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Biomedical subjects

B F Trump

Publications and source records attributed to B F Trump.

At least 37 records · Page 2Linked to original sources
PubMed1979

The subcellular pathology of shock in trauma patients: studies using the immediate autopsy.

In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.

Adult↗
PubMed1979

The role of ion shifts in cell injury.

The present paper reviews studies which utilize x-ray microanalysis to determine intracellular ion shifts following several types of cell injury. New data from our own laboratory on several cell injury systems are discussed. Concentration estimates are made by comparison of data from tissues with a series of standards prepared in 20% albumin followed by cryosectioning. Hemorrhagic shock in rats is followed by rapid changes of ions in both muscle and liver. These include increased levels of sodium and chlorine and decreased levels of potassium which can be correlated with deficits in the energy charge. Measurements made over hepatocellular carcinomas in the mouse, induced by safrole show marked changes in comparison with non-transformed cells. These include striking increases in sodium and chloride and decreases in potassium and phosphorus which may be related to growth control. Studies on ischemia produced by arterial clamping in the rat kidney and the dog heart show somewhat similar changes. Moreover, in these models much interest is directed at early increases of cytoplasmic calcium with decreased mitochondrial calcium levels at later intervals. Following reflow, there is a prominent increase of calcium in the cytosol. These changes in calcium may be related to activation of phospholipases producing permeability changes which may contribute to further ion shifts as well as ultimately to cell death. The paper also comments on the use of cryostat sections for some types of routine pathological analysis.

Animals↗
PubMed1979

Studies on carcinogenesis of human prostate. IV. Comparison of normal and neoplastic prostate during long-term explant culture.

Morphologic responses of neoplastic human prostate to long-term explant culture were monitored at serial intervals by LM, TEM and SEM, and compared to normal prostate. Explants were cultured at 37 degrees C in CMRL-1066 supplemented with fetal calf serum and antibiotics. At 0-time culture, normal prostate of young adult males obtained at immediate autopsy, consisted of glandular spaces and ducts lined by columnar to cuboidal secretory epithelial cells and basal cells embedded in fibromuscular stroma. Neoplastic tissue was obtained surgically by transurethral resection (TUR), and consisted of stroma widely infiltrated by well-to moderately-differentiated tumor cells arranged in variable sized, gland-like structures. Secretory activity was evident; basal cells were absent in these glands. During early periods of culture up to several weeks, secretory cells of normal prostate became necrotic. Basal cells remained viable, repopulated acinar structures and epithelialized explant surfaces. At these sites, basal cells, or their derivatives, formed a multicellular epithelium. Exaggerated intercellular spaces separated cells, and synthesis of mucus-like material was seen. Epithelial characteristics included microvilli, junctional complexes, and basal lamina. In marked contrast, tumor cells covered explant surfaces forming an irregular, disorganized layer of squamous-like cells with elongated nuclei and prominent nucleoli. Microvilli, junctional complexes, and basal lamina were poorly developed or absent. Intercellular attachments appeared tenous. Some tumor cells accumulated lipid; synthesis of mucus-like material was not seen. At later intervals of culture up to 10 weeks, synthesis of mucus-like material by basal cells, or their derivatives, declined. Surface cells of neoplastic prostate gradually became more anaplastic in appearance; cells contacted neighboring cells with pseudopodia and filopodia.

Adenocarcinoma↗
PubMed1978

Studies on the cellular toxicity of polychlorinated biphenyls (PCBs). I. Effect of PCBs on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver- a morphological and biochemical study.

The acute effects of the PCB (polychlorinated biphenyls) mixture (Aroclor 1254) on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver were investigated. Six daily i.p. injections of 25 and 50 mg PCB/kg body weight resulted in increased liver weight and liver to body weight ratios. When compared to controls PCB treatment resulted in a six-fold increase in amount of cytochrome P-450. Activities of NADPH-cytochrome c reductase, ethylmorphine demethylase and inosine diphosphatase were increased whereas glucose-6-phosphatase values were decreased by PCB exposure. Analysis of liver homogenate and microsomal fraction revealed an increase in lipid in PCB-exposed animals. Phospholipids, cholesterol and triglyceride were significantly increased after PCB exposure; however, the greatest percentage increase was seen in the triglyceride pool. The finding of an increase in microsomal triglyceride to phospholipid ratios with exposure to PCB is suggestive of an increase in membrane-enclosed lipid (liposomes). Studies with labelled glycerol indicated that the PCB-induced fatty liver resulted from increased half life but not increased synthesis of liver lipid moieties. The rate of incorporation of leucine into microsomal membrane and albumin was somewhat enhanced in rats exposed to PCB indicative of increased protein synthesis. Morphological studies showed increased occurrence of lipid material, both in cytoplasmic droplets and within rough and smooth-surfaced endoplasmic reticulum. Proliferation of smooth endoplasmic reticulum and flattened Golgi cisternae with no secretion granules containing lipoprotein particles characterized the liver from animals exposed for 6 days. The increase in lipid within membranes of the endoplasmic reticulum together with the flattened Golgi lacking typical secretory vesicles indicates a defect in transport of lipoproteins from the endoplasmic reticulum to the Golgi apparatus and may be the cause of the PCB-induced fatty liver.

