bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Haemoglobin Abnormalities in about 9000 Black and 7000 White Newborns; Haemoglobin F Dickinson (Aγ97 HisÅg), a New Variant
Authors: Schneider R. G. , Haggard M. E. , Gustavson L. P. , Brimhall B. , Jones R. T. 
Published: March 2008

Summary. Electrophoretically detectable haemoglobin abnormalities are readily identified in umbilical cord blood haemolysates by cellulose acetate electrophoresis, followed by citrate agar electrophoresis of those samples exhibiting an abnormality, and, if necessary, by globin electrophoresis. In samples from 9224 Black newborns, the prevalence of all such abnormalities was about 13%, with 12 cases of sickle‐cell anaemia, seven of Hb‐SC disease and five of Hb‐S β thalassaemia. Clinical and haematologic manifestations of these conditions usually appeared in the first few years of life. The prevalence of sickle‐cell trait was about 7%, Hb‐C trait 2%, and Hb Bart's 5%. Several new or rare haemoglobins, both adult and foetal, were found in individual families.Of 7006 White newborns, 76 or 1.1% had electrophoretically detectable haemoglobin abnormalities, all in the simple trait condition. Sixty‐one of these (0.8% of the total) had Hb‐Bart's and 10 had adult variants—four Hb S, four Hb C, one Hasharon and one unidentified α chain variant. Five samples contained structural γ chain abnormalities. One new variant—Hb‐F Dickinson (Aγ97 HisÅg), was found in two siblings.
The Variability of Measurements of the Prothrombin Time Ratio in the National Quality Control Trials: a Follow‐up Study
Authors: Leck Ian , Gowland E. , Poller L. 
Published: March 2008

Summary. British hospitals which use the one‐stage prothrombin time tat my participatc in one of two schemes. Those in the Routine Supply Scheme use a standardized tissue thromboplastin, the Manchester Comparative Reagent (MCR). Those in the National Referencc Scheme use other reagents routinely, but calibrate thcm against the British Comparative Thromboplastin (BCT) which consists of batches of thc MCR which have been checked for accuracy by a group of expert Monitoring Centrcs selected from the hospitals in each scheme. The performance of hospitals in both schemes is monitored by trials in which they are asked to measure prothrombin time ratios, using BCT, on lyophilized plasma preparations which are sent to them.Four trials are reported here. In one, a single plasma preparation was used. In each of thc other three, samples of three plasmas were sent. There was considerable variation in the ratios reported by different hospitals for each plasma. In the trials involving three plasma samples, a marked tendency was demonstrated for hospitals which obtained a particularly high or low reading for one plasma to deviate in the same direction when measuring other plasmas in the same trial, but this was not found when readings from different trials (separated by several months) were compared.A breakdown of the results by type of hospital suggested that those obtained by the participants in the Routine Supply Scheme, and especially by the Monitoring Centres m this group, were more accurate than those of the National Reference Scheme hospitals, but within each group no persistent differences in accuracy between hospitals and no general improvement between the earlier and later trials could be demonstrated. Confidence limits estimated com the results of all mals suggest that even in Routine Supply Scheme hospitals, the chances of having a true prothrombin time ratio outside what is usually quoted as the therapeutic range (1.8‐3.0) should be regarded as higher than I in 20 for every patient whose reported ratio @ad on duplicate readings) is below 2.1 or above 2.45.It is concluded that the National Reference Scheme should be phased Out in favour of the Routine supply Scheme, and that even among most of the hosPimls in the latter scheme there is scope for greater accuracy, which the experience Of the Correspondence: Dr L. Poller, National Reference Laboratory for Anticoagulant Control Reagents, Withington Hospital. Manchester M20 8LR.
Prolymphocytic Leukaemia
Authors: Galton D. A. G. , Goldman J. M. , Wiltshaw E. , Catovsky D. , Henry K. , Goldenberg G. J. 
Published: March 2008

