bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Macromolecular Components in Anti‐γ, α, μ, κ, λ, C3 and C4 Antiglobulin Sera*
Authors: Haynes Carolyn R. , Chaplin Hugh
Published: March 2008

Summary. Studies are described of the early and late responses of rabbits immunized with human IgG protein. Early macroglobulins (19S) antiglobulin antibody is compared with 7S antibody in tests against red cells strongly and weakly coated by IgG anti‐Rh(D) antibody. The 19S antibody, when reacted on a glass plate, is slower to produce maximum agglutination than 7S antibody, is enhanced by 4% human serum albumin, and is of at least equal sensitivity in detecting very weakly sensitized erythrocytes. The 19S antibody shows no loss of potency during 1 yr storage at ‐ 20°C, but is unstable beyond 6 mth storage at 4°C. The 19S antibody is non‐precipitating against its specific antigen, which complicates assessment of its specificity. It is shown that admixture of 19S with 7S antiglobulins alters the manifestation of the prozone characteristic of the 7S antibody alone. Macroglobulin antiglobulin reagents raised against human γ, α, μ, K, λ, C3 and C4 antigens are compared with 7S reagents of similar specificities in tests against coated cells from 14 patients with acquired autoimmune haemolytic anaemia (AAHA), three patients receiving methyldopa, and against normal cells sensitized with anti‐D, anti‐Fya, anti‐Kell, anti‐Lea and anti‐Jka isoantibodies. The results put macroglobulin antiglobulin reagents in perspective in relation to the broad field of antiglobulin testing.
Inhibitors of Fibrinolysis in Platelets in Polycythaemia Vera and Thrombocytosis
Authors: Kwaan Hau C. , Suwanwela Nibha
Published: March 2008

Summary. The role of platelets in fibrinolysis was studied in relation to their content of fibrinolytic inhibitors. An antiplasmin was present in platelets when studied by the caseinolytic method, but this antiplasmin was weak when the fibrin plate method was used. Thus the fibrin plate method could be used for the study of the inhibitory action of platelets against three different types of plasminogen activator: urokinase, human heart tissue activator and human plasma plasminogen activator. It was found that normal human platelets contained inhibitors against all three plasminogen activators with the highest inhibitory activity against urokinase. Platelets from patients with thrombocytosis due to polycythaemia vera or secondary to bronchogenic carcinoma also showed similar inhibitory activity. The platelets from one patient with polycythaemia vera had an unusually high degree of inhibitory activity. The significance of these findings is discussed with respect to the relative resistance of a platelet thrombus to lysis and to its role in haemostasis.
Metabolic and Bactericidal Activities of Human Eosinophils*
Authors: Baehner Robert L. , Johnston Richard B.
Published: March 2008

Summary. Eosinophils obtained from three patients with transient eosinophilia and polymorphonuclear neutrophils(PMN) obtained from young adults with acute suppurative infections were compared with regard to their metabolic and bactericidal responses to phagocytosis. Eosinophils ingested zymosan particles and staphylococci more slowly and to a lesser extent than did PMN, and displayed a more potent oxidative response during phagocytosis which led to a greater production of intracellular hydrogen peroxide. This enhanced oxidative response was primarily due to increased activity of TPNH oxidase, a granule enzyme, rather than the soluble DPNH oxidase which mediates hydrogen peroxide production in neutrophils. Despite the enhanced peroxide production, eosinophils were less bactericidal than PMN.
Stimulation and Inhibition by Normal Human Serum of Colony Formation in Vitro by Bone Marrow Cells
Authors: Chan S. H. , Metcalf D. , Stanley E. R.
Published: March 2008

Summary. Normal human sera were able to stimulate granulocyte and macrophage colony formation in vitro by mouse bone marrow cells, but only following removal of inhibitory material either by dialysis or by heat‐ or ether‐treatment. Inhibitors were shown to be present in all normal human sera tested, to exhibit partial species specificity, to be multiple and to be probably lipoprotein in nature. The in vivo function of these inhibitors is unknown but they may modulate the action of the colony stimulating factor (CSF) in stimulating granulopoiesis and macrophage formation.
Serum Vitamin B12 Concentrations in the General Population: A Ten‐year Follow‐up
Authors: Waters W. E. , Withey J. L. , Kilpatrick G. S. , Wood P. H. N.
Published: March 2008

Summary. Community samples of 673 subjects who had had serum vitamin B12 concentrations measured in 1958 were followed‐up 10 yr later. 134 of these subjects had died; the death rates showed no consistent trend in relation to the original serum vitamin B12 concentrations. Comparisons of concentrations in 1958 and 1968 in 480 subjects showed correlation coefficients (r) of between 0.46 and 0.71 in various subgroups. The oldest age group had a slightly lower mean concentration, and a larger proportion of this group had values below 100 pg/ml. Several subjects with a consistently low serum vitamin B12 concentration for 10 yr maintained an apparently satisfactory circulating haemoglobin concentration.
Myeloid Stem Cell Kinetics during Erythropoietic Stress
Authors: Rickard K. A. , Rencricca N. J. , Shadduck R. K. , Monette F. C. , Howard D. E. , Garrity Marianne , Stohlmann F.
Published: March 2008

Summary. The committed myeloid stem cell compartment, monitored by the agar colony technique, has been assayed in the bone marrow, spleen and blood of mice during erythropoietic stress. When red cell production appeared maximal, the size of the committed myeloid stem cell comparment was reduced in the bone marrow and there was usually a reciprocal rise in the spleen with varying numbers of these cells in the circulation. The role of stem cell competition and migration in the development of these changes is discussed.
Leucocyte Response to Bacterial Endotoxin in Mice Pre‐treated with Cytotoxic Agents
Authors: Twentyman P. R.
Published: March 2008

