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Biomedical subjects

J L Ericsson

Publications and source records attributed to J L Ericsson.

At least 73 records · Page 4Linked to original sources

Cytoplasmic effects of X-irradiation on cultured cells in a nondividing stage. 3. Alterations in plasma membrane motility.

Cultured, density-dependent growth inhibited human glia cells were exposed to X-radiation, generated by an 8-MeV linear accelerator, at a dose of 200 Gy. Phase contrast microscopy, time-lapse cinemicrography and scanning electron microscopy showed the irradiated cells to have increased ruffling activity of plasma membranes and enhanced macropinocytosis with a maximum approximately 24 hours after irradiation. "Atypical" central ruffles arising from the upper cell surface were demonstrated on some irradiated cells. The turnover of plasma membranes was supposed to be increased in the irradiated cells resulting in the formation of the observed branched, thread-like cells. The diminished cell surface area was believed to result from an unbalance between degradation and renewal of the plasma membranes in the irradiated cells.

Cell Line↗

Giant cell tumor of bone: fine structural localization of acid phosphatase.

The fine structural localization of acid phosphatase in the different cells in a benign giant cell tumor of bone has been studied. Stromal cells type 1 and 2 (fibroblast-like and macrophage-like, respectively) showed the presence of lead phosphate precipitate following incubation in a Gomori-type lead salt medium only in conventional lysosomes. In the multinucleated giant cells, the final product was deposited over lysosome-like organelles, and also over Golgi cisternae, vesicles, and vacuoles. Furthermore, evidence for presence of acid phosphatase was obtained in smooth-surfaced tubular, sausage-, horse-shoe-, and ring-shaped structures and over digestive vacuoles of autophagic or heterophagic origin. Finally, in these cells, many of the tubular and vacuolar elements located subjacent to areas of the plasma membrane with microvillous specializations (abortive brush borders?) were shown to carry acid phosphatase.

Acid Phosphatase↗

Cytoplasmic effects of X-irradiation on cultured cells 2. Alterations in lysosomes, plasma membrane, Golgi apparatus, and related structures.

Topoinhibited human glia cells in vitro were exposed to X-radiation generated by an 8-MeV linear accelerator at a dose of 20,000 rad. Transmission electron microscopy of irradiated cells at intervals varying between 30 min. and 5 days following irradiation revealed alterations mainly in the plasma membrane and the lysosomal vacuome. Increased ruffling of plasma membranes, augmented endocytosis and extensive intracellular autophagy developed within 24 hours after irradiation. The implications of the plasma membrane alterations are discussed, and a tentative model covering possible mechanism involved in the development of autophagic vacuoles is presented. The possibility is entertained that alternative mechanism may be operative during the formation of the autophagic vacuole in irradiated glia cells. The origin of the isolation membrane appears to be (a) preexisting lysosomes; and (b) flattened vacuolar cytoplasmic elements.

Cell Membrane↗

Cytoplasmic effects of x-irradiation on cultured cells in a nondividing stage. 1. Establishment of an experimental model.

The investigation was initiated with the aim of establishing a suitable experimental model with respect to mode of radiation and radiation dose for elucidating morphologically the sequential development of radiation induced damage of interphase cells (human glia cells in vitro). Adequately defined and reproducible cellular changes were obtained using X-radiation generated by an 8 MeV linear accelerator at a dose of 20,000 rad. The cellular alterations were studied in the light microscope and by scanning and transmission electron microscopy. The most conspicuous changes--first appreciable about 5 hours after irradiation--occurred in the lysosomal vacuome, and the plasma membrane and associated structures.

Cell Line↗

The osteoclast: review of ultrastructure, origin, and structure-function relationship.

Multinucleated cells of the giant cell tumor and the genuine osteoclasts exhibit a number of common morphological characteristics and may or may not originate from similar progenitor cells. Judging from the present preliminary results, it is obvious that the differentiation of the plasma membrane into a specialized area, the ruffled border, is not as conspicuous in the giant cell as in the osteoclast. A series of interrelated investigations including histochemical methods at the ultrastructural level applied both in giant cell tissue and cultured giant tumor cells are in progress. These studies may further elucidate the possible relationship between the osteoclast and the multinucleated giant cell tumor as well as the possible relationships between giant cells and other cell types of tumors.

Animals↗

Studies on the synthesis and intracellular transport of lipoprotein particles in rat liver.

Lipoprotein particles (d less than 1.03 g/ml) were isolated from rough and smooth microsomes and from the Golgi apparatus of rat liver, and were characterized chemically and morphologically. The rough endoplasmic reticulum (ER) particles were rich in protein (50%) and contained phospholipids (PLP) and triglycerides (TG) in smaller amounts, whereas the lipoprotein particles emanating from the smooth ER, and especially the Golgi apparatus, were rich in TG and PLP, resembling very low density lipoproteins (VLDL) of serum. The difference in chemical composition among the particles was associated with change in size both in situ and in isolated lipoprotein fractions. The rough ER particles were 200-800 A in diameter (mean similar to 420 A); the smooth er particles 200-900 A (mean similar to 520 A); the Golgi particles 350-950 A (mean similar to 580A); and serum VLDL 300-800 A (mean similar to 450 A). Generally, lipoprotein particles were rare in the rough ER, frequent but diffusely dispersed in smooth ER, and occurring mainly in clusters in "secretory vesicles" of the Golgi complex. They were seldom observed in the cisternal compartments of the Golgi complex. At short intervals (less than 15 min), intravenously injected radioactive glycerol was preferentially channelled into TG, whereas at later time points the majority of the isotope was recovered in the PLP. Three TG pools were distinguished: (a) a cytoplasmic pool with a slow turnover rate; (b) a membrane-associated TG pool; and (c) a pool corresponding to the TG moiety of lipoprotein particles, which showed the highest initial rate of labeling and fastest turnover. When, after pulse labeling, the appearance of incorporation of radioactive glycerol into TG or PLP of isolated lipoproteins was followed from one subcellular fraction to the other, a sequence of labeling was noted. During the first interval, TG from both rough and smooth microsomal lipoproteins displayed a high rate of labeling with peak value at 6 min, followed by a quick fall-off, while the Golgi lipoproteins reached maximal level at 10-20 min after administration. There was an interval of 10-15 min before the appearance of labeled VLDL in serum. It is concluded that the assembly of the apoproteins and lipid moieties into lipoprotein particles-presumed to be precursors of liver VLDL-begins in the rough ER and continues in the smooth ER. Also, there is a parallel change in chemical composition and size of the lipoprotein particles as they make their way through the ER and the Golgi apparatus. Some remodeling of the particles may take place in the Golgi apparatus before discharge into the circulation.

