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Under the assumption that the more hyperreactive the bronchial muscles are, the greater their work hypertrophy, we analyzed the distribution of hypertrophic smooth muscles along airways to see where in the bronchial tree asthmatic constrictions mainly occur. Autopsy lungs from 16 patients with bronchial asthma, 13 with other COPDs, and 20 controls were submitted to morphometry of the bronchial muscles. In microscopic slides, cross sections of airways were taken from the segmental bronchi to the terminal bronchioles. The perimeter length L of the basement membrane and the area S of muscles were measured, and the anatomic radius R and the muscular thickness D were calculated in a standardized circular state, in which the basement membrane was stretched into a circle without changing L or S. On bilogarithmic coordinates of D and R on which data from the asthmatics were pooled, it was shown that hypertrophy of muscles was the most pronounced in larger bronchi where constriction was most likely to occur. Closer analysis of patients, however, revealed that besides this typical pattern, which we designated Type I asthma, there was a group of patients (Type II) in whom hypertrophy involved the entire range of airways, including the bronchioles, suggesting that the site of asthmatic response varies among patients. In nonasthmatic patients with COPD, only mild hypertrophy of muscles was found in the large airways, despite the presence of obstructive lesions mainly in the small airways.

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Cytochromes P450 (CYPs) compose a superfamily of similar proteins involved in detoxification and elimination, as well as activation of a wide variety of compounds. Most CYP family members are localized in the liver. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for the determination of CYP gene expression levels in the liver, we compared CYP gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, etabolism of foreign compounds in the body to polar, hydrophilic metabolites is an important prerequisite for detoxification and elimination of xenobiotics from the body. The cytochromes P450 (CYPs) are a superfamily of similar heme-containing proteins that are involved in the oxidative metabolism of xenobiotics. CYPs also catalyze the bioactivation and inactivation of a wide variety of endogenous compounds, including steroid hormones and eicosanoids. Most of the CYP family members are located in the liver.1-3) Many environmental factors, stress, drugs and diseases influence the expression levels of CYP family members, which may lead to alterations of hepatic drug metabolism in man. Studies on such alterations generally require systemic administration of a drug or probe substance and the application of standard pharmacokinetic approaches. 4,5) Although small amounts of needle biopsy material from the liver can be used for assessment of gene expression, the process of biopsy is accompanied by practical and ethical problems. Some CYPs are also expressed in extra-hepatic tissues such as the lung, the kidney and the small intestine. Although xenobiotics are transported via the blood and peripheral blood is obtained for routine medical examination, little is known about CYP expression in peripheral blood cells. So far, CYP1A1, 1B1, 2D6, 2E1 and 3A genes have been shown to be expressed in peripheral blood.6, 7) In order to determine whether peripheral blood leukocytes (PBL) are applicable as a surrogate for assessment of CYP gene expression in the liver, we measured CYP gene expression levels in PBL and the liver, and studied the intra-individual correlation between them. Approximately 70% of human liver CYPs is accounted for by CYP1A2, 2A6, B6, 2C, 2D6, 2E1 and 3A.8) Here, we measured the expression levels of 19 CYP genes, i.e., CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 3A4, 3A5, 3A7, 4A11, 4B1 and CYP27, by real-time reverse-transcription (RT)-PCR. Furthermore, we compared the CYP gene expression levels in tumor and non-tumor tissues from liver cancers to assess whether carcinogenesis is associated with specific changes in CYP gene expression levels or not. Materials and MethodsWe investigated 18 patients with hepatocellular carcinoma (HCC), 2 patients with intrahepatic cholangiocarcinoma (ICC), 2 with bile duct cancer (BDK) and 1 with colon cancer metastasized to the liver (META) who underwent surgical r...

Papillary adenoma of type II pneumocytes is a rare tumour. It is considered to be a benign neoplasm and is derived from immature cells in the bronchioloalveolar epithelium, however, its biological nature has not been elucidated. We report a case of an adenomatous tumour; a papillary adenoma of type II pneumocytes, which we regard as possessing malignant potential. Light microscopically, as well circumscribed, papillary tumour of predominantly cuboidal cells resembling type II pneumocytes was found, but Clara type and ciliated cells were also present. Immunohistochemically, the tumour cells reacted positively with antibodies to surfactant apoproteins (A, B), carcinoembryonic antigen, cytochrome P-450 1A1-2 and 2B1-2. Ultrastructurally, many osmiophilic lamellar bodies and electron-dense granules were demonstrated. Semi-serial sections revealed signs of transbronchial dissemination and vascular invasion. Morphometry using 12-dimensional cluster analysis disclosed features of the tumour cells which resembled those of pneumocyte type II adenocarcinoma. These findings suggest that the present case has some malignant characteristics and originates from immature bronchiolar or alveolar cells, with a potential to develop into both type II pneumocyte and Clara cell type adenocarcinomas.

An outbreak of epidemic gastroenteritis associated with astrovirus, the first case reported in Japan, is described. Not only children (5-6 years of age), but also staff members of a kindergarten were affected. the virus particles detected in stools were 28-30 nm in diameter with a circular outline and had the characteristic star-like configuration which allowed identification as astrovirus. Significant immune responses to the virus were confirmed by immune electron microscopy. Out of 84 children, 43 (54.2%) were affected; the common symptoms were vomiting, abdominal pain, diarrhea, and fever. All the patients recovered completely within 48 hours. Occurrence of gastroenteritis due to contact with these patients was observed in 14 of 43 families.

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Background. Atypical adenomatous hyperplasia (AAH) of the human lung is considered to be an important lesion preceding adenocarcinoma, but its difference from well‐differentiated adenocarcinomas is so subtle as to cause diagnostic uncertainty. In view of this, the authors undertook to establish reproducible microscopic criteria for AAH, Type II pneumocyte type, and Clara cell type adenocarcinomas. Methods. Twelve‐parameter morphometry of atypical cells was performed on 97 lesions selected from 303 surgical specimens of lung by routine microscopic examination: all were considered by premorphometry examination to correspond to one of the above three diseases. Measurements were performed on photomicrographs using a digital image analyzer. The data of morphometry were subjected to 12‐variate cluster analysis using a mainframe computer. Results. It was demonstrated that the lesions were classifiable into three groups: Cluster 1 (Type II cell adenocarcinoma and AAH), Cluster 2 (AAH), and Cluster 3 (Clara cell adenocarcinoma). Whereas the latter two were created as homogeneous clusters, Cluster 1 was a mixture of Type II tumors and AAH. Conclusions. AAH in the strict sense of the word is definable by the features of those classified into Cluster 2, with atypia milder than overt adenocarcinomas. These AAH are likely to correspond to one of the steps of carcinogenesis forgoing the final one. The lesions, diagnosed as AAH before morphometry and being assigned to Cluster 1 and therefore not separable from Type II carcinoma, are considered to have been Type II carcinoma from the very beginning, which were however underdiagnosed in routine microscopic examination.