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Biomedical subjects

M Toyoshima

Publications and source records attributed to M Toyoshima.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reversal of multidrug resistance by kopsiflorine isolated from Kopsia dasyrachis.

Kopsiflorine, an indole alkaloid of the aspidofractinine-type isolated from Kopsia dasyrachis, was examined for its effect in enhancing drug cytotoxicity in multidrug-resistant tumor cells. The cytotoxicity of vincristine was enhanced in a concentration-dependent manner by kopsiflorine in drug-resistant KB cells (VJ-300). Kopsiflorine alone had no effect on the growth of drug sensitive or resistant cells, but the intracellular accumulation of vincristine was enhanced by kopsiflorine in VJ-300 cells. Kopsiflorine (10 micrograms/ml) significantly inhibited the binding of [3H]azidopine to P-glycoprotein in VJ-300 cells. The results suggest that kopsiflorine interacts directly with P-glycoprotein and inhibits the efflux of antitumor agents in drug-resistant cells.

Drug Resistance, Multiple↗
PubMed1999

Somatic cell mutation induced by sunlight in Drosophila.

There is ample epidemiological evidence showing that sunlight can cause skin cancer in the human. In experimental studies, simulated sunlight or UV lamps are used for demonstrating carcinogenesis and other biological effects. Little studies, however, have been performed using natural sunlight itself. In this work, we have examined the mutagenicity of natural sunlight in Drosophila. The Drosophila wing spot test is useful to detect somatic cell mutations. Third instar larvae in petri dishes were exposed to sunlight (ultraviolet region with < 290 nm wavelength cut off by a plastic cover) in the yard of Okayama University campus (north latitude: 34 degrees 39', east longitude: 133 degrees 55'). The sunlight was mutagenic in Drosophila larvae and produced pyrimidine dimers in their DNA. In the observed mutagenicity, there was dependence on the exposure period and UV fluence. During the two-year monitoring, the highest induction of mutant spot observed was 1.98 total spots/wing on June 25, 1998, and the lowest was 0.64 on December 29, 1998, while non-exposure spontaneous spots were 0.29 and 0.32 on these days, respectively. Thus, solar radiation was mutagenic both in summer and in winter.

Animals↗
PubMed1999

[A case of pulmonary alveolar proteinosis presenting with peripheral infiltrates].

We report a case of pulmonary alveolar proteinosis (PAP). A 39-year-old asymptomatic woman was admitted to our hospital because of abnormal shadows on chest X-ray films. Chest X-ray films revealed peripheral infiltrates in both lungs. Computed tomographic examination showed patchy peripheral ground-glass attenuation, concentrated subpleurally. Bronchoalveolar lavage fluid was clear. Because transbronchial lung biopsy findings were inconclusive, a VATS-biopsy was performed. The specimens demonstrated accumulation of proteinaceous materials within alveolar spaces. The patient was given a diagnosis of PAP. Although the distribution of radiographic shadows varies in patients with PAP, perihilar or centralized shadows usually predominate. In our patient, subpleural areas of the lung were affected almost exclusively.

Adult↗
PubMed1998

Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids.

A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.

Alkaloids↗
PubMed1998

Ataxia-telangiectasia without immunodeficiency: novel point mutations within and adjacent to the phosphatidylinositol 3-kinase-like domain.

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, telangiectasia, sinopulmonary infections, hypersensitivity to ionizing radiation, and combined immunodeficiency. Recently, the AT gene (ATM) was cloned and shown to be mutated in AT patients. In this report, mutation analysis of ATM was performed in a 24-year-old AT patient without immunodeficiency. ATM amplified with reverse transcriptase-polymerase chain reaction (RT-PCR) was screened with a ribonuclease (RNase) cleavage assay and auto-sequenced. This patient, a compound heterozygote, showed two mutations in ATM: one missense mutation leading to a Leu2656Pro substitution and the other to the truncation at codon 3047 (Arg-->ter). The latter mutation is within the phosphatidylinositol 3-kinase (PI 3-kinase)-like domain and the former is outside but close to the domain. The particular phenotype in our patient, no immunodeficiency, suggests incomplete functional loss of ATM protein. The clinical spectrum of AT caused by ATM mutations may be broader than previously thought. Further analysis of patients with similar phenotypes will make the relation between ATM genotype and phenotype clear.

Adult↗
PubMed1998

Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii.

The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.

Alkaloids↗
PubMed1998

Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.

We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.

Animals↗
PubMed1998

Enhancement of drug accumulation by andrastin A produced by Penicillium sp. FO-3929 in vincristine-resistant KB cells.

In the course of our screening for compounds that reverse multidrug resistance, we found that the cytotoxicity of vincristine was enhanced 1.5-20-fold depending on the concentration of andrastin A in vincristine-resistant KB cells (VJ-300). Andrastin A alone had no effect on the growth of drug sensitive KB cells and VJ-300 cells. On the other hand, andrastin A (25 and 50 micrograms/ml) significantly enhanced accumulation of [3H]vincristine in VJ-300 cells. Andrastin A (50 micrograms/ml) completely inhibited the binding of [3H]azidopine to the P-glycoprotein in VJ-300 cells. The result suggests that andrastin A directly interacts with P-glycoprotein and inhibits the efflux of antitumor agents in drug resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Pulmonary cryptococcosis exhibiting diffuse multiple nodular shadows].

