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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 91 records · Page 5Linked to original sources
PubMed2000

Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation.

Air pollutants including diesel exhaust particles (DEPs) have been shown to enhance allergic responses. DEPs stimulate airway epithelial cells to produce various cytokines; however, the intracellular signal transduction pathway and the involvement of reduction and oxidation (redox) control in DEP-activated signaling have not been determined. In the present study, we therefore examined the role of p38 mitogen-activated protein (MAP) kinase in DEP-induced interleukin 8 (IL-8) and RANTES production by human bronchial epithelial cells (BECs) in order to clarify the intracellular signal transduction pathway that regulates IL-8 and RANTES production. In addition, we also examined the effect of a thiol-reducing agent, N-acetylcysteine (NAC), on DEP-induced p38 MAP kinase activation and cytokine production in order to clarify the redox control mechanism in DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. The results showed that DEP induced IL-8 and RANTES production and the threonine and tyrosine phosphorylation of p38 MAP kinase, reflecting the activation of p38 MAP kinase in BECs. SB 203580, as the specific inhibitor of p38 MAP kinase activity, inhibited DEP-induced IL-8 and RANTES production. NAC inhibited DEP-induced p38 MAP kinase activation and IL-8 and RANTES production. These results indicate that p38 MAP kinase plays an important role in the DEP-activated signaling pathway that regulates IL-8 and RANTES production by BECs and that the cellular redox state is critical for DEP-induced p38 MAP kinase activation leading to IL-8 and RANTES production.

Acetylcysteine↗
PubMed2000

PAF-induced RANTES production by human airway smooth muscle cells requires both p38 MAP kinase and Erk.

Airway smooth muscle (ASM) cells, which have been regarded as having contractile properties in response to contractile inflammatory mediators, may also participate in airway inflammatory response by expressing various cytokines, including RANTES. However, the intracellular signal that regulates cytokine expression in ASM cells has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase and extracellular signal-regulated kinase (Erk) in RANTES production by ASM cells stimulated by platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha. The results showed that PAF induced the threonine and tyrosine phosphorylation of p38 MAP kinase and Erk, and p38 MAP kinase and Erk activity. SB 203580 and PD 98059 almost completely inhibited p38 MAP kinase and Erk activity, respectively. SB 203580 and PD 98059 partially inhibited and acted additively to inhibit PAF-induced RANTES production. PAF also induced c-Jun-NH(2)-terminal kinase ( JNK) phosphorylation. TNF-alpha induced p38 MAP kinase and Erk phosphorylation, but neither SB 203580 nor PD 98059 inhibited RANTES production. These results indicate that both p38 MAP kinase and Erk involve RANTES production by ASM cells stimulated with PAF, but not TNF-alpha, and that the role of p38 MAP kinase and Erk in RANTES production by ASM cells appears to be stimulus-dependent.

Bronchi↗
PubMed2000

Inhalant corticosteroids inhibit hyperosmolarity-induced, and cooling and rewarming-induced interleukin-8 and RANTES production by human bronchial epithelial cells.

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH(2)-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

Administration, Inhalation↗
PubMed2000

Auto-induction of E5110 metabolism, a novel non-steroidal anti-inflammatory drug, during toxicokinetic studies in beagle dogs.

Following single-dose intravenous and oral studies to determine the absolute bioavailability of E5110 in beagle dogs, repeated dose pharmacokinetic studies were conducted as toxicokinetics in a subacute toxicity test. E5110 was administered orally once a day for 91 days at doses of 0, 1, 10, 50 and 250 mg/kg/day to dogs. On the first day during repeated administration, the Cmax and AUC values of E5110 in females were lower than those for males, and it seems that this may be due to a sex-related difference in the activity of cytochrome P450 (CYP) 3A. During repeated administration of E5110, the plasma levels of E5110 on day 15 and day 91 were markedly lower than those on the first day. On day 91, the AUCs for E5110 were 55.9%, 38.8%, 10.9% and 7.8% in males, and 76.2%, 80.3%, 10.5% and 11.9% in females on the first day, for doses of 1, 10, 50 and 250 mg/kg/day, respectively. Liver microsomes prepared after the last dose of E5110 showed increased activities of benzphetamine N-demethylase, p-nitroanisole O-demethylase, and aminopyrine N-demethylase, at doses of 1 mg/kg/day or more. A dose-dependent increase in P450 content was also observed. Furthermore, the capacity for 5-hydroxylate E5110 was increased, and Western blot analysis indicated an induction of CYP2B and 3A; therefore CYP3A may contribute to a main metabolic pathway of E5110. These results suggested that the decrease in plasma concentrations of E5110 that were observed during repeated administration represents a typical case of auto-induction of the phenobarbital type.

