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Biomedical subjects

C A Finch

Publications and source records attributed to C A Finch.

At least 55 records · Page 3Linked to original sources
PubMed1986

Hematopoiesis in the rat: quantitation of hematopoietic progenitors and the response to iron deficiency anemia.

To determine the quantitative effects of iron deficiency on erythropoiesis and to assess the response of erythroid progenitors to sustained anemia, we developed quantitative assays for various hematopoietic progenitors in the adult, Sprague-Dawley rat including erythroid colony- and burst-forming cells (CFU-E and BFU-E), granulocyte/macrophage colony-forming cells (CFU-GM), and megakaryocytic colony-forming cells (CFU-Meg). CFU-E were cultured in methylcellulose and grew best in the presence of fetal calf serum. CFU-GM, BFU-E, and CFU-Meg grew better in normal rat plasma and required the presence of pokeweed mitogen-stimulated rat spleen cell conditioned medium. The numbers of progenitors and nucleated erythroblasts in total marrow were estimated by the ratios of radioactivity in the humerus to the total skeleton as determined by radioiron dilution. The numbers of progenitors and erythroblasts in the spleen were measured by simple dilution. Sustained anemia was brought about through chronic iron deficiency. The response to iron deficiency anemia (IDA) was monitored by the numbers of the various progenitors and their cell cycle characteristics as measured by the tritiated thymidine suicide technique. With IDA, the number of CFU-F in the body (marrow plus spleen) was increased to 3.5 times control, whereas the numbers of BFU-E and CFU-GM were unchanged. There was no difference in the percentage of CFU-E, BFU-E, and CFU-GM in DNA synthesis (68%, 19.4%, and 18.8%, respectively). With iron therapy of IDA, CFU-E numbers in marrow began to decrease by day 1 and fell in a manner reciprocal to changes in the hematocrit. Marrow and spleen erythroblasts, 1.7 times control in IDA, increased further to 3.9 times control by the fourth day after iron administration. There was no change in BFU-E or CFU-GM numbers in response to iron repletion, although the fraction of progenitors increased in the spleen. Thus, IDA does not limit the increase in CFU-E seen with anemia, but does restrict erythroid maturation. Furthermore, the increase in CFU-E and the state of chronic anemia occur without detectable changes in the number of cell cycle state of the more primitive BFU-E.

Anemia, Hypochromic↗
PubMed1986

Rat transferrin gene expression: tissue-specific regulation by iron deficiency.

Rats raised on a low-iron diet were used as a model system for investigating the regulation of transferrin gene expression by iron deficiency. We quantitated transferrin mRNA in a variety of tissues from normal and iron-deficient rats and found that the level of transferrin mRNA in normal rat liver was about 6500 molecules per cell, while the level in iron-deficient animals was 2.4-fold higher. The increase of transferrin mRNA in iron deficiency was the result of a specific induction of transferrin gene transcriptional activity as measured in isolated nuclei. This increase in transferrin gene expression resulted in a corresponding increase in serum total-iron-binding capacity. Of the other tissues examined, moderate amounts of transferrin mRNA were found in brain (83 molecules per cell) and testis (114 molecules per cell), and low levels were measured in spleen and kidney. The transferrin mRNA content of brain, testis, spleen, and kidney remained unchanged in iron deficiency. The small intestine had no detectable transferrin mRNA in either normal or iron-deficient rats; however, transferrin protein was present, and its level was 2-fold higher in the iron-deficient group. We hypothesize that intestinal transferrin is synthesized in the liver and is delivered to the gut via the bile. Consistent with this idea, bile transferrin content was found to be elevated in iron deficiency and appeared to be sufficient to account for intestinal transferrin levels. In addition, treatment of plasma transferrin with bile caused an acidic shift in its isoelectric-focusing behavior so that it comigrated with intestinal transferrin.

Animals↗
PubMed1986

The effect of transferrin saturation on internal iron exchange.

