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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 685 records · Page 38Linked to original sources

Transient activation of 1-O-alkyl-sn-glycero-3-phosphocholine: acetyl-CoA acetyltransferase during the incubation of macrophages.

The activity of the platelet-activating factor (PAF)-synthesizing enzyme, 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF):acetyl-CoA acetyltransferase (EC 2.3.1.67) in alveolar macrophage lysate was found to be elevated after warming the cells to 37 degrees C. Such an increase in enzyme activity was detectable only when intact cells were warmed. The stimulation was transient, reaching a peak at 2 min, and then gradually decreased to the control level. We could not find increased PAF formation in warmed cells which had increased acetyltransferase activity, even though substantial amounts of lysoPAF were shown to be present within cells. In contrast, considerable amounts of PAF were formed after treatment of the cells with exogenous lysoPAF. These results suggest that the activation of acetyltransferase is not sufficient to induce PAF formation and that the increased availability of substrates, especially lysoPAF, in the cells is indispensable for triggering PAF biosynthesis in this type of cells.

Acetyl Coenzyme A↗

Production of platelet-activating factor by human normodense and hypodense eosinophils.

Normodense eosinophils and neutrophils from normal donors produced considerable amounts of platelet-activating factor (PAF) when stimulated with ionophore A23187. PAF produced by eosinophils appeared to be degraded more rapidly than PAF formed by neutrophils, suggesting a higher activity of PAF-degrading enzyme in eosinophils. Substantial proportions of PAF newly formed by both eosinophils and neutrophils were shown to be cell-associated. By comparison, hypodense eosinophils obtained from a patient with idiopathic hypereosinophilic syndrome produced an extremely large amount of PAF and released much of it into the incubation medium. The accelerated formation of PAF in hypodense eosinophils may be related to various cardiovascular complications associated with hypereosinophilic syndrome.

Eosinophilia↗

Synergistic effects of phorbol ester and interferon-alpha: target cell class I HLA antigen expression and resistance to natural killer and lymphokine-activated killer cell-mediated cytolysis.

This study was undertaken to investigate whether target cell class I HLA antigen expression induced by phorbol ester and interferon-alpha (IFN-alpha) was associated with resistance to natural killer (NK) cells and lymphokine-activated killer (LAK) cell-mediated cytotoxicity. Class I antigen expression on the surface of the K562 erythroleukemia cell line was enhanced by either IFN-alpha or phorbol ester (PDBu). Addition of PDBu together with IFN-alpha had a synergistic effect on class I antigen expression on the cells. Furthermore, synergism between IFN-alpha and PDBu was also found in class I antigen expression by MOLT-3 cells. This synergistic effect on class I antigen expression was blocked by the protein synthesis inhibitor (cycloheximide). Pretreatment of K562 cells with PDBu and IFN-alpha made them more resistant to lysis by NK and LAK cells than did either PDBu or IFN-alpha. In contrast to PDBu, 4 alpha PDD, a biologically inactive phorbol analogue, alone or combination with IFN-alpha, had no effect on class I antigen expression and susceptibility to lysis by NK and LAK cells. Kinetic experiments showed an inverse relationship between the expression of class I antigens and susceptibility to NK cell-mediated cytolysis. Using cold target competition analysis, target cells pretreated with PDBu and IFN-alpha clearly competed less effectively than did untreated cells for lysis of untreated target cells. These results demonstrate that target cells pretreated with PDBu and IFN-alpha decrease their sensitivity to natural killer and lymphokine-activated killer cells inversely with target cell class I HLA antigen expression.

Cell Line↗

Calcium channel blockers and prostaglandin generation by gastric surface epithelial cells.

We investigated the effects of calcium channel blockers on generation of prostaglandin (PG) E2 and 6-keto PGF1 alpha by gastric mucosal surface epithelium. Surface epithelial cells (SEC) isolated from rat gastric mucosa were incubated with either verapamil (1 or 10 micrograms/ml), diltiazem (2.5 or 25 micrograms/ml) or nifedipine (2.5 or 25 micrograms/ml) for 30 min at 37 degrees C in calcium containing or calcium-free medium. Verapamil (both doses) significantly increased PGE2 and 6-keto PGF1 alpha generation by the surface epithelial cells but only in calcium containing medium. Diltiazem did not affect PG generation in calcium containing nor calcium-free medium. Nifedipine 25 micrograms/ml decreased PGE2 but increased 6-keto PGF1 alpha generation. The inhibitory effect of nifedipine on PGE2 generation was abolished in calcium-free medium, while the calmodulin antagonist did not affect verapamil-induced increase in PG generation.

