bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Synthesis of Folate‐binding Protein in Lymphocytes during Transformation
Authors: Costa Maria da , Sharon Michael 
Published: March 2008

Summary.The blast transformation of human lymphocytes exposed to phytohaemagglutinin was associated with an increase in the intracellular concentration of a folate‐binding protein. The protein was measured by a radioinimunoassay and by immunofluorescent microscopy using an antiserum raised against purified folatebinding protein prepared from chronic myelogenous leukaemia cells. Because it has been previously shown that protein‐bound folate cannot function as a cofactor or substrate, the synthesis of this binder during some phase of the replicative cycle may serve to modulate folate‐dependent RNA and DNA synthesis by controlling the concentration of free folate.
Use of lllIndium‐labelled Platelets to Measure Spleen Function
Authors: Peters A. M. , Klonizakis I. , Lavender J. P. , Lewis S. M. 
Published: March 2008

Summary.The distribution of 111In‐labelled platelets following intravenous bolus injection has been studied using a gamma camera and computer system. Liver uptake, which accounted for about 10% of the dose, was completed between 6 and 10 min after injection. Blood pool and splenic 111In, which accounted for the remainder of the dose, reached constant levels simultaneously about 20 min after injection. The kinetics of splenic uptake are consistent with a two compartmental model in which circulating and splenic platelets are in dynamic equilibrium with each other. From analysis of the kinetics, splenic blood flow and the mean transit time of platelets through the spleen have been calculated in normal subjects and in patients with haematological disorders. Blood flow, which was about 200 ml per min in normals, tended to increase with increasing spleen size. Transit time was not dependent on spleen size; it was about 10 min in all but one of the subjects.
Radionuclide Distribution folowing Injection of 111Indium‐labelled Platelets
Authors: Klonizakis I. , Peters A. M. , Fitzpatrick M. L. , Kensett M. J. , Lewis S. M. , Lavender J. P. 
Published: March 2008

Summary.Platelets labelled with 111In displayed similar survival curves after incubation with 111In‐oxine in plasma, plasma‐saline and dextrose saline media. The use of autologous red cells to cushion platelets during high‐speed centrifugation facilitated platelet resuspension without greatly affecting the duration of the labelling procedure. Quantitative scanning after reinjection of labelled platelets in haematologically normal subjects showed that, initially, splenic indium amounted to about 35% of the injected dose and hepatic indium about 12%; these levels rose only slightly over the subsequent duration of the platelet life span. Subtraction of the signal from indium in platelets thought to be normally pooled within the spleen from the total indium signal gave splenic indium uptake curves which reflected splenic platelet destruction. Initially, the sum of indium levels in spleen, liver and blood equalled 100% of the dose. Thereafter, the sum fell progressively at a rate thought to be approximately equal to the rate of bone marrow uptake.
Fetal Hb Production during Acute Erythroid Expansion: I. OBSERVATIONS IN PATIENTS WITH TRANSIENT ERYTHROBLASTOPENIA AND POST‐PHLEBOTOMY
Authors: Papayannopoulou Th. , Vichinsky E. , Stamatoyannopoulos G. 
Published: March 2008

Summary. In order to study fetal haemoglobin production during acute erythroid expansion we did sequential measurements of Hb F‐containing erythrocytes (F‐cells) and of relevant haematological parameters in 10 subjects recovering from erythroid aplasia, iron deficiency anaemia or following phlebotomy. An increased production of F‐cells was consistently observed during the acute marrow expansion, but there were significant differences in the maximum F‐cell response among individuals. These differences could not be explained by differences in the degree of anaemia alone, nor could they be correlated with the level of peak reticulocytosis. Two patients who reached the highest F‐cell numbers were probably carriers of heterocellular hereditary persistence of Hb F, suggesting that this gene may play a role in determining the magnitude of F‐cell production in anaemic patients.It is speculated that the main reason for the consistently observed increase in F cell production during acute marrow expansion is the premature terminal differentiation of earlier erythroid precursors (burst forming units; BFUe). This proposition is in accord with observations in vitro which suggest that Hb F is expressed in erythroid clones derived from BFUe's. It is further proposed that differences in the degree of BFUe recruitment may underly the disparities in Hb F response among individuals subjected to similar anaemic stimuli.
An Identical Translocation between Chromosome 1 and 7 in Three Patients with Myelofibrosis and Myeloid Metaplasia
Authors: Geraedts J. P. M. , Ottolander G. J. den , Ploem J. E. , Muntinghe O. G. 
Published: March 2008

