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Biomedical subjects

D E Bockman

Publications and source records attributed to D E Bockman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Impaired development of the thymic primordium after neural crest ablation.

Impaired thymic development as a result of ablation of neural crest has been observed in embryos late in development. The present study was initiated to determine what changes are effected early in thymic development by neural crest ablation. The epithelial primordia of the thymus were studied in chick embryos on the sixth day of incubation. Embryos with neural crest ablations were compared with sham-operated and untreated controls. Neural crest ablation inhibited formation of epithelial thymic primordia. Primordia in experimental embryos were fewer in number and were smaller than in shams and untreated controls. When primordia from shams and controls were transplanted to the chorioallantoic membrane of chick hosts, they were able to develop into organs with the typical features of embryonic thymus. Similar transplantation from neural crest-ablated animals, on the other hand, led to small, predominantly epithelial structures with meager lymphoid development. These findings are consistent with the hypothesis that mesenchyme derived from cranial neural crest is critical in initiating and sustaining the development from pharyngeal pouches of epithelial structures competent to attract and support the proliferation and differentiation of lymphoid stem cells.

Allantoin↗
PubMed1990

The participation of neural crest derived mesenchymal cells in development of the epithelial primordium of the thymus.

The purpose of this study was to correlate the contributions by derivatives of the neural crest with the development of the epithelial primordium of the thymus. The monoclonal antibody E/C8 was used to localize derivatives of the neural crest in chick embryos. Neural crest was ablated by microcautery of neural folds. Evaluation of thymic development was carried out on serial sections of embryos sacrificed on the sixth day of incubation. The size of the epithelial thymic primordium was smaller in experimental animals than in shams. E/C8-immunoreactivity was concentrated around the periphery of the primordium. It was determined, by quantifying reaction product using the Core-SCAN computer color analysis program, that the amount of immunoreactivity was decreased after ablation of neural crest. Statistical analysis showed that the quantity of reaction product was positively and significantly correlated with the size of the thymic primordium. It is concluded that mesenchymal derivatives of the neural crest, through participation in the early development of the epithelial primordium, play an important role in thymic development, and therefore with development of the immune system.

Animals↗
PubMed1989

Localization of fibronectin in megakaryocytes of fetal liver.

Antibodies specific for fibronectin were utilized to determine the sites of localization in the liver during development. The livers of fetal rats from each of gestation days 11-19, and from days 1 and 8 postpartum, were studied by fluorescence microscopy. Fibronectin was localized predominantly in megakaryocytes and megakaryocyte precursors, and to a lesser extent in the extracellular matrix surrounding blood vessels and between hepatocytes and sinusoids. The cytoplasm of megakaryocytes and their precursors displayed bright fluorescence but their nuclei were negative for fibronectin. Hepatocytes had negative or faint fluorescence. Megakaryocytes were present in the liver from day 12, and were numerous from day 13 through most of the rest of gestation. The relative numbers of megakaryocytes decreased in later gestation; at 8 days postpartum only a few were observed per section. Hepatic megakaryocytes appeared before megakaryocytes were established in spleen and bone marrow. The early and persistent high levels of fibronectin in hepatic megakaryocytes, in the absence of comparable localization within hepatocytes, leads us to the hypothesis that megakaryocytes are important in establishing circulating fibronectin levels in the fetus. Similarly, bone marrow megakaryocytes may contribute to circulating fibronectin in the adult.

Animals↗
PubMed1989

Alteration of early vascular development after ablation of cranial neural crest.