We report a case of pulmonary cryptococcosis showing diffuse multiple nodular shadows in all lung fields. A 39-year-old woman with no immunological abnormalities was admitted with complaints of cough and sputum. She had experienced measles 4 weeks prior to admission. Chest x-ray films revealed diffuse nodular opacities throughout the lung fields, a finding suggestive of metastatic lung cancer. Detailed examinations, including transbronchial lung biopsy, were not conclusive. A diagnosis of pulmonary cryptococcosis was made on the basis of findings from video-assisted thoracoscopic biopsy. Primary pulmonary cryptococcosis usually appears as a solitary nodule or limited infiltration. Immunologically compromised hosts commonly demonstrate various abnormal shadows, such as the multiple nodular shadows observed in our patient. It has been reported that measles infection can cause temporary immune suppression. Secondary immunodeficiency resulting from the preceding infection with measles could explain the unusual chest x-ray findings in this case.

Adult↗
PubMed1998

[Effect of pharmacist's instruction on the treatment of asthmatics with inhaled steroid].

Pharmacist's instruction is provided to asthmatic patients who received an inhaled steroid in Hamamatsu University Hospital. We studied influences of pharmacist's instruction on the repeutic effects of an inhaled steroid, beclomethasone dipropionate (BDP). In 29 patients who had been treated with inhaled BDP under the physician's instruction for more than 3 months, we examined drug compliance, correctness of inhalation procedure and treatment score, symptom score, peak expiratory flow (PEF) values, and compared these before and after the instruction. The instruction was repeatedly provided at an interval of about one month. Patients who followed the indicated regimen were 55.2 and 93.1% before and after the instruction, respectively. An appropriate inhalation maneuver was respectively. An appropriate inhalation maneuver was performed in 24.1 and 93.1% of patients before and after the instruction, respectively. PEF values increased by 12.9 +/- 9.3% (mean +/- standard deviation, p < 0.01) after the instruction. In conclusion, pharmacist's repeated instruction enhanced the therapeutic effects of inhaled BDP in patients with asthma.

Administration, Inhalation↗
PubMed1998

[Interstitial pneumonia preceding systemic sclerosis].

We describe a 57-year-old man with interstitial pneumonia associated with systemic sclerosis. About 3 years prior to the appearance of distinctive signs of systemic sclerosis, he was admitted to our hospital with a chronic dry cough. A chest roentgenogram on admission revealed reticulonodular shadows in both lung fields. There were no abnormal laboratory findings. Open lung biopsy specimens revealed patterns indicative of usual interstitial pneumonia, and myxomatous connective tissue within the lumen of the airways. Skin biopsy specimens showed heightened levels of collagen in the dermis, a finding consistent with systemic sclerosis. The patient was given a diagnosis of lung involvement preceding systemic sclerosis despite the absence of concurrent skin symptoms.

Cryptogenic Organizing Pneumonia↗
PubMed1997

[Activation of endothelium in cardiac surgery: the circulating levels of soluble E-selectin as a marker of the activation of endothelium].

Cardiopulmonary bypass (CPB) is associated with a whole body inflammatory response which may have detrimental consequence resulting in post perfusion syndrome. Adhesion molecule E-selectin plays a pivotal role in the inflammatory response, especially in the interaction of endothelium and neutrophils. Soluble form of E-selectin (sE-selectin) is thought to be a marker of endothelial activation. To evaluate the activation of endothelium during CPB with heparin coated and un-coated extracorporeal circuits, we measured plasma levels of sE-selectin, tumor necrosis factor alpha (TNF alpha), and neutrophil elastase in 16 patients having coronary artery bypass grafting. sE-selectin plasma concentration increased during or after CPB. Significantly lower maximum levels of sE-selectin are observed in patients perfused with heparin coated extracorporeal circuits. Maximum values of sE-selectin correlated with plasma levels of TNF alpha and neutrophil elastase in each patient. These observations suggest that endothelium is activated by extracorporeal circulation in cardiac surgery, and this activation was attenuated by heparin coating of extracorporeal circuits.

Aged↗
PubMed1997

[Clinicopathological features of interstitial pneumonia associated with amyopathic dermatomyositis].

We studied clinicopathological characteristics of interstitial pneumonia associated with amyopathic dermatomyositis. The subjects comprised two men and three women, and their mean age was 58.2 years. All subjects had cruptions specific for dermatomyositis, but had no signs of myositis. They all presented with acutely or subacutely developed coughing and dyspnea. Results of tests for anti-Jo-1 antibody were negative in all cases. Chest X-ray films showed infiltrations or streaky shadows, or both in the middle and lower lung fields. Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of lymphocytes and neutrophils. In one patients a specimen obtained by open lung biopsy showed homogeneous cell infiltrations in alveolar septa and regional alveolar damage. That patient was successfully treated with cyclosporin and corticosteroids in early phase of the disease. The other four patients received immunosuppressive agents after respiratory failure developed. All four died despite having received high-dose corticosteroid and immunosuppressive therapy. Examination of autopsy specimens showed diffuse alveolar damage.

