Biomedical subjects

R Maruyama

Publications and source records attributed to R Maruyama.

At least 55 records · Page 3Linked to original sources

PubMed1999

Induction of apoptosis by gallic acid in lung cancer cells.

The apoptosis-inducing effect of gallic acid (3,4,5-trihydroxybenzoic acid) was investigated in four human lung cancer cell lines, SBC-3 (small cell carcinoma), EBC-1 (squamous cell carcinoma), A549 (adenocarcinoma) and SBC-3/CDDP (cisplatin-resistant subclone of SBC-3). Gallic acid induced apoptosis in a dose-dependent manner as evidenced by analyses of DNA fragmentation, changes in cell morphology and loss of viability. Fifty percent inhibitory concentration (IC50) values of gallic acid on the cell viability of SBC-3, EBC-1 and A549 were around 10, 20 and 60 microg/ml, respectively. The IC50 value for SBC-3/CDDP cells was almost the same as that of SBC-3, suggesting that susceptibility of cells to gallic acid-induced apoptosis is not altered by the acquisition of cisplatin resistance. The apoptotic process was effectively triggered by 30 min exposure to gallic acid. A caspase inhibitor and alpha-tocopherol effectively prevented the gallic acid-induced apoptosis, indicating the involvememt of caspase activation and oxidative processes during the course of apoptosis in gallic acid-treated cancer cells. These findings suggest the possible applicability of gallic acid in lung cancer therapy, especially to circumvent resistance to anti-cancer drugs.

Adenocarcinoma↗

PubMed1999

Norepinephrine release and ventricular fibrillation in myocardial ischemia/reperfusion: roles of angiotensin and bradykinin.

Exogenous bradykinin (BK), acting at B2-receptors, enhances norepinephrine (NE) release and exacerbates arrhythmias (VF) in myocardial ischemia/reperfusion. Inhibition of BK formation (with serine proteinase inhibitors) alleviates NE release and VF, whereas prevention of BK degradation (with kininase inhibitors) potentiates them. Yet serine proteinase and kininase inhibitors also prevent the formation of angiotensin (AII), a potent NE-release enhancer. Thus we assessed the respective contribution of AII and BK to NE release and VF by using selective B2- and AT1-receptor antagonists. Isolated guinea pig hearts were subjected to 10- and 20-min global ischemia and 45-min reperfusion. NE overflow (pmol/g) was approximately 8 (exocytotic) and approximately 750 (carrier mediated). VF, associated with carrier-mediated NE release, lasted approximately 2 min. The B2-receptor antagonist Hoe 140 (30 nM) affected neither NE overflow nor VF. In contrast, the AT1-receptor antagonist EXP3174 (100 nM) markedly reduced exocytotic and carrier-mediated NE release and shortened VF. When EXP3174 was combined with Hoe 140, NE overflow and VF were decreased even further. Thus in myocardial ischemia, local AII production contributes to NE release and VF via AT1-receptors. Although BK production increases in myocardial ischemia, the effects of BK on adrenergic nerve terminals are uncovered only when BK half-life is prolonged and/or when AII effects are suppressed.

Angiotensin Receptor Antagonists↗

PubMed1999

A case of Unna-Thost disease accompanied by Epidermophyton floccosum infection.

We report herein a case of 61-year-old man with Unna-Thost disease (nonepidermolytic hereditary palmoplantar keratoderma) who had been suffering from refractory dermatophyte infection. Diffuse palmoplantar hyperkeratosis developed in his infancy. Coarse scaling, fissures, marked erythema, and nail deformities appeared in his early adult life. Microscopic examination revealed fungal elements in scales and nail particles. Cultures of those scales isolated Epidermophyton floccosum. Genealogical study demonstrated that his mother, sister, brother, daughter, and niece had had similar tylosis, and all of the affected individuals except his daughter had been proved to have E. floccosum or Trichophyton rubrum infection. Oral itraconazole (100mg/day) was highly effective in treating his dermatophytosis without any adverse effects. Scaling, fissures and underlying erythema disappeared within four months.

