Metabolic studies of HgCl2-induced acute renal failure in the rat.
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Biomedical subjects
Publications and source records attributed to B F Trump.
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This report describes the training of pathologists' assistants in three training programs: at Duke University, at Quinnipiac College associated with Yale University, and at the University of Maryland School of Medicine. The role of this new health profession is described as well as the job situation, experience, and current status of accreditation.
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An unusual bronchial carcinoid tumor was studied by light and electron microscopy. The tumor cells, which appeared to be monotonously uniform in hematoxylin and eosin stained sections, were found to be morphologically heterogeneous at the ultrastructural level with regard to the size, number, and morphology of the endocrine granules. Presumptive endocrine granules were seen in all tumor cells, but some cells contained only small round granules (2000 A largest diameter), other cells contained large round granules (some with as large a diameter as 1.0 mu), and some cells contained large polymorphic granules. Many of the cells stained positively at the light microscopic level when selective stains for endocrine cells were applied. All types of granules showed argyrophilia at the ultrastructural level. Numerous clusters of endocrine cells were observed in the otherwise normal bronchial and bronchial glandular epithelium. The spectrum of granule morphologies, as seen in the tumor cells, was displayed in cells of the intraepithelial clusters. Some mucous cells and sparsely ciliated cells within these clusters contained argyrophilic granules. Multiple continuities existed between the epithelial endocrine cell clusters and the underlying tumor mass. The intraepithelial clusters represent foci of carcinoma in situ, the genesis of which is discussed.
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Seven malignant peripheral lung tumors that were diagnosed using light microscopy as large-cell carcinomas or as epidermoid or adenocarcinomas were studied by light and electron microscopic histochemistry. All tumors contained numerous dense-core granules. The cells were joined by desmosomes and contained well-developed tonofilament bundles. Serotonin was demonstrated in six of seven tumors and argyrophilic granules were demonstrated in five of six tumors tested. Four tumors produced mucus. All tumors extended to the visceral pleura and two invaded the chest wall. The existence of lung tumors that contain serotonin and bear argyrophilic putative endocrine granules, but that do not have a light-microscopic histology characteristic of either carcinoid or oat-cell carcinomas, is confirmed. The presumptive endocrine nature of such tumors usually passes unrecognized because they lack criteria to allow diagnosis by routine methods.
The inducibility of aryl hydrocarbon hydroxylase (AHH) in human bronchial epithelium and blood monocyte was studied in 11 immediate autopsy patients without lung cancer. When the bronchus was exposed to 10 microgram of benz[a]anthracene (BA)/ml medium in explant culture, the levels of AHH induction in the bronchus were 3- to 29-fold above control levels. The specific enzyme activity ranged from not detectable (i.e., < 0.14) to 2.9 nmol/hour/mg DNA in untreated tissue and from 1.2 to 30 nmol/hour/mg DNA in BA-treated bronchus. The optimum pH for the bronchus AHH was 7.7. Control AHH and BA-induced AHH in bronchus were both inhibited by 100 microM 7,8-benzoflavone in vitro. Induction of AHH in monocytes ranged from 1.5- to 30-fold above that of controls when the cells were exposed to 2 microgram of BA/ml medium in culture. The specific enzyme activity ranged from 1.6 to 19 pmol/hour/10(6) cells in untreated monocytes and from 5.8 to 53 pmol/hour/10(6) cells in BA-treated monocytes. The extent of AHH induction in monocytes depended on BA concentration (from 0.1 to 10.0 microgram) in a dose-related manner. AHH activity increased linearly with the number of monocytes (from 0.5 to 2x10(6)) in the assay system. 7,8-Benzoflavone inhibited the BA-induced but not the basal levels of monocyte AHH activity. The data are consistent with a correlation between the inducibility of AHH in human bronchus and blood monocyte from the same individual.
