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Biomedical subjects

A M Konijn

Publications and source records attributed to A M Konijn.

At least 19 recordsLinked to original sources
PubMed1995

Ferritin does not accumulate iron oxidized by caeruloplasmin.

Ferritin is an iron-storage protein ubiquitous in mammals, plants and bacteria. It can be reconstituted, in vitro, from the apoprotein and Fe(II) salts in the presence of dissolved oxygen. Recently it has been reported that caeruloplasmin can facilitate apoferritin reconstitution and that iron oxidized by caeruloplasmin is sequestered within the ferritin shell. Here we show that the primary effect of adding caeruloplasmin to horse spleen ferritin during reconstitution is the competition between the two molecules for the iron. This competition results in overall increased rates of iron oxidation and a mixture of products, namely iron-containing ferritin and iron hydroxy polymers attached to caeruloplasmin. Iron oxidized by caeruloplasmin is not incorporated, to any significant extent, into horse spleen ferritin.

Animals↗
PubMed1994

Iron metabolism in inflammation.

Alteration in iron metabolism is one of the proposed mechanisms underlying the anaemia of inflammation and chronic disease, the most common disorder in hospitalized patients. Iron metabolism parameters in inflammatory disease are characterized by blockage of tissue iron release, decreased serum iron and total iron binding capacity and an elevated serum ferritin level, reflecting augmented ferritin synthesis as part of the acute-phase response. The altered iron metabolism in inflammation is proposed to be a part of the host defence mechanism against invading pathogens and tumor cells and is suggested to be mediated by inflammatory cytokines and NO.

Anemia, Iron-Deficiency↗
PubMed1994

Binding and uptake of exogenous isoferritins by cultured human erythroid precursor cells.

The interaction of extracellular human isoferritins with normal erythroid precursors developing in a two-phase liquid culture was studied. Cells at the stage of polychromatic normoblasts exhibited substantial specific binding of radioiodinated placental isoferritins. Considerably more acidic isoferritin was bound than basic isoferritin. The binding of ferritin was significantly higher at 37 degrees C than at 4 degrees C. All of the 125I-acidic isoferritin bound at 4 degrees C, but only part of that bound at 37 degrees C, could be dislodged by the addition of 500-fold excess of non-labelled acidic isoferritin. Acidic isoferritin displaced radio-iodinated acidic isoferritin from the erythroid cells more efficiently than intermediate or basic isoferritins. Kinetic analysis suggests a dissociation constant (Kd) of 3.9 x 10(-8) M for acidic ferritin and 3.7 x 10(-7) M for basic isoferritin. The average number of binding sites for acidic isoferritin was 1.3 x 10(5) per cell. The results point to specific binding and receptor-mediated internalization for predominantly acidic isoferritin by developing human erythroid cells.

Cells, Cultured↗
PubMed1992

Non-transferrin-bound iron species in the serum of hypotransferrinaemic mice.

Serum from homozygous hypotransferrinaemic mice (a mixed group of males and females, aged 6-8 wk) was found to contain low levels of iron (mean 0.9 +/- 0.5 microM (SEM, n = 4), as assayed by conventional serum iron assays. Similarly, low levels of non-transferrin-bound iron were determined with a nitrilotriacetate chelation assay (1.3 +/- 0.4 microM, n = 4) (Singh, S., Hider, R.C. and Porter, J.B. (1990) Analytical Biochemistry 186, 320-323). Mononuclear Fe (citrate) was undectable by electron paramagnetic resonance spectroscopy (EPR). Significantly larger quantities of iron (16 +/- 5 microM, n = 8) were detected by the bleomycin assay (Gutteridge, J.M.C., Rowley, D.A. and Halliwell, B. (1981) Biochemical Journal 199, 263-265), while non-haem iron assay or atomic absorption spectrophotometry revealed up to 96 microM iron. Haemoglobin iron was detectable at approximately 10 microM by spectrophotometry. Ferri-haem was undetectable by EPR spectroscopy. Serum ferritin levels of 641 +/- 128 micrograms/l (n = 14) in hypotransferrinaemic mice (wild-types 44 +/- 6 micrograms/l, n = 14) were observed and these cannot account for the non-transferrin-bound iron. Hypotransferrinaemic mouse serum therefore contains large quantities of non-transferrin-bound iron which is unreactive in some assays used to detect such iron in human iron overload. Fractionation by Sephadex G200 chromatography revealed three distinct species with apparent molecular weights of > or = 150 kDa, 40-80 kDa and 1-5 kDa. The iron may be distinguished from known extracellular iron proteins and haem-proteins by its availability to hot acid extractions.

