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Biomedical subjects

M Tavassoli

Publications and source records attributed to M Tavassoli.

At least 109 records · Page 6Linked to original sources
PubMed1989

Relationship of the glycan structure of glycoproteins to the desialylation process by rat liver endothelium.

To investigate the variations in desialylation of glycoproteins by liver endothelium, we compared endothelial desialylation for 3 glycoproteins, human ceruloplasmin, human and rat transferrin. Radiolabeled glycoproteins were chased through purified rat liver endothelium and then fractionated by lectin affinity chromatography. Endothelium processed glycoproteins were fractionated by RCA120 chromatography into sialylated and desialylated components. The latter was then studied by Con A chromatography. Desialylation occurred only when the molecule contained at least a single triantennary chain of glycan. Desialylation was minimal in the case of human transferrin which contains mostly biantennary branching pattern. Thus, it appears that a single triantennary glycan chain is necessary and sufficient to trigger desialylation of glycoproteins by liver endothelium and this process is an all-or-none phenomenon.

Animals↗
PubMed1988

Homing of hemopoietic stem cells to hemopoietic stroma.

The existing knowledge of the molecular mechanism that underlies the successful engraftment of hemopoietic progenitor cells in their specific stromal microenvironment has been discussed. It appears that membrane lectins on the surface of the stem cell with specificity for galactose with and/or mannose-bearing glycoconjugates on the surface of the stromal cell are involved. This recognition and binding of hemopoietic stem cells which is called "homing" initiates the processes of differentiation, proliferation, and maturation of hemopoietic cells.

Animals↗
PubMed1988

Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow.

Bone marrow transplantation is done by introducing a source of hemopoietic stem cells into general circulation in anticipation of their recognition and selective lodging into the bone marrow. We tested the hypothesis that the molecular basis of this recognition is by means of a lectin-carbohydrate interaction. We synthesized a number of neoglycoproteins by covalently binding pyranose derivatives of various monosaccharides to bovine serum albumin (BSA). These reagents and the galactosyl-terminating glycoprotein asialofetuin were used to inhibit engraftment of intravenously transplanted marrow cells into lethally irradiated mice. In splenectomized mice, in whom engraftment occurs only in the bone marrow, galactosyl-BSA, mannosyl-BSA, and asialofetuin but not fucosyl-BSA inhibited homing of transplanted cells. Both the survival and cellular content of marrow, including hemopoietic stem cells and granulocyte-macrophage progenitors, were reduced. In nonsplenectomized mice, in whom engraftment occurs in both spleen and marrow, the reagents did not inhibit splenic homing. Both the survival and cellular content of spleen, including hemopoietic stem cells and granulocyte-macrophage progenitors, were similar to those of the control group. But even in this group, marrow homing of transplanted cells was inhibited by these reagents. We conclude that the recognition and homing of intravenously transplanted hemopoietic cells by marrow, but not by spleen, occurs by means of a recognition system with galactosyl and mannosyl specificities.

Animals↗
PubMed1988

A modified method for application of indirect immunofluorescent staining for factor VIII/vWF to capillary endothelia.

Immunofluorescent staining for factor VIII/von Willebrand factor (VIII/vWF) as applied to capillary endothelia has sources of false negativity and false positivity. False negativity occurs because capillary endothelia are not as rich as endothelia of larger vessels in this factor. To overcome this problem we enriched liver endothelium by preincubation with the factor. The source of false positivity is the presence of Fc receptors on freshly isolated capillary endothelia. These receptors may bind antibody to this factor through the Fc portion of the molecule. To overcome this problem we preincubated the cells with IgG not against VIII/vWF (irrelevant antibody) to cover Fc receptors. The results presented indicate that considerable improvement in the immunofluorescent staining of capillary endothelia can be achieved by application of our method.

Animals↗
PubMed1988

Desialation of transferrin by rat liver endothelium.

