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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 253 records · Page 14Linked to original sources
PubMed1986

The effect of isoferritins on granulopoiesis.

The evidence for a regulatory role of acidic isoferritins on hemopoiesis is not entirely consistent with our knowledge of ferritin biochemistry, and no clear picture of this phenomeonon has emerged. In the present study, we have been unable to confirm a consistent effect of purified heart (acidic), spleen (basic), or serum (glycosylated) isoferritins on CFU-GM colony formation in vitro. Inhibition of colony formation by cell extracts or conditioned media does not relate to the presence of acidic isoferritins, nor is this effect neutralized by a monoclonal antibody to acidic isoferritins. The composition of ferritin preparations previously described as inhibitory to CFU-GM colony growth could not be confirmed, and they were not found to be predominantly acidic in nature. Our data do not support a role for acidic isoferritins as inhibitors of granulopoiesis.

Bone Marrow Cells↗
PubMed1985

Structure-function relationship in allosteric aspartate carbamoyltransferase from Escherichia coli. I. Primary structure of a pyrI gene encoding a modified regulatory subunit.

In a previous article, we have identified a lambda bacteriophage directing the synthesis of a modified aspartate carbamoyltransferase lacking substrate-co-operative interactions and insensitive to the feedback inhibitor CTP. These abnormal properties were ascribed to a mutation in the gene pyrI encoding the regulatory polypeptide chain of the enzyme. We now report the sequence of the mutated pyrI and show that, during the generation of this pyrBI-bearing phage, six codons from lambda DNA have been substituted for the eight terminal codons of the wild-type gene. A model is presented for the formation of this modified pyrI gene during the integrative recombination of the parental lambda phage with the Escherichia coli chromosome. An accompanying paper emphasizes the importance of the carboxy-terminal end of the regulatory chain for the homotropic and heterotropic interactions of aspartate carbamoyltransferase.

Allosteric Site↗
PubMed1985

Iron deficiency and iron overload.

An up to date review of our knowledge of human iron metabolism is given including problems of iron balance, internal transport, and intracellular mechanisms. Current knowledge of the iron proteins is summarized and this background is used in discussing the pathophysiology of iron deficiency and overload, together with the internal derangements such as sideroblastic anemia which form much of the clinical practice associated with disorders of iron metabolism. The therapeutic approach to these problems will be described.

Absorption↗
PubMed1985

The effect of retinoids on CFU-GM from normal subjects and patients with myelodysplastic syndrome.

Five retinoid analogues differ in their effects on the growth of CFU-GM from normal human marrow. At concentrations above 10(-6) M all have inhibitory activity. This is maximal with 13-cis-retinoic acid. At lower concentrations the effect of retinoids is usually to reduce clone size rather than clone numbers though 10(-8)-10(-7) M etretinate increases clone size. The incubation of marrow cultures in the presence of 10(-6) M all-trans retinoic acid showed that in normal subjects colony counts are never reduced to less than 45% of the control value and total clone counts to less than 70% of the control value. In cultures from patients with myelodysplastic syndrome 20 out of 34 cases showed a greater inhibition of colony numbers than normal and 14 out of 35 cases showed a greater reduction in total clone numbers than normal. The results suggest that CFU-GM from some patients with myelodysplastic syndrome may have a greater sensitivity than normal to the inhibitory effect of retinoic acid.

Adult↗
PubMed1985

The myelodysplastic syndrome: analysis of laboratory characteristics in relation to the FAB classification.

A detailed study of 43 newly diagnosed cases of myelodysplastic syndrome (MDS) shows that many of the morphological features of blood and bone marrow are common to the different FAB groups. In addition, there is no clear distinction between the groups with regard to CFU-E, BFU-E or CFU-GM colony growth in vitro or ferrokinetic assessment of erythropoiesis in vivo. The interrelationships between all the parameters we have studied have been examined and there is little correlation between erythroid colony formation in vitro, the percentage erythroblasts in the bone marrow, erythroid output measured by ferrokinetics and the peripheral blood reticulocyte count, all of which appear to measure different aspects of erythropoiesis. Reduced erythroid colony growth and a high degree of ineffective erythropoiesis in vivo are common in all groups and appear to be an early manifestation of abnormal function. Decreasing marrow iron turnover is more closely related to increasing numbers of marrow blast cells than any other index of erythropoiesis.

Adult↗
PubMed1985

Sideroblastic colonies in erythroid cultures grown from normal human marrow.

Normal human erythroid progenitor cells from bone marrow were grown in culture using a methyl cellulose clonal assay technique. Sideroblastic erythroid cells were found in the majority of colonies examined at 14-17 days, and a few sideroblasts were found in some of the colonies examined after shorter periods of culture. Electron microscopy confirmed the presence of both intramitochondrial iron deposits and cytoplasmic ferritin aggregates. These morphological appearances probably represent an abnormality induced by the in vitro culture conditions and cannot be used as evidence for an intrinsic defect in haem synthesis.

Cells, Cultured↗
PubMed1985

Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.

The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities.

