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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 469 records · Page 26Linked to original sources

Effects of lansoprazole on ethanol-induced injury and PG synthetic activity in rat gastric mucosa.

Lansoprazole, a proton pump inhibitor, has been reported to inhibit ethanol-induced injury in rats. However, the mechanism of the protective effect is not known. This study was carried out to investigate the role of prostaglandin (PG) in the protective effect of lansoprazole. Male Wistar rats were given either 30 mg/kg of lansoprazole or vehicle alone intragastrically 30 min before administration of ethanol. They were killed to measure the gross mucosal lesions in the stomach as the ulcer index. In another experiment, 5 mg/kg of indomethacin was injected 30 min before administration of lansoprazole. The effects of 16,16-dimethyl PGE2 (dmPGE2) on ethanol-induced injury over time were compared with lansoprazole. PGE2 synthesis in gastric mucosa after administration of lansoprazole was measured by radioimmunoassay. Lansoprazole reduced gastric mucosal injury by lansoprazole. DmPGE2 significantly reduced gastric mucosal injury from 5 min after exposure to ethanol. Lansoprazole did not affect PGE2 synthesis in the gastric mucosa. These results suggest that PG may not be involved in the protective effect of lansoprazole.

16,16-Dimethylprostaglandin E2↗

Prevention by methionine of enhancement of hepatocarcinogenesis by coadministration of a choline-deficient L-amino acid-defined diet and ethionine in rats.

The effects of methionine on hepatocarcinogenesis induced by coadministration of a choline-deficient L-amino acid-defined (CDAA) diet and ethionine were examined. F344 male rats were divided into 4 experimental groups. Groups 1 and 2 received the CDAA diet and a choline-supplemented L-amino acid-defined (CSAA)++ diet, respectively. Group 3 received the CDAA diet containing 0.05% ethionine, and group 4 the CDAA diet containing 0.05% ethionine and 0.47% methionine. Animals were killed after 12 weeks of treatment. Histologically, the CDAA diet induced intracellular fat accumulation and foci. In contrast, ethionine caused not only foci, but also hyperplastic nodules, cholangiofibrosis and the proliferation of oval cells without such fat accumulation. Methionine abolished the development of all of the liver lesions induced by coadministration of the CDAA diet and ethionine. To investigate the effects of methionine on induction of c-myc and c-Ha-ras expression, as well as generation of 8-hydroxyguanine (8-OHGua) and 2-thiobarbituric acid-reacting substances (TBARS), by coadministration of the CDAA diet and ethionine, subgroups of 3 to 5 animals were killed at 2, 4, 8, or 11 days after the beginning of the experiment. Coadministration of the CDAA diet and ethionine markedly enhanced the level of expression of c-myc and c-Ha-ras, 8-OHGua formation and TBARS generation as compared with the CDAA or CSAA diet within 11 days, and methionine blocks these actions. These results indicate that addition of methionine prevents the induction of c-myc and c-Ha-ras expression, 8-OHGua formation and TBARS generation, as well as hepatocellular lesions, by coadministration of the CDAA diet and ethionine in rats, and suggest a possible involvement of oxidative stress and gene expression in hepatocarcinogenesis by these agents.

Amino Acids↗

Unusually located lymphocutaneous nocardiosis caused by Nocardia brasiliensis.

We report a patient with primary lymphocutaneous Nocardia brasiliensis infection affecting the face and left arm. The mode of infection was via skin abrasions which occurred 2 weeks prior to the development of the skin lesions. Treatment with intravenous minocycline for 4 weeks resulted in a cure. We also review 12 previously reported Japanese cases of lymphocutaneous nocardiosis.

Aged↗

Immunohistochemical profile of primary sclerosing lipogranuloma of the scrotum: report of five cases.

Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed common histological features: a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophage/monocytes in the interstitium. Immunohistochemistry disclosed the epithelioid cells and multinucleated giant cells of the granuloma to be monocytes in nature, as both types of cells were positive for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and S-100 protein positive Langerhans-like cells were frequently found. S-100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.

Adult↗

Pulmonary myxoid leiomyosarcoma.

A primary myxoid leiomyosarcoma arising from the peripheral bronchus of the right middle lobe was removed from a 20 year old man and examined by immunohistochemistry and electron microscopy. The tumor was well circumscribed, yellow-whitish focal polypoid growth into the bronchial lumen and consisted of spindle cells with abundant myxoid substance in the stroma. Intrapulmonary metastasis, invasion to the bronchial wall and a few mitotic figures were found. Immunohistochemically, several, but not all, tumor cells were positive against anti-vimentin, anti-S-100 protein, anti-myosin and anti-muscle specific actin. Ultrastructurally, tumor cells had thin filaments with dense bodies, pinocytic vesicles and discontinuous basal lamina. These findings indicate a myoxoid variant of leiomyosarcoma arising from mesenchyme in the peribronchial area.

Adult↗

Non-X histiocytoma, similar to fibrous histiocytoma, in an infant.