Summary. The leucocyte response to bacterial endotoxin has been observed in normal mice and in mice which had been treated, either 5 or 9 days previously, with dimethyl myleran (DMM) or methotrexate (MTX). Following administration of endotoxin, the number of polymorphonuclear leucocytes in tail vein blood rose by a factor of 7 over a period of 8–12 hr, and subsequently declined slowly. Mononuclear leucocytes, on the other hand, fell by a factor of 2 within 2 hr and then slowly recovered. The response patterns in mice pretreated with the cytotoxic agents were little changed, despite a considerably lower initial cell count in animals which had received dimethyl myleran. Such a tendency towards a constant ‘mobilization ratio’ of polymorphonuclear cells must reduce the value of the endotoxin response test as a method of examining the status of marrow reserves.
Congenital Dyserythropoietic Anaemia, Type III
Authors: Goudsmit R. , Beckers Do , De Bruijne J. I. , Engelfriet C. P. , James J. , Morselt A. F. W. , Reynierse E.
Published: March 2008

Summary. Cytochemical and serological properties of the erythroid cells of a patient with a congenital dyserythropoietic anaemia, type III, are analysed. Especially striking was the great spread in DNA content per normoblast nucleus. The red cells of the patient were much more readily agglutinated by anti‐i sera than normal cells. Absorption of anti‐I and anti‐i antibodies by the patient's red cells was increased, and there was increased lysis by these antibodies.
Erythrocyte Enzymatic Abnormalities in HEMPAS (Hereditary Erythroblastic Multinuclearity with a Positive Acidified‐Serum Test)
Authors: Valentine W. N. , Crookston J. H. , Paglia D. E. , Konrad Patricia N.
Published: March 2008

Summary. In one type of hereditary dyserythropoietic anaemia, HEMPAS (hereditary erythroblastic multinuclearity with a positive acidified‐serum test) striking increases in the activity of some, but not all, erythrocyte enzymes have been detected in three cases. Since there was only minimal reticulocytosis, these enzyme changes cannot be accounted for by the presence of a young erythrocyte population. It is suggested that the enzymatic abnormalities of HEMPAS result from abnormal karyo‐ and cyto‐kinesis of the erythroid precursors.
The Growth of Bone Marrow Cells in Liquid Culture
Authors: Sumner M. A. , Bradley T. R. , Hodgson G. S. , Cline M. J. , Fry P. A. , Sutherland L.
Published: March 2008

Summary. Liquid suspension cultures of mouse bone marrow cells at high and low density were prepared in supplemented Eagle's medium containing 10% of a partially purified extract of mouse embryos and pregnant mouse uterus (PMU). In the low cell density cultures the number of cells decreased for 2 days; by 4 days the agar colony‐forming cells (agar CFC) had risen ten‐fold and the spleen colony‐forming units (spleen CFU) had fallen to one tenth; between 4 and 8 days the total cell count showed a four‐fold increase and the final cell number exceeded the number of the original culture. The cells produced were mainly macrophages. If PMU was not included in the culture the agar CFC disappeared after 4 days and there was no cell multiplication. In the high cell density cultures a similar pattern was observed; in the presence of PMU the agar CFC showed an increase in number, the spleen CFU decreased and an increase in cell number occurred between 4 and 8 days. However, the cells produced were predominantly granulocytes. In the absence of PMU from this cell culture, agar CFC were maintained for 6 days and the cell population remained predominantly granulocytic. These methods of growing cell enable cell recovery from the cultures to be made at any stage and provide an opportunity to study the kinetics and functional capacity of the cells produced.
Haematological Status of the Central American Population: Prevalence of Individuals with Haemoglobin Levels below ‘Normal’
Authors: Viteri F. E. , Guzmán M. A.
Published: March 2008

Summary. A statistically representative sample of 6009 subjects in Central America has been studied to determine the prevalence of individuals with haemoglobin values carrying different risks of belonging to a population with deficient haemoglobin concentration. Haemoglobin values associated with 20% and 75% chance of belonging to the latter population have been determined, for various altitude‐age‐sex categories by studying a highly selected, biochemically normal population, and by determining the mean and standard deviation of the normally distributed segment of the total distribution for each altitude‐age‐sex category.

The prevalence of individuals with greater than 20% chance of belonging to a population with subnormal haemoglobin values is, on average, 27.6% (range 19.3‐54.7) for altitudes between 0 and 749 m above sea level, 25.5% (range 6.2‐35.0) for altitudes between 750 and 1499 m above sea level, and 24.9% (range 18.6‐30.7) for altitudes between 1500 and 2800 m above sea level. The prevalence of individuals with more than a 75% chance of belonging to a population with subnormal haemoglobin for the same three altitudes above sea level is, on average, 19.7%, 12.6% and 11.7%, respectively. Their corresponding ranges are 12.1‐38.7, 3.0‐17.5 and 7.4‐16.7.

This study shows that the prevalence of anaemia (haemoglobin concentration below the level which carries a risk greater than 75% of belonging to a population with subnormal haemoglobin) is very high in Central America. Particularly vulnerable groups are 1–4‐yr‐old children, and 13–16‐yr‐old females at altitudes between 0 and 750 m, and both males and females of 17 yr and older. The adult male population does not differ from the adult female population as far as the prevalence of anaemia is concerned.

