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Biomedical subjects

C A Finch

Publications and source records attributed to C A Finch.

At least 19 recordsLinked to original sources
PubMed1992

Is there a role for the tumor cell integrin alpha IIb beta 3 and cytoskeleton in tumor cell-platelet interaction?

In vitro tumor cell-platelet interaction was examined using B16 amelanotic (B16a) melanoma cells. These tumor cells express the alpha IIb beta 3-type cytoadhesin. Aggregation studies demonstrated that tumor cell surface alpha IIb beta 3 mediates the recognition of platelets since pretreatment of tumor cells with antibody against alpha IIb beta 3 prevents platelet-tumor cell interaction as well as platelet activation measured by aggregometry, platelet eicosanoid metabolism and ultrastructural analysis. In B16a cells, disruption of the microfilaments and intermediate filaments inhibits mobility of alpha IIb beta 3 on the cell surface. Microtubules do not play a role in receptor mobility, because B16a cells do not possess well-defined microtubules in interphase and colchicine does not affect receptor mobility. Disruption of microfilaments or intermediate filaments results in an inhibition of tumor cell-platelet interaction as evidenced by aggregometry studies and ultrastructural analysis. We suggest that platelet interaction with tumor cells begins with alpha IIb beta 3-mediated receptor recognition followed by not only platelet activation but also microfilament- and vimentin intermediate filament-dependent tumor cell activation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Intact transferrin receptors in human plasma and their relation to erythropoiesis.

Intact transferrin receptor molecules complexed with transferrin were found in human plasma. The concentration of receptors was determined by an enzyme-linked immunosorbent assay that uses polyclonal antibodies. The mean concentration of 8,279 micrograms/L in 56 normal adults appears to be unrelated to age or sex. Additional receptor measurements were performed on plasmas from 260 subjects with erythropoietic disorders. Decreased concentration of plasma receptors was found in patients with erythroid hypoplasia and increased numbers in those with erythroid hyperplasia. Ferrokinetic measurements of erythropoiesis were compared with numbers of receptors in 148 subjects, and a close correlation was found (r = .86). Both sets of values, measured in different conditions and expressed in relation to normal, were consistent with expected values. Receptor values were unproportionally increased only in conditions of iron deficiency. It is concluded that plasma receptors have a constant relationship to tissue receptors, and their number in most instances reflects the rate of erythropoiesis.

Erythropoiesis↗
PubMed1990

Transferrin-reticulocyte cycle time in rat reticulocytes.

The uptake and release of 131I-labelled diferric transferrin by rat reticulocytes was examined both in vitro and in vivo. Cycle time in vitro was estimated to be 2.5 min in iron-deficient reticulocytes and 2.3 min in phenylhydrazine-produced reticulocytes. In vivo reticulocyte uptake and release of labelled diferric transferrin injected in the iron-deficient rat averaged 1.7 min.

Animals↗
PubMed1990

Iron absorption in the iron-deficient rat.

Iron absorption in the iron-deficient rat was compared with that in the normal rat to better understand the regulation of this dynamic process. It was found that: Iron uptake by the iron-deficient intestinal mucosa was prolonged as a result of slower gastric release, particularly when larger doses of iron were employed. The increased mucosal uptake of ionized iron was not the result of increased adsorption, but instead appeared related to a metabolically active uptake process, whereas the increased mucosal uptake of transferrin iron was associated with increased numbers of mucosal cell membrane transferrin receptors. Mucosal ferritin acted as an iron storage protein, but its iron uptake did not explain the lower iron absorption in the normal rat. Iron loading the mucosal cell (by presenting a large iron dose to the intestinal lumen) decreased absorption for 3 to 4 days. Iron loading of the mucosal cell from circulating plasma transferrin was proportionate to the plasma iron concentration. Mucosal iron content was the composite of iron loading from the lumen and loading from plasma transferrin versus release of iron into the body. These studies imply that an enhanced uptake-throughout mechanism causes the increased iron absorption in the iron-deficient rat. Results were consistent with the existence of a regulating mechanism for iron absorption that responds to change in mucosal cell iron, which is best reflected by mucosal ferritin.

Anemia, Hypochromic↗
PubMed1989

The Journal of clinical Investigation, Volume 41, 1962: iron absorption. IV. The absorption of hemoglobin iron.

The absorption of radioiron in rabbit hemoglobin, hemin, and ferritin has been compared to that of ferrous salt in healthy volunteers and in subjects with iron-deficiency anemia. At a dosage level of 5 mg elemental iron, hemoglobin iron was as well or better absorbed than ferrous salts in the normal subject. Absorption of hemoglobin iron increased less, however, in the iron-depleted or iron-deficient subject. In contrast to the absorption of ferrous salts, that of hemoglobin iron was not decreased by food or by phytate nor increased by ascorbic acid. The absorption of hemin iron was also not decreased by food. Iron absorbed from hemoglobin appeared in the plasma later than that from ferrous salts, but was found to be similarly dialyzable at acid pH with EDTA. These findings suggest that iron in heme complexes is absorbed as a porphyrin complex without conversion to the free ionized form. It is further apparent that there is less effective mucosal regulation of absorption of iron in this form. Finally, the present hypothesis of iron absorption based on the behavior of iron salts is not adequate for all types of food iron.

