Search PubMed⌕ Search

Biomedical subjects

M Mikami

Publications and source records attributed to M Mikami.

At least 55 records · Page 3Linked to original sources

[Relationship between cancer chemotherapeutic drug-induced delayed emesis and plasma levels of substance P in two patients with small cell lung cancer].

We investigated the relationship between delayed emesis caused by cisplatin (CDDP) based chemotherapy and plasma levels of serotonin, 5-hydroxy-indoleacetic acid (5-HIAA), and substance P in two patients with small cell lung cancer. In each of the cases, we used the 5-HT3 receptor antagonist ramosetron every morning on day 1-4 of the chemotherapy. In case 1, plasma levels of serotonin were low, whereas substance P levels increased since 24 hours after the injection of CDDP. The increase in substance P levels paralleled the onset of vomiting. In this case, however, substance P levels decreased and yet vomiting occurred. Similarly, in case 2, plasma levels of serotonin were low, whereas substance P levels increased since 24 hours. The increase in plasma levels of substance P and the onset of vomiting were observed at the same time 2-3 days after cisplatin administration. In this case, however, vomiting was not observed during the 5 days when the substance P was highest. Therefore, we suggested that substance P was closely associated with CDDP-induced delayed emesis, though some chemical mediators other than substance P might also be related to the emesis.

Adult↗

[A case of gastric stromal tumor with chest pain and diaphragm elevation].

A 66-year-old woman presented with left chest pain. Left pleural effusion was seen on a chest X-ray film and a large mass disclosed by chest computed tomography. However, the patient refused to undergo a recommended operation. Six months later, she was admitted without any symptoms. A huge (18 cm diameter) mass was detected by magnetic resonance imaging (MRI), and consisted of heterogeneous solid and cystic components. Angiography and endoscopic sonography disclosed a suspected abdominal tumor, which was resected by thoracolaparotomy. Gastric stromal tumor was diagnosed on the basis of histological findings. Chest pain and pleural effusion are rare as initial clinical symptoms of such tumors.

Aged↗

[Utilization of NIH image for quantification of emphysema by computed tomography].

The percentage of the low attenuation area (LAA%) is understood to be the most accurate index in quantifying emphysema by computed tomography (CT). To date, CT scanners with enhanced post-processing programs have been used for measurements of LAA%. In this study, we sought develop a method of LAA% determination using a conventional density mapping program for CTs and NIH Image, an image-analysis software package for personal computers. Our results for overall LAA%, together with the correlations between overall LAA% and pulmonary function tests, agreed well with the findings of earlier reports. In reproducibility trials utilizing our method interoperator error for LAA% was within +/- 2%. A phantom experiment indicated that there was little difference between LAA% values obtained by this method and the values obtained by direct CT measurements. Therefore, we concluded that this method is sufficiently reliable for clinical use and capable of facilitating LAA% measurements with CT scanners that are not equipped with enhanced post-processing software.

Aged↗

The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine.

Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.

Chemotaxis↗

The inhibitory effect of lycorine on tumor cell apoptosis induced by polymorphonuclear leukocyte-derived calprotectin.

We recently demonstrated that calprotectin, an abundant calcium-binding protein complex in polymorphonuclear leukocytes (PMNs), has the capacity to induce growth inhibition and apoptotic cell death against a variety of tumor cell lines and normal cells such as fibroblasts. Therefore, calprotectin which is released to extracellular spaces, might cause tissue destruction in severe inflammatory conditions. In search of drugs to suppress the cytotoxic effects of calprotectin, we screened plant products that have been used as Chinese medicines. Using MM46 mouse mammary carcinoma cells as targets, we found that hot water extracts of Crinum asiaticum showed strong inhibition of calprotectin-induced cytotoxicity in vitro. By purification studies, we identified the alkaloid, lycorine, as the active inhibitory molecule. Lycorine inhibits not only induction of MM46 cell death by calprotectin but also inhibits the suppressive effect of calprotectin on target DNA synthesis at a half effective concentration of 0.1-0.5 microg/ml. Lycorine has been reported to posses inhibitory activity against protein translation. Since we previously showed that target protein synthesis is necessary for induction of cell death and that calprotectin actually upregulates the net protein synthesis of MM46 cells, we compared the dose-response relationship between the inhibitory effects of lycorine on calprotectin action and target protein synthesis. Although 1 microg/ml lycorine did not bring about marked inhibition of protein synthesis in MM46 cells without calprotectin, it attenuated the protein synthesis that was augmented by calprotectin to the level of protein synthesis in cells not treated with calprotectin. These results suggest that lycorine inhibition for calprotectin cytotoxicity is not solely due to its inhibitory effect on protein synthesis.

