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S Sone

Publications and source records attributed to S Sone.

At least 145 records · Page 8Linked to original sources

Interleukin-12 inhibits production of interleukin-5 but not of granulocyte/macrophage colony-stimulating factor by antigen-stimulated blood mononuclear cells in allergic bronchial asthmatics.

Bronchial asthma, characterized by eosinophilic inflammation in airways, may involve Th2-type cytokines such as interleukin-5 (IL-5). IL-12, a newly established cytokine, induces IFN-gamma production, which may have a regulatory effect on the production of Th2-type cytokines. We examined the effects of IL-12 on the productions of IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) by antigen (Dermatophagoides farinae, Df)-stimulated mononuclear cells (MNCs) from asthmatic patients in vitro. IL-12 enhanced IFN-gamma production and inhibited the production of IL-5 but not of GM-CSF by Df-stimulated MNCs from asthmatic patients. Exogenous IFN-gamma directly inhibited IL-5 production by Df-stimulated MNCs and the inhibition of IL-5 production by IL-12 was partially blocked by anti-IFN-gamma antibody in culture, indicating that inhibitory effect of IL-12 on IL-5 production by antigen-stimulated MNCs is partially dependent on IFN-gamma production. IL-12 also inhibited the release of eosinophil survival-stimulating factor from MNCs. These results indicate that IL-12 may be therapeutically beneficial in correcting Th1/Th2 imbalance in bronchial asthma.

Adult↗

Pulmonary infection with Mycobacterium avium-intracellulare leads to air trapping distal to the small airways.

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.

Airway Obstruction↗

Comparison of the regulations by Th2-type cytokines of the arachidonic-acid metabolic pathway in human alveolar macrophages and monocytes.

The effects of a Th1-cell-associated cytokine (interferon-gamma [IFN-gamma]) and Th2-cell-associated cytokines (interleukin [IL]-4, IL-10, and IL-13) on prostaglandin (PG) production by human alveolar macrophages (AM) were examined in terms of four parameters: PGE2 synthesis, cyclooxygenase (COX) activity, and the protein and mRNA of two COX isozymes (COX-1 and COX-2). Lipopolysaccharide (LPS)-stimulated PGE2 synthesis and COX activity were suppressed significantly by IL-4, but were not affected significantly by IL-10, IL-13, or IFN-gamma. The LPS-dependent increase in COX activity in AM was attributable to COX-2 because it was inhibited by NS-398 (a COX-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in COX-2 protein and mRNA were attenuated by IL-4 but hardly affected by IL-10, IL-13 or IFN-gamma. In contrast, COX-1 protein and mRNA were hardly detected in any of the AM preparations. In AM and monocytes from the same individuals, LPS induced the synthesis of large amounts of PGE2 and COX-2 mRNA in AM, and of lesser amounts in monocytes. IL-4, IL-10, and IL-13 significantly suppressed LPS-dependent PGE2 synthesis and COX-2 mRNA induction in monocytes, whereas only IL-4 significantly suppressed them in AM. Furthermore, 15-lipoxygenase mRNA was detectable only in monocytes incubated with LPS plus IL-4. These results suggest that IL-4 is a potent regulator of PG production in AM, and that regulation of the arachidonic-acid (AA) metabolic pathway in cells of monocyte-macrophage lineage by Th2-cell-associated cytokines depends on the stage of cell differentiation.

Adult↗

The mobile hospital--an experimental telemedicine system for the early detection of disease.

To detect early disease, especially lung disease, we created a new telemedicine system, called the Mobile Hospital. It consists of a satellite or ground communication system using a large vehicle in which is installed a whole-body spiral computerized tomography scanner and a multimedia telecommunications system. The Mobile Hospital goes to small villages and carries out mass screening for early lung disease, especially lung cancer. It travelled over 8000 km from May 1996 to March 1997. In this period 6358 persons aged 50-85 years and younger heavy smokers were screened in the Matsumoto area. As a result, 37.7% of the subjects were suspected of having various latent lung diseases. The cost of medical treatment for the lung cancers detected by the Mobile Hospital was 44% of that for a conventional medical care group, and the length of hospital treatment with surgical operation was 30% of that of the conventional group.

Aged↗

Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH in healthy volunteers.