A previous study has shown that, subsequent to ablation of cranial neural crest, heart morphology and pharyngeal arch vessels (aortic arches) are altered before septation of the outflow tract normally occurs. In the present study, we concentrated on very early development of the aortic arch apparatus in the chick (incubation days 3-5). The three-dimensional organization of the arch vessel apparatus was studied by scanning electron microscopy after intravascular injection of Mercox, and by serial sections of embryos embedded in plastic. Alterations in the arch vessel apparatus were already present by day three in embryos with neural crest ablation at stage 9-10. Bilateral symmetry frequently was lost. Arch vessels sometimes were enlarged and occupied most of the arch, with little surrounding mesenchyme. Some arch vessels were small or occluded. Mesenchyme was significantly reduced in quantity in the arches, and was not condensed and symmetrical as in controls. There was a significant increase in the proportion of direct apposition of vessel endothelium with epithelium, without the intervening mesenchyme typical of controls. The surgical manipulation used in this study leads to distinct alterations in the arches of components and relationships which are important in development. Altered blood flow likely affects the development of the heart.

Animals↗
PubMed1989

Bypass circuits as the source of thromboemboli during extracorporeal membrane oxygenation.

To determine the presence and extent of thrombus formation in the apparatus used for extracorporeal membrane oxygenation we studied various portions of the polyvinylchloride circuit from five infants who received extracorporeal membrane oxygenation for 70 to 330 hours. All infants had right-sided cannulation. Sections were cut from the circuit at the time of decannulation and subjected to light and scanning electron microscopy. The site that contained the most thrombus formation was the membrane oxygenator bypass circuit, which is subjected to repeated periods of unclamping and clamping to direct blood flow through the membrane oxygenator. Autopsy results from nonsurvivors showed evidence of pulmonary and renal infarcts, a left frontal lobe infarct, a thromboembolus of the left external and internal carotid arteries, and thrombi in the lungs, kidney, brain, and coronary arteries. One survivor had computed tomographic evidence of infarction of the left middle cerebral artery distribution. We suggest that the areas of the extracorporeal membrane oxygenation circuit subjected to repeated changes in flow dynamics may be the source of microemboli.

Catheters, Indwelling↗
PubMed1988

Early association of duodenal contents and blood with acini during experimental pancreatitis.

This study was directed toward understanding the mechanism by which the closed duodenal loop induces experimental pancreatitis. Carbon black was introduced into the duodenal lumen as a tracer before formation of the closed loop. Within four hours, the carbon, marking the location of duodenal contents, had passed retrogradely through pancreatic ducts and broken out to localize at the periphery of acini in various regions of the pancreas. In this periacinar location the tracer was mingled with erythrocytes, neutrophils, platelets, and fibrin. Acinar cells were damaged as the mixed duodenal and blood components passed along their base and between cells. It is concluded that acinar cells are involved very early and directly in the initiation of pancreatitis by this method, and not secondary to ductal inflammation.

Acute Disease↗
PubMed1988

Analysis of nerves in chronic pancreatitis.

We sought to identify characteristics of pancreatic nerves that were altered in chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed for the number and size of nerves, their association with inflammatory infiltrates, and their fine structure. The mean diameter of nerves in these patients was significantly greater than in controls, whereas the mean area of tissue served per nerve was significantly less than in controls. Foci of inflammatory cells, prominent in some specimens, sometimes were associated with nerves and ganglia, but inflammatory foci and neural elements also existed separately. Invasion of nerve tissue by inflammatory cells was observed but was not massive. Ultrastructural changes were detected in nerves. Individual nerve fibers showed evidence of damage, and there was evidence of edema in the nerve bundle. The perineurial sheath was altered so that it no longer provided a barrier between the surrounding connective tissue and the internal neural components. The results of this study indicate that nerves are preferentially retained while parenchyma degenerates and is replaced by fibrosis during chronic pancreatitis, but that they are retained in an altered condition. Increased mean diameters of nerves in chronic pancreatitis argues against pain being caused by constriction due to fibrosis. It is likely that both sensory and motor nerve fibers are affected by this alteration.

Adult↗
PubMed1987

Effect of neural crest ablation on development of the heart and arch arteries in the chick.