Amaryllidaceae Alkaloids↗

A novel method to immobilize bioactive substances on hydrophobic surfaces using a polymerizable cationic lipid.

We have successfully developed a novel method to stably immobilize bioactive substances that have anionic groups, such as heparin and succinylated collagen (SC), on hydrophobic surfaces through ionic complexation using a polymerizable cationic lipid, diallyl(dioleyl)ammonium bromide (DADOA). It is composed of a hydrophobic part consisting of long hydrocarbon chains and a hydrophilic head with double bonds which render it polymerizable. Analysis of the modification with DADOA and heparin suggested that the modification formed a thin layer, roughly 60 nm in thickness, as a result of the spontaneous deposition of DADOA and heparin dissolved in water, through the hydrophobic interaction between DADOA and the surface and the ionic complexation between DADOA and heparin. The heparin deposition and its rate of release in plasma were 1.5 microg/cm2 and 0.0017 U/cm2/min, respectively. Cytotoxicity test results showed that the polymerization of the deposited DADOA rendered the modified surface stable and noncytotoxic. Further, antithrombogenicity and cell attachability test results demonstrated that heparin and SC were effectively immobilized on hydrophobic surfaces through ionic complexation. This method has proved useful for the modification of the hydrophobic surfaces of medical devices because the modification process can be performed under aqueous conditions without the use of organic solvents which induce crazing/cracking of plastic casings.

Allyl Compounds↗

Kinetical analysis of tumor cell death-inducing mechanism by polymorphonuclear leukocyte-derived calprotectin: involvement of protein synthesis and generation of reactive oxygen species in target cells.

We have previously shown that calprotectin, the most abundant cytosolic protein existing in polymorphonuclear leukocytes (PMNs), induces apoptotic cell death in various tumor cells, suggesting that calprotectin is an effector molecule against tumor cells in PMNs. To explore the cell death-inducing mechanism of the factor, we examined the involvement of target protein synthesis and generation of reactive oxygen species (ROS) in the reaction. Calprotectin induced cell death in MM46 mouse mammary carcinoma cells after a 14-16 hr lag time. When the factor was removed from the medium up to about 12 hr after culturing, the effect was diminished. The induction of cell death by calprotectin was markedly inhibited by the presence of the RNA synthesis inhibitor actinomycin D or the protein synthesis inhibitor cycloheximide. However, the addition of these inhibitors after 12 hr of culturing was unable to inhibit the reaction. Up to 12 hr of culturing, the net protein synthesis of MM46 cells was augmented by the presence of calprotectin, but thereafter was impaired. The induction of cell death was also inhibited by the antioxidative reagents N-acetyl-L-cysteine (NAC) or propyl gallate. The addition of NAC even 15 hr later significantly attenuated the calprotectin effect. Flow cytometry analysis showed that calprotectin began to increase the ROS content in MM46 cells after 8-12 hr of culturing, and that the increase was abrogated by the antioxidants. Thus, protein synthesis and ROS generation may be essential elements in the early or later phases of the cell death-inducing reaction of calprotectin, respectively.

Animals↗

Anti-Candida activity of calprotectin in combination with neutrophils or lactoferrin.