Summary. The clinical and haematological features of 15 patients with a rare variant of chronic lymphocytic leukaemia (CLL) are described. The disease predominantly affects males in the sixth and seventh decades of life and presenting symptoms include fatigue, weakness, weight loss, sweats and fevers. Massive enlargement of the spleen (mean weight at autopsy 1383 g, range 227–3500 g) and to a lesser extent of the liver (mean weight 2445 g, range 2030–3079 g) are regular findings. In contrast, peripheral lymphadenopathy is inconspicuous or absent. The characteristic cell in the peripheral blood is a relatively large lymphoid cell with a large vesicular nucleolus, relatively well‐condensed nuclear chromatin and moderate amount of cytoplasm. The counts of these cells in the peripheral blood at the time of diagnosis are very high (mean 355 000/μl, range 26000–1 11 000/μl). The clinical response to methods of treatment that are usually effective in classical CLL (particularly alkylating agents and corticosteroid drugs) is uniformly poor and the patients’survival after diagnosis is in most cases quite short.We believe that the clinical and haematological features of this condition justify its recognition separately from classical CLL, from lymphosarcoma cell leukaemia and from acute lymphoblastic leukaemia. We have therefore designated it ‘prolymphocytic leukaemia’. On the basis of a single case we suggest that further trials of splenectomy are indicated.
Heparin, Platelets and Blood Coagulation: Implications for Low‐Dose Heparin Prophylactic Regimens in Venous Thrombosis
Authors: Han P. , Ardlie N. G. 
Published: March 2008

Summary. Heparin has been shown to inhibit the second phase of aggregation and the platelet release reaction induced by ADP. These platelet responses to ADP are mediated by thrombin, generated through the coagulation pathways, on the platelet membrane (Ardlie & Han, 1974), and evidence was obtained that the inhibitory action of heparin is due to inactivation of coagulation factor Xa in the presence of XaI. In contrast, it has been shown that thrombin adsorbed to the platelet surface is protected from destruction by its natural inhibitor and heparin. Since trace amounts of heparin were able to augment the inhibitory action of XaI on factor Xa, this phenomenon has relevance to low‐dose heparin regimens for prophylaxis of venous thrombosis. It is proposed that postoperative thrombosis is due to abnormal platelet function caused by accelerated coagulation, and that heparin prevents thrombosis through its anticoagulant action on factor Xa. It is also suggested that trace amounts of heparin which may be present normally in the circulation may act as a natural anticoagulant.One of two commercial preparations of heparin caused washed platelets, prepared by some, but not all, of the methods used, to aggregate and release their constituents. However, it was shown that these effects of heparin on washed platelets are simply a consequence of storage of platelets at 4°C, emphasizing the need to keep platelets at 37°C for in vitro studies. Heparin failed to inhibit the release reaction of platelets in citrated‐plasma, and it is suggested that this may be due to interference by citrate. These observations with washed platelets and citrated plasma are considered to be artefacts and thus have no relevance to heparin action in vivo.
Chronic Myelomonocytic Leukaemia
Authors: Geary C. G. , Catovsky D. , Wiltshaw Eve , Milner Gillian R. , Scholes Muriel C. , van Noorden Susan , Wadsworth L. D. , Muldal S. , Maciver J. E. , Galton D. A. G. 
Published: March 2008

Summary. The natural history and haematological features of 18 patients with a chronic form of myelomonocytic leukaemia are described. The majority were elderly and, in this series, females predominated. Haematological prodomata, such as unexplained monocytosis, leucopenia, or thrombocytopenia were common, and the clinical onset was insidious. Splenomegaly was variable but tended to increase as the disease progressed.Anaemia was usually less than in the acute disease, unless compounded by iron deficiency. The blood film typically showed a mixed monocytosis and granulo‐cytosis, cells in both lines showing abnormalities. ‘Paramyeloid’ cells, appearing in Romanowsky stained films intermediate between myelocytes and monocytes, were characteristic, although cytochemical and electron microscopical analysis suggests that these cells may be allotted to one or other cell line. The marrow aspirate was characteristically hypercellular, showed granulocytic hyperplasia, and, in contrast to the well‐differentiated blood picture, the proportion of poorly differentiated cells, including blasts, was high. Serum lysozyme levels were usually raised. Five of the 18 cases survived more than 5 years, while 10 lived 2 years or longer.The morphological and clinical features form part of a spectrum including acute myelomonocytic leukaemia, into which several of the patients transformed. Recognition of the syndrome is important because the patients are probably best managed without intensive chemotherapy.
Hypocholesterolaemia and Anaemia
Authors: Westerman M. P. 
Published: March 2008