Mesenchymal derivatives of the neural crest contribute to the connective tissues and blood vessels of the pharyngeal arches, and participate in the septation of the outflow tract of the heart. The present study was designed to determine the nature and timing of alterations in the development of the heart and arch arteries subsequent to diminished neural crest contributions. The neural crest contributing to the three caudalmost pharyngeal arches was ablated bilaterally in chick embryos and compared with sham or unoperated controls. Heart development was studied by scanning electron microscopy. Arch artery development was studied microscopically after intravascular injection of India ink and clearing of the specimen. Neural crest ablation caused morphological changes in most hearts. Hearts in experimental animals commonly were elongate and were subject to inappropriate development of ventricular and atrial areas. A surgical effect delayed the disappearance of arch arteries one and two, and removal of neural crest produced an additional delay. Neural crest ablation caused failure of arch arteries three, four (right), and six to develop to the proper size in some animals. Survival of those whose sixth arch arteries achieved the proper size caused group measurements to reach normal values again by stage 32. Closure of arch arteries in some animals and maintenance in others produced greater variability in experimental animals than in controls. It is significant that heart morphology was altered before septation of the outflow tract normally occurs. This indicates at the least that another factor, such as altered blood flow, contributes to the abnormal development. Altered flow may result from changes in pharyngeal arch mesenchyme and arch artery endothelium.

Animals↗
PubMed1987

Chronic obstructive pancreatitis, nesidioblastosis, and small endocrine pancreatic tumor.

A patient is described in whom a small 0.8-mm-diameter endocrine tumor was found in association with localized pancreatitis, stricture of the main pancreatic duct, and nesidioblastosis. The endocrine tumor, localized 7 mm from the main duct, obstructed a collateral pancreatic duct and four of its branches. Pancreatitis was localized into two areas. It was fairly severe in a small area of the body drained by the obstructed collateral duct and extended around it, reaching the main pancreatic duct which was partly occluded at this level by periductal fibrosis. Pancreatitis was mild in the left part of the pancreas distally from the incomplete stricture of the main duct. The head and body of the pancreas between the stricture and the duodenum were normal. Nesidioblastosis was present in the obstructed parts of the pancreas. It is suggested that the tumor could have caused pancreatitis, stenosis of the main duct, and nesidioblastosis.

Chronic Disease↗
PubMed1987

Pancreatic extracellular matrix alterations in chronic pancreatitis.

The proliferation of pancreatic extracellular matrix, which characterizes chronic pancreatitis, has been analysed using immunohistochemistry. The relationship of matrix components to intraductal precipitates and the presence of serum proteins in precipitates were also studied to investigate the suggestion that ductal permeability increases in chronic pancreatitis. Pancreatic tissue from organ donors was compared with that from patients with chronic calcifying or chronic obstructive pancreatitis. Frozen sections were labeled with monospecific antibodies to collagen types I, III, pro-III and IV, laminin, fibronectin, IgG, IgA, and IgM and then visualized by indirect immunofluorescence. In chronic pancreatitis, interstitial collagens and fibronectin appeared increased and disorganized in both fibrous tissue and areas that appeared histologically normal. Type IV collagen distribution was abnormal and in some sites was present with interstitial collagen. In addition, intraductal precipitates were shown to contain immunoglobulins, and defects were identified in the duct basal lamina associated with precipitates. These results demonstrate that in chronic pancreatitis interstitial collagens are extensively disorganized, the fibrosis possibly being relatively labile. The presence of serum proteins in intraductal precipitates confirms an increase in ductal permeability, and associated defects in the basal lamina appear to define a route via which serum proteins may enter the intraluminal compartment.

Adult↗
PubMed1986

Ultrastructure of human acute pancreatitis.