Animals↗
PubMed1992

Glycosylated serum ferritin in patients with hematological malignancies before and after bone marrow transplantation.

Glycosylated and total serum ferritin levels were monitored in patients with acute leukemia and lymphoma undergoing bone marrow transplantation (BMT). Serum ferritin was high in relapsing patients and normal in most patients in complete remission (CR). In patients with an uncomplicated course, levels of ferritin increased during the first month after BMT with subsequent decrease. Three patients with lymphoma and five with acute leukemia had high serum ferritin levels despite achieving apparent complete hematological remission which was of short duration. The results were compared with groups of lymphoma patients at presentation and during remission and with healthy normal controls. In all the lymphoma patients and in 3 of the 5 leukemia patients the percent of ferritin glycosylation was normal at CR. It was low at the time of diagnosis in all patients. Thus, the percent glycosylation proved a more reliable marker for clinical remission than total serum ferritin. During follow up after BMT in uncomplicated cases, the percent of glycosylated ferritin returned to normal levels earlier than the total serum ferritin. These findings indicate that the evaluation of the amount of glycosylated ferritin may provide useful information in hematological patients in whom there is a discrepancy between high serum ferritin levels and the clinical condition.

Bone Marrow Transplantation↗
PubMed1990

Specific binding of placental acidic isoferritin to cells of the T-cell line HD-MAR.

Acidic placental isoferritin inhibited the blastogenic response of peripheral human lymphocytes to T-cell activating lectins. We measured specific binding of radioiodinated placental isoferritin to cells of the T-cell line HD-MAR and found specific high-affinity binding. Binding was faster and more ferritin was bound at 37 degrees C than at 4 degrees C. Displacement experiments indicated that most of the binding occurred at the cell surface. Acidic placental ferritin and isolated H-type ferritin subunits but not isolated L-type subunits, competed for the binding. Scatchard plot analysis showed characteristics of a single binding species with a dissociation constant (Kd) of 1.3-4.4 x 10(-11) M. The results suggest the presence of receptors for acidic isoferritin on T-lymphocytes and thus, a regulatory role for the acidic ferritin H-type subunit in T-cell function.

Binding, Competitive↗
PubMed1988

Diagnostic value of ferritin in malignant pleural and peritoneal effusions.

The diagnostic usefulness of ferritin measurements in pleural and peritoneal effusions has been evaluated in 57 patients. Mean (+/- standard error [SE]) ferritin levels were 291 +/- 50 ng/ml in 24 patients with noninflammatory transudates (Group I), 942 +/- 253 in 15 patients with nonmalignant exudates (Group II), and 1805 +/- 257 in 18 patients with malignant exudates (Group III). The mean (+/- SE) ratio of effusion/serum ferritin in Groups I, II, and III was 0.7 +/- 0.1, 2.7 +/- 0.7, and 5.7 +/- 1.2, respectively. The specificity and predictive value of a ferritin ratio in excess of 1.5 in distinguishing transudates from all exudates and in distinguishing transudates from malignant exudates were both very high (94%) to 96%). In the lower range of values considerable overlap existed between ferritin ratios obtained in patients with benign versus malignant inflammatory exudates. However, very high ferritin levels (greater than 3000 ng/ml) and ferritin ratios (greater than 20:1) were only encountered in malignant exudates. These results indicate that the measurement of ferritin levels and ferritin ratios may be a useful aid in the diagnosis of malignant pleural and peritoneal effusions.

Adult↗
PubMed1988

Serum ferritin levels in preterm infants after multiple blood transfusions.

We have examined the effect on iron stores of blood transfusions given to premature neonates during hospitalization in the neonatal intensive care unit as reflected by serum ferritin levels measured for 6 months after discharge. Premature infants who were transfused with more than 100 ml packed cells (group D; n = 11) had higher ferritin levels for a longer period than premature infants who were transfused with smaller volumes (group c; n = 9) or premature and mature infants who were not transfused at all (group B; n = 24 and group A; n = 21, respectively). At 4-5 months the serum ferritin levels in group D (489.8 +/- 132.1 micrograms/L; mean +/- SEM) were significantly higher (P less than 0.001) than those of the other groups. The level of group A term infants (77.5 +/- 12.5 micrograms/L) was higher than those of group B premature infants who did not receive a blood transfusion (33.0 +/- 7.1 micrograms/L) or group C who received less than 100 ml (36.5 +/- 8.8 micrograms/L packed red blood cells. However, these differences were not statistically significant. Our data demonstrate that very-low-birthweight infants who receive a large volume of packed cells during hospitalization may accumulate iron stores sufficient for red cell production during the first 6 months of life. Administration of large amounts of supplemental iron, in such cases, may be curtailed.

