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W J Mergner

Publications and source records attributed to W J Mergner.

At least 55 records · Page 3Linked to original sources
PubMed1977

Studies on the pathogenesis of ischemic cell injury. VII. Proton gradient and respiration of renal tissue cubes, renal mitochondrial and submitochondrial particles following ischemic cell injury.

Electron transport in tissue cubes, isolated mitochondria and submitochondria particles were examined as a function of ischemic time. It was found that electron transport remains active in all systems beyond the 2 hour ischemic time interval. The NADH stimulated respiration, however, declined after 2 hours of ischemia in ASU (Ammonia-Sephadex-Urea) particles followed by respiration with matrix-located dehydrogenases tested by substrates such as glutamate, alpha-ketoglutarate and pyruvate plus malate. Succinate dependent respiration remains active at control levels. In contrast proton gradient reveals changes in two phases: Phase A is characterized by gradually increasing gradient without valinomycin and by a rapidly declining gradient with valinomycin in the medium. Phase B is characterized by a declining proton gradient with or without valinomycin. It is suggested that the alteration of the proton gradient between 1 and 2 hours ischemia is an important factor contributing to irreversible cell injury.

Animals↗
PubMed1976

Studies on the pathogenesis of ischemic cell injury. V. Morphologic changes of the pars convoluta (P1 and P2) of the proximal tubule of rat kidney made ischemic in vitro.

In summary, we have described the time course of changes of mitochondria following ischemia of the kidney proximal tubule. The sequence of morphological changes of matrix as well as inner membrane corresponds well with certain functional or physical parameters such as swelling, respiration, substrate metabolism, acceptor control and P/O ratio. This indicates that morphological parameters can be utilized to predict the functional alterations of mitochondria following ischemia in cells. The significant mitochondrial changes are early loss of granules (15-30 min) and condensation (15 min), swelling (30 min), appearance of fluffy densities (30 min) and flocculent densities (after 60 min), degeneration of cristal structure (240 min) and disintegration of mitochondria as structural units (24 h).

Animals↗
PubMed1976

Recent studies on the pathophysiology of ischemic cell injury.

We can summarize the results of our studies as follows (Fig. 15). The critical cellular factors involved in the loss of reversibility following ischemia appear to be the mechanisms involved in the membrane function of energy transduction. Irreversibility appears to correlate with an irrepairable defect in energy transduction. This could involve both the mitochondrial energy transduction functions and those in the plasma membrane. The mechanisms involved in this transition are not presently clear but they are associated with increased leakiness or permeability of these membranes accompanied by changes in lipid content, alterations in membrane proteins, and presumably in lipid-protein interactions. There are two prominent theories to explain energy transduction. These are the "proton pump" hypothesis of Mitchell (1972) and the "paired moving charge" hypothesis of Blondin and Green (1975). Both of these hypotheses require integrated function of membrane components, i.e., lipid and protein. The hypothesis of Blondin and Green, however, can work even with discontinuous membrane sheets because it involves the concept of ribbons of protein embedded in the protein-lipid membrane matrix. The characteristic finding of our studies following ischemic injury, namely, the continuous electron flow well into the irreversible phase while the energy transduction is impaired, could be explained by both hypotheses. What do these observations have to say about theories of energy conservation? We have observed that the vectorial nature of the proton separation is stopped. Charge separation may not occur at this time across the membrane since proton gradient and possible membrane potential are abolished. Electron transport, however, continues indicating the generation of protons. Since the decline of P/O ratio, decline of proton gradient and the cellular "point-of-no-return" coincide, these observations point toward the important membrane defects acquired at that particular time. The "paired moving charge" model which involves moving ions encapsulated in endogenous ionophores such as lecithin and maintenance of magnesium is favpred by the observation that phosphatidyl choline and phosphatidyl ethanolamine are lost in correlation with irreversibility. Furthermore, the decrease in magnesium content of cells is closely associated with the loss of viability following ischemia. The "paired moving charge" hypothesis has the attractive feature in that it involves antagonistic effects of calcium and magnesium. During reflow, calcium may inhibit magnesium mediated transport of inorganic phosphate by lecithin. Also, according to this theory fatty acids or their cyclic anions which act as uncouplers may foster the loss of phosphorylation capacity.

Animals↗
PubMed1976

Aging changes in the human aortic valve in relation to dystrophic calcification.

