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D E Bockman

Publications and source records attributed to D E Bockman.

At least 55 records · Page 3Linked to original sources

Alcohol and the integrity of the pancreas.

Alcohol may affect the integrity of the pancreatic parenchyma, as seen in alcoholic pancreatitis, some cases of chronic alcoholism without clinical pancreatitis, and experimental studies. The composition of pancreatic juice may reflect some of these changes. One type of parenchymal alteration is the loss of differentiative features of acinar cells, so that they take on the characteristics of ductular cells. Concomitant fibrosis completes the formation of the tubular complexes found in association with alcoholic chronic pancreatitis. Sustained alcohol intake may produce the accumulation of lipid droplets in parenchymal cells, some of which may be shown to be within the rough endoplasmic reticulum of acinar cells. Epithelial cells may undergo mucous metaplasia. The epithelial-basal lamina barrier frequently is breached in the area of intraluminal aggregates, with or without obvious inflammation in the immediate area. Loss of barrier function may lead to interaction among components of the external compartment (lumen) and the internal compartment (stroma). Increased levels of blood proteins and glycosaminoglycans in the juice, enzyme activation, fibrin formation, and complement activation are potential consequences of barrier loss. Increased lactoferrin levels could result in part from the activity and degranulation of polymorphonuclear leukocytes.

Alcoholism↗

Neural crest interactions in the development of the immune system.

The thymus is formed by contributions from different sources which must interact in a precisely timed sequence for proper development. Pharyngeal pouch epithelium interacts with embryonic connective tissue in preparation for migration of blood-borne lymphoid stem cells into the thymic primordium. The embryonic connective tissue in this region is derived from neural crest. Ablation of small portions of neural crest prevents or alters the development of the thymus. Other pharyngeal pouch derivatives such as thyroids and parathyroids are affected. Furthermore, defects in the heart and great vessels are produced. These observations establish experimentally the role of neural crest in defective immune development such as that seen in the DiGeorge syndrome. It seems likely that various combinations of defects will be rendered more understandable through recognition of the contributions made from neural crest.

Animals↗

Dependence of thymus development on derivatives of the neural crest.

Elimination of limited areas of the cephalic neural crest in stage 9 or 10 chick embryos markedly reduced the size of the thymus gland or resulted in its absence. Small thymic lobes contained both thymocytes and epithelial cells but showed delayed development. Parathyroid and thyroid glands sometimes were reduced in size or missing from the normal location on one or both sides. Heart defects were consistently present. Thymus development may depend on direct interaction of mesenchymal derivatives of the neural crest with pharyngeal epithelium. Multiple defects, such as the Di George syndrome, may result from failure of neural crest derivatives to migrate and interact properly.

Animals↗

Neural crest and normal development: a new perspective.

Several clinical syndromes, including the DiGeorge syndrome, are characterized by clusters of developmental defects of the heart and great vessels with structures derived from the embryonic pharyngeal apparatus including thymus and parathyroids. The connective tissue derivatives of neural crest are necessary for the normal development of these structures, and there is new experimental evidence that depletion of neural crest causes defects similar to these clinical syndromes. Therefore it is proposed that many of these syndromes are due to inappropriate development of neural crest. The implications of this hypothesis include the predictions 1) that asplenia and certain other anomalies have the same etiology, and 2) that it is possible to observe the effects of teratogenic agents upon a cellular population (neural crest) at the time when it is being altered, rather than waiting until definitive organs may be examined.

Abnormalities, Multiple↗

The role of epithelial cells in gut-associated immune reactivity.

Epithelial cells and their products are essential participants in both initial and final stages of reactivity to foreign materials in the gut lumen. Follicle-associated epithelial cells, called "M"-cells by others, more efficiently transport antigens from the lumen than do columnar absorptive cells. Epithelial cells degrade antigens intracellularly. The presence of Ia-like antigens on epithelial cells of the gastrointestinal tract and thymus suggests a role in antigen presentation. Actively phagocytic macrophages are present within the epithelium of Peyer's patches and appendix, providing antigen degradation and presentation. Follicle-associated epithelial cells transport materials from lamina propria into intestinal lumen. Therefore, FAE cells are capable of bidirectional transport. Plasma cells are located within and immediately beneath the epithelium of Peyer's patches and appendix, where defects in the basal lamina indicate diminished capability for molecular selection. Transmission of antibodies into the lumen would modulate further antigen uptake and provide for interaction with organisms.

Animals↗

Functional histology of appendix.

