bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune Thrombocytopenia: Detection of Platelet Autoantibodies with the Suspension Immunofluorescence Test
Authors: von dem Borne A. E. G. Kr. , Helmerhorst F. M. , van Leeuwen E. F. , Pegels H. G. , von Riesz E. , Engelfriet C. P. 
Published: March 2008

Summary An immunofluorescence test on paraformaldehyde‐fixed platelets in suspension was used for the detection of antibodies on platelets and in the sera of patients with idiopathic or secondary thrombocytopenia.In idiopathic thrombocytopenia, a positive test was found on the patients' platelets in 55 out of 80 cases. The indirect immunofluorescence test with the patient's serum was positive in 28 out of 80 cases. In thrombocytopenia accompanied by other autoimmune diseases, the direct test was positive in 35 out of 39; the indirect test in 13 out of 39 patients. These results are similar to those obtained with other techniques recently described in the literature.By using FITC‐labelled monospecific anti‐immunoglobulin reagents, immunochemical characterization of the autoantibodies was possible. Of the 90 patients with a positive direct test, 80 were analysed in this way. Of these, platelet‐bound IgG was detected in 76. This was accompanied by IgM in 17 and IgA in three. In four, only IgM was found. The IgG subclasses of platelet‐bound IgG were studied in 48 patients. Mainly IgG1 was found (45), often together with IgG3 (22) or IgG4 (14), but rarely with IgG2 (1). Only a few patients had just IgG3 (2) or IgG4 (1) on their platelets.Platelet‐bound autoantibodies could often be eluted (41 out of 86 cases) with ether and were demonstrable in the eluate with the indirect immunofluorescence test. This test was usually positive when the direct test was strongly positive (40 out of 44) and usually negative when it was weakly positive (1 out of 24) or negative (1 out of 18).
Lymphoid Cell Sets and Serum Immunoglobulins in Patients with Thalassaemia Intermedia: Relationship to Serum Iron and Splenectomy
Authors: Kapadia Asha , de Sousa Maria , Markenson Alicejane L. , Miller Denis R. , Good Robert A. , Gupta Sudhir 
Published: March 2008

Summary Peripheral blood lymphocyte sets and serum immunoglobulins were examined in 15 patients with thalassaemia intermedia, aged between 5 and 30 years. They were divided in three clinical groups: Group I, non‐splenectomized, with serum iron (SI) lower than 200 μg/dl; Group II, splenectomized with serum iron lower than 200 μg/dl; and Group III, splenectomized with serum iron levels greater than 200 μg/dl. High absolute lymphocyte counts were observed in the majority of patients, whether splenectomized or not. Following splenectomy, marked increases were observed in absolute number of lymphocytes and percentages of circulating surface immunoglobulin (SIg) bearing B lymphocytes, mouse rosette forming cells (MRFC) and ‘null’ cells. The increases in circulating B lymphocytes following splenectomy were due exclusively to cells bearing SIgM and/or SIgD. No changes were observed in numbers and proportions of circulating SIgA or SIgG bearing cells. Serum IgA levels were high in the majority of patients studied whether splenectomized or not. Following splenectomy increases in serum IgA and serum IgG were observed which seemed to relate to increasing SI levels. No significant changes occurred in serum IgM levels.Absolute numbers of circulating T lymphocytes were unaffected by splenectomy or SI levels. Changes were observed, however, in distribution of T lymphocyte subsets with decreases in number of Tμ cells and concomitant increases in numbers of non‐Tμ, non‐Tγ cells. Tγ cells were the least affected by splenectomy and increasing SI. The results are compatible with the proposition that iron participates in the regulation of lymphoid cell migration and in the modulation of expression of cell surface markers. The findings also illustrate the role of the spleen in the control of lymphocyte migration and immunoglobulin production.
Histological Study of Bone Marrow Regeneration following Chemotherapy for Acute Myeloid Leukaemia and Chronic Granulocytic Leukaemia in Blast Transformation
Authors: Islam Anwarul , Catovsky Daniel , Galton David A. G. 
Published: March 2008