6-Ketoprostaglandin F1 alpha↗

Antidopaminergic effects of the stereoisomers of N-[(1-alkyl-2- pyrrolidinyl)methyl]-5-sulfamoylbenzamides and -2,3-dihydrobenzofuran-7-carboxamides.

The stereoisomers of some N-[(1-alkyl-2-pyrrolidinyl)methyl]-5- sulfaoylbenzamides (3-8) and -2,3-dihydrobenzofuran-7-carboxamides (9-18) were prepared to compare their dopamine D2 receptor binding affinities (in vitro) and inhibitory effects on apomorphine-induced hyperactivity (in vivo). In the 1-ethyl substituted compounds of the two series, the stereoisomers with S absolute configuration at the 2-position of the pyrrolidine moiety (S enantiomer 3 and 2S diastereomers 9 and 10) were more potent in both of the above activities than those with R absolute configuration (R enantiomer 4 and 2R diastereomers 11 and 12, respectively), whereas the R enantiomer (8) was more potent than the S enantiomer (7) in the 1-n-hexyl-substituted-benzamides and the 2R diastereomers (15, 16, and 18) were more potent than the 2S diastereomers (13, 14, and 17) in the 1-n-butyl- and 1-n-hexyl-2,3-dihydrobenzofuran-7-carboxamides. It was found that the stereospecificity of the compound activities altered from the S configuration to the R configuration as the 1-alkyl side chain became longer in the two series. How these stereoisomers meet the configurational requirements to interact with the dopamine D2 receptors is also discussed.

Animals↗

Differential effects of phospholipids on two similar forms of UDP-glucuronyltransferase purified from rat liver and kidney microsomes.

Two isoforms of UDP-glucuronyltransferase purified from rat liver (named GT-1) and kidney (named GT-2) have various properties in common but differ in their NH2-terminal sequences. In this study, the two forms were further found to have common immunochemical properties, i.e., they could not be distinguished by Ouchterlony double diffusion and immunoblotting analyses. These isoforms also had the same inducibility as shown by immunoblotting analysis: GT-2 protein in rat was increased by treatment with beta-naphthoflavone and 3-methylcholanthrene, whereas GT-1 was inducible by 3-methylcholanthrene. However, the effects of phospholipids on these enzymes were extremely different. 1-Naphthol glucuronizing activity of GT-1 was increased 7.5-8-fold by lysophosphatidylcholine, but the activity of GT-2 was increased only 3-3.6-fold. The transferase activity of GT-1 toward 4-methylumbelliferone was increased 2-2.5-fold by dilauroylphosphatidylcholine, but that of GT-2 was reduced, while its 4-nitrophenol glucuronidation activity was increased 1.5-fold by the phospholipid. These results indicate that the two similar UDP-glucuronyltransferases from rat liver and kidney interact differently with phospholipids and that the activation level of UDP-glucuronyltransferase activity with phospholipids depends on the aglycone substrates.

Animals↗

H2-receptor antagonist-refractory ulcer: its pathophysiology and treatment.

We assessed the intraluminal pH and mucosal prostaglandin E2 (PGE2) concentrations in patients (nonresponders) whose gastric ulcer did not heal after an initial 2 months and subsequent 3 months of treatment with one of five H2-receptor antagonists (H2RAs). The efficacy of misoprostol, a PGE1 analogue, or AG-1749, a proton-pump inhibitor, on ulcer healing in nonresponders was also tested. The percentage of time (24-h measurement) during which the pH was 3 or more was higher in the basal condition (no H2RA) in nonresponders than in good responders with healing in the first 2 months. H2RAs increased this percentage satisfactorily in nonresponders as well as in good responders. The mean mucosal PGE2 concentration in the ulcer rim was 26 ng/g of tissue in nonresponders, much lower than in good responders. Treatment with misoprostol combined with an H2RA resulted in 60% success for ulcer healing within the next 2 months in nonresponders, without affecting the intraluminal pH measured during treatment with an H2RA alone. AG-1749 raised the percentage of time with high pH to 99% from the 68% obtained with an H2RA and cured 88% of this type of ulcer. These results suggest that extremely low PGE2 levels in gastric mucosa are related to the effectiveness of the H2RA. In such a condition, the small amount of gastric acid that is still secreted even during treatment with an H2RA may interrupt ulcer healing. Therefore, treatment with a prostaglandin analogue combined with an H2RA or treatment with a proton-pump inhibitor may be useful for ulcer healing in nonresponders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Peptide tyrosine tyrosine-positive ovarian carcinoid tumor arising from a dermoid cyst.

