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Biomedical subjects

W J Mergner

Publications and source records attributed to W J Mergner.

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

Vascular reactivity during the progression of atherosclerotic plaque. A study in Watanabe heritable hyperlipidemic rabbits.

The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3-5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium-dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium-mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells.

Animals↗
PubMed1989

ATP hydrolysis by ischemic mitochondria.

Cellular ATP levels are determined by the rates of ATP production and ATP hydrolysis. Both phenomena are affected by ischemia. Mitochondrial enzymes are damaged, inhibiting this organelle's ability to make ATP. Mitochondria are also uncoupled by ischemia and have the ability to hydrolyze ATP. We designed a series of experiments to determine whether decreased production or increased hydrolysis of ATP was the primary effect of mitochondrial damage. Rat hearts were subjected to 45 min of warm ischemia in order to induce irreversible cell damage. ATP or ADP was injected into cuvettes containing mitochondria isolated from normal myocardium or myocardium damaged by ischemia. Luciferin-luciferase, which fluoresces in the presence of ATP, was also added to the tubes as an indicator of ATP levels. Mixtures of uncoupled and coupled mitochondria were made and compared with the mitochondria damaged by ischemia. The results showed that mitochondria damaged by prolonged ischemia hydrolyze ATP more rapidly than normal mitochondria; however, normal mitochondria can easily compensate for increased ATP hydrolysis when in mixture with equal amounts of uncoupled mitochondria. These data suggests that the low cellular levels of ATP following irreversible ischemia are primarily due to decreased ATP synthesis and not to increased hydrolysis.

Adenosine Triphosphate↗
PubMed1989

The role of the lymphatics in aiding regression of hypokalemic lesions in rat cardiac muscle.

This study describes the role of lymphatics in the removal of macrophages from inflammatory lesions in the heart of hypokalemic rats and rats recovering from hypokalemia. The inflammatory lesions are characterized by focal cardiomyocyte necrosis, edema, and mononuclear infiltrate. The vascular and lymphatic capillaries are maintained along with the basement membrane of the necrotic cardiomyocyte. Through prior investigation, it was revealed that refeeding potassium led to a rapid reduction in lesion area. The purpose of the current investigation was to establish the role of the lymphatics as a means of reducing the lesion area by removal of the cellular infiltrate and edema. Using a limited potassium diet, hypokalemic rats were sacrificed via perfusion fixation during the hypokalemic and the potassium re-supplementation periods. Heart tissue was examined by light and electron microscopy. During the hypokalemic period, phagocytic mononuclear cells were found engulfing necrotic cardiac muscle cells. With refeeding of potassium, these phagocytic cells appeared to be diminished in number, a reduction that coincided with a decrease in the lesion size. Lymphatic channels were dilated and full of mononuclear cells. These channels were differentiated from the vascular capillaries by standard morphological criteria. In conclusion, the lymphatics play an important role in the healing process by reducing the lesion size through the removal of phagocytic cells and the uptake of proteinaceous material.

Animals↗
PubMed1988

The effect of arterial pressure alterations during halothane anesthesia on residual flow and infarct size with transient regional ischemia of the dog.

The present study was designed to determine if infarct size under halothane anesthesia could be reduced by increasing the pressure gradient across the collateral vascular bed, thereby increasing flow within the occluded vascular bed. Forty-nine mongrel dogs were anesthetized with halothane under identical physiologic conditions with the exception of systemic arterial blood pressure. The control group of 18 animals anesthetized with halothane was compared to two experimental groups. In one group of 15 dogs, the mean systemic pressure was raised 25% above control with phenylephrine (BP25). In the second group of 15 dogs, systemic pressure was raised 50% above control (BP50). Adjacent marginal branches of the left circumflex coronary artery were ligated for 90 minutes followed by 90 minutes of reflow. The area of the occluded vascular bed was similar in all groups, but the area of infarction as a percentage of the occluded vascular bed was reduced from 47.7 +/- 4.7% to 25.4 +/- 4.3% in the BP25 group (P < or = .05 v control) and to 33.1 +/- 5.0% in the BP50 group. Flow measurements using microspheres showed a larger zone of ischemic tissue receiving adequate residual flow in the BP25 and BP50 groups compared to the control. It is concluded that infarct size during halothane anesthesia in the dog can be reduced by increasing systemic blood pressure with phenylephrine.

Analysis of Variance↗
PubMed1986

Immature renal tissue in colonic wall of patient with caudal regression syndrome.

We report an incidental microscopic finding of ectopic renal tissue in a newborn with multiple congenital anomalies. The ectopic renal tissue was located in the wall of the distal blind end of the colon. The tissue was composed of undifferentiated renal blastema with primitive and well-formed glomeruli and tubules. The potential for malignant transformation of this lesion into extrarenal Wilms' tumor is not known.