Anemia, Refractory, with Excess of Blasts↗
PubMed1985

Granulocyte and monocyte surface membrane markers in the myelodysplastic syndromes.

The expression of lineage specific surface antigens on granulocytes and monocytes was quantitated using monoclonal antibodies in 16 healthy adults and 21 patients with myelodysplastic syndromes. In nine of 19 patients the granulocytes showed a decrease in myeloid or an increase in monocyte antigen expression or both. In 11 of 19 patients the monocytes showed a decreased expression of monocyte antigens or an increase in myeloid antigens or both. The data suggest that in the myelodysplastic syndromes the granulocyte-macrophage progenitors do not develop along two divergent lines but differentiate with the emergence of dual characteristics.

Adult↗
PubMed1984

Evolutionary divergence of genes for ornithine and aspartate carbamoyl-transferases--complete sequence and mode of regulation of the Escherichia coli argF gene; comparison of argF with argI and pyrB.

The complete nucleotide sequence of argF is presented, together with that of an operator-constitutive mutant. ArgF is compared with the other gene coding for ornithine carbamoyltransferase (OTCase) in E. coli K-12, argI, and with pyrB, encoding the catalytic monomer of aspartate carbamoyltransferase (ATCase). ArgF and argI appear very closely related having emerged from a relatively recent ancestor gene. The relationship between OTCase and ATCase appears more distant. Nevertheless, the homology observed between the two proteins (mainly in the polar domain) suggests a common origin.

Arginine↗
PubMed1984

Interaction of ferritin with serum: implications for ferritin turnover.

An interaction between human and rabbit ferritins and serum was demonstrated by a coated tube binding assay, a shift in molecular size on gel filtration and by precipitation of complexes with 3.5% polyethylene glycol 6000. With polyethylene glycol and labelled ferritins, complex formation was inhibited by heating sera to 56 degrees C for 30 min and by addition of EDTA or excess unlabelled ferritins. Human heart ferritin showed the greatest interaction with serum, followed by human spleen ferritin and least of all human plasma ferritin. Ferritins did not appear to bind to IgG or IgM in normal sera. The interaction of 'H' subunit-containing ferritins with serum or plasma may be partly responsible for the rapid clearance of tissue ferritins from the circulation and the absence of acidic isoferritins in the plasma of normal subjects.

Animals↗
PubMed1984

Prolonged survival in acute myelogenous leukaemia without maintenance chemotherapy.

46 adults with previously untreated acute myelogenous leukaemia who achieved complete remission with 6-thioguanine, cytarabine, and daunorubicin (TAD) received two courses of intensive consolidation chemotherapy. The first cycle consisted of 5-azacytidine and doxorubicin followed by a second consolidation cycle with TAD. Maintenance chemotherapy was not administered. Median remission duration was 14 months and 26% (95% confidence interval, 11%-41%) remained in continuous remission at 5 years. Actuarial 5 year survival was 31% (+/- 15%). Results were most favourable in patients who achieved complete remission within 60 days of chemotherapy being initiated. These data indicate that prolonged disease-free survival can be achieved in patients treated with intensive induction and consolidation treatment alone without maintenance chemotherapy.

Adolescent↗
PubMed1984

Serum ferritin and malignant tumours.

Increased concentrations of serum ferritin are common in patients with malignant disease and appear to be a non-specific response. The present evidence does not suggest that serum ferritin assay is useful either for specific diagnosis or monitoring of malignant disease. A special role for acidic isoferritins in malignancy remains to be substantiated.

Animals↗
PubMed1984

Biochemical and immunological characteristics of ferritin from HL-60, U-937 and K-562 cell lines: implications for haemopoietic regulation.

It has been suggested that acidic isoferritins play a major role in the regulation of human granulocyte-macrophage (CFU-GM) proliferation. Such regulatory isoferritins are said to occur in some human tissues including both leukaemic and normal leucocytes, and certain established cell lines. They are glycosylated and bind to Con A. Extracts from HL-60, U-937 and K-562 cell lines are said to contain inhibitory activity but only in HL60 cells is the activity neutralized by antibody to acidic isoferritins. The properties of ferritin from these cell lines have been investigated. HL60 and U-937 extracts contained predominantly basic (spleen-type) isoferritins and K-562 extracts predominantly acidic (heart-type) isoferritins on immunoradiometric assay. None of the ferritin bound to Con A. On anion exchange chromatography ferritin from U-937 was basic in character, that from K-562 was acidic and HL-60 contained a variety of isoferritins. The identification of glycosylated acidic isoferritins as inhibitors of granulopoiesis appears to be an oversimplification and the classification of isoferritins on the basis of two subunit types may also need revision.

Cell Line↗
PubMed1984

Testosterone, erythropoietin and anaemia in patients with disseminated bronchial cancer.

In 21 newly diagnosed male patients with disseminated bronchial cancer, anaemia was associated with a reduced serum concentration of testosterone. Erythropoietin levels were increased in anaemic patients. The results suggest a normal erythropoietin response to anaemia in this condition. The reduced testosterone concentration is associated with normal levels of luteinizing hormone and its significance in the pathogenesis of the anaemia is uncertain.

Adult↗