The appendix is a prominent example of gut associated lymphoepithelial tissue, whose function is to react to the wide variety of antigens present in the gastrointestinal tract. It is composed of a large number of repeating units, the lymphoid follicles, each of which is divided into an apical dome, a large basal nodule with a germinal center, and laterally extending thymus dependent areas. The dome epithelium consists mainly of columnar absorptive cells and of specialized follicle associated epithelial (FAE) cells which are efficient at transporting material from the lumen to the underlying lymphoid tissue, and may also transport macromolecules from the lymphoid follicle into the lumen. The dome epithelium normally has large numbers of lymphocytes within it, as well as smaller numbers of macrophages and plasma cells. Macrophages, and perhaps FAE cells, are capable of processing and presenting antigens to reactive lymphocytes. Lymphocyte proliferation and differentiation in response to antigenic stimulation begins in the lymphoid follicles, but most of the lymphocytes leave by the lymphatics, migrate through lymph nodes and spleen, frequently to complete differentiation into IgA-secreting plasma cells in the lamina propria of mucosal surfaces. Normal function of appendix probably helps suppress potentially destructive humoral antibody responses while promoting local immunity.

Animals↗

Architecture of human pancreas: implications for early changes in pancreatic disease.

An increased proportion of ductulelike structures, sometimes dilated, occurs in association with pancreatic adenocarcinoma, chronic pancreatitis, cystic fibrosis, and pancreatic ectasia associated with conditions such as uremia. This frequently is interpreted as ductular proliferation, implying origin in ductal elements. Recent animal studies have provided an altered view of pancreatic architecture that is consistent with acinar dedifferentiation leading to the ductulelike structures, or tubular complexes. The architecture of pancreas from organ donors was studied by light and scanning electron microscopy and by wax reconstruction of serial sections. It is concluded that the zymogen granule-containing cells of normal human exocrine pancreas are arranged as branching tubules that vary in diameter and curve acutely. The tubules frequently end blindly to form acinar structures; less frequently they anastomose. This arrangement is consistent with the interpretation that tubular complexes associated with pancreatic disease result from dedifferentiative changes in acinar cells. Tubular complexes may reflect a defect or defects common to pancreatic disease rather than ductular proliferation specific to each one.

Adolescent↗

Origin of tubular complexes in human chronic pancreatitis.

Tissue samples from seven patients with chronic pancreatitis were studied by light and electron microscopy, using samples from the pancreas of seven organ donors as a reference group. Tubular complexes were observed in four of the patients with chronic pancreatitis. Tubular complexes, which have been interpreted as resulting from "ductular reduplication" in other studies of chronic pancreatitis, and "ductular proliferation" in studies of pancreatic adenocarcinoma, were studied carefully to determine their origin. Extensive retrogressive changes in acinar cells leading to diminished zymogen granules, decreased cell height, and concomitant increase in luminal diameter were consistent with the interpretation that phenotypic modulation of acinar cells to take on the characteristics of ductular cells produced the tubules. This it is concluded that in chronic pancreatitis, as has been shown for pancreatic adenocarcinoma, the tubular complexes originate from acinar cells rather than from proliferation of preexisting ductules. Fibrosis and thickening of the basal lamina of exocrine pancreatic cells and capillaries were consistent with an altered capability for transmission of material between blood vessels and exocrine cells.

Adult↗

Pancreatic acinar cell function and morphology in rats chronically fed an ethanol diet.

The aim of the present study was to determine the effect of prolonged ethanol intake on the morphology and protein metabolism in the rat pancreatic acinar cells. Weight-matched triplets of Sprague-Dawley rats were fed Lieber-DeCarli diet containing 5% (wt/vol) concentration of ethanol, isocaloric amounts of Lieber-DeCarli diet, or rat chow ad libitum for 6, 12, and 18 mo. In the ethanol-fed group, histologic studies by light microscopy showed absence of protein plugs in the pancreatic ducts and/or pancreatitis, but electron-microscopic evaluation revealed progressive accumulation of lipid droplets in acinar and ductal cells. No definite changes in the mitochondria and endoplasmic reticulum were noticed. Biochemical studies revealed increased specific activity of trypsinogen, chymotrypsinogen, and lipase, and decreased specific activity of amylase. Trypsin-inhibiting capacity was decreased in the tissue and in the medium in a progressive fashion. There was no increase in the secretion of total protein. These data show a complex and a nonparallel alteration of specific digestive enzymes and trypsin inhibitor in this model of chronic ethanol intoxication that may be of relevance to occurrence of pancreatitis.

