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Biomedical subjects

M Tavassoli

Publications and source records attributed to M Tavassoli.

At least 163 records · Page 9Linked to original sources
PubMed1985

Liver endothelium binds, transports, and desialates ceruloplasmin which is then recognized by galactosyl receptors of hepatocytes.

Incubation of 125I-labeled ceruloplasmin with various fractions of liver cell suspensions at 4 degrees C led to its exclusive binding to the endothelium. At 37 degrees C the uptake was followed by internalization and subsequent release of the labeled molecule which, then, had acquired the capacity to bind to the hepatocytes. Unlabeled CP did not inhibit this hepatocyte binding, but two galactose-containing molecules, asialofetuin and asialoceruloplasmin, did. Incubation of double-labeled CP (sialic acid with 3H, protein with 125I) with endothelial cells led to the dissociation of two labels, indicating desialation of CP. The findings indicate that liver endothelium takes up and desialates CP which is subsequently released and recognized by hepatocytes through their membrane galactosyl receptors. This work offers a physiological function for the galactosyl receptors on hepatocyte membrane.

Animals↗
PubMed1985

Development of specific surface receptors recognizing mannose-terminal glycoconjugates in cultured monocytes: a possible early marker for differentiation of monocyte into macrophage.

Surface receptors for mannose-terminal glycoconjugates have been reported in various macrophage populations and are thought to be involved in specific binding and internalization of mannose-rich substances. They thereby may serve a function in such phenomena as phagocytosis of yeast and tumor cell recognition. Little is known of mannosyl receptors in blood monocytes. We synthesized a probe by covalently linking D-mannose to bovine serum albumin (BSA). Using this probe in fluoresceinated or latex minibead-derivatized forms, we searched the surface of human monocytes for the presence of mannosyl receptors. 125I-labeled probe was further used to quantify the number of receptors and the kinetics of the binding. Freshly isolated monocytes did not bind the probe, indicating the absence of mannosyl receptors. When placed in a culture system that preserves functional and morphological homogeneity of the cells, surface receptors for D-mannosyl glycoproteins developed within four days, reached a peak after one week, and then remained fairly stable. Binding parameters (Kd, Bmax, and receptor number) also remained stable and were not dissimilar to those reported for macrophages, although the Kd was consistently larger in cultured monocytes. When studied at 37 degrees C, the ligand-receptor complex was internalized through a system of coated pits and vesicles. The development of these receptors before evidence of morphological or functional differentiation suggests that these receptors may constitute an early marker for differentiation of monocytes into macrophages.

Cell Differentiation↗
PubMed1985

Identification of lectin-like substances recognizing galactosyl residues of glycoconjugates on the plasma membrane of marrow sinus endothelium.

Plasma membrane components capable of specific binding to the sugar residues of glycoproteins have recently been identified in several cell systems and implicated in the recognition and specific uptake of soluble or membrane-bound glycoproteins. Because the endothelium of bone marrow sinuses is the site of massive cellular and molecular traffic that is often specific, we studied the surface of sinus endothelium for the presence of sugar-recognizing systems. Neoglycoprotein probes were synthesized by covalently binding bovine serum albumin (BSA) to activated pyrannose form of galactose, fucose, or mannose. The probe was then labeled with colloidal gold. Galactosyl-BSA gold bound to endothelial membrane at 4 degrees C and was internalized at 37 degrees C. Both the binding and the internalization were inhibited in the presence of excess unlabeled galactosyl-BSA. Gold-labeled mannosyl-BSA and fucosyl-BSA did not bind to the endothelium. Nor did BSA-gold without galactosyl residues bind to endothelial membrane, confirming that galactosyl moiety was responsible for the binding. The uptake of galactosyl-BSA was further confirmed by perfusion of 125I-galactosyl-BSA into the abdominal aorta. Small but highly specific uptake was noted in tibias and femurs. These data provide evidence for the presence of a lectin-like substance on the luminal surface of marrow endothelial membrane capable of specific interaction with galactosyl residues of circulating and cell-bound glycoproteins and may provide a mechanism for specific recognition of these glycoproteins.

Animals↗
PubMed1985

Hemopoiesis in cellulose ester membrane: characterization of the epilayer responsible for recognition and lodgement of hemopoietic cells.