Animals↗

Isolation of liver lysosomes by iron loading. Ultrastructural characterization.

In summary, the data demonstrate that, by the use of repeated injections of an iron sorbitol complex, it is possible to isolate a fraction highly enriched in hydrolytic enzymes (60 times over the homogenate) and in well preserved lysosomes emanating almost entirely from liver parenchymal cells. The advantage of adding fixative to the bottom of the gradient and of using en bloc staining with uranyl acetate is also demonstrated.

Animals↗

Lysosomal degradation of cell organelles. I. Ultrastructural analysis of uptake and digestion of intravenously injected mitochondria by Kupffer cells.

An experimental model comparable to autophagocytosis is presented to evaluate lysosomal degradation of biologic membranes in vivo. This design takes advantage of the efficient phagocytic capacity of Kupffer cells. For this purpose, mitochondria were isolated from one rat liver (inbred strain) and subsequently injected intravenously into a series of rats, which were sacrificed at various time points. The uptake and intralysosomal digestion were examined by electron microscopy. Mitochondria were seen in the sinusoids and attached to the surface of Kupffer cells 1 to 3 minutes after injection. One or two mitochondrial profiles were trapped in cavelike structures often embraced by long hyaloplasmic pseudopods. By 5 and 10 minutes, the mitochondria were in single membrane-bound phagosomes within the Kupffer cells and early signs of mitochondrial alterations were present, e.g., loss of cristae and condensation. At 30 minutes and 1 hour the mitochondria were seen in large vacuoles which contained up to 20 profiles in a single section. The mitochondria showed evident signs of digestion such as membrane fragmentation and flocculent densities. By 4 hours and especially by 8 hours, most digestive vacuoles were laden with flocculent membrane debris. By 24 hours, the Kupffer cells showed multiple lysosomal structures which were irregular in shape and small. These often contained a number of lipid-like droplets of various electron densities and pentalaminar structures. By 2 and 5 days, the Kupffer cells had returned to their normal appearance although the lysosomal apparatus was still prominent. No uptake of mitochondria was seen in endothelial cells, fat-storing cells, or hepatocytes. It is concluded that lysosomes have an efficient capacity to digest mitochondria. Some lipid remnants are not completely or slowly degraded by Kupffer cell lysosomes but remain in "residual bodies" for up to 1 or 2 days.

Animals↗

Lysosomal degradation of cell organelles. II. Ultrastructural analysis of uptake and digestion of intravenously injected microsomes and ribosomes by Kupffer cells.

Rough and smooth microsomes, "mixed" or total microsomes, and ribosomes were isolated from one single rat liver and subsequently injected intravenously into a series of inbred rats. The uptake and the degradation of the injected organelles by Kupffer cells were followed by means of electron microscopic analysis. By 1 minute after injection, microsomes were seen attached to the surface of Kupffer cells separated by a gap of 200 to 300 A. No attachment to hepatocytes, fat-storing cells, or endothelial cells was seen. By 5 and 10 minutes, most microsomes were phagocytosed and sequestered in large numbers within single membrane-enclosed vacuoles or phagosomes. The engulfment proceeded by two mechanisms: (1) most frequently, flaplike processes of cytoplasm embraced aggregates of microsomes, concomitant with the formation of indention of the cytoplasm; (2) occasionally, single microsomal profiles were taken up by bristle-coated endocytic vacuoles. Ribosomes were also seen penetrating into the wormlike structures (micropinocytosis vermiformis) at the cell surface. At 30 minutes after injection, clear signs of alteration were noted starting with vesicle aggregation, clumping, and elongation of the microsomal profiles. The ribosomes were quickly stripped from their microsomal membranes and marginated to the inside of the vacuoles but separated from the limiting membrane by a distance of 200 to 300 A. By 1 and 2 hours, disruption of the vesicles into membrane fragments and formation of dense material in and between the profiles occurred. By 8 hours it was difficult to recognize the degradation products as membrane derivatives. The digestive vacuoles retained their size at this time interval. Typical pentalaminar structures were observed. By 14 to 24 hours the digestive vacuoles became electron lucent and appeared to shrink, and in addition to containing various types of granular material, many were laden with lipid-like droplets presumed to be conglomerates of phospholipid remnants. Rough microsomes, when compared to smooth microsomes, gave rise to more granular material within the digestive vacuoles. Ribosomes were still identifiable 24 hours after injection, indicative of a somewhat slower rate of degradation. Accumulation of various types of lipid-like droplets in the "residual bodies" was typical after microsomal injections. It is concluded that although microsomes appear to be phagocytosed at a quicker rate than mitochondria, they are digested within the lysosomal apparatus of the Kupffer cells at a somewhat slower rate. This especially seems to be the case for ribosomes. Heterophagy of microsomes is one source of residual bodies.

Animals↗