bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Metabolic Inhibitors on the Autohaemolysis Test and its Relevance to the Mechanism of the Red Cell Lysis
Authors: Eys Janvan , Patterson Janis H.
Published: March 2008

Summary.

The effect of various inhibitors on autohaemolysis was investigated. Inhibitors of the sodium pump, pentose phosphate pathway, anaerobic glycolysis, or ATP synthesis and loose haemoglobin ligands had little effect. Azide was a powerful haemolytic agent, completely counteracted by glucose. Heinz bodies were seen in the cell after azide haemolysis. Fluoride had a special effect causing greater haemolysis when it was measured after 24 hr than when the cells were left undisturbed for 48 hr. From these data a working hypothesis was deduced that haemolysis seen with the autohaemolysis test requires participation of altered haemoglobin. Cells from patients with pyruvate kinase deficiency have a haemolysis pattern that fits that hypothesis making the older theories of ATP depletion as the mechanism of cell instability less tenable.
Bioassay of Erythropoietin Using Foetal Mouse Liver Cells
Authors: Wardle D. F. H. , Baker I. , Malpas J. S. , Wrigley P. F. M.
Published: March 2008

Summary.

In answer to the need for a less time‐consuming assay of erythropoietin, the establishment of an in‐vitro method using foetal mouse liver cells is described. This could be completed in 26 hr and was capable of detecting erythropoietin in concentrations as low as 0.005 or less International Units/ml. It was found to be useful both for clinical measurements and as a system for the study of erythropoietin production.
Uptake of Vitamin B12 by Phytohaemagglutinin‐Transformed Lymphocytes
Authors: Hoffbrand A. V. , Tripp Edith , Das K. C.
Published: March 2008

Summary.

Phytohaemagglutinin (PHA)‐transformed lymphocytes have been used as a model cell system to study the uptake of radioactive vitamin B12 by haemopoietic cells. Both mature granulocytes and PHA‐transformed lymphocytes took up more vitamin B12 than mature, non‐transformed lymphocytes. Uptake of vitamin B12 by PHA‐stimulated lymphocytes was greatest at 48–72 hr of culture, i.e. at about the time or just before the time of peak DNA synthesis.

Vitamin B12 deficient lymphocytes took up significantly less vitamin B12 than normal lymphocytes. Folate deficient lymphocytes took up an average of about 50% more vitamin B12 than normal but the difference was not statistically significant for the numbers tested. Vitamin B12 uptake by PHA‐stimulated lymphocytes was related to their rate of RNA synthesis (measured by 3H‐uridine uptake) and was closely related to active cytoplasmic protein synthesis since it was rapidly inhibited by puromycin and cycloheximide.
The Haemolytic Action of Dapsone: The Effect on Red‐Cell Glycolysis
Authors: Rasbridge Marian R. , Scott G. L.
Published: March 2008

Summary.

Some aspects of red‐cell metabolism were studied in blood samples taken from patients on long‐term dapsone therapy. Glucose consumption by the Enibden‐Meyerhof pathway (EMP) was not abnormal and adenosine‐triphosphate (ATP) levels lay within the normal range and were well maintained during incubation. Hexose monophosphate pathway (HMP) activity was increased above that which would be expected from the age of the red‐cell population. Red‐cell reduced glutathione (GSH) levels tended to be lower than normal, proportional to the dose of dapsone and GSH levels were unstable on incubation. Red‐cell fractionation studies showed that the older cell fraction had lower GSH levels and more Heinz bodies but proportionally greater HMP activity than the younger cell fraction. It is suggested that the low GSH levels are probably due to the binding of GSH to sulphydryl groups in haemoglobin and possibly the red‐cell membrane. The increased HMP activity in the older cells may, in part, be a compensatory mechanism.
Further Observations on the Serological Specificity C of the A‐B‐O Blood Group System
Authors: Wiener A. S. , Socha W. W. , Gordon Eve B.
Published: March 2008

Summary: *A simple method has been described for producing antisera containing anti‐C antibodies of high titre and avidity, by immunizing group O individuals having low titres of isoagglutinins with porcine blood group substance A. Such injections can stimulate a rise not only of the anti‐A titre but also of anti‐C with no noticeable effect on the anti‐B titre. The only disadvantage is that although the suitably diluted reagents are potent, they contain anti‐A in addition to anti‐C, and therefore can be used for testing for the presence of C only those red cells or other materials which lack group A specificity. However, reagents suitable for testing for C in the presence of A could be prepared by immunizing group O subjects with group B red cells or B group substance.

Evidence is presented that the specificity C is shared by all red cells and other materials having A‐like and or B‐like specificities, though rare individuals exist having red cells agglutinable by anti‐C though lacking both A and B. It is suggested that the specificity C is not due to a determinant group shared by A and B group‐specific substances, but, instead, that overall similarities in the surface structure of their molecules are responsible. Analogies are pointed out which are comparable to the relationship of factor C to the A‐B‐O system; namely, of U to the M‐N‐S and rhG to the Rh‐Hr system, and also of Cc to the simian C‐E‐F blood system of chimpanzees.

* To avoid ambiguity, symbols for blood factors (serological specificities) of red cells and their corresponding antibodies are printed in boldface type, symbols for genes and genotypes are printed in italics, and symbols for agglutinogens, phenotypes and blood group systems are printed in regular type.
The Effects of Ascorbic Acid Supplementation on the Absorption of Iron in Maize, Wheat and Soya
Authors: Sayers M. H. , Lynch S. R. , Jacobs P. , Charlton R. W. , Bothwell T. H. , Walker R. B. , Mayet F.
Published: March 2008

Summary.