Following intraperitoneal (i.p.) insertion of cellulose ester membranes in the mouse, the membranes develop a cellular coat that after sublethal irradiation and i.p. infusion of marrow cells supports the growth of hemopoietic colonies. The uppermost layer of this cellular coat (the epilayer) becomes extremely attenuated and develops numerous microvilli that interact with infused cells to trap and lodge them. This phenomenon is analogous to specific lodging of hemopoietic stem cells in the marrow after bone marrow transplantation. The mechanism of this interaction is not clear, but attention has recently focused on specific interaction of sugar residues of membrane glycoproteins. We have characterized the free surface of this epilayer with various lectins, glycosylated ferritins, and antifactor VIII antibody. There is strong binding of the three lectins Ricinis communis agglutinin (RCA II), phytohemagglutinin (PHA), and wheat germ agglutinin (WGA), but not Ulex europeaus agglutinin, concanavalin A, the tested glycosylated ferritins, or antifactor VIII antibody. The highest density of binding is on microvilli. Since marrow sinus endothelium also strongly binds RCA II, PHA, and WGA, it is possible that the sugar residues of membrane glycoproteins specifically binding these lectins are responsible for cellular and molecular recognition and transport across the epilayer.

Animals↗
PubMed1984

Fulminant and fatal angioedema caused by bleomycin treatment.

We encountered a case of fulminant and fatal angioedema involving skin and lungs. This reaction, hitherto unreported, occurred 48 hours after termination of a course of bleomycin sulfate. It was not predictable by skin testing, nor was it reversible with steroid therapy. The only predictive clue was the development of eosinophilia during the course of therapy. Fulminant angioedema should be added to the list of potential reactions to bleomycin.

Aged↗
PubMed1984

Cellular and subcellular distribution of iron in the lamina propria of rat duodenum.

Cellular and subcellular distribution of iron in the lamina propria of rat duodenum was studied after a single i.p. injection of iron dextran, using electron microscopy and peroxidase cytochemistry. X-ray spectrum microanalysis was used for positive identification of iron. Iron-containing particles (IP) were found in the cytoplasm of three cell types, viz. macrophages, pericytic reticular cells and sheathing fibrocytes. IP-containing organelles in lamina propria cells were more heterogeneous compared to absorptive cells and, in addition, some differences were noted in the subcellular distribution of IP in the 3 cell types. A common denominator in these 3 cell types was the presence of endogenous peroxidase, also shared by Kupffer cells which are known to be involved in iron storage. Peroxidase activity was absent in absorptive epithelial cells. It is hypothesized that the cells of the lamina propria, like Kupffer cells, may be the site of storage of excess iron absorbed, releasing iron upon demand and migrating into the lumen to prevent iron overload. In this fashion they may regulate the exchange of iron with the environment. The presence of peroxidase in these as well as Kupffer cells, and its absence in absorptive cells also raises the possibility that this enzyme may be related to certain aspects of iron storing process.

Animals↗
PubMed1984

Polarization of membrane glycoproteins during monocyte chemotaxis.

Distribution of membrane glycoproteins was studied in chemotactic monocytes using ferritin-conjugated lectins. The cells became polarized forming a pseudopodia at a leading head. Membrane glycoproteins were redistributed at the head. This phenomenon was not observed in chemokinetic or non-chemotactic cells suggesting that membrane glycoproteins may have a role in recognition of the chemoattractant.

Chemotaxis↗
PubMed1984

Ceruloplasmin receptors in liver cell suspensions are limited to the endothelium.

The interaction of ceruloplasmin (CP) with isolated liver cell suspensions was studied using 125I-labeled and latex minibead-derivatized CP. Fractionation of liver cell suspensions was done using metrizamide gradient centrifugation. In crude liver cell suspensions only endothelial cells, but not hepatocytes and Kupffer cells bound the minibead probe. The binding was specific and inhibited by excess native CP. These results were confirmed using 125I-CP combined with cell fractionation technique. Kinetic data, obtained from the latter system, indicated a dissociation constant (Kd) of 1 X 10(-7) M and the number of receptors to be 5.7 X 10(5) per endothelial cell. The exclusive binding of CP to liver endothelium suggests that this cell may mediate the hepatocytes uptake of CP and is, therefore, a crucial element of the tissue-blood barrier.