The reasons for these findings are discussed, particularly with regard to iron and folate intakes, hookworm infection and iron sweat loss.
Experimental Transfusion Reactions in Monkeys: Haemolytic, Coagulant and Renal Effects of Transfused Isoimmune IgG and IgM
Authors: Lopas H. , Birndorf N. I. , Bell C. E. , Robboy S. J. , Fortwengler H. P. , Biddison W. E.
Published: March 2008

Summary. IgG and IgM fractions were purified from plasmas of six pairs of monkeys cross‐immunized with each others' red cells. Essentially all haemolytic activity was found in IgG fractions. Immune IgG or IgM was transfused into incompatible recipients. A dose of immunoglobulin equivalent to that present in 10 ml of plasma per kg of recipient body weight was used. Red cell mass decreased in direct proportion to quantitative haemolysin content of IgG during the first 4 hr after transfusion. A small decrease was also noted after one IgM transfusion. Parallel increases in plasma and urinary haemoglobin were observed. Disseminated intravascular coagulation (DIC) and anuria or oliguria were seen after every immune IgG infusion. DIC, characterized by falls in platelet count, fibrinogen content, levels of factors V and VIII, and fibrin clots at autopsy varied in severity with the extent of the haemolysis. The amount of haemolysis in vivo was accurately predictable by the QH50, a sensitive in vitro assay of antibody haemolytic activity. No coagulation changes or decreases in urinary volume were noted after immune IgM or control immunoglobulin infusions. These immune IgG infusions in monkeys provide a model for the study of the pathophysiology and therapy of human transfusion reactions.
The Clinical Relevance of Platelet Function Tests
Authors: McBride J. A. , Wallett L. H.
Published: March 2008

Summary.The increasingly used tests of platelet function have been briefly reviewed and an attempt has been made to correlate the result of these tests with their clinical significance. It may be said that the platelet count and bleeding time are still the most important information for the clinician. It has seldom been shown that isolated abnormalities of morphology, adhesion, aggregation or platelet factor 3 release have any clinical relevance unless accompanied by a prolongation of the bleeding time. A long bleeding time in an otherwise healthy patient is most frequently due to aspirin ingestion.
Megaloblastic Maturation Masked by Iron Deficiency: a Biochemical Basis
Authors: Weyden Martinvander , Rother Mary , Firkin Barry
Published: March 2008

Summary

In vitrobone marrow cultures, obtained from haematologically normal individuals and from patients with iron deficiency, were used to study the effect of the iron chelating agent, desferrioxamine, on the abnormal deoxyuridine suppression of3H‐thymidine incorporation into DNA produced by the dihydrofolate re‐ductase inhibitor, methotrexate.

Desferrioxamine reduced the degree of impaired deoxyuridine suppression induced by methotrexate in marrow cultures of normal controls. However, in the iron‐deficient marrow cultures, the abnormal deoxyuridine suppression induced by methotrexate was less marked than that in controls, and desferrioxamine failed to reduce the degree of abnormal deoxyuridine suppression. After replacement of the iron stores, the degree of abnormal deoxyuridine suppression was increased, and desferrioxamine in this situation reduced the abnormal deoxyuridine suppression.

In four marrow cultures obtained from patients with megaloblastic anaemia, the impaired deoxyuridine suppression in this situation was reduced towards normal by desferrioxamine.

These findings provide biochemical evidence for the morphological findings of normoblastic maturation in vitamin B12‐ or folate‐deficient states complicated by iron deficiency.
Mechanism of Eosinophilia. VII. EOSINOPHILIA IN RATS WITH LYMPHOMA
Authors: Spry Christopher J. F.
Published: March 2008

Summary

Inbred rats developed an increased blood eosinophil count 2 weeks after injection of syngeneic or semi‐syngeneic lymphoma cells. An eosinophilia did not occur in allogeneic recipients. Autoradiographic studies of bone marrow eosinophil production showed that additional eosinophils were not being made, and tissue eosinophil levels were also normal. Moreover injections of prednisolone did not lower blood eosinophil counts significantly in the rats with the lymphoma. Other experiments showed that the eosinophilia was probably not due to a graft‐versus‐host reaction. It was concluded that the mechanism of eosinophilia was a prolongation of eosinophil survival in the blood, possibly due to blockage of normal emigration pathways into tissues, by large numbers of blood‐borne lymphoma cells.
The Preparation and Clinical Use of a New Concentrate Containing Factor IX, Prothrombin and Factor X and of a Separate Concentrate Containing Factor VII
Authors: Dike G. W. R. , Bidwell Ethel , Rizza C. R.
Published: March 2008

Summary

A method of preparation for therapeutic use of a concentrate of factors IX, II and X and a separate concentrate of factor VII is described. The method is based upon adsorption of the factors on DEAE‐cellulose from plasma or from the supernatant after removal of factor VIII. Conditions of elution are selected so that, in a single step, the factors are obtained at a suitable salt concentration and potency to permit injection of a therapeutic dose by syringe. The yield of factor IX in vitro is about 50–75% and the purification about 300‐fold. The yield of factor VII is lower and variable. Experience in the use of 14 batches of factor‐IX concentrate in the treatment of 29 patients and on the use of a batch of factor‐VII concentrate in the treatment of one patient is described. The in vivo dose response to factor IX made by different methods is compared.
Fibrinolytic Enhancement by Stanozolol: A Double Blind Trial
Authors: Davidson J. F. , Lochhead M. , McDonald G. A. , McNicol G. P.
Published: March 2008