Animals↗
PubMed2000

Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis.

OBJECTIVE: To examine the relationship between serum levels of interleukin-1 receptor antagonist (IL-1Ra) and its gene expression in peripheral blood mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). METHODS: IL-1Ra levels in sera from patients and supernatants of unstimulated monocyte cultures were measured by enzyme-linked immunosorbent assay. Expression of IL-1Ra mRNA was analyzed by Northern blotting, and an 86-base pair variable repeat polymorphism in intron 2 of the IL-1Ra gene was determined by polymerase chain reaction. RESULTS: Serum IL-1Ra was significantly elevated in 27 patients with active-stage PM/DM when compared with levels in 16 patients with inactive-stage PM/DM and 19 normal controls. Serum concentrations of IL-1Ra were correlated with PM/DM disease activity. IL-1Ra mRNA was detected in freshly isolated PBMC from patients with active-stage PM/DM, but not in controls. Moreover, IL-1Ra concentrations were increased significantly in unstimulated monocytes from patients with active-stage PM/DM compared with monocytes from normal controls. However, there were no significant differences in IL-1Ra allele frequencies between patients and normal controls. CONCLUSION: Elevation of both IL-1Ra mRNA and protein in sera of patients with active-stage PM/DM suggest that higher levels of serum IL-1Ra may reflect increased IL-1Ra production in myositis, and that IL-1Ra may regulate IL-1-mediated muscle fiber damage in PM/DM.

Adolescent↗
PubMed2000

Slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease.

We report a case of slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease. A 69-year-old man presented with apathetic thyrotoxicosis and weight loss. Laboratory findings indicated insulin-dependent diabetes mellitus (IDDM) with Graves' disease. Human leukocyte antigens DR4 and DR9, which are recognized as markers for IDDM with autoimmune thyroid disease, were detected. The clinical course of the IDDM was compatible with the slowly progressive type. Onset of this disease during old age is rare, and such cases should be analyzed with a thyroid function test because the symptom of thyrotoxicosis may be masked in the elderly.

Age Factors↗
PubMed2000

Possible mechanism of hepatocyte injury induced by diphenylamine and its structurally related nonsteroidal anti-inflammatory drugs.

Diphenylamine is a common structure of nonsteroidal anti-inflammatory drugs (NSAIDs) to uncouple mitochondrial oxidative phosphorylation and to cause a decrease in hepatocellular ATP content and hepatocyte injury. The mechanism for acute cell injury induced by diphenylamine and its structurally related NSAIDs was investigated with rat liver mitochondria and freshly isolated hepatocytes, focusing on the relation to the uncoupling of oxidative phosphorylation. Incubation of mitochondria with diphenylamine as well as mefenamic acid and diclofenac caused pseudoenergetic mitochondrial swelling, indicating that these compounds induce mitochondrial membrane permeability transition. Diphenylamine also caused changes in safranine-binding spectra to mitochondria that was energized by succinate oxidation. This spectral shift indicates the loss of mitochondrial membrane potentials, which is known as one of the characteristics for uncouplers of oxidative phosphorylation, and also was caused by mefenamic acid and diclofenac. Incubation of hepatocytes with mefenamic acid, diclofenac, and diphenylamine diminished cellular ATP content, followed by leakage of lactose dehydrogenase from hepatocytes. Fructose, a low K(m) substrate for glycolysis, partially protected against the ATP depletion and hepatocyte injury induced by these compounds. Further addition of oligomycin, which blocks ATPase, pronounced the protection against cell injury. These results suggested that decreases in cellular ATP content, mainly caused by uncoupling of mitochondrial oxidative phosphorylation, were responsible for acute hepatocyte injury induced by diphenylamine and structurally related NSAIDs.

