Biomedical subjects

J S Mooney

Publications and source records attributed to J S Mooney.

8 recordsLinked to original sources

PubMed1979

Alterations in hepatic pericanalicular cytoplasm during enhanced bile secretory activity.

In an attempt to demonstrate the morphology of the bile secretory apparatus, male rats were restrained and maintained on an isocaloric diet with (experimental) and without (control) taurocholate, which was continuously infused via a duodenal cannula. This method of taurocholate administration promotes a 2-fold increase in the bile acid pool size and bile secretory rate and increases the transport maximum of taurocholate by approximately 50%. After 48 hours, the livers from both the control and experimental animals were perfusion-fixed and whole hepatocytes as well as pericanalicular cytoplasm (defined as a 1-micron. wide zone of cytoplasm adjacent to the bile canaliculus) in both centrolobular and periportal cells were subjected to a stereologic analysis. Although taurocholate infusion produced relatively few changes in the amounts of organelles or inclusionswithin hepatocytes, it caused highly significant increases in the amount ofGolgi-rich area, Golgi membranes, and the number of vesicles with diameters greater than 1000 A in the pericanalicular area of cytoplasm. In addition to these changes, which occurred in both central and periportal zones, decreases in the volume of lysosomes and the surface area of smooth surfaced endoplasmic reticulum were observed. These data provide new evidence that the "bile secretory apparatus" may encompass several hepatocellular components which include the Golgi complex and a vesicular transport system.

Animals↗

PubMed1978

Entry of insulin into human cultured lymphocytes: electron microscope autoradiographic analysis.

Electron microscope autoradiographs were prepared of IM-9 human cultured lymphocytes incubated with iodine-125-labeled insulin. With the use of [125I]insulin and Ilford L-4 emulsion, the technique had a resolution half-distance of approximately 0.085 micrometer. Autoradiographs revealed a time-dependent entry of insulin into the cell interior that was maximal after 30 minutes of incubation. At this time point nearly 40 percent of the [125I]insulin was in the interior of the cell at a distance 1 micrometer or greater from the plasma membrane. Grain distribution and volume density analyses revealed that the intracellular insulin was concentrated in the endoplasmic reticulum and nuclear membrane.

Autoradiography↗

PubMed1978

A quantitative analysis of hepatic ultrastructure in rats during enhanced bile secretion.

The ultrastructural changes in hepatocytes of rats subjected to selective biliary obstruction (SBO), wherein the biliary system draining approximately two-thirds of the liver is obstructed, were evaluated by quantitative electron microscopy or stereology. The remaining unobstructed portion of the organ compensates for this loss of bile secretion by functioning in a hypersecretory mode. This animal model permits the comparison of hepatocellular fine structure associated with the conditions of nonsecretion and hypersecretion of bile with that found in normal secreting sham-operated rats. Since recent evidence suggests the presence of lobular gradients in hepatic structure and function, both centrolobular and periportal hepatocytes were examined. The low incidence of Golgi membrane profiles in high magnification electron micrographs results in a low confidence level of sampling and, thus, necessitates the application of a novel parameter for estimating the amount of Golgi complex, i.e., the Golgi-rich area. For the most part, the lobular variation in hepatic fine structure in the sham-operated animals was similar to that described by Loud ('68). However, the periportal parenchyma contained approximately twice the volume of Golgi-rich area as the centrolobular tissue. The amount of cytoplasmic lipid increased significantly in the SBO unobstructed lobes, although there were few or no changes in the other intracellular organelles or inclusions except those related to the Golgi complex. The volume of Golgi-rich area increased significantly in the centrolobular tissue of the SBO unobstructed (hypersecretory) lobes to the extent that both intralobular zones contained similar amounts of this component. These data suggest that the Golgi complex is a dynamic unit which responds to changes in hepatocellular activity and may be involved in bile secretion.

Animals↗

PubMed1978

Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age.

Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1, 6, 10, 16, 20, 25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume. The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) there are remarkable similarities in hepatocyte ultrastructure between very young and senescent animals, including cell size and the amount of SER.

Aging↗

PubMed1978

A quantitative analysis of fine structure and drug metabolism in livers of clofibrate-treated young adult and retired breeder rats.