Summary Haemopoietic regeneration following chemotherapy was studied on serial bone‐marrow trephine specimens from 10 patients with acute myeloid leukaemia (AML), and seven with chronic granulocytic leukaemia (CGL) in blast transformation. In AML following the stage of treatment‐induced hypoplasia during which the marrow was extremely hypocellular, oedematous, and contained widely dilated sinuses, areas of large, uniform, unilocular fat cells, designated ‘structured fat’ developed from multilocular precursor fat cells. Early foci of haemopoietic regeneration were present almost exclusively in areas of structured fat: only scattered small erythropoietic foci were seen in the earliest specimens taken 1 week after the completion of treatment; small granulopoietic foci were first seen 2 weeks later, and the first megakaryocytes were not seen until the third week. Transient regeneration was observed in two patients who subsequently failed to enter remission and died.The pattern of haemopoietic regeneration in CGL in blast transformation treated by intensive therapy and autografting with cryopreserved buffy‐coat cells differed from that seen in AML. Bone marrow regeneration occurred earlier than in AML and appeared to be independent of the presence of structured fat. Regeneration in all three cell lines appeared simultaneously within 2 weeks of autografting. Regeneration tended to be focal, each aggregate consisting almost exclusively of erythroid, granulocytic or megakaryocytic cells.The proximity of regenerating haemopoietic foci to structured fat in AML suggests that, in some circumstances, haemopoietic stem cells require the presence of fat cells in their immediate environment before they proliferate.
The Regulation of Iron Release from the Perfused Rat Liver
Authors: Baker E. , Morton A. G. , Tavill A. S. 
Published: March 2008

SummaryFactors affecting iron efflux from the isolated perfused rat liver were studied following the intravenous administration of transferrin‐59Fe or transferrin‐55Fc administered to the rat from 1·5 h to 3·5 d before perfusion of the liver.The liver was perfused with rat red cells suspended either in rat plasma or Eagle's Basal Medium (EBM). The mean rate of efflux into a plasma pool containing normal iron and transferrin concentrations was 0·9% of the initial hepatic radioactive iron pool per hour. In EBM the average rate of efflux was 0·1%/h and this could be increased to the rate observed with plasma by the addition of apotransferrin. The rate of iron release from the liver in the presence of apotransferrin or other chelators was inversely proportional to the time of prelabelling. Maximal release rates were observed in livers perfused within 5 h of administering transferrin‐59Fe to the rat. The effect of apotransferrin on efflux into EBM was concentration dependent. However, the maximum release of liver iron by apotransferrin occurred at physiological apotransferrin concentrations and addition of apotransferrin to plasma produced no increase in the rate of iron efflux. The stimulation of iron release in EBM caused by apotransferrin could be reversed by reducing the unsaturated iron binding capacity of the perfusate, either by addition of iron or removal of apotransferrin. However, increasing the iron concentration in the perfusate by the addition of iron‐saturated transferrin without any reduction in the unsaturated iron binding capacity additionally increased iron release into plasma and EBM. This presumably reflects the exchange of plasma transferrin‐36Fe for liver59Fe. Hence iron release measured in these studies represents the sum of two processes—net release of59Fe induced by apotransferrin and iron exchange between plasma and liver iron pools.Apotransferrin and desferrioxamine were equally effective, per unit iron binding capacity, in mobilizing liver iron, and may compete for the same parenchymal iron pool. This suggests that mobilization of iron by apotransferrin may depend solely onits ability to chelate ferric iron and not on a more specific ferroxidase activity or interaction with membrane receptors.
Coagulation Factors in the Human Fetus of about 20 Weeks of Gestational Age
Authors: Terwiel Jack Ph. , Veltkamp Jan J. , Bertina Rogier M. , Muller Hein P. 
Published: March 2008

Summary In plasma samples of 11 fetuses of about 20 weeks of gestational age the following coagulation factors have been determined (mean values found are given in parentheses): fibrinogen (0·30 U/ml), prothrombin (±0·17 U/ml), factor V (0·28 U/ml), factor VII (0·21 U/ml), factor VIII coagulant activity (factor VIII:C) (0·12 U/ml), factor VIII‐related antigen (factor VIIIR:Ag) (1·04 U/ml), coagulant factor VIII‐related antigen (factor VIII:CAg) (0·19 U/ml), factor IX coagulant activity (0·05 U/ml), factor IX antigen (≤0·03 U/ml), factor X (0·19 U/ml) and antithrombin III (AT‐III) (0·23 U/ml).Our data support the evidence that prenatal diagnosis of haemophilia A is at present possible; less optimism is warranted where haemophilia B is concerned. The number of samples is sufficient to establish normal values for the age group.Means of quality control of the sample—which is often difficult to obtain—are discussed.
Prognostic Significance of Bone‐Marrow Patterns in Chronic Lymphocytic Leukaemia
Authors: Rozman C. , Hernandez‐Nieto L. , Montserrat E. , Brugues R. 
Published: March 2008