Adenosine Triphosphate↗
PubMed2000

[Analysis of pulmonary function in leukemia patients after bone marrow transplantation: effects of prior chemotherapy].

To evaluate the effects of prior chemotherapy on pulmonary function after bone marrow transplantation(BMT), pulmonary function tests were performed prior to and after BMT on 7 acute leukemia (AL) and 13 chronic myelogenous leukemia (CML) patients given with CY (60 mg/kg x 2 days), total body irradiation (3 Gy x 4 days, 10 cGy/min), and CyA plus short-term MTX. No patient had graft-versus-host disease or lung complications. Pulmonary function after BMT did not deteriorate in the AL patients; however, both %Vital Capacity(%VC) and DL/VA decreased significantly in the CML patients (%VC before BMT: 112.1 +/- 11.5%, after BMT: 93.7 +/- 9.4%; DL/VA before BMT: 79.2 +/- 14.6%, after BMT: 54.1 +/- 10.6%). Although prior regimens of busulfan (BU) or interferon (IFN) were equal risk factors for decreased %VC after BMT, decreases in DV/VA were more significant in CML patients who received IFN. CML patients, especially those who have received BU or IFN, should be carefully monitored for pulmonary function to prevent respiratory failure after BMT.

Acute Disease↗
PubMed2000

Selective inhibitor of p38 mitogen-activated protein kinase inhibits lipopolysaccharide-induced interleukin-8 expression in human pulmonary vascular endothelial cells.

Adult respiratory distress syndrome (ARDS) characterized by permeability edema is observed in severe insults such as bacteremia sepsis. Interleukin (IL)-8, which chemoattracts and activates neutrophils, has been suggested to play an important role in the production of ARDS. Therefore, the inhibition of IL-8 production is an important strategy for the treatment of ARDS. Recent studies have revealed the role of p38 mitogen-activated protein (MAP) kinase in cytokine expression and the inhibition by a selective inhibitor of p38 MAP kinase activity of cytokine expression in a variety of cell types. However, little is known about the role of p38 MAP kinase in lipopolysaccharide (LPS)-induced IL-8 expression in pulmonary vascular endothelial cells and the effect of a selective p38 MAP kinase inhibitor on it. In the present study, we therefore attempted to clarify these issues. The results showed that LPS induced p38 MAP kinase phosphorylation and activity, and SB 203580 as a selective inhibitor of p38 MAP kinase activity inhibited p38 MAP kinase activity and IL-8 expression in LPS-stimulated pulmonary vascular endothelial cells. These results indicate that p38 MAP kinase regulates LPS-induced IL-8 expression in pulmonary vascular endothelial cells. Although it is currently not known whether SB 203580 is capable of producing beneficial effects on ARDS, a strategy of inhibiting p38 MAP kinase activity by a selective p38 MAP kinase inhibitor may apply to the therapy for ARDS.

Blotting, Northern↗
PubMed2000

[Sarcoidosis differentially diagnosed from mediastinal tumor by thoracoscopic biopsy].

A 46-year-old man presented with swallowing difficulty and dyspnea when in the supine position. Chest X-ray and computed tomographic (CT) films disclosed left pleural effusion and a tumor shadow extending invasively from superior to anterior mediastinum around the heart and large arteries. These observations called for a differential diagnosis from malignant lymphoma, invasive thymoma, and small cell carcinoma. Bronchofiberscopy and percutaneous tumor biopsy were performed, but the findings were inconclusive. Thoracoscopic biopsy yielded a diagnosis of sarcoidosis. No extrathoracic lesions were detected. Corticosteroid therapy (30 mg/day of prednisolone) was started. After 6 months of treatment (7.5 mg/day of prednisolone), the tumor shadow was reduced in size and the patient's swallowing difficulty and dyspnea subsided. This was a rare case of sarcoidosis extending invasively around the heart and large arteries, and that needed to be differentiated from mediastinal tumor. Thoracoscopic biopsy should be actively enlisted as a diagnostic procedure in difficult cases of this kind.

