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Biomedical subjects

J L Ericsson

Publications and source records attributed to J L Ericsson.

At least 55 records · Page 3Linked to original sources

Degradation of phagocytosed lysosomes by Kupffer cell lysosomes.

Lysosomal membranes are apparently resistant to hydrolytic attack from their own enzymes. Alternatively, degradation occurs but is compensated for by continuous insertion of new membrane components. It may be hypothesized that a mechanism operating exclusively on the luminal side of the lysosomal membrane serves to protect the membrane from being degraded. To evaluate this notion the cytoplasmic side of the lysosomal membrane has been exposed to lysosomal enzymes in vivo. Lysosomes were isolated and subsequently injected into the portal vein of a series of rats. The uptake of the injected organelles by Kupffer cells and their subsequent degradation in lysosomes were monitored by means of electron microscopy. Four minutes after injection lysosomes were seen attached to the surface of the Kupffer cells. After 30 minutes the injected material was present in Kupffer cell phagolysosomes, and signs of degradation of the phagocytosed lysosomes were seen. By 2 hours only a few distinct membranes were left, and by 12 hours the injected lysosomes were no longer recognizable. Instead, the phagolysosomes of Kupffer cells were laden with lipid-like droplets and irregular membranous structures. Acid phosphatase histochemistry and labeling of preexisting Kupffer cell lysosomes with marker particles indicated that the phagosomes engulfing the injected lysosomes acquired hydrolytic enzymes within 30 minutes after their formation. The degradation rate of injected lysosomes was estimated by measuring the decay of radioactivity from a rat liver mitochondrial lysosomal fraction after administration of lysosomes isotopically prelabeled with 14C-leucine and 14C-glycerol. The half-life of the lysosomal membrane proteins varied between 1.5 and 2.0 hours, whereas that of the lipid component was in the range of 2.0 to 3.5 hours. These findings demonstrate that lysosomal membranes are degraded if their outer surface is exposed to lysosomal enzymes. Both the ultrastructural analysis and the isotopic studies indicate that proteins are degraded faster than lipids. Apparently, the cytoplasmic surface of the lysosomes is susceptible to lysosomal hydrolytic attack.

Acid Phosphatase↗

Human osteogenic sarcoma. Study of the ultrastructure, with special notes on the localization of alkaline and acid phosphatase.

The morphology of 26 cases of osteogenic sarcoma was studied using electron microscopic techniques, and the localization of acid and alkaline phosphatase activity at the ultrastructural level elucidated. Four different cells were present in the tumours: osteoblast-like, fibroblast-like, chondroblast-like, and multinucleated giant cells. The osteoblast-like cell was present in most of the tumours studied. Acid phosphatase activity was present in lysosome-like structures of almost all the cell-types studied. Alkaline phosphatase activity was noted in or on the plasma membranes and associated vesicles of osteoblast-like, fibroblast-like, and multinucleated giant cells. The abundant reaction product deposition of alkaline phosphatase as compared with the lower acid phosphatase activity is in agreement with the nature of this bone-forming tumour. The results of the histochemical studies have added to the understanding of the pathobiology of the different cells composing osteogenic sarcomas.

Acid Phosphatase↗

Cytoplasmic effects of X-irradiation on cultured cells in a non-dividing stage. 4. Studies of sparsely grown, serum-deprived cells.

Cultured human glial cells were blocked in interphase (G1) by 24 h of serum starvation and subsequently subjected to 200 Gy, 8 MV X-radiation. Immediately following irradiation the cultures were transferred to serum-containig medium. Time-lapse cinemicrography performed during the next 48 h showed a profoundly disturbed motility with decreased ability for polarization and locomotion of the irradiated cells. Specimens fixed 24 and 48 h after irradiation and investigated by immunofluorescence with tubulin-antibodies and DNase/DNase-antibodies, and by whole cell transmission electron microscopy showed derangements in the distribution of microfilament bundles related to the cytoplasmic ramification of the irradiated cells, but otherwise no detectable alterations in structure or distribution of either microtubules or microfilaments. It is suggested that the alteration in the arrangement of filament bundles is of importance to the impaired locomotion of the irradiated cells.

Cell Movement↗

Studies on the rat liver following iron overload.