The effect of an anti-microbial protein, calprotectin, in combination with neutrophils on the growth of Candida albicans was investigated. The growth inhibition of C. albicans by murine neutrophils was augmented by the addition of a low concentration of calprotectin prepared from rat peritoneal exudate cells. The concentrations of calprotectin causing 50% inhibition of growth of C. albicans in the absence or presence of neutrophils at an effector-to-target (E/T) ratio of 30 and 60 were estimated to be 0.45, 0.34 and 0.28 U/ml, respectively. The anti-Candida activity of calprotectin was completely inhibited by 2 microM of zinc ion, while it only partially lowered the activity of the combination of calprotectin and neutrophils. Lactoferrin, which is an anti-microbial protein released from neutrophils, strongly inhibited the growth of C. albicans in combination with calprotectin. These results suggest that calprotectin and lactoferrin released from neutrophils may cooperate to inhibit the growth of C. albicans at a local lesion of the infection where there is an accumulation of neutrophils.

Animals↗

The chemotactic activity of sputum from patients with bronchiectasis.

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Acute Disease↗

Amelogenin protein in tooth germs of the snake Elaphe quadrivirgata, immunohistochemistry, cloning and cDNA sequence.

In the snake, Elaphe quadrivirgata, the occurrence of amelogenin was immunohistochemically demonstrated in the enamel of developing tooth germs. Teeth of the snake are covered with a thin true enamel layer about 1-2 microns in thickness. Light and electron microscopic immunohistochemistry indicated an intense amelogenin immunoreactivity occurring in the enamel layer during the secretory stage of tooth development. Cloning and cDNA sequence of snake amelogenin was performed by RT-PCR. The amino acid sequence of the snake amelogenin cDNA--in its portion corresponding to the area from exon 5 to exon 7 of human X189 amelogenin gene--showed 45% homology with humans. Regions of both the N-terminus and C-terminus were well conserved. Furthermore, the positions of prolin in the amino acid alignment of the snake amelogenin corresponded well with those of human amelogenin. It is suggested that prolin is an essential constituent of amelogenin and therefore its positions in the molecule have been conserved after the evolutionary divergence of reptiles and mammals. This study using reptiles is the first detection of specific amelogenin immunoreactivity by high resolutional immunoelectron microscopy and the first cloning of amelogenin cDNA in a non-mammalian animal.

Amelogenin↗

[Pulmonary pseudallescheriasis in a patient with diabetes mellitus and alcoholic liver cirrhosis].

A 62-year-old man with diabetes mellitus and alcoholic liver cirrhosis was admitted to the hospital because of hemoptysis. Chest X-ray films and computed tomograms showed a dense infiltrative lesion and a healed tuberculous cavity with a possible fungus ball in the upper lobe of the right lung. Bronchoscopy revealed that the hemoptysis originated from the right upper-lobe bronchus. The bleeding stopped after thrombin was applied into the bronchus. Filamentous fungi were seen in lavage fluid from the right upper-lobe bronchus. The fungi were identified as Pseudallescheria boydii, and pulmonary pseudallescheriasis was diagnosed. the patient was treated successfully with miconazole (400 mg/day) for 2 months. Pseudallescheriasis should be taken into account in the differential diagnosis of aspergilloma-like lesions.

Antifungal Agents↗

Anemia-inducing factor expressed in gastric cancer is homologous with complement regulatory factor CD59?

