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Using 40 tumor cell strains derived from various organs of Japanese tumor patients and also 12 normal cell strains, we have measured the activity of O6-methylguanine-DNA methyltransferase (MT), which can repair O6-methylguanine produced in DNA by alkylating agents. Then, the lethal sensitivities of the strains to the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-)2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were measured. The MT activity was assayed by measuring the 3H radioactivity transferred from the substrate DNA containing [methyl-3H]-O6-methylguanine to acceptor molecules in the cell extracts. Extracts from the majority of tumor strains and all normal cell strains contained substantial MT activity of varying degree, while the extracts of 6 tumor strains showed virtually undetectable MT activity. Hence these 6 strains were assigned as Mer-, the phenotype which is characterized by the inability to repair O6-methylguanine in DNA due to the lack of MT. The Mer- tumor strains were much more sensitive to ACNU than the rest of Mer+ strains, as measured by colony-forming ability. Furthermore, with all the tumor and normal strains tested, a good correlation was observed between MT activity and cellular resistance to ACNU. These results indicate that the frequency of Mer- strain is about 15% among Japanese tumor cell strains so far analyzed, and further suggest that MT may be the only system able to repair lethal DNA damage induced by ACNU.

A 71-year-old man was admitted complaining of cough and high fever. Chest X-ray and CT scanning showed diffuse thickening of both pleurae and malignant mesothelioma was suspected. Upon pleural biopsy, a diagnosis of lymphosarcoma, well differentiated type, was made. Postmortem examination revealed diffuse, extensive fibrous thickening of both pleurae with multifocal spreading of tumor cells. These occasional Hassal's bodies. The latter cells were spindle-shaped and ovoid. Therefore, the tumor was diagnosed as "malignant thymoma, mixed type".

Lethal effects of mitomycin C (MMC), 4-nitroquinoline 1-oxide (4NQO) and ultraviolet light (UV) on fibroblast cell lines derived from a colon cancer-prone substrain of Wistar-Furth rats (WF/OSAKA rats) were measured in terms of the cellular colony-forming ability, and compared with the sensitivity to these agents of human fibroblasts from patients with adenomatosis coli and rectum (ACR). All 6 fibroblast strains from the cancer-prone WF/OSAKA rats were significantly more sensitive (though to various extents) to MMC as well as 4NQO than normal rat fibroblasts derived from the parental WF Hiroshima rats. These WF/OSAKA cell strains were slightly more sensitive to UV than normal rat cell strains. Similarly, 5 out of 6 fibroblast strains derived from ACR patients were hypersensitive to both MMC and 4NQO. Further, the WF/OSAKA cell strains were more susceptible to morphological transformation induced by Kirsten murine sarcoma virus than normal rat strains. The observed higher sensitivity to chemical agents and to viral transformation suggests a close similarity in cellular terms between the colon cancer-prone WF/OSAKA rats and human individuals affected with ACR.

Testicular and plasma testosterone levels were found to be decreased markedly in streptozotocin diabetic rats compared with those of controls. Treatment with 6 units NPH insulin daily for one week almost normalized plasma testosterone levels parallel to the increase in body and liver weights in diabetic rats, while testosterone levels in testicles were not significantly changed. Plasma prolactin and LH levels were unchanged among control, diabetic and diabetic insulin-treated rats. Thus, testosterone reduction in the testis might play a role in diabetic impotence.

In the present study, 96 cases of HD selected from 937 cases of malignant lymphomas in Osaka, Japan were reviewed to evaluate a time trend of HD. The results showed that, during the periods from 1964-74 to 1975-85, (1) ratio of HD among all malignant lymphomas decreased from 14.8% to 8.9%, (2) MC decreased and NS increased, and (3) the age of onset fell.

Lectin binding sites and immunohistochemically detectable fibronectin and carbonic anhydrase II (CA II) were examined in induced bone structure of calcifying epithelioma of Malherbe. Pathological features of ossification were particularly evident in the border zone between tumor epithelium and stroma, and epithelial foci adjacent to sites of bone formation were conspicuously basophilic. The use of lectin binding in these foci coincided with the basophilic epithelial zones: Con A, RCA-1, PNA, SBA, and WGA bound strongly, indicating the presence of glucose (Glu), mannose (Man), galactose (Gal), N-acetyl-D-galactosamine (GalNAC), and N-acetyl-D-glucosamine (GlcNAC). Fibronectin was also detected in the same epithelial-mesenchymal interacting layers as the positive lectin-binding sites. Staining for CA II was strongly positive in giant cells and in epithelial zones in the bone-inducing areas. The bond induction mechanism in the stromal tissue of calcifying epithelioma of Malherbe may initially involve the action CA II in the epithelial-mesenchymal interacting zone, which then brings about ossification of the matrix which is fibronectin-positive and rich in lectin-binding sites.

We report on an autopsy case of cholangiocarcinoma associated with Caroli's disease. A 38-year-old woman was admitted to our hospital suffering from epigastralgia. A diagnosis of Caroli's disease was made after CT, US, and ERCP testing. Because of diffuse intrahepatic bile duct dilatation, the patient was treated with antibioticus. In August 1985, her CA 19-9 level was 3,800 U/ml. This data suggested the development of a carcinoma secondary to Caroli's disease, but no tumor in the liver had been detected in the US and CT examinations. The patient died on February 1, 1986, of hepatorenal failure, approximately seven years after her first admission. An autopsy revealed diffuse dilatation of the intrahepatic bile duct (Caroli's disease) with a cholangiocarcinoma.

T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.

Immunosuppressive acidic protein (IAP), a substance purified from cancer ascitic fluid, is released into the culture medium of macrophages and neutrophils, and is supposed to suppress an immune function of the host. Elevation of serum IAP in cancer patients has been reported. In the current study, presence of IAP in proliferating diseases of macrophage was examined. Macrophages in reactive proliferation, histiocytosis X, and neoplastic proliferation gave positive reaction for IAP. Diffuse cytoplasmic staining was usual, but dot-like or globular and surface staining also were observed. Proliferating cells in malignant fibrous histiocytoma were more sensitively stained by IAP than by other ordinary used markers for macrophage. These findings provide useful information to understand the mechanism of elevation of serum IAP in cancer patients.