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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 307 records · Page 17Linked to original sources
PubMed1980

Serum ferritin in patients with cancer: determination with antibodies to HeLa cell and spleen ferritin.

Some malignant tissues and cell lines contain acidic isoferritins and it has been suggested that the assay of such isoferritins in serum may be of value in the diagnosis of malignancy. This paper describes a radioimmunoassay for acidic ferrtin purified from HeLa cells. Examiniation of purified heart, kidney, liver and spleen ferritin showed that the assay was highly specific for acidic isoferritins. Ferritin concentrations have been measured with antibodies to HeLa cell and spleen ferritin in extracts of normal and tumour tissue. Although the tumours contained more HeLa type ferritin than the corresponding normal tissue the HeLa/spleen type ferritin ratio was low. HeLa-type ferritin concentrations have been compared with values obtained with anti-spleen ferritin in over 1000 sera from normal subjects and patients with cancer and leukaemia. HeLa-type ferritin as not detected ( less than 2 micrograms/l) in most normal sera. Concentrations of up to 53 micrograms/l were found in sera from patients with malignant disease but the HeLa/spleen type ferritin ratio was always very low. There appears to be little application for antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of cancer.

Breast Neoplasms↗
PubMed1980

Transferrin-bipyridine iron transfer mediated by haemoproteins.

Rabbit reticulocyte cytosol was able to mediate transferrin-bipyridine iron transfer in the presence of ATP. The cytoplasmic factor responsible for the mediation of iron transfer was identified as haemoglobin. Other cytoplasmic proteins and the membrane fraction were ineffective. Human alpha and beta subunits and human myoglobin were over three times more effective than human haemoglobin A. Carbon monoxide strongly inhibited the mediation of iron transfer. Oxidation of haemoglobin abolished it but methaemoglobin could be reactivated with NADH, even when azide was bound to the haem iron. Neither globin nor haem alone were able to mediate iron transfer, even when NADH was present. Together, the reconstituted methaemoglobin A could be reactivated wtih NADH. Although the physiological significance of this pehnomenon is not clear, the involvement of haemoproteins in intracellular iron metabolism seems likely.

2,2'-Dipyridyl↗
PubMed1980

Trypsin activation of human factor XI.

Human factor XI circulates as a zymogen composed of two similar or identical chains of Mr = 80,000. Upon activation either by trypsin or by blood-clotting proteins involving clotting factors XII and high molecular weight kininogen, it undergoes proteolytic cleavage in which the Mr = 80,000 chain reportedly is cleaved to a heavy and light chain of Mr of about 48,000 and 33,000, respectively. In these studies, we have reinvestigated trypsin activation of factor XI and demonstrate that trypsin-activated factor XI contains three chains of apparent Mr = 46,000, 37,000, and 26,000. Kinetic studies lead to the conclusion that the parent chain of Mr = 80,000 is cleaved into chains of Mr = 46,000 and 37,000. This cleavage is followed by a second nondestructive cleavage, most probably of the chain of Mr = 46,000, to yield the third product which migrates as a band of Mr = 26,000.

Enzyme Activation↗
PubMed1980

Binding of serum ferritin to concanavalin A: patients with homozygous beta thalassaemia and transfusional iron overload.

Serum ferritin concentrations have been measured in 124 patients with homozygous beta thalassaemia who were between 2 and 21 years old, had received 11--504 units of blood but had not undergone splenectomy. There were highly significant correlations between serum ferritin concentration and both the amount of blood transfused and alanine amino-transferase (ALT) activity. However, multivariate analysis showed that units of blood and ALT activity together only accounted for about 30% of the variation in serum ferritin concentration. Little of the remaining variation could be explained by other variables related to iron metabolism or liver damage. The concentration of concanavalin A binding ferritin increased rapidly with the number of units of blood up to 100 units but thereafter showed no further increase with number of transfusions. The concentration of non-binding ferritin was more closely related to transfusion load. These results suggest that the secretion of glycosylated ferritin from reticuloendothelial cells reaches a maximum with increasing iron accumulation, perhaps reflecting a maximum rate of synthesis. Ferritinaemia in patients with transfusional iron overload therefore seems to be the result of the combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells. A simple relationship between serum ferritin and iron stores cannot be assumed when ferritin concentrations exceed 4000 microgram/l or in patients who have received more than 100 units of transfused blood.