Animals↗
PubMed1984

Modulation of WGA binding sites on marrow sinus endothelium in state of stimulated erythropoiesis: a possible mechanism regulating the rate of cell egress.

To study the regulation of cellular and molecular traffic across the marrow-blood barrier, rat marrow endothelial surface was incubated with ferritin-conjugated concanavalin A, wheat germ agglutinin (WGA), recinus communis agglutinin I, and phytohemagglutinin. Normal animals were compared with those after erythropoietic stimulation (phenylhydrazine-induced hemolysis, phlebotomy). A selective and significant reduction in the density of WGA receptors, but not other lectins was noted congruent to the degree of reticulocytosis. Neuraminidase treatment also reduced WGA binding sites and the surface negative charge as detected by polycationic ferritin (PCF). Thus, the reduction in WGA binding sites, may reflect a decrease in the density of membrane sialic acid, rendering the endothelial surface charge less negative and providing an electrostatic attraction for the negatively charged surface of reticulocytes. The findings may also be explained by an increase in the frequency of WGA-excluding fenestrae in the endothelium. These areas, lacking sialic acid, may provide unstable areas in the membrane suitable for the passage of cells and molecules in both directions. It is concluded that, by modulating the density of sialic acid residues, the endothelium may regulate the traffic of cells and molecules across the marrow-blood barrier.

Animals↗
PubMed1984

Transendothelial transport (transcytosis) of iron-transferrin complex in the bone marrow.

To determine the transport pathway of iron-transferrin complex (Fe-TF) across the marrow-blood barrier, we labeled Fe-TF with colloidal gold and perfused rat femoral marrow with this probe. At 4 degrees C, the probe bound to the luminal surface of marrow sinus endothelium. The binding was inhibitable in the presence of excess native Fe-TF indicating the specificity of the binding. At 37 degrees C, the probe was internalized largely via a system of coated pits and vesicles and transported across the endothelium via a system of tubules and endosomal vesicles. It could not be ascertained if all Fe-TF was still associated with the colloidal gold probe within the endothelium, but the probe appeared to be externalized on the abluminal side into the interstitium where it subsequently bound to the surface of marrow erythroblasts and was internalized. Endothelium appeared to store part of the probe within a large vesicular system. No transport of Fe-TF was noted through diaphragmed fenestrations, diaphragmed vesicles, or interendothelial junctions. No endothelial uptake of this magnitude was noted when native gold particles or gold-labeled bovine serum albumin was used. Our findings indicate that in the bone marrow, gold-labeled Fe-TF is first taken up by sinus endothelium through a receptor-mediated mechanism and is possibly transported transendothelially via a vesicular system (transcytosis).

Animals↗
PubMed1984

Fatty involution of bone marrow in rabbits.

The developmental pattern of red and yellow bone marrow was studied in rabbits of different ages from newborn to 6 months of age. At birth no adipose cells were seen in any of the marrow cavities. Most bones were still developing and marrow cavities were relatively limited. Nonetheless a distinct difference in the cellularity of marrow in the trunk versus limb bones was noted, the latter being significantly less cellular. Adipose cells began to develop at 2 weeks of age and proceeded so that the adult pattern of red and yellow marrow was fully established by 4 months. The development of adipose cells occurred in both trunk and limb bones; the magnitude of the process, however, was considerably greater in the limb bones. Adipocyte precursors may be present in the marrow at birth with a differential distribution in the areas of prospective red and yellow marrow. Thus, fatty involution of marrow appears to be a programmed developmental event.

Adipose Tissue↗
PubMed1984

Synthetic neoglycoproteins: a class of regents for detection of sugar-recognizing substances.

Specific interactions between proteins and sugars have recently been emphasized in many biological systems. To detect sugar-recognizing substances, known as lectin-like substances or endogenous lectins, we describe a method in which various sugars were covalently bound to a carrier protein such as albumin. This neoglycoprotein was stable at -20 degrees C for a period of 6 months. It was conjugated to various cytochemical markers (125I, fluorescein isothiocyanate, colloidal gold, or latex minibead). Detection of the marker then indicates the presence of the sugar-binding protein. Control experiments in the presence of unlabeled neoglycoprotein or specific sugar indicated the specificity of the reaction. This method was used to analyze the kinetics of binding for a mannose-recognition system in the mouse peritoneal macrophages. The data obtained were in agreement with those previously reported. The method can be used for detection of other sugar-recognizing systems as virtually every simple sugar can be bound to a carrier protein to produce these neoglycoproteins. Some of the consideration required for successful production of these reagents are discussed. These synthetic neoglycoproteins are useful in studying the distribution and kinetics of sugar-recognizing systems and may help to further our understanding of this rapidly developing area.