Radioiron was introduced into the intestinal lumen to evaluate absorption, injected as nonviable red cells to evaluate reticuloendothelial (RE) processing of iron, and injected as hemoglobin to evaluate hepatocyte iron processing. Redistribution of iron through the plasma was evaluated in control animals and animals whose transferrin was saturated by iron infusion. Radioiron introduced into the lumen of the gut as ferrous sulfate and as transferrin-bound iron was absorbed about half as well in iron-infused animals, and absorbed iron was localized in the liver. The similar absorption of transferrin-bound iron suggested that absorption of ferrous iron occurred via the mucosal cell and did not enter by diffusion. The decrease in absorption was associated with an increase in mucosal iron and ferritin content produced by the iron infusion. An inverse relationship (r = -0.895) was shown between mucosal ferritin iron and absorption. When iron was injected as nonviable red cells, it was deposited predominantly in reticuloendothelial cells of the spleen. Return of this radioiron to the plasma was only 6% of that in control animals. While there was some movement of iron from spleen to liver, this could be accounted for by intravascular hemolysis. Injected hemoglobin tagged with radioiron was for the most part taken up and held by the liver. Some 13% initially localized in the marrow in iron-infused animals was shown to be storage iron unavailable for hemoglobin synthesis. These studies demonstrate the hepatic trapping of absorbed iron and the inability of either RE cell or hepatocyte to release iron in the transferrin-saturated animal.

Animals↗
PubMed1986

Iron metabolism.

Major aspects of iron metabolism are reviewed including iron absorption, internal iron distribution and iron storage along with the development of laboratory tests for the evaluation of iron status.

Anemia, Hypochromic↗
PubMed1986

Erythropoietic reserve in marrow-transplanted dogs.

The effect of marrow transplantation on erythropoiesis was studied in three normal dogs (T0), three irradiated dogs receiving compatible marrow (T1), and three irradiated dogs (T2) who donated their marrow to a recipient animal and then at a later date underwent a marrow transplant from the initial marrow recipient. Plasma iron turnover was measured (a) under basal conditions, (b) after plasma iron was elevated by iron infusion, and (c) after hemolytic anemia had been produced by phenylhydrazine. Basal plasma iron turnover in T0, T1, and T2 animals averaged 1.3, 1.0, and 1.3 mg/dl whole blood/day. Turnover of the three groups increased to 7.1, 6.2, and 6.4 mg/dl whole blood/day after the induction of anemia by phenylhydrazine. These values were converted from the transferrin saturation present at the time of the measurement to the calculated turnover at 100% saturation, thereby expressing the maximum capacity of tissues to assimilate iron. After this correction, the calculated maximum uptake was shown to be increased over basal by 3.7, 4.0, and 3.8 times. To validate this approach, an additional comparison was made between baseline turnovers at elevated levels of plasma iron and anemic animals at similarly elevated plasma iron levels. The increment of the three groups was shown to be 3.7, 3.9, and 4.0 times basal. These studies illustrate the use of a refined method of ferrokinetic evaluation of erythropoiesis and indicate that the proliferative reserve in transplanted animals is unimpaired.

Anemia↗
PubMed1986

Plasma ferritin determination as a diagnostic tool.

Plasma ferritin is a secretory component of intracellular ferritin synthesis. In normal persons its amount reflects the size of iron stores. A decrease to less than 12 mug per liter indicates iron deficiency. Increased iron stores are associated with an increased plasma ferritin level. Various other conditions, however, can increase the plasma ferritin concentration including increased metabolism, inflammation, tissue damage and neoplastic disease. The use of the plasma ferritin determination in diagnosing iron overload depends on excluding these other causes, leaving storage iron as the only explanation for the increased plasma ferritin. It is then necessary to establish the parenchymal nature of the iron overload by showing an elevated transferrin saturation and, if elevated, the more definitive liver biopsy should be done.

Ferritins↗
PubMed1986

Absorption of carbonyl iron.

The mechanism of carbonyl iron absorption has been studied in rats. Solubilization by gastric acid was a prerequisite for subsequent absorption. The slow rate of solubilization resulted in a more prolonged absorption, responsible for the low toxicity of carbonyl iron. Large doses of carbonyl iron were held for several days by the gastric mucosa of iron-deficient animals. Once it had been solubilized, the subsequent pathway of absorption by the intestinal mucosa and the amount absorbed was similar to that of ferrous ammonium sulfate.