Sprague-Dawley rats were given Jectofer injections to obtain iron overload in rat liver Kupffer and parenchymal cells. The release of iron was studied on the light and electron microscopical level by bleeding of the iron loaded animals and comparing the results with non bled controls. During the mobilization of iron. Kupffer cells showed a rapid and almost complete disappearance of electron dense iron containing particles (IP) while there was only limited decline of IPs in the parenchymal cells. Iron was demonstrated with X-ray microanalysis at the ultrastructural level, and presence of acid phosphatase was revealed using a histochemical method based on precipitation of lead phosphate at sites of enzyme activity in combination with X-ray microanalysis. It was demonstrated that all IP-containing cytoplasmic bodies also showed presence of acid phosphatase implying that all of them represented lysosomes. The mechanism of release of iron from Kupffer and parenchymal cells was discussed with special emphasis on the role of the lysosomes and the relationship between their contents and other cellular structures.

Acid Phosphatase↗

Giant cell tumor of bone. Variations in patterns of appearance of different cell types.

Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.

Acid Phosphatase↗

Ultrastructural features of cultured human glia and glioma cells.

The fine structure of three lines of human normal glial cells and eight established lines of malignant glioma cells are described. The glial cell lines were ultrastructurally very similar whereas the glioma cell lines differed greatly from one another. In sparse proliferating cultures there were no consistent findings which distinguished the glioma cell lines as a group from the normal glial cells. Only in post-confluent cultures could the consistently irregular cell surfaces and ruffling, both at the cell periphery and centrally on the upper cell surface, with associated pinocytosis, distinguish the glioma from the post-confluent glial cultures, which did not possess these properties. The common attributes of post-confluent glioma cells reflect the cells' continued proliferation. The glioma lines did display individual ultrastructural characteristics which appear to be stable, the glioma lines having retained these during a number of years of continual passage.

Cell Division↗

Studies on the rat liver following iron overload. Electron probe x-ray microanalysis of acid phosphatase and iron.

Previous electron-microscopic studies on the liver have shown that following excessive administration of iron to experimental animals, small particles believed to represent ferritin and/or hemosiderin (electron-dense iron-containing particles [IPs]) accumulate in membrane-bound bodies--many with a lysosome-like structure--in liver parenchymal and Kupffer cells. Further identification of the IP-containing bodies has been facilitated by the application of histochemical techniques for the demonstration of acid phosphatase. The results have shown that reaction product was deposited over organelles similar in appearance to the IP-containing ones, indicating that they were lysosomes. However, the granular nature of the reaction product makes it difficult or impossible to decide whether IPs are present simultaneously with reaction product in the organelle. In order to clarify this qualitative aspect, x-ray microanalysis has been utilized to identify iron and lead (reaction product) in the various structures thought to represent lysosomes. The results indicate that all IP-containing bodies also show the presence of reaction product, and thus can be regarded as lysosomes. However, in the parenchymal cells there may exist a small population of iron-deficient lysosomes (only lead could be shown). The latter may correspond to "primary lysosomes."

Acid Phosphatase↗

Ultrastructure of the aorta in experimental uraemia.

The effect of chronic experimental uraemia on the ultrastructure of the aorta was studied in rats. Pathological changes were found essentially in the media, in which the smooth muscle cells commonly had increased amounts of endoplasmic reticulum, Golgi structures and mitochondria, probably reflecting an increased synthetic and metabolic activity. In other areas of the media, degenerative and necrotic changes of the smooth muscle cells dominated. Increased amountes of collagen and the appearance of vesicular structures, probably cell debris, were noted in the extracellular space. Diffusely spread needle- and plate-shaped electron dense structures were seen in some necrotic areas. By X-ray microanalysis these structures could be demonstrated to have a high content of calcium, and probably represented hydroxyapatite crystals. Two types of circumscribed rounded electron dense conglomerates also appeared. At least one of these structures, in which X-ray microanalysis showed a high calcium content, is thought to represent a site of early calcification. Electron dense deposits in the elastic structures were only occasionally seen. The alterations occurred in both parathyroidectomized and non-parathyroidectomized uraemic animals. The study revealed no signs of intracellular calcification and suggests a close relation between necrosis of the smooth muscle cells and calcification of the aortic wall in experimental uraemia.

Animals↗

Arterial lesions of the radial artery in uraemic patients.