Absorption↗
PubMed1989

Hepatocyte iron release in rats.

Hepatocyte iron release was studied in vivo in rats. After the injection of iron 59-labeled ferritin, hemoglobin, or human asialotransferrin, the proportions of the radioactive iron returned to the plasma and incorporated into stores were determined under various conditions. Iron 55-labeled rat transferrin was injected at the same time as the 59Fe-labeled compound, and storage iron release was calculated from the cumulative incorporation of the two isotopes in the red cell mass over 2 weeks. The various 59Fe-labeled compounds were processed differently by the hepatocyte, but the radioactive iron was incorporated in the same iron stores. About 6% of the hepatocyte storage iron was released daily in normal rats, but a pool of iron that is not mobilized spontaneously was clearly identified in iron overload. Iron turnover in the hepatocyte was regulated by the rate of erythropoiesis and iron status of the animal, and inflammation blocked hepatocyte iron release. A strong correlation between hepatocyte iron release and plasma transferrin receptor levels was observed (p less than 0.001), suggesting that plasma transferrin receptors could mediate the regulation of hepatocyte iron mobilization in rats.

Animals↗
PubMed1988

Random distribution of iron among the two binding sites of transferrin in patients with various hematologic disorders.

The distribution of iron among the two binding sites of transferrin was studied by isoelectric focusing in 41 patients with a variety of disorders of iron metabolism and erythropoiesis. The proportion of diferric and the two monoferric transferrins were very close to the values predicted from the transferring saturation. It is concluded that iron distribution on transferrin is random or close to random within the experimental error in patients with a variety of clinical disorders.

Hematologic Diseases↗
PubMed1988

The behavior of asialotransferrin-iron in the rat.

The effect of desialylation of rat and human transferrins on hepatocyte processing of the protein and its iron was studied in rats. No alteration in early transferrin catabolism was observed. Radioiron disappearance from the plasma and liver iron uptake were more rapid for asialotransferrins than for normal transferrins (P less than .001). Furthermore, radioiron plasma clearance of human tri-sialotransferrin was faster (P less than .05) and liver uptake higher (P less than .002) than for human pentasialotransferrin. When the asialoglycoprotein receptor was blocked by the prior injection of asialofetuin, asialotransferrin behaved like normal transferrin. When the transferrin receptor was blocked by the prior injection of 50 mg human diferric transferrin, iron uptake from all transferrins was delayed to such an extent that uptake through both receptors seemed to be affected. Approximately 90% of the hepatic radioiron from all transferrins was chelated by desferrioxamine and excreted into the bile, indicating its uptake by the hepatocyte rather than the reticuloendothelial (RE) cell. The rate of iron release into the plasma and its subsequent accumulation in the red cell mass over a 2-week period was similar for human asialotransferrin, ferritin, and hemoglobin iron. This study 1) confirmed that asialotransferrin-iron uptake by the hepatocyte is mediated by both transferrin and asialoglycoprotein receptors; 2) demonstrated that not only asialotransferrin but also transferrin of low sialic acid content will increase iron turnover and lead to excessive iron loading of the hepatocyte; 3) and showed that the intrahepatocyte metabolism of asialotransferrin-iron did not differ from that of iron delivered by normal transferrin.

Animals↗
PubMed1988

Iron binding proteins and their roles in the tobacco hornworm, Manduca sexta (L.).

Manduca sexta larvae accumulate large amounts of iron during their larval feeding period. When 59Fe was fed to 5th instar larvae, it was evenly distributed among the hemolymph, gut and carcass until the cessation of feeding. By pupation 95% of the labelled iron was found in the fat body. In the adult a significant portion of this iron was found in flight muscle. Studies of the hemolymph disclosed two iron-containing proteins. The first was composed of a single polypeptide chain of 80 kD, containing one atom of iron. This protein bound ionic iron in vitro and was able to transfer this iron to ferritin when incubated with fat body in vitro. Therefore, it appeared to serve a transport function. The second protein had a molecular weight of 490 kD with subunits of 24 and 26 kD and contained 220 micrograms of iron/mg protein. Its chemical and ultrastructural characteristics were those of ferritin. These studies demonstrate the presence of both a transport protein and a unique circulating ferritin in Manduca sexta, the latter serving a storage function during development and possibly also a transport function.

Animals↗
PubMed1988

Blocking action of parenteral desferrioxamine on iron absorption in rodents and men.

