Biomedical subjects

K Dobashi

Publications and source records attributed to K Dobashi.

At least 73 records · Page 4Linked to original sources

PubMed1998

Suppression of macrophage activation by peritoneal fluid from patients with endometriosis.

To investigate the effects of peritoneal fluid from patients with endometriosis on mouse peritoneal macrophages (Mphi), peritoneal fluid from endometriosis patients (n = 15) were added to a monolayer of C3H/HeJ mouse peritoneal Mphi. Tumor necrosis factor-producing activity was measured by the L929 assay activated with FK-23 (a preparation of heat-killed Enterococcus faecalis). Tumor necrosis factor-producing activity of C3H/HeJ mouse peritoneal Mphi incubated with peritoneal fluid was suppressed in 14 endometriosis patients. Interestingly, in nine endometriosis patients, tumor necrosis factor-producing activity was much lower than seen with mouse peritoneal Mphi incubated with corticosterone. Peritoneal fluid contains suppressive properties for the activation of peritoneal Mphi, which might allow the implantation of free endometrial cells or the metaplastic phenomena stimulated by retrograde menstruation.

Adult↗

PubMed1998

Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD-1151T).

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.

Adult↗

PubMed1998

Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine.

Dihydropyrimidine dehydrogenase (DPD) deficiency with a defect of the pyrimidine catabolic pathway has recently become the focus of considerable attention, due to the severe 5-fluorouracil (5-FU) toxicities occurring in DPD deficiency patients. Studies also suggest that 5-FU toxicities could occur in another pyrimidine metabolic disorder, dihydropyrimidinuria (DHPuria). This study shows that urinary dihydrothymine (DHT) and thymine (THY) are useful indexes for detection of DPD deficiency and DHPuria. We measured urinary DHT and THY in 276 Japanese adults to establish reference ranges. When males and females were compared, both DHT and THY levels were found to be significantly higher in females. The reference ranges (mean +/- SD with logarithmic values) for males were found to be 1.56-5.70 micromol/g of creatinine for DHT and 0.40-1.47 micromol/g of creatinine for THY. The reference ranges for females were found to be 1.89-8.33 micromol/g of creatinine for DHT and 0.58-2.30 micromol/g of creatinine for THY. In addition to this study we analyzed a DPD deficiency case and a DHPuria case. In the DPD deficiency case, the THY concentrations of all urine samples were out of the reference range. However, uracil levels in most of the samples were within the normal range. The DHPuria case excreted large amounts of DHT and dihydrouracil, both out of the normal range.

Adolescent↗

PubMed1998

K1115 A, a new anthraquinone that inhibits the binding of activator protein-1 (AP-1) to its recognition sites. II. Taxonomy, fermentation, isolation, physico-chemical properties and structure determination.

A new inhibitor of the action of activator protein-1 (AP-1), designated K1115 A, was isolated from the fermentation broth of an actinomycete strain Mer-K1115. K1115 A was determined to be a new anthraquinone, 3,8-dihydroxy-1-propylanthraquinone-2-carboxylic acid, based on spectroscopic analysis, derivatization experiments and biosynthetic studies with 13C-enriched acetic acid. Two co-produced compounds, K1115 B1 and B2, were also isolated and characterized as new members of the naphthopyranomycin and exfoliamycin group.

Anthraquinones↗

PubMed1998

Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity.

5-Fluorouracil (5-FU) is used widely in the treatment of several common neoplasms. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. Several recent studies have described a pharmacogenetic disorder in which cancer patients with decreased DPD activity develop life-threatening toxicity following exposure to 5-FU. We reported recently the first Japanese case of decreased DPD activity accompanied by severe 5-FU toxicity. The present study describes the results of molecular analysis of this patient and her family, in which three novel mutations (Arg21Gln, Val335Leu, and Glu386Ter) of the gene coding for DPD were identified. We also revealed that Arg21Gln and Glu386Ter are on the same allele and that Val335Leu is on the other allele, on the basis of analysis of the family genome. Expression analysis in Escherichia coli showed that Val335Leu and Glu386Ter led to mutant DPD protein with significant loss of enzymatic activity and no activity, respectively. The Arg21Gln mutation, however, resulted in no decrease in enzymatic activity compared with the wild type. The present data represent the first molecular genetic analysis of DPD deficiency accompanied by severe 5-FU toxicity in a Japanese patient.

Antimetabolites, Antineoplastic↗

PubMed1997

Micrometastatic P53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance.

