bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferritin in Human Liver Cells of Homozygous Beta‐Thalassaemia: Ultrastructural Observations
Authors: Iancu T. C. , Neustein H. B. 
Published: March 2008

Summary. Homozygous beta‐thalassaemia is a disease in which there is a progressive iron overload from infancy to death in early adulthood. Liver biopsies from 10 patients in various stages of this disease were examined by electron microscopy. A number of round or oval lysosomal structures, containing lamellae different from myelin figures, were seen in all patients, including those with minimal iron overload. Ferritin molecules were seen either in relationship with the lamellae forming arrays, or in paracrystalline arrangement, or with no organized form. There were practically no ferritin molecules in sub‐cellular compartments other than cell sap and lysosomes. The density of cell sap ferritin was constant beyond infancy, but the number of iron‐laden lysosomes increased with age.The stages in the process of iron seclusion, seen even in advanced phases of iron overload, are described. Ferritin is thought to accumulate in lysosomes by a transmembraneous movement, but other explanations are considered.
Identification of Sources of Inter‐Laboratory Variation in Factor VIII Assay
Authors: Kirkwood T. B. L. , Rizza C. R. , Snape T. J. , Rhymes I. L. , Austen D. E. G. 
Published: March 2008

Summary. A repeated finding of national and international collaborative studies of standard factor VIII preparations has been that systematic differences exist between laboratories in their measurement of the relative activities of the same pairs of factor VIII preparations.A workshop meeting was held at the Oxford Haemophilia Centre during 23–26 November 1976 to investigate which of the possible sources of variation between laboratories were responsible. Participants from 16 British laboratories (nine using one‐stage assays and seven using two‐stage assays) performed a total of 273 valid assays using three freeze‐dried preparations of differing purity (a plasma, an intermediate and a high purity concentrate). The results of assay with each participant using their normal system established that, if the participants were a representative cross‐section, approximately one‐third of one‐stage laboratories would show a systematic difference from the overall mean of at least 16% with a corresponding figure for the two‐stage laboratories of 9%. Various features of the assay systems were then modified in a controlled series of experiments. The results showed conclusively that (i) differences between reagents accounted for most of the variation between laboratories, and (ii) the two‐stage assays were, on average, detecting relatively more activity in the more purified preparations than the one‐stage assays. The results also suggested that the use of buffer or citrate‐saline as opposed to haemophilic plasma for the initial dilution of concentrates did not affect the assay results.
Thyroid Hormones Stimulate Erythropoiesis in Vitro
Authors: Golde D. W. , Bersch N. , Chopra I.J. , Cline M.J. 
Published: March 2008

SUMMARY.Thyroid hormones have important effects on erythropoiesis in man and animals. We performed in vitro culture studies with murine and human bone marrow in order to define the interaction of these hormones with erythroid and granulocyte‐monocyte progenitor cells. The methylcellulose clonogenic assay was used with the appropriate addition of erythropoietin or colony‐stimulating activity. L‐Thyroxine, D‐thyroxine and L‐triiodothyronine potentiated erythropoietin‐stimulated erythroid colony formation in concentrations of 50–100 ng/ml. These hormones had no effect on granulocyte‐monocyte colony formation at concentrations up to 500 ng/ml. Testing of various thyroid analogues showed no clear correlation between potentiation of erythropoiesis and known calorigenic potency. Reverse triiodothyronine also had potentiating activity in this system. The active thyroid hormones stimulated erythroid colony formation at several concentrations of erythropoietin but could not substitute for erythropoietin. These data suggest that thyroid hormones have a direct effect on erythroid precursor proliferative capacity, a finding which may have relevance to the mechanism of erythropoietic dysfunction in human thyroid disease.
The Blast Crisis of Chronic Granulocytic Leukaemia: Megakaryoblastic Nature of Cells as Revealed by the Presence of Platelet‐Peroxidase—A Cytochemical Ultrastructural Study
Authors: Breton‐Gorius J. , Reyes F. , Vernant J. P. , Tulliez M. , Dreyfus B. 
Published: March 2008