Few studies have been published on the ultrastructural changes which accompany human acute pancreatitis, and these have concentrated primarily on parenchyma. The present study concentrates on extraparenchymal changes, compares acute pancreatitis occurring alone with that on a background of chronic pancreatitis, and tests for similarity with observations made previously in an experimental model. Pancreatic tissue came from 16 patients undergoing surgery for pancreatic disease and five subjects without pancreatic disease. Regressive changes in parenchymal cells were consistent with ischemia, and with previously described studies. Polymorphonuclear leukocytes infiltrated into stroma and parenchyma. Platelets accumulated intra- and extravascularly. Fibrin deposits were common in the connective tissue, and could be observed in intercellular spaces at the base of acini, mingled with degenerating acinar cells and secretion product. Microthrombi occurred in blood vessels. These alterations were consistent with those in experimental acute pancreatitis. Similar changes were observed whether or not acute pancreatitis occurred on a background of chronic pancreatitis. The vascular component is important in acute pancreatitis, and altered epithelial barriers allow interaction between blood-borne material and pancreatic exocrine secretions.

Acute Disease↗
PubMed1986

Structure and function of specialized cilia in the exocrine pancreas.

Cilia are found in acinar and ductular lumina. Most descriptions of human or dog pancreatic tissue have indicated that these are probably motile structures which move and/or mix pancreatic secretion. A recent study interpreted arrangements of microtubules within cilia which deviated from the classic 9 + 2 pattern as indicating pathological change. There have been suggestions, however, from studies on nonmammalian and human pancreas, that the structure of pancreatic cilia suggests a sensory function. The present paper reports studies on the ultrastructural organization of the specialized cilia in human and canine pancreatic tissue. The pattern of microtubular organization resembles that of cilia modified for chemoreception rather than that of classic kinocilia. It is concluded that pancreatic ductular cilia are sensory rather than motile, providing a mechanism for monitoring general or specific molecular concentrations.

Animals↗
PubMed1986

Pancreatic acinar cell function and morphology in rats fed zinc-deficient and marginal zinc-deficient diets.

The prevalence of marginal zinc nutriture in several populations of people in this country and the lack of reports on the effect of marginal zinc nutriture in experimental animals prompted us to look at pancreatic acinar cell function and morphology in rats fed a zinc-deficient diet ad libitum: 4 and 50 ppm zinc-supplemented diets in amounts isocaloric to a zinc-deficient diet and Rodent-Blox fed ad libitum for a period of 49 +/- 1 (SEM) days. Because of a diminished rate of energy expenditure in zinc-deficient rats, animals receiving 50 ppm zinc-supplemented diets were offered less food, resulting in decreased body weight and pancreas weight, DNA, RNA, total protein, lipase, amylase, and secretion of protein. Specific changes due to zinc deficiency included (a) further decrease in body weight and (b) increase in content, specific activity, and secretion of lipase. Both the size and volume fraction of zymogen granules were reduced in zinc deficiency. The lumina of acinar and small ducts were collapsed with paucity of secretion products. Zinc deficiency may therefore lead to a defect in discharge mechanism. A further reduction in volume fraction of zymogen granules in the 4 ppm zinc-supplemented group was associated with increased secretion of serine proteases (trypsinogen and chymotrypsinogen), which constitute approximately 46% of total secretory protein in the pancreas under normal dietary conditions. This indicated an accelerated discharge due to an unknown mechanism. Changes in the secretion of digestive enzymes in the present study simulated ethanol-induced secretory alterations that were previously observed. Because abnormal zinc nutriture and chronic alcoholism are commonly associated, it is speculated that zinc deficiency may play a role in the ethanol-induced secretory alterations.

Amylases↗
PubMed1986

Three-dimensional pattern of ductuloacinar associations in normal and pathological human pancreas.