Summary.The present study has examined the relationship and significance of hypocholesterolaemia to anaemia and to the red cell. The level of plasma cholesterol is closely related to haematocrit levels both initially and throughout the course of the anaemias associated with hypocholesterolaemia. The association is maintained, regardless of the cause of the haematocrit change, i.e. transfusion or response to treatment. Hypocholesterolaemia does not affect the red cell, i.e. its survival, cholesterol concentration or osmotic fragility and occurs in a diverse group of anaemias. As such, it is not causally related to anaemia. The changes in plasma cholesterol are most likely related to its ‘redistribution’ or to plasma ‘dilution’, with contributory factors occurring. The presence of anaemia, even to a modest degree, would be important to consider when comparing cholesterol levels between groups of individuals.
Chromosomal Abnormalities and Dyserythropoiesis in the Preleukaemic Phase of Multiple Myeloma
Authors: Dahlke Miriam B. , Nowell Peter C. 
Published: March 2008

Summary.Two patients with multiple myeloma and one patient with a plasmacytoma are reported in whom acute leukaemia developed following long‐term treatment with melphalan. Each patient had a complete remission of the plasma cell disorder during which time the bone marrow was moderately to severely hypplastic. The end of the clinical remission was heralded by a dyserythropoietic anaemia which persisted several months before the emergence of the terminal acute leukaemia. Marked chromosomal abnormalities were observed in marrow cells during the dyserythropoietic phase.
Hypoplastic Acute Myelogenous Leukaemia
Authors: Beard M. E. J. , Bateman C. J. T. , Crowther D. C. , Wrigley P. F. M. , Whitehouse J. M. A. , Fairley G. Hamilton , Scott Ronald Bodley 
Published: March 2008

Summary.The clinical course, diagnosis and management of nine cases of hypoplastic acute myelogenous leukaemia are described. Such cases may follow a slowly progressive course and should not receive anti‐leukaemic chemotherapy unless the disease is advancing rapidly or unless some specific complication develops. If chemotherapy has to be given, usually because of severe and recurrent infections, then prompt and prolonged remission of disease may occur.
The Significance of Abnormal Circulating Cells in Patients with Hodgkin's Disease
Authors: Schiffer Charles A. , Levi John A. , Wiernik Peter H. 
Published: March 2008

Summary.Buffy coat preparations of peripheral blood from two patients with Stage IVB Hodgkin's disease, 33 patients with Hodgkin's disease undergoing complete staging including laparotomy, 12 normal controls and eight patients with viral upper respiratory infections were examined for the presence of abnormal cells. Primitive histiocytic cells were seen in the two patients with IVB disease and in two patients with IIIB disease all of whom proved to be refractory to chemotherapy. Reed‐Sternberg cells were seen in one IVB patient. Large cells with basophilic, agranular cytoplasm and moderately convoluted nuclei often with a perinuclear halo and nucleoli were detected in 30 of 35 patients with Hodgkin's disease, five of eight patients with viral infections but in none of 12 normal controls. Other abnormal large cells with round nuclei, occasional prominent nucleoli, grey to lightly eosinophilic cytoplasm and diffuse granulation were seen almost exclusively in Hodgkin's disease. There was no correlation between histology, stage, splenic involvement, skin test positivity and response to therapy with the presence or frequency of either of these cell types. This observation suggests that these cells are more likely to be ‘reactive’rather than malignant. It is unusual for abnormal histiocytic cells to circulate in Hodgkin's disease and their presence may be a poor prognostic sign. The presence of other types of large atypical cells is not indicative of either haematogenous spread of Hodgkin's disease or of poor prognosis after treatment with radiotherapy alone.
Sodium Periodate Modification of Factor VIII Procoagulant Activity
Authors: Kaelin A. C. 
Published: March 2008