Animals↗
PubMed1978

Explant culture of rat colon: a model system for studying metabolism of chemical carcinogens.

An explant culture system has been developed for the long-term maintenance of colonic tissue from the rat. Explants of 1 cm2 in size were placed in tissue-culture dishes to which was added 2 ml of CMRL-1066 medium supplemented with glucose, hydrocortisone, beta-retinyl acetate, and either 2.5% bovine albumin or 5% fetal bovine serum. The dishes were placed in a controlled-atmosphere chamber which was gassed with 95% O2 and 5% CO2. The chamber then was placed on a rocker platform which rocked at 10 cycles per min causing the medium to flow intermittently over the epithelial surface. The explants were incubated at 30 degrees C. The viability of the tissue was measured both by incorporation of specific precursors into cellular macromolecules and by monitoring of tissue morphology with light and electron microscopy. Cultured rat colon was able to metabolize benzo[alpha]pyrene, 7,12-dimethylbenz[alpha]anthracene, aflatoxin B1, dimethylnitrosamine, 1,2-dimethylhydrazine, and methylazoxymethanol acetate into chemical species that bind to cellular DNA and protein.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Isolation and characterization of epithelial cells from bovine pancreatic duct.

Epithelial cells derived from bovine pancreatic duct have been grown continuously in culture for 30 weeks (approximately 90 doublings of the cell population). The cells were grown in Eagle's minimal essential medium supplemented with 10% heat-inactivated fetal bovine serum, 2 mM glutamine, 0.1 mM nonessential amino acids, and antibiotics. In confluent cultures, the cells are multilayered and form circular structures. When tested at various passages, the cells neither formed colonies in soft agar nor produced tumors after inoculation into athymic, nude mice. Hydrocortisone (1 and 5 microgram per ml) and insulin (1,5 and 10 microgram per ml) had no effect on the growth of the cells. beta-Retinyl acetate inhibited growth rate and cell yield at a concentration of 5 microgram per ml but was not growth-inhibitory at lower concentrations. By electron microscopy the cells have numerous mitochondria, Golgi and microvilli. Mucous droplets were observed in a small proportion of the cells. Desmosome-like structures and occluding junctions were observed more frequently between cells that had been transferred as aggregates than between cells transferred as single cells. Cytochemical studies indicated that some cells produce PAS positive granules that were not removed after treatment of the cultures with diastase. Eleven cell clones were isolated from the mass culture. The growth rates of the clones are different as well as the period of time in which the clones can be propagated in vitro.

Animals↗
PubMed1978

Long-term organ culture of adult rat colon.

Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants that remained viable, there was an initial phase of degeneration of the surface and crypt cells, later these areas were repopulated in one week, showing well-formed crypts, goblet cells, and ultrastructural features such as extensive lateral interdigitations, microvilli and glycocalyx--typical of colon. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial differentiation with well-formed crypts up to 13 weeks.

Animals↗
PubMed1978

Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polynuclear aromatic hydrocarbons.

Cultured human bronchial explants activated benzo[alpha]pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-7,8-dihydrobenzo[a]pyrene], was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor the 7,8-diol increased the mutation frequency in V-79 cells when they were cultured without bronchial explants. The mutation frequency was directly related to the binding levels of BzaP to bronchial DNA and the concentratin of either BzaP or the 7,8-diol in the medium.

Adenosine Triphosphatases↗
PubMed1978

Glomangioma of the lung.

An unusual pulmonary tumor was identified on the basis of light and electron microscopic findings as glomangioma. The ultrastructural findings of intracytoplasmic fibrils with dense bodies, electron-dense plaques, pinocytotic vesicles, and basement membranes are consistent with smooth muscle origin. The differential diagnosis between our tumor and other unusual tumors is discussed. The occurrence of a glomangioma in the lung may indicate the existence of pulmonary glomera.

Aged↗
PubMed1978

The respiratory epithelium. V. Histogenesis of lung carcinomas in the human.

One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer.

Adenocarcinoma↗
PubMed1978

Studies of the ischemic pancreas in shock.

Exocrine pancreatic tissue from 65 male Sprague-Dawley rats was studied by light and electron microscopy to determine if acute lethal and sublethal alterations seen in the human exocrine pancreas following shock could be duplicated in an animal model. Two models were used: one in which 50% of the blood was withdrawn via cardiac puncture with no reinfusion and another in which the animal was subjected to a hypovolemic episode (40 mm Hg) for 60 minutes, with reinfusion of the blood. Animals were killed at various intervals, and pancreatic tissue was sampled for morphological study. No differences were seen between experimental and control animals by light microscopy. The main subcellular alteration seen using these models was the formation of numerous autophagic vacuoles. From these studies it appears that the alterations seen in the human pancreas in shock can be duplicated in the rat and that a shock model that involves removal of more than 50% of the animal's blood volume is necessary to cause irreversible cell damage to the exocrine pancreas.

Animals↗