The absorption of iron from three staple vegetables was measured by the red cell utilization method in iron deficient subjects. The food iron had been labelled with 55Fe by the hydroponic cultivation method. In addition, 59Fe was added with or without carrier iron in the form of ferric ammonium citrate, prior to cooking. The constant relationship reported by others between the absorption of the two isotopes was confirmed, suggesting that the extrinsic iron and the food iron were absorbed from a common pool. The addition of ascorbic acid to maize porridge before cooking significantly enhanced the absorption of both the intrinsic and the added iron. However, no effect was noted with soya biscuits or with whole wheat bread (100% extraction). Evidence was obtained that these differences were due to the oxidative destruction of the ascorbic acid by the high temperatures required for baking. If, therefore, a feasible method were found for supplementing vegetable foodstuffs with ascorbic acid and inorganic iron, nutritional benefit would only be anticipated with uncooked or boiled foods.
Microangiopathic Haemolytic Anaemia Associated with Hypercakaemia in an Experimental Rat Tumour
Authors: Hilgard Peter , Hohage Roderich , Schmitt Werner , Köhle Walter
Published: March 2008

Summary.

A severe microangiopathic haemolytic anaemia develops during the course of tumour growth in rats bearing the solid Walker carcinosarcoma 256. Early changes of blood coagulation are the prolongation of the clotting and clot‐forming time in the thrombelastogram, a reduction of factor‐VIII activity and impaired platelet aggregation. Subsequent decrease of plasma fibrinogen and blood platelets indicate intravascular coagulation as the cause of the haematological changes. Fibrinogen turnover studies with homologous 131I‐fibrinogen showed a significantly shortened half time. Concomitant with the alterations of the clotting mechanism a decrease of plasminogen level as well as an increasingly prolonged euglobulin lysis time were found; these may be interpreted as the result of the fibrinolytic response to intravascular fibrin deposition. Histological examination of the animals’ organs demonstrated fibrin strands and large fibrin thrombi exclusively in the capillaries of the tumour. Simultaneously with the intravascular coagulation syndrome the animals develop a hypercalcaemia caused by a parathyroid hormone‐like substance elaborated by the tumour tissue. Since clinical reports point to an interrelation between thrombotic disorders and hyperpara‐thyroidism, the possible role of hypercalcaemia in triggering intravascular coagulation is briefly reviewed.
The B‐Lymphocyte Nature of the Hairy Cell of Leukaemic Reticuloendotheliosis
Authors: Catovsky D. , Pettit J. E. , Galetto J. , Okos A. , Galton D. A. G.
Published: March 2008

Summary. Functional studies were performed on the ‘hairy’ cells of five cases of leukaemic reticuloendotheliosis (LRE) to see whether they behaved as histiocytes or lymphocytes. The ‘hairy’ cells were less active than normal or leukaemic monocytes in respect of adhesion to glass, transformation to macrophages and phagocytosis and killing of Candida; they also lacked IgG and C3 receptors for immune phagocytosis. Surface‐bound immunoglobulins were demonstrated in a high proportion of ‘hairy’ cells; and they did not form rosettes with sheep red cells. Similar results were obtained with the lymphocytes of chronic lymphocytic and prolymphocytic leukaemia. In addition, the majority of the ‘hairy’ cells in one case were found to have C3 receptors for immune complexes. The ‘hairy’ cells of three patients did not respond to phytohaemagglutinin (PHA) or to pokeweed mitogen (PWM) but, in another case, half the cells transformed normally with PHA. It is concluded that the ‘hairy’ cell is of lymphocytic origin (resembling B lymphocytes) and that LRE should be included within the lymphoproliferative disorders and differentiated from histiocytic‐cell disorders.
Bleeding Time from Incisions Standardized by Protruding Skin Fold Method
Authors: Stavem Per
Published: March 2008

Summary. A modification of the Ivy bleeding time is described. The incision is made through a protruding skin fold, and constant depth of the incision is ensured by standardizing the amount of protrusion. The method gives reproducible results, within a narrow normal range. Acetylsalicylic acid (ASA) medication approximately doubles the bleeding time with this method. The incisions are only about 3 mm long. The method combines the advantages of the free blood flow of the linear incision methods with the small scar of the punctate methods.
An Electron Microscopic Study of the Nuclear Abnormalities in Erythroblasts in Beta‐Thalassaemia Major
Authors: Polliack A. , Yataganas X. , Thorell B. , Rachmilewitz E. A.
Published: March 2008

Summary. Erythroblasts in the peripheral blood of 20 splenectomized patients with β‐thalassaemia were examined by electron microscopy. A number of alterations in the structure and integrity of the nucleus and nuclear membrane was noted and these included apparent widening of the nuclear pores, partial absence and areas of reduplication of the nuclear membrane. Intranuclear inclusions were found, some identical to the electron‐dense inclusions (Heinz bodies) present in the cytoplasm, while others contained aggregates of finer particles, probably iron micelles. Some erythroblast nuclei appeared to contain portions of cytoplasm with similar inclusions. Nuclear alterations were most prominent when inclusion bodies were abundant in the cytoplasm and when they were in close approximation to or in contact with nuclear material. These nuclear abnormalities may be related to the recognized disturbance in proliferation of thalassaemic erythroblasts and the ineffective erythro‐poiesis encountered in this disease.
Changes in 32P‐Content of Phosphatidic Acid and the Phosphoinositides of Rabbit Platelets during Aggregation Induced by Collagen or Thrombin
Authors: Lloyd J. V. , Mustard J. F.
Published: March 2008