Although the colon of the inbred F344 rat is not distinctly demarcated into ascending, transverse, and descending segments as in the human colon, it can roughly be divided into ascending and descending portions that show distinct light microscopic, histochemical, and ultrastructural features. The ascending colon is characterized by a "herringbone" pattern of mucosal folds and test-tube-shaped uniform crypts that contain mucous cells (MC) with abundant mucin (acidic mucopolysaccharide--mostly sialomucin) in the lower one-third of the crypt, whereas the upper one-third contains two putative cell populations: 1) MC containing large globules of neutral mucopolysaccharide or sulfomucin and 2) columnar cells (CC), the full capabilities of which are unknown. The descending colon has longitudinal folds and contains sparse MC with small mucous granules at the lower one-third of the crypt, whereas the upper one-third contains numerous goblet cells. Neutral mucopolysaccharide is sparse and the acidic mucin is exclusively sulfated. Histochemically, the descending segment of the rat colon resembles the human descending colon in that the predominant type of mucus is sulfomucin. Ultrastructurally, the cell types observed in both the ascending colon and the descending colon are: a) MC, b) CC, c) endocrine cells, and d) undifferentiated cells.
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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.
Bronchi, pancreatic ducts, and colons from adult human were maintained as xenografts in congenitally athymic nude N:NIH(S) mice for 715, 145, and 89 days, respectively. After an ischemic crisis and revascularization of the human tissue, the epithelium regenerated to a normal differentiated morphology. The long-term survival of normal adult human epithelial tissues as xenografts provides model systems for the study of the interactions of chemical and/or physical carcinogens with human tissues.
A sequential, histologic analysis of the livers of male BALB/c mice chronically fed the hepatocarcinogen safrole (4,000 ppm) was performed at 2, 4, 8, 16, 24, 36, 52, and 75 weeks. The transplantability of selected lesions to syngeneic hosts was also assessed. Histopathologic liver alterations at 2, 4, 8, and 16 weeks induced hypertrophy of centrolobular hepatocytes, oval cell proliferation, fatty change in periportal hepatocytes, including basophilic, acidophilic, and clear cell, were noted. At 36 and 52 weeks, hepatocellular adenomas occurred in 4 of 10 and 7 of 10 mice, respectively. At 75 weeks they occurred in 5 of 5 mice. Adenomas were larger than a lobule in diameter compressed the adjacent parenchyma, and distorted the hepatic architecture. Individual adenomas were composed of a mixture of basophilic, acidophilic, clear, and lipid-laden cells, arranged in disorganized cords, one to three cells in thickness. None of the 10 adenomas tested grew upon subcutaneous transplantation into syngeneic hosts. Hepatocellular carcinomas (HPC) developed in 2 of 10 safrole-exposed mice at 52 weeks and 3 of 5 mice at 75 weeks. These lesions were large, multilobed and, unlike adenomas, seemed to invade adjacent parenchyma. The HPC were heterogeneous in cell composition. Their architecture was disorganized with trabeculae of 1-10 or more cells in thickness. No central veins or portal tracts were seen. All HPC proliferated when transplanted into syngeneic hosts. The results of this study demonstrated a sequential development of altered hepatocyte populations leading to HPC in safrole-treated mice. The transplantability of HPC indicated their malignant nature.
Sequential alterations in enzyme histochemical profiles and reaction of hepatocytes to rapid iron overload were examined in male BALB/c mice during chronic, safrole exposure. At 24 weeks after initiation of safrole treatment, foci of enzyme-altered hepatocytes were noted. These foci were composed of cells showing a decrease in reactivity for glucose-6-phosphatase (Glc-6-Pase) and succinate dehydrogenase (SDH) and an increase for gamma-glutamyl transpeptidase (gamma-Glu-T). In control, iron-loaded mice, the livers were intensely siderotic. In safrole-exposed, iron-loaded mice, foci of iron-negative hepatocytes, varying from a few cells to a lobule in diameter, were initially noted at 24 weeks. Both enzyme-altered and iron-negative foci occurred in the livers of exposed mice at all time periods after 24 weeks. After 36, 52, and 75 weeks of safrole treatment, hepatocellular adenomas were noted with altered enzyme histochemical profiles. Hepatocytes from adenomas were characterized by a decreased staining for Glc-6-pase and SDH and increased staining for gamma-Glu-T and glucose-6-phosphate dehydrogenase (Glc-6-PD). In addition, a few nodules showed a decrease in staining for 5'nucleotidase. In iron-loaded mice, hepatocytes of adenomas showed a decreased to negative reaction for iron when the surrounding parenchyma was siderotic. Hepatocellular carcinomas (HPC) occurred in livers of mice exposed to safrole for 52-75 weeks. The cells of HPC displayed similar enzyme histochemical reactions as cells of adenomas. They were decreased for Glc-6-Pase and SDH activity and increased for gamma-Glu-T and Glc-6-PD. In iron-loaded mice, the HPC cells were negative for stainable iron. Foci, adenomas, and HPC displayed some variability in enzyme histochemical reactions. Variability existed between lesions as well as between cells of the same lesion.