To examine the role of liver endothelium in desialation of transferrin (TF), pulse-chase studies were done by incubation of either 3H (sialic acid labeled)-, or 125I, or 59Fe (protein core labeled)-TF with fractionated liver endothelium. While 125I or 59Fe labels were externalized after initial binding and internalization, a large proportion of 3H label was internalized and remained within the cell. When the supernatant of these experiments was studied by isoelectricfocusing and Ricinus communis agglutinin (RCA120) affinity chromatography, generation of asialotransferrin was noted by both techniques. Incubation of liver endothelium with double-labeled TF (sialic acids with 3H and protein core with 125I or 59Fe) led initially to a concordant uptake of the two labels, which were then dissociated and 3H was retained by the cell. These findings indicate desialation of TF by liver endothelium. The significance of these findings in the pathogenesis of hepatic siderosis is discussed.

Animals↗
PubMed1988

Marrow uptake of galactosyl-containing neoglycoproteins: implications in stem cell homing.

Tissue distribution of synthetic neoglycoproteins was studied after intravenous injection of 125I-labeled galactosyl-, mannosyl- and fucosyl-BSA. The highest uptake of all three reagents occurred in the bone marrow. Spleen also took up considerable proportions of galactosyl and mannosyl reagents, while liver only took up galactosyl-BSA. Implication of these findings in the recognition and homing of intravenously transplanted hemopoietic cells to bone marrow is discussed.

Animals↗
PubMed1988

An electron microscopic study of hemopoietic tissues in the course of Lewis lung carcinoma.

Lewis lung carcinoma of C57Bl/6 mice causes a progressive anemia with reticulocytosis and splenomegaly, metastasizes to lungs, liver, and kidneys but does not invade hemopoietic tissues. The cause of this anemia is uncertain. We studied the structure of spleen and bone marrow in these tumor hosts by light and electron microscopy. Splenic congestion of the red pulp with numerous erythropoietic islands and marrow hyperplasia characterized the hemopoietic tissues of these mice, which, when coupled with other hematological parameters suggested a hemolytic condition. However, the erythropoietic response appeared to be in part ineffective as evidenced by phagocytosis of immature as well as mature red blood cells within the spleen and marrow. Thus, the condition of anemia in Lewis lung carcinoma may result from a multifactorial response of hemolysis and ineffective erythropoiesis and hemolysis.

Anemia↗
PubMed1988

Analysis of the microheterogeneity of the glycan chain of rat transferrin.

To investigate the microheterogeneity of the glycan chain of rat transferrin, either the protein moiety was labeled with 125I or the sialyl residues with 3H. The molecule was then subjected to Con A chromatography. Three components were obtained. Each was enzymatically desialylated and sialyl/protein molar ratios were calculated. The native protein as well as the 3 components were also subjected to isoelectric focusing. The results indicated that rat transferrin may have 3 types of glycan chain: The major type (60%) corresponds to a molecular species with triantennary branching, while 30% consists of molecules with biantennary and 10% with tetraantennary branching. The last species has not been previously described.

Animals↗
PubMed1988

Transcription of the c-myc oncogene is altered in spontaneously immortalized rodent fibroblasts.

Cellular immortalization seems generally to be a necessary, but not sufficient step in tumourigenesis. We have analysed the role of the cellular oncogene, c-myc in the process of in vitro cellular ageing and spontaneous cellular immortalization using rodent fibroblasts. The steady-state level of c-myc of mouse and rat fibroblasts does not change significantly during cellular ageing in vitro. By contrast, the steady state level of c-myc mRNA increases 3- to 20-fold upon spontaneous establishment of these rodent fibroblasts. The increase in the steady-state level of this mRNA is essentially due to an increase in the transcriptional rate. Not all oncogenes respond in this way; the mRNA levels of both c-fos and c-K-ras do not show the same alteration. The changes in the steady-state level of c-myc mRNA are not due to gene amplification nor to gross gene rearrangements or translocations. However, the response of the myc gene to growth factor stimulation is present apparently equally in both mortal and immortal cells; a difference is seen in an increased maintenance of high c-myc mRNA levels after growth stimulation in established cell lines. Both young and senescent mortal cells, as well as immortal cells, respond to mitogen stimulation with a sharp increase in c-myc mRNA levels. Thus, senescent cells are able to see mitogen signals, but do not go on to initiate DNA synthesis. We also demonstrated that the c-myc mRNA levels do not respond to serum concentration above a minimum level, nor do they respond to factors in the conditioned medium of immortal cell cultures.

Animals↗
PubMed1988

Kinetics of inhibition of CFU-C homing in long-term marrow culture.