Summary.Chemical treatment of human factor VIII by sodium periodate resulted in increased levels of procoagulant activity when measured by the two‐stage assay. Increased levels of factor‐VIII activity were observed following periodate treatment of factor‐VIII concentrates and normal, haemophilic and von Willebrand's disease plasmas. However, sodium periodate treatment of haemophilic plasmas which were completely deficient in factor‐VIII activity did not cause any reduction in the clotting times of two‐stage assays. No increase in procoagulant activity following oxidation of factor VIII could be detected by the one‐stage assay method. Gel filtration of factor‐VIII concentrates before periodate treatment showed that the protein exhibiting factor‐VIII activity had an apparent molecular weight in excess of 1 000 000, whilst after periodate treatment the apparent molecular weight was reduced to 690 000.
Solid‐Phase Immunoradiometric Assay of Factor‐VIII Protein
Authors: Counts Richard B. 
Published: March 2008

Summary.A solid phase immunoradiometric assay for factor‐VIII protein has been developed using 125I‐labelled rabbit antibody made against highly purified factor VIII. Antibody specific for high molecular weight factor‐VIII protein was isolated using an immunoadsorbent consisting of highly purified factor VIII bound to diazotized m‐aminobenzyl (oxymethyl)‐cellulose. The purified anti‐factor VIII antibody was labelled with 125I while bound to the immunoadsorbent and then eluted at pH 2.9. Dilutions of plasma samples for assay were incubated for 48 h in anti‐factor VIII antibody‐coated tubes. The tubes were washed to remove unbound proteins and the 125I‐labelled, purified antibody was added. After 48 h incubation the tubes were washed to remove unbound antibody and counted. The concentration of immunoreactive factor‐VIII protein in pooled normal human plasma was determined to be 8 μg/ml. The minimum amount of factor VIII measured by the assay is less than 0.16 ng. Factor‐VIII protein was present in normal concentration in haemophilia A plasma, and in reduced concentration in von Willebrand's disease plasma. This method has the advantages of improved sensitivity, specificity, efficiency and economy as compared with previous factor‐VIII immunoassays.
Quantitative Measurement of Splenic and Hepatic Red‐Cell Destruction
Authors: Bowring C. S. , Ferrant A. E. , Glass H. I. , Lewis S. M. , Szur L. 
Published: March 2008

Summary.A method has been developed by means of which independent measurement can be made of the amount of red‐cell destruction occurring in the spleen and the liver. The technique involves a standard red‐cell survival study and surface‐counting measurements together with quantitative scanning of the spleen and liver with 113mIn colloid in order to calibrate the surface counter. The rate of destruction in each organ is obtained by fitting the measured uptake curve for the organ to a theoretical uptake curve by computer. In addition, if whole body counting is also performed, the amount of red‐cell destruction occurring in the rest of the reticulo‐endothelial system may be deduced. Results are given for measurements on a series of 11 patients.
Acquired Erythroenzymopathies in Blood Disorders: Study of 200 Cases
Authors: Boivin Pierre , Galand Colette , Hakim Jacques , Kahn Axel 
Published: March 2008

Summary.Enzyme abnormalities are frequently found in the red cells of patients with various acquired blood disorders. In leukaemias, preleukaemic states and bone marrow insufficiencies with or without sideroblastosis, changes in enzyme activity are usually characterized by the coexistence of deficiency of some enzymes and an increased activity of others.The most frequently decreased activities are those of pyruvate kinase, phosphofructokinase,2,3‐diphosphoglycerate mutase and adenylate kinase; the most frequently increased activities are those of hexokinase, aldolase, enolase, 6‐phosphogluconate dehydrogenase and glucose‐6‐phosphate dehydrogenase.In primary myelofibrosis and in polycythaemia rubra vera, enzyme deficiencies are infrequent and differ from those observed in leukaemias and related disorders. Phosphohexose isomerase and phosphoglucomutase deficiencies seem relatively specific for polycythaemia rubra vera.Explanations for the acquired enzymopathies are still at the stage of hypothesis. The theory of multiple genetic damage may explain some findings but has not yet been proved right. The possibility of post‐translational molecular modification is suggested as a working hypothesis.
Molecular Basis of Thalassaemia
Authors: Weatherall D. J. , Clegg J. B. 
Published: March 2008