Summary. During the ADP‐induced shape change and aggregation of washed platelets that have been labelled with 32PO4 there is increased incorporation of 32P into phosphatidic acid (PA) and the phosphoinositides of the platelets. When added to suspensions of washed platelets, collagen and thrombin cause not only a change in shape and aggregation, but also the release reaction. The present experiments were carried out to study the effect of collagen and thrombin on the 32P‐content of PA and the phosphoinositides of washed platelets from rabbits. Both collagen and thrombin caused an increase in the labelling of PA that was apparent when the platelets had changed shape and before aggregation of platelets was detected. Unlike the change in labelling of PA that occurs during ADP‐induced aggregation, there was a marked increase in labelling of PA after the commencement of platelet aggregation. Comparison with the maximum response caused by ADP showed that both collagen and thrombin caused a greater increase in the 32P‐content of PA than can be obtained with ADP. Like ADP, collagen and thrombin also caused an increase in labelling of mono‐phosphatidylinositol (MPI). Collagen caused an increase in labelling of diphosphatidylinositol (DPI) but not triphosphatidylinositol (TPI). As with ADP in previously reported experiments, the increase in labelling of DPI occurred after the increase in labelling of PA but preceded the increase in labelling of MPI. An increase in the 32P‐content of DPI has not been demonstrated previously in similar in vitro experiments with other cells using other stimuli. The changes in extent of incorporation of 32P into PA and phosphoinositides may reflect changes in these phospholipids which are important in the mechanism of the change in platelet shape and the release reaction.
The Absorption of Human Factor VIII Neutralizing Antibody by Factor VIII
Authors: Biggs Rosemary
Published: March 2008

Summary. A new technique has been devised for measuring the amount of human factor VIII neutralizing antibody that is absorbed by factor VIII. The method has been applied to factor VIII from normal donors and to factor VIII‐like antigen from haemophilic persons. When the absorption was tested for in relative antibody excess it was found that most haemophilic samples absorbed some antibody but that generally the amount absorbed was less than normal. When a lower antibody concentration was used and most of the antibody present was absorbed by the normal factor VIII, then the haemophilic antigens could be divided into two types. Patients previously diagnosed as haemophilia A + (Denson et al, 1969) provide an antigen which absorbed the normal amount of antibody, while those previously diagnosed as haemophilia A — provided an antigen which did not absorb antibody.
A New Haemorrhagic Disorder with Defective Fibrin Stabilization and Cryofibrinogenaemia
Authors: Rosenberg R. D. , Colman R. W. , Lorand L.
Published: March 2008

Summary. An acquired haemorrhagic syndrome is described in which the failure of haemostasis is due to impaired crosslinking of fibrin. This defect, demonstrated by both monochloroacetic acid clot‐solubility test and disc‐gel electrophoretic analysis of individual fibrin chains, existed despite normal fibrin stabilizing factor (factor XIII) levels in the patient's plasma. Activation of the factor by thrombin, measured by amine incorporation into casein, was normal.

The unique molecular defect in this patient could be fully accounted for by the presence of an inhibitory IgG antibody against the crosslinking sites in fibrinogen‐fibrin. No alteration could be seen in either the rate or in the extent of the reversible aggregation of fibrin. However, large amounts of cryoprecipitate were found in the patient's plasma. This phenomenon could be reproduced in vitro by incubating the chromatographically purified IgG of the patient with normal fibrinogen at 4°C.

It is conceivable that the antibody in the patient could have arisen in response to the modification of normal fibrinogen by isonicotinic acid hydrazide which the patient had ingested for 8 yr.
Separation and Partial Characterization of a Coagulant Enzyme from Bitis gabonica Venom
Authors: Marsh N. A. , Whaler B. C.
Published: March 2008

Summary. The venom of the Gaboon viper (Bitis gabonica) has been shown to possess both coagulant and anticoagulant activities in vitro. These findings confirm in part previous results, the latter effect probably being achieved by proteolytic breakdown of fibrinogen.

A partially purified coagulant has been recovered by ion‐exchange chromatography and gel filtration. Initial results indicate that this material may be similar in some respects to ancrod and reptilase. Anaesthetized rabbits were totally defibrinated without any apparent short‐term deleterious effects.
Enzymatic Basis for Platelet Aggregation and Release: The Significance of the ‘Platelet Atmosphere’ and the Relationship between Platelet Function and Blood Coagulation
Authors: Ardlie N. G. , Han P.
Published: March 2008