Summary. An identical chromosome abnormality was observed in three unrelated patients with myelofibrosis and myeloid metaplasia, two of the patients showing a history of polycythaemia vera (PV) before development of the myelofibrosis. Unstimulated peripheral blood cultures showed a translocation between chromosomes 1 and 7 replacing a homologue of pair 7. It was identified by G‐ and C‐banding as t(1;7)(7pter→7p11::1p1?→1qter).While the first patient also showed trisomy 21 and the third patient had some extra material on the short arm of chromosome 17, all three had trisomy 1q and monosomy 7q. Although each of these abnormalities is frequently observed separately in various haematological disorders, the combination of the two in the form of an identical translocation in three patients is an example of induced non‐random cytogenetic change in myelofibrosis.
Studies on the Concentration and Intracellular Localization of Iron Proteins in Liver Biopsy Specimens from Patients with Iron Overload with Special Reference to their Role in Lysosomal Disruption
Authors: Selden Clare , Owen Marie , Hopkins J. M. P. , Peters T. J. 
Published: March 2008

Summary. Liver biopsies were collected from control subjects and patients with iron overload due to either primary or secondary haemochromatosis. They were analysed for iron proteins by cation exchange chromatography and flameless atomic absorption spectrophotometry.In control tissue the transferrin fraction contains 25%, ferritin 50% and haemprotein and haemosiderin 10–15% each, of the total iron. In iron overloaded tissue the ferritin and haemosiderin iron increases approximately 10‐ and 100‐fold, respectively, compared with control tissue.There was a close positive correlation between enhanced lysosomal fragility as determined by measurements of latent N‐acetyl‐β‐glucosaminidase and haemosiderin content of the tissue; it is suggested that the haemosiderin is responsible for the lysosomal disruption and hence the tissue damage in iron overload.Studies were performed on the intracellular localization of ferritin and of total iron in biopsy extracts from control subjects and from patients with iron overload. In control tissue, ferritin contains most of the iron and is apparently free in the cytosol. In iron overload, ferritin is the major iron protein in the post‐nuclear supernatant sedimenting into the gradient as the free protein. There are, however, significant amounts of immunoreactive ferritin deeper in the gradients but this cannot be assigned to any particular subcellular organelle. The extreme fragility of lysosomes in iron overloaded human tissue makes isolation of these organelles for detailed biochemical analysis extremely difficult.
Identifying Carriers of Mild Haemophilia
Authors: Graham John B. , Barrow Emily S. , Flyer Paul , Dawson Deborah V. , Elston R. C. 
Published: March 2008

Summary. The problems of carrier identification in mild haemophilia were examined by studying a large kindred transmitting VIII:C levels which averaged 17 u/dl in affected males. Fifteen obligatory carriers and 13 normal women from this kindred were used as reference groups to produce a set of linear discriminants. The utility of these discriminants in identifying carriers of mild haemophilia was compared with that of a similar set of discriminants which had been prepared for use with carriers of severe haemophilia, each set of discriminants being tested against both data bases. It was found that both sets of discriminants had large error rates when applied to the mild data base, and that both had much smaller error rates when applied to the severe data base. This outcome resulted from the greater overlap between the factor VIII‐related activities of mild carriers and normal women than the overlap of these activities between severe carriers and normal women.Our conclusions were that (i) correct classification of many but not all women from families of mild haemophilia would be difficult, (ii) discriminants prepared using obligatory carriers of severe haemophilia were not more inefficient in mild haemophilia than those prepared using obligatory carriers of mild haemophilia, (iii) a single set of discriminants prepared from reference groups of normal women and obligatory carriers of severe haemophilia may be used for identifying potential carriers of all grades of haemophilia, and (iv), statistically speaking, VIIIR:Ag assays provide a limited amount of information for this purpose.
Haemoglobin Synthesis in Human Erythroid Bursts during Ontogeny: Reproducibility and Sensitivity to Culture Conditions
Authors: Darbre Philippa D. , Lauckner S. M. , Adamson J. W. , Wood W. G. , Weatherall D. J. 
Published: March 2008

