Biomed Central LtdActa Medica Okayama1465-993X142013IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in miceENEtsukoKurimotoNobuakiMiyaharaArihikoKanehiroKoichiWasedaAkihikoTaniguchiGenyoIkedaHikariKogaHisakazuNishimoriYasushiTanimotoMikioKataokaYoichiroIwakuraErwin W.GelfandMitsuneTanimotoBackground: Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear.
Methods: In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.
Results: Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.
Conclusions: These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.No potential conflict of interest relevant to this article was reported.Biomed Central LtdActa Medica Okayama1465-993X142013Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responsesENHikariKogaNobuakiMiyaharaYasukoFuchimotoGenyoIkedaKoichiWasedaKatsuichiroOnoYasushiTanimotoMikioKataokaErwin W.GelfandMitsuneTanimotoArihikoKanehiroBackground: Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice.
Methods: BALB/c mice were sensitized and challenged (primary) with ovalbumin (OVA). Six weeks later, a single OVA aerosol (secondary challenge) was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge.
Results: Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN) T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-beta 1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice.
Conclusion: These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the neutrophil elastase inhibitor reduced AHR to inhaled methacholine indicating the potential for its use as a modulator of the immune/inflammatory response in both the neutrophil-and eosinophil-dominant phases of the response to secondary allergen challenge.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6652012Detection of Torque Teno Virus DNA in Exhaled Breath by Polymerase Chain Reaction387397ENKumikoChikasueMiyukiKimuraKazuyukiIkedaTakumaOhnishiSatoshiKawanishiTomoeIioMikioKataokaYujiroAraoOriginal Article10.18926/AMO/48963To determine whether exhaled breath contains Torque teno virus (TTV) or not, we tested exhaled breath condensate (EBC) samples by semi-nested PCR assay. We detected TTV DNA in 35% (7/20) of EBC samples collected from the mouth of one of the authors, demonstrating that TTV DNA is excreted in exhaled breath with moderate frequency. TTV DNA was detected also in oral EBC samples from 4 of 6 other authors, indicating that TTV DNA excretion in exhaled breath is not an exception but rather a common phenomenon. Furthermore, the same assay could amplify TTV DNA from room air condensate (RAC) samples collected at distances of 20 and 40cm from a human face with 40 (8/20) and 35% (7/20) positive rates, respectively. TTV transmission has been reported to occur during infancy. These distances seem equivalent to that between an infant and its household members while caring for the infant. Taken together, it seems that exhaled breath is one of the possible transmission routes of TTV. We also detected TTV DNA in 25% (10/40) of RAC samples collected at a distance of more than 180cm from any human face, suggesting the risk of airborne infection with TTV in a room.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6422010Experimental Pulmonary Granuloma Mimicking Sarcoidosis Induced by Propionibacterium acnes in Mice7583ENKoujiIioTomoe UenoIioYuheiOkuiHirohisaIchikawaYasushiTanimotoNobuakiMiyaharaArihikoKanehiroMitsuneTanimotoYasunariNakataMikioKataokaOriginal Article10.18926/AMO/32852<p>Propionibacterium acnes has been implicated as an etiologic agent of sarcoidosis since the isolation of this bacterium from sarcoid lesions. We experimentally produced a murine pulmonary granuloma model using P. acnes with several features that simulate sarcoidosis. Mice were sensitized with heat-killed P. acnes and complete Freund's adjuvant and were subsequently challenged with heat-killed P. acnes at 2-week intervals. P. acnes-challenged mice developed epitheloid cell granulomas in the lungs. These mice showed a pulmonary immune response characterized by an increased number of T-lymphocytes, especially CD4 cells, and the ratio of CD4/CD8 in bronchoalveolar lavage (BAL) fluid also increased. Furthermore, significant elevations in both angiotensin-converting enzyme (ACE) serum levels and antibody titers against P. acnes were observed. Mice sensitized with P. acnes without complete Freund's adjuvant were capable of forming pulmonary granulomas, which appeared to be caused by indigenous P. acnes. The genome of P. acnes was found in the lungs, BAL cells, hilar lymph nodes, liver, and spleen in non-sensitized mice, which were thought to be germ-free. These results suggest that the immune response against indigenous P. acnes may play an important role in the pathogenesis of granuloma formation in a murine model.</p>No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4611992Clinical features of 125 patients with sarcoidosis: Okayama University Hospital review of a recent 10-year period.3136ENShigeeHosoyaMikioKataokaYasunariNakataTsuyoshiMaedaHiroshiNishizakiTohruHiokaYoshihiroMoriTougoEjiriKatsuhikoShiomiHiroshiUeokaTakeyukiNumataKenjiNishiiTsuyoshiKodaniYoshiakiMoritaniTaisukeOhnoshiIkuroKimuraArticle10.18926/AMO/32676<p>Clinical features were studied in 125 patients with sarcoidosis (72 females and 53 males) diagnosed at Okayama University Hospital during a recent 10-year period. The age distribution had two peaks in patients in their 20s and the 50s. Over half of the patients were detected at health screening check and were asymptomatic, while the remaining were symptomatic. Twelve patients were in stage 0, 41 were in stage I, 54 were in stage II, 16 were in stage III, and 2 were in stage IV according to the chest x-ray findings. Serum angiotensin converting enzyme levels and serum lysozyme levels were elevated in 60% and 76% of the patients, respectively. The bronchoalveolar lavage fluid showed lymphocytosis, especially of helper T-cells. The clinical features of sarcoidosis appear to depend on the duration of the disease.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X3361979Immuno-chemotherapy of malignant lymphoma using OK-432, a streptococcal agent471478ENIkuroKimuraTaisukeOhnoshiYasunariNakataKentaTakasugiMasafumiFujiiKyoichiHayashiMikioKataokaMasaharuSatoRyujiNishiharaArticle10.18926/AMO/32044<p>Clinical trials of immuno-chemotherapy were conducted on malignant lymphoma patients. Patients during the period from 1972 through 1977 were allocated to two groups retrospectively according to the mode of treatment, i.e., chemotherapy alone (historical control group, 35 patients) and chemotherapy with OK-432 (treated group, 15 patients). Comparisons were made of the two groups, which were homogeneous with regard to induction chemotherapy, maintenance chemotherapy, stage and histologic type of disease. The treated group had a higher remission rate, and a longer remission duration and survival than the control groups, especially in patients with Hodgkin's disease but the difference was not statistically significant owing to the limited number of cases.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5522001The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients.8389ENMasashiOhkeShinyaTadaMakotoNabeKiyoshiMatsuoMikioKataokaMineHaradaArticle10.18926/AMO/32009<p>Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5542001Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia.205211ENHidekiTakeharaShinyaTadaMikioKataokaKiyoshiMatsuoYoshikiUenoShinjiOzakiToshitsuguMiyakeYoshiakiFujimoriIchiroYamadoriMineHaradaArticle10.18926/AMO/31991No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X4051986Alveolar lymphocyte proliferation induced by Propionibacterium acnes in sarcoidosis patients.257264ENYasunariNakataTogoEjiriToshiyukiKishiYoshihiroMoriTohruHiokaMikioKataokaTaisukeOhnoshiIkuroKimuraArticle10.18926/AMO/31929<p>The proliferation of lymphocytes induced by Propionibacterium acnes (P. acnes) was measured by the in vitro incorporation of 3H-thymidine. The mean response rate of alveolar lymphocytes obtained by bronchoalveolar lavage was 2.23 +/- 0.89 in nine untreated sarcoidosis patients, 0.85 +/- 0.17 in five sarcoidosis patients given corticosteroids and 0.78 +/- 0.29 in 11 controls. The proliferation was significantly enhanced in the untreated patients compared to both the treated patients (p less than 0.01) and controls (p less than 0.001), but there was no significant difference in response rates between the treated patients and controls. The response rate of alveolar lymphocytes was significantly higher in four active patients (3.05 +/- 0.61) than in four inactive patients (1.77 +/- 0.44) (p less than 0.05) and in the controls (p less than 0.001). In sarcoidosis patients, the response rates showed a good correlation with activities of serum lysozyme (r = 0.695, p less than 0.01), and with percentages of lymphocytes in bronchoalveolar lavage fluid (r = 0.591, p less than 0.05). There was a low correlation between angiotensin-converting enzyme activities and the response rates (r = 0.508, p less than 0.1). Neither peripheral blood lymphocytes in sarcoidosis patients nor in controls showed any response to P. acnes, but alveolar lymphocytes of the untreated active sarcoidosis patients were sensitive to P. acnes. The lymphocytes activated by P. acnes may play a central role in the induction of alveolitis in sarcoidosis patients.</p>
No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X5011996Factors affecting prognosis of idiopathic interstitial pneumonia.3746ENKiyoshiMatsuoShinyaTadaTakuoShibayamaYoshikiUenoToshituguMiyakeHidekiTakeharaMikioKataokaMineHaradaIkuroKimuraArticle10.18926/AMO/30510<p><P>Idiopathic interstitial pneumonia (IIP) is a progressive and often fatal pulmonary disorder, and evaluating the prognosis of patients with IIP has never been sufficient. Accordingly, factors including clinical features, laboratory data, cellular components in bronchoalveolar lavage (BAL) fluid and response to corticosteroid therapy were analyzed in 35 patients with IIP whose median age of respiratory onset was 60 years (range; 37-77 years). Nineteen patients (54.3%) were in the active stage of IIP and 16 of them were treated with corticosteroids. Significant prognostic factors were the neutrophil percentage in BAL fluid, interstitial shadows on chest radiograph, pulmonary function, blood oxygen level, grade of dyspnea, and disease activity at the initial examination. Patients in the active stage showed higher proportions of neutrophils and eosinophils in BAL fluid than those in the non-active stage. Despite corticosteroid therapy, the survival of patients in the active stage was significantly shorter than those in the non-active stage. Fifty percent of the patients treated with corticosteroids were regarded as responders at 1 month after the initiation of therapy; however, there was no significant difference between responders and non-responders in terms of survival time. In conclusion, disease activity and neutrophils in BAL fluid may be important predictors of the prognosis of IIP.</P></p>
No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558935-61981ヒト末梢血単球の走性に関する研究 第2編 肺癌患者の単球走性499506ENMikioKataokaThe chemotactic responsiveness of peripheral blood monocytes was measured in 71 patients with bronchogenic carcinoma, 13 patients with sarcoidosis, 14 patients with pulmonary tuberculosis and 91 normal controls. The monocyte chemotactic response (MCR) was significantly depressed in patients with bronchogenic carcinoma (mean=19.6±6.6,P<0.001) as compared to normal controls (mean=33.7±7.4). On the other hand, MCR was significantly enhanced in patients with pulmonary tuberculosis (mean=41.6±7.9,P<0.01). There was no significant difference from normal controls in patients with sarcoidosis (mean=27.5±8.5). In bronchogenic carcinoma patients, depression of the MCR was observed in all clinical stages. The MCR was further depressed in patients with evidence of distant metastasis compared to those without metastasis. There was no significant correlation between the MCR and histologic types of tumors. The MCR was significantly lowered by combination chemotherapy in 21 cases who received chemotherapy, but was elevated in 5 of 6 patients who had a remission after combination chemotherapy. These data showed that monocyte function in patients with bronchogenic carcinoma was suppressed, and suggested that malignant tumors themselves might affect monocyte function.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-1558935-61981ヒト末梢血単球の走性に関する研究 第1編 単球走性測定法の検討489498ENMikioKataokaThe human monocyte is an important member of the host defence system, but has been little studied in vitro. In this report, I describe a reproducible and simple method for monocyte chemotaxis in man, using a Boyden chamber. Monocyte suspension was prepared by Ficoll-Hypaque gradient sedimentation. The purity of the suspension was checked with Peroxidase-Giemsa staining. Chemotaxis assay was performed using a 5 μm pore sized Millipore filter(thickness:150 μm) and a Nuclepore filter (thickness:13 μm). When the Millipore filter was used, migrated cells stayed in the filter, while it appeared that cells detached from the filter when the Nuclepore filter was used. In the modified Boyden method using a Millipore filter, more than 3×10(5) monocytes had to be added to the upper room of the chamber, and the duration of 90 minutes was adequate for incubation. Zymosan activated human serum diluted 20 percent was used as the chemoattractant. To estimate chemotaxis in the Millipore filter, migrated cells in the filter were counted at 30 μm depth.No potential conflict of interest relevant to this article was reported.岡山大学医療技術短期大学部Acta Medica Okayama0917-4494911998皮膚サルコイドーシスの臨床 ―最近20年間に岡山大学第2内科にて経験した65症例について―4957ENYasunariNakataMikioKataokaJunichiHiramatsuKazunoriOkazakiMineHarada10.18926/152751976年から1996年に岡山大学第2内科を受診したサルコイドーシス255例のうち,65例(71病変)の皮膚サルコイドーシス(皮膚サ症)について,臨床経過,臨床検査成績,胸部病変との関連,予後について検討した。皮膚サ症患者の年齢は18歳から77歳で中央値は51歳であった。女性例が42例(65%)と多
く,特に50歳代女性に43%と最も高率であった。皮膚病型では結節型33例,皮下型16例,び慢浸潤型3例,局面型6例,結節性紅斑様皮疹3例,苔癬様型1例,瘢痕浸潤9例であった。皮膚サ症では非皮膚サ症に比して気管支肺胞洗浄液中リンパ球の低率が見られたが,その他の臨床成績に差は認められなかった。皮膚病型別に検討すると,局面型,び慢浸潤型では気管支肺胞洗浄液中リンパ球CD4/CD8比は高く,3年後の皮膚および肺病変の残存率は高かった。一方皮下型ではCD4/CD8比は低く皮膚,肺病変の残存率も低かった。No potential conflict of interest relevant to this article was reported.岡山大学医学部附属病院三朝分院Acta Medica Okayama0918-7839691998The clinical effects of dietary supplementation with n-3 fatty acids in bronchial asthma compared with n-6 fatty acids.4048ENMakotoOkamotoKozoAshidaFumihiroMitsunobuTakashiMifuneYasuhiroHosakiHirofumiTsugenoSeishiHaradaEiichiroYumotoShingoTakataYoshiroTanizakiMikioKataokaMineHarada10.18926/14959N-3 fatty acids, such as fish oil, have been reported to have some beneficial effects in patients with bronchial asthma by suppressing leukocyte function, followed by reduction of the need for pharmacologic agents. To examine the effects of dietary supplementation with perilla seed oil rich in α-linolenic acid (ALA), 23 patients with asthma took corn oil rich in linoleic acid (LA) for the former two weeks, perilla seed oil for the later two weeks. The asthmatic patients were classified into two groups by the changes of the generation of leukotrienes B4 (LTB4), C4 (LTC4), and B5 (LTB5) during the two courses of dietary modification: one was sensitive to dietary modification, and the other was insensitive to dietary supplementation. We compared the two groups in clinical characteristics. Significant differences were observed in peak flow (PEF), forced expiratory volume in one second (FEV1.0), IgE, sex, obesity index (OI), concentration of
serum total cholesterol, albumin, low density lipoprotein {LDL)-cholesterol, β-lipoprotein and phospholipids between two groups. This study indicated that these factors influence the generation of LTB4, C4 and B5 of asthmatic patients in dietary supplementation.No potential conflict of interest relevant to this article was reported.岡山大学医学部附属病院三朝分院Acta Medica Okayama0918-7839701999Factors influencing the effects of dietary supplementation with PUFAs on leukotriene generation by leucocytes in patients with asthma4352ENMakotoOkamotoFumihiroMitsunobuKozoAshidaTakashiMifuneYasuhiroHosakiHirofumiTsugenoSeishiHaradaShingoTakadaYoshiroTanizakiMikioKataokaKenjiNiiyaMineHarada10.18926/14933Dietary supplementation with perilla seed oil, a vegetable oil rich in α -lin- olenic acid, inhibits the generation of leukotrienes(LTs) by leucocytes in patients with bronchial asthma. We examined the factors that affect the suppression of LT generation by leucocytes with perilla seed oil-rich supplementation in patients with asthma, by comparing the clinical features of patients with asthma, whose generation of leukotriene (LT) C4 was suppressed by dietary supplementation with perilla seed oil (n-3 fatty acids) (group A), with those of patients who showed no suppression of LTC4 generation (group B). Group A showed a significant increase in the generation of LTB4 and L TC4 by leucocytes after corn oil-rich supplementation (n-6 fatty acids), and a significant decrease in the generation of LTB4 and LTC4 after perilla seed oil-rich supplementation (n-3 fatty acid). However, this was not observed in group B. The level of serum IgE and peak expiratory flow (PEF) in group A were significantly higher
than in group B. Furthermore, the serum levels of LDL-cholesterol, β-lipoprotein and phospholipid were significantly lower in group A than in group B. These results suggest that the clinical features differ between these two asthmatic populations with respect to suppression of LTB4 and LTC4 generation by n-3 fatty acids in perilla seed oil-rich supplementation.No potential conflict of interest relevant to this article was reported.岡山大学医療技術短期大学部Acta Medica Okayama0917-449451995Propionibacterium acnes感作肺肉芽腫モルモットの特異抗体の測定6570ENYasunariNakataYoshihiroMoriTohgoEjiriMikioKataokaJun-ichiHiramatsu10.18926/11917P.acnesを皮内前感作した後、P.acnes菌体壁成分をimcomplete Freund's adjuvantと共に気管内に投与して作製した実験的肺肉芽腫症モルモットにおける抗P.acnes抗体について検討した。気管支肺胞洗浄液中抗P.acnes抗体価は気管内投与後1週目ピークを示し2週目までは上昇が認められ、4週目では気管内投与前の値に復した。この経過は肺胞内リンパ球数の変動と軌を一にしており、抗体価とリンパ球数の間には正の強い相関が認められた。血清中の抗P.acnes抗体価は1週目に低下が認められ、2週以後に徐々に回復して4週以後は元に戻った。P.acnesの気管内投与により血清中の抗体は肺へと移行し、リンパ球浸潤による胞隔炎、更には類上皮細胞肉芽腫の形成にP.acnesの関与を示すものであった。No potential conflict of interest relevant to this article was reported.岡山大学医療技術短期大学部Acta Medica Okayama0917-449431993サルコイドーシス病態へのPropionibacterium acnesの関与1936ENYasunariNakataMikioKataokaIkuroKimura10.18926/11822Although there have been numerous reports on the isolation of bacteria, fungus, and aetiological agents of chemical substances from specimens of patients with sarcoidosis, none of them have been substantiated. In any event, an understanding of the pathogenesis of pulmonary sarcoid is intimately linked to that of the processes involved in the accumulation of T-cells in the lower respiratory tract of individuals with sarcoidosis. Propionibacterium acnes was isolated at high rates and in high concetrations from lymph nodes in patients with sarcoidosis. However, the precise mechanism of granuloma formation and immunomodulation by P. acnes has not been elucidated yet. In patients with sarcoidosis, it was found that the high levels of interleukin-2 (IL-2) released from alveolar lymphocytes as well as interleukin-1, tumor necrosis factor (TNF) and interleukin-6 (IL-6) released from alveolar macrophages were stimulated by P. acnes. These cytokines (mainly IL-2), released by P. acnes in large quantities, play a major role in the compartmentalization of the T-cell population in the lung and lead to the formation of an alveolitis and granuloma in the lung parenchyma of patients with sarcoidosis. This paper focuses primarily on the role of the cytokine network in the pulmonary mononuclear cells in the lung of patients with sarcoidosis.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1982ヒト末梢血単球の走性に関する研究 第1編 単球走性測定法の検討 第2編 肺癌患者の単球走性ENNo potential conflict of interest relevant to this article was reported.