Acute Disease↗
PubMed1997

[Pneumonitis induced by the herbal medicine Sho-saiko-to in Japan].

We studied the clinical characteristics of pneumonitis induced by Sho-saiko-to (SST). Of 94 cases reported to a drug maker, 72 were judged to be SST-induced pneumonitis (52 men and 20 women, mean age 63.7 years). Most patients took SST for chronic liver diseases due to infection with the hepatitis C virus. The mean duration of SST therapy before the onset of pneumonitis was 50.2 +/- 42.1 days. Most patients presented with coughing, dyspnea, and fever of acute onset. Chest X-ray films showed diffuse ground-glass shadows and infiltration. Abnormally high levels of C-reactive protein and lactate dehydrogenase were common, as was hypoxia. Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of lymphocytes and neutrophils and a low CD4/CD8 ratio. Although 64 of 72 patients survived after cessation of SST only or steroid therapy, 8 died of respiratory failure despite high-dose steroid therapy. Compared with patients who survived those who died were more likely to have an underlying lung disease, had been taking SST longer after the onset of pneumonitis, and had more severe hypoxemia.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

[Epidural buprenorphine and epidural droperidol for post-operative nausea or vomiting].

For 120 young patients who had undergone reconstruction of anterior cruciate ligament of the knee, we investigated the effect of epidural administration of buprenorphine on the incidence of nausea or vomiting, and the anti-emetic effect of epidural administration of droperidol. In the group who had received bolus injection of buprenorphine 0.1 mg, nausea or vomiting occurred early most often, and the injection was not useful to prolong analgesic effect. In the another group who had received continuous epidural infusion of buprenorphine 0.3 mg, nausea or vomiting occurred late. Bolus injection of droperidol 2.5 mg was not useful to prevent nausea or vomiting caused by continuous epidural infusion of buprenorphine. While, continuous infusion of droperidol 5 mg was effective in decreasing nausea or vomiting caused by continuous epidural infusion of buprenorphine. In conclusion, continuous epidural administration of droperidol is useful to prevent nausea or vomiting.

Adolescent↗
PubMed1996

Intra-arterial blood gas monitoring system: more accurate values can be obtained.

OBJECTIVE: To compare values measured by a continuous intra-arterial blood gas monitoring system with those measured by conventional blood gas analyzer for the assessment of the clinical performance of a new device for measurement of PaO2, PaCO2, and arterial pH. METHODS: Forty-six patients undergoing cardiopulmonary bypass were enrolled in this study. All patients had a continuous intra-arterial sensor (PB 3300) placed into the radial artery through a 20-gauge catheter. A total of 319 arterial blood gas and pH values were obtained for comparison with a conventional blood gas analyzer. The measurements were performed every 12 hrs after the initial in vitro calibration of the sensor for each patient. RESULTS: Measurements were made over a range of 12 to 192 hrs. The overall bias and precision determined by the two methods were 4.5 and 17.1 mmHg for PaO2; 4.5 and 6.2 mmHg for PaCO2; and 0.009 and 0.035 for pH, respectively. For the range of PO2 less than 150 mmHg, the bias and precision improved to 4.2 and 9.5 mmHg. The sensor-derived PCO2 value, PCO2 (IABG), increased significantly more than the conventional blood gas analysis value, PCO2(ABG), even within 72 hrs (2.8 and 4.1 mmHg). The relationship between the two measurements can be described as: PCO2(IABG)/PCO2(ABG) = 1 + 0.0026.t where t is the time period of use (in hours). By correcting the PCO2(IABG) value using this formula, the overall bias and precision of the values measured by two methods decreases to -0.4 and 3.6 mmHg. CONCLUSIONS: The PO2 and pH values derived from an intra-arterial blood gas monitoring system agreed well with the values measured by a conventional blood gas analyzer. However, the PCO2 value must be corrected due to an increase of drift, especially with extended use for more than 72 hours.

Blood Gas Analysis↗
PubMed1996

Possible involvement of an environmental agent in the development of acute eosinophilic pneumonia.

BACKGROUND: Although the pathogenesis of acute eosinophilic pneumonia remains largely unknown, it has been suggested that it may include a hypersensitivity phenomenon induced by inhaled environmental antigens. METHODS: To investigate this possibility, we studied the effect of environmental challenges in three patients with acute eosinophilic pneumonia. Symptoms and laboratory findings were evaluated before and after the challenge tests in the patient's homes and their places of work. RESULTS: After the provocation challenges to their homes, all three patients developed fever, cough, and fatigue and two of them presented with dyspnea. Inspiratory crackles became audible in all cases, and there was a decreased Pao2 level in two. Similar challenges at their workplaces were negative. After moving out of their homes, the patients engaged in their usual work but had no recurrent episodes. CONCLUSIONS: These results suggest that environmental factors in the home can be the cause of acute eosinophilic pneumonia. In order to elucidate the pathogenesis of the disease, it is important to further investigate environmental factors.

Acute Disease↗