Epidermophyton↗

PubMed1999

Skin invasion of Hodgkin's disease mimicking scrofuloderma.

We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node. Clinical and pathological presentations mimicked infectious disease such as scrofuloderma. The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments. Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck. A diagnosis of Hodgkin's disease was then made. Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission.

Aged↗

PubMed1999

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter.

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.

Acute Disease↗

PubMed1999

Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts.

We previously reported that bradykinin (BK; 1-1000 nM) facilitates norepinephrine (NE) release from cardiac sympathetic nerves. Because BK production increases in myocardial ischemia, endogenous BK could foster NE release and associated arrhythmias. We tested this hypothesis in guinea pig and human myocardial ischemia models. BK administration (100 nM) markedly enhanced exocytotic and carrier-mediated NE overflow from guinea pig hearts subjected to 10- and 20-min ischemia/reperfusion, respectively. Ventricular fibrillation invariably occurred after 20-min global ischemia; BK prolonged its duration 3-fold. The BK B2 receptor antagonist HOE140 (30 nM) blocked the effects of BK, whereas the B1 receptor antagonist des-Arg9-Leu8-BK (1 microM; i.e., 2.5 x pA2) did not. When serine proteinase inhibitors (500 KIU/ml aprotinin and 100 microg/ml soybean trypsin inhibitor) were used to prevent the formation of endogenous BK, NE overflow and reperfusion arrhythmias were diminished. In contrast, when kininase I and II inhibitors (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and enalaprilat, each 1 microM) were used to prevent the degradation of endogenous BK, NE overflow and reperfusion arrhythmias were enhanced. B2 receptor blockade abolished these effects but was ineffective if kininases were not inhibited. B2 receptor stimulation, by either exogenous or endogenous BK, also markedly enhanced carrier-mediated NE release in the human myocardial ischemia model; conversely, inhibition of BK biosynthesis diminished ischemic NE release. Because atherosclerotic heart disease impairs endothelial BK production, in myocardial ischemia BK could accumulate at sympathetic nerve endings, thus augmenting exocytotic and carrier-mediated NE release and favoring coronary vasoconstriction and arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

Adult↗

PubMed1999

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

Animals↗

PubMed1999

UFT plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.

A phase II study of combined-modality treatment consisting of uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus cisplatin (Platinol) and concurrent radiotherapy was conducted to evaluate the activity of this regimen in patients with locally advanced non-small-cell lung cancer. Eligible patients with cytologically or histologically confirmed, unresectable stage III non-small-cell lung cancer received UFT (400 mg/m2 orally on days 1 through 52) and cisplatin (80 mg/m2 intravenously on days 8, 29, and 50). Radiotherapy, with a total dose of 60.8 Gy, was delivered in 38 fractions on days 1 through 52. Among the 17 patients entered, 16 experienced partial responses (94%; 95% confidence interval, 83% to 100%). The median time to tumor progression was 30 weeks (range, 8 to 87 weeks), and the 1-year survival rate was 80%. Hematologic toxicity was moderate. Grade 3 leukopenia occurred in 10 patients (59%), but no grade 4 hematologic toxicity was observed. No grades 3 or 4 nonhematologic toxicities were reported. These observations suggest that oral UFT plus cisplatin with concurrent radiotherapy can be safely administered to patients with locally advanced non-small-cell lung cancer. The demonstrated antitumor activity is high, making this combined-modality treatment worthy of further investigation in a multi-institution trial.

Adult↗

PubMed1999

Extended resection of the pulmonary artery and the aorta for primary lung cancer. Report of a case.