Summary. Blood coagulation and platelet reactions such as aggregation and release are both essential to haemostasis and, although relationships between these two processes have been demonstrated, they have been regarded as different phenomena. The results reported here show that the two are inseparable, and that platelet aggregation and release are dependent on the ‘plasmatic atmosphere’ of coagulation factors surrounding platelets. Test systems were developed for studying platelets in plasma (Han & Ardlie, 1973) and in artificial media. When coagulation factors were removed from platelets by washing, only slight reversible aggregation occurred upon the addition of ADP and fibrinogen. Trace amounts of thrombin restored aggregation and TAMe completely inhibited aggregation. Irreversible aggregation and the release reaction of platelets were shown to be dependent on the generation of thrombin by the interaction of clotting factors on the platelet surface. Polymerizing fibrin caused irreversible aggregation and, conversely, inhibitors of fibrin polymerization prevented irreversible aggregation. Irreversible aggregates were insoluble in 5 M urea and 1% monochloroacetic acid suggesting involvement of factor XIII in this aspect of aggregation. It is proposed that aggregation of platelets by ADP is mediated initially by thrombin‐fibrinogen complexes between adjacent adhering platelets. It is also proposed that the nature of the bond between platelets changes when the enzymatic phase of the thrombin—fibrinogen reaction is followed by the polymerization phase, and aggregation then becomes irreversible under the influence of factor XIII, activated by thrombin. Thrombin action also results in the release of platelet constituents. A scheme for haemostasis which emerges from this unification of platelet reactions and blood coagulation is presented in Fig 15, and possible ways in which various other platelet and plasma factors may be involved in haemostasis are briefly discussed.
Erythroid Cell Proliferation in Human Bone Marrow Suspension Cultures
Authors: Wood W. G.
Published: March 2008

Summary. A simple suspension type culture system has been described for the in vitro maintenance of erythroid cells obtained from adult human bone marrow. In the presence of erythropoietin, normoblasts of all stages of maturation were still present after more than 10 days in culture. Following an initial decline, the numbers of basophilic normoblasts showed an absolute increase, reaching a maximum after about 5 days. Evidence of continued DNA synthesis in these cells, the observation of mitotic figures and the tracing of [3H]thymidine label from early normoblasts to intermediate and late normoblasts in culture further suggests that these cells arise by differentiation from unrecognizable erythroid precursor cells. Despite an apparent reduction in proliferation during the maturation of these cells, this system offers a method for investigating various aspects of erythroid cell differentiation and development.
Haemoglobin Synthesis in Suspension Cultures of Human Bone Marrow
Authors: Wood W. G.
Published: March 2008

Summary. The pattern of haemoglobin and individual globin chain synthesis was examined in suspension cultures of adult human bone marrow. Haemoglobin A synthesis continued as long as normoblasts remained in culture and was not observed after their disappearance. The addition of erythropoietin increased and prolonged haemoglobin synthesis up to 12 days, an effect which showed good correlation with the numbers of immature erythroid cells present in culture. Previous reports of Hb F and γ chain synthesis by adult marrow in vitro could not be confirmed.
Leucocyte Glycogen Response in Inflammatory Exudates
Authors: Scott Robert B. , La Cooper Verne W.
Published: March 2008

Summary. Leucocyte glycogen responses in inflammatory exudates were studied in guinea‐pigs. Inflammatory exudates were produced by sterile casein injection intraperitoneally. Glycogen content, incorporation of [14C]glucose into glycogen, and activity of glycogen synthetase and glycogen phosphorylase were studied in both exudate leucocytes and blood leucocytes of the same animals. Glycogen content rises dramatically in exudate leucocytes and remains above control blood values for at least 5 days. Glycogen content of circulating blood leucocytes also rises to less extreme but significant levels during inflammation. Fasting had no effect on the ability of the animals to sustain the glycogen‐loading response in the leucocytes over a 3‐day period. Incorporation of [14C]glucose into glycogen was low in exudate leucocytes and high in blood leucocytes. An inverse correlation between glycogen content and glucose incorporation into leucocyte glycogen was demonstrated for exudate leucocytes. Glycogen synthetase activity was found significantly higher in exudate leucocytes than blood leucocytes, the increase being primarily in the glucose‐6‐phosphate‐dependent (D) form of the enzyme. Glycogen phosphorylase activity was no different in blood and exudate leucocytes. The striking rise in glycogen content of inflammatory leucocytes is probably part of a normal physiologic response, and can be accounted for by a relative increase in glycogen synthesis (synthetase activity) while glycogen degradation in these constantly turning‐over molecules remains constant.
Vitamin E and Oxidative Damage by Tryptophan Metabolites in Experimental Enterogenous Cyanosis and Anaemia
Authors: Westphal R. G. , O'Meara T. M.
Published: March 2008

Summary. Experiments in rats with jejunal blind pouches and bacterial overgrowth demonstrate increased levels in red cells of reduced glutathione, suggesting oxidative stress on red cells, and decreased serum levels of vitamin E, a known anti‐oxidant. The urine of such animals contains increased amounts of tryptophan metabolites, some of which demonstrate strong oxidant activity as measured by methaemoglobin production in vitro. It is felt that enterogenous cyanosis, or intestinal autointoxication, does exist in this experimental model. Whether the oxidative damage previously described is due to the presence of the tryptophan metabolites, the low levels of vitamin E or both, cannot be unequivocally ascertained.
Red‐Cell Organic Phosphates in Patients with Chronic Renal Failure on Maintenance Haemodialysis
Authors: Chillar R. K. , Desforges Jane F.
Published: March 2008

Summary. The red cells of 17 patients with chronic renal failure and anaemia were studied after a mean duration of 4 hr haemodialysis; red‐cell 2, 3‐diphosphoglycerate (DPG) showed a significant fall whereas red‐cell adenosine triphosphate (ATP) remained unchanged. During the same period arterial blood pH showed a significant rise and in 10 out of 17 instances, reached frankly alkalotic values (> 7.45). Serum inorganic phosphate (Pi) fell by 40% during this time and may have been a factor in the fall of 2, 3‐DPG. This fall in 2, 3‐DPG in red cells was more pronounced in four patients who were given transfusions of banked blood during the haemodialysis period.