The origin of cells in the blast crisis of some cases of chronic granulocytic leukaemia (CGL) remains controversial. Difficulties arise from the lack of cytochemical characteristics of differentiation. This report concerns the nature of cells in the blast crisis of a case of CGL in which blast cells exhibited an undifferentiated or lymphoid appearance by light and electron microscopy. The majority (90%) of such cells contained a peroxidase in the endoplasmic reticulum distinct from myeloperoxidase. In addition, some micromegakaryocytes could be recognized among the peroxidase reactive cells, by the presence of typical granules and demarcation membranes. Since this peroxidase exhibited identical characteristics to that of normal megakaryocytic precursors, these blast cells could be identified as megakaryoblasts.These data emphasize the possible megakaryoblastic nature of cells occurring in other cases of CGL blast crisis.
Chromosomes in Ph1‐Positive Chronic Granulocytic Leukaemia
Authors:   FIRST INTERNATIONAL WORKSHOP ON CHROMOSOMES IN LEUKAEMIA
Published: March 2008

Information about the type, frequency, and clinical significance of chromosome abnormalities in leukaemia has been reported from a number of laboratories located in various countries. A small international Workshop was organized to examine the combined data of the participating investigators for chronic granulocytic leukaemia (CGL) and acute nonlymphocytic leukaemia (ANLL). In this report the results of the analysis of chromosomes in CGL are presented; the results of a similar analysis in ANLL are presented in the subsequent paper.The Workshop addressed itself primarily to: (I) the incidence of various karyotypic abnormalities, in the different phases of Ph1‐positive CGL, based on the data of the various members of the group; (2) a comparison of the findings with those in the literature; and (3) the possible utilization of unique cytogenetic phenomena as predictive parameters for the blastic phase and other clinical aspects of CGL.
Myeloid Karyotype and the Malignant Phase of Chronic Granulocytic Leukaemia
Authors: Lilleyman J. S. , Potter A. M. , Watmore A. E. , Cooke P. , Sokol R. J. , Wood J. K. ,   THE TRENT REGION AND ASSOCIATED HOSPITALS WORKING PARTY ON ADULT LEUKAEMIA
Published: March 2008

During the course of a 30 month study period, 26 patients with typical chronic granulocytic leukaemia (CGL) developed karyotype abnormalities in addition to the Philadelphia (Ph1) chromosome. All cases had received at least 14 months continuous low dose busulphan, and the chromosome changes were found before clinical transformation in six patients and at the time this occurred in 20.Survival following the discovery of these additional abnormalities was short, with a median of 11 weeks for the whole group. Trisomy 8 was the commonest additional chromosome abnormality, but no one karyotype change was clearly associated with shorter survival than another.23 of the 26 have died as a direct result of their disease, forming part of a total of 40 deaths from typical CGL encountered during the study period where karyotype analyses were performed during the terminal stages of the disease. Of these 40, only two (5%) patients showed no chromosome abnormalities extra to the Ph1 prior to death. (The 17 non‐study patients who died were similar in all respects to the 23 from the study group, but had no prior chromosome studies performed during the chronic phase of the disease.)It is suggested that an expanding aneuploid or pseudodiploid clone arising from the leukaemic cells during the benign phase of CGL can be used to mark the sometimes ill‐defined onset of the malignant phase in all but a small proportion of cases.
A Comparative Study of the Buoyant Density Distribution of Normal and Malignant Lymphocytes
Authors: Huber Christoph , Zier K. , Michlmayr G. , Root H. , Nilsson K. , Theml H. , Lutz D. , Braunsteiner H. 
Published: March 2008