OBJECTIVES: Approximately one fourth of all patients with stage I non-small-cell lung cancer die of tumor recurrence, despite radical removal of their tumors. We thus tried to detect micrometastasis in the regional lymph nodes indicated to be tumor free by conventional histopathologic methods in patients with non-small-cell lung cancer by using immunohistochemical staining for p53 protein. We also investigated the relation between micrometastatic p53-positive cells in the lymph nodes and the prognosis of the patients. METHODS: Samples from 480 regional lymph nodes were taken from 47 patients who underwent pulmonary resection for non-small-cell lung cancer and whose primary lesions were positive for p53 immunohistochemical staining. These samples were fixed in formalin and embedded in paraffin. We used p53 immunohistochemical staining to detect micrometastatic tumor cells in the lymph nodes. RESULTS: Cells positive for p53 protein were found in 14 of 31 (45%) patients with a negative pathologic lymph node status and in 26 of 315 (8.3%) lymph nodes in these patients. The proportion of patients with micrometastasis who survived was also significantly lower than the proportion of patients without micrometastasis who survived (p = 0.0001). CONCLUSIONS: Immunohistochemical staining for the p53 protein offers a rapid, sensitive, and useful way of detecting for micrometastasis to the regional lymph nodes in patients with non-small-cell lung cancer that is positive for p53 staining. The patients with such micrometastases have a poor prognosis and thus need to be carefully followed up after the initial pulmonary resection.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Receptor-dependent G protein-mediated Ca2+ sensitization in canine airway smooth muscle.

To determine the mechanisms of receptor-dependent Ca2+ sensitization in airway smooth muscle, canine tracheal smooth muscle (CTSM) was permeabilized with alpha-toxin or beta-escin. Although the effects of 5-hydroxytryptamine (100 microM), histamine (100 microM), and the thromboxane A2 analogue U-46619 (100 microM) were negligible, carbachol (100 microM) and endothelin-1 (ET-1, 1 microM) evoked additional contractions of 47.0 +/- 5.90% and 25.0 +/- 5.37% (n = 6) at pCa 6.7 with GTP (3 microM) (normalized to the maximum contraction at pCa 4.5) in alpha-toxin-permeabilized CTSM. GDP-beta-S (1 mM) reversed the carbachol and ET-1 responses completely. GTP-gamma-S (30 microM) and 4 beta-phorbol 12,13-dibutyrate (PDBu, 3 microM) increased the Ca2+ sensitivity (median effective pCa) of contraction by 1.8- and 4.4-fold, respectively (n = 4-11, P < 0.05). The effects of saturating concentrations of GTP-gamma-S and PDBu were additive. A synthetic peptide (T2) corresponding to the actin-binding site of calponin caused a dose-dependent contraction of beta-escin permeabilized CTSM, with the peak effect (25 +/- 4%, n = 4) at 1200 microM, PDBu (3 microM) caused contraction of the T2 peptide-treated CTSM. In conclusion, Ca2+ sensitization of CTSM depends on receptor type and is mediated by G proteins and protein kinase C whose effects are additive, with a partial contribution by calponin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Decreased pulmonary perfusion in hypersensitivity pneumonitis caused by Shiitake mushroom spores.

Hypersensitivity pneumonitis is an occupational hazard of mushroom workers. We describe a patient with severe hypersensitivity pneumonitis caused by spores of the Shiitake mushroom (Lentinus edodes) who showed a marked decrease in pulmonary perfusion, as demonstrated by pulmonary scintigraphy. This patient was treated successfully with prednisolone. These results suggest that pulmonary vasculitis may be associated with patients with hypersensitivity pneumonitis, and that steroid therapy may be clinically useful in treatment.

Alveolitis, Extrinsic Allergic↗

PubMed1997

Modulation of endogenous antioxidant enzymes by nitric oxide in rat C6 glial cells.