The effects of clofibrate on the fine structure and drug-metabolizing capacity of livers of normolipidemic young adult virgin (YA) and hypercholesterolemic retired breeder (RB) male rats were measured by morphometric and biochemical procedures. The oral administration of clofibrate for 7 days significantly increased liver weight and reduced the cholesterol concentrations in the serum and liver tissue in both groups of animals. The hepatic triglyceride (TG) concentration and the volume of cytoplasmic lipid droplets, presumably TG, as well as the serum TG concentration, increased only in the drug-treated RB rats. Clofibrate treatment resulted in significant increases in the volumes of the hepatocytes and their constituent mitochondria and microbodies and caused a proliferation of the smooth-surfaced endoplasmic reticulum. Although the magnitude of the hypocholesterolemic response was considerably greater in the RB animals, the morphological changes were much more marked in the YA group. However, the surface area of the rough-surfaced endoplasmic reticulum was reduced in the livers of the drug-treated RB rats. NADPH cytochrome c reductase specific activity was significantly increased in both the RB and YA animals, but the concentration of cytochrome P-450 (per mg microsomal protein) increased only in the YA rats. Neither the cytochrome b5 concentration nor the rate of ethylmorphine N-demethylation was significantly affected by clofibrate administration. The results suggest that there is no positive correlation between the hypocholesterolemic response to clofibrate and the degree of subcellular changes in the hepatocytes and that this hypolipidemic drug elicits a minimal effect on the concentrations of the components of the hepatic microsomal drug-metabolizing system.

Aging↗

PubMed1977

Age-related changes in the hepatic endoplasmic reticulum: a quantitative analysis.

Morphometric analysis demonstrated a twofold increase in the surface area of the hepatic endoplasmic reticulum in Fischer 344 rats between 1 and 20 months of age, followed by a significant decrease in this parameter between 20 and 30 months. These changes are attributed to the smooth-surfaced endoplasmic reticulum, since neither the rough-surfaced variety nor the Golgi membranes underwent any significant change in surface area as a function of the age of the animal.

Aging↗

PubMed1976

The antibacterial effect of the bladder surface: an electron microscopic study.

To explore an intrinsic bladder defense mechanism we examined interaction between Escherichia coli and bacterial size particles (polystyrene latex balls) and the vesical luminal surface by scanning and transmission electron microscopy. The bacteria and the latex spheres were held in folds of the cellular luminal surface. Voiding (bladder contraction) resulted in the entrapment of a large number of bacteria and particles by these microplicae, with their apparent engulfment in vesicles below the cell surface. Some urine was probably contained in the folds and vesicles, thus reducing the volume of residual urine in the bladder. Since leukocytes were rarely seen in the model studied they presumably do not play an immediate role against acute infection in the normal bladder. These observations indicate that fixation of bacteria to the mucosa is 1 step in the mechanism whereby the normally functioning bladder resists infection.

Animals↗

PubMed1976

Morphometric analysis of rat hepatocytes after total billary obstruction.

Using light and electron microscopic morphometric techniques, the effects of 48 hr of extrahepatic biliary obstruction on hepatocyte structure were examined in the rat. Liver cells near the portal area were compared to those in the centrilobular regions of the hepatic lobule. Observations on the normal animals confirm earlier evidence of quantitative differences in the surface density of organelles in hepatocytes located within different regions of the lobule. A striking difference in the quantity of the Golgi complex in the two areas of the lobule was noted for the first time, with the portal cells containing a significantly greater quantity of this organelle than centrolobular hepatocytes. After 48 hr of total obstruction, most of the previously reported qualitative changes in the canalicular and pericanalicular regions were confirmed. Morphometric analysis at the light-microscopic level showed an increase in the number of cells and a decrease in cell size in those cells near the portal area were compared to those in the centrolobular regions of the helar level demonstrated a significant decrease in both rough and smooth surfaced endoplasmic reticulum in cells of both zones, a finding in marked contrast to the hypertrophy of smooth endoplasmic reticulum suggested by other investigators on the basis of qualitative assessments. There was also a striking decrease in the amount of the Golgi complex, limited to cells in the portal regions. In addition, in all zones a decrease in the volume density of mitochondria and lysosomes was noted, whereas the volume of microbodies was increased. It is suggested that this loss in total membrane material within the cell may be secondary to the degranulation and decrease in total surface area of rough surfaced endoplasmic reticulum, an organelle thought to be responsible in part for the synthesis of new cellular membranes. These observations suggest that present concepts concerning the pathogenesis of cholestatic liver disease require reappraisal.

Animals↗