Biopsy↗
PubMed2000

[Plasma cell leukemia presenting with circulating villous lymphocytes and an indolent clinical course].

A 73-year-old man was admitted to our hospital in July 1996 because of lymphoctyosis and lumbago. Physical examination revealed hepatomegaly and anemia. Hematologic examination showed a hemoglobin concentration of 9.6 g/dl and a leukocyte count of 32,700/microliter with 74% abnormal mononuclear cells. In Wright-Giemsa stained blood films, these cells had short villi arising from 1 or 2 poles. Immunophenotyping of peripheral mononuclear cells showed moderate to strong expression of CD10, CD24, CD38, and sIg lambda, but not of CD19, CD20, or CD25. Southern blot analysis of the peripheral mononuclear cells demonstrated rearranged monoclonal bands in the C lambda. Urine immunoelectrophoresis detected a monoclonal band identifiable as lambda-type Bence Jones protein. In addition, bone X-ray studies disclosed multiple osteolytic lesions. A diagnosis of plasma cell leukemia was made, and the patient was placed on chemotherapy consisting of cyclophosphamide and prednisolone. No notable improvement in laboratory findings was seen but the patient experienced an indolent clinical course. He died of pneumonia in January 1998. The morphological and clinical findings were unusual for a case of plasma cell leukemia. This case study suggested that signs of lymphocytosis require immunophenotypic and electron microscopic studies for the differential diagnosis of plasma cell leukemia.

Aged↗
PubMed2000

[Evaluation of hematopoiesis by granulocyte elastase after hematopoietic stem cell transplantation].

To evaluate hematopoietic restoration after hematopoietic stem cell transplantation (HSCT), we sequentially monitored the post-HSCT level of granulocyte elastase (GE), a sensitive parameter of qualitative and quantitative changes in granulopoiesis. We compared it with routinely used hematopoietic recovery indices, such as leukocyte and reticulocyte count. We also compared levels of GE in the clinical administration of different colony stimulating factors (granulocyte-colony stimulating factor (G-CSF) versus macrophage-colony stimulating factor (M-CSF) and in different types of hematopoietic stem cell transplantation (allogeneic bone marrow transplantation (BMT) versus autologus peripheral blood stem cell transplantation (PBSCT)). Days to first increase of GE after HSCT were 3.0 and 2.3 days earlier than increase of leukocytes in allo-BMT and auto-PBSCT, respectively. Recovery of highly fluorescent reticulocytes and monocytes were later than recovery of GE. These results indicated that granulopoiesis after transplantation started before the increase in peripheral leucocyte count, and that GE was the earliest indicator of hematopoietic recovery. On the basis of GE level, M-CSF had the same stimulating effect on granulopoiesis as G-CSF. The nadir of GE in PBSCT was significantly higher than that in BMT, indicating continuous granulopoiesis in PBSCT. From these results, we concluded that measurements of GE can be used for the clinical evaluation of myelosuppression by different conditioning regimens as well as of granulopoiesis induced by various cytokines.

Adolescent↗
PubMed2000

[Transient left ventricular dysfunction is still present one hour after exercise stress test: evaluation by gated SPECT with 99mTc-labeled perfusion agent].

It has been reported that quantitative gated SPECT (QGS) has revealed post-stress dysfunction of the left ventricle (LV) 30 minutes after a stress test. The purpose of this study was to determine whether post-stress dysfunction of LV is still present one hour after an exercise stress test. The subjects comprised 152 patients (124 males and 28 females, mean age 59 +/- 10 years). Exercise stress myocardial scintigraphy was performed using a one-day, stress and rest protocol. 99mTc labeled myocardial perfusion tracer, tetrofosmin, 370 MBq was injected at the end-point of a supine ergometer stress test for stress imaging. ECG gated SPECT was carried out 1 hour after injection. Three hours later, 740 MBq to 1100 MBq of 99mTc labeled myocardial perfusion tracer was injected for rest imaging. ECG gated SPECT was again performed 1 hour after injection. We divided the subjects into four groups according to the severity score of defects on the stress image and the presence or absence of fill-in; normal (NOR, n = 59), myocardial infarct (MI, n = 65), small ischemia (S-IS, n = 13) and large ischemia (L-IS, n = 15). Post-stress dysfunction is defined according to two criteria: 1) rest LVEF--post-stress LVEF > or = 5% and 2) post-stress ESV--rest ESV > or = 5 ml. The frequency of post-stress dysfunction was 3.4%, 9.1%, 23.1% and 40% in NOR, MI, S-IS and L-IS, respectively. Post-stress LV dysfunction was found to be more frequent in the large ischemia group. In conclusion, post-stress dysfunction was present 1 hour after the stress test and was more frequent in the large ischemia group.