Summary

Thirty‐four men with ischaemic heart disease were given 10 mg stanozolol per day, 10 mg stanozolol plus 100 mg phenformin per day, or a placebo for 12 mth, in a double blind randomized study. A panel of fibrinolytic and coagulation tests was performed at monthly intervals. Throughout the study the groups on active treatment showed significant enhancement of plasma fibrinolytic activity compared with their base‐line values, and compared with the placebo group. No significant difference was found in the enhancement of fibrinolysis wliich was produced by either active treatment regimens, and it is concluded that 10 mg stanozolol daily‐is as effective as 10 mg stanozolol plus 100 mg phenformin daily in increasing plasma fibrinolytic activity in men with ischaemic heart disease.
Blood Serum Surface Tension and its Potential
Authors: Lewin S.
Published: March 2008

Summary

Surface tension values of human sera were determined, figures for freshly separated material being compared with samples from the same sources that had been stored at either 4°C or at — 20°C. Blood for these investigations was obtained from normal individuals as well as from antenatal, diabetic and myeloma patients. Comparisons were performed at 15, 20, 25, 37 and 45°C. Freezing of sera, whether normal or abnormal, resulted in the lowering of surface tension values by a maximum of 3 dynes/cm. Such a reduction was computed to be symptomatic of a partial denaturation, the most likely component involved being a lipoprotein. Human γ‐globulin and human serum albumin were hardly affected by freezing but reconstituted lyophilized serum and reconstituted lyophilized plasma showed the same surface tension depression values as denatured sera. Sera subjected to freezing and thawing displayed increased opalescence as well as increasing the pH value from 7.2 to 7.8 on increased exposure to freezing.

It is advocated that the surface tension parameter be included with osmotic pressure and hydrostatic pressure in the consideration of plasma transport and transvascular fluid and solute transport.
Clearance from Plasma and Excretion in Urine, Faeces and Bile of an Intravenous Dose of Tritiated Vitamin K1 in Man
Authors: Shearer M. J. , Mallinson C. N. , Webster G. R. , Barkhan P.
Published: March 2008

Summary

Vitamin K1‐3H (1 mg; 12 μCi) was injected intravenously into three normal men, into three patients undergoing duodenal intubation and into a patient with T‐tube drainage of the common bile duct. In the normal subjects lipid‐soluble radioactivity (representing the injected vitamin K1‐3H) disappeared rapidly from the plasma: the clearance curve for the first 6 hr could be resolved graphically into two exponential functions, the first with a T® of 20–24 min and the second with a T® of 121–150 min: water‐soluble radioactivity, presumed to be metabolic products, appeared in the plasma within 30 min after injection, reached a peak at 2 hr and remained near this level for 24 hr. Of the injected radioactivity in the normal subjects, 19–26% was recovered in the urine after 3 days and 34–38% in the faeces after 5 days: most of the radioactive material in the faeces was lipid‐soluble, which on thin‐layer chromatography had a polarity between that of vitamin K1 and vitamin K1γ‐lactone. In the patients undergoing duodenal intubation, radioactivity was detected in the duodenal juice within 20–40 min after injection of vitamin K1‐3H. Radioactivity was also detected in the bile in the patient with T‐tube drainage of the common bile duct. Most of the radioactivity in the duodenal juice and bile was water‐soluble. It seems likely that the radioactivity appearing in the faeces after intravenous injection of vitamin K1‐3H is derived from biliary excretion of water‐soluble conjugated metabolites which become lipid‐soluble by decon‐jugation during their passage through the bowel.
Metabolism and Distribution of Fibrinogen. I. FIBRINOGEN TURNOVER IN PHYSIOLOGICAL CONDITIONS IN HUMANS
Authors: Collen D. , Tytgat G. N. , Claeys H. , Piessens R.
Published: March 2008

Summary

The metabolism of human fibrinogen, labelled with radioactive iodine, was studied in 35 healthy subjects over a 5 yr period using eight fibrinogen preparations in 23 labelling procedures. The labelled fibrinogen was highly clottable and homogeneous on agarose gel filtration, immunoelectrophoresis and auto‐radiography. Results in the control subjects were: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half‐life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool/day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool/day. Comparable results were obtained for all labelled fibrinogen batches. Anticoagulation with heparin in five control subjects had no influence on the fibrinogen half‐life. Inhibition of the fibrinolytic system with tranexamic acid in five control subjects had no influence on the fibrinogen half‐life in four of them but resulted in a prolongation in one subject.

A mathematical compartmental model for the metabolism of fibrinogen is proposed, consisting of one extra vascular compartment and three catabolic pathways (basic protein turnover, intravascular fibrin formation, and intravascular fibrino(geno)lysis). In physiological conditions intravascular fibrin formation or fibrino(geno)lysis are not essential in the fibrinogen turnover.
Metabolism and Distribution of Fibrinogen 11. FIBRINOGEN TURNOVER IN POLYCYTHAEMIA, THROMBOCYTOSIS, HAEMOPHILIA A, CONGENITAL AFIBRINOGENAEMIA AND DURING STREPTOKINASE THERAPY
Authors: Tyigate G. N , Veremylen J. , Marder V. J.
Published: March 2008