Adolescent↗
PubMed1980

Biochemical and immunological characterization of ferritin from leukaemic cells.

Ferritin was prepared from the leucocytes of four patients with acute myeloblastic leukaemia (AML) and eight patients with chronic myeloid leukaemia (CML). Isoelectric focusing demonstrated a prominent relatively basic band in all the CML cell ferritins. The iron content of all the ferritins was very low (max 180 atom/molecule). Thus there was little evidence for the role of leucocyte ferritin as an iron store or for iron as the major factor responsible for the initiation of ferritin synthesis. The iron uptake properties, subunit analyses, immunological reactivities and other immunological studies indicated that leukaemic cell ferritins had similar properties to tissue ferritins.

Acute Disease↗
PubMed1979

Erythropoiesis and iron metabolism in Hodgkin's disease.

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.

Adolescent↗
PubMed1979

Binding of human serum ferritin to concanavalin A.

1. A high proportion of the ferritin in normal serum binds to concanavalin A. Binding is prevented by the addition of alpha-D-methylglucoside to the reaction mixture. 2. Ferritin in extracts of normal heart, liver and spleen or serum ferritin from patients with massive hepatic necrosis does not bind to concanavalin A. 3. Isoelectric focusing of preparations of serum ferritin from patients with primary haemochromatosis shows that the ferritin fraction binding to concanavalin A consists, predominantly, of the more acidic isoferritins. 4. These findings suggest that carbohydrate residues may be added to ferritin during its secretion into the plasma. Glycosylation may account for the heterogeneity of serum ferritin on isoelectric focusing. 5. Direct release of intracellular ferritin from damaged tissue may be indicated by an increase in the proportion of circulating ferritin which does not bind to concanavalin A. Such an increase has been found in sera from patients with iron overload.

Concanavalin A↗
PubMed1979

Erythropoiesis, iron stores and tissue iron exchange in man.

1. The exchange of iron between plasma and erythroid and non-erythroid tissues was measured in 14 normal subjects, 17 iron-deficient patients, nine patients with primary idiopathic haemochromatosis and in 13 patients with haemolytic disorders. 2. The two main factors determining tissue iron turnover were shown to be the level of iron stores and the erythropoietic activity of the bone marrow.

Adult↗
PubMed1979

Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects.

Plasma concentrations of desferrioxamine and ferrioxamine were measured following bolus injections of desferrioxamine and during 24 h infusions of the drug. [59Fe]ferrioxamine clearance and urinary iron excretion were also measured. Higher plasma ferrioxamine concentrations were found in iron loaded subjects and higher desferrioxamine concentrations in subjects with normal ironloads. There is a correlation between the circulating concentration of ferrioxamine during an infusion and the 48 h urinary iron excretion. The data suggests that the amount of iron chelated in vivo is related to an increase in the size of an intermediate chelatable pool rather than the total amount of the iron load. The well-recognized delay in urinary iron excretion appears to be related to active tubular reabsorption of ferrioxamine.

Blood Transfusion↗
PubMed1979

The effect of desferrioxamine on fibroblasts and collagen formation in cell cultures.

Iron is essential for the activity of proline hydroxylase and is an important co-factor in collagen synthesis. Fibroblast cultures exposed to desferrioxamine show impairment of DNA synthesis and reduced collagen formation, as measured by hydroxyproline synthesis and the deposition of hydroxyproline in the cell mat. In patients with transfusional iron overload long-term treatment with desferrioxamine is said to result in the inhibition of hepatic fibrosis. It is suggested that this may be a direct effect on collagen synthesis rather than an effect of reduced iron stores.

Cell Division↗
PubMed1979

Effective iron chelation following oral administration of an isoniazid-pyridoxal hydrazone.

When isoniazid and pyridoxal are mixed in equimolar quantities a hydrazone is formed which is able to complex with iron. The oral administration of this compound to rats in single doses of 25--100 mg/kg leads to an increase in faecal iron excretion up to 8 times the normal level. In tissue culture the compound is able to remove iron from Chang cells. The results suggest that this compound may be of potential value for the oral therapy of iron overload.

Animals↗