To understand the possible mechanism of nitric oxide (NO)-mediated cytotoxicity, we investigated the effect of NO on the endogenous antioxidant enzymes (AOEs) catalase, glutathione peroxidase (GPX), and CuZn- and Mn-superoxide dismutases (SODs) in rat C6 glial cells under conditions in which these cells expressed oligodendrocyte-like properties as evidenced by the expression of 2',3'-cyclic-nucleotide 3'-phosphohydrolase. The 24-h treatment with S-nitroso-N-acetylpenicillamine (SNAP), a NO donor, decreased the activities and the protein levels of catalase, GPX, and Mn-SOD in a dose-dependent manner. Alternatively, the activity and the protein level of CuZn-SOD were increased. 2-Phenyl-4,4, 5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a NO scavenger, blocked the effect of SNAP. Moreover, the treatment of C6 cells with sodium nitroprusside, another NO donor, or with a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), which induce excessive production of NO, also significantly modulated the AOE activities in a manner similar to that seen with SNAP treatment. The compounds/enzymes that inhibit the production of NO (e.g., N-nitro-L-arginine methyl ester hydrochloride, arginase, and PTIO) blocked the effects of LPS and IFN-gamma on the activities of AOEs. Treatment with SNAP and a combination of LPS and IFN-gamma also modulated the mRNA levels of AOEs, parallel to the changes in their protein levels and activities, except for Mn-SOD where the combination of LPS and IFN-gamma markedly stimulated the mRNA expression. In spite of the stimulation of mRNA level, LPS and IFN-gamma significantly inhibited the activity of Mn-SOD within the first 24 h of incubation; however, Mn-SOD activity gradually increased with the increase in time of incubation. These results suggest that alterations in the status of AOEs by NO may be the basis of NO-induced cytotoxicity in disease states associated with excessive NO production.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1997

A selective pulmonary thrombosis associated with sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a pathologic condition associated with critical illnesses, including sepsis. Recent studies have suggested that endogenous cytokines and leukocytes are involved in major roles of its pathophysiology. We report a case of sepsis-induced DIC due to pneumonia that was associated with diffuse and selective thrombosis in pulmonary arteries, yielding to sudden death from pulmonary massive embolism. This report suggests that the selective and lethal pulmonary thromboembolism progresses under the standard therapies in sepsis-induced DIC.

Adult↗

PubMed1997

[Removal of bronchial foreign bodies by suction with a bronchoscope].

We report two cases in which intrabronchial foreign bodies were removed with a fiberoptic bronchoscope. In both cases the foreign body was a seed of a small Japanese apricot. Atelectasis or obstructive pneumonia was seen on chest roentgenograms. The foreign bodies were associated with slight inflammation and polyps on the bronchial epithelium. The foreign bodies were removed by applying suction with a fiberoptic bronchoscope. This method may also be useful for removing other large, hard, uneven, and ball-like foreign bodies.

Aged↗

PubMed1997

[Malignant hemangioendothelioma associated with chronic pyothorax].

A 67-year-old man was admitted to the hospital because of a fever. A chest CT scan showed multilobular heterogeneous shadows on the right side in the chest wall and the lung, but clinical examinations and examination of a biopsy specimen did not lead to a diagnosis. At autopsy, a hemorrhagic tumor was found on the right side in the chest wall. Microscopical examination showed that large atypical cells had proliferated and formed vascular structures, which were stained positively with anti-factor VIII antibody. The histological findings led to the diagnosis of malignant hemangioendothelioma. Chronic empyema-associated malignant hemangioendothelioma is rare.

Aged↗

PubMed1997

Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion.

The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p < 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p < 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.

Alanine Transaminase↗

PubMed1996

Induction of muscarinic receptor subtypes in monocytic/macrophagic cells differentiated from EoL-1 cells.

We demonstrated that eosinophilic leukemia cell line-1 (EoL-1 cells) differentiated into monocytic/macrophagic cells by a treatment with interferon-gamma. Muscarinic receptor mRNA was not detected in untreated EoL-1 cells, and the cytosolic concentration of Ca2+ ([Ca2+]i) did not rise either in these cells. Interestingly, when EoL-1 cells were treated with interferon-gamma, mRNAs for muscarinic M3 and M5 receptors could be detected in these cells, along with an increase in [Ca2+]i and chemotaxis induced by carbachol that could be blocked with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and pirenzepine. These data support the functional importance of muscarinic M3 and M5 receptors in monocytic/macrophagic cells differentiated from EoL-1 cells. This model also provides evidence of a significant functional interaction between muscarinic M3 and M5 receptors.

Calcium↗

PubMed1996

Immunolocalization of cellular glutathione peroxidase in adult rat lungs and quantitative analysis after postembedding immunogold labeling.

