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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 325 records · Page 18Linked to original sources
PubMed1978

Iron uptake by Chang cells from transferrin, nitriloacetate and citrate complexes: the effects of iron-loading and chelation with desferrioxamine.

Iron uptake by Chang liver cells in culture is about thirty times as great when ferric nitriloacetate is used as a donor as when iron-transferrin is used. Iron uptake from ferric citrate is no greater than from iron-transferrin. Most of the intracellular iron derived from transferrin is found in the supernatant after 20 000 x g centrifugation of the cell homogenate for 40 min: about half of this is in the form of ferritin. Iron derived from ferric nitriloacetate is found largely in the membranous pellet after centrifugation and very little of this is in the form of ferritin. Iron incorporated in cytosol ferritin is easily available for chelation by desferrioxamine and this process is facilitated by ascorbic acid. Membrane-bound iron is less available for chelation. This tissue culture model forms a convenient basis for the study of iron overlead and iron chelation.

Cells, Cultured↗
PubMed1978

Properties of human tissue isoferritins.

1. Human liver ferritin was separated by preparative isoelectric focusing into six fractions. 2. Except for the least acidic fraction the reactivity with antibody against spleen ferritin increased with rising pI, but with antibody against heart ferritin the reactivity decreased. 3. The highest iron content was found in the most acidic isoferritins and progressively decreased with rising pI. 4. Iron uptake was studied in apoferritin prepared from heart and liver ferritin fractions separated by ion-exchange chromatography. There was good correlation between the rate of iron uptake and pI. The most acidic fractions took up iron more rapidly than did the more basic ones. 5. Ferritin was prepared from heart, liver, spleen and kidney. There was little difference on isoelectric focusing between ferritin obtained from normal tissues and the corresponding iron-loaded tissues from patients who had received multiple blood transfusions. The iron-loaked heart ferritin invariably contained relatively more of the basic isoferritins. Normal and iron-overloaded heart ferritins were separated into isoferritin fractions by ion-exchange chromatography, and in each case there was a fall in iron content as the pI increased. The iron content of ferritin from the iron-overloaded heart was higher throughout than that from normal heart. 6. There is a relationship between the rate of iron uptake by apoferritin and pI, and this probably accounts for the variation in iron content of the isoferritins found in human liver and heart.

Apoferritins↗
PubMed1978

Synthesis and analgesic-antiinflammatory activity of some 4- and 5-substituted heteroarylsalicylic acids.

We have made a series of 4- and 5-aryl- and 4- and 5-heteroarylsalicylic acid derivatives with the objective of reducing gastric irritation and increasing potency. Here we describe a series of 4- and 5-heterocyclic salicylic acids and their antiinflammatory-analgesic potencies measured in comparison to aspirin. An improvement of the therapeutic index over aspirin of 100 was achieved; however, the heterocyclic salicylic acids lacked antipyretic activity. Some physicochemical parameters which may bear on the antiinflammatory activity of these compounds are discussed.

Animals↗
PubMed1978

The development of new iron-chelating drugs. II.

For the past several years, we have searched for an orally effective iron-chelating drug and report here on several compounds which warrant further investigations based on their ability to promote iron excretion in the hypertransfused rat. Administrered orally, 2,3-dihydroxybenzyolglycine induced both urinary and fecal iron excretion, suggesting that a conjugate of 2,3-dihydroxybenzoic acid may be more efficacious than the parent compound. Tropolone, although rather toxic, stimulated fecal excretion of iron when given p.o. at low doses. Evaluation of less toxic derivatives of tropolone appears to be justifiable. L-Histidine may also be of use in chelatin therapy. Fecal iron excretion is significantly increased in response to oral doses of this essential amino acid. Lastly, cholylhydroxamic acid proved to be the most efficacious oral agent examined thus far. A marked increase in fecal iron excretion results from its administration.

Animals↗
PubMed1977

Isoferritins in acute leukaemia.

Leucocytes containing a high proportion of blast cells were obtained from 11 patients with acute myeloid leukaemia, and leucocytes were also obtained from 2 normal subjects. Ferritin was partially purified from leucocyte extracts and subjected to anion-exchange chromatography and isoelectric focusing. The Fe content of leucocyte ferritin was low, and in all but one case the preparations contained isoferritins corresponding to those found in normal tissues or serum. Only some of the preparations contained the relatively acidic isoferritins which have been described as "carcinofoetal", but which are also present in normal heart and kidney. Ferritin from one patient contained isoferritins of lower isoelectric point than heart ferritin. These results show that there does not appear to be any specific isoelectric focusing pattern for leukaemic cells, and that assays for acidic isoferritins are unlikely to be of use in the diagnosis of leukaemia and in monitoring treatment. However, the very acidic protein found in one preparation suggests that the search for abnormal subunits of ferritin may be fruitful in acute leukaemia.

Chromatography, Ion Exchange↗
PubMed1977

Ferrokinetics and erythropoiesis in man: red-cell production and destruction in normal and anaemic subjects.

Recent advances in the analysis of plasma 59Fe clearance have produced a unified method for measuring effective and ineffective erythropoiesis (Ricketts et al, 1975). We have used this method to investigate the balance between red-cell production and destruction in normal subjects and in patients with megaloblastic anaemia, iron deficiency anaemia, and refractory hypoplastic anaemia. The results show that the normal marrow can maintain an appropriate red-cell mass by altering red-cell production to match destruction. In the anaemias we have studied there is an increased rate of either intra- or extra-medullary red-cell destruction. The response of the marrow may be limited by iron supply, by defective nuclear maturation or by some intrinsic marrow defect.

Adult↗
PubMed1977

Ferrokinetics and erythropoiesis in man: an evaluation of ferrokinetic measurements.

The plasma iron clearance half-time and plasma iron turnover have usually been interpreted as measures of total erythroid activity and the red-cell utilization of 59Fe has been equated with effective red-cell production. Erythrocyte iron turnover has sometimes been calculated as the product of plasma iron turnover and percentage utilization. We have assessed these measurements as estimates of erythroid activity by comparing them with total marrow iron turnover and red-cell iron turnover determined by the method of Ricketts et al (1975) in 10 normal subjects and 51 patients with an uncomplicated haematological disorder. The results show that the plasma iron clearance half-time does not reflect erythroid activity and that plasma iron turnover can be particularly misleading in patients with reduced marrow activity. Red-cell utilization and erythrocyte iron turnover give a distorted reflection of effective erythropoiesis except in patients with erythroid hypoplasia. Marrow iron turnover and red-cell iron turnover provide more realistic and generally applicable assessments of the degree and effectiveness of erythroid activity.

Bone Marrow↗
PubMed1977

Low molecular weight intracellular iron transport compounds.

Evidence is presented for the existence of an intracellular pool of low molecular weight iron compounds which acts as an intermediate between extracellular iron and a wide variety of intracellular processes. It is in equilibrium with storage iron and iron enzymes and is of major importance in iron toxicity and chelation therapy.

Biological Transport↗