Abnormalities, Multiple↗
PubMed1985

Anesthetics influence myocardial infarct size.

This study compares the effect of three anesthetics on infarct size and regional myocardial blood flow. The anesthetics--fentanyl, Na-pentobarbital, and halothane--differ in their effects on such hemodynamic parameters as blood pressure and heart rate. The mean blood pressure during ligation was 144/91 mm Hg with fentanyl, 141/104 mm Hg with Na-pentobarbital, and 113/82 mm Hg with halothane. The heart rate was 98, 146, and 135 beats/min, respectively. The most significant finding of our study following 90 min of reflow was the infarct size of 26 +/- 8% of the occluded vascular bed under the influence of fentanyl; infarct size under Na-pentobarbital and halothane was 32 +/- 5 and 47 +/- 7%, respectively. The regional flow in relation to the zones of the infarction also differed among the groups. Regional flow under Na-pentobarbital was 24 +/- 6% of normal flow at 90 min of occlusion in the infarcted tissue; regional flow under fentanyl and halothane was 9 +/- 2 and 5 +/- 1%, respectively. The flow in the nitroblue-tetrazolium-staining zone of the occluded vascular bed was 69 +/- 11% (fentanyl), 77 +/- 11% (Na-pentobarbital), and 83 +/- 25% (halothane). It is concluded that anesthetics may well influence infarct size and the outcome of a myocardial infarction following a 90-min ischemia. Hemodynamic effects induced by these anesthetics may well be responsible for this outcome and could be determinants of infarct size, possibly by influencing collateral flow.

Anesthetics↗
PubMed1981

Pathologists' assistant training programs: a report.

This report describes the training of pathologists' assistants in three training programs: at Duke University, at Quinnipiac College associated with Yale University, and at the University of Maryland School of Medicine. The role of this new health profession is described as well as the job situation, experience, and current status of accreditation.

Accreditation↗
PubMed1980

A rapid method of cryofixation of tissues in situ for ultracryomicrotomy.

A device is described for the rapid freezing of tissue in situ by a punch biopsy approach using a specially designed cryogun with a highly thermal conductive specimen holder. The cryogun consists of a sampling device using a double, spring-loaded gun mechanism and a system of cryochambers. Ultrathin freeze-dried sections cut from samples obtained with this cryogun are relatively free of artifacts and have few ice crystals. Organelles are seen by natural contrast when cryosections of approximately 1000 A are observed with a transmission electron microscope or in the transmission mode of a scanning electron microscope. The construction of the cryogun is described along with a method of obtaining improved, ultrafast cryofixation of tissue specimens. The reliability of obtaining x-ray microanalysis measurements of diffusible ions where movement within cell compartments has been retained is discussed.

Basement Membrane↗
PubMed1980

To answer questions. A review of an autopsy service.

Autopsies are important in the quality control of medical practice, in research, and in teaching. We have attempted to realize more of the service, teaching, and research potential from doing autopsies. The key of all efforts is the involvement of the senior staff. This involvement should be made possible by supporting such a person by a qualified team that consists of the mortuary service, pathologist's assistants, and highly trained and qualified residents. Such a staff person can direct his or her attention toward improving communication with clinicians, answering open questions in-depth, encouraging collaborative clinicopathological projects, developing new approaches to the performance of autopsies, such as the immediate autopsy, and using special laboratory modalities, such as electron microscopy and immunofluorescence. Computer storage of autopsy data and retrieval for special studies seem to make autopsy data available and usable. It is most important that autopsies be performed, that they be done well, and that their findings be carefully evaluated using all available scientific tools and, finally, that the results are adequately communicated.

Autopsy↗
PubMed1980

The role of calcium in cell injury. A review.

The role of calcium in cell injury is currently under investigation in many laboratories. It appears that movement of calcium between extra- to intracellular compartments and between various intracellular compartments plays a key role in determining many important reactions of cells both to lethal and sublethal injuries of diverse types as well as in adaptive new steady states. Prevention and/or modification of calcium movements has implication for the control of cell population growth, the prevention of cancer, and the retrieval of victims of shock, myocardial infarction and stroke. Regardless of what type of initial injury occurs, for example ischemia or direct cell membrane damage, the cell undergoes calcium accumulation either by impaired energy metabolism and/or plasmalemmal alterations. This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification. Although such changes have been partially characterized biochemically and morphologically, some obscure points continue to need clarification. The importance of determing the event(s) responsible for cell death is directly related to the potential capability of their manipulation. Therefore, this could result in the development and/or modification of pharmacologic interventions for the control and prevention of many human diseases. It is the purpose of this paper to review the present state of the art regarding the role of calcium in cell injury, to put it into perspective concerning organelle changes from the standpoint of morphology, and to indicate the present and future role of analytical microscopy in furthering the understanding of these processes.