Animals↗
PubMed1985

Molecular advantage of diferric transferrin in delivering iron to reticulocytes: a comparative study.

The delivery of transferrin iron from four animal species and man to homologous reticulocytes was measured at different transferrin saturations. Total iron uptake in the in vitro reticulocyte incubation model employed followed a hyperbolic curve, increasing as the transferrin saturation increased but at a progressively slower rate. In all species, there was a much greater iron delivery from diferric as compared to monoferric transferrin, the molecular advantage varying from 8:1 to 14:1. The majority of iron was delivered from diferric transferrin when transferrin saturations exceeded 13-19% depending on the species. Thus a general similarity exists in the transferrin-iron interactions in these mammalian species. Formuli have been provided whereby the iron utilization curve may be calculated when uptake has been determined at any one transferrin saturation.

Animals↗
PubMed1985

Transferrin saturation, plasma iron turnover, and transferrin uptake in normal humans.

The relationship between plasma iron, transferrin saturation, and plasma iron turnover was studied in 53 normal subjects whose transferrin saturation varied between 17% and 57%, in 25 normal subjects whose transferrin saturation was increased by iron infusion to between 67% and 100%, and in five subjects with early untreated idiopathic hemochromatosis whose transferrin saturation was continually elevated to between 61% and 86%. The plasma iron turnover of all of these subjects ranged from 0.45 to 1.22 mg/dL whole blood/d. The mean values for the above-mentioned three groups were 0.71 +/- 0.17, 1.01 +/- 0.11, and 1.01 +/- 0.13 mg/dL whole blood/d, respectively. Most of this variation, estimated at 72% by regression analysis, was due to a direct relationship between transferrin saturation and plasma iron turnover. This effect was attributed to a competitive advantage of diferric over monoferric transferrin in delivering iron to tissues. This was confirmed by the demonstration of a more rapid clearance of diferric as compared to monoferric transferrin in an additional group of eight normal subjects. Calculations were made of the amount of transferrin reacting with membrane receptors per unit time. Allowance was made for the noncellular (extravascular) exchange and for the 4.2:1 preference of diferric over monoferric transferrin demonstrated in vitro. The amount of iron-bearing transferrin leaving the plasma to bind to tissue receptors for 53 subjects with a transferrin saturation between 17% and 57% was 71 +/- 13; for 25 subjects with a saturation from 67% to 100%, 72 +/- 12; and for five subjects with early idiopathic hemochromatosis, 82 +/- 11 mumol/L whole blood/d. There were no significant differences among these groups. These studies indicate that while the number of iron atoms delivered to the tissues increases with increasing plasma iron and transferrin saturation, the number of iron-bearing transferrin molecules that leave the plasma per unit time to bind to tissue receptors is relatively constant and within the limits studied, independent of transferrin saturation.

Adult↗
PubMed1985

Assessment of an enzyme immunoassay for diagnosing gonorrhea.

Gonozyme, a nonculture enzyme immunoassay for the detection of Neisseria gonorrhoeae antigens from urogenital swab specimens, was approved by the FDA and introduced in the United States in 1982. This assay was compared to standard culture for N. gonorrhoeae in a number of independent studies. In 1983 a modification of the original Gonozyme was developed to improve the specificity of the assay. This modification, which has now replaced the original Gonozyme, was evaluated in clinical studies at eight sites in the U.S.

Diagnostic Errors↗
PubMed1985

Storage iron exchange in the rat as affected by deferoxamine.