Summary.The kinetics of fibrinogen metabolism in humans were investigated by turnover studies in various pathological conditions in order to evaluate the proposed flow diagram of labelled fibrinogen. Six patients with primary or secondary polycythaemia had a significantly shortened fibrinogen half‐life of 2.87 ± 0.35 days and a signlficantly increased fractional catabolic rate of 0.33 ± 0.06 of the plasma poollday. This shortened fibrinogen half‐life together with the correcting effect of heparinization on the fibrinogen turnover indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. The average fibrinogen half‐life of 3.17 ± 0.54 days and the average fractional catabolic rate constant of 0.31 rt: 0.08 in eight patients with thrombocytosis were significantly different from the cor‐ responding control values. A prolongation of the plasma radioactive decay was induced by anticoagulation as well as by fibrinolytic inhibition, demonstrating the close relationship between in vivo coagulation and (secondary?) fibrinolysis. The turnover of fibrinogen in 11 haemophilia A patients was significantly shortened, the half‐life being 3.73 k 0.36 days and the fractional catabolic rate being 0.271 0.05 of the plasma poollday. Autologous and homologous fibrinogen, prepared in different ways, behaved identically in haemophiliacs. The accelerated fibrinogen catabolism could be explained either by consumption in tissue repair mechanisms, by fibrino(geno)lytic breakdown or by immunological phenomena. No influence on the first order fibrinogen catabolism was observed, either during elevation of the plasma fibrinogen concentration by cryoprecipitate transfusion in two haemo‐ philiacs or during decrease in fibrinogen level as seen in two patients with congenital afibrinogenaemia. Activation of the fibrinolytic system by streptokinase in six patients resulted in a markedly accelerated fibrinogen turnover by in vivo fibrino‐ (gen0)lysis. These experiments demonstrate that fibrinogen catabolism by in uiuo coagulation and (or) fibrino(gen0)lysis are distinct pathways in the flow diagram of labelled fibrinogen metabolism.
The Relevance of Factor VIII Inactivation Characteristics in the Treatment of Patients with Antibodies Directed against Factor VIII
Authors: Kernoff P. B. A.
Published: March 2008

Summary

The management of a patient with acquired haemophilia who sustained a compound fracture of the tibia is described. Haemostasis was achieved with infusions of large doses of porcine antihaemophilic globulin (AHG) and human cryoprecipitate. Investigations of the patient's antibody showed that when it was in excess it initially inactivated both porcine and human factor VIII rapidly, and then at a rate which decreased with progressive incubation. This decreasing rate of factor VIII inactivation differs from the action of a classically described factor VIII antibody which inactivates factor VIII in a linear manner when the antibody is in excess. It is suggested that the patient was more amenable to treatment with concentrated preparations of factor VIII than a patient with the classical type of factor VIII antibody, infused factor VIII persisting for longer in the patient's circulation than might be expected.
Changes in 32P‐Labelling of Platelet Phospholipids in Response to ADP
Authors: Lloyd J. V. , Nishizawa E. E. , Haldar J. , Mustard J. F.
Published: March 2008

Summary. Suspensions of washed platelets from rabbits were labelled in vitro with 32PO4, washed, and then stimulated with ADP. Thirty seconds after the addition of ADP or of a control solution, samples of the suspension were subjected to lipid extraction. The phospholipid classes were isolated by thin layer chromatography. The results of phosphate estimation on the isolated phospholipids were in agreement with the previously described amounts of diphosphatidylinositol (DPI) and triphosphatidylinositol (TPI) in human platelets. In both ADP‐treated and control plateletes the label in phospholipid was mainly in phosphatidic acid (PA), phosphatidylinositol (MPI), DPI and TPI. Thirty seconds after the addition of ADP there was an increase in labelling of PA, DPI and TPI but the amounts of PA, DPI and TPI in platelets did not change. The results indicate that ADP probably induces an increase in turnover of the phosphate moieties of these phospholipids. The changes observed represent changes in the metabolism of the phospholipids of the platelet membrane which may be important in the mechanism of platelet aggregation.
Vitamin B12‐Binding Protein Abnormality in Subjects without Myeloproliferative Disease: I. ELEVATED SERUM VITAMIN B12‐BINDING CAPACITY LEVELS IN PATIENTS WITH LEUCOCYTOSIS
Authors: Carmel Ralph
Published: March 2008

Summary. In a group of 41 patients with leucocytosis of varying degrees and diverse aetiologies, 88% had elevated serum unsaturated vitamin B12‐binding capacity (UBBC). All but three had normal serum vitamin B12 levels.

The UBBC abnormality occurred even with apparently mild leucocytosis. When leucocytosis subsided, spontaneously or due to therapy, UBBC invariably fell, whereas it remained high if granulocyte counts did not fall. Serum vitamin B12 levels usually showed no change.

Factors other than leucocytosis could not be related to the UBBC elevation. However, high UBBC was also found in 15 of 248 subjects with normal granulocyte counts. Seven of these were in states of granulocyte flux. In the eight remaining subjects (3% of the sample), leucocytosis apparently did not exist.

Although by the screening method used here the main UBBC elevation appeared to be of beta‐globulin binder, a subsequent report shows a third protein to be responsible (being apparently elevated even in a subject with leucocytosis whose UBBC level was normal). Alpha‐globulin binding was only slightly elevated in most cases.
Vitamin B12‐Binding Protein Abnormality in Subjects without Myeloproliferative Disease: II. THE PRESENCE OF A THIRD VITAMIN B12‐BINDING PROTEIN IN SERUM
Authors: Carmel Ralph
Published: March 2008

Summary. An elevated unsaturated vitamin B12 binding capacity (UBBC) had been observed in the sera of most subjects with leucocytosis of varying degrees and a few without evident leucocytosis. Although true alpha‐ and beta‐globulin binder increases of varying degree occurred, the increase in UBBC in most subjects was due mainly to a third vitamin B12‐binding protein. In addition, when UBBC fell as leucocytosis subsided, the third binder was no longer detectable. This protein resembles alpha‐globulin binder, or Transcobalamin (TC) I, in molecular weight, antigenic characteristics, and poor mediation of 57Co B12 uptake by reticulocytes. It resembles beta‐globulin binder, or TC II, in its behaviour on DEAE‐cellulose batch separation, electrophoretic mobility at pH 8.6, and, as suggested by indirect evidence, probably not carrying endogenous vitamin B12. Thus it appears identical to a serum binder previously thought to occur only in polycythaemia vera.