Anemia-inducing factor (AIF) was isolated from gastric cancer tissue; however, the human placenta used as the volume of AIF for further analysis did not prove sufficient. This substance was named placental anemia-inducing factor (PAIF). PAIF directly reduces the number of erythrocytes in vitro and reduces the RBC count in rabbits to 80% when i.v. administration of 27 microg/kg of body weight is given. The aim of this study is to better define PAIF and to examine whether the identifical substance expresses on either the surface or in the cytoplasm of established gastric cancer cell lines. PAIF is a glycoprotein with about 20 KD, whose 17 amino acid residues of N terminus were sequenced after Edman treatment. The N-terminus of PAIF were determined as Lqcyncpnptadcktav. This is homologous with that of CD59, which is thought as a regulator of membrane attack complex of complement system. Expression of PAF or CD59 in four established gastric cancer cell lines were examined by indirect immunofluorescence method and by Northern blot hybridization. The cells (1 x 106) were seeded into plastic plates for three days and reacted overnight at 4 degrees C in 0.5 ml of PBS with anti-PAIF polyclonal antibody or with anti CD59 rat monoclonal antibody. Both PAIF and CD59 were stained positively on the surface and/or in the cyroplasm. The total RNAs were prepared from the four kinds of cell lines and normal human lymphocytes. CD59 mRNA was probed in all cell lines by BamH1-EcoR1 fragment of PSRa CD59. The signal levels of MKN-28, MKN-45 and KATO-III were stronger than that of MKN-74, whereas the signal of normal lymphocytes was the lowest. Although there is no decisive evidence that PAIF is exactly the same substance as CD59, and although the biological functions of these two substances are conflictive, and still to be further investigated, the 17 amino acid residues of N-terminus of PAIF expressed in gastric cancer cells were homologous with those of CD59. A derivative of CD59 may exist in gastric cancer.

Amino Acid Sequence↗

Flow cytometric analysis of cell surface antigen recognized by monoclonal antibody (MSN-1) in normal, hyperplasia, and carcinoma of endometrial cells: its diagnostic value for endometrial carcinoma.

A monoclonal antibody, MSN-1, was used for flow cytometric analysis of cells from normal endometrium, endometrial hyperplasia, and endometrial carcinoma. The 90th percentile of the specimen control was used as a threshold. Reactivity was defined by the percentage of stained cell about the thresholds, adjusted for the expected percentage. A sample was considered positive if the reactivity exceeded 10%. The positivity rate for normal endometrium, endometrial hyperplasia, and endometrial carcinoma specimens was 9.2%, 19.2%, and 84.6%, respectively. The mean (+/-SD) reactivity rate of MSN-1 for normal endometrium, endometrial hyperplasia, and endometrial carcinoma was 3.3 +/- 6.2%, 7.4 +/- 13.8%, and 34.4 +/- 24.2%, respectively. There was a significant difference of the reactivity rates between normal endometrium and endometrial hyperplasia, and between endometrial hyperplasia and endometrial carcinoma (P < 0.01). In the subgroup of endometrial carcinoma patients with confined muscular invasion, the reactivity and the positivity rates were also analyzed. There was no relationship between the depth of muscular invasion and the reactivity rate or the positivity rate. In endometrial carcinoma patients who simultaneously underwent endometrial cytology, the relationship of the results of cytology and the positivity rate was also analyzed. When the results of cytology and flow-cytometric analysis were combined, the positivity rate of endometrial carcinoma was 100% (30/30). In conclusion, flow-cytometric analysis of endometrial cells employing MSN-1 could be a useful supplementary diagnostic method for endometrial carcinoma.

Animals↗

Increase of heat-shock protein and induction of gamma/delta T cells in peritoneal exudate of mice after injection of live Fusobacterium nucleatum.

Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans are Gram-negative rod periodontal pathogens. The peritoneal cavity of Institute of Cancer Research (ICR) mice was used as the local infection model. In vivo production of heat-shock proteins (hsp) was studied by injection of 1/10 minimum lethal dose (MLD) of each live bacteria into mice. Heat-shock proteins 70 and 60 were examined in the extract of peritoneal exudate cells (PEC) from mice injected intraperitoneally with either F. nucleatum or A. actinomycetemcomitans by using sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting analysis. Although hsp are present in PEC without injection of the bacteria, both hsp increased and reached a peak on day 3 after F. nucleatum injection but not after A. actinomycetemcomitans. Kinetic study of gamma/delta cells in PEC after injection of bacteria showed that the increase of gamma/delta T cells was observed only in the PEC from mice injected with F. nucleatum but not A. actinomycetemcomitans. The gamma/delta T cells in PEC were either CD3+ and CD4+ or CD3+ and CD8+. The differential cell count of PEC suggested that gamma/delta T-cell induction is related to the expansion of the macrophage population. The phagocytic and chemiluminescence responses of macrophages against the same bacteria were compared after intensive immunization with live F. nucleatum and A. actinomycetemcomitans. Elevations of chemiluminescence response and phagocytic function by immunization were observed in the macrophages of mice immunized with F. nucleatum. These results suggest the sequential appearance of hsp, gamma/delta T cells and macrophage activation after fusobacterial infection.

