bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Heterologous Anti‐lymphocyte and Anti‐granulocyte Sera on Haematopoietic Progenitor Cells in the Rat
Authors: Benestad H. B. , Iversen J.‐G. , Warhuus K. 
Published: March 2008

Summary.The effect on haematopoietic progenitor cells of specific antisera against mature haemic cells has been investigated.Heterologous anti‐lymphocyte and anti‐granulocyte sera were prepared by injecting suspensions of rat target cells into rabbits. Recirculating lymphocytes were obtained from thoracic duct lymph, non‐recirculating ones from blood of rats in which thoracic duct lymph had been drained away for 3 days, and mature granulocytes were isolated from blood of normal rats. Preliminary assaying of the cytotoxic activity of the sera was done by measuring isotope release from target cells proper, labelled with 51 Cr. When absorption procedures had been carried out the antisera were apparently specific for recirculating lymphocytes, nonrecirculating lymphocytes, or granulocytes.The effect of these antisera on progenitor cells for granulocytes and on mature cell types were then evaluated with the diffusion chamber culture technique. Mononuclear cells from rat blood, bone marrow cells, or a mixture of both were incubated with different dilutions of antisera before culturing for I or 4 days. The yield of the cell types used for immunization was reduced with all employed dilutions of antisera. The number of proliferative granulocytes harvested from 4‐day cultures was taken to reflect the number of progenitors inoculated. Anti‐recirculating lymphocyte sera never affected progenitor cells, and they could be spared with some dilutions of antisera against nonrecirculating lymphocytes and granulocytes.It is thus possible to prepare specific antisera against lymphocytes with no harmful effect on progenitor cells.
Renal Fibrin Deposition Associated with Isoimmune Haemolysis in Monkeys: Observation by Light, Electron and Immunofluorescence Microscropy
Authors: Roth G. J. , Poskitt T. R. , Bobrow J. C. , Fortwengler H. P. 
Published: March 2008

Summary.Following control renal biopsies, five cynomolgus monkeys received an infusion of incompatible isoimmune plasma. Renal biopsies were obtained at 2 or 4 hr, 24 hr, and 7 days after infusion and were examined by light and electron microscopy, as well as immunofluorescence microscopy for platelet antigens and fibrinogen related antigen(s) (FRA). Test animals receiving incompatible plasma showed evidence of haemolysis and disseminated intravascular coagulation. Renal tissue changes varied according to the severity of the transfusion reaction and the time of biopsy. Light microscopy revealed mild glomerular and tubular changes. In early biopsies, immunofluorescence studies showed deposition of FRA in glomerular capillaries and tubule cells. By day 7, glomerular FRA was no longer present, and tubule cell FRA had been displaced into the renal interstitium. Platelet antigen was not seen in any biopsy. Electron microscopy demonstrated proximal tubule cell damage with phosphotungstic acid positive staining granules, intravascular clot formation, and foot process fusion. Two control monkeys received compatible plasma and showed no evidence of renal injury. It appears that renal fibrin deposition and tubule cell damage occur even during mild haemolytic transfusion reactions. This study provides evidence for local fibrinolysis of glomerular fibrin and the transfer of FRA from tubular lumens to the interstitium. In addition, tubule cell FRA appears to be associated with structural damage.
Ferritin in Blood Cells from Normal Subjects and Patients with Leukaemia
Authors: Worwood M. , Summers M. , Miller F. , Jacobs A. , Whittaker J. A. 
Published: March 2008

Summary. Normal human leucocytes contain about 7 fg ferritin protein per cell. In 16 patients with acute myeloblastic leukaemia the mean concentration was 46 fg per cell, in acute myelomonocytic leukaemia 175 fg per cell, and in chronic granulocytic leukaemia 16 fg per cell.It is suggested that the high serum ferritin concentration in leukaemic patients is derived from the leukaemic cells themselves and that it may be due to increased synthesis.
The Anti‐Rho(D) Responses of Immunized Volunteers following Spaced Antigenic Stimuli
Authors: Gunson H. H. , Stratton F. , Phillips P. K. 
Published: March 2008