A case is presented of a female infant with an atypical histiocytoma. A gradually enlarging brown lesion was noted on the left side of the chest at the age of 2 weeks. Microscopic study of a biopsy revealed an ill-defined infiltration of spindle cells with indented nuclei. The tumor cells were positive for CD14, HLA-DR, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin, and negative for CD1, CD3, CD8, CD10, CD19, CD68 and S-100 by immunohistochemistry. Electron microscopy demonstrated no distinct Birbeck's granules, but aberrant granules were seen in a small number of cells. At 7 months of age, a nodule with similar histologic features was noted in the nuchal region, but was incompletely resected. The patient remains recurrence-free at 36 months of age. This case is thought to be a benign form of non-X histiocytoma.

Diagnosis, Differential↗

Unsuccessful effort to detect human papillomavirus DNA in urinary bladder cancers by the polymerase chain reaction and in situ hybridization.

The association of human papillomavirus (HPV) with urinary bladder carcinogenesis is now a controversial issue. In order to certify the presence of HPV DNA in urinary bladder cancers, the polymerase chain reaction (PCR) using five primer sets for detecting various HPV types was used in this study as well as in situ hybridization (ISH) for HPV 16 and 18 detection. In the PCR study of 93 DNA samples extracted from formalin-fixed and paraffin-embedded urinary bladder cancers, no HPV DNA was detected in these tumor samples. The ISH study was also performed on the same tumor samples, but failed to demonstrate any HPV 16- or 18-positive signals in all except one of the tumor samples. However, the PCR failed to demonstrate HPV 16 DNA even in the bladder cancer positive for HPV 16 DNA by the ISH. This ISH technique was able to demonstrate HPV 16 and 18 DNA in eight of 13 paraffin-embedded cervical cancers, in which HPV 16 or 18 DNA had already been detected by the PCR. Our HPV study using PCR and ISH revealed that the HPV status of urinary bladder carcinomas was far different from that of cervical cancers.

DNA Probes, HPV↗

Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics.

Three major traditional Chinese medicines (TCM), Sho-saiko-To, Saiboku-To, and Sairei-To, consist of similar herbal prescriptions containing glycyrrhizin, which is a strong inhibitor of 11 beta-hydroxysteroid dehydrogenase. We performed cross-over open trials in healthy subjects to clarify prednisolone pharmacokinetics on co-administration of these preparations. All subjects received a single oral dose of 10 mg prednisolone before oral treatment with one of the test preparations. After a 2-week wash-out interval, they received one of the test preparations for three days at daily doses of 7.5 or 9.0 g. On the third study day, 10mg prednisolone was administered orally in combination with the test preparation. Area under the curves (AUC) of prednisolone before and after the treatment decreased from 0.94 to 0.78 mg h L-1 (P < 0.05) in the Sho-saiko-To group, increased from 0.92 to 1.06 mg h L-1 (P < 0.01) in the Saiboku-To group, and did not change in the Sairei-To group. AUC ratios of prednisone and prednisolone, which reflect the 11 beta-hydroxysteroid dehydrogenase activity, increased in the Sho-saiko-To group (P < 0.01), decreased in the Saiboku-To group (P < 0.01), and did not change in the Sairei-To group after the treatments. Similar results were observed in ratios of endogenous cortisone to cortisol. Because of the equal glycyrrhizin content in all three preparations, it was unexpected that the 11 beta-hydroxysteroid dehydrogenase effect was different amongst the three groups. These observations suggest that some unknown metabolic enzyme modifiers, promoters or inhibitors, may be involved in these traditional treatments.

Administration, Oral↗

Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome.

The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA2 activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA2 activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA2 activities were increased in BALF of ARDS patients. The PLA2 activity that bound to heparin was identified as a group II PLA2 by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA2 activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80-90 kDa. Neither anti-pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are increased in activity in BALF of patients with ARDS, a group II PLA2 and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA2. Increased lung PLA2 activity may be important for the pathophysiology of ARDS.

Adult↗

Role of platelet-activating factor in the release of neutrophil and eosinophil chemotactic attractants from cultured guinea-pig tracheal epithelial cells.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of allergic disease, particularly bronchial asthma, by recruitment and activation of inflammatory cells. In an effort to further elucidate this function of PAF, guinea-pig tracheal mucosa was cultured in the presence of PAF in vitro, and culture supernatants were injected intradermally into normal guinea-pigs. After 6 h, recruitment of the inflammatory cells in the tissue was evaluated as a marker of chemotactic activity. Neutrophil and eosinophil recruitment increased significantly 1 h after PAF stimulation, the latter more than the former. After fractionation of the culture supernatant using molecular sieve filters, the fraction of 10-30 kDa showed greater chemotactic activity than the fractions of below 10 kDA or greater than 30 kDA. This activity was inhibited in a dose-dependent manner (over about 1-100 mg/ml) by treatment with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody. These results suggest that PAF induces the release of chemotactic factors for neutrophils and eosinophils from guinea-pig tracheal epithelial cells, and one of these factors may be GM-CSF.