SUMMARY Density distribution patterns of normal and malignant lymphocytes were compared following centrifugation to equilibrium on linear density gradients.For normal lymphocytes differences in the distribution patterns were observed between: (1) B and T cells, (2) central and peripheral cells, and (3) resting and activated cells. The findings suggested that cell density is determined by cell lineage, the degree of differentiation and the stage of functional activation.Marked differences in the density distribution profiles were also observed among certain types of morphologically distinguishable lymphoproliferations. To some extent density analyses enabled the discrimination between CLL, follicular lymphomas and lymphoblastic lymphomas as well as between O‐ALL and T‐ALL. Density profiles of malignant lymphocytes failed to disclose any features specific for malignancies. But they revealed some similarities with distinct subsets of normal lymphocytes, i.e. between: (1) CLL and bone marrow lymphoid cells, (2) follicular lymphomas and follicular centre cells, and (3) lymphoblastic lymphomas and activated lymphocytes. These findings arc further evidence supporting the hypothesis that the malignant trarisformation of phenotypicalIy different lyrnplioproliferations takes place at different levels of lymphocyte differentiation.
Plasma Levels of Platelet Factor 4 Measured by Radioimmunoassay
Authors: Chesterman C. N. , McGready Jennifer R. , Doyle D. J. , Morgan F. J. 
Published: March 2008

Summary. A radioimmunoassay has been developed to measure platelet factor 4 (PF4) in biological fluids both in vitro and in vivo. The assay has been shown to be highly specific for PF4 and has a sensitivity of 0.08 ng/assay tube and 1.6 ng/ml of plasma. The preparation of plasma for the measurement of in vivo levels of PF4 requires the use of an anticoagulant containing EDTA, theophylline and prostaglandin E1, the immediate cooling of the blood and high speed or prolonged centrifugation to reduce platelet contamination. Plasma levels of PF4 are normally between 4 and 24 ng/ml with a median of 7.4 ng/ml.Plasma PF4 levels are markedly increased during cardiopulmonary bypass surgery with shortened 51Cr‐labelled platelet survival times and during arterial thrombosis. However, despite similarly shortened platelet survival times, the level of PF4 is normal in immune thrombocytopenia. Elevations of plasma PF4 levels are found following surgery, acute myocardial infarction and frequently during acute infections and in inflammatory states. On the contrary, normal levels are usual in disseminated malignancy, in severe hepatic and renal disease and in chronic arterial disease.The measurement of PF4 is a useful addition to the study of platelet pathophysiology. It is apparent, however, that raised levels are by no means specific for thromboembolic disease and similarly platelet destruction is not invariably associated with abnormally increased plasma PF4 levels.
Some Features of Bone Marrow Macrophages in Patients with Homozygous β‐Thalassaemia
Authors: Wickramasinghe S. N. , Hughes Madeleine 
Published: March 2008

SummaryThe bone marrow macrophages of patients with homozygous β‐thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated α‐chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily‐iron‐loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly‐synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed that the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division.
Autoimmune Antibodies in Chronic Lymphatic Leukaemia
Authors: Lewis C. M. , Pegrum G. D. 
Published: March 2008

SummaryIn chronic lymphocytic leukaemia a factor in patients' serum enhances the in vitro viability of the abnormal cells and this has been identified as an antibody. The activity of this factor can be removed by interaction with anti‐immunoglobulin and by ammonium sulphate precipitation with a degree of saturation in excess of 46%. Cohn fractionation and chromatography with A‐50 Sephadex show that the factor is not a complex but an immunoglobulin. No activity is removed after reaction of sera with 2‐mercapto‐ethanol and di‐thiothreitol. The evidence therefore suggests that a γ‐G immunoglobulin is involved. Concentrated washings from the leukaemic cells behave in exactly the same way as patients' sera and activity is retained in the same fraction during precipitation and purification procedure.The extensive cross‐reactivity of the sera suggests a common chronic lymphatic leukaemic antibody and it is considered that an active autoimmune response may be an integral part of the disease.
Stereological Analyses of Leukaemic Cells
Authors: James V. 
Published: March 2008

Summary. With the development of different treatment schedules for acute and chronic leukaemias it has become essential that a uniform, standardized classification of malignant cell type is achieved. Without a standardized diagnosis it is impossible to compare the results of differing treatment regimes. Present diagnosis is still based on clinical criteria and subjective assessment of cell morphology; objective and quantitative data are required. Stereological analyses are capable of providing quantitative data. Stereological techniques have been applied to the study of malignant cell types in different leukaemias for the first time and quantitative data has been obtained. The nuclear and mitochondrial volume fractions of the cells have been estimated for normal lymphocytes, the lymphocytes of chronic lymphocytic leukaemia, acute lymphoblastic leukaemia, the abnormal cells of hairy cell leukaemia and several other haematological malignancies.The results clearly indicate that the cell types of different leukaemias possess measurably different properties and that stereological methods can be used to investigate the leukaemic cell quantitatively.
Red Blood Cell Enzyme Abnormalities in Patients Treated with Chemotherapy
Authors: Etiemble J. , Bernard J. F. , Picat Ch. , Belpomme D. , Boivin P. 
Published: March 2008