Summary. Twenty‐six Rho(D) negative male volunteers previously immunized with Rho(D) positive red cells have received spaced antigenic stimuli in an attempt to produce high serum anti‐D activity during the secondary responses.Although there is a considerable individual variation in magnitude, there is, in general, either a rapid or slow fall from the maximum anti‐D concentration achieved to some steady state of anti‐D concentration which persists with little change for several months.A case is made for the acceptance of an anti‐D concentration of 20 International Units (i.u.) per cm3 (about 7μ g/cm3) as the minimum requirement for accepting plasma donations for immunoglobulin preparations. On this basis 19 of the 26 volunteers could contribute regularly, although in only 10 volunteers was a concentration of 100 i.u./cm3 or more maintained for periods of several months following an antigenic stimulus.No correlation was observed between the maximum concentration achieved in the primary response and that at the steady state following further antigenic stimulation. The potential of a volunteer cannot, therefore, be predicted from the early immune response. Indeed with certain volunteers after regular spaced antigenic stimuli, markedly reduced antibody responses have been observed.The implications of these findings are discussed with respect to the collection of suitable donations of anti‐D plasma.
Oxygen Binding to Haemoglobin in Subjects with Hypoproliferative Anaemia, with and without Chronic Renal Disease: Role of pH
Authors: Lichtman M. A. , Murphy M. S. , Whitbeck A. A. , Kearney E. A. 
Published: March 2008

Summary. The relationships of haenioglobin concentration and blood pH to red cell 2,3‐dipliosphoglycerate and oxygen binding by haenioglobin have been studicd in healthy subjects and subjects with hypoproliferative anaemia with or without severe chronic renal disease. Red cell 2,3‐DPG was inversely correlated with haemoglobin deficit and directly and equally strongly associated with blood pH in anaemic subjects without chronic renal disease. In subjects with chronic renal disease receiving regular haemodialysis, predialysis pH was not increased despite severe anaemia, and red cell 2,3‐DPG was not significantly elevated, except in subjects who had a sustained alkalosis due to the use of sodium bicarbonate.In hypoproliferative anaemia, the incrcmcnt in pH was associated with the decrease in haenioglobin concentration such that 80% of the increase in p50 measured at standard conditions which occurred with anaemia was explicable by the relationship of (a) pH with haemoglobin concentration, (b) red cell 2,3‐DPG with pH, and (c) pso std with red cell 2,3‐DPG. However, p50 at the pH and base excess present in vivo was similar in all anaemic subjects whether an increase in red cell 2,3‐DPG occurred or not. Blood alkalosis and the accumulation of 2,3‐DPG cancelled each other's effect on oxygen binding by haemoglobin. Hence, increased red cell 2,3‐DPG and p50 compensated for the alkalosis of hypoproliferative anaemia, not for the deficit in haemoglobin concentration.
Colony Formation by Human Haemopoietic Precursor Cells Cultured in Semi‐solid Agar in Diffusion Chambers
Authors: Gordon M. Y. , Blackett N. M. , Douglas I. D. C. 
Published: March 2008

Summary.A technique which allows colony growth of haematologically normal human bone marrow cells is described. The cells are supported by semi‐solid agar‐medium inside modified Millipore diffusion chambers implanted in the peritoneal cavity of irradiated mice. After 9 days incubation colonies containing up to 1000 cells are found in these Agar Diffusion Chambers. All haematologically normal patients studied so far produced colonies, the majority with between 10 and 40 colonies per 2 × 105 bone marrow cells inoculated.This culture system therefore provides a convenient and reliable clonal assay for human bone marrow cells which, in contrast to the agar colony assay in vitro, does not require a source of Colony Stimulating Factor (CSF).
Serum Inhibitors of Fibrinolysis
Authors: Gallimore M. J. 
Published: March 2008

Summary.Four protease inhibitors have been identified in human serum and methods for their isolation are described. After removal of the euglobulin fraction, serum was submitted to ion exchange chromatography and gel filtration, and fractions were tested for inhibition of the lysis of plasminogen‐deficient fibrin clots by plasmin, trypsin and elastase. In addition inhibitors of plasminogen activation were sought by studying the effects of separated fractions on the lysis of plasminogenrich fibrin clots by urokinase. Examination by immunophoresis showed that three of the separated inhibitors were α2‐macroglobulin, α1‐antitrypsin and inter‐α‐trypsin inhibitor. The fourth antiprotease was a powerful inhibitor of both urokinase‐induced and plasmin‐induced clot lysis, and was identified as an inter‐α‐globulin from its electrophoretic mobility in agarose gels.
Portal Hypertension in Chronic Leukaemia
Authors: Datta D. V. , Grover S. L. , Saini V. K. , Datta B. N. , Aikat B. K. , Chhuttani P. N. 
Published: March 2008