A systematic, ultrastructural analysis wsa performed on safrole-induced hepatocellular adenomas and hepatocellular carcinoma(s) (HPC) in BALB/c mice. Adenomas were heterogeneous in cell composition containing dark-staining basophilic cells, pale-staining acidophilic cells, clear cells, and lipid-laden cells. Darkly staining cells resembled fetal hepatocytes. They had large nuclei with irregular borders and limited diversity of organelles. Rough endoplasmic reticulum was prominent and seen as parallel cisternae in single or double tracts often in association with mitochondria. Pale-staining cells contained abundant smooth endoplasmic reticulum. Other organelles were often displaced to the perinuclear or peripheral region of the cell. The clear cells resembled dark-staining or pale-staining cells but also containing large areas of glycogen deposition. Lipid-laden cells contained numerous, multisized lipid droplets in the cytoplasm. HPC contained cell types similar to those of the adenoma. In addition, they contained many anaplastic cells. These resembled hepatocytes but contained several other alterations. The most striking was an apparent increase in the number of altered mitochondria. The cytoplasm was often fluid with enlarged mitochondria with dense or pale matrices. The cristae were few and had altered configurations. Also, an apparent increase was seen in the number of microbodies. These were often clustered in one region of the cytoplasm. An increase in microbodies was also noted in other cell types of hepatocellular carcinomas. The results of this study demonstrated similarities in the cell types of the adenomas and HPC. This study also demonstrated differences, with the anaplastic cell being common only to the carcinoma. Due to the similarity of cell types, the adenoma should be considered a possible site of HPC development.
The highly sensitive peroxidase-antiperoxidase immunocytochemical method was used to demonstrate the presence of the beta-subunit of human chorionic gonadotropin (HCG) within paraffin sections of human lung tumors of diverse histologic patterns. Of the 61 tumors studied, 51 (84%) displayed HCG-like immunoreactivity. This is a much higher incidence than was expected considering studies by other investigators in which serum samples from patients with lung cancer were assayed for HCG. Our results are, however, consistent with data from studies by other investigators in which tumor extracts were assayed for HCG. In addition, it was found that HCG production was often linked with glycogen storage within tumor cells. This may explain the association of HCG production with large-cell carcinomas of the lung, because these tumors often contain copious quantities of glycogen.
Normal primary epithelial cell cultures devoid of fibroblastic cells have been developed from tissue explants of adult human bronchi. Conditions for clonal growth of secondary cultures of bronchial epithelial cells were optimized by coculturing the human cells with mitomycin C growth-arrested Swiss 3T3 mouse feeder cells, lowering the calcium concentration of medium M199, and supplementing it with hydrocortisone, insulin, cholera toxin, epidermal growth factor, and 1.25% fetal bovine serum. The epithelial cells grew for an average of 35 population doublings and had the normal human karyotype, expressed keratin and blood group antigen epithelial cell markers, metabolized benzo(a)pyrene, and were capable of differentiating into both ciliated and squamous cells. This culture system makes it potentially possible to investigate various aspects of differentiation and carcinogenesis in human bronchial epithelial cells.