Summary. Bone‐marrow biopsy has been performed in 63 cases of chronic lymphocytic leukaemia (CLL). Four different histological patterns were observed: (a) interstitial (lymphoid infiltration without displacement of fat cells) in 12 cases; (b) nodular (abnormal lymphoid nodules without interstitial infiltration) in 10 cases; (c) mixed (combination of the first two patterns) in 21 cases; and (d) diffuse (replacement of both haemopoietic and fat cells by lymphoid infiltration) in 20 cases.Statistical analysis of actuarial curves showed a significant difference of survival probability according to the bone marrow infiltration patterns. Thus, in patients with interstitial or nodular patterns the life expectancy is significantly longer than in those with mixed or diffuse patterns. Furthermore, a significant degree of correlation between bone marrow infiltration patterns and different methods of clinical staging in CLL was apparent.The different bone marrow infiltration patterns in CLL probably reflects variations in the amount of lymphoid accumulation during the natural course of this disease. Because of its prognostic significance, bone marrow biopsy should have a place in CLL evaluation and staging.
Immunologically Defined Subclasses of Acute Lymphoblastic Leukaemia in Children: their Relationship to Presentation Features and Prognosis
Authors: Greaves Melvyn F. , Janossy George , Peto Julian , Kay Humphrey 
Published: March 2008

Summary. Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, ‘null’ (or ‘unclassified’) ALL and a rare lymphoma/leukaemia type B‐ALL. A T‐cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T‐ALL patients but was not observed in any unequivocal non‐T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T‐ALL, better in ‘null’ ALL, and highest in cALL (P trend < 0·0001; P=0·0002 for comparison of cALL versus T‐ALL). There was a much higher incidence of CNS involvement in the T‐ALL group than in the cALL group or ‘null’ ALL group and although this was strongly correlated with WBC count it was also significantly associated with T‐ALL independent of WBC count.Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant.It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic
Collagen Heterogeneity in Normal Human Bone Marrow
Authors: Bentley S. A. , Alabaster O. , Foidart J. M. 
Published: March 2008

Summary. Paraffin embedded sections of formalin fixed, decalcified, normal, human, vertebral bone were stained immunohistochemically for collagen types I, III and IV using the peroxidase—anti‐peroxidase (PAP) technique. Preparations stained for collagen types I and III were virtually identical in appearance. These substrates were localized to the cytoplasm and fibrillar processes of a population of cells which were sparsely distributed within the haemopoietic compartment of the bone marrow, being particularly prominent in relation to the marrow sinusoids and fat spaces. They would thus appear to parallel the known distribution of reticulum cells, although their morphology differed in some respects from classical descriptions of the latter cell type.Type IV collagen was found in association with the endothelial lining of the sinusoids. Other connective tissue elements (bone, periosteum, endosteum, blood vessels, etc.) showed characteristic collagen heterogeneity.These results indicate that collagen is a significant component of the bone marrow connective tissue.
Changes in Energy Metabolism, Structure and Function in Alveolar Macrophages under Anaerobic Conditions
Authors: Butterick Charles J. , Williams David A. , Boxer Laurence A. , Jersild Ralph A. , Mantich Jr Nancy , Higgins Coleen , Baehner Robert L. 
Published: March 2008