The initial tissue localization and redistribution of radioactive iron injected intravenously into the rat as ferritin, chondroitin sulfate, and nonviable red cells was determined. Ferritin iron, initially localized in the hepatocyte, showed minimal redistribution over 24 hours in the normal animal. This may be compared with the active release of iron from the reticuloendothelial cell after the intravenous injection of nonviable red cells and chondroitin sulfate iron. All forms of iron were actively mobilized in iron-deficient animals. The effect of chelation of iron by deferoxamine (DFO) on the redistribution pattern over 4 to 6 hours was determined in iron-deficient, normal, iron-loaded, and phenylhydrazine-treated rats to evaluate the effect of iron stores and erythropoiesis. Use of DFO resulted in extensive chelation of radioactive iron within the hepatocyte and greatly reduced the amount of hepatocyte iron available for erythropoiesis. Very little chelation of reticuloendothelial cell-processed iron occurred, and there was little decrease in its utilization for red cell production. Total urinary chelate iron was independent of erythropoiesis but varied in parallel with the iron load of the animal. These studies suggest that DFO does not act on the reticuloendothelial cell but does have at least two sites of action, both of which relate to total storage iron. One involves hepatocyte stores with excretion into the intestinal tract. The other, possibly located at the hepatocyte membrane, results in urinary iron excretion.

Anemia, Hemolytic↗
PubMed1984

Occupancy of the iron binding sites of human transferrin.

The in vivo distribution of iron between the binding sites of transferrin was examined. Plasma was obtained from normal subjects under basal conditions and after in vitro and in vivo iron loading. Independent methods, including measurement of the transferrin profile after isoelectric focusing and cross immunoelectrophoresis, and determination of the iron content in the separated fractions were in agreement that there was a random distribution of iron on binding sites. This held true with in vitro loading, when iron was increased by intestinal absorption and with loading from the reticuloendothelial system. The data indicate that the distribution of apo-, monoferric, and diferric transferrins is predictable on the basis of the plasma transferrin saturation and negate the concept that iron loading of transferrin in vitro is a selective process with possible functional consequences in tissue iron delivery.

Adult↗
PubMed1984

Iron deficiency.

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Adolescent↗
PubMed1984

Protein depletion and iron deficiency in rats.

Rats were fed on low iron diets containing 5, 10 and 30% protein. All animals demonstrated typical iron deficiency. Body size was reduced as protein intake decreased. The severity of anemia was related to the growth of the animal. Erythropoiesis appeared to be stimulated in proportion to the severity of the anemia. Iron absorption from the iron-deficient diet appeared unaffected by the associated protein deficiency. When doubly depleted animals were refed with iron, there was active red blood cell production despite the protein-depleted state, whereas with protein refeeding there was resumption of growth and increased anemia. These studies demonstrate the inverse relationship between protein and iron deficiency states when they coexist.

Anemia, Hypochromic↗
PubMed1984

High-altitude adaptation and maximum work performance.

The treadmill work performance of rats at sea level with normal or elevated hematocrits was compared with that of rats conditioned in a hypobaric chamber at 450 Torr for 3 wk with similar hematocrit adjustments. A mean increase in hematocrit to 62 significantly improved the work performance of rats at sea level and at ambient O2 tensions of 100, 75, and 35 Torr. By contrast, rats conditioned in a hypobaric chamber with mean hematocrits of 40 and 58 performed similarly at all O2 tensions compared with sea-level rats with hematocrits of 43. Thus, although an increase in O2-carrying capacity of the blood of sea-level animals increased work capacity, altitude adaptation did not appear to result in any positive effect on work capacity, and indeed, seemed to interfere with the beneficial effect of polycythemia on maximum work performance.

Adaptation, Physiological↗
PubMed1984

Heterogeneity of the plasma iron pool: explanation of the Fletcher-Huehns phenomenon.

Observations on iron uptake by reticulocytes led Fletcher and Huehns to suggest differences in the behavior of the two iron-binding sites of the transferrin molecule. To clarify the continued controversy relating to this hypothesis, the original studies employing control plasma labeled with radioiron and the same plasma preincubated with reticulocytes were reexamined. Regardless of whether human or rabbit plasma was employed, there was a considerably higher uptake from the control plasma. Isoelectric focusing procedures and electrophoresis in urea gels revealed that the conspicuous difference in the amount of iron uptake is the result of differences in the proportion of di- to monoferric transferrin in the two plasmas and the competitive advantage of the diferric moiety. These studies provide an explanation for the Fletcher-Huehns phenomenon without invoking functional differences between the two sites for iron on the transferrin molecule.

Animals↗