There was no correlation between 2, 3‐DPG and arterial blood pH or between ATP and pH. There was no correlation between the degree of change of 2, 3‐DPG and the predialysis serum Pi or the degree of change, although the mean value of both declined after dialysis. Similarly, no correlation was observed between ATP and predialysis Pi. Constantly occurring complex biochemical alterations may be limiting factors responsible for this lack of expected relationship between these measurements.

These changes might result in decreased oxygen delivery to tissues in uraemic patients since the haemoglobin oxygen affinity may be increased after haemodialysis by the dual effect of a fall in red‐cell 2, 3‐DPG and an increase in blood pH.
Tissue Localization and Synthesis of Factor‐VIII‐Related Antigen in the Human Foetus
Authors: Tuddenham E. G. D. , Shearn Sonia A. M. , Peake I. R. , Giddings J. C. , Bloom A. L.
Published: March 2008

Summary. Human foetuses ranging in gestational age from 8 to 20 weeks were obtained at hysterotomy for therapeutic termination of pregnancy. Factor VIII related antigen was detected immunologically by Laurell's technique using specific antisera produced in rabbits. It was present in all foetal sera tested. It was not present in amniotic fluid and foetal cerebro‐spinal fluid. An inhibitor of procoagulant factor VIII was neutralized by foetal serum but not by amniotic fluid. The distribution of factor VIII or factor‐VIII‐related antigen in foetal tissues was studied histologically by an indirect immunofluorescent technique. Specific fluorescence was seen on the endothelium of blood vessels in all tissues examined but in other cells the results were less conclusive. In tissue culture studies synthesis of factor‐VIII‐related antigen by explants of foetal spleen was demonstrated by incorporation of [35S]L‐methionine into specific immunoprecipitate. The results indicate that factor‐VIII‐related antigen and possibly procoagulant factor VIII or its precursor are synthezised at an early stage of foetal development.
Studies of Red‐Cell Membrane Function in Heterozygous β Thalassaemia and Other Hypochromic Anaemias
Authors: Knox‐Macaulay H. H. M. , Weatherall D.J.
Published: March 2008

Summary.

Red‐cell membrane function in normal individuals has been compared with that of a group of patients with either heterozygous β thalassaemia, irondeficiency anaemia or sideroblastic anaemia. The metabolic abnormalities in β‐thalassaemic red cells were very similar to those observed in other forms of hypochromic anaemia. The hypochromic cells showed a marked increase in osmotic resistance after incubation for 24 hr which was corrected by buffered glucose but not by D‐xylose. Maximal inhibition of the Na + K‐+ membrane pumps by 10‐4 ouabain and 10‐3 M ethacrynic acid caused a significant increase in osmotic resistance of both normal and thalassaemic cells. The Na+ and K+ concentrations of ‘young’ and ‘old’ thalassaemic cell populations separated by centrifugation did not differ from normal. There was an increased rate of K+ flux across the membrane of both thalassaemic and iron‐deficient red cells, with a net increase in the rate of K+ loss from the cells. The rate of movement of Na+ in and out of the cells was normal in all the hypochromic anaemias studied. The rates of glucose utilization and lactate production were increased in normal and thalassaemic ‘young’ cells but there was no increase in the ‘old’ populations of thalassaemic cells with increased K+ fluxes. ATP levels were normal in all the abnormal cells studied. It is concluded that all the forms of hypochromic anaemia examined are characterized by increased K+ fluxes and excessive loss of K+ from the cells. The possible relationship between red‐cell haemoglobin content and membrane function is discussed.
Sporadic G6PD Deficiency with Haemolytic Anaemia in Two Children of West European Ancestry
Authors: Sonnet J. , Lievens M. , Verpoorten C. , Kriekemans J. , Eeckels R.
Published: March 2008

Summary.

Two unrelated children of Western European ancestry, originating from the North Flemish part of Belgium were found to have a deficiency of red‐cell glucose‐6‐phosphate dehydrogenase (D‐glucose‐6‐phosphate: NADP oxidoreductase, G6PD) activity, with chronic non‐spherocytic haemolytic disease. The first hemizygous propositus exhibited subsequent episodes of haemolytic jaundice precipitated by upper respiratory infections. The second hemizygous propositus had neonatal hyperbilirubinaemia and later chronic haemolytic disease enhanced by febrile upper respiratory tract infections.

Characterization of the enzyme of the first case revealed that it was a variant which had not been previously reported and it was tentatively named G6PD Kessel‐Lo.
Red‐Cell Life Span in the Acute Rat Leukaemia L 5222
Authors: Harriss Eileen B.
Published: March 2008

Summary.

The life span of red cells produced under leukaemic conditions has been measured in the experimental rat leukaemia, L 5222. Red cells in leukaemic donors were labelled by injection of 59Fe and their survival studied over a period of 11 weeks after transfusion to normal recipients. No difference in potential life span or random destruction could be detected from similarly treated red cells from normal 59Fe‐injected donors. It is concluded that the red cells produced during this leukaemia have no intrinsic defect.
Measurement of Red Cell Folate Levels by 3H‐Pteroylglutamic Acid (3H‐PteGlu) Radioassay
Authors: Schreiber Carol , Waxman Samuel
Published: March 2008