A case of ovarian carcinoid tumor of the trabecular type is presented. The small carcinoid tumor was found incidentally in a resected dermoid cyst. Histologically, the tumor was surrounded by a smooth muscle layer with focal stromal invasion. Non-carcinoid papillary mucosa and a few small glands, simulating the mucosa of the fallopian tube and remnant müllerian glands, respectively, were also present adjacent to the carcinoid tumor and enclosed by the same smooth muscle layer. The tumor cells revealed argyrophilia, and were positive for peptide tyrosine tyrosine (PYY) in the cytoplasm and for CEA in part of the luminal surface. This case was considered to be a rare ovarian carcinoid tumor arising from a dermoid cyst, without association of struma ovarii. PYY may be a potential marker for determining the histogenesis of ovarian carcinoid tumors.

Adult↗

Transitional cell carcinoma with sarcomatous elements in the urinary tract. Six cases examined by immunohistochemistry.

We report six cases of carcinoma showing sarcomatous change in the urinary tract examined by conventional histochemistry and immunohistochemistry. All of the cases were transitional cell carcinoma with or without focal squamous cell carcinoma. Sarcomatous components resembling spindle cell sarcoma with a marked myxoid stroma or chondrosarcomatous element were also observed in all cases. The sarcomatous elements were closely associated with the areas of squamous cell carcinoma in three cases. Various histochemical staining procedures demonstrated mesenchymal features in the stroma of sarcomatous areas. By immunohistochemical examination, the epithelial components showed positive reactions for keratin, epithelial membrane antigen and, focally, carcinoembryonic antigen. The sarcomatous components revealed a positive immunoreaction for keratin but lacked other epithelial markers in all cases. Chondrosarcomatous elements in two cases were positive for both keratin and S-100 protein. These findings indicate that sarcomatous elements in carcinoma may represent mesenchymal metaplasia with partial or complete loss of epithelial features. However, further study will be necessary in order to determine whether heterogeneous elements, such as chondrosarcomatous areas, are epithelial or truly mesenchymal in origin.

Aged↗

Abnormal granulopoiesis of leukemic cells with basophil/mast cell features. Cytochemical and ultrastructural observations.

We have carried out cytochemical and ultrastructural examination of human leukemic cells showing basophil/mast cell features derived from patients with acute myelogenous leukemia or basophilic crisis in chronic myelogenous leukemia. Leukemic cells in each case initially showed metachromasia with toluidine blue and various degrees of positivity for astra blue. Other cytochemical results showed considerable variety among cases. The number of granules increased in short-term culture in every case. Ultrastructurally, small membrane-bound granules with or without myelinoid bodies or glycogen particles were present in immature blasts, followed by production of other granule types. In some cases, leukemic cells before and after liquid culture contained the typical basophil granules with or without myelinoid bodies, but the matrix was more loose than normal. Granules showing whorl or scroll matrix profiles, which were typical for mast cells, were present in two cases. In one case, immature leukemic cells contained theta granules, and some mature forms after short-term culture contained typical basophil/mast cell granules as well as theta granules. Leukemic cells occasionally contained multivesicular granules predominantly. These results indicate that leukemic cells with basophil/mast cell features show a heterogeneous configuration and contain abnormal granules differing from normal ones. This abnormal granulopoiesis may be attributable to the results of leukemic events and may be a hallmark for recognition of leukemic basophils/mast cells.

Adolescent↗

Unusual pancreatic tumor resembling solid and cystic tumor, with somatostatin production and aberrant crystalloid structures.

An unusual pancreatic tumor in a middle-aged man is reported. The tumor was a large encapsulated mass with necrosis and hemorrhage, and microscopically, it showed a predominant microcystic pattern with solid pattern areas. The clinical and histological features of this tumor were similar to those of solid and cystic tumor. Immunohistochemical studies showed that the tumor was positive for alpha 1-AT, NSE, CA 19-9 and somatostatin. Electron microscopy studies showed neurosecretory granules, intercellular junctions, annulate lamellae and aberrant crystalloid structures. These findings indicated that the tumor had differentiated into acinar, ductal and endocrine cells, suggesting that solid and cystic tumor originates from multipotential immature cells.

Adult↗

A case of malignant duct-islet cell tumor of the pancreas immunohistochemical and cytofluorometric study.

A rare duct-islet cell tumor of the pancreas was studied using immunohistochemical, cytofluorometric and histochemical methods. Histology and immunohistochemistry revealed that the tumor contained two distinct cell types; islet cell-like neuroendocrine cells and exocrine duct cell components, suggesting an endodermal origin for both types. The cells showed marked pleomorphism an vascular and perineural invasion at the tumor periphery. Cytofluorometric study of the tumor cell DNA revealed an increased mean nuclear DNA content, without any aneuploidy. Histochemically, the tumor cells contained an increased number of argyrophilic nucleolar organizer regions (AgNORs) in their nuclei. The malignant potential of this duct-islet cell tumor was suggested.