Desferrioxamine (DFO) is an iron chelating agent that, when administered orally, interferes with gut absorption of inorganic iron and, when administered parenterally, binds body iron and is excreted as ferrioxamine in bile and urine. Studies were carried out in normal and iron-deficient male rats and in normal, iron-replete male volunteers to investigate the blocking action of parenteral DFO on the absorption of radioiron. Radiolabeled ferrous ammonium sulfate, transferrin iron, or hemoglobin iron was injected directly into the jejunum of rats with or without intramuscular injections of DFO. Radioiron administered as ferrous sulfate or as transferrin iron was given to the volunteers by mouth or by direct duodenal infusion, respectively, with or without intravenous infusions of DFO. In iron-deficient rats, intramuscular DFO injections commencing 1 h before direct jejunal injection of radioiron significantly blocked absorption of inorganic iron (26% with DFO, 64% without DFO), transferrin iron (4% with DFO, 69% without DFO), and hemoglobin iron (3% with DFO, 19% without DFO). In normal rats, DFO injections also significantly blocked absorption of inorganic iron and transferrin iron. In normal volunteers, intravenous DFO infusions commencing 1 h before administration of radioiron significantly blocked absorption of physiologic doses of inorganic iron (3% with DFO, 21% without DFO) and transferrin iron (1% with DFO, 20% without DFO). The quantity of radioiron excreted in urine by both rats and humans with administration of DFO did not account for the observed decrement in absorption of radioiron. Biochemical analysis of rat intestinal mucosal scrapings after injection of DFO and administration of radioiron demonstrated the accumulation of a small molecular weight fraction containing iron that was ferrioxamine (iron-chelate) complex. We conclude that parenterally administered DFO can enter the small intestinal mucosa, bind intracellular iron, and block iron absorption. Parenteral DFO blocks the absorption of inorganic iron, transferrin iron, and hemoglobin iron, suggesting that all three iron species enter a common chelatable pool within the small intestinal mucosa and may share a common pathway of absorption.

Adult↗
PubMed1988

Transferrin receptors in rat plasma.

Antigenic material in rat plasma reacting with rat transferrin receptor antibodies was identified as an intact receptor molecule complexed with transferrin. Plasma transferrin receptors were measured by ELISA in rats of different age and sex, of different iron status, with different degrees of erythropoiesis, and with inflammation. An inverse relationship between iron status and receptor number was found, whereas a direct relationship existed between erythropoiesis and receptors. These changes in receptor number can be explained by assuming that the number of tissue receptors determined the number of plasma receptors and that the erythroid cells possessed most of the body's receptors. Increases in plasma receptors lagged behind the appearance of circulating reticulocytes, suggesting that receptors were released to the plasma during the terminal phase of erythrocyte maturation.

Animals↗
PubMed1988

Iron deficiency: effect on plasma luteinizing hormone and testosterone levels in the adult male rat.

We studied four groups of animals, all of which received an iron-deficient diet for 6 wk followed by a 4-wk recovery period during which all groups received Fe supplements. Group 1 (n = 12) and group 2 (n = 10) were intact male rats; group 1 received a dietary Fe supplement whereas group 2 received no Fe supplement. Group 3 (n = 12) and group 4 (n = 12) were castrated male rats; group 3 received a dietary Fe supplement whereas group 4 received no supplement. Analysis of circulating hormone values revealed that after 6 wk of dietary treatment, neither LH nor testosterone levels were affected by the Fe-deficient diet in either the castrated or intact groups. These observations suggest that neither testosterone secretion per se nor its feedback control by LH is affected by short-term Fe deficiency.

Animals↗
PubMed1988

In vivo transferrin-iron receptor relationships in erythron of rats.

Quantitative measurements of transferrin receptors, tissue transferrin, tissue iron uptake, and erythroid cellularity have been carried out in rats with altered erythropoiesis and altered iron balance. Erythroid receptors increased with erythroid hyperplasia, with the increase in proportion to the increased number of red cell precursors in phenylhydrazine-treated rats. Receptors increased disproportionately in iron deficiency due to both erythroid hyperplasia and an increase in receptors in the individual cell. There was a ratio of 1:1 between cell-related transferrin and receptors in circulating reticulocytes but a disproportionate amount of cell-related transferrin in fixed erythroid tissues (marrow and spleen), suggesting that there was some other reason for the concentration of transferrin in these tissues. Erythron iron uptake was increased in proportion to the increased receptor number in phenylhydrazine-treated animals but was reduced in iron deficiency because of the limited amount of iron-bearing transferrin. These studies demonstrate the dominant role of erythron cellularity and iron status in vivo in determining total receptor number and the importance of receptor number and iron supply in tissue iron uptake.

Anemia, Hemolytic↗
PubMed1988

Ferrokinetic measurement of erythropoiesis.

Ferrokinetic measurements have proved useful because of the dominant role of the erythron in tissue iron uptake. Detailed measurements of the plasma iron disappearance curve coupled with in vivo counting have defined the major pathways of iron utilization and early refluxes of iron into plasma. Recent studies have disclosed two separate plasma kinetic pools consisting of mono- and diferric transferrin, and have demonstrated the effect of their relative abundance on tissue iron uptake. Allowance for the amount of each has made possible the calculation of iron-bearing transferrin uptake, which is independent of plasma iron concentration as long as receptors are saturated. This refinement permits the measurement of functional erythron transferrin receptors, and thereby the relative number of immature erythroid cells.

Anemia↗