Biomedical subjects
Publications and source records attributed to A K Shamsuddin.
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Colon explants from the inbred F344 rat descending colon pretreated in vivo with azoxymethane and maintained in explant culture were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). One week after the MNNG treatment, the colon crypts showed marked crowding, hypercellularity, and stratification of cells. Nine weeks after the treatment, the explants showed epithelial papillary projections on the surface epithelium and within the crypts, in addition to hypercellularity and stratification. The control untreated explants maintained a single layer of epithelium during the entire culture period. Ultrastructurally, the treated cells showed an unusual concentration of free polysomes and thin and thick filaments, multiple and bizarre nucleoli, nuclear indentations and pseudoinclusions, and intracellular lumina. Sulfomucin was the predominant component in the control untreated explants as well as in the normal descending colons of rats and humans. One week after treatment the crypts of the carcinogen-treated explants showed an increase in sialomucin, and by 9 weeks after treatment, they showed mostly sialomucin. These features, compared and correlated with those of the parallel in vivo animal model as well as with human material, lend additional support to de novo histogenesis of colon carcinoma.
To verify the popular belief that the mucosa of the colon remote from a carcinoma is normal, in a retrospective study colon mucosae from 30 patients were studied; 15 patients had colon carcinoma and the other 15 patients without any obvious tumor in their colons served as controls. All the patients having colon carcinoma showed definite abnormalities in the mucosa remote from the tumor. None of the 15 control patients showed such morphologic changes in the mucosal sections sampled at random. The mucous changes observed were: dilatation and distortion of the crypts with flattening of the lining cells, overcrowding of crypts with mucous cells and basophilic cells, lining of the crypt with eosinophilic surface epithelial cells, and focal cellular stratification in the crypts. These abnormalities were also consistently observed in the transitional mucosa adjacent to the tumor in all of the 15 patients with colon cancer. Histochemical studies for the detection of epithelial acidic mucosubstances showed that sialomucin predominated in the colon mucosa harboring a carcinoma irrespective of the location of the tumor, whereas colon mucosa from otherwise normal individuals and patients with noncarcinomatous diseases showed a predominance of sulfomucin. Therefore, mucosa of the colon harboring a carcinoma was conclusively demonstrated to be morphologically and histochemically abnormal. The significance of these abnormalities and their possible role in the de novo histogenesis of colon carcinoma are discussed.
Barr bodies are described in the interstitial cells of testes of a chromatin-positive patient with Klinefelter syndrome. Ultrastructural studies confirm the origin of the Barr body from the nuclear chromatin. Ultrastructurally the interstitial cells showed diminished, smooth endoplasmic reticulum and lipid droplets probably indicating impaired function.
A case of in-situ and "micro invasive" carcinoma of the colon is reported in a patient who was neither a member of familial polyposis nor had suffered from ulcerative colitis. The in-situ and "micro-invasive" areas were seen in the flat otherwise non-raised mucosa of the colon remote from a large fungating carcinoma. Similar foci were also observed in random sections distal to the large mass. This is the first report of an in-situ and "micro-invasive" carcinoma of colon in a "non-ulcerative colitis" individual.