Summary. Patterns of haemoglobin (Hb) synthesis were analysed in erythroid bursts grown in vitro from human fetal, umbilical cord and adult blood to determine the reproducibility of the system and its sensitivity to various alterations in culture conditions. The proportion of Hb F synthesis in duplicate plates from the same sample showed little variation but when an individual was studied under the same conditions but at different times, far more variability was observed.We have confirmed that the synthesis of Hb F and Hb A in the cultures is asynchronous, relatively more Hb F being synthesized earlier in the maturation of the colony. Hence factors affecting colony maturation are likely to change the apparent pattern of Hb synthesis. Removal of adherent cells prior to plating resulted in the presence of more mature colonies and lower levels of Hb F synthesis at any fixed time in culture. Furthermore, the overall ratio of γ:β chain synthesis measured in the whole plate was dependent on the proportion of large, immature multicluster bursts present. The significance of measurements of Hb synthesis in erythroid bursts can be assessed only if all of these factors are recognized and taken into account.
Interaction between Homozygous β0 Thalassaemia and the Swiss Type of Hereditary Persistence of Fetal Haemoglobin
Authors: Cappellini M. D. , Fiorelli G. , Bernini L. F. 
Published: March 2008

Summary.The interaction between β0 thalassaemia and an heterocellular form of hereditary persistence of fetal haemoglobin (HPFH), presumably of the Swiss type, has been studied in three generations of a family in which both traits occur. The haematological parameters and the segregation of the two characters in the family suggest that the propositus, a 52‐year‐old male from southern Sardinia, is homozygous for β0 thalassaemia and carrier of the HPFH.In spite of the complete suppression of adult haemoglobin synthesis, the patient is not anaemic and shows only morphological abnormalities of the red cells associated with a moderate decrease of the erythrocyte life span. Studies of the synthesis of haemoglobin chains in vitro have revealed only a mild degree of unbalance in the propositus, with a γ/α ratio of 0–67, and a very slight unbalance in a 3‐year‐old child heterozygous for β thalassaemia and HPFH.Preliminary analysis of the linkage between this kind of heterocellular HPFH and the β Hb locus has been performed, utilizing all the suitable families reported in the literature. Although positive lod scores (1.535) have been obtained at a recombination fraction of 0.20, the data available are not sufficient to conclude in favour or against the linkage between the β Hb locus and the heterocellular type of HPFH.
Unstable Haemoglobin Haemolytic Crises: Contributions of Pyrexia and Neutrophil Oxidants
Authors: Winterbourn Christine C. , Williamson David , Vissers Margret C. M. , Carrell Robin W. 
Published: March 2008

Summary. Pyrexia and the production of oxidants by phagocytic cells have been examined as two possible causes of haemolytic crises associated with infections in carriers of unstable haemoglobins. Three unstable haemoglobins were examined, both in red cells and after purification. Incubation at 40°C rather than 37°C resulted in only a slight increase in autoxidation rate, but a considerable increase in the rate of precipitation of the haemoglobins as Heinz bodies. Oxidants produced by activated neutrophils were capable of oxidizing haemoglobin both in solution and red cells, though there was no preferential effect on the unstable as opposed to the normal haemoglobin.It is concluded that haemolytic crises associated with infections in carriers of unstable haemoglobins can be explained by increased intracellular precipitation of the haemoglobin as Heinz bodies caused by the accompanying pyrexia.
Serum Ferritin in Patients with Hereditary Spherocytosis
Authors: Blacklock Hilary A. , Meerkin Matthew 
Published: March 2008

Summary. Serum ferritin was measured in 61 patients with autosomal dominant hereditary spherocytosis (HS), 44 splenectomized and 17 with intact spleens. In the majority (78%) the serum ferritin concentration was not elevated. Thirteen (22%) had mildly elevated levels, including five splenectomized females (range 181‐236 μg/l), and eight males, two with intact spleens (range 236‐436 μg/l). The serum ferritin was not raised in 15 of the 17 non‐splenectomized individuals. This group included one female who had been venesected for iron overload and further investigations have shown that both the genes for HS and haemochromatosis are present in her family.These results demonstrate that iron stores are usually normal in HS, and that prevention of iron overload alone is not an indication for splenectomy. The rare report of a patient with HS and severe iron overload may perhaps be explained by the fact that the gene frequency for haemochromatosis is common in the population.
Monosomy 7 in Childhood: a Myeloproliferative Disorder
Authors: Sieff C. A. , Chessells J. M. , Harvey B. A. M. , Pickthall V. J. , Lawler S. D. 
Published: March 2008