It is apparent that the protein is present in large amounts in a variety of conditions involving leucocytosis, and possibly occurs in normal serum in small quantities also. It is possible that the binder may be an altered form of TCI. The reason for the predominance of TCI in some conditions involving granulocytic proliferation, and this binder in others, is unknown.
Acute Promyelocytic Leukaemia: A Report of Five Cases with a Comment on the Diagnostic Significance of Serum Vitamin B12 Determination
Authors: Rachmilbwitz D. , Rachmilewitz E. A. , Polliack A. , Hershko Ch.
Published: March 2008

Summary. Five patients with acute promyelocytic leukaemia presenting with initial leucopenia are reported. Severe and fatal bleeding complicated the course of the disease in four patients, associated with hypofibrinogenaemia in three of them. In addition, disseminated intravascular coagulation was found in three autopsied patients. An interesting and hitherto undescribed finding was the presence of high serum vitamin B, levels (2000=16000 pg/ml) found in all our patients in the absence of liver damage. In three of these patients an increased serum vitamin B12 binding capacity was observed (1500=6500 pg/ml). The diagnostic significance of these findings is discussed and it is suggested that the determination of serum vitamin 12 concentration and vitamin 12 binding proteins may be useful aids in the diagnosis of promyelocytic and myeloblastic leukaemia.
Granulopoiesis in Chronic Granulocytic Leukaemia*
Authors: Galbraith P. R. , Abu‐Zahra H. T.
Published: March 2008

Summary: The disappearance from the blood was studied of (1) leucocytes of patients with chronic granulocytic leukaemia labelled in vitro with DF32P and irradiated with 1500 rad, and (2) in vitro labelled normal marrow leucocytes. These studies made it possible to estimate the intravascular phase of the lifespan of mature leukaemic neutrophils and to compute the granulocyte turnover rate when immature leucocytes (myelocytes) were present in the blood. The studies support the hypothesis that immaturity of the leucocytes per se may result in their sequestration from the blood stream. The results suggest that granulocyte production is increased in chronic granulocytic leukaemia in relapse, and that the tendency for the leucocytosis to occur may be potentiated by a prolongation of the lifespan of the mature neutrophils. However, this prolongation is only manifest in the presence of leucocytosis.
A Method for the Measurement of Platelet Adhesiveness by Use of Dialysis Membranes in a Test‐Cell
Authors: Lindsay R. M. , Prentice C. R. M. , Ferguson D. , Muir W. M. , Mc Nicol G. P.
Published: March 2008

Summary.As part of a study of the thrombogenic properties of dialysis membranes a test‐cell has been devised in which the retention of platelets in the presence of different membranes can be measured. This provides a test for platelet adhesiveness which in certain aspects is more sensitive and reproducible than a glass bead column technique. The normal range for platelet adhesiveness was found to be 31 ± 9% using whole blood and 19 ± 3% using platelet‐rich plasma. The platelet adhesiveness value was largely independent of the packed red cell volume but was, in part, dependent upon the presence of adenosine diphosphate. The membrane test‐cell system was sensitive enough to demonstrate a constant and significant fall in platelet adhesiveness following salicylate ingestion. It was convenient in use as blood anticoagulated with 3.8% sodium citrate allowed delays of up to 1 hr without influencing the result. Heparin was found to have an inhibitory effect on platelet adhesiveness. The use of twin test‐cells allowed platelet adhesion to two different dialysis membranes to be studied simultaneously. It was found that fewer platelets adhered to Cuprophan PT 150 membranes than to PT 300 membranes suggesting that PT 150 membranes may be less thrombogenicin vivo.
The Significance of Microangiopathic Haemolytic Anaemia in Accelerated Hypertension
Authors: Sevitt L. H. , Naish P. , Baker L. R. I. , Bulpitt C. J. , Archer D. F. J. , Nelson D. A. , Peters D. K.
Published: March 2008

Summary. Twenty‐two patients with accelerated hypertension and varying degrees of renal involvement have been studied in order to assess the significance of microangiopathic haemolytic anaemia (MAHA) and the possible pathogenic role of intravascular fibrin deposition in this condition. Vascular damage was assessed by retinal photography including fluorescein angiography. Haematological investigations including examination of peripheral films and assessment of red cell fragmentation were carried out. Fibrinogen catabolism was measured using radio‐iodine labelled fibrinogen.

No correlation between the degree of vascular damage in the retinal vessels and the blood pressure, degree of red cell fragmentation or evidence of renal damage was found. There was a significant increase in red cell fragmentation when the creatinine clearance was 20 ml/min or less. Fibrinogen derivatives were demonstrated in the serum in the minority and in the urine of the majority of those patients with MAHA. Fibrinogen catabolism was normal in all cases.