Summary.Portal haemodynamic studies were carried out in 11 subjects, seven with chronic myeloid leukaemia and four with chronic lymphatic leukaemia, and results compared with those obtained in five patients with ‘idiopathic’splenomegaly and with control subjects.All 11 patients with chronic leukaemia had intrasplenic pressures above 11 mmHg and of these four had pressures above 20 mmHg. Portosystemic collaterals were seen on splenovenography in four of these patients. Hepatic vein wedge pressure was above 7 mmHg in nine patients and these high levels were a result of increased free hepatic vein pressure. The corrected sinusoidal pressure and post sinusoidal resistance were essentially normal in all patients. Evidence of increased pre‐sinusoidal resistance was seen in six patients. Estimated hepatic blood flow above 1500 ml/min was seen in six patients and all had evidence of histological portal or sinusoidal infiltration.Patients with ‘idiopathic’splenomegaly regardless of increased liver blood flow did not have a significant increase in intrasplenic pressure and no alteration in other haemodynamic parameters. It appears that increased liver blood flow alone in a normal liver can only minimally elevate intrasplenic pressure but can play a significant part in the pathogenesis of portal hypertension when liver structure is altered.
Ultrastructural Studies of the Bone Marrow in Sickle Cell Anaemia
Authors: Grasso J. A. , Sullivan A. L. , Sullivan L. W. 
Published: March 2008

Summary.Electron microscopic studies of bone marrow aspirates obtained from patients with homozygous sickle cell anaemia (HbSS) were fixed immediately without attempts to deoxygenate the samples. Erythroblasts and normoblasts in these preparations were devoid of haemoglobin polymers or other indications of sickling. Furthermore, the nucleated erythroid cells from sickle‐cell patients presented an ultrastructural morphology indistinguishable from that of identically‐processed erythroid cells in marrow samples from normal human volunteers. This report presents a description of the ultrastructural features of pronormoblasts and normoblasts in normal and sickle‐cell marrows and stresses the essentially normal appearance of nucleated erythroid elements in sickle cell anaemia. Exposure of sickle‐cell marrow aspirates to nitrogen at 37°C for 30 min resulted in haemoglobin polymerization in most erythrocytes and reticulocytes but only in 10–20% of the nucleated erythroid cells. Haemoglobin polymers in the form of intertwining tibre mesh works were observed in reticulocytes, orthochromatic and polychromatophilic normoblasts, but were absent in basophilic normoblasts and pronormoblasts. The results suggest that the concentration of haemoglobin in intramedullary normoblasts may be the limiting factor determining the predisposition of these cells to undergo sickling as well as the pattern of haemoglobin aggregation. Under the physiological conditions prevailing in the marrow, haemoglobin concentration in normoblasts may be insufficient to result in aggregation and polymerization.
Splenectomy in Homozygous Beta Thalassaemia: A Retrospective Study of 30 Patients
Authors: Engelhard Dan , Cividalli Gabriel , Rachmilewitz Eliezer A. 
Published: March 2008