Anemia, Hypochromic↗
PubMed1987

Serum ferritin in patients undergoing bone marrow transplantation.

Serum ferritin levels were monitored in nine patients with acute lymphoblastic leukemia (ALL), nine patients with acute nonlymphoblastic leukemia (ANLL), four patients with chronic myelogenous leukemia (CML), three patients with non-Hodgkin's lymphoma (NHL), and three patients with severe aplastic anemia (SAA) undergoing bone marrow transplantation (BMT) for hematologic malignancies or aplastic anemia. Serum ferritin analysis was performed before and after BMT at monthly intervals and/or according to the clinical condition of the patient. Serum ferritin increased considerably during the first 3 months following BMT and then decreased in patients with an uncomplicated course. Ferritin levels in the serum of patients who had undergone BMT decreased gradually when complete remission was achieved, but increased with any clinical complication. Thus, elevation of serum ferritin concentration was predictable for clinical complications and for relapse. Patients with acute leukemia with serum ferritin levels above 400 micrograms/l at time of BMT had a risk of relapse within 1 year, triple that patients with lower ferritin levels. All patients who underwent BMT to treat severe aplastic anemia have completely recovered. Accordingly, following an initial increase after BMT, serum ferritin levels returned to normal and remained so in line with the patients' good clinical condition. The findings indicate that serum ferritin yields useful information in the clinical evaluation of patients undergoing BMT.

Adolescent↗
PubMed1987

Effect of extracellular hemin on hemoglobin and ferritin content of erythroleukemia cells.

Mouse (MEL) and human (K-562) erythroleukemia cell lines can be induced to undergo erythroid differentiation, including hemoglobin (Hb) synthesis, by extra cellular hemin. In order to study the effect of extracellular hemin on intracellular ferritin and Hb content, we have used Mossabauer spectroscopy to measure the amount of 57Fe incorporated into ferritin or Hb and a fluorescent enzyme-linked immunosorbent assay (ELISA) to measure the ferritin protein content. When K-562 cells were cultured in the presence of a 57Fe source either as transferrin or citrate, in the absence of a differentiation inducer, all the intracellular 57Fe was detected in ferritin. When the cells were cultured in the presence of 57Fe-hemin, 57Fe was found in both ferritin and Hb. 57Fe in ferritin increased rapidly, and after 2 days it reached a plateau at 5 X 10(-14) g/cell. 57Fe in Hb increased linearly with time and reached the same value after 12 days. Addition of other iron sources such as iron-saturated transferrin, iron citrate, or iron ammonium citrate caused a much lower increase in ferritin protein content as compared to hemin. When K-562 cells were induced by 57Fe-hemin in the presence of 56Fe-transferrin, 57Fe was found to be incorporated in equal amounts into both ferritin and Hb. However, when the cells were induced by 56Fe-hemin in the presence of 57Fe-transferrin, 57Fe was incorporated only into ferritin, but not into Hb, which contained 56Fe iron. These results indicate that in K-562 cells, when hemin is present in the culture medium it is preferentially incorporated into Hb, regardless of the availability of other extra- or intracellular iron sources such as transferrin or ferritin. In MEL cells induced to differentiate by dimethylsulfoxide (DMSO) a different pattern of iron incorporation was observed; 57Fe from both transferrin and hemin was found to incorporate in ferritin as well as in Hb.

Animals↗
PubMed1986

Cerebrospinal fluid ferritin in malignant CNS involvement.

Cerebrospinal fluid (CSF) ferritin was measured in patients with benign inflammatory and noninflammatory neurologic disorders and in patients with malignant disease with and without documented central nervous system (CNS) involvement. CSF ferritin levels were increased in the majority of patients with inflammatory neurologic disease and in patients with malignant involvement of the CNS. In contrast, in patients with noninflammatory neurologic disorders and in malignant disease without CNS involvement, CSF ferritin levels were normal. These findings indicate that although the specificity of CSF ferritin measurement is limited, it is a highly sensitive test that may be useful in the initial evaluation of patients with malignant CNS involvement, and in assessing their response to therapy.

Adult↗
PubMed1985

Isolation and fractionation of ferritin from human term placenta--a source for human isoferritins.

A method for isolating ferritin from human term placenta was described. The placenta was homogenized in water containing protease inhibitor and heated at 70 degrees C. The ferritin was precipitated with ammonium sulfate at pH 5.2 and purified by repeated cycles of ultracentrifugation and molecular sieve chromatography through Sepharose 4B columns. Isoelectric focusing revealed a broad spectrum of isoferritins. These isoferritins were separated by ion-exchange chromatography on Sephadex A-25 at pH 7.5 and stepwise elution with increasing concentrations of NaCl. By this method "basic," "intermediate," and "acid" isoferritins were separated. The most basic placental isoferritin was shown to be identical to splenic ferritin by isoelectric focusing, subunit analysis, and fluorescent ELISA. The acid placental isoferritin had similar characteristics to heart-type ferritin. It was suggested that the easily available placental tissue could serve as a source for human isoferritins in research and in clinical assays.