Adenoma, Islet Cell↗

Histological and immunohistochemical observations of dedifferentiated leiomyosarcoma of the uterus.

A case of dedifferentiated leiomyosarcoma of the uterus was examined using immunohistochemistry. The tumor arose in the myometrium, and was a whitish large nodule with hemorrhage and necrosis. Histologically it was a well differentiated leiomyosarcoma with foci showing epithelioid pattern, and in part resembling malignant fibrous histiocytoma (MFH) and giant cell tumor (GCT). Additionally, small round neoplastic cells arranged in an alveolar manner, simulating alveolar rhabdomyosarcoma, were seen in some areas. Neoplastic cells in well differentiated areas expressed desmin, muscle-specific actin and LeuM1, whereas those in epithelioid and poorly differentiated areas lacked these antigens. Instead, tumor cells in epithelioid and small round cell areas were positive for keratin. Interestingly, most tumor cells in well differentiated, epithelioid and small round cell areas were also positive for MB1. However, tumor cells in GCT- and MFH-like areas reacted with none of the antibodies used. Ultrastructurally, some tumor cells possessed various amounts of microfilaments with or without dense patches, whereas others lacked them. These findings suggest that the divergent antigen expression was attributable to different levels of differentiation, and that poorly differentiated components had lost their native features.

Actins↗

Experimental study about removal of the implanted tined polyurethane ventricular lead by radiofrequency waves through the lead.

Polyurethane pacemaker leads are widely used nowadays. However, only a few studies have been done to investigate the fixation mechanism of polyurethane leads. To elucidate how pacemaker leads are fixed at the early phase after implantation, polyurethane-insulated tined ventricular leads were implanted in seven mongrel dogs. One to 4 months later, tips of the leads were anchored among the trabeculae and the distal part of the leads were encapsulated by whitish fibrous tissue. It was found that not organized thrombi, but cell reaction with various stages of inflammatory cells was responsible for forming the fibrous tissue. We attempted to remove the lead by delivering radiofrequency wave through the lead. However, no lead could be removed.

Animals↗

Screening of natural waters for viruses which infect chlorella cells.

By using a plaque assay with the unicellular green alga Chlorella sp. strain NC64A as a host, viruses were screened from natural pond waters collected in Kyoto and Higashi-Hiroshima, Japan. From some samples tested, two kinds of plaques, large (phi = 6 to 10 mm) and small (phi = 2 to 3 mm), were detected with various frequencies. The frequency of plaques in each of the water sources was seasonal; generally, it reached a peak value (8,000 PFU/ml) in May and gradually decreased to the limit of detection (<1) in November before increasing again in early spring. Electron microscopy revealed that the purified and negatively stained viruses were very large (125 to 200 nm) icosahedral particles. The genome isolated from these particles was always a linear double-stranded DNA of 340 to 370 kbp. Electrophoresis patterns of the DNA fragments produced by digestion with restriction enzymes differed considerably from plaque to plaque, even for plaques from the same water source. However, Southern hybridization showed strong homology among all of the virus DNAs tested, indicating relatedness of those viruses. A possible use of the Chlorella virus assay system to monitor the natural population of algal cells and water quality is discussed.

Journal Article↗

Immunological analysis of acquired factor VIII inhibitor in a case with immunologic disorder.

Coagulation factor VIII inhibitor arising in a patient with autoimmune disease was immunologically analyzed. A 63-year-old man who had been diagnosed as suffering from polyarteritis nodosa was treated with prednisolone for 10 years. Severe bleeding tendency developed and coagulation studies demonstrated a high titer of inhibitor to factor VIII:C. As a result of immunological analysis, the inhibitor was found to be IgG type autoantibody having both kappa and lambda light chains. The subclasses were IgG1 and IgG4. The inhibitor recognized the COOH-terminal light chain (72-kDa thrombin fragment) on the factor VIII molecule as an epitope.

Autoantibodies↗

Inhibition of antigen-induced late asthmatic response and bronchial hyperresponsiveness by cyclosporin and FK 506.

Using a guinea pig model of asthma, we have shown that the administration of cyclosporin, a T-lymphocyte-selective immunosuppressive agent, from the beginning of the immunization period inhibits the development of the late asthmatic response and bronchial hyperresponsiveness after antigen challenge. Similar results were obtained with FK 506, a new potent immunosuppressive agent. Since these compounds have been shown to suppress the activation of guinea pig T lymphocytes, the present data suggest that T lymphocytes may be important for the elicitation of the late asthmatic response and bronchial hyperresponsiveness.

Animals↗