Arterial specimens from the radial artery were removed in connection with Brescia fistula operations on 15 uraemic patients and were studied by light and electron microscopy. The patients lacked clinical signs of arterial insufficiency. Radial artery specimens from 15 humans that underwent forensic post-mortem examination served as controls. The intima of the uraemic patients was significantly thicker than that of the controls. In 8 of the uraemic arteries light microscopy disclosed necrotic areas in the media and in 2 cases such areas in the intima, compared to only one case with patchy medial necrosis in the controls. Calcification was histochemically demonstrated in 6 of the uraemic arteries while none of the controls showed this change. The presence of degenerated and necrotic smooth-muscle cells was verified at the ultrastructural level. Furthermore, modified smooth-muscle cells appeared in the intima and the media and were probably of significance for the synthesis of the increased amounts of collagen and mucopolysaccharides that could be demonstrated. Ultrastructurally evidence of calcification could be demonstrated in the internal elastic membrane and in necrotic areas in the intima and the media. In the latter localization the calcification process seemed to start in relation to extracellular vesicular structures, probably representing cell debris. The possible significance of the observed changes for the development of symptom-giving arterial disease is discussed.

Adult↗

Malignant giant cell tumor of bone. Fine structure and localization of acid phosphatase.

The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.

Acid Phosphatase↗

Giant cell tumor of bone. Fine structural localization of alkaline phosphatase.

The fine structural localization of nonspecific alkaline phosphatase was elucidated in two giant cell tumors of bone using lead as capturing ion and beta-glycerophosphate as substrate in the incubation solution. Lead phosphate precipitate--indicating presence of alkaline phosphatase--was demonstrated on the plasma membranes, and the membranes bordering vesicles and vacuoles of presumed endocytotic nature, in giant cells and type 1 stromal cells (fibroblast-like cells). The findings support the view that stromal cells type I and giant cells are histogenetically related.

Adult↗

Studies on the fine structure of osteoblastoma with notes on the localization of nonspecific acid and alkaline phosphatase.

Electron microscopy of two osteoblastomas revealed the existence of three distinct types of cells in this tumor: osteoblast like, macrophage like, and multinucleated giant cells. In addition to the lysosomes, most Golgi cisternae and vesicles in the osteoblast like cells showed evidence of acid phosphatase activity. Deposits of lead phosphate indicating the site of this enzyme in the macrophage like cells were confined to the large and abundant lysosomes. Wide spread deposition of final product was noted in the cytoplasm of the multinucleated giant cells, both in conventional lysosomes, Golgi regions and special organelles probably corresponding to GERL. With regard to nonspecific alkaline phosphatase, final product indicating the location of enzyme activity was confined to the plasma membranes and associated vesicular and vacuolar structures in the osteoblast like cells. The findings suggest that the giant cells in osteoblastomas participate in lytic bone destructive and resorptive processes while osteoblast like cells appear to be osteoid and bone forming carriers of the neoplastic properties of the tumor.

Acid Phosphatase↗

Childhood cancer in Sweden, 1958-1974. I. Incidence and mortality.

All cases of tumours and tumour-like conditions in children 0-14 years reported to the Swedish cancer registry during the period 1958-74 have been studied. The material consists of 3797 individuals on file in this registry. The most common cancer diagnoses in children 0-14 years are leukemia and tumours of the central nervous system (together constituting approximately 58% of all cases). Almost half of the cancers affect children below five years of age. The lowest incidence occurs in the ages 7-8 years, and the highest occurs during the first year of life. The types of tumours below one year of age show a different distribution than in any other age groups. A significant increase in the incidence of childhood cancer occurred, while the mortality rates showed a slight decrease during the period studied. A remarkable increase in the incidence figures was noted concerning tumours of the nervous system, especially in boys. The decrease in the mortality rates was most obvious regarding Wilms' tumour, and leukemia in children 0-4 years of age.

Adolescent↗

Contribution to the knowledge of the fine structure of chondrosarcoma of bone. With a note on the localization of alkaline phosphatase and "ATPase".

Seven well differentiated chondrosarcomas of bone have been analyzed by electron microscopy, and the fine structural localization of adenosine triphosphatase and nonspecific alkaline phosphatase has been elucidated. On the basis of the fine structural appearance, two distinct cell types were shown to constitute the tumor tissue: chondrocyte-like cells and large "mitochondria-rich cells". Large, multinucleated cells in the tumor did not seem to correspond to osteoclasts but rather were likely to represent true neoplastic cells. Some chondrocyte-like cells appeared to be binucleated by virtue of deep, groove-like nuclear indentations. Adenosine triphosphatase and alkaline phosphatase were associated with the plasma membrane of both chondrocyte-like and mitochondria-rich cells suggesting that they might be of common origin. Normal chondroblasts and chondrocytes lack histochemically demonstrable adenosine triphosphatase on their plasma membrane. Presence of this enzyme in the tumor cells may indicate that they are histogenetically related to immature non-chondroid matrix forming cells (known to carry the enzymes).

Adenosine Triphosphatases↗