Summary.In order to clarify the indications for splenectomy in patients with homozygous β thalassaemia we studied, retrospectively, the basal pre‐transfusion haemoglobin levels and blood transfusion requirements before and after splenectomy, in a series of patients with this disorder.Thirty‐six patients, of whom 20 underwent splenectomy, were included in this study. Three groups of patients with homozygous β thalassaemia were identified on the basis of clinical and laboratory findings. Two of the three groups consisted of 24 patients with β thalassaemia major, subdivided retrospectively according to their response to splenectomy. The third group consisted of six patients with β thalassaemia intermedia who had a comparably mild clinical course.In the first group of 16 patients with β thalassaemia major, monthly transfusions were required from the age of 6 months to 24 months and splenectomy resulted in temporary improvement for a period of 1–2 years. Thereafter, the transfusion requirements returned to pre‐operative levels with no sustained improvement in base‐line pretransfusion haemoglobin levels. Despite the fact that haematological improvement was temporary, it is felt that splenectomy is indicated in this group since the development and the general well‐being of the children was significantly improved.In the second group of eight patients with β thalassaemia major, transfusion requirements were relatively infrequent before 1–2 years, but after several years the transfusion requirement increased simultaneoulsy with the development of‘hypersplenism’. In these cases splenectomy was found to be beneficial for longer periods of time as manifested by a decrease in the transfusion requirement and an increase in the pretransfusion haemoglobin levels. Patients who developed hypersplenism relatively late in the course of their disease were usually the ones who derived long‐term benefit from splenectomy.In the third group of six patients with β thalassaemia intermedia and a benign clinical course, with higher basal haemoglobin levels and lower blood transfusion requirements, most of the splenectomies were performed because of mechanical pressure due to splenomegaly. After splenectomy, these patients showed continued improvement in their haemoglobin levels and decreased transfusion requirements.
Partial Characterization of the Factor VIII‐Stimulating Material of Rabbit Liver Perfusates: Relationships to Rabbit Plasma Factor VIII
Authors: Benson R. E. , Jean Dodds W. 
Published: March 2008

Summary.Previous studies in our laboratory showed that effluent from perfused rabbit livers stimulates the production of factor‐VIII activity in perfused rabbit spleens. When concentrated supernatants of the hepatic perfusates were chromatographed on Sephadex G‐200, BioGel A‐15M and Sepharose 4B, the fractions with the greatest factor VIII‐stimulating capacity eluted in the void volume (V°). Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the Sephadex G‐200 V° fraction revealed components with a wide range of molecular weights. Rabbit factor VIII was isolated from ethanol‐concentrated, citrated rabbit plasma by Sepharose 4B filtration. The factor‐VIII activity appeared in the V° when eluted with physiological saline but was retarded on columns eluted in 0.8 M sodium chloride. Further analysis with SDS gels demonstrated that the Sepharose‐purified factor‐VIII preparation entered the polyacrylamide gels only after reduction with 2‐mercaptoethanol. Goat antirabbit factor VIII antiserum prepared against the gel‐purified antigen contained factor VIII‐neutralizing activity, was apparently monospecific by double‐diffusion and produced faint, single peaks by electro‐immunodiffusion. Antibody neutralization studies with the antiserum showed that the concentrated supernatants of hepatic perfusates contain fourfold greater factor VIII‐neutralizing antigen than procoagulant activity, whereas control perfusates, lacking factor VIII‐stimulating capacity, had negligible antibody‐blocking effect. The presence in hepatic perfusates of both high‐molecular‐weight factor VIII‐stimulating material and large amounts of factor VIII‐neutralizing antigen lacking procoagulant activity suggests that they are interrelated.
Microthrombocytosis and Platelet Fragmentation Associated with Idiopathic/Autoimmune Thrombocytopenic Purpura
Authors: Khan Iqbal , Zucker‐Franklin Dorothea , Karpatkin Simon 
Published: March 2008

Summary.Platelet volume distribution curves were obtained in 20 control subjects and in 21 patients with idiopathic/autoimmune thrombocytopenic purpura. A striking increase in microthrombocytes as well as megathrombocytes was noted in 86% of patients on one or more occasions, particularly in the presence of severe thrombocytopenia. The entire spectrum of platelet volume distribution curves noted in patients could be reproduced experimentally in rabbits following intravenous injection of anti‐platelet antibody. Differential centrifugation studies with control subjects revealed that microthrombocytes were light platelets and megathrombocytes were heavy platelets. Electron microscopy in patients with thrombocytopenia revealed that microthrombocytes were composed of intact small platelets as well as platelet fragments. It is concluded that severe peripheral destruction of platelets is associated with an increase in microthrombocytes as well as megathrombocytes.
Interactions between Genetic Red‐Cell Defects and the Environment
Authors: Luzzatto Lucio 
Published: March 2008

Summary.Environmental factors can affect the course of genetically determined disorders of red cells. On the other hand, genetically‘abnormal’red cells can respond to environmental agents differently from normal red cells. Some of the best characterized interactions of this sort, e.g. the haemoglobin S system and the G6PD system, are briefly reviewed. Additional established or postulated interactions are mentioned, and some suggestions are made as to how pertinent evidence could be obtained and exploited with a view to optimizing the interactions between genetic characters of red cells and the environment.
The Cellular Basis of Autoimmunity
Authors: Playfair J. H. L. 
Published: March 2008