Summary. A siniple, rapid radioassay is described for the determination of red cell folate activity utilizing commercially available beta lactoglobulin as thc folate binding protein. The standard curve is prepared with a pteroylpolyglutamate and 3H‐pteroylglutamic acid. The test is performed with a maximum of 20 nicrolitres of whole blood and multiple samples can be processed within 1 hr. Values of red cell folate in normal subjects range from 200 to 875 ng/ml packed cells giving good correlation with established microbiological procedures. Red cell folate levels were lowest in patients whose folate deficiency was accompanied by anaemia. This assay may be useful for measurement of pteroylpolyglutamates in other tissues since an equimolar amount of N‐5‐methyl tetrahydrofolate is barely measurable under the conditions of this assay.
Inhibition of Uridine Incorporation in Proerythroblasts of Patients with α‐Methyldopa Induced Haemolytic Anaemia
Authors: Djaldetti M. , Bessler H. , Lewinski U. , Mandel E. M.
Published: March 2008

Summary. Procrythroblasts of three patients with α‐methyldopa induced haemolytic anaemia showed inhibition of [3H]uridine incorporation after incubation with α‐methyldopa as compared with proerythroblasts of healthy individuals; incorporation of [3H]thymidine was not affected. It was shown that the inhibitory effect of α‐methyldopa on uridine incorporation is due to the drug itself and not to plasma factors, nor to the haemolytic process. The possibility that this phenomenon might serve as a test for demonstration of α‐methyldopa sensitivity is discussed.
Anti‐Bg Antibodies in Sera Used for Red Cell Typing
Authors: Pavone Beverly G. , Issitt Peter D.
Published: March 2008

Summary. A number of sera used to type red cells for various blood group antigens have been examined for the simultaneous presence of anti‐Bg antibodies. Of 65 scra prepared from single donor sources 15 (23%) have been shown to contain anti‐Bg. Of 62 reagents purchased commercially 21 (33.8%) have been shown to contain anti‐Bg. The significance of the presence of these antibodies is discussed.
Delayed Cutaneous Hypersensitivity in Leukaemic Patients to Autologous Blast Cells
Authors: Baker Michael A. , Taub Robert N. , Brown Shelley M. , Ramachandar Kmhatala
Published: March 2008

Summary. Thirty‐four patients with acute mycloblastic and lymphoblastic leukaemia have been skin tested in relapse (30 patients) and remission (13 patients) with autologous irradiated leukaemic blast cells and standard skin test antigens. The timing, clinical appearance and histology of the positive skin tests were typical of classical delayed hypersensitivity. Thirteen of 29 paticnts in relapse and six of of 13 patients in remission showed delayed hypersensitivity responsiveness to autologous irradiated blast cells, indicating that skin test positivity did not correlate with the clinical status of the patient tested. Although tendency to a favourable clinical course was seen in patients with positive delayed hypersensitivity to standard skin test antigens, no such correlation was seen in those patients positive to skin tests with autologous blast cells. Membrane extracts of autologous blast cells failed to elicit skin test responsiveness in all but two of 19 patients tested.
The Identification of Fibrinopeptide B as a Chemotactic Agent Derived from Human Fibrinogen
Authors: Kay A. B. , Pepper D. S. , McKenzie Robin
Published: March 2008

Chemotactic activity for human peripheral blood leucocytes was generated by the action of thrombin on human fibrinogen, a reaction known to release low molecular weight fibrinopeptides. Following gel filtration of the clot supernatant most of the activity eluted at the same Kd as synthetic fibrinopeptides. Fibrinopeptides present in the clot supernatant were then identified and separated by high voltage electrophorcsis in two dimensions. Chemotactic activity was a property of fibrinopeptide B and not of fibrinopeptides A, AP or AY. Supernatants prepared with contortrix venom, which cleaves the B peptide, were also chemotactic whereas no activity was present in supernatants prepared from Arvin venom which cleaves peptides A, AP and AY. Synthetic fibrinopeptide B and a B analogue, 1‐glutamic acid, were found to be chemotactic but not synthetic fibrinopeptide A. Thus chemotaxis of human leucocytes represents a further biological activity of fibrinopeptide B.
Transferrin and Iron Uptake by Rabbit Bone Marrow Cells in Vitro
Authors: Kailis S. G. , Morgan E. H.
Published: March 2008

Summary. The interaction between rabbit transferrin and rabbit bone marrow cells and reticulocytes was investigated using transferrin labelled with 125I and 59Fe. The pattern of transferrin and iron uptake by bone marrow was found to be similar to that by reticulocytes and occurred in four stages, viz (1) adsorption of transferrin, (2) progressive uptake of transferrin, (3) release of the iron to the cell, (4) release of transferrin from the cell.

Total transferrin uptake per bone marrow erythroid precursor cell was eight times that per reticulocyte, while the rate of iron uptake was at least twice as great with marrow cells. Transferrin uptake and release and iron uptake were temperature dependent. Transferrin and iron uptake were inhibited by metabolic inhbitors, particularly those affecting oxidative metabolism. The activation energies for the association and dissociation reaction of transferrin and the activation energy for iron uptake by bone marrow cells were higher than those reported for reticulocytes. A further difference between the two cell types was that at a constant iron concentration, iron uptake by bone marrow cells decreased with decreasing degrees of transferrin saturation with iron. Small increases in transferrin uptake by bone marrow cells were also obtained with increasing transferrin saturation. The data support the view that both iron and transferrin uptake are dependent upon cellular metabolism.
Some Effects of Splenectomy in Thalassaemia Major
Authors: Blendis L. M. , Modell C. B. , Bowdler A. J. , Williams Roger
Published: March 2008

