No abstract

Observations in 136 liver biopsies from patients with alcoholic and nonalcoholic liver diseases reveal that IgA deposition in liver tissues appears to have a high degree of morphologic specificity for alcohol injury. Using a direct immunofluorescence technic with fluorescein-conjugated anti-IgG, anti-IgA, anti-IgM, and anti-C1q, four different staining patterns are recognized. These are labelled as "continuous," "discontinuous," "granular," and "pericellular" types depending on their morphologic characteristics and distribution patterns. Fifty of 64 biopsies from alcoholics showed a "continuous" pattern of anti-IgA activity while only three of 72 biopsies from nonalcoholics showed a similar pattern (P less than 0.001). A "pericellular" pattern of anti-IgA activity appears to indicate a more aggressive behavior of alcoholic liver disease. "Continuous" and "pericellular" patterns are seen in "chronic active hepatitis of alcoholics" but not in chronic active hepatitis in nonalcoholics. Anti-IgM activity appears to indicate chronicity of the disease process but does not have any specificity.

Examination of liver biopsy specimens from 59 patients with alcoholic liver disease and 21 nonalcoholics by immunofluorescence and immunoperoxidase methods using fluorescein-conjugated and peroxidase-labeled antisera against IgA, IgA1, IgA2, and S-IgA showed that 47 of 59 biopsy specimens from alcoholics and 0 of 21 from non-alcoholics showed a "continuous" pattern of IgA and IgA-subclass deposition (P less than 0.001). Grading the intensity of immunofluorescence on 1-4 scale, biopsies with the continuous pattern showed grade 3-4 activity against IgA2 and S-IgA and only grade 1-2 activity against IgA1. Biopsies with the discontinuous pattern showed only grade 1-2 activity against S-IgA, IgA2, and IgA1. Grade 3-4 activity was persistent in all the 47 specimens with the continuous pattern, despite pretreatment with blocking anti-IgA1, whereas 20 and 38 biopsies showed the same activity after blocking with anti-IgA2 and anti-S-IgA sera, respectively. It is concluded from these studies that IgA2 subclass formed a major subclass component contributing to the continuous pattern of IgA deposition in hepatic tissues and that the major source for this IgA in alcoholics was probably derived from the gastrointestinal tract.

Recent studies of colon adenocarcinomas in humans and experimentally induced colonic tumors in rodents have demonstrated selective elevations in the level of N1-acetylspermidine in these malignant tissues. The exact relationship of these alterations in acetylated polyamine levels to the malignant transformation process, however, remains unclear. In order to clarify this issue, rats were given s.c. injections of 1,2-dimethylhydrazine (DMH; 20 mg/kg body wt/week) or diluent for up to 26 weeks. After 10 weeks of carcinogen treatment, one-half of the animals in each group were also concomitantly given i.p. injections of MDL 72527 (20 mg/kg body wt/week), a specific inhibitor of polyamine oxidase, until they were killed. Animals were killed after 15 weeks of DMH treatment and polyamine levels as well as the activities of polyamine oxidase, ornithine decarboxylase and spermidine-N1-acetyltransferase were measured and compared in rat proximal and distal colonic mucosa of each group. Polyamine levels were also assessed in each of these groups after 26 weeks of treatment with this carcinogen +/- MDL 72527. In addition, in view of recent studies that have indicated that polyamines may influence certain oncogenes in human colonic carcinoma cells, tumors from DMH +/- MDL 72527 were analyzed for K-ras mutations. The results of these experiments demonstrated for the first time that: (i) MDL 72527 was a specific inhibitor of polyamine oxidase in normal and malignant colonic tissue; (ii) concomitant administration of this agent with DMH enhanced the elevation of colonic N1-acetylspermidine and significantly reduced the mean colonic tumor burden, as assessed by total tumor area per rat, produced by this carcinogen alone; (iii) analysis of K-ras mutations revealed a similar incidence (62-69%) in adenocarcinomas for both groups (+/- MDL 72527); (iv) however, analysis of the K-ras-mutated and non-mutated tumors revealed that in both carcinogen-treated groups (+/- MDL 72527), tumors with such mutations were smaller than their counterparts without such genetic alterations. Moreover, MDL 72527 reduced the average size of tumors, with and without such mutations, to a similar extent.

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.