Summary. Sixteen red blood cell enzyme activities and fetal haemoglobin level have been assayed in 60 patients treated for haematologic or nonhaematologic malignant diseases with various combinations of cytostatic drugs. Acquired enzyme deficiency was found in 20 patients. The most frequently decreased activities were those of G6PD (12 cases), PK (seven cases), PFK (six cases) and AK (three cases). In many patients decreased activity of some enzymes contrasted with increased activity of others such as ALD, TPI, G3PD, PGK, ENOL and 6PGD. The number of abnormalities seems to be related to the duration of the treatment.Incidence of enzyme deficiencies was similar in patients previously treated or not with radiotherapy. Enzyme abnormalities were correlated neither with haemoglobin level nor with reticulocyte count. They were very similar to those observed in primary acquired dyserythropoietic and preleukaemic states. Their prognostic value and mechanism are discussed.
Coagulation Activation and Hyperviscosity in Infection
Authors: Richardson S. G. N. , Matthews K. B. , Cruickshank J. K. , Geddes A. M. , Stuart J. 
Published: March 2008

Summary. A serial study of coagulation activation and whole‐blood viscosity was performed on 37 patients with local or systemic bacterial infection, malaria, or a viral infection. Thrombocytopenia, without consumption of coagulation factors, was the main feature of benign tertian malaria and viral infection, whereas in septicaemia and malignant tertian malaria it was associated with activation of coagulation and fibrinolysis. Patients with evidence of intravascular coagulation showed the highest levels of factor VIII related antigen which did not correlate with fibrinogen and probably reflected vascular endothelial cell damage rather than an acute‐phase protein reaction.Hyperviscosity, which has been implicated in the pathogenesis of endotoxic shock and cerebral malaria, occurred in parallel with the acute‐phase rise in plasma fibrinogen. There was, however, no evidence to implicate hyperviscosity as a major causative factor in the pathogenesis of septic shock or severe infective illness.
Membrane Abnormalities of Pyruvate Kinase Deficient Red Cells
Authors: Zanella A. , Brovelli A. , Mantovani A. , Izzo C. , Rebulla P. , Balduini C. 
Published: March 2008

Two experimental systems have been applied to the study of PK‐deficient red cells in an attempt to reveal possible membrane abnormalities of these erythrocytes: (1) the glycoprotein self‐digestion of intact erythrocytes during in vitro incubation at 37°C; (2) the red cell sensitivity to the lytic action of mouse macro‐phages.PK‐deficient erythrocytes display a more precocious than normal membrane glycoprotein self‐digestion and are much more susceptible than normal to the cytotoxic activity of mouse macrophages. This latter effect is more pronounced in young than in old PK‐deficient red cells. These observations indicate the existence of membrane abnormality in PK‐deficient red cells other than those so far suspected.
The Heterogeneity of Normal Hb A2‐β Thalassaemia in Greece
Authors: Kattamis C. , Metaxotou‐Mavromati A. , Wood W. G. , Nash J. R. , Weatherall D. J. 
Published: March 2008