Summary.To determine whether the change in energy metabolism of guinea‐pig alveolar macrophages (AM) would alter their function to resemble peritoneal macrophages (PM), AM were exposed to strict anaerobic environments for 96 h. Exposure of cultivated AM to hypoxic conditions resulted in a decreased activity of cytochrome oxidase, a key enzyme in oxidative phosphorylation, whereas pyruvate kinase activity, a key enzyme in glycolysis, increased to levels observed in PM. Under hypoxic conditions the total mitochondrial structure available for respiratory activity also decreased in the glycolytic energy‐dependent AM.Accompanying the shift in energy metabolism, adaptive changes in the functional responses of lectin‐receptor activity occurred in the AM exposed to hypoxic conditions. Culture of AM in an anaerobic environment led to a loss in their ability to mobilize their lectin receptors in response to cytochalasin B, whereas AM maintained in an aerobic environment could mobilize their receptors in response to either cytochalasin B and D. Alterations in O2 tension affect AM metabolism, morphology and function and indicate that the AM is able to change its energy metabolism according to environmental circumstances.
The Role of Synovectomy in the Management of Recurrent Haemarthroses in Haemophilia
Authors: Kay Lesley , Stainsby David , Buzzard Brenda , Fearns Maureen , Hamilton P. J. , Owen Philip , Jones Peter 
Published: March 2008

Summary. Between August 1973 and May 1979, 18 patients suffering from severe haemophilia A underwent synovectomy for recurrent haemarthroses, resistant to medical management. A total of 23 joints (11 knees and 12 elbows) were subjected to operation, five patients undergoing two synovectomies on different joints. Post‐operative follow‐up period ranged from 12 to 58 months for elbow synovectomy and from 29 to 76 months for knee synovectomy. All patients experienced fewer haemarthroses, the average number of bleeding episodes per joint over a 12 month period being reduced from 19 to 3 for knee joints, and from 24 to 3 for elbow joints. This improvement was apparent in the immediate post‐operative year and maintained thereafter. Over the same follow‐up period nine of the 11 knee joints were found to have lost an average 42° mobility. Following elbow synovectomy five out of 12 patients lost an average of 28° mobility; six patients gained an average 11° mobility.The post‐operative complication rate was high for knee synovectomy, 54% suffering haemorrhage despite haemostatic factor VIII levels. For elbow synovectomy the rate was much lower, 75% of operations being uncomplicated. The average in‐patient time for knee operation was 75 d, and for the elbow 19 d.We conclude that synovectomy of the knee joint is to be avoided when other means of reducing bleeding episodes are available, whereas elbow synovectomy retains a useful role in the treatment of recurrent haemarthroses which do not respond to clotting factor prophylaxis.
The Mechanisms which Produce Vacuolated and Degranulated Eosinophils
Authors: Tai P.‐C. , Spry C. J. F. 
Published: March 2008

Summary. As blood eosinophils in patients with an eosinophilia may contain refractile‘vacuoles’(vacuolated eosinophils), and some cells contain only a few granules (degranulated eosinophils) which show ultrastructural changes, experiments were done to see whether similar morphological alterations could be induced in blood eosinophils from normal people. Overnight culture of normal eosinophils with serum treated with cobra venom factor induced refractile‘vacuoles’and ultrastructural changes in granule matrix material. On the other hand, concanavalin A, 10 μ/ml for 2 h, led to the formation of larger perinuclear vacuoles containing granule contents, and ultrastructural changes were more marked in granule crystalloid material. Cytochalasin B inhibited these effects of concanavalin A. Neither of these stimuli caused a marked reduction in the number of cytoplasmic granules, but lysolecithin and insoluble (but not soluble) immune complexes produced large endocytic vacuoles into which partially solubilized and whole eosinophil granules were discharged.These results suggest that eosinophil granules can be affected in two distinct ways. In one, the granule matrix is altered leading to the light microscopy appearances of small refractile ‘vacuoles’. In the second, the crystalloid material is dispersed into the matrix. These apparently distinct steps precede the release of the granule contents into large cytoplasmic spaces or to the outside of the cell. Also, as patients' eosinophils may show one or both of these alterations it is suggested that they are distinct events. As concanavalin A induced solubilization of granules did not result in release to the outside, it is also proposed that an additional stimulus may be required to produce exocytosis of eosinophil granule contents. Further studies may show how these processes are linked, and their relative importance in eosinophil effector functions.
Relationship of Raised Platelet IgG in Thrombocytopenia to Total Platelet Protein Content
Authors: Pfueller Sharron L. , Cosgrove Leah , Firkin Barry G. , Tew Deborah 
Published: March 2008