Actinobacillus Infections↗

A 15N GC/MS study of in vivo glutamine synthesis in liver failure rats.

To clarify the nature of nitrogen metabolism between branched chain amino acid (BCAA) and glutamine (Gln) in liver failure, we measured arterial plasma concentrations of Gln and 15N uptake to amino-N and amide-N of Gln in normal and D-galactosamine-induced fulminant hepatic failure (FHF) rats after 15N-leucine (Leu) injection. Fifteen, 30 and 60 min after Leu injection, the arterial plasma concentrations of Gln were significantly higher in FHF rats than in controls. The concentrations of amino-15N Gln were also significantly higher in FHF rats than in controls at 5, 15, 30 and 60 min after injection. The concentrations of amide-15N Gln did not significantly differ between FHF and controls at 5, 15 and 30 min. However, at 60 min, the concentration was significantly higher in the FHF rats. The higher uptake of 15N to amino-N of Gln in FHF rats suggests the presence of an enhanced ability to synthesize Gln from Leu in FHF rats. The higher uptake of 15N to amide-N of Gln in FHF rats at 60 min after injection suggests that excessive administration of BCAA to patients with severely impaired urea-cycle capacity suffering with hepatic failure may lead to greater levels of hyperammonemia.

Animals↗

Growth-inhibitory and apoptosis-inducing activities of calprotectin derived from inflammatory exudate cells on normal fibroblasts: regulation by metal ions.

We have shown previously that a calcium-binding protein complex, calprotectin, derived from polymorphonuclear leukocytes exerts a cytostatic and cytolytic effect against a very broad range of tumor cell lines. We also described that calprotectin is an apoptosis-inducing factor for certain tumor cells and that zinc ion attenuates the calprotectin activities. The titers of the factor in body fluids are known to increase greatly in various types of inflammation. In this study, to learn the role of calprotectin in inflammation, the growth-inhibitory and the apoptosis-inducing activities of the factor against normal fibroblasts were examined because fibroblasts are a cell type constituting a local inflammatory site. Rat calprotectin inhibited the growth of murine embryonic as well as human dermal fibroblasts. Although calprotectin induced apoptotic morphology in both fibroblasts, the reaction was slower and less efficient than cases using tumor cells as targets. The activities were significantly abrogated by 10-50 microM Zn2+, Cu2+, Mn2+, or Fe2+, respectively, whereas the trivalent cations Al3+ and Fe3+ had no effect. The dose-response curves of the calprotectin effects were shifted to about 10-fold lower concentration ranges in the divalent metal ion-depleted medium. These results suggest that calprotectin extracellularly affects the inflammatory processes by modulating the growth and survival states of normal fibroblasts, and that the effects are physiologically controlled by several metal ions.

Animals↗

[Flutropium bromide was effective in relieving symptoms of lymphangioleiomyomatosis--a case report].

A 32-year-old woman was admitted with persistent dyspnea. Chest roentgenogram showed hyperinflation of the lungs, and diffuse reticular shadows in both lung fields. Chest CT showed diffuse cystic lesions and thickened vasculature. Examinations revealed severe hypoxemia, restrictive and obstructive ventilatory impairments, increased residual volume, and decreased carbon monoxide diffusing capacity. Lymphagioleiomyomatosis was strongly suspected, and a diagnosis confirmed histopathologically by lung biopsies. Inhalation of flutropium bromide was remarkably effective in relieving dyspnea and impaired pulmonary functions. It is suggested that flutropium bromide is beneficial for symptomatic improvement in patients with lymphangioleiomyomatosis.

Administration, Inhalation↗