Summary. The effect of splenectomy in the thalassaemia syndrome has been investigated by isotopic studies of red cell mass and life span, and plasma volume, before and after splenectomy, in a group of mainly untransfused patients. The plasma volume was grossly expanded in all patients both before and after splenectomy and it decreased moderately in some patients following the operation. The autologous red cell life span increased in all patients after splenectomy, but the red cell mass did not rise proportionately, indicating a substantial decrease in erythropoiesis in some patients. This was accompanied in some cases by a spurt of growth. It is suggested that severe ineffective erythropoiesis in thalassaemia can cause both blood volume expansion as a result of diversion of blood through the bone marrow, and growth retardation, possibly on a competitive basis.
Haemoglobin Constant Spring Synthesis in Red Cell Precursors
Authors: Kan Yuet Wai , Todd David , Dozy Andree M.
Published: March 2008

Summary. The synthesis of α Constant Spring (αcs) chain was studied in the peripheral blood and bone marrow of five patients with haemoglobin H Constant Spring disease. Relative to the normal α and β chains, the production of αcs chain was found to be less efficient as the erythroid cells mature.
The Ultrastructure of Erythropoiesis in Two Haemoglobinopathies
Authors: Frisch B. , Lewis S. M. , Sherman D. , White J. M. , Gordon‐Smith E. C.
Published: March 2008

Summary. The ultrastructural features of the bone marrow have been studied in two patients with haemoglobinopathy, Hb Hammersmith and Hb Nottingham respectively. Multiple anomalies were observed in erythroblasts in both cases, together with islands of normal erythropoiesis. The incidence of abnormalities was higher in the case of Hb Nottingham, but many of the features seen were similar in the two cases. The findings included bi‐ and multinucleated erythroblasts, cytoplasmic bridges and microtubules, abnormalities of the nuclear envelope, widened nuclear pores, alterations in the structure and density of the chromatin, abundant iron‐laden mitochondria, a variety of nuclear and cytoplasmic inclusions, and the presence within the cytoplasm of membranous material which is presumed to be endoplasmic reticulum. Many of these ultrastructural alterations are similar to those which have been observed in the congenital dyserythropoietic anaemias. A particular feature of the present cases was localized myelinization in both nuclear envelope and the membranes of the endoplasmic reticulum. The implications of the findings are discussed in relation to known cellular responses to various stimuli, including injury. It is concluded that the wide range of ultrastructural aberrations which occur in the erythroblasts are not specific to the haemoglobinopathies or the congenital dyserythropoietic anaemias, but are indicative of cellular injury, irrespective of the fundamental aetiology.
Primary Acquired Sideroblastic Anaemia Associated with Chronic Lymphocytic Leukaemia
Authors: Papayannis A. G. , Stathakis N. E. , Kyrkoy K. , Panani A. , Gardikas C.
Published: March 2008

Summary.The case of a 71‐yr‐old man with primary acquired sideroblastic anaemia associated with chronic lymphocytic leukaemia is described. Cytogenic studies of the peripheral‐blood lymphocytes and the bone‐marrow cells provided evidence for chromosomal abnormalities common to erythroblasts and leukaemic lymphocytes. This finding strongly suggests that in this patient the two diseases are related.
The Radioimmunoassay of Serum and Salivary Blood Group A and LeaGlycoproteins
Authors: Houlburn A. M. , Masters Carole A.
Published: March 2008

Summary.A radioimmunoassay was developed for the detection of A and Leablood group activities in glycoprotein fractions extracted with perchloric acid (PCA) from normal serum. The technique was also applied to studies of salivary blood group glycoproteins.

Blood group A activity was detected in all group A sera tested. Higher levels of A activity were found in sera from group A1than from A2donors, and sera from both group A1and A2secretor donors gave higher levels of A activity than sera from non‐secretor donors. No difference was found in the levels of A activity in group A1and A2secretor salivas but only small numbers were assayed. Parallel radioinimunoassay inhibition lines, indicating immunological identity, were obtained with PCA‐extracts of A1and A2secretor plasma and with extracts of A1and A2secretor salivas.

Leaactivity was detected in all sera tested. The levels of Leaactivity were higher in sera from Le(a + b ‐) donors than from h(a ‐ b +) or Le(a ‐ b ‐) donors and were unaffected by ABO group. Radioimmunoassay inhibition lines indicated qualitative differences in the Leaantigen in salivas from secretors and non‐secretors, consistent with a lower density of Leaantigen on salivary glycoprotein from secretor donors.
Proliferation of Haemopoietic Stem Cells in Vitro
Authors: Dexter T. M. , Lajtha L. G.
Published: March 2008

Summary. A liquid culture system for murine haemopoietic cells is described where proliferation of granulocytes (G‐cultures) or mononuclear cells (M‐cultures) can be maintained for many weeks. In M‐cultures there is a rapid loss of spleen colony forming cells (CFUs). Agar colony forming cells (CFUc) are present for 6 weeks, then decline rapidly. Colonies formed from these CFUc contain only large mononuclear cells. In G‐cultures there is proliferation of CFUs, grafts of which (after 7‐9 weeks in culture) protect lethally irradiated mice from haemopoietic death. Similarly, there is proliferation of CFUc, which form colonies in agar consisting of granulocytes, in all stages of differentiation.
Willebrand Factor and Ristocetin II. RELATIONSHIP BETWEEN WILLEBRAND FACTOR, WILLEBRAND ANTIGEN AND FACTOR‐VIII ACTIVITY
Authors: Meyer D. , Jenkins C. S. P. , Dreyflis M. D. , Fressinaud E. , Lariueu M.‐J.
Published: March 2008