To explain the changes that must occur to produce the characteristic lesions of chronic calcifying pancreatitis, a three-dimensional reconstruction of pancreatic ductules and acini has been undertaken in normal subjects and in patients presenting with disease. This has been done with 3-micron serial sections of tissue embedded in plastic. Two approaches were used. In the first, ductules were reconstructed along with the acini directly associated with them. Using this method, adhesions or anastomoses between acini were not evident in normal specimens, and the quantity of acini associated with the ductules seemed small. The second method involved tracing the association of acini and ductules, beginning in the periphery of lobules, with the aid of a drawing tube. It became evident that an acinus was not necessarily the termination of the glandular system, but that intercalated ducts could be formed on the other side of the acinus, extending the quantity of acinar contributions that could be made to a primary ductular system. Evidence of dilation of ducts, atrophy of acini, formation of cul-de-sacs, and localized obstruction were found by three-dimensional reconstruction of serial sections from patients with chronic pancreatitis along with anastomosis between acini. It is probable that anastomosis becomes more detectable in patients as duct lumina enlarge. Anastomoses in the ductules in chronic pancreatitis may result from loss of some lobular structures, emphasizing preexisting connections or fusions of pancreatic elements, or both, as part of the pathological process.

Adult↗
PubMed1986

Fine structure of the organic matrix of human pancreatic stones.

Pancreatic stones that were removed from the pancreatic ducts of patients with chronic calcifying pancreatitis were decalcified so the organic matrix could be studied by scanning and transmission electron microscopy. The observations made by scanning electron microscopy were compared with those made on undecalcified stones, and the findings were correlated with light microscopic observations. After the calcium carbonate was removed, the stones consisted of multiple partitions arranged like a sponge. They were embedded in a gel-like matrix. The organic partitions frequently were composed of dense surface layers and sparse central reticular accumulations, which had surrounded and bound calcium carbonate crystals. The organic matrix was heterogeneous in texture. Some areas had dense, regular, proteinaceous fibrous material. Deposits resembling fibrin were observed. Altered cellular constituents appeared to make up minor portions of the matrix. Calcium carbonate, which was precipitated in vitro in pancreatic juice, resembled the morphology of pancreatic stones more than that of pure calcium carbonate crystals. These results are consistent with the coformation of pancreatic stones from constituents in the pancreatic juice [including pancreatic stone protein (PSP), glycosaminoglycans, and occasional cells] and precipitated calcium carbonate.

Calcium Carbonate↗
PubMed1986

Interaction between marginal zinc deficiency and chronic alcoholism: pancreatic structure and function in rats in vitro.

The present study was done to determine interaction of ethanol and marginal zinc nutriture on morphology and function of rat pancreas. Sprague-Dawley rats were maintained on Wayne Rodent-Blox ad libitum; marginal zinc-deficient diet plus ethanol ad libitum and pair fed with animals fed marginal zinc-deficient liquid diet and zinc-supplemented liquid diet with ethanol for 33 (+/- 1 SEM) days. Body, pancreas, liver, heart, and kidney weights were determined, and studies of pancreatic DNA, RNA, total proteins and newly labeled proteins, amylase, lipase, trypsinogen, and chymotrypsinogen were done on pancreatic lobules in vitro. Ethanol feeding independent of the zinc content of the diet caused a decrease in zinc content of the liver, body weight, liver and pancreas weight, pancreatic DNA, total protein, and amylase concentration and an increase in lipase and trypsinogen concentrations and in secretion of amylase and lipase. Interaction of the marginal zinc diet and ethanol feeding resulted in a decreased synthesis of RNA and secretion of newly synthesized protein and an increase in secretion of serine proteases. Morphological studies revealed a reduction in the number of zymogen granules in animals fed low levels of zinc, also with an accumulation of lipid droplets when the diet contained ethanol. These studies confirmed our previous observations of specific injury to the pancreas due to marginal zinc nutriture or to ethanol, independent of each other. Marginal zinc nutriture in concert with ethanol resulted in impaired RNA synthesis and secretion of nascent proteins and increased secretion of serine proteases. These data indicate that altered zinc metabolism induced by ethanol per se may contribute to ethanol-induced disturbance of pancreatic function.

Alcoholism↗