Alcoholism↗

Participation of follicle associated epithelium (fae), macrophages, and plasma cells in the function of appendix.

Rabbit appendix was studied by correlated scanning and transmission electron microscopy and light microscopy, taking advantage of luminal bacteria as naturally occurring markers for following antigen uptake. The three-dimensional relationship of lymphoid follicles to other structures was revealed clearly. The smooth luminal surface of the appendix is interrupted by stomata each leading to a recessed interval between the dome epithelium covering the apical pole of each follicle and the goblet cell-rich epithelium forming a cupola on the opposing surface. Bacteria abound in this recess. They are taken up by follicle associated epithelial (FAE) cells which comprise part of the dome epithelium. Intraepithelial macrophages phagocytize the bacteria. Bacteria-laden macrophages are numerous in the dome area of the follicle and in the germinal center. Large lymphatic sinuses surrounding the follicles are well visualized following stimulation of fluid movement. Plasma cells are located within the dome epithelial layer and immediately beneath it. Plasma cells may be concentrated along the base of epithelial cells, with the absence of a basal lamina indicating an absence of the molecular selection which it would normally provide. The appendix, like Peyer's patches, takes up antigens, processes them, and gives evidence of reaction to them locally, with the secretions from plasma cells possibly modulating antigen entry.

Animals↗

Cells of origin of pancreatic cancer: experimental animal tumors related to human pancreas.

Human pancreatic adenocarcinoma is traditionally believed to be ductal in origin, primarily due to the presence of complexes of tubules interpreted as being derived from ductular proliferation. Although observations in various animal models of pancreatic tumors suggested that acinar cells wee undergoing dedifferentiation to form tubular complexes, this process was difficult to reconcile with an acinar arrangement of the pancreas. Using three-dimensional reconstructions and retrograde injections, it was concluded that the normal pancreas actually has a tubular arrangement. The tubules branch, curve, and anastomose. By losing zymogen granules and decreasing in height, acinar units become recognized as ductule-like structures. Therefore, the presence of tubular complexes should not be taken to indicate that carcinogenesis has taken place or to eliminate acinar cells as possible cells of origin of adenocarcinoma, which by present criteria would be classified as ductal.

9,10-Dimethyl-1,2-benzanthracene↗

Heterogeneity, position, and functional capability of the macrophages in Peyer's patches.

Peyer's patches are thought to be deficient in macrophages capable of sustaining the induction of an immune response. The present study examined the position, morphology, and phagocytic activity of Peyer's-patch macrophages, and their ability to take up, in situ, a tracer antigen introduced through the intestinal lumen. Peyer's-patch macrophages were isolated in vitro, and nonspecific esterase activity of individual cells was quantitated. Macrophages concentrated within the epithelium overlying Peyer's patches and in the subepithelial zone showed phagocytic activity and the ability to take up exogenous ferritin. Adherent macrophages demonstrated heterogeneity of esterase activity, with approximatley 15% having none. However, esterase activity in macrophages from lymph nodes was equally heterogeneous. The profile of esterase activity of Peyer's-patch macrophages seemed intermediate between those of macrophages from submandibular and mesenteric nodes. Tingible body macrophages were concentrated in germinal centers and were poorly adherent. The results of this study indicate that macrophages similar to those in lymph nodes are concentrated in the region where they may intercept antigens entering through overlying specialized epithelium. The presence of plasma cells in the same region suggests that local reaction to antigens, perhaps modulating further antigen entry, is supported by these macrophages. Perhaps the proportion of functional macrophages in the entire Peyer's patch is too low to support immune induction in in vitro-tests.

Animals↗

Architecture of normal pancreas as revealed by retrograde injection.

The architecture of the pancreas was revealed by retrograde injection of the pancreatic ductal system of normal rats with a silicone rubber compound, and subsequent study of the preparation by light microscopy and scanning electron microscopy. The injected material became associated with both ducts and "acinar" areas. Examination of these specimens suggests that the arrangement of the exocrine pancreas is that of a complexly curving and branching system of tubules which anastomose and end blindly. This architecture, which is not that of a true acinar gland, provides a rational basis for the understanding of the simple dedifferentiative changes that accompany pancreatic carcinogenesis, and which have been generally interpreted as representing ductular proliferation.

Animals↗

Anastomosing tubular arrangement of dog exocrine pancreas.

Wax reconstructions of zymogen granule-containing cells in dog show the arrangement of the exocrine pancreas to be a branching, anastomosing system of tubules which vary in diameter and end blindly. This arrangement is not that of a true acinar gland.

Animals↗