Summary. Between 1976 and 1979 a myeloproliferative disease associated with cells monosomic for chromosome number 7 in the bone marrow was seen in six boys aged 51/2 months to 8 years (median 10 months). Presenting features included hepatosplenomegaly (5/6), respiratory infections (4/6), pallor (2/6) and skin infections (1/6). Haematological features included a leucoerythroblastic anaemia with leucocytosis and thrombocytopenia, and a hyperplastic marrow with a slight excess of blasts. Fetal haemoglobin was normal in four patients and mildly raised in the other two. Neutrophil function tests showed defective chemotaxis with reduced killing, despite a normal NBT test. Cytogenetic analysis of the marrow showed a preponderance of cells with monosomy 7; the blood lymphocytes were cytogenetically normal.In three patients the disease progressed to acute myeloid leukaemia (AML) after 3 weeks to 23 months; the only patient who remitted did so in response to 6‐mercaptopurine and prednisolone, but relapsed 16 months later. A fourth child developed massive splenomegaly which initially responded to 6‐mercaptopurine and prednisolone, but progressed to myelofibrosis 11 months later. A fifth child died from anaemia and respiratory infection without progression to leukaemia and the sixth patient has not yet developed leukaemia.Monosomy 7 is the diagnostic criterion of one of the more common myeloproliferative states in childhood and carries a high risk of progression to AML. The acute phase is usually resistant to chemotherapy, but even in responsive cases treatment does not result in elimination of the abnormal clone. Allogeneic bone marrow transplantation should be considered in cases with a suitable donor.
Bone Marrow Fibroblastoid Colony‐Forming Cells (F‐CFC) in Aplastic Anaemia: Colony Growth and Stimulation of Granulocyte‐Macrophage Colony‐Forming Cells (GM‐CFC)
Authors: Gordon M. Y. , Gordon‐Smith E. C. 
Published: March 2008

Summary. Colonies of fibroblast‐like cells have been grown from the mononuclear cell fractions of bone marrow aspirated from normal individuals and patients with aplastic anaemia. Some of the characteristics of the fibroblastoid cells have been determined and their granulocyte‐macrophage colony‐stimulating activity (CSA) in semi‐solid agar culture has been used as a functional test of their influence on granulopoiesis.The incidence and growth rates of fibroblastoid colony‐forming cells (F‐CFC) from aplastic patients’bone marrows were not markedly different from normal either before or after treatment by allogeneic bone marrow transplantation or with antilymphocyte globulin (ALG).Confluent monolayers of fibroblastoid cells grown from normal marrow were, on the whole, poor stimulators of granulocyte‐macrophage colony‐forming cells (GM‐CFC) and CSA was not detected in the supernatant medium. Fibroblastoid monolayers derived from many of the aplastic bone marrows studied were efficient stimulators of GM‐CFC but, like the monolayers grown from normal cells, did not release CSA into the culture medium.Addition of methylprednisolone (MP) to the cultures had little effect on fibroblastoid cell growth, induced fat‐accumulation by some of the fibroblastoid colonies comprising the monolayer and reduced the abilities of the monolayers to stimulate GM‐CFC.
Megaloblastic Change is a Feature of Colonies Derived from an Early Erythroid Progenitor (BFU‐E) Stimulated by Monocytes in Culture
Authors: Reid C. D. L. , Baptista Luisa C. , Deacon R. , Chanarin I. 
Published: March 2008

Summary. The morphology of stained preparations of cells from human bone marrow and peripheral blood erythroid colonies cultured in methylcellulose, were examined by light microscopy. Although the morphology of 7 d erythroid colonies (CFU‐E) was largely normoblastic, bone marrow and peripheral blood erythroid bursts (BFU‐E) showed a variable degree of megaloblastic and dyserythropoietic change. This was not due to nutritional deficiencies of the culture system and the deoxyuridine suppression test demonstrated active thymidine synthesis.Megaloblastic morphology was correlated with the growth induced by the addition of monocytes to erythroid progenitors. It was concluded that megalo‐blastosis was a feature of the erythroblasts derived from an early BFU‐E which required monocytes for their development.
Haemoglobin Constant Spring has an unstable α chain messenger RNA
Authors: Hunt D. M. , Higgs D. R. , Winichagoon P. , Clegg J. B. , Weatherall D. J. 
Published: March 2008