To determine the distribution of cellular glutathione peroxidase in rat lungs, the tissues were stained immunohistochemically. Quantitative analysis was performed in certain cell types of alveolar linings, after the ultrathin sections were stained by a postembedding immunogold technique. Immunoblot analysis revealed that homogenates of rat liver, heart, and lungs all gave a single band. Under the light microscope, the following tissues were stained intensely: epithelial cells, smooth muscle cells and glands of bronchi and bronchioles, type II alveolar cells, and alveolar macrophages. Under immunoelectron microscopy, type II alveolar cells and macrophages were abundant in mitochondria. The mitochondria, nucleus, and cytoplasm of macrophages were labeled almost twice as densely as the respective compartments of type II alveolar cells. Within cell types, the mitochondria were labeled twice as densely as the nuclei. The other particles were less than half as densely labeled as the nuclei. The labeling was slightly less dense in the cytoplasm than in the nucleus. The present study revealed that glutathione peroxidase occurred predominantly in the epithelial linings and metabolically active sites in rat lungs. The tissues that were previously found to be rich in superoxide dismutases were also rich in glutathione peroxidase.

Animals↗

PubMed1996

The direct effect of interferon-gamma on human eosinophilic leukemia cell lines: the induction of interleukin-5 mRNA and the presence of an interferon-gamma receptor.

The EoL-1 and EoL-3, human eosinophilic leukemia cell lines, have been used as models for studying the maturation and the function of human eosinophils. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production of these cell lines and interleukin-5 (IL-5) mRNA expression in the EoL-1. O2- was measured by chemiluminescence of MCLA, one of cypridina luciferin analogs. The O2- production of fMLP-stimulated EoL-1 and EoL-3 was increased by the IFN-gamma treatment. IL-5 mRNA expression was detected in the IFN-gamma-treated EoL-1 by reverse transcription-polymerase chain reaction (RT-PCR). Further, we examined IFN-gamma receptor 1 mRNA expression in these cell lines and peripheral blood eosinophils by means of northern blot hybridization. IFN-gamma receptor 1 mRNA was detected in the EoL-3 and the IFN-gamma-treated EoL-1. A weak expression of IFN-gamma receptor 1 mRNA was detected in peripheral blood eosinophils isolated from a patient with eosinophilia. These results suggest that IFN-gamma may act on eosinophils directly through its receptor.

Antigens, CD↗

PubMed1996

Immunohistochemical localization and quantitative analysis of cellular glutathione peroxidase in foetal and neonatal rat tissues: fluorescence microscopy image analysis.

To quantitate the developmental changes in selenium-dependent cellular glutathione peroxidase during the perinatal period, tissue sections from foetal (day 12 to day 22) and neonatal (day 6) rats were stained immunohistochemically using specific polyclonal antiserum. The intensity of the staining was quantified by fluorescence microscopy image analysis. There was a general trend of enriched glutathione peroxidase in the epithelial linings and metabolically active sites. Significant fluorescence was detected in cardiomyocytes, hepatocytes, renal tubular epithelium, bronchiolar epithelium and intestinal epithelium at day 15. The intensity increased in a stepwise manner thereafter. The overall increase in the intensity of staining in the heart, liver, kidneys, lungs and intestine was 1.5-, 2.3-, 1.6-, 1.7- and 3.0-fold, respectively. The phase of most rapid increase occurred during the foetal period in the liver, intestine and heart. In the kidneys and lungs, glutathione peroxidase increased significantly during foetal life, and to a similar extent postnatally. These results suggest that the intracellular H2O2-scavenging system develops during the foetal period as an essential mechanism for living under atmospheric oxygen conditions. The late development observed in the kidneys and lungs is consistent with the relative biological immaturity of these organs in full-term neonates.

Animals↗

PubMed1996

Induction of apoptosis by ubenimex (Bestatin) in human non-small-cell lung cancer cell lines.

We studied the direct anti-tumor effects of ubenimex on five human lung cancer cell lines; ABC-1, RERF-LC-OK, RERF-LC-MS (adenocarcinoma) and SQ-5, EBC-1 (squamous cell carcinoma). Ubenimex dose-dependently inhibited the growth of these cancer cell lines except RERF-LC-MS. The results indicated that lung squamous cell carcinoma cell lines were more sensitive to ubenimex than lung adenocarcinoma cell lines. Coincidentally, histological observation by Hematoxylin eosine (HE) staining revealed that ubenimex induced nuclear condensation and apoptic body in the cancer cell lines. Immunohistochemical study showed ubenimex-treated cells expressed LeY antigen which is a useful phenotypic marker predictive of apoptosis. The induction of DNA fragmentation was also observed in the ubenimex treated cancer cell lines by ELISA. We conclude that ubenimex exhibits its direct anti-tumor effect against non-small-cell lung cancer cell lines, more effectively against squamous carcinoma cell lines, through the induction of apoptosis.

Adenocarcinoma↗