We report a case of squamous cell carcinoma of the lung in which a left pneumonectomy combined resection of the pulmonary artery and aorta was performed using a cardiopulmonary bypass. The bifurcation of the pulmonary artery was repaired with a pericardial patch and the descending aorta was replaced with an artificial vessel Eleven months later, the patient underwent dissection of the contralateral mediastinal lymph nodes because of a recurrence of the disease. Even though pulmonary metastases have again recently appeared, he is alive and doing well two years after operation. To obtain a better prognosis in cases demonstrating an involvement of the bifurcation of pulmonary artery, more effective combined treatment still needs to be developed.

Adult↗

PubMed1998

High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

Animals↗

PubMed1998

Comparison of chromosomal aberrations detected by fluorescence in situ hybridization with clinical parameters, DNA ploidy and Ki 67 expression in renal cell carcinoma.

To evaluate the significance of chromosomal aberrations in renal cell carcinoma, fluorescence in situ hybridization (FISH) was used to determine its prevalence and correlation with clinical parameters of malignancy. In addition, correlation of chromosomal aberration with Ki 67 expression was analysed. We performed FISH with chromosome-specific DNA probes, and the signal number of pericentromeric sequences on chromosomes 3, 7, 9 and 17 was detected within interphase nuclei in touch preparations from tumour specimen. The incidence of loss of chromosome 3 was significantly higher than those of chromosomes 7, 9 and 17 (P < 0.001, P = 0.03 and P < 0.001 respectively). Hyperdiploid aberration of chromosomes 3 and 17 was significantly correlated with tumour stage (P = 0.03, P = 0.02 respectively), whereas hyperdiploid aberration of chromosome 9 was associated with nuclear grade (P = 0.04). Disomy of chromosome 7 was correlated with venous involvement (P = 0.04). Ki 67 expression was significantly associated with hyperdiploid aberration of chromosome 17 (P = 0.01), but not with aberration of chromosome 3. There was a significant relationship between hyperdiploid aberration of chromosome 7 and Ki 67 expression (P = 0.01). In conclusions, gain of chromosome 17 may reflect tumour development, and aberration of chromosome 7 may affect metastatic potential of malignancy, whereas loss of chromosome 3 may be associated with early stage of tumour development in renal cell carcinoma.

Adult↗

PubMed1998

Necrobiosis lipoidica-like skin lesions in systemic sarcoidosis.

A 62-year-old woman with systemic sarcoidosis developed erythematous plaques on her lower legs. Clinically, two kinds of skin lesions were distinguished; one type formed brownish-red plaques with induration suggesting plaque-type skin sarcoid, and the other formed purplish erythematous plaques with atrophic centers resembling necrobiosis lipoidica. In spite of this clinical appearance, a biopsy specimen from one of the latter lesions revealed typical skin sarcoid histology composed of discrete non-caseating granulomas, while that from one of the other lesions showed necrobiotic changes of collagen bundles surrounded by epitheloid histiocytes and foreign-body giant cells. Because cutaneous involvement of sarcoidosis may mimic necrobiosis lipoidica clinically and/or histologically, we diagnosed her skin lesions as necrobiosis-like skin sarcoid.

Collagen↗

PubMed1998

Cathepsin D expression in skin metastasis of breast cancer.

Cathepsin D, an aspartic proteinase, correlates with invasion and metastasis in breast cancer and with poor prognosis. In the present study, we examined the immunohistological expression of cathepsin D in both primary (5 cases) and skin-metastatic breast cancers (13 cases) and compared it to those in gastric (2 cases) and lung (4 cases), and primary eccrine cancers (3 cases). All breast and gastric cancers were adenocarcinomas. The 2 gastric cancers were poorly differentiated, while the 4 lung cancers consisted of 2 poorly differentiated adenocarcinomas, 1 poorly differentiated large cell carcinoma, and 1 moderately to poorly differentiated squamous cell carcinoma. We also surveyed the immunohistological distribution of cathepsin B, carcinoembryonic antigen, gross cystic disease fluid protein-15, c-erbB-2, and estrogen receptor. In almost all breast cancer samples, the cancer cells demonstrated strong expression of cathepsin D in the cytoplasm, but weak staining patterns with other antibodies. Gastric and lung cancer cells did not respond with cathepsin D (except one metastatic lung cancer) or the other immunohistological markers. Since cathepsin D is strongly expressed in primary and metastatic lesions of breast cancer, cathepsin D could be useful as an adjunct to a panel of immunohistochemical stains in determining the primary site of origin of metastatic cancer in the skin.

