Induction of CD8+ Cytotoxic T Lymphocytes With MHC Class I Restriction by a Soluble Truncated Oncoprotein

CD8+ cytotoxic T lymphocytes (CTLs), which play a major role in the immunological defense against cancer, recognize endogenously produced peptides in the context of MHC class I molecules. We investigated how to induce CD8+ CTL responses against the HER2/neu/c-erbB2 (HER2) oncoprotein often overexpressed in a wide range of human adenocarcinomas. The immunization of BALB/c mice with a syngeneic cell line transduced with HER2 cDNA led to a successful induction of CD8+ CTLs which specifically destroyed HER2-expressing tumor cells. The CTLs recognized the HER2-derived peptide 1 (TYLPTNASL, pos. 63rd-71st amino acid) in the context of MHC class I Kd. The immunization of mice with a truncated HER2 oncoprotein containing 144 amino acids of HER2 (N terminus to 144th amino acid) failed to elicit measurable CTL activity for HER2-expressing target cells. We reconstituted the truncated HER2 protein into a mannan-coated liposome, and complexed the protein with a cholesterol-bearing mannan polysaccharide respectively. Both of these complexes were capable of inducing killer cells specific for HER2-expressing cells in murine model after immunization. These killer cells are Kd restricted CD8+ CTLs which recognize peptide 1. The cholesterol-bearing mannan polysaccharide facilitated the induction of specific CD8+ CTLs by an exogenous HER2 oncoprotein, and may therefore be useful in the development of cancer vaccines

Induction of CD8+ Cytotoxic T Lymphocytes With MHC Class I Restriction by a Soluble Truncated Oncoprotein

CD8+ cytotoxic T lymphocytes (CTLs), which play a major role in the immunological defense against cancer, recognize endogenously produced peptides in the context of MHC class I molecules. We investigated how to induce CD8+ CTL responses against the HER2/neu/c-erbB2 (HER2) oncoprotein often overexpressed in a wide range of human adenocarcinomas. The immunization of BALB/c mice with a syngeneic cell line transduced with HER2 cDNA led to a successful induction of CD8+ CTLs which specifically destroyed HER2-expressing tumor cells. The CTLs recognized the HER2-derived peptide 1 (TYLPTNASL, pos. 63rd-71st amino acid) in the context of MHC class I Kd. The immunization of mice with a truncated HER2 oncoprotein containing 144 amino acids of HER2 (N terminus to 144th amino acid) failed to elicit measurable CTL activity for HER2-expressing target cells. We reconstituted the truncated HER2 protein into a mannan-coated liposome, and complexed the protein with a cholesterol-bearing mannan polysaccharide respectively. Both of these complexes were capable of inducing killer cells specific for HER2-expressing cells in murine model after immunization. These killer cells are Kd restricted CD8+ CTLs which recognize peptide 1. The cholesterol-bearing mannan polysaccharide facilitated the induction of specific CD8+ CTLs by an exogenous HER2 oncoprotein, and may therefore be useful in the development of cancer vaccines

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

Reevaluation of Neutron Electric Dipole Moment with QCD Sum Rules

We study the neutron electric dipole moment in the presence of the CP-violating operators up to the dimension five in terms of the QCD sum rules. It is found that the OPE calculation is robust when exploiting a particular interpolating field for neutron, while there exist some uncertainties on the phenomenological side. By using input parameters obtained from the lattice calculation, we derive a conservative limit for the contributions of the CP violating operators. We also show the detail of the derivation of the sum rules.Comment: 33 pages, 5 figure

高速道路における道路交通情報の提供と運転者の交通対応行動に関する研究

取得学位：博士(工学)，学位授与番号：博甲第316号，学位授与年月日：平成11年3月25日,学位授与年：199

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

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

’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