We have previously shown that galactosyl- and mannosyl-BSA inhibit the binding of hemopoietic progenitor cells to their supporting stroma (homing) in long-term marrow culture, suggesting that the homing is mediated by a molecular recognition with galactosyl and mannosyl specificities. In the present work we studied the kinetics of this inhibition. In the absence of inhibiting reagents, total cell and CFU-C production continued linearly as a function of time in culture. When inhibiting reagents were incorporated at the time of initiation of cultures, cell and CFU-C production was halted, suggesting that the binding of progenitor cells to stroma was necessary for subsequent cell proliferation and differentiation. When inhibiting reagents were introduced 1 week after the initiation of culture, cell and CFU-C production continued at a much lower rate than that of control, suggesting that although the inhibiting reagents can inhibit the binding of progenitor cells to stroma, they are less effective in displacing those already bound. Finally, when the inhibiting reagents were removed from the cultures, cell and CFU-C production resumed at a rate similar to that of controls, indicating that these reagents do not alter the integrity of progenitor cell or stroma.

Animals↗
PubMed1988

Detection of membrane lectins on the surface of hemopoietic progenitor cells and their changing pattern during differentiation.

To probe for the presence of membrane lectins on hemopoietic progenitors capable of reacting with specific sugars, we synthesized a group of neoglycoprotein reagents by covalently binding biologically relevant monosaccharides to bovine serum albumin (BSA). These reagents were incubated with marrow cells that were subsequently agglutinated on a layer of BSA. The concentrations of various progenitor cells were determined in agglutinated and nonagglutinated fractions using standard clonal assays. Spleen colony-forming units, mixed lineage colony-forming units, and colony-forming units in culture were preferentially agglutinated by galactosyl- and mannosyl-BSA, but not by fucosyl-BSA, indicating the presence of membrane lectins on the surface of these cells with galactosyl and mannosyl specificities. Differentiation in the erythroid direction was associated first with the loss of galactosyl-recognizing system so that erythroid burst-forming units demonstrated only mannosyl-recognizing system. Further differentiation into erythroid colony-forming units was associated with the loss of mannosyl-reacting system as well but the development of a new fucosyl-reacting system. In every case, the agglutination was reversible and preventable in the presence of competing sugars, indicating the specificity of the reaction. Further characterization of these membrane lectins may shed light on their function in cellular interactions in hemopoiesis.

Agglutination↗
PubMed1988

Cytoskeletal organization of a cloned hemopoietic stromal cell line during attachment and spreading.

The cell membrane of a cloned murine bone marrow stromal cell line D2XRII was extracted in situ using Triton X-100 detergent and the cytoskeletal structure studied during the process of adherence and spreading. During this process, three zones can be identified in the cytoplasm: the perinuclear zone, which was the fixed part of the cell; the peripheral mixed filamentous zone, which formed the core of long cytoplasmic projections; and an outer zone, which formed the boundary of cytoplasmic projections and contained only intermediate filaments. The process of spreading appeared to originate from very long strips of microfilaments emanating from the second zone, crossing the width of the outer zone, and extending beyond for a long distance. The second and third zones then appeared to "stream out" around the axis of this strip, and in this fashion the cytoplasm spreads over the substratum.

Animals↗
PubMed1987

Receptors for transferrin and transcobalamin II display segregated distribution on microvilli of leukemia L1210 cells.

Simultaneous addition of uniform latex particles derivatized with transferrin (0.532 micron) and transcobalamin II (0.345 micron) to leukemia L1210 cells resulted in segregated binding to individual microvilli as demonstrated by scanning electron microscopy. This segregated distribution suggests that individual microvilli are endowed either transferrin or transcobalamin II receptors but not both. Intracellular sorting and segregation of newly synthesized or recycling receptors probably occur prior to expression on the plasmalemma microvilli.

Animals↗
PubMed1987

Granular cell tumor. Clinical spectrum of the benign and malignant entity.

The clinical records of all patients with granular cell tumor seen at our institution over a 20-year period were reviewed. Three patients with malignant, and 37 with benign tumor, were identified. Eleven patients had multiple benign lesions. Three had a history of familial occurrence. Clinical and pathologic features and the management of this nebulous entity, in both its benign and malignant forms, are reviewed and discussed.

Adolescent↗