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Reviewed are studies on alterations of the plasma membrane of neoplastic epithelial cells. Changes in the plasma membrane are probably of unique importance in the major clinical manifestations of cancer. Discussed are sequences in cell membrane changes in vivo and in vitro in both human tumors and chemical-induced animal models of carcinogenesis. Emphasis is placed on alterations in specializations of the plasma membrane, including cell junctions, antigenic and enzyme markers, intramembranous components, ion regulation, and the cytoskeleton. In general, the plasma membrane of neoplastic cells is less specialized than the cell of origin. In mammalian bladder, pleomorphis microvilli may occur concomitant with neoplastic transformation. Cell junctions in tumor cells may be reduced in number of functional characteristics compared to normal cells, which may affect cell-cell communication. Such alterations may be related to tumor cell invasion and metastasis. Normal membrane antigens may be lost or new ones gained in neoplasia. Thus, ABO blood group antigens may be lost in the case of human bronchus and bladder, while carcinoembryonic antigen occurs de novo in tumors of the colon and lung. Similarly, several marker enzymes may be reduced in activity, or appear de novo. Alterations in the number and pattern of distribution of intramembranous particles have been observed in bladder tumors, possibly related to changes in membrane function. Shifts in ion ratios (Na+/K+/Ca++) within neoplastic cells may result in abnormalities in cell shape, cell movement, and cell-cell communication. Many of these changes may reflect defects in function of the Golgi apparatus, which synthesizes components of the plasma membrane. Alterations in one or more components of the cytoskeleton may adversely affect cell shape, mobility of membrane proteins, cell-cell adhesion, etc., and play a major role in malignant cell behavior.
Transmission electron microscopic study of the bizarre infiltrating cells from a case of lymphomatoid papulosis reveals intranuclear and intracytoplasmic virus-like particles. These cells have large nuclei with multiple nucleoli, scant to moderate profiles of rough endoplasmic reticulum, mitochondria and a variable number of lysosomes. It is suggested that these abnormal cells are macrophages showing viral cytopathogenic effects.
A primary tumor of bone, the light microscopic features of which were suggestive of malignant fibrous histiocytoma, proved to be a primary leiomyosarcoma upon electron microscopic examination. Ultrastructurally the tumor cells were smooth muscle cells having all the characteristic features, such as cytoplasmic filaments, cytoplasmic and sarcolemmal dense bodies, and pinocytotic vesicles, with a basal lamina surrounding the cells. This example emphasizes the importance of electron microscopy in diagnostic pathology. This is the second ultrastructural report of a primary leiomyosarcoma of bone.
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An explant culture system has been developed for the long-term maintenance of colonic tissue from the rat. Explants of 1 cm2 in size were placed in tissue-culture dishes to which was added 2 ml of CMRL-1066 medium supplemented with glucose, hydrocortisone, beta-retinyl acetate, and either 2.5% bovine albumin or 5% fetal bovine serum. The dishes were placed in a controlled-atmosphere chamber which was gassed with 95% O2 and 5% CO2. The chamber then was placed on a rocker platform which rocked at 10 cycles per min causing the medium to flow intermittently over the epithelial surface. The explants were incubated at 30 degrees C. The viability of the tissue was measured both by incorporation of specific precursors into cellular macromolecules and by monitoring of tissue morphology with light and electron microscopy. Cultured rat colon was able to metabolize benzo[alpha]pyrene, 7,12-dimethylbenz[alpha]anthracene, aflatoxin B1, dimethylnitrosamine, 1,2-dimethylhydrazine, and methylazoxymethanol acetate into chemical species that bind to cellular DNA and protein.
Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants that remained viable, there was an initial phase of degeneration of the surface and crypt cells, later these areas were repopulated in one week, showing well-formed crypts, goblet cells, and ultrastructural features such as extensive lateral interdigitations, microvilli and glycocalyx--typical of colon. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial differentiation with well-formed crypts up to 13 weeks.
The granulomagenic properties of serologically active glycolipids A1, B2, B3, and C isolated from Mycobacterium bovis BCG were studied. Glycolipid A1, dissolved in olive and injected intradermally in guinea pigs, was able to elicit a granulomatous response that seemed to be of the nonallergic type. This granulomagenic activity was quite striking since only 2 mug was necessary to elicit the reaction. The B and C glycolipids were milder granulomagenic agents. Glycolipid A1, dissolved in olive oil and injected intraperitoneally, was toxic for mice. Mice lost weight after the injection of as little as 10 mug of A1, although not even a dose of 100 mug was lethal. Glycolipid A1 failed to immunize mice against aerogenic infection with virulent tubercle bacilli.
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