Summary.Haemoglobin Constant Spring (Hb CS) is a variant with an elongated α‐chain associated with an α+ thalassaemia phenotype. The amount of α mRNA relative to β mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of α+ thalassaemia. In a patient with Hb CS‐H disease there was greater α/β mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the α mRNA in the patient's peripheral blood was derived from the α1 (αA) gene. The data suggest that αCS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3’non‐coding region during translation.
Decreased glycosylation of band 3 and band 4‐5 glycoproteins of erythrocyte membrane in congenital dyserythropoietic anaemia type II
Authors: Scartezzini P. , Forni G. L. , Baldi M. , Izzo C. , Sansone G. 
Published: March 2008

Summary.We report a study of HEMPAS erythrocyte membrane glycoproteins in relation to proteolytic digestion and surface labelling with galactose‐oxidase/NaB[3H]4. The proteolytic digestion of band 3, the major intrinsic glycoprotein of the human erythrocyte membrane, reveals an abnormality in the outer glycosylated segment of this protein. 3H incorporation in band 3 and band 4‐5 glycoproteins after treatment with galactose‐oxidase/NaB[3H]4 is reduced in HEMPAS red cells suggesting a defective glycosylation of these proteins. These findings together with the persistence of i antigen and the normal presence of I antigen lead us to conclude that erythroblastic membrane features may persist in HEMPAS erythrocytes.
Synthesis of thromboplastin by U‐937 cells
Authors: Lyberg T. , Nilsson K. , Prydz H. 
Published: March 2008

Summary.A human monocytoid cell line (U‐937) produces a procoagulant identified as thromboplastin when stimulated with phytohaemagglutinin (PHA), endotoxin, immune complexes, the phorbol ester 12‐O‐tetradecanoyl‐phorbol 13‐acetate (TPA) or the divalent ionophore A 23187. The basal thromboplastin expression of these cells and the increased activity induced by the stimulants were dependent on supply of fresh medium suggesting that the synthetic rate was highest when the cells were in logarithmic growth. Inducible thromboplastin synthesis was inhibited by actinomycin D or cycloheximide, indicating dependence on messenger RNA and protein synthesis. Differentiation of the cells in the macrophage direction by TPA did not make the cells more responsive to PHA. Thromboplastin induction in U‐937 cells was potentiated by the presence of lymphocytes, especially when stimulated with PHA or endotoxin. This supporting effect was also obtained by conditioned medium from lymphocyte cultures, suggesting a role for a soluble lymphocyte product.
Platelet associated IgG, platelet survival, and platelet sequestration in thrombocytopenic states
Authors: Mueller‐Eckhardt C. , Mueller‐Eckhardt G. , Kayser W. , Voss R.M. , And J. Wegner , Küenzlen E. 
Published: March 2008

Summary. Platelet‐associated IgG (PAIgG), platelet mean life span (MLS), and platelet sequestration sites were studied in 69 patients with immune (ITP) and presumed nonimmune thrombocytopenias (NTP). A shortened MLS was associated with elevated PAIgG (N=46), and with normal PAIgG (N=15), Four patients had a normal MLS, but elevated PAIgG, four patients were normal for both parameters. The highest PAIgG values occurred in ITP patients with a very short MLS. Nine NTP patients had also elevated PAIgG, but a normal or slightly shortened MLS. There was a significant double log correlation between PAIgG and MLS for ITP, but not for NTP patients. Judged from the coefficient of determination, only 10% of PAIgG were directly related to a shortened MLS.70% of patients (N= 63) had exclusively splenic and 30% hepatosplenic sequestration. PAIgG was elevated in 29/44 patients with splenic (66%) and in 16/19 patients with hepatosplenic sequestration (84%). In ITP, PAIgG‐positive cases were observed in 69% of splenic v82% of hepatosplenic sequestration, while in NTP the corresponding figures were 6/11 and 2/2. No significant correlation between PAIgG and either sequestration type was demonstrable.We conclude that in immunologically mediated thrombocytopenia only a small portion of PAIgG accounts for a decreased MLS, and that the concentration of PAIgG per se does not determine the platelet sequestration type.