Osamu Kitada

Prostate Cancer-Induced Oncogenic Hypophosphatemic Osteomalacia

A 65-year-old male with prostate carcinoma showed mild hypocalcemia of 7.9 mg/dl, marked hypophosphatemia of 1.7 mg/dl, hyperphosphaturia (tubular reabsorption of phosphorus 43% and tubular threshold for phosphorus of 0.6 mg/dl), low serum 1,25 (OH)2D level of less than 5 pg/ml and osteomalacia indicated by a marked increase of relative osteoid volume and fractional formation rate in the undecalcified section. Oncogenic osteomalacia due to prostatic carcinoma with suppression of 1,25 (OH)2D production and phosphaturia was suggested.

Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.

Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1‐promoting cytokine, interleukin‐12, is capable of inhibiting the T helper 2‐driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin‐12 actions are unclear. The anti‐allergic response to interleukin‐12 is only partially dependent on interferon‐γ, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti‐allergic action of interleukin‐12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin‐12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin‐12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase‐mediated deoxyribonucleoside triphosphate nick end‐labelling.

Renin-Angiotensin System Component Gene Polymorphism in Japanese Bronchial Asthma Patients

The influence of renin-angiotensin system (RAS) component gene polymorphism in the pathogenesis of bronchial asthma was investigated in an association study involving 119 bronchial asthma patients and 208 control subjects. The selected RAS polymorphisms were angiotensinogen (Agt) T235/M235 and angiotensin I-converting enzyme (ACE) insertion/deletion (I/D). The control allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.63/0.37) in this study were similar to the previous reports in Japanese normal population. The allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.65/ 0.35) among the asthma patients were not significantly different from those among the control subjects. There was no association between severity of bronchial asthma and the selected RAS component gene polymorphism. From these data, we conclude that in the Japanese population, the RAS component gene polymorphism is not associated with increased risk for bronchial asthma.

The 150-Kilodalton Oxygen-Regulated Protein Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice

The 150-kd oxygen-regulated protein is a novel stress protein that is located in the endoplasmic reticulum and contributes to cell survival when this organelle is under stress. Expression of this protein was strongly increased in alveolar macrophages and alveolar epithelial cells from mice with acute lung injury induced by lipopolysaccharide. Transgenic mice overexpressing the 150-kd protein showed decreased histological severity of this lung injury, accompanied by lower total protein concentrations, and lactate dehydrogenase activity in bronchoalveolar lavage fluid. As indicated by nick end-labeling, lipopolysaccharide induced apoptosis in fewer alveolar wall cells in transgenic than in wild-type mice. Transgenic mice also showed increased survival after lipopolysaccharide injection (a log-rank test). Thus, the 150-kd protein, an endoplasmic reticulum-related molecular chaperone, is pivotal in resisting acute lung injury from lipopolysaccharide.

Effects of hydrocortisone and aminophylline on plasma leukotriene C4 levels in patients during an asthmatic attack

To study the role of leukotriene C4(LTC4) and the effect of hydrocortisone and aminophylline on plasma LTC4 levels in patients with asthmatic attacks, we measured LTC4 in plasma of 18 asthmatics during a wheezing attack and of 7 normal subjects. Blood samples were obtained before and after treatment with aminophylline and/or hydrocortisone injections. We extracted LTC4 using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay. The plasma levels of immunoreactive LTC4 (i-LTC4) of the normal subjects were 142 +/- 25 pg/ml (n = 7), while those of nonatopic type asthmatic patients with wheezing attacks were 208 +/- 68 pg/ml (n = 15) (p less than 0.01). Before and after treatment with both hydrocortisone succinate (100 mg) and aminophylline (250 mg), 6 asthmatic patients with wheezing attacks had a mean plasma level of i-LTC4 181 +/- 24 and 132 +/- 18 pg/ml (p less than 0.01), respectively. On the other hand, the treatment with aminophylline 250 mg alone increased the i-LTC4 levels from 178 +/- 19 pg/mg to 213 +/- 16 pg/mg (n = 6)(p less than 0.05), while treatment with hydrocortisone succinate 100 mg decreased the i-LTC4 level 0.05 from 284 +/- 99 pg/ml to 249 +/- 85 pg/ml (n = 4)(p less than 0.05). In conclusion, the present study shows that the i-LTC4 level in venous blood of patients with asthmatic attacks is decreased significantly by treatment with hydrocortisone succinate.

Two cases of eosinophilic gastroenteritis associated with analgesic‐induced bronchial asthma

Abstract Two patients (one male and one female) with bronchial asthma were diagnosed as having eosinophilic gastroenteritis (EG). The condition was revealed by biopsies through fibrescopic endoscopy. According to the Klein classification, they had mucosal disease. The symptoms were abdominal pain and nausea. The symptoms subsided with corticosteroid administration in one patient and with palliative treatment in the other patient. It was suggested that fibrescopic endoscopy biopsy is needed to identify coexisting EG if a bronchial asthma patient complains of severe gastrointestinal symptoms.

Primary mediastinal choriocarcinoma with elevated serum CYFRA 21-1

Abstract We report here the first case of primary mediastinal choriocarcinoma in a patient whose serum level of CYFRA 21-1 (a cytokeratin 19 fragment) was initially elevated but declined with chemotherapy. Tumor cells were immunohistochemically positive for cytokeratin 19 fragment. This is the first case report of primary mediastinal choriocarcinoma in a patient with elevated serum CYFRA 21-1 level.

STUDY ON A CASE WITH PULMONARY EMPHYSEMA COMBINED WITH ALPHA 1-ANTITRYPSIN DEFICIENCY AND IT'S FAMILY

49才,主婦.喫煙歴,大気汚染地区での居住歴はない. 44才頃より喘息が出現, 46才頃より労作時息切れを自覚, 48才時某病院にて気管支喘息として加療され一時軽快. 49才時呼吸困難,喘鳴発作にて当科に緊急入院した.特徴的所見としては血清α1-globulinが0.1%と著明に低下, α1-antitrypsinは70mg/dlと中間型を示した.免疫グロブリンではlgEが軽度上昇,皮内テストではカンジダが陽性,肺機能検査では著明な1秒率の低下,残気率の上昇,拡散機能の低下,吸気不均等分布指数の上昇, Pao2値の軽度低下, A-aDo2値の増大が認められた.胸部X線所見では両側中下野の透過度亢進とその領域における血管影の細りがみられ,気管支造影所見ではいわゆる“leafless tree pattern”を呈する.ラジオアイソトープによる局所血流換気機能検査では右中下野および左下野の血流および換気の低下が認められた.家系の調査では発端者の母親,同胞3名(発端者も含めて),発端者の子供1名がM-で,他はMMと判明した.欧米ではα1-antitrypsin欠乏症と肺気腫との合併例は少なくなく,それらの臨床症状,肺機能所見, X線学的所見などと本症例の所見とはよく一致している.本邦におけるα1-antitrypsin欠損症の家系の報告例はあるが,肺気腫との合併例は本症例の報告(昭和50年1l月)以前にはみられないようである.