Adenocarcinoma↗

PubMed1997

Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer.

OBJECTIVE: This retrospective study was designed to detect occult micrometastases in the lymph nodes with the use of monoclonal anti-cytokeratin reagent, which is specific for epithelial cells but not for lymphocytes or plasmacytes, as well as to assess the relationship between the presence of occult micrometastases in the lymph nodes and an early relapse in patients with stage I non-small-cell lung cancer. METHODS: The paraffin-embedded sections of 973 regional lymph nodes from 44 patients with stage I non-small-cell lung cancer were studied. We used CAM-5.2 as the primary monoclonal anti-cytokeratin reagent and an indirect staining technique with the streptavidin-biotin-peroxidase complex method. RESULTS: We identified cytokeratin-positive cells in 31 (70.5%) of 44 patients and in 91 (9.4%) of the 973 lymph nodes. Of these 31 patients with cytokeratin-positive cells, 19 and 12 were restaged as having N1 and N2 disease, respectively. Thirteen patients had recurrent disease at 17 sites during the follow-up. Two of these recurrences were in the mediastinal nodes and the other 15 occurred at distant organs. Twelve of the 13 patients had micrometastatic disease in the regional lymph nodes. Disease-free survival duration was significantly shorter in the patients with micrometastases in the mediastinal lymph nodes than in patients with node-negative disease (p = 0.004). The independence of this prognostic significance was demonstrated by a multivariate analysis. CONCLUSION: These findings indicate that the detection of occult micrometastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can thus be used to predict an early relapse in patients with stage I non-small-cell lung cancer.

Aged↗

PubMed1997

Uterine sarcoma: can it be differentiated from uterine leiomyoma with Doppler ultrasonography? A preliminary report.

Our objective was to evaluate whether intratumoral-blood flow analysis could differentiate uterine sarcoma from uterine leiomyoma. Color and pulsed Doppler findings obtained from 41 patients with histologically proven uterine leiomyoma and five with uterine sarcoma (four leiomyosarcoma, one mixed mesodermal tumor) were retrospectively assessed. Intratumoral blood flow velocity waveforms were recorded, and the resistance index (RI) and peak systolic velocity (PSV) were calculated. There was no significant difference between the RI (median 0.647; range 0.422-0.896) in the uterine leiomyomas and the RI (median 0.663; range 0.330-0.774) in the uterine sarcomas. The PSV (median 61.6 cm/s; range 40.0-124.0 cm/s) in the uterine sarcomas was significantly higher (median 21.6 cm/s, range 6.3-48.6 cm/s) than that in the uterine leiomyomas (p < 0.05). When a cut-off value for the PSV of 41.0 cm/s (mean PSV of the uterine leiomyomas plus 2 standard deviations) was considered, the detection rate for uterine sarcoma was 80.0%, and the false-positive rate was 2.4%. These results suggest that the PSV within the tumor detected by color and pulsed Doppler ultrasonography could be useful for the preoperative differential diagnosis of uterine sarcoma.

Adult↗

PubMed1997

Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.

Administration, Oral↗

PubMed1997

Aggressive pulmonary metastasectomies for synovial sarcoma.

A 51-year-old woman underwent a bilateral wedge resection of lung metastases through a median sternotomy 10 months after an initial operation for synovial sarcoma of the left lower extremity. Since then, five right and two left posterolateral thoracotomies have been performed over a 6-year period. The patient is presently doing well 7 years after the initial operation of the left lower extremity without any evidence of recurrence.

Adult↗