Summary.The thalassaemias are a heterogeneous group of conditions characterized by imbalanced globin chain production. In some forms there is a total absence of globin chain synthesis while in others globin chains are synthesized but at a reduced rate. There is increasing evidence that inefficiently synthesized structural haemoglobin variants can produce an identical clinical picture to thalassaemia.The molecular defect in the β thalassaemias is not yet worked out but in all forms studied, except the Ferrara type, there is an absolute reduction in the amount of β‐chain messenger RNA. In the Ferrara type there appears to be messenger RNA present but β‐chain synthesis does not occur unless induced by a soluble fraction from normal cells. The molecular pathology of the α thalassaemias is understood better. The severe type, α‐thalassaemia 1, results from a deletion of all or most of the α‐chain genes. There is good circumstantial evidence that the milder form, α‐thalassaemia 2, results from a loss of one of a pair of linked α‐chain genes. About half of the individuals with the haematological picture of α‐thalassaemia 2 are heterozygous for Hb Constant Spring, a chain‐termination mutant which is synthesized inefficiently. The chain‐termination mutants form a class of disorders which can produce the clinical picture of thalassaemia due to inefficient production of elongated α chains.
Nucleic Acid Studies on the Pathogenesis of Leukaemia
Authors: Polli Elio E. , Corneo Gianmarco 
Published: March 2008

Summary.Recent work has lent strong support for the viral hypothesis of pathogenesis of human leukaemia. In laboratory animals both horizontal transmission from one individual to another by inoculation of leukaemia virus in the newborn, and vertical transmission through subsequent generation, have been shown to occur. With some animal leukaemias, and in general in human leukaemia, virus‐like particles cannot be detected by the electron microscope. It is generally accepted, however, that oncogenic virus infection can be transmitted through viral nucleic acids alone. Although oncogenic DNA viruses such as the Ebstein‐Barr virus might be the agent of Burkitt's lymphoma, tumour viruses which cause leukaemia in animals are usually RNA, and RNA viruses are the more likely candidates as viral agents for human leukaemia.RNA molecules with nucleotide sequences related to those of animal RNA tumour viruses have been found in human leukaemia, lymphoma, sarcoma and carcinoma cells. Such RNA molecules have the size of 70S RNA and are contained in a complex with reverse transcriptase. Nucleotide sequences, related to sequences of known RNA tumour viruses, have also been detected in human leukaemic cell DNA.Viral DNA sequences appear to be integrated into the genome mainly in the DNA fraction having an intermediate repetition frequency. They are not enriched in the satellite DNAs, which are the most highly repeated sequence of the cellular genome.Normal cell genomes may contain endogenous viral sequences which are inactive and might have been transmitted vertically through many generations. Recent work indicates that inherited endogenous tumour virus nucleotide sequences are related in evolutionary related species. Therefore, it appears likely that a possible human leukaemia virus might be related to primate leukaemia viruses.
Factor VIII‐Related Antigen and von Willebrand's Disease
Authors: Rizza C. R. 
Published: March 2008

Summary.Immunological methods for the detection and assay of factor VIII‐related antigen have proved to be valuable tools in the study of factor VIII, haemophilia and von Willebrand's disease. The antibody neutralization tests, with their inherent difficulties and variability, have been largely replaced by the electroimmunoassay based on the method of Laurell. Using this latter method, it has been convincingly shown that whereas normal individuals and haemophiliacs have an antigen which precipitates with the rabbit anti‐factor VIII antibody, patients with von Willebrand's disease have a reduced amount of the antigen.The relationship of the antigen to factor VIII activity is not yet clear; nevertheless the assay of factor VIII‐related antigen is proving of some value in the diagnosis of von Willebrand's disease and in the detection of carriers of haemophilia. In von Willebrand's disease the test for the antigen along with the ristocetin test for platelet aggregation has thrown new light on the condition and has helped to define several variants of the disease.
Chamber Centrifugation: A Harvesting Technique for Estimation of the Growth of Human Haemopoietic Cells in Diffusion Chambers
Authors: Jacobsen Niels 
Published: March 2008

Summary. A harvesting technique which gives information about the spatial relationships between cells grown in diffusion chambers in mice has been designed. The principle is that cells are centrifuged directly from the chamber clot onto a slide during pronase treatment.The technique has been applied to normal human bone marrow cells grown in diffusion chambers. The slides show that the cells are situated in clusters. A limiting dilution assay of progenitor cells based on the presence of granulopoietic clusters in the chambers demonstrates the use of the method for quantitation of progenitor cells.