Animals↗

A Japanese case of the fibrillar type of dermatitis herpetiformis.

BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, this disease is very rare in Asian populations including the Japanese. METHODS AND RESULTS: We present a Japanese DH patient, who showed a fibrillar pattern of deposition of IgA, IgG, IgM and C3. The HLA typing revealed no B8/DR3. The survey of the Japanese literature and the comparison to studies on American or European DH revealed several interesting differences: high frequency of the fibrillar pattern, relatively high incidence of deposits of immunoglobulins other than IgA, rarity of gluten-sensitive enteropathy and HLA-B8/DR3 in Japanese DH. CONCLUSION: The present study suggests that there may be a significant difference in pathophysiology between Caucasian and Japanese DH patients.

Complement C3↗

Transforming growth factor-beta 1 expression and phenotypic modulation in the kidney of hypertensive rats.

We have previously reported that renal mRNA levels for transforming growth factor-beta 1, fibronectin, and collagens were increased in 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) with severe nephrosclerosis. To elucidate the mechanism of hypertension-induced nephrosclerosis, we examined gene expression and localization of transforming growth factor-beta 1 and cellular phenotype in the kidney of 25-week-old SHRSP with moderate renal damage. Renal mRNA was measured by Northern blot analysis. The localization of transforming growth factor-beta 1 and cellular phenotype was determined by immunohistochemistry. In the kidney of 25-week-old SHRSP, renal transforming growth factor-beta 1 mRNA was elevated compared with Wistar-Kyoto rats (WKY), whereas renal collagen mRNAs of SHRSP were not increased. Immunoreactive transforming growth factor-beta 1 in SHRSP was mainly localized in glomerular cells. Furthermore, alpha-smooth muscle actin and desmin were significantly expressed in SHRSP glomerular cells, in contrast to negligible expression of these proteins in WKY. alpha-Smooth muscle actin staining was also observed in interstitial cells, and vimentin, another phenotypic marker, was expressed in atrophic tubular cells of SHRSP, despite no staining of these proteins in WKY. Furthermore, all these phenotypic changes in SHRSP were associated with increased cell proliferation, as shown by the increased number of proliferating cell nuclear antigen-positive cells. Treatment of SHRSP with cilazapril and nifedipine (from the age of 13 to 25 weeks) prevented the increase in transforming growth factor-beta 1 expression and the cellular phenotypic modulation and was accompanied by a reduction of urinary albumin excretion and inhibition of cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Eosinophil viability-enhancing activity in sputum from patients with bronchial asthma, Contributions of interleukin-5 and granulocyte/macrophage colony-stimulating factor.

To investigate the mechanisms of eosinophil activation in the airways of patients with asthma, we attempted to detect eosinophil-activating cytokines in sputum extracts obtained from asthmatic patients during acute attacks or in remission by eosinophil survival assay. Purified guinea pig eosinophils were cultured in the presence or absence of sputum extracts, and the eosinophil viability was measured on Day 4. Eosinophil viability in the presence of sputum extracts derived from patients during moderate or severe attacks was significantly higher than that for sputum obtained from patients in remission or during mild attacks or from those with other respiratory diseases, including bronchiectasis and diffuse panbronchiolitis (p < 0.05). The total symptom score during the week prior to sputum collection correlated with the eosinophil viability (rs = 0.79, p < 0.01). Eosinophil viability-enhancing activity (EVEA) in the sputum of asthmatic patients with moderate or severe attacks was neutralized by anti-IL-5 antibody and by anti-GM-CSF antibody by 19.9 +/- 13.7% and 76.9 +/- 8.2% (mean +/- SEM, n = 7), respectively. EVEA was completely neutralized by a combination of anti-IL-5 and anti-GM-CSF antibodies. There was a significant correlation between the concentration of eosinophil cationic protein (ECP) in sputum extracts and the eosinophil viability (rs = 0.54, p < 0.05). These findings suggest that IL-5 and GM-CSF are present in the sputum during asthma attacks and that these cytokines are at least partially responsible for eosinophil activation in asthma.

Animals↗

Hemoglobin denaturation caused by surfactants.

The properties of hemoglobin denaturation caused by two anionic surfactants (sodium dodecylsulfate and sodium lauroylmethyltaurate) were examined using spectrophotometry (multi-plate reader), circular dichroism (CD) and high-performance liquid chromatography (HPLC), and their denaturating action on hemoglobin and sorption to it were examined by various methods. Correlation and factorial analyses were applied to the experimental data and the following results were obtained: (1) High correlations were found among sorption, denaturation and alpha-helix content and the random structure of hemoglobin. (2) The alpha-helix of hemoglobin is randomized as the surfactants denature hemoglobin. (3) Factorial analysis indicates that there are two factors involved in hemoglobin denaturation, one related to the destruction of the alpha-helix and the other related to a change in the beta-structure. These two factors are related to change in the environment around the heme group. (4) Destruction of the alpha-helix seems to be one of the causes of the eye irritation produced by anionic surfactants.

Chromatography, High Pressure Liquid↗