In this study, we examined the effect of rabeprazole (E3810), a novel proton pump inhibitor, on gastric acidity under physiological conditions in healthy volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour intragastric pH monitoring was performed three times to seven subjects randomly assigned in a cross over fashion to one of the following groups; without drug administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The median pH for 24 hours was 2.15 in the basal study, while the corresponding median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole, respectively. Significant differences in the median pH were observed between the basal study and that after administration of the 10 mg and 20 mg doses of rabeprazole. The cumulative percentage of pH readings above the threshold pH 4 value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10 mg and 20 mg doses of rabeprazole, respectively. This result indicates that the efficacy of rabeprazole allows for substantial control of gastric acidity with once-daily dosing, and that both the 10 mg and 20 mg doses result in potent inhibition of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Sarcoidosis associated with acute renal failure and increased levels of interleukin-6 in urine.

A 24-year-old man who had uveitis and showed intrathoracic lymph node swelling on a chest X-ray, was admitted to our hospital for further examination. Transbronchial lung biopsy specimens revealed non-caseating granulomas compatible to sarcoidosis. As the renal function became progressively worse, a specimen was obtained by renal biopsy. It showed a granuloma formation, and was diagnosed as renal sarcoidosis. A high level of interleukin (IL)-6 was detected in his urine. After oral administration of prednisolone, the renal function improved, and the urinary IL-6 level was reduced. These findings suggest that in sarcoidosis associated with renal failure, steroid therapy is effective and that IL-6 plays an important role in the pathogenesis of renal involvement of sarcoidosis.

Acute Kidney Injury↗

An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases.

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.

Biomarkers, Tumor↗

Spontaneous pneumomediastinum: origin identified by chest computed tomography.

Spontaneous pneumomediastinum (SPM) is an uncommon disorder. The mechanism of spontaneous pneumomediastinum has been speculated as follows: when air pressure in the alveoli rapidly increases, free air leaks from ruptured alveoli and accumulates along the bronchovascular tissue sheath, and then free air moves toward the mediastinum. In this case report of a 19-year-old man of SPM, a chest computed tomography (CT) revealed air in a tubular shape along the pulmonary artery in the apico-posterior segment of the left lung field. This is the first case in which the process of SPM could be identified by chest CT.

Adult↗

Acute pulmonary edema caused by accidental aspiration of sweetened water in two cases of diabetes mellitus.

We treated two cases of diabetes mellitus who developed acute pulmonary edema following accidental aspiration of sweetened water for emergency treatment, when they had fallen into hypoglycemic coma following an overdose of injectable insulin. Although they showed hypoxemia and radiological examinations revealed pulmonary edema, they improved by giving only oxygen and antibiotics in a few days. The osmotic pressure of the sweetened water in each case was approximately 2,600 mOsm and 1,900 mOsm. We suppose that the pathogenesis of the pulmonary edema was due to the sweetened water causing water within the pulmonary vessels to permeate into the alveoli.

Acute Disease↗

Expression level of G1-cyclins and cell proliferation in human cultured leukemia/lymphoma cell lines.

We observed the expression of wild-type retinoblastoma protein (RB) in all 17 hematologic cultured cell lines tested. However, no p16INK4 expression was detected in any cell line among 16 leukemia/lymphoma cell lines, although an EBV-transformed cell line expressed p16INK4. The expression levels of cyclin D1 and CDK4 varied widely among the cell lines. The correlation coefficient (r2) between doubling time (DT) and cyclin D1 in the 14 cell lines that doubled within 47.2 h was 0.4856, while the r2 between DT and cyclin dependent kinase 4 (CDK4) and that between DT and RB among those cell lines were 0.3761 and 0.0874, respectively. The levels of protein expression in vincristine (VCR)-resistant cell lines was not different from those in corresponding wild-type cell lines. Thus, we concluded that the loss of p16INK4 protein and inactivation of RB protein could be an essential step for oncogenesis of leukemia/ lymphoma, and that cyclin D1 may possibly be a target protein to control cell growth of hematologic cell lines which lack the expression of p16INK4.

Cell Division↗

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis.

PURPOSE: The purpose of this study was to ascertain the usefulness of MR imaging in the diagnosis of nodal metastasis of papillary thyroid carcinoma and to establish the most indicative MR criteria of metastasis. METHODS: Pathologic records and MR images in 50 patients with papillary thyroid carcinoma were reviewed. Each neck was divided into four nodal levels, so that 200 nodal levels were assessed in all. The maximum of the minimum transverse diameters of the lymph nodes on each nodal level measured on MR images and the certainty of metastasis as determined by a head and neck radiologist on the basis of morphologic aspects were compared with the pathologic findings by using receiver operating characteristic curves. The presence or absence of cystic nodes on each nodal level was also evaluated. RESULTS: Metastasis was found on 87 (44%) of the nodal levels in 34 (68%) of the patients. A cystic node was identified on 33 (17%) of the nodal levels in 13 (26%) of the patients and was seen only on positive nodal levels. Morphologic diagnosis by the radiologist was better than that obtained by measurement. With the combined criteria of a cystic node or a node of 13 mm or more for the maximum of the minimum transverse diameters, specificity was 100% with an 82% accuracy and always indicated metastasis (100% positive predictive value). However, 41% of the metastatic nodes were missed with this criterion (59% sensitivity). CONCLUSION: MR imaging was useful for diagnosing metastatic nodes; a nodal diameter threshold of 13 mm or the presence of a cystic node strongly indicated metastasis from papillary thyroid carcinoma.