Nine patients have been observed with homozygous β thalassaemia in each of whom one parent has a normal level of Hb A2. On the basis of clinical, haematological and globin chain synthesis studies these families have been divided into two groups. Group 1 (six families). Heterozygotes for normal Hb A2–β thalassaemia in this‐group showed minimal red cell abnormalities, normal osmotic fragility but imbalanced globin chain synthesis (α/β= 1.6), and appear to correspond to previous descriptions of ‘silent’β thalassaemia. Double heterozygotes with high Hb A2‐β thalassaemia have a clinical picture of mild β thalassaemia intermedia characterized by relatively low levels of Hb F (<20%) and γ chain synthesis. Group 2 (three families), β Thalassaemia heterozygotes with normal Hb A2 levels in this group showed more marked red cell abnormalities, decreased osmotic fragility and more imbalanced globin chain synthesis (α/β=2.5) than those in group 1. Double heterozygotes with high Hb A2‐β thalassaemia are more severely affected and are transfusion dependent. Haemoglobin F and γ chain synthesis are high in these cases.The frequency of normal Hb A2‐β thalassaemia in Greece may be as high as 10% of all β thalassaemia genes and this poses a significant problem for genetic counselling. Various molecular mechanisms are discussed which could account for the heterogeneity within these disorders.
Thrombin Receptors of Human Platelets: Thrombin Binding and Antithrombin Properties of Glycoprotein I
Authors: Ganguly P. , Gould N. L. 
Published: March 2008

Washed human platelets were solubilized and the proteins were separated by preparative gel electrophoresis in the presence of sodium dodecyl sulphate. The gel was cut into slices and the effect of the eluted proteins on the clotting of fibrinogen by thrombin was evaluated. The isolate from only one gel slice strongly inhibited the clotting of fibrinogen. The prolongation of the clotting time was dependent on the concentration of the protein and reached a plateau around 5 μg. Gel electrophoresis of this isolate showed a prominent glycoprotein with an apparent Mr=150 000. Gel filtration studies with [125I]thrombin showed that the protein isolate bound a significant amount of thrombin which could be displaced with unlabelled thrombin. Another preparation from the same gel or purified γ‐globulin did not bind thrombin or prolong the clotting time of fibrinogen.Glycoprotein I was isolated from human platelets by affinity chromatography on lectin–Sepharose columns. The isolated glycoprotein prolonged the clotting of fibrinogen and bound [125I]thrombin which could be displaced by unlabelled thrombin. It is proposed that the high affinity receptor of thrombin on human platelets is glycoprotein I. In addition, the antithrombin activity of intact platelets is due to binding of thrombin to this glycoprotein.
Erythrocyte Membrane Lipid Reorganization during the Sickling Process
Authors: Chiu Danny , Lubin Bertram , Shohet Stephen B. 
Published: March 2008

Summary. In order to study possible alterations in membrane lipids during sickling, we have measured the difference in susceptibility to lipid peroxidation, binding of trinitrobenzenesulfonic acid (TNBS) to aminophospholipids, and fatty acid uptake in cells containing sickle haemoglobin under aerobic and anaerobic conditions. We have also examined TNBS binding in irreversibly sickled cells in an attempt to evaluate the permanent effects of any such alterations.We found that when erythrocytes were sickled by deoxygenation, the susceptibility to lipid peroxidation and binding of TNBS to aminophospholipids was markedly increased, while normal control cells showed no change. These effects appeared to be specific for the sickled state rather than a nonspecific consequence of cell age or the concentration of sickle haemoglobin within the cell. In contrast, fatty acid incorporation into membrane phospholipids, representing potential lipid renewal, was decreased in the sickle state. Cell fractions enriched in irreversibly sickled cells showed increased TNBS labelling in air and only modest rises with anoxia. Taken together, these data imply a rearrangement of membrane lipids during the sickling process and suggest a permanent reorganization of membrane lipids in the irreversibly sickled cell.
Isozymes of Amino Acid Naphthylamidase in Human Haematopoietic Cell Lines
Authors: Slnna G. Afbu , Lundgren E. , Nllsson K. , Roos G. 
Published: March 2008

Summary.The occurrence of isozymes of the proteolytic enzyme amino acid naphthylamidase was investigated in a panel of 44 neoplastic and non‐neoplastic haematopoietic cell lines by polyacrylamide gel electrophoresis. Two isozymes (A and C) were common for all lines, whereas different forms of a third isozyme with intermediate electrophoretic mobility (B) appeared in nine lines. Isozyme A seemed to be associated with cell proliferation and was not a marker for malignancy. The appearance of different B isozymes not present in normal peripheral blood lymphocytes, occurred in some Burkitt lymphoma lines and in two non‐malignant lines maintained for a long time in culture. In three lines derived from myeloid leukaemia a variant of isozyme B seemed to be a marker for cell origin.