Summary. Two methods of assay of Willebrand factor activity have been used in the study of 20 patients with congenital and acquired von Willebrand's disease. The relationship between the three entities of factor‐VIII complex, Willebrand factor activity, Willebrand antigen and factor‐VIII activity is discussed. Data from thermo‐stability and dissociation studies favour the hypothesis that factor‐VIII complex consists of two closely related but separate proteins.
Monocyte Production of Colony Stimulating Factor in Familial Cyclic Neutropenia
Authors: Moore M. A. S. , Spitzer G. , Metcalf D. , Penington D. G.
Published: March 2008

Summary. Granulocyte‐macrophage colony formation in agar culture of marrow is dependent on the presence of a glycoprotein colony stimulating factor (CSF). Measurement of the plasma levels of this factor in a 15‐yr‐old child with familial cyclic neutropenia revealed regular cycles with peak levels coinciding with nadirs of neutrophils and peaks of monocytes. A close correlation was observed between the incidence of monocytes and the capacity of the patient's leucocytes to elaborate CSF in culture. The frequency and amplitude of the blood monocyte cycles together with in vitro measurements of monocyte CSF‐producing capacity adequately accounted for the observed fluctuations of plasma CSF levels. A model of granulopoiesis is presented in which a positive stimulus for granulopoiesis is provided by CSF elaborated by nionocytes and a negative or neutral influence exerted by mature granulocytes.
Preparation, Characterization, and Activation of a Highly Purified Factor XI: Evidence that a Hitherto Unrecognized Plasma Activity Participates in the Interaction of Factors XI and XII
Authors: Schiffman Sandra , Lee Pearl
Published: March 2008

Summary. Highly purified native factor XI has been prepared from normal plasma using a five step purification scheme. Purified factor XI is essentially free of factors II, V, VII, VIII, IX, X, XII, and Fletcher factor. No plasminogen‐plasmin could be detected. Purified factor XI decays rapidly but can be stabilized with human serum albumin. Factor XI migrates between the β and γ globulins on starch block electrophoresis. It has an apparent molecular weight on gel filtration of 210 000. Purified factor XI is activated by weak trypsin. No detectable BAEe esterase activity accompanies this activation. Neither factor XII adsorbed to kaolin nor activated factor XII in solution could activate purified factor XI; both reagents activate factor XI in dilute factor XII deficient plasma. Hence, plasma appears to supply a third activity which facilitates the interaction of factors XI and XII. This activity is shown to be distinct from Fletcher factor.
The Synthesis of Globin Peptide Chains in Sickle‐Cell Disease
Authors: Sarup B. M. , White J. M.
Published: March 2008

Summary. The relative rates of synthesis of the globin chains (α, βs and γ) have been measured in vitro in the reticulocytes of eight patients homozygous for Hb S. The results indicate that the synthesis of the βs chain and its association with α chains are normal in the majority of homozygous patients. In two patients an excess synthesis of α chains was detected. The cause for this has not been determined, but it appears to be a transient phenomenon.

The explanation is discussed for the normal synthesis of the βs globin in home zygotes and the fact that in sickle heterozygotes the specific activities of α‐ and β‐chains have usually been unity, i.e. that they are being produced at the same rate as they appear in the peripheral blood is discussed.
The Effect of Some Liver Enzyme Inhibitors on the Hepatic Inactivation of Erythropoietin in Mice
Authors: Loeber J. G. , Bosch E. , Goudsmit R. , Kolk‐Vegter Annette J.
Published: March 2008

Summary. In a series of experiments with polycythaemic mice the influence of liver enzyme inhibitors on erythropoietin activity was studied. SKF 525‐A was found to increase the half disappearance time of the activity of administered sheep erythropoietin. Both the administration of SKF‐525‐A and Disulfiram were found to increase the half disappearance time of endogenous erythropoietin activity. It is concluded that these compounds block the inactivation of erythropoietin in the liver. A model in which the action of such inhibitors on the disappearance of endogenous erythropoietin activity can be tested, is proposed.
Transferrin Iron, Chelatable Iron and Ferritin in Idiopathic Haemochromatosis
Authors: Beamish M. R. , Walker R. , Miller F. , Worwood M. , Jacobs A. , Williams R. , Corrigall A.
Published: March 2008

Summary. In 12 patients with idiopathic haemochromatosis and varying degrees of iron overload the serum ferritin concentration was related to the amount of iron mobilized by venesection. There was no correlation between iron load and chelatable iron. In 25 patients with normal iron stores following venesection therapy, both transferrin iron and chelatable iron was pathologically increased.

The initial stages of iron accumulation in idiopathic haemochromatosis are characterized by an imbalance between chelatable iron and ferritin, a phenomenon that could explain the pathogenesis of the disease.
Characteristics of a Novel Serum Vitamin‐B12‐Binding Protein Associated with Hepatocellular Carcinoma
Authors: Waxman Samuel , Gilbert Harriet S.
Published: March 2008

Summary. A novel protein designated as hepatoma B12 binder (HBB), the predominant vitamin‐B12‐binding protein in the serum of two adolescents with hepatocellular carcinoma, has been characterized. HBB is more acidic and has different electrophoretic mobility and elution behaviour on gel filtration than normal or chronic myeloid leukaemia transcobalamin I. HBB is a member of the family of‘R’type vitamin‐B12‐binding proteins since it immunologically cross reacts with anti‐R antibody and does not deliver vitamin B12 to the cell. HBB is unique in that it is tumour‐related, elaborated in enormous quantity and possesses physical characteristics best explained by a different carbohydrate composition from that of transcobalamin I.