Adult↗

The role of cyclosporin A on antibody-dependent monocyte-mediated cytotoxicity against human multidrug-resistant cancer cells.

A P-glycoprotein (P-gp) inhibitor, cyclosporin A (CsA) was found to enhance the susceptibility of multidrug resistant (MDR) cancer cells to anti-P-gp antibody-dependent cellular cytolysis (ADCC) by monocytes, but the exact mechanism is unknown. In this study, we examined whether CsA enhanced the susceptibility of MDR cells through its inhibitory effect of P-gp function by using anti-ganglioside GM2 (GM2) monoclonal antibody (Ab), KM966, instead of anti-P-gp Ab, MRK16. Monocyte-ADCC induced by both KM966 and MRK16 against P-gp positive human MDR ovarian cancer cells was significantly augmented by addition of CsA. KM966, but not MRK16, induced monocyte-ADCC against P-gp negative human ovarian cancer cells and CsA enhanced this ADCC activity, indicating that suppressive effect of P-gp function by CsA was not essential to the enhancement of ADCC. Moreover, pretreatment of tumor cells with CsA augmented their susceptibility to monocyte-ADCC irrespective of P-gp expression. Interestingly, KM966 or MRK16 induced monocyte-ADCC against various human lung cancer cells expressing either GM2 or P-gp, but CsA did not affect these ADCC. These findings suggest that CsA may enhance the susceptibility to the monocyte-ADCC of ovarian cancer cells, but not of lung cancer cells, irrespective of its suppressive effect of P-gp function.

Antibodies, Monoclonal↗

Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice.

Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 micrograms/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction.

Animals↗

Differential effect of interleukin 10 on interleukin 12- and interleukin 2-mediated killer induction from blood mononuclear cells.

We investigated the regulatory effect of interleukin (IL) 10 on IL-12-inducible killer activity of blood mononuclear cells (MNC) of healthy subjects. IL-10 suppressed non-MHC-restricted killer activity induced by IL-12 in a dose-dependent manner. Cytotoxicity against Daudi cells of blood MNC activated with optimal dose (100 U/ml) of IL-12 was significantly suppressed from 36.6 +/- 6.8% (mean +/- SE) to 26.0 +/- 5.0% by 100 ng/ml of IL-10 (n = 5; P < 0.05) at an E/T ratio of 20. IL-10, however, did not suppress killer induction by IL-2 from blood MNC. On the other hand, IL-4, a known inhibitor of IL-2-mediated killer induction, had no effect on IL-12-mediated killer induction from blood MNC. Moreover, production of interferon-gamma by IL-12-stimulated MNC was suppressed by IL-10. Because the presence of IL-10 is reported in the tumor-growing site, these observations suggest that IL-10 acts as a key cytokine in the suppression of IL-12-mediated antitumor response in situ.

Cells, Cultured↗

A case of sarcoidosis associated with chronic eosinophilic pneumonia.

A 38-year-old man was hospitalized in our university hospital because of pulmonary opacities with bilateral hilar and mediastinal lymphadenopathy seen on chest radiograph. Eosinophilia was observed in the circulation and bronchoalveolar lavage (BAL) fluid. Histological examination revealed noncaseating epithelioid granulomas and eosinophilic infiltration in the lung. Based on these findings, a diagnosis of sarcoidosis combined with chronic eosinophilic pneumonia was made. The infiltrates on chest radiograph and BAL eosinophilia were promptly reduced with corticosteroid therapy, but only mild reduction was observed in diffuse nodular shadows and hilar and mediastinal lymphadenopathy, and high amounts of lymphocytes in BAL fluid remained. Increased IFN-gamma, IL-4 and IL-5 were detected in the BAL fluid, and corticosteroid therapy reduced IL-4 and IL-5 (Th-2 cytokines) but not IFN-gamma (Th-1 cytokine). These cytokine levels in BAL fluid were intimately correlated with the clinical course of sarcoidosis and chronic eosinophilic pneumonia.

Adrenal Cortex Hormones↗