Systems of life No 79. Systems and signs: digestive system - 5. The acute abdomen.
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The urogenital and digestive systems in 23 centenarians (7 males and 16 females) were examined pathologically. In the urogenital system, macroscopic scar formation, chronic pyelonephritis and arterio- and arteriolosclerosis of the kidney usually were pronounced. Six instances of prostatic glandular hyperplasia were demonstrated, and three of these were associated with well-differentiated adenocarcinoma. The testis, ovary and uterus usually showed a strong tendency toward atrophic changes. In the digestive system, senile atrophy of the liver and formation of colonic diverticula were noted. In this series of aged subjects, malignant lesions of the gastrointestinal tract were rare. It is also noteworthy that the unsuspected lesion of massive gastrointestinal hemorrhage associated with the various observed disorders might have been the cause of death in some of these centenarians.
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The review included author's own studies and emphasizes the problem of peptides participating in transmission of central influences to the intramural nervous system in the digestive tract's organs, to their endocrine cells or directly to the secretory (or smooth muscle) cells. The role of endocrine apparatus of the digestive tract's organs is discussed as well as the role of the so called peptidergic fibers of the vegetative nervous system in regulation of secretory function of the stomach and pancreas.
Neuroendocrine tumors of the digestive system are slow growing neoplasms which often present with pronounced fibrosis around tumor cells and in the peritoneal cavity. In this report 30 midgut carcinoids and endocrine pancreatic tumors were examined for the expression of peptide growth factors and their receptors, both by immunohistochemistry and in situ hybridization. Our data indicate that multiple peptide growth factors, PDGF, TGF-beta, and bFGF are expressed by these tumors. PDGF was expressed on tumor cells and stroma in 70% of tissues examined. PDGF alpha-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas PDGF beta-receptor was seen only in the stroma. Our data suggest that PDGF may be involved in the autocrine stimulation of tumor cells and stimulation of stromal cell growth through paracrine and possibly autocrine mechanism. In addition, tumor tissues express all three isoforms of TGF-beta in more than half of the tissues examined. Tumor cells produce small latent complexes causing an escape from potent inhibitory effect of TGF-beta and stimulation of stromal cell growth and matrix deposition through paracrine mechanism. bFGF, a potent stimulant of endothelial cell growth, was expressed by all tumor tissues examined. Our data suggest that multiple peptide growth factors may have an important role in tumor progression and desmoplastic reaction accompanying these tumors.
Neuroendocrine tumors of the digestive system are slowly growing neoplasms which often present pronounced fibrosis around tumor cells and in the peritoneal cavity. In this study, 23 midgut carcinoids and 7 endocrine pancreatic tumors were examined for the presence of TGF-beta with affinity-purified polyclonal antibodies raised against synthetic peptides coding for a specific region of latency-associated peptide sequences of TGF-beta 1, -beta 2, -beta 3, a rabbit anti serum against TGF-beta binding protein (LTBP) and a rabbit polyclonal antibody against TGF-beta type II-receptor (TGF-beta RII). Tumor cells from most tissues expressed all three isoforms of TGF-beta but LTBP was only weakly expressed. In stromal cells abundant expression of TGF-beta 2 and LTBP was found, whereas TGF-beta 1 and TGF-beta 3 were expressed only weakly. TGF beta RII immunoreactivity was observed mostly in the stromal cells. Tissue sections from 4 of these neuroendocrine tumors were also investigated by in situ hybridization. Strong signals on tumor cells were detected with TGF-beta 2 and TGF-beta 3 cRNA probes and also weakly with TGF-beta 1 and LTBP cRNA probe. Strong positive signals were observed on stromal cells with TGF-beta 2 and LTBP probe whereas only weak signals were observed on the stromal cells with TGF-beta 3 probe. Strong signals were detected on stromal cells with TGF-beta RII probe whereas no signals were observed on tumor cells. Our data suggest that TGF-beta might play an important role in the interaction of tumor and stromal cells. Thus TGF-beta might stimulate matrix production and angiogenesis of stromal cells, whereas tumor cells themselves are unaffected by the growth inhibitory activity of TGF-beta.
Environmental factors are important mediators of many diseases of the digestive system, defined as the alimentary tract and the accessory organs of digestion, the liver and pancreas. In this review, we principally focus on the action of chemical agents which are classified as (1) naturally occurring compounds, (2) occupational hazards, (3) therapeutic drugs, and (4) constituents of substances of abuse. In addition, the putative role of dietary habits in the pathogenesis of malignant diseases of the digestive system is discussed.
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