Summary.The cellular basis of normal antibody formation is reviewed, and the stages are indicated at which the process may be interrupted in order to prevent the formation of autoantibodies. Evidence is presented for several types of interruption, including clonal elimination of lymphocytes, blocking of receptors, active suppression, and target blocking.
Autoimmunity to DNA
Authors: Fournié Gilbert J. , Lambert Paul H. 
Published: March 2008

Summary.The development of an immune response to DNA appears to be under a genetic control similar to that regulating the immune response to complex antigens. The predisposition of high responders is particularly marked at the B cell level, while a major role of suppressor T cells is not evident in this response. Various triggering factors may induce the formation of anti‐DNA antibodies: viral, bacterial or parasitic infections; tissue destruction or some drugs. A mechanism which may play an important role is the‘non‐specific’triggering of anti‐DNA antibodies by agents or substances which, like bacterial lipopolysaccharides, exert a potent mito‐genic effect on B cells and simultaneously induce a release of DNA in extracellular fluids.Pathogenic effects of anti‐DNA antibodies are mainly due to the formation of DNA‐anti‐DNA complexes and to their subsequent localization in tissues.
Bone Marrow Transplantation for Aplastic Anaemia
Authors: Storb Rainer , Thomas E. Donnall 
Published: March 2008

Summary.Indications for treatment of aplastic anaemia (AA) by marrow transplantation are discussed. Selection of donor‐recipient pairs by histocompatibility testing, conditioning of patients for transplantation, technique of grafting, post‐grafting care and immunosuppressive drug regimens are reviewed. Data are presented on 28 patients with advanced AA treated by marrow grafts from HL‐A matched siblings following conditioning with cyclophosphamide (50 mg/kg) on each of 4 successive days. Survival and haematological reconstitution in more than half the patients indicates that marrow grafting in patients with advanced AA should be undertaken early, before major infections and refractoriness to blood transfusions occur provided that an HL‐A matched sibling can be identified as a donor. The results have shown that survival in marrow grafted patients with severe AA compares favourably to that of patients treated with conventional therapy.
Immunotherapy in the Management of Leukaemia
Authors: Fairley G. Hamilton 
Published: March 2008

Summary.Now that it has been clearly established that tumour associated antigens exist in acute leukaemia in man, as in animals, the possibility of stimulating the patient's immune system to react against them arises. In animal experiments the most effective method of influencing the progress of leukaemias and lymphomas after the implantation of living malignant cells has been a combination of nonspecific stimulation of the reticulo‐endothelial system, with agents such as BCG or Corynebacterium parvum, either with chemotherapy or with specific immunization with irradiated leukaemic cells. However, such treatment is only effective if the number of living malignant cells is small as it takes a powerful immune response to overcome even a small number of malignant cells. It is for these reasons that most of the studies in man have been on patients with acute leukaemia in remission. Mathé, in 1969, produced evidence that BCG and irradiated allogeneic leukaemia cells could lengthen the duration of remission in ALL in children, but the subsequent results of intensive combination chemotherapy together with prophylactic treatment of the central nervous system by Pinkel and his colleagues are so encouraging that immunotherapy is not being extensively used in this form of leukaemia at the moment. The situation in AML, particularly in adults, is completely different. The maintenance of remission with chemotherapy in this type of leukaemia is difficult and relapses occur quite rapidly. Various centres have now shown that both remission lengths and overall survival are significantly prolonged by using BCG with or without irradiated allogeneic leukaemia cells. The significance of these are reviewed and the problems for the future are discussed.
A Serum Haemagglutinating Property Dependent upon Polycarboxyl Groups
Authors: Beck M. L. , Freihaut B. , Henry R. , Pierce S. , Bayer W. L. 
Published: March 2008

Summary. A serum agglutinin reactive with red cells in the presence of polycarboxyl groups is reported. It is likely that this represents an additional example of the type of agglutinin previously described as agglutinating red cells in the absence of ionized calcium.Experimental evidence is presented indicating that it is free polycarboxyl groups that potentiate agglutination and that any metal ion, such as calcium, capable of chelating with these groups will prove to be inhibitory.