{"title":"The evolution of morphologic changes in the gallbladder before stone formation in mice fed a cholesterol-cholic acid diet.","authors":"S P Lee, A J Scott","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mice were fed a lithogenic diet containing 1% cholesterol and 0.5% cholic acid, and the sequence of morphologic changes in the gallbladder was followed. Histologic changes were studied with light microscopy and cell proliferation with autoradiography. Mucus glycoprotein production was studied with a spectrum of glycoprotein histochemical stains and electron-microscopic morphometry of membrane-bound mucus secretory granules. There was a rapid and early increase in cell proliferation of the epithelial cells and an increase in mucus production, which took place long before any observable cholesterol crystal precipitation. The gallbladder epithelial cells showed early focal pseudostratification and large numbers of degenerative cells. These changes culminated in glandular metaplasia and the formation of Rokitansky-Aschoff sinuses later in the gallstone induction phase. These observations clearly indicated that gallbladder epithelial injury had taken place before gallstone formation. The authors hypothesize that the consequences of these cellular changes play a contributory role in causing gallstone formation.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"1-8"},"PeriodicalIF":6.0,"publicationDate":"1982-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916021/pdf/amjpathol00202-0005.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35263340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Melanoma: Sinclair swine melanoma.","authors":"R R Hook, J Berkelhammer, R W Oxenhandler","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"130-3"},"PeriodicalIF":6.0,"publicationDate":"1982-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916032/pdf/amjpathol00202-0134.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35263343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neonatal adrenoleukodystrophy: clinical, pathologic, and biochemical delineation of a syndrome affecting both males and females.","authors":"R Jaffe, P Crumrine, Y Hashida, H W Moser","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We describe the detailed clinical, pathologic, and biochemical features of brother and sister with the neonatal onset form of adrenoleukodystrophy, together with evidence of the biochemical defect. When compared with reports of previous cases, it becomes clear that this is a newly described clinical entity with remarkable uniformity of signs and very different from the usual childhood form. Some pathologic features are shared, including the morphologic abnormality of the adrenal in both neonatal and childhood forms, but deposition of abnormally metabolized lipids is more systemic and widespread in the neonatal form. The biochemistry of the disease is presented in both children and parents. Plasma values of long-chain fatty acid C26:0 are 0.328 +/- 0.18 micrograms/ml in a control population and 0.381 +/- 0.312 micrograms/ml in the father and mother. Values for C26:0 in the plasma of childhood adrenoleukodystrophy are 1.62 +/- 0.87 micrograms/ml and in our two cases, 2.79 micrograms/ml in the male, 1.83 micrograms/ml in the female. The basic biochemical defect appears to be a diminished capacity to oxidize these fatty acids leading to accumulation in cholesterol esters. Fatty acid oxidation to CO2 by cultured skin fibroblasts was 51% of control value for stearic acid, 5% for lignoceric acid in the male, and 39% of control value for stearic acid, 5% for lignoceric acid in the female. The genetics of this disease is different; whereas childhood adrenoleukodystrophy is X-linked, the neonatal onset form affects males and females equally and is most probably autosomally recessive in inheritance.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"100-11"},"PeriodicalIF":6.0,"publicationDate":"1982-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916022/pdf/amjpathol00202-0104.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35263341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The appearance and significance of phospholipase A2 in lymph draining tuberculin reactions.","authors":"P Vadas, J B Hay","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Popliteal and prefemoral lymphatics of sheep were cannulated, and lymph was collected before and during the course of responses to PPD and concanavalin A. Hyperemia-inducing activity (HIA) and phospholipase A2 (PLA2) were released into lymph in response to antigenic stimulation, whereas lymph plasma draining unstimulated lymph nodes had consistently little or no detectable HIA and PLA2 activity. HIA appeared in the lymph efferent to the stimulated node at a time when blood flow to the responding node was enhanced. While the appearance of HIA did not directly correlate with changes in lymphocyte output, lymph protein concentration, or lymph flow rates, there was, however, a statistically significant correlation between HIA and PLA2 levels in lymph plasma, suggesting that extracellular PLA2 may contribute to the vasoactivity in lymph and thereby modulate blood flow to areas of antigenic stimulation. Vasoactive lymph, injected into rabbits, induced hyperemia via an indomethacin-sensitive pathway, since the induction of hyperemia was abrogated by pretreatment of injection sites with indomethacin. The extracellular release of PLA2 in response to inflammatory stimuli may represent an amplification mechanism for the generation of high levels of prostaglandins found in lymph draining stimulated nodes.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"285-91"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916231/pdf/amjpathol00207-0007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35257295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aortic morphology in salt-dependent genetic hypertension.","authors":"C Limas, B Westrum, J Iwai, C J Limas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Excessive salt intake is an important determinant of human essential hypertension. Hypertension resulting from genetically determined salt sensitivity can be studied by the used of the salt-sensitive (S) and -resistant (R) rat strains developed by Dahl. A longitudinal morphometric and ultrastructural study of S and R Dahl rats fed different amounts of salt (0.6%, 4.0%, and 8.0% NaCl) for 2-14 weeks was undertaken. Only S rats responded to high-salt (4.0% and 8.0%) diets with an increase in blood pressure, and the rate of hypertension development was proportional to the daily amount of salt consumed. Likewise, S but not R rats fed high-salt diets showed thickening of the aortic media which paralleled the rise of blood pressure. Intimal lesions were characterized by the accumulation of an amorphous, electron-dense substance in the subendothelial space (SES), adherence or penetration of lymphoid cells, and subendothelial fibrin deposition. The extent and severity of SES expansion correlated more closely with the duration of salt feeding than with the level of blood pressure. Fibrin deposition was noted only in severely hypertensive animals and was not related to the salt concentration in the diet. Morphologic abnormalities in endothelial cells were noted in hypertensive animals by transmission and scanning electron microscopy as well as by en face preparation, but endothelial denudation and junctional disruptions were notably absent. In contrast to the large numbers of lymphoid cells, neither platelets nor fibrin were seen adherent on the endothelium. These results, in conjunction with previous studies in other hypertensive models, indicate that the nature and extent of vascular lesions depend not only on the severity of hypertension but also on its rate of development, duration, and pathophysiologic characteristics.