Aged↗
PubMed2000

[Relapse of small cell carcinoma of the lung with metastasis to iris].

We reported a case of small cell carcinoma of the lung with metastasis to the iris during a stage of complete remission obtained with chemotherapy and radiation therapy. The patient was a 55-year-old man hospitalized for hoarseness and abnormal chest radiographs in August 1996. Small cell carcinoma of the lung had been diagnosed, and the stage was limited disease. Treatment consisted of 3 cycles of chemotherapy with cisplatin and etoposide, together with radiation therapy. The patient achieved complete remission and was discharged. In mid-December, he visited an eye clinic with the complaints of blurred vision and congestion in the right eye. Metastatic tumor of the iris was diagnosed. At that time, neither local recurrence of the lung cancer nor metastasis to other organs were observed. The patient was treated with cisplatin and etoposide again, resulting in a reduction of the iris tumor's size. After chemotherapy, the right eye was treated with electron irradiation, and the iris tumor and other clinical signs almost entirely disappeared. The patient retained normal vision during the clinical course.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

An incident involving blood sucking by a tick in a suburb in Japan.

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan.

Aged↗
PubMed2000

[Effect of a leukotriene antagonist, pranlukast hydrate, on exercise-induced asthma for 14 days].

Exercise is a common stimulus of bronchoconstriction in subjects with asthma. Exercise-induced asthma (EIA) may be caused by heat loss and/or water loss during exercise. These changes cause the release of mediators and the development of bronchoconstriction. Recent studies have implicated the cysteinyl leukotrienes in the pathogenesis of EIA. Therefore we investigated the effect of a leukotriene antagonist, pranlukast hydrate, on EIA. Subjects were 11 EIA positive patients and were all atopic type bronchial asthma. 450 mg of pranlukast hydrate was given for 14 days and the exercise test was performed before and after treatment. Pulmonary function tests were done before and 0, 5, 15 and 30 min after completion of the each exercise. Prostaglandin E2, thromboxane B2, leukotriene E4 and B4 in urine were measured before and after the treatment. Pranlukast hydrate did not affect FEV1.0, PF and Flow volume curve at rest and also levels of mediators in urine. The mean maximal percentage fall in FEV1.0 after exercise was--54.9 +/- 5.7% without therapy and--30.1 +/- 7.5% after pranlukast hydrate therapy. There was a significant difference between FEV1.0 values before and treatment at each time (p < 0.05). This study demonstrated that pretreatment with a potent and selective leukotriene antagonist, pranlukast hydrate, attenuated EIA, and it suggests that leukotriene plays a role in EIA.

Adult↗
PubMed2000

[Development of Sweet's syndrome during all-trans retinoic acid therapy for acute promyelocytic leukemia].

A 54-year-old woman visited our hospital because of gingival bleeding on May 31, 1998. After hematological and bone marrow examinations, she was diagnosed as having acute promyelocytic leukemia (APL) and given all-trans retinoic acid (ATRA) therapy starting on June 1. Anti-cancer drugs were administered for 5 days from June 12 because of an increase in the number of APL cells. The patient developed fever on June 20, and nodular erythematous eruptions appeared on June 23. Sweet's syndrome was diagnosed from biopsy samples of the eruption. ATRA was therefore discontinued, and prednisolone was started on June 29. The fever and skin eruptions improved rapidly, and complete remission was obtained on July 13. Sweet's syndrome due to ATRA may be a partial form of retinoic acid syndrome, in which the differentiated leukemic neutrophils increase and invade various organs. However, Sweet's syndrome must be considered regardless of the WBC count because in this case the syndrome occurred even when the WBC count was not high.

Female↗