Hideo Mashimoto

Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis

We report a case of Wegeners granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegeners granulomatosis.

A Sequential Ultrastructural and Histoautoradiographic Study of Early Neoplastic Lesions in Ethylnitrosouyea‐induced Rat Glioma

A sequential study of the early stage of development of ethylnitrosourea (ENU) induced glioma in the rat was performed by electron microscopy and [3H]thymidine histoautoradiography. Hyperplasia, the earliest neoplastic change that was detectable morphologically, consisted of a few or several immature oligodendroglia like cells which were connected with one another or with preexisting neural tissue by junctional apparatus, and showed no reactive changes in the astrocytes or microglia. The labelling index of hyperplastic cells was 2.6%. Foci of early neoplastic proliferation (ENP) showed mild destructive changes in the neighboring neural tissue, and their major constituent cells had characteristics of immature oligodendroglias. The labelling index of cells showing ENP was 3.3%. The intercellular spaces exhibited slight enlargement with accumulation of extracellular matrix and a decrease in the number of junctional apparatus on the neoplastic cells. Microtumors showed apparent destruction of the preexisting neural tissue to form a tumor mass with an increase in the extracellular matrix. Constituent cells of the microtumors were similar to those of the ENP, although reactive astrocytes and microglias occurred more frequently. The labelling index was 9.6% in the central area of microtumors and 5.3% in the peripheral area. These findings suggest that in the initial or very early stages of glial cell neoplastic proliferation, it is necessary for the neoplastic cells to maintain contact with the neurons for metabolic purposes, and that after losing contact, these cells can proliferate autonomously with the accumulation of extracellular matrix.

LEIOMYOBLASTOMA OF THE GREATER OMENTUM

A case of leiomyoblastoma of the greater omentum, occurring in a 36‐year‐old man was described. Leiomyoblastoma of the omentum is extremely rare and only 6 cases have been reported in the Japanese and English literature up to date. According to the review of these cases, including the present case, 1) females were affected more frequently than males, and the age ranged from 36 to 76 years; 2) leiomyoblastoma was usually a large tumor which caused abdominal fullness and pain, and occasionally complicated with anemia and bloody ascites; 3) mitosis was rare, and there was no sign of metastasis and recurrence. Finally the morphological criteria and clinical parameters of malignancy in leiomyoblastoma were discussed. ACTA PATHOL. JPN. 37: 1691‐1698, 1987.

Cryptophthalmia Syndrome with Laryngeal Atresia and Bilateral Renal Agenesis: A Case Report and a Review of the Literature

Abstract An autopsy case of the unilateral cryptophthalmia syndrome was presented, showing the lack of the eyelids formation on the right and the facial skin being continuous over the right eye. Potters face, partial cutaneous syndactyly, clitorial hypertrophy, bilateral renal agenesis and absence of uterus were associated, and further laryngeal atresia was noted, leaving a small posterior opening and allowing a survival of only 10 min at birth. Histologic analysis of the right eye revealed that the cyst in the anterior segment was formed by the destruction of the lens itself. The pathogenesis of cryptophthalmia and laryngeal atresia was discussed.

A Case of Granulocyte Colony-Stimulating Factor (G-CSF)-Producing Lung Cancer Proved by Immunohistochemical Analysis.

症例は59歳, 男性で全身倦怠感および咳噺を主訴として来院した. 胸部X線写真では左下肺野に浸潤影を伴う腫瘤影を認めた. 検査成績では, 明らかな感染症がないにもかかわらず32, 000/μlと著明な白血球増多がみられた. 血清中のG-CSF値は酵素標識免疫法で298pg/mlと高値を示していた. 臨床的に病期IIIAの肺扁平上皮癌と診断し, 左肺全別術を施行した. 手術時に得られた腫瘍組織の抽出液および腫瘍細胞の組織培養上清のGCSF濃度は高値であった. rh G-CSFに対する特異的モノクローナル抗体を用いた免疫染色法では手術標本の腫瘍細胞は陽性に染まった. 術後, 白血球数および血清中のG-CSF値はすみやかに正常化した. 現在, 術後2年経過しているが, 再発もなく健在である.

A case of synchronous multiple lung cancers associated with hamartoma in the same lobe

近年, 肺癌の診断・治療技術の進歩により, 同時性および異時性肺多発癌は稀れではなくなってきた.しかし, 同一肺葉内肺多発癌は比較的稀れであり, 更に良性腫瘍が混在した場合, その診断は非常に困難である.今回我々は左下葉に3個の腫瘤影を認め, 同時性肺多発癌 (腺癌, 扁平上皮癌) および肺過誤腫であった一手術例を経験した.症例は72才, 男性.胸部X線上, 左S6に1個, およびS10に2個の腫瘤影が認められた.手術により, 各々扁平上皮癌, 腺癌および肺過誤腫の診断が得られ, リンパ節転移, 遠隔転移は認められなかった.肺の多発腫瘤影に対しては一つ一つの腫瘤に対して細胞診もしくは組織診を得る努力が必要である.また, 肺過誤腫には肺癌の合併率が高いとする報告もあるが, その検討のためには今後多施設における症例の集積が必要であると思われた.