Summary. Platelet‐associated IgG (PA IgG) of washed platelets of 20 normal controls and 45 thrombocytopenic patients was measured by radioimmunoassay and related to total platelet protein content.Mean values (±2 SD) for 20 normals were 4.4 ± 3.5 fg IgG per platelet (fg IgG/pl), 2.1 ± 1.0 pg protein per platelet (pg protein/pl) and a ratio of IgG per g platelet protein of 2.1 ± 1.8 mg IgG/g protein. Patients could be divided into two groups: Group I (31) with normal IgG/g protein ratios and either normal (16) or raised (15) fg IgG/pl, and Group II (14) with both fg IgG/pl and IgG/g protein raised. Of the 21 patients with idiopathic thrombocytopenia (ITP), 13 were in Group I (seven with raised and six with normal fg IgG/pl), and eight in Group II. There was significant correlation between PA IgG (fg IgG/pl) and platelet protein for the entire Group I (r=0.95, P < 0.001). The ITP patients in this group showed a similar correlation (r=0.77, P < 0.001), suggesting that raised PA IgG levels in Group I patients may be a result of protein‐rich platelets.60‐90% of PA IgG was found in the soluble fraction of lysates of platelets from both normals and patients. Thus, it is either non‐specifically associated with platelets or is antibody directed towards easily solubilized platelet antigens. Nine thrombocytopenic patients without immune disorders had raised PA IgG. These results question the assumption that raised PA IgG always indicates specific antiplatelet antibody.
Depressed Responsiveness to Adrenaline in Platelets from Apparently Normal Human Donors: a Familial Trait
Authors: Scrutton M. C. , Clare K. A. , Hutton R. A. , Bruckdorfer K. R. 
Published: March 2008

Summary. Decreased responsiveness to adrenaline has been observed in five apparently normal unrelated human donors. In four of the donors this trait is inherited. Three of the donors, as well as their affected relatives, also exhibit depressed responsiveness to collagen and vasopressin but normal responsiveness to ADP and thrombin. The other two affected donors exhibit normal responsiveness to most other agonists.Normal responsiveness can be restored in all instances either by incubating the platelet‐rich plasma at 20°C or by addition of a low concentration of the divalent cation ionophore, A‐23187. All affected platelets which have been examined have ATP and ADP contents, cholesterol to phospholipid ratios, and phospholipid class compositions within the normal range. Both the resting level of cyclic‐3′,5′‐AMP and the ability of adrenaline to prevent elevation of cyclic‐3′.5′‐AMP levels by prostaglandin E1 are normal. Mixing experiments demonstrate the absence of a circulating inhibitor of platelet function and suggest that the defect resides in the platelets. We conclude that the depressed responsiveness of human platelets to adrenaline may result from a defect in Ca2+ mobilization to the cytosol.
Busulphan aplasia in rabbits: a model for human aplastic anaemia
Authors: den Ottolander Gerard J. , te Velde Jan , Veenhof Wil , Kleiverda Karin , Haak Hans L. , Spaander Piet Jan 
Published: March 2008

Summary. Bone marrow histology plays a crucial role in the clinical diagnosis of aplastic anaemia. The nature of the disease means that few studies are available on the histological changes which occur in the early stages of the development of aplasia. We describe here an animal model which may have some relevance in this respect. Rabbits were chronically exposed to busulphan (BU) to induce aplasia. Sequential histological monitoring of the bone marrow was performed to obtain information about the events preceding full‐blown aplasia. There was an early decrease and ultimate disappearance of granulo‐ and megakaryopoiesis with relative sparing of erythropoiesis which showed severe dysplasia. Increasing lymphoplasma‐cytoid infiltrate resembling that seen in human aplasia could be observed in the majority of the animals, together with a decrease of the peripheral lymphocyte number. Lymph nodes and spleen did not show lymphocyte depletion and serum gamma‐globulin remained stable. Fibrosis was observed in 50%, which is in contrast with human aplasia at diagnosis. In half of the animals there was a rise in MCV, which was not correlated with reticulocytosis or degree of dyserythropoiesis.BU‐induced aplasia in rabbits, which resembles long‐standing grade II human aplasia in many respects, might be a suitable model for the study of aplastic anaemia due to stem cell defects.