the degree of thrombocytopenia. These data suggested that dosing of carboplatin should be determined individually on the basis of renal function, as recommended earlier. The reason for the enhancement of thrombocytopenia is yet to be determined in future trials.

Aged↗
PubMed1996

Effect of capsaicin inhalation on methacholine responsiveness in normal subjects.

It has been reported that capsaicin stimulates bronchial C-fibers to release neuropeptides and enhances bronchial responsiveness in animal studies. This study was conducted to examine the effect of inhaled capsaicin on bronchial responsiveness in humans. A provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20-FEV1) was measured before and one hour after, one minute inhalation of 15.6 microM capsaicin solution (capsaicin day) or saline (saline day) in seven normal subjects whose PC20-FEV1 values were 40 mg/ml or less. Geometric mean value of PC20-FEV1 measured one hour after saline inhalation following pretreatment methacholine challenge was 89.3 (GSEM, 1.69) mg/ml which was significantly (p = 0.018) greater than that of the pre-treatment methacholine challenge [19.1 (GSEM, 1.37) mg/ml] on a saline day. However, PC20-FEV1 was not different before and one hour after inhalation of capsaicin [18.1 (GSEM, 1.40) and 23.1 (GSEM, 1.80) mg/ml] on a capsaicin day. The PC20-FEV1 value of the post-treatment methacholine test was significantly (p = 0.0277) lower after capsaicin inhalation than after saline inhalation while the value of pre-treatment methacholine provocation was not different between capsaicin and saline days. Change of the post-treatment PC20-FEV1 from the pre-treatment value shown as doubling concentrations was 0.35 +/- 0.60 on a capsaicin day which was significantly lower than that (2.23 +/- 0.47) on a saline day. These results confirm the decreased responses to repeated inhalation of methacholine (methacholine tachyphylaxis) in normal subjects and indicate that capsaicin inhalation reduces the methacholine tachyphylaxis.

Administration, Inhalation↗
PubMed1996

Modulation of sensitivity to cis-diamminedichloroplatinum (II) by thromboxane A2 receptor antagonists in non-small-cell lung cancer cell lines.

We examined the effect of selective thromboxane A2 (TXA2) receptor antagonists, calcium 5(Z)-1R, 2S, 3S, 4S-7-[3-phenylsulphonylaminobicyclo [2.2.1] hept-2-yl]-5-heptonoate hydrate (S-1452) and +/- -7-(3,5,6,-trimethyl-1,4-benzoquinon-2-yl)-7-phenylhaptanoic acid (AA-2414), on sensitivity to cis-diamminedichloroplatinum (II) (CDDP) in non-small-cell lung cancer cell lines. IC50 values to CDDP using MTT assay were decreased 2.1- and 4.6-fold respectively by treatment with 250 or 500 microM S-1452, for a 2 h simultaneous drug exposure, and those of PC-9/CDDP, a CDDP-resistant cell line, were decreased 3.1- and 6.1-fold. Sensitivity to carboplatin was also enhanced by the treatment with S-1452. IC50 values to CDDP and carboplatin were decreased by treatment with AA-2414 in a dose-dependent manner. Isobologram analysis showed that the combination of CDDP with S-1452 or AA-2414 produced supra-additive or additive effects in each cell line. Neither glutathione content nor glutathione S-transferase activity was changed in either cell line by treatment with 500 microM S-1452. Accumulation of platinum into PC-9 and PC-9/CDDP was increased by the treatment in a dose-dependent manner. Na+, K+-ATPase activity of PC-9 and PC-9/CDDP was enhanced by the treatment of S-1452 in a dose-dependent manner. These data show that the TXA2 receptor antagonists may enhance the sensitivity of non-small-cell lung cancer cell lines to platinum agents. Increase in Na+, K+-ATPase activity induced by S-1452 may be the mechanism of its sensitising effect through increase in platinum accumulation.

Adenocarcinoma↗