Animals↗
PubMed1979

Long-term culture of human aortas. Development of atherosclerotic-like plaques in serum-supplemented medium.

Segments of human thoracic aorta were maintained in long-term explant culture for 18 weeks in serum-supplemented medium. The aortas were grossly normal in appearance, and random samples fixed for light microscopy prior to culture revealed a normal morphology. The intima contained no more than five layers of smooth muscle cells. After 7 days in culture, the intima was noticeably thicker than the uncultured segments. The increased thickness was due to proliferating smooth muscle cells and production of extracellular material. After several months in culture, extracellular material consisting of collagen and flocculent material was present in areas resembling atherosclerotic fibrous plaques. A peripheral growth, which formed around the explant, was composed of fibroblastlike cells and added to the overall thickness of the intima. However, aortic segment maintained for up to 2 months in serum-free culture medium showed no cellular proliferation. This study demonstrates that changes resembling early stages of atherosclerosis occur in human aortas maintained in explant culture using routine culture procedures.

Adolescent↗
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↗
PubMed1978

The use and application of autopsy in research.

The only limit to the use and application of the autopsy in research is the imagination of the investigator. As pathologists, it would appear that we have really neglected this powerful tool in recent decades and have undersold the potentiality of this method. As we hope to have made evident by the foregoing discussion, the field of research utilizing autopsy tissues is truly as broad as medicine itself, and if developed properly, becomes an indispensable part of the fabric of on-going research in areas of carcinogenesis, environmental disease, atherosclerosis, and aging.

Animals↗
PubMed1978

Energy dispersive x-ray microanalysis of mitochondrial deposits in sideroblastic anemia.

Energy dispersive x-ray microanalysis was used to analyze mitochondrial and lysosomal iron-containing deposits in sideroblastic anemia. Although it has been previously known that these deposits contain iron by inference from Prussian blue staining, the possible presence of other cations as well as the nature of the anions present has not been identified. The results show that the mitochondrial deposits in erythroid cells have peaks for iron and phosphorus indicating that they do not represent calcifications which commonly occur following injury and that the principal anion may be phosphorus. Studies of hemosiderin and ferritin aggregates in lysosomes of macrophages in the same bone marrow samples again reveal similar peaks for iron and phosphorus. The results also indicate the probable similarity of mitochondrial and macrophage deposists although ferritin itself was never identified in the mitochondrial deposits. The results illustrate the potential of this method for diagnostic and investigative pathology.

Aged↗
PubMed1977

Studies on the pathogenesis of ischemic cell injury. XI. P/O ratio and acceptor control.

Acceptor control index, P/O ratio and inner membrane permeability were examined in isolated mitochondria following periods of renal ischemia for 15, 30, 60, 120, and 240 min. It was noted that the P/O ratio remained unchanged until 1-2 h after the onset of ischemia. A similar change was noted in the contraction rate of isolated ischemic mitochondria after swelling in KCl and addition of ATP+Mg2+. Both changes are probably indications of a basic membrane alteration which correlates with the occurrence of irreversibility of cell injury. In contrast, the swelling rate in KCl and the acceptor control index are altered almost simultaneously with the onset of ischemia. Therefore, acceptor control index and the rate of swelling are affected prior to the point of irreversible cell injury. They are not, therefore, good as indicators of irreversible changes in the inner membrane of mitochondria leading to the "point-of-no-return."

Animals↗
PubMed1977

Studies on the pathogenesis of ischemic cell injury. VI. Accumulation of calcium by isolated mitochondria of ischemic rat kidney cortex.

Mitochondria isolated from rat kidney subject to in vitro ischemia at various time intervals demonstrated a continuous decline of the ability to accumulate calcium following a high initial stable phase of accumulation of calcium which is dependent both on ATP and respiration. This decline occurs during the reversible phase of cell injury and appears to be a sensitive indicator of membrane changes in a binding and/or transport protein or of other membrane permeability characteristics. The morphology of mitochondrial densities related to calcium accumulation in mitochondria varied. Any form of calcium accumulation, resulted in marked swelling of mitochondria. Control renal mitochondria in sucrose were highly condensed. Partially inhibited calcium accumulation in the presence of phosphate was also associated with numerous small spheric or punctate deposits in close relationship to the inner membrane. Uninhibited calcium accumulation resulted in the formation of needle-like structures radiating from such inner membrane associated sites.

Adenosine Triphosphate↗