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"378-94"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916236/pdf/amjpathol00207-0100.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell cycle models for the aberrant coupling of growth arrest and differentiation in hyperplasia, metaplasia, and neoplasia.","authors":"R E Scott, D L Florine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The control of cell proliferation can be regulated by the coupling of growth arrest and differentiation. Since this process has been demonstrated both in vivo and in vitro, it is thought to be of considerable physiologic significance. The mechanisms that serve to couple growth arrest and differentiation were, however, poorly defined prior to our recent studies. We established that the coupling of growth arrest and differentiation of proadipocytes occurs at a distinct state in the G1 phase of the cell cycle, GD, and that it consists of at least five phases. These include: 1) growth arrest at GD; 2) nonterminal differentiation; 3) terminal differentiation; 4) loss of the differentiated phenotype, and 5) reinitiation of cell proliferation. On the basis of these observations we developed a cell cycle model to explain the biologic mechanisms of the coupling process. This model is now used to predict where defects in the coupling of growth arrest and differentiation may occur in hyperplastic, metaplastic, and neoplastic cells.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"342-8"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916246/pdf/amjpathol00207-0064.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intracerebral arteriolar permeability to lanthanum.","authors":"S Nag, D M Robertson, H B Dinsdale","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lanthanum, an electron-dense tracer, has been used extensively in the study of the structure of cell junctions. The present study was undertaken to determine whether the interendothelial junctions of normal intracerebral arterioles allow passage of lanthanum and to document the alterations occurring in these structures in acute hypertension. Perfusion of lanthanum for 12-40 minutes in control animals resulted in passage of tracer into arteriolar walls and into the extracellular compartment of the surrounding brain. The two principal mechanisms associated with tracer extravasation into the brain were diffuse passage through endothelial cytoplasm and through interendothelial spaces bypassing tight junctions. The latter finding has not been previously reported in normal cerebral arterioles and suggests that the tight junctions of these vessels are different from those of capillaries and consist of a meshwork of closely arranged maculae occludentes rather than complete circumferential occluding bands as was previously believed. Hypertensive animals showed accelerated passage of lanthanum, it being demonstrable not only in arteriolar walls but in capillary and venular walls and the surrounding neuropil after only 5 minutes of circulation. Passage of tracer through vessel walls occurred by the same routes as in control. In addition, increased numbers of pinocytotic vesicles were observed in the endothelium, confirming our previous studies that increased vesicular transport occurs in cerebral arteriolar endothelium in acute hypertension.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"336-41"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916235/pdf/amjpathol00207-0058.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lactate dehydrogenase (LDH) isozymes of human atherosclerotic plaques.","authors":"A M Gown, E P Benditt","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have been searching for additional markers to explore differences between the smooth muscle cells of human atherosclerotic fibrous plaques and their putative cells of origin in an aortic media and intima. Lactate dehydrogenase (LDH) isozyme analysis was performed on samples of human fibrous plaques selected by gross and microscopic criteria, and significant shifts in M4/M2H2 LDH isozyme ratios were found, relative to the underlying media and adjacent intima specimens. These changes are in the same direction seen in neoplastic tissues in vitro and in vivo and are probably not secondary to positional factors, inflammatory changes, or degenerative changes. The significance of these findings in relation to the monoclonal hypothesis of atherosclerosis is discussed.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"316-21"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916248/pdf/amjpathol00207-0038.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemically induced urolithiasis in weanling rats.","authors":"R Wolkowski-Tyl, T Y Chin, J A Popp, H D Heck","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"419-21"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916232/pdf/amjpathol00207-0141.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D H Walker, J B McCormick, K M Johnson, P A Webb, G Komba-Kono, L H Elliott, J J Gardner
{"title":"Pathologic and virologic study of fatal Lassa fever in man.","authors":"D H Walker, J B McCormick, K M Johnson, P A Webb, G Komba-Kono, L H Elliott, J J Gardner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Postmortem examination of 21 virologically documented cases of Lassa fever, including 6 complete autopsies, was performed as part of a field study of community-acquired Lassa fever in Sierra Leone. The most consistently observed lesions were hepatocellular, adrenal, and splenic necrosis and adrenal cytoplasmic inclusions. Neither these lesions, nor other milder and less constantly observed lesions such as myocarditis, renal tubular injury, and interstitial pneumonia, appeared severe enough to explain the cause of death in Lassa fever. The central nervous system (CNS) contained no specific lesions. Viral titrations demonstrated high viral content in liver, lung, spleen, kidney, heart, placenta, and mammary gland. Clinical laboratory data included elevation of hepatic enzymes, creatine phosphokinase (CPK), and blood urea nitrogen (BUN). Because of the paucity of pathologic lesions in spite of widely disseminated viral infection, further investigation of humoral inflammatory mechanisms is indicated.</p>","PeriodicalId":501602,"journal":{"name":"The American Journal of Pathology","volume":" ","pages":"349-56"},"PeriodicalIF":6.0,"publicationDate":"1982-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916239/pdf/amjpathol00207-0071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35212294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}