Animals↗
PubMed1984

Hemopoiesis in ectopically implanted bone marrow.

Ectopically implanted bits of marrow undergo a regenerative process that recapitulates the marrow ontogeny. This process is possible only because marrow tissue has considerable angiogenic potential. The regenerative process originates from marrow stroma, leading to the formation of primitive mesenchyme, osteoid bone, reconstitution of marrow organization including its distinctive sinusoidal system, and repopulation with circulating hemopoietic stem cells. Expansion of hemopoiesis is then associated with bone resorption. Also, few adipose cells develop and they are interspersed with hemopoiesis. The final product is a hemopoietic nodule surrounded by a shell of bone. A similar process occurs within the marrow cavity after ablation of the marrow tissue. In yellow marrow implants, the subsequent development of adipose tissue replaces entirely the hemopoietic tissue. Splenic implants can also regenerate in an analogous fashion despite their lack of significant angiogenic potential. As a model system, ectopic implantation of marrow has been the forerunner of long-term marrow culture and has provided important information on the relationship between hemopoietic cells and their supporting stroma. It has also led us to further understanding of the relationship between the marrow and its surrounding bone. Moreover, it has been an excellent system to study the relationship between red and yellow marrow and their interconversion. The full potential of this model system has not yet been fully realized. In application, for example, the conversion of yellow to red marrow can be exploited to reactivate the areas of hemopoietically inactive marrow in the limbs. Such exploitation may permit more liberal use of ablative radiotherapy in malignant diseases, particularly those of the lymphoreticular system. In basic research, in conjunction with long-term bone marrow culture, ectopic marrow implantation can yet provide considerable information on the role of stroma and bone in hemopoiesis.

Abdomen↗
PubMed1984

Liver endothelium and not hepatocytes or Kupffer cells have transferrin receptors.

Using a visual probe, consisting of latex minibeads covalently linked to transferrin (TF), we found that, in rat liver cell suspensions, transferrin receptors were limited to endothelial cells. Neither hepatocytes nor Kupffer cells contained an appreciable number of TF receptors. Specificity of this reaction was demonstrated by preincubation with non-derivatized TF, which inhibited the binding. This was further confirmed by fractionation of liver cell suspensions on metrizamide gradients. The uptake of either the visual probe or 125I-labeled TF was again limited to the endothelium-rich fraction. Transferrin bound to endothelial membrane was internalized at 37 degrees C, but not at 4 degrees C, via a coated pit system. Again, hepatocytes and Kupffer cells did not internalize the probe. The findings suggest that iron may be first taken up by liver endothelium and then transmitted to parenchymal cells. These results emphasize the generally unappreciated role of endothelium in the transport across the tissue-blood barrier.

Acid Phosphatase↗
PubMed1984

Studies on conversion of yellow marrow to red marrow by using ectopic bone marrow implants.

Previous work has suggested that an increase in temperature in conjunction with hemopoietic stimuli can convert yellow marrow to red marrow. Ectopic implantation of yellow marrow in rabbits was used to confirm this suggestion and to determine whether sustained stimulation is needed to maintain hemopoiesis. Tibial marrow (temperature 28.5 degrees C) was implanted in the subcutaneous tissue of the abdomen (temperature 33 degrees C). Phenylhydrazine-induced hemolysis was used as a hemopoietic stimulus. Implants of yellow marrow in control animals, not subjected to modulation of hemopoiesis, led to the formation of fatty marrow nodules. These nodules became hemopoietically active when the hemopoietic stimulus was applied to the animals, either concomitantly with implantation or even two months after implantation. The stimulus was required continuously to maintain the hemopoietic activity of the nodules. These findings confirm that increased temperature acts synergistically with hemopoietic stimuli to induce hemopoiesis in yellow marrow. This supports the concept that, while the total volume of hemopoietic tissue is determined by the body's demands, its distribution may be determined by such factors as local temperature.

Adipose Tissue↗