Carbonic Anhydrases↗
PubMed1985

Changes in cellular ferritin content during myeloid differentiation of human leukemic cell lines.

The human promyelocytic cell lines HL-60 can be induced to undergo differentiation to either granulocyte- or macrophage-like cells. We followed the changes in the synthesis and content of ferritin in this and other cell lines during differentiation. Ferritin content of HL-60 cells ranged from 11 to 81 fg/cell, depending on the clone tested. Following exposure to dimethylsulfoxide (DMSO) or retinoic acid (RA) an increase in ferritin and a decrease in total protein synthesis was observed, resulting in increased ferritin content, reaching a peak after 2 days. This increase occurred prior to the appearance of the typical morphological and functional characteristics of mature granulocytes. A correlation was found between concentrations of DMSO effective in inducing differentiation and the increase in ferritin content. Other inducers of granulocyte differentiation had a similar effect, while 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of macrophage differentiation, had not. Another human cell line (U-937), which was induced into monocyte-like cells by RA, showed a twofold increase in ferritin content following differentiation. Addition of iron to the culture medium increased ferritin content of both differentiating and non-differentiating cells, but the former responded to lower concentrations of iron. The increase in ferritin during differentiation, however, was not related to an accelerated iron uptake. The present results suggest that changes in the intracellular ferritin of the developing myeloid cells may play a regulating role in the process of maturation of these cells.

Cell Differentiation↗
PubMed1985

Differential effect of isolated placental isoferritins on in vitro T-lymphocyte function.

The effect of isoferritins isolated from human term placenta on certain T-lymphocyte parameters was studied in vitro using normal human lymphocytes. These isoferritins differed in ion exchange affinity, isoelectric point, and subunit composition. Only the acidic isoferritins caused a marked suppression of phytohaemagglutinin (PHA) blastogenesis and the most acidic isoferritin ('Acid I') was suppressive at a concentration as low as 0.25 microgram/ml. All four isoferritins suppressed concanavalin A (Con A) blastogenesis in a similar concentration dependent manner, with maximum effect at an isoferritin concentration of 1 microgram/ml. Both basic and acidic isoferritins reduced the Con-A-capping phenomenon in normal lymphocytes at concentrations higher than 0.5 microgram/ml, but at 0.25 microgram/ml only the acidic isoferritin was effective. The above findings support our previous report concerning the suppressive effect of splenic ferritin on T-lymphocyte function in vitro and indicate that acidic isoferritins, which often predominate in malignancy, demonstrate a higher degree of immunosuppressive activity. Thus, acidic isoferritins may play a role in the development of abnormal lymphocyte function encountered in certain proliferative disorders.

Concanavalin A↗
PubMed1985

Combined use of zinc protoporphyrin (ZPP), mean corpuscular volume and haemoglobin measurements for classifying microcytic RBC disorders in children and young adults.

The diagnostic potential of the combined use of zinc-protoporphyrin (ZPP), mean corpuscular volume (MCV) and haemoglobin measurements for discriminating between iron deficiency anaemia, beta-thalassaemia minor and lead poisoning has been studied. Lead poisoning could be identified by ZPP greater than 50 micrograms/dl in the presence of normal MCV or ZPP greater than 150 micrograms/dl in the presence of microcytosis (MCV less than 80 fl) with a sensitivity of 97% and specificity 94%. Beta-thalassaemia minor was identified by the coexistence of microcytosis and ZPP less than 50 micrograms/dl with a sensitivity of 91% and specificity 79%. Iron deficiency anaemia defined by the combination of microcytosis and ZPP ranging from 50 to 150 micrograms/dl was identified with a sensitivity of 95%, but the specificity was only 51%, with many of the patients overlapping with thalassaemia minor. This problem did not exist in iron-deficiency anaemia with haemoglobin less than 10 g/dl as at that range no patients with uncomplicated thalassaemia minor have been encountered. A great advantage of the combined use of ZPP, MCV and haemoglobin for the initial screening of microcytic anaemia is its ease of performance and low cost. However, this information should only be regarded as presumptive evidence of disease, requiring subsequent confirmation by appropriate direct measurements such as transferrin saturation, serum ferritin, haemoglobin electrophoresis, or blood lead determinations.

Adolescent↗