bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemolysis and Erythropoiesis
Authors: Sánchez‐Medal L. , Pizzuto J. , Rodríguez‐Moyado H. , Espósito L.
Published: March 2008

Summary. Case records of patients with anaemia due to lack of iron, vitamin B12 or folate, or to abnormal haemolysis were reviewed with regard to magnitude of reticulocytosis and rate of haemoglobin rise after therapy. Greater absolute reticulocyte values were observed in hereditary and acquired haemolytic anaemias. Furthermore, and more significantly, the rate of haemoglobin rise in autoimmune haemolytic anaemia responding to corticosteroid administration was greater than in the deficiency anaemias during adequate therapy. Additional data are presented supporting the old concept that erythrocytic production is greater in haemolytic anaemias than in deficiency anaemias after specific therapy.
Wiskott—Aldrich Syndrome: Qualitative Platelet Defects and Short Platelet Survival
Authors: Gröttum K. A. , Hovig T. , Holmsen H. , Abrahamsen A. Foss , Jeremic M. , Seip M.
Published: March 2008

Summary. Investigations of the haemostatic functions in three patients with the Wiskott‐Aldrich syndrome are presented. All patients had severe thrombocytopenia and prolonged bleeding times. The platelets had abnormal morphology with reduced size and variations of shape. Electron microscopy revealed ultrastructural abnormalities with a reduced number of organelles, and many of the platelets contained large numbers of tubules. Platelet electrophoretic mobility in citrated plasma was not reduced by collagen, and platelet aggregation by collagen and ADP was deficient. Biochemical studies revealed a lack of the storage pool of adenine nucleotides. Platelet adhesiveness in vitro in whole blood was reduced. Platelet factor‐3 release by kaolin, ADP and freezing and thawing was normal in one and reduced in another of the patients.

Platelet survival studies showed a normal survival time of normal donor platelets in one patient, while autologous platelets had a markedly reduced survival time in two of the patients. The bone marrow contained normal numbers of megakaryocytes. By electron microscopy of the bone marrow, blood platelets were found to be phagocytosed by macrophages and reticulum cells. The main cause of the thrombocytopenia is most probably incrcased peripheral destruction of platelets. It is suggested that the qualitatively defective platelets are recognized in the reticulo‐endothelial system as foreign particles and phagocytosed.
The Original Haernorrhagic Fever: Yellow Fever
Authors: Dennis Lewis H. , Reisberg Boