Monosodium glutamate(MSG)誘発によるICR(CD-1)系肥満マウスの糖尿病病態に関する研究

取得学位：博士(薬学)，学位授与番号：博甲第809号，学位授与年月日：平成18年3月22日,学位授与年：200

Characteristics of the elderly in high - resolution computed tomography lung densitometry

To determine the characteristics of the elderly in high - resolution computed tomography (HRCT) lung densitometry, mean lung density (MLD) and relative area of the lungs showing attenuation values less than -950 HU (RA(950)) on HRCT were evaluated in nonsmoking control subjects (n = 80) and patients with asthma (n = 80) in relation to their age and pulmonary function. MLD was significantly decreased, and RAW was significantly increased with increasing age in both asthmatics and controls. The MLD values were significantly lower in asthmatics compared with controls in subjects aged between 60 and 69 years and over age 70. RAgsov alues were significantly higher in asthmatics compared with controls in subjects aged between 50 and 59 years, between 60 and 69, and over 70. % FEV(1) and FEV(1) / FVC were significantly decreased in elderly asthmatic patients over 70 years of age compared with the values in those under 49. Percent residual volume (% RV) was significantly larger in patients over 70 years of age than in those between 50 and 59, and under 49 years. RAW was significantly larger in patients with steroid-dependent intractable asthma (SDIA) between 50 and 59 years of age, and between 60 and 69 compared with RA 950 in those without SDIA. However, RAW did not differ significantly between SDIA and non-SDIA in patients over age 70. The results suggested that in % LAA of the lungs on HRCT was significantly increased in the elderly subjects with and without asthma, and it was significantly higher in the elderly asthmatics than the elderly controls.高齢者の病態的特徴を明らかにするために，健常者80例および非喫煙喘息患者80例を対象として，平均肺CT値（MLD）ならびに高分解能CT（HRCT）による－950HU以下の肺low attenuation area（RA950）を評価し，年齢及び肺機能との関連を検討した。　 1．健常者，喘息患者いずれにおいても年齢とともにMLDは有意に減少し，RA(950)は有意に増加した。MLDは，60－69歳と70歳以上の年 齢層において，健常者に比して喘息患者で有意に低値を示した。RA(950)。は，50－59歳・60－69歳・70歳以上の年齢層において，健常者に比して喘息患者で有意に高値を示した。　 2．喘息患者において，1秒量（% FEV(1)）および1秒（FEV(1)/ FVC）は，49歳以下の年齢層に比して70歳以上の年齢層で有意に低値を示した。一方，残気量（% RV）は，50－59歳ならびに49歳以下の年齢層に比して70歳以上の年齢層で有意に高値を示した。 3．50－59歳および60－69歳の年齢層では，RA(950)は，ステロイド依存性重症難治性喘息（SDIA）患者において非SDIA患者に比して有意に高値を示した。しかし，70歳以上の年齢層では両者に有意の差は認められなかった。これらの結果より，HRCT上の肺low attenuation areaは高齢者において有意に増加すること，さらに嘱息患者の方が健常者に比してより高値を示すことが示唆された

’あくび’と胸痛を訴えた気管支喘息の1症例

We present a case of a patient with asthma who developed yawning associated with anterior chest pain. She was admitted due to severe anterior chest pain, wheezing and dyspnea. Although the frequency of the symptoms decreased, she began to experience frequent episodes of yawning at night accompanied by tears. While she experienced yawning, although PEF (peak expiratory flow) decreased, no asthmatic symptoms, such as wheezing or dyspnea were observed. The yawning was improved markedly by bronchodilators and a leukotriene receptor antagonist, and moderately improved by corticosteroids. We speculated that yawning is a clinical manifestation of asthma that responds to treatment.64歳の女性｡1993年2月に高度の前胸部痛,職場,呼吸困難を主訴として入院した｡入院後,前胸部痛,喘鳴,呼吸困難は徐々に軽快傾向であったが,夜間流涙を伴う`あくびが頻回に出現するようになった｡`あくび'が出現する時には,喘息症状(喘鳴,呼吸困難)は伴わないが,ピークフローに低下を認めた｡`あくび'に対する治療としては,気管支拡張剤,ロイコトリエン受容体結抗剤は著効,副腎皮質ステロイド剤は中等度 有効であった｡`あくび'は治療に反応する喘息の-症状であることが示唆された

高齢者喘息のIgEにmediateされるアレルギー反応におよぽす喫煙の影響

The influence of cigarette smoking on the pathophysiology of asthma in the elderly remains controversial. In this study, the inluence of cigarette smoking on IgE - mediated allergy including the generation of leukotrienes B4 (LTB4) and C4 (LTC4) was examined in forty asthmatics over the age of 70 years (20 ex-smokers and 20 never-smokers), and 20 patients with pulmonary emphysema over age 70 (all ex - smokers). The frequency of patients with serum IgE more than 200 IU/ml was significantly larger in smoking asthmatics than in non - smoking asthmatics. The incidence of patients with positive RAST score for inhalant allergens, was also significantly higher in patients with a history of smoking than in those without a smoking history. There were no significant differences in the frequency of patients with positive RAST and those with serum IgE more than 200 IU/ml between non-smoking asthmatics and patients with pulmonary emphysema. The generation of leukotriene B4 (LTB4) by leukocytes was significantly more increased in ex-smokers than in never-smokers in the elderly asthmatics. The results suggest the possibility that cigarette smoking enhances IgE - mediated allergy in elderly patients with asthma.高齢者喘息の病態に対する喫煙の影響については,なお不明な点が多い｡本研究では,70歳以上の気管支喘息40例(喫煙歴20年以上の症例20例,非喫煙症例20例)および70歳以上の肺気腫20例(全例喫煙者)を対象に,IgE-mediatedallergy(LTB4,LTC4の産生を含む)に対する喫煙の影響について検討した｡血清IgE値が200IU/ml以 上を示す症例の頻度は,喘息の喫煙例で非喫煙例や肺気腫症例と比べ有意に高い値を示した｡吸入抗原に対する特異的IgE抗体が陽性を示す症例の頻度は,喘息の喫煙例で非喫煙例や肺気腫に比べ有意に高い値を示した｡しかし,血清IgEが200IU/ml以上の症例の頻度およびRAST陽性例の頻度は,喘息の非喫煙例と肺気腫例の間には有意 の差は見られなかった｡LTB4の産生は,喘息の喫煙例で,非喫煙例と比べ有意の亢進が見られた｡また,肺気腫例では,喘息の非喫煙例に比べ,有意に高い産生が見られた｡しかし,LTC4の産生には喘息の喫煙例,非喫煙例,肺気腫例の間に有意の差は見られなかった

Airflow, the volume and transfer factor of lungs in elderly asthmatics with long-term cigarette smoking

The influence of cigarette smoke on pulmonary function, airflow, lung volume, and transfer factor in patients with asthma was examined in 40 subjects over the age of 70 years (20 ever-smokers and 20 never-smokers), and 20 patients with pulmonary emphysema over age 70 (all ex-smokers). The ventilatory parameters showing airflow limitation (% FEV(1) and FEV(1)%) were not significantly different between ever-smokers and never-smokers of elderly asthmatics. In contrast, % FEV(1) and FEV(1) % values were significantly lower in patients with pulmonary emphysema than in those with asthma with or without a history of smoking. The % RV value was significantly larger and % DLco value was significantly more decreased in ever-smokers compared with neversmokers of the elderly asthmatics. However, there were no significant differences in % RV and % DLco values between asthmatics with a history of smoking and patients with pulmonary emphysema. The results show that cigarette smoke inflluences % RV and % DLco, but not % FEV(1) and FEV(1) %, suggesting airflow limitation of large and moderate size airways.高齢者気管支喘息40例(20年以上の喫煙者20例,非喫煙者20例)および肺気腫(全症例喫煙者)20例を対象に,長期間喫煙の肺機能,airflow,lung volume およびlung transfer factor,に及ぼす影響について検討した｡まずFVC値は,喘息の喫煙例,非喫煙例,および肺気腫症例の間に有意の差は見られなかった｡% FEV(1)およびFEV(1)/FVC値は,喫煙例,非喫煙例いずれの喘息症例も肺気腫と比 べ有意に高い値を示したが,喘息の喫煙例と非喫煙例の間には有意差は見られなかった｡一方,% RVおよびDLco値は,喘息の非喫煙例に比べ,喫煙例および肺気腫症例で有意に低い値を示した｡ これらの結果は,長期間の喫煙は% FEV(1)やFEV(1)/FVCにはあまり影響しないこと, しかし,% RVや% DLcOにはかなり影響することを示している

高齢者喘息における HRCT 上の肺の low attenuation area (LAA) に及ぼす長期間喫煙の影響．肺気腫症例との比較．

The influence of cigarette smoking on the pathophysiology in elderly patients with asthma. Forty asthmatics over the age of 70 years (20 ex-smokers and 20 never-smokers), and 20 patients with pulmonary emphysema over age 70 (all ever-smokers) were studied to determine the influence of cigarette smoke on the low attenuation area (LAA) <-950 HU (RA950) of the lungs on high resolution CT (HRCT) scans, and the ratio of expiratory LAA to inspiratory LAA of the lungs in relation to pulmonary function. The LAA value was significantly higher in patients with pulmonary emphysema compared with ever-smokers of asthmatics. The LAA ratio was significantly higher in ever-smokers than in never-smokers of asthmatics, and the ratio was less than 0.5 in all never-smokers, and the ratio was more than 0.5 in 10 of 20 ever-smokers of asthmatics and in all patients with pulmonary emphysema. The % RV (residual volume) was significaltly larger and % DLco (diffusing capacity for carbon monoxide) was significantly lower in subjects with the ratio more than 0.5 than in those with the ratio less than 0.5. These results suggest that cigarette smoke influences LAA of the lungs in relation to % RV value and % DLco value.70歳以上の気管支喘息40例(20例喫煙者,20例非喫煙者)および肺気腫20例を対象に,長期間喫煙のHRCT上の-950 HU以下の肺のlow atenuation area(LAA)に及ぼす影響について検討した。 HRCT上の肺の% LAAは,喘息の喫煙例で非喫煙例に比べ有意に高い値を示した｡また,この% LAAは,肺気腫症例で喘息の喫煙例に比べさらに高い値を示した｡LAA比(呼気時LAA/吸気時LAA)は,職息症例では喫煙例で非喫煙例比べ有意に高い値を示したが,肺気腫症例ではさらに高い値を示した｡LAA比0.5以上を示す症例は,喘息の非喫煙例では見られず,喫煙例で20例中10例,肺気腫症例では全例に見られた｡そして,喘息喫煙例でLAA比が0.5以上を示す症例は,0.5以下の症例に比べ,% RVは有意に高く,また% DLcoは有意に低い値を示した｡しかし,% RV,% DLco値いずれも喘息のLAA比0.5以上の症例と肺気腫の間には有意差は見られず,喘息における喫煙の影響の高いことが示唆された

lgEにmediatedされるアレルギ反応― 、肺機能、HRCT上の肺のlow attenuatjonarea (LAA)、およびLTB4,LTC4産生から見た喘息の病態に対する加齢の影響

The influence of aging on the pathophysiology of asthma in the elderly was examined in 40 patients (20 younger asthmatics under the age of 50 years, mean age 32.5 years and 20 elderly asthmatics over the age of 70 years, mean age 74.3 years), relating to IgE - mediated allergy, pulmonary function, low attenuation area (LAA) of the lungs on HRCT, and the generation of leukotrienes B4 (LTB4) and C4 (LTC4) by leukocytes. The frequency of patients with serum IgE of more than 200 IU/ml, and the incidence of those with a positive RAST score for inhalant allergens were significantly higher in younger patients than in elderly subjects. The values of % FVC, % FEV1 and FEV 1% were significantly larger in younger patients compared with elderly subjects. The % RV was significantly larger in elderly patients than in younger patients, however, the difference in % DLco was not significant between the two age groups. The LAA of the lungs on HRCT and the ratio of expiratory LAA (exp LAA) to inspiratory LAA (ins LAA) were also significantly larger in elderly asthmatics than in younger subjects. The generation of LTB4 and LTC4 was larger in younger patients than in elderly subjects, and LTB4 generation was significantly larger in younger subjects compared with elderly subjects. These results suggest that changes in IgE-mediated allergy, airflow and lung volume accompanied with hyperinflation are often observed in elderly asthmatics.70歳以上の気管支喘息20例(平均年令74.3歳)および50歳以下の気管支喘息20例(32.5歳)を対象に,IgEにmediateされるアレルギー反応,肺機能,HRCT上の肺のLAAの程度,白血球によるLTB4,LTC4産生などに対する加齢の影響について検討した｡血清IgE値が200IU/ml以上の症例の頻度および吸入抗原に対するRAST scoreが陽性を示す症例の頻度は,いずれも若青年者喘息で高齢者喘息と比べ有意に高い傾向を示した｡ % FVC,% FEV(1),FEV(1) % 値はいずれも若青年者喘息で高 齢者喘息に比べ有意に高い値を示し,また,% RVは高齢者で有意に高い値が示された｡一方,% DLcoは両者間に有意の差は見られなかった｡ HRCT上の% LAAおよびLAA比(呼気/吸気)いずれも高齢者喘息で有意に高い値を示し,加齢により肺のLAAが明らかに影響を受けることが判明した｡LTC4の産生は若青年者喘息でやや高い値が示されたが,高齢者との間に有意差は見られなかった｡一方,LTB4産生は,若青年者喘息で高齢者喘息と比べ有意に高い値が示された｡これらの結果は,70歳以上の高齢者喘息では加齢による影響を広範囲にわたり受けている可能性が高いことを示している

Spa therapy for patients with respiratory disease. Analysis of 2129 patients admitted at Misasa Medical Center for last 21 years from 1982 to 2002

1982年から2002年までの21年間の当医療センターで入院加療した2129例を対象に5年間毎にその年次推移を検討した．2129例のうちわけは，気管支喘息1311例（61.5％），COPD467例（21.9％），その他351例であった．1. 気管支喘息は，第1期（1982-1986年）の5年間では，平均11.4例/年であったが第4期（1997-2001年）では平均93例と初期と比べ8.1倍の増加が見られた．また，そのなかのSDIA （steroid-dependent intractable asthma）の頻度は初期の68.4％から第4期では28.9％にまで低下する傾向を示した．2. COPD症例は，初期の5年間（1982-1986年）では平均5.2例/年から第4期には45.4例へと8.7倍の増加が見られた．また，そのなかの肺気腫が占める割合いは初期の19.2％から第4期では78.5％と明らかな増加傾向を示した．なお，昨年度の1年間では，第4期の5年間（1997-2001年）とほぼ同様の傾向を示したが，全般的な傾向としては気管支喘息症例がやや減少し，一方肺気腫症例が増加する傾向が見られた．3. 気管支喘息およびCOPD症例の年齢別検討では，60歳以上の症例の頻度は第1期では30.1％だあったが，第4期では68.0％，そして昨年度は85.4％と，年々その頻度は高くなっていく傾向が見られた．すなわち，最近21年間の年次推移からは，温泉療法を必要とする呼吸器疾患患者が増加しつつあること，そしてその年令は年々高くなる傾向にあることが示された．Analysis of 2129 patients with respiratory disease admitted at Misasa Medical Center for last 21 years from 1982 to 2002 was performed every five years. Of all patients with respiratory disease, 1778 (83.5%) patients had asthma and chronic obstructive pulmonary disease (COPD). 1. Of 1778 patients showing obstructive ventilatory dysfunction, 1311 (73. 7%) patients had asthma. The frequency of asthma in all patients with respiratory disease was 53.8% for the first 5 years from 1982, 71. 7% for the second 5 years, 73.6% for the third 5 years, 53.9% for the last 5 years and 43.6% in 2002. 2. The frequency of steroid -dependent intractable asthma (SDIA) was from 25.9% to 41. 3% except the frequency (68.4%) for the first 5 years. The frequency of patients with SDIA showed a tendency to decrease in recent years. The frequency of patients with pulmonary emphysema in those with COPD was very low 09.2% for the first 5 years) tended to increase and 76. 7% for the last 5 years and 88.5% in 2002. The frequency of patients over age 60 was 30. 1% for the first 5 years, and showed a tendency to increase, and 68.0% for the last 5 years and 85.4% in 2002. 3. The frequency of patients from distant areas outside Tottori prefecture was larger compared to the frequency inside Tottori prefecture. The number of patients from Okayama, Osaka, Hyogo, Tokyo, Ehime, Yamaguchi, and Kyoto was larger than the number from other distant areas

高齢者喘息における喫煙による気道過敏性の亢進について

Influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study was undertaken to clarify the influence of cigarette smoking on IgE-mediated allergy, bronchial hyperresponsiveness, and the generation of leukotrienes B4 (LTB4) and C4 (LTC4) by leukocytes in 48 elderly patients (25 patients with a history of smoking for more than 20 years and 23 never-smokers) with asthma over the age of 70 years. 1. The incidence of positive IgE antibodies for inhalant allergens was significantly higher in asthmatics with a history of smoking than in never-smokers of asthmatics. 2. In bronchial hyperresponsiveness for methacholine, the Cmin was significantly lower in ever-smokers than in never-smokers of elderly asthmatics. 3. The generation of LB4 was significantly increased in patients with a history of smoking compared with those without a smoking history. However, the difference in LTC4 generation was not significant between ever-smokers and never-smokers of asthmatics. These results suggest that cigarette smoking increases bronchial hyperresponsiceness through IgE-mediated allergy and LTB4 generation.高齢者喘息の病態におよぽす喫煙の影響についてはなお不明な点が多い｡本論文では,IgEにmediateされるアレルギー反応,気道過敏性,ロイコトリエンB4 (LTB4),C4(LTC4)産生に及ぼす喫煙の影響について,48例(20年以上の喫煙歴のある症例25例,非喫煙例23例)の70歳以上の高齢者喘息症例を対象に検討した｡ 1.吸入抗原に対する特異的IgE抗体の陽性頻度は,喫煙歴のある症例で,非喫煙例と比べ有意に高い値を示した｡ 2.メサコリンに対する気道過敏性の検討では,平均Cminは,喫煙例(949μg/ml)において非喫煙例(1677μg/ml)に比べ有意に低い値 を示し,喫煙例でより気道の過敏性が高いことが示された｡ 3.LTB4の産生は喫煙例で非喫煙例に比べ有意に高い傾向を示したが,LTC4に関しては両群間に有意の差は見られなかった｡以上の 結果より,長期間の喫煙は,IgEにmediateされるアレルギーやLTB4産生の亢進などを通じて気道過敏性を亢進させる可能性が示唆された

Clinical effects of long-term spa therapy on pulmonaryemphysema. Evaluation by pulmonary function and pathological changes of terminal airspace of the lung

Clinical effects of long-term spa therapy for 4 years were estimated in 8 patients of pulmonary emphysema (4 with spa therapy and 4 without spa therapy) by pulmonary function and morphological changes of peripheral airspaces of the lung on high - resolution computed tomography (HRCT). 1 . The values of % FVC, % FEV1.0, and FEV 1.0% did not significantly change for 4year observation both in patients with spa therapy and those without spa therapy. 2. The OLco value significantly decreased from 69.9% at the initial level to 48.8% after 4-year observation in patients without spa therapy (p<O.02). However, the DLco value did not significantly decrease in patients with spa therapy. 3. The values of % RV and % LAA of the lung showed a significant increase in patients without spa therapy (% RV: p<O.05, % LAA: p<O.Ol after 4-year observation compared with the initial levels), however, a change in % RV and % LAA was not significant in patients with spa therapy. 4. The CT number also significantly decreased in patients without spa therapy, but not in those with spa therapy. The results suggest that spa therapy improves % DLco, % RV and morphological changes of peripheral airspaces, chiefly overinflation, of the lung in patients with pulmonary emphysema.肺気腫に対する4年以上にわたる温泉療法の臨床効果を,肺機能の面および末梢肺領域の形態学的変化により評価した｡ 1.FVC,% FEV1.0,およびFEV1.0%値は,温泉療法を受けた症例と受けなかった症例の間に有意の差は見られなかった｡ 2.拡散能(DLco)は,温泉療法を受けなかった症例では,観察初期の69.9%から4年後には48.8%と有意の低下を示したが,温泉療法を続 けた症例では,有意の低下は見られなかった｡ 3.% RVおよびHRCT上の-950HU以下の肺のlow attenuation area(LAA)は,いずれも温泉療法を受けなかった症例では有意の増加傾向を示したが,温泉療法を受けた症例では有意の増加傾向は見られなかった｡ 4.Crnumberは,温泉療法を受けなかった症例では有意の低下を示したが,温泉療法を続けた症例では有意の変化は見られなかった｡これらの結果より,肺気腫に対する温泉療法を続けることにより,% DLcoや % RVは改善する傾向を示し,同時に肺胞の過膨脹の部分(破壊された部分ではなく)が改善されていく可能性が示唆される