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R Seljelid

Publications and source records attributed to R Seljelid.

139 records · Page 8Linked to original sources
PubMedDate not supplied

Fate of intravenously injected aminated beta(1----3) polyglucose derivatized with 125I-tyraminyl cellobiose.

Aminated beta(1----3)glucan (polyglucose, AG), a potent soluble immunomodulator, was radio-iodinated and traced after intravenous administration to rats. Since the glucose polymer cannot be 125I-labelled directly by conventional methods, the polysaccharide had to be substituted with an adduct which binds the radiolabel. To this end, tyraminyl cellobiose (TC) was coupled to amino groups of AG by means of cyanuric chloride. This procedure resulted in a degree of substitution corresponding to 3.6% (or 1 molecule of tyraminyl cellobiose being incorporated per 28 molecules of glucose). AG substituted with TC (TC-AG) could be labelled with 125I by conventional procedures. After intravenous administration of 125I-TC-AG the serum concentration dropped about 50% from 1 min to about 15 min after injection, while a further drop from 50% to about 25% was observed during the next 15-60 min. The finding that 60 min after injection most of the radioactivity was recovered in the kidneys and urine, together with the results from gel chromatography showing that the low Mw fraction of the injected material disappeared first from the circulation, suggests that the initial rapid phase of elimination is due mainly to glomerular filtration. The molecules that are too large for kidney excretion are taken up mainly by the liver (about 10% of injected dose) at a slower speed. This notion was supported by the finding that a preparation of high Mw glucan obtained by gel chromatography survived for a long period in the circulation, and was eliminated mainly by accumulation in liver, whereas a preparation of low Mw glucan was rapidly eliminated by glomerular filtration. Several days after injection the liver contained nearly 90% of the recovered radioactivity, whereas the kidneys and other organs contained only insignificant amounts. This indicates that radioactivity associated with the kidneys after 60 min reflects glomerular filtration, whereas radioactivity in liver results from uptake leading to lysosomal accumulation. Isolation of liver cells after injection disclosed that the radioactivity per cell was the same in Kupffer cells (KC) and liver endothelial cells (LEC), whereas the uptake per parenchymal cell (PC) was about 30% of the uptake per KC and LEC. It could be calculated that in the intact liver, the population of PC was responsible for 50% of the uptake, whereas the populations of LEC and KC contained 35% and 15%, respectively, of the total liver radioactivity. These findings raise the question whether not only KC, but also LEC and PC may be mediators of the immune responses caused by beta(1----3) polyglucose.

Adjuvants, Immunologic↗
PubMedDate not supplied

The synergistic effect of trauma and infection on interleukin-1 but not tumor necrosis factor liberation during posttraumatic gram-negative septicemia.

The release profiles of interleukin 1 (Il-1) and tumor necrosis factor (TNF) were studied during experimental Escherichia coli septicemia and peritonitis with and without a preceding (-48 h) moderate trauma (femur marrow nailing). The trauma alone did not induce significant Il-1 or TNF liberation to plasma. During septicemia, a rapid IL-1-rise (+30 min) and subsequent normalization (+120 min) was seen. A previous trauma delayed (30 min), but accentuated (2x) and prolonged (> 4 h) the Il-1 response. During peritonitis, a delayed (30 min) but otherwise similar Il-1-response was observed. TNF levels rose rapidly (+30 min) in all animals, and remained high throughout the experimental period (6 h). The trauma did not influence the TNF response. We conclude that a synergism exists between trauma and infection with regard to the magnitude of the Il-1 response.

Animals↗
PubMedDate not supplied

Tumor stroma.

The accumulated evidence indicates that tumor stroma with its cells and cell products plays a much more active and important role than previously believed. Growth factors and cytokines produced by macrophages and other cells are crucial for stroma formation and angiogenesis. Lytic enzymes provided by stromal cells may be essential for invasion. TNF and other inflammatory mediators may be operative in the systemic effects of tumors, e.g. cachexia. All these effects may come about through the action of soluble substances produced by tumor cells or by more intimate interactions. There is no evidence that stromal cells are directly involved in carcinogenesis--i.e. the cellular transformation to produce the malignant cell. On the other hand, stromal cells and other components of the interstitia are instrumental in tumorigenesis--i.e. the development of a real malignant tumor from its start on the cellular or subcellular level. In one way of looking at it, the stromal cells, e.g. macrophages may be considered as "slaves", kept to carry out certain functions, synthesize essential substances e.g. growth factors that the tumor cells do not have the capacity or the degree of finely tuned machinery to produce. The objective of immunomodulation should then be to create a "slave uprising", to make the macrophages and other cells turn against their masters, stop producing growth factors and start producing harmful factors that would lead to the elimination of the malignant growth. The first target of immunomodulation in tumor disease should probably be local malignancies where no effective treatment exists today- and selected cases of metastatic prevention (181, 182).

Extracellular Matrix↗