The significance of microangiopathic haemolytic anaemia in accelerated hypertension is discussed. It is suggested from these data that the red cell fragmentation occurs predominantly within the kidney and that there is no evidence that fibrinogen deposition plays an important role in red cell damage, or that it is an important pathogenic factor in producing accelerated hypertension.
Bone‐Marrow Toxicity of Methotrexate: A Reassessment
Authors: Douglas I. D. C. , Price L. A.
Published: March 2008

Summary. The effects of methotrexate on the haemopoietic system are considered in the light of an experimental kinetic model. This model explains why toxicity occurs and suggests how it may be avoided.
Studies on the Defective Haematopoietic Microenvironment of Sl/Sld Mice
Authors: Fried Walter , Chamberlin William , Knospe William H. , Husseini Salah , Trobaugh Frank E.
Published: March 2008

Summary. Femurs and spleens of both Sl/Sld and +/+ origin were implanted into both Sl/Sld and +/+ hosts. Eight weeks later the +/+ grafts incorporated more radioactive iron than did the Sl/Sld ones. The number of colony forming units (CFU) in the marrow of +/+ femur grafts and in +/+ spleen grafts was several fold greater than that in Sl/Sld grafts. X‐irradiation of femur and spleen donors with 950 R reduced the number of CFU in the grafts to 40–60%, whereas grafts from donors exposed to 2500 R supported no CFU growth at all. The haematopoietic cells in the grafts after 6 weeks were almost entirely of host origin.

These studies suggest that Sl/Sld mice have a congenital defect in some stromal elements of their haematopoietic tissues which are essential for the normal growth of CFU. These stromal factors are likely to be cellular, are less radiosensitive than are the CFU, and support the growth of CFU rather than actually differentiate into these cells. These stromal factors are present in both spleens and femurs of mice. The model described here appears to be a useful one for further characterizing stromal factors essential for supporting haematopoiesis.
Prolonged Prothrombin Time and Partial Thromboplastin Time in Disseminated Intravascular Coagulation not Due to Deficiency of Factors V and VIII
Authors: Mant M. J. , Hirsh J. , Pineo G. F. , Luke K. H.
Published: March 2008

Summary. In an investigation of 34 patients with laboratory evidence of disseminated intravascular coagulation (DIC), 17 were found to have a prolonged prothrombin time, 11 a prolonged partial thromboplastin time, and only 10 a prolonged thrombin time. Coagulation factor assays in these patients revealed deficiency patterns compatible with vitamin K deficiency and/or liver disease. In addition, a prolonged prothrombin time rapidly returned to normal in five of seven patients given vitamin K1. It is suggested that vitamin K deficiency and liver dysfunction occurred as a complication of the primary condition that led to DIC. The practical implications of these findings are that a prolonged prothrombin time and partial thromboplastin time may occur in patients with laboratory evidence of DIC in the presence of a normal thrombin time. Under these circumstances bleeding in patients with laboratory evidence of DIC is likely to be caused by vitamin K deficiency or liver dysfunction and therefore may be more appropriately treated with vitamin K than with heparin.
Study of Two in Vitro Diagnostic Tests for Paroxysmal Nocturnal Haemoglobinuria
Authors: Sirchia G. , Marubini E. , Mercuriali F. , Ferrone S.
Published: March 2008

Summary. The variability with time of the serum haemolytic activity of normal subjects in the acidified‐serum and sucrose‐haemolysis tests towards the red cells of paroxysmal nocturnal haemoglobinuria (PNH) and PNH‐like cells (i.e. normal red cells treated in vitro with the sulfhydryl compound AET) was investigated. A wide variability was observed in samples of serum obtained from individual donors at intervals of months, days, and even hours, without evidence of a circadian rhythm. In spite of this variability each donor of serum, considered in respect to other donors, maintained unchanged with time his rank of serum haemolytic activity towards both PNH and AET cells in the acidified‐serum test, but not in the sucrosehaemolysis test. From the practical point of view it seems convenient for the laboratory diagnosis of PNH to carry out acidified‐serum tests with the serum of one selected normal subject (in addition to the patient's own serum) and sucrosehaemolysis tests with a few random normal sera.
An Analogue Model of Granulopoiesis for the Analysis of Isotopic and Other Data Obtained in the Non‐steady State
Authors: Reeve J.
Published: March 2008

Summary. An analogue model of human granulopoiesis incorporating feedback control is presented which is less restricted than previous models. The model simulates kinetic data from human DF32 P and 3H‐thymidine labelling experiments, and the data obtained by Morley & Stohlman in mice (1970) following destruction of four‐fifths of the marrow. Support for King‐Smith & Morley's (1970) suggestion that cyclic neutropenia may be a stem cell defect is forthcoming, but only after the addition of a further negative feedback loop simulating a granulocyte‘chalone’ or a considerable reduction in the time required for precursor cell division. The value of the model in the interpretation and design of kinetic studies, particularly in the non‐steady state, is discussed.
Effect of α‐Chain Precipitates on Bone Marrow Function in Homozygous β‐Thalassaemia
Authors: Wickramasinghe S. N. , Letsky E. , Moffatt B.
Published: March 2008

Summary. An autoradiographic study of protein synthesis by erythropoietic cells in liomozygous β‐thalassaemia has shown that a high proportion of non‐dividing, late polychromatic erythroblasts fail to become labelled when incubated with radioactive amino acids. It is possible that this abnormality and the previously described disturbance of cell proliferation in the early polychromatic erythroblasts result from damage by intracellular α‐chain precipitates. This possibility has been investigated by correlating the extent of α‐chain precipitation with protein or DNA synthetic activity in individual cells. Over 80% of late polychromatic cells with the largest α‐chain inclusions failed to label with 3H‐leucine or 3H‐phenylalanine but 10–23% of cells with no inclusions were also unlabelled. None of the dividing, early polychromatic cells with moderate or large quantities of insoluble α‐chains incorporated 3H‐thymidine. These results support the hypothesis that a‐chain precipitates are associated with and possibly responsible for the ineffectiveness of erythropoiesis in thalassaemia, provided it is assumed that such precipitates are continuously degraded or extruded. The latter assumption is necessary to account for the presence of several metabolically abnormal cells with no α‐chain precipitates.
A Second Type of Hereditary Persistence of Foetal Haemoglobin in India
Authors: Schroeder W. A. , Huisman T. H. J. , Sukumaran P. K.
Published: March 2008