To elucidate the pathogenesis of aging changes and their relation to age associated calcification, a morphological study of 27 human aortic valves was carried out. Nine valves were obtained from immediate autopsies and 18 valves from routine autopsies done within four hours after death. Calcium deposition was present deep in the zona fibrosa along a zone of lipid accumulation. Fibrocytes in the zona fibrosa showed predominant age associated changes, i.e., a massive accumulation of residual bodies in the cytoplasm probably derived from autophagic vacuoles. Light microscopic lipid accumulation corresponded with both intracellular accumulation of electron dense spherules and membranous vesicles derived from degenerate fibrocytes. Calcium deposition in various stages, including needle shaped hydroxyapatite crystals, was seen in close association with these cellular degradation products rather than collagen or elastic fibers. Dystrophic calcification in the aortic valve appears to result from cellular aging and death followed by petrification of cellular degradation products, which may progress to calcific aortic stenosis.

Adolescent↗
PubMed1976

Studies on the subcellular pathophysiology of ischemia.

The loss of ability to synthesize adenosine triphosphate (ATP) by mitochondria in ischemic cells even in a favorable medium correlates with the loss of cell viability. The early lesion at the molecular level needs further investigation but appears to involve an increased permeability of the mitochondrial membrane possibly promoting proton leak and obviating oxidative phosphorylation. The nature of this leak could involve changes in phospholipid-protein interactions, especially since the early release of free fatty acids and changes in phospholipid composition occur.

Adenosine Triphosphate↗
PubMed1976

GM3 gangliosidosis: a novel human sphingolipodystrophy.

A male infant of nonconsanguinous Jewish parents had clinical features of pseudo-Hurler's syndrome. A maternal uncle with similar features had previously died at 21/2 months of age. Following death at 3 1/2 months of age, analysis of the patient's brain and liver revealed increased amounts of ganglioside GM3, a virtual absence of higher ganglioside homologues (GM3, GM1, GD1a, and GT1) and a deficiency of the biosynthetic enzyme, UDP-Gal NAc:GM3 N-acetylgalactosaminyl-transferase. Since the biochemical findings denote a novel state of ganglioside deficiency, clinical findings emphasizing points of distinction from other causes of pseudo-Hurler's syndrome are presented.

Brain↗
PubMed1975

The application of electron microscopy and cellular biochemistry to the autopsy. Observations on cellular changes in human shock.

A method based on the utilization of electron microscopy, morphometric analysis, tissue culture, and biochemical analysis in the study of human autopsies is described. In this method rapid sampling immediately following somatic death is conducted in order to make meaningful the application of such techniques. In addition to describing the procedure, we present some new findings relating to cellular changes associated with shock. As in cellular pathobiology, it is of utmost importance that ultrastructural changes be correlated with alterations in chemistry and function.

Adolescent↗
PubMed1975

Effects of shock on the pancreatic acinar cell. Cellular and subcellular effects in humans.

Pancreatic tissues from 22 patients with a wide variety of types of shock were obtained within minutes of somatic death for light and electron microscopy and for cytochemical studies. By light microscopy, it was difficult to ascertain any differences between the shock groups; however, electron microscopy disclosed subcellular alterations that could be correlated well with the type, severity, and duration of shock. Mild cases of shock or shock of short duration showed mild cell damage, while extreme cases of hemorrhagic or septic shock showed cell death and necrosis. No morphological evidence for lysosomal initiation of damage was seen, but it is clear that the pancreas can undergo severe cell injury during shock that could result in release of further damaging enzymes, most probably from zymogen granules rather than from lysosomes.

Adolescent↗
PubMedDate not supplied

A method for the determination of therapeutic and toxic concentrations of tricyclic antidepressant drugs in post mortem fluids and tissues.

A sensitive and reliable procedure is presented for the measurement of the common tricyclic antidepressant (TCA) drugs in a variety of biological specimens at therapeutic as well as toxic concentrations. The method employs GC/NPD and a column packed with 3% OV-17 on Chromosorb W-HP. The pH of specimen extraction was optimized at 8.6, and 1-chlorobutane:ethyl ether (3:1) was found to be an efficient solvent for the primary extraction. Recoveries for all TCA drugs were at least 50% for each specimen. Linearity of extraction was observed over a range of therapeutic and toxic concentrations with a correlation coefficient greater than 0.99.

Antidepressive Agents, Tricyclic↗