Summary. Six individuals in four Indian families have 25–30% foetal haemoglobin in which the two types of γ chains (the Gγ chain with glycine in position 136 and the Aγ chain with alanine in that position) are present in a ratio of 70:30. It is suggested that these heterozygotes form a distinct subgroup of the HbGγ HbAγ class of the hereditary persistence of foetal haemoglobin. In three relatives this HPFH condition occurs together with β‐thalassaemia. It is concluded that the β‐thalassaemia is of the type in which the ratio of Gγ:Aγ chains is 3:1 as in the newborn.
Reticuloendothelial Phagocytic Function in Human Liver Disease and its Relationship to Haemolysis
Authors: Cooksley W. G. E. , Powell L. W. , Halliday J. W.
Published: March 2008

Summary. This study was undertaken to examine the hypothesis that enhanced reticuloendothelial (RE) phagocytosis and splenic sequestration of red blood cells are important aetiological factors in the haemolysis accompanying liver disease. RE phagocytic capacity (REPC) was measured by the rate of plasma disappearance of radio‐iodinated microaggregated human serum albumin (125I‐MAA) in 57 patients with acute or chronic liver disease, and its relationship to splenic size, RBC survival and splenic sequestration of RBC was analysed. In addition, RE perfusion was measured using a tracer dose of 125I‐MAA, and the RE phagocytic index (REPI), an index of the individual cellular RE activity, independent of perfusion, was calculated.

An increased REPI was found in all forms of liver disease, largely independent of aetiology or severity. REPC was normal in most forms of cirrhosis but was decreased in patients with alcoholic cirrhosis, many of whom had diminished RE perfusion, associated with clinical or radiographic evidence of portal systemic shunting. This decreased REPC was due to decreased RE perfusion since a close correlation between REPC and RE perfusion was demonstrated.

The relationship between spleen size and REPC in patients with cirrhosis depended on the aetiology of the disease, since in alcoholic cirrhosis splenomegaly was usually indicative of portal hypertension, whereas in patients with active chronic hepatitis splenomegaly was often an integral part of the disease.

A shortened RBC survival was demonstrated in 24 of 30 patients studied, but the degree of haemolysis did not correlate with REPC, REPI or splenic size. Furthermore, splenic sequestration of RBC could be demonstrated in only two patients.

It would appear that in hepatic cirrhosis, the RE system, whether its phagocytic capacity is increased or decreased, removes effete RBC presented to it, but is not primarily responsible for the mild haemolytic process.
Acute Plasma Cell Leukaemia following Chronic Lymphatic Leukaemia: Transformation or Two Separate Diseases?
Authors: Fitzgerald P. H. , Rastrick Joan M. , Hamer J. W.
Published: March 2008

Summary. A 68‐yr‐old woman, a carrier of a Gp‐ (Ch1) constitutional chromosome abnormality, presented with chronic lymphatic leukaemia and was treated with chlorambucil during an 8.5 yr course. The number of lymphocytes in the blood increased steadily during the final 3 yr, and immature lymphocytes were present. During the final 8 days, the WBC count rose extremely rapidly and IgM production was increased. Many blasts and smaller cells having the appearance of plasma cell precursors were present in the blood and bone marrow, and these showed a distinctive long marker chromosome. Acute plasma cell leukaemia was diagnosed. The relationship of the two leukaemias in this patient is examined, and transformation of chronic lymphatic leukaemia to an acute form of leukaemia with disturbed cell differentiation is suggested.
Evaluation of 51Cr as a Leucocyte Label
Authors: Spivak Jerry L. , Perry Seymour
Published: March 2008

Summary. A double label technique has been developed to compare the behaviour of 51Cr labelled leucocytes with DF32P labelled leucocytes. Whole blood is divided into two aliquots and the leucocytes in each are labelled with a different isotope. After infusion of labelled cells, the radioactivity of each isotope can be determined simultaneously on the same blood sample using liquid scintillation counting. In studies of seven patients with solid tumours and one with leukaemia, the intravascular disappearance of autologous leucocytes labelled with 51Cr and DF32P appeared similar in five of the eight patients during the initial 6 hr following infusion. Thereafter in all but one instance, 51Cr labelled leucocytes had slightly higher specific activities. 51Cr labelled lymphocytes and DF32P labelled lymphocytes also behaved in the same manner. It is concluded that51Cr is a suitable leucocyte label and may be substituted for DF32P under certain circumstances.
Significance of Large Red Blood Cells
Authors: Chanarin I. , England J. M. , Hoffbrand A. V.
Published: March 2008

Summary. Two observers examining marrow films from 81 patients for the presence of normoblastic and megaloblastic haemopoiesis obtained good agreement when the underlying disorder gave rise to definite vitamin B12 or folate deficiency confirmed by microbiological assay. When microbiological assay of serum vitamin B12 and red cell folate excluded vitamin B12 or folate deficiency, the marrow changes were often too minor in degree for decisive diagnosis despite the presence in many cases of large red cells.

The normal mean corpuscular volume (MCV) set in relation to a PCV excluding trapped plasma was 80–90 fl. The MCV of red cells was often elevated above 90 fl in patients without a megaloblastic anaemia and in this series was often above 100 fl in patients with aplastic anaemia, sideroblastic anaemia, myxoedema, and neoplasia. The larger the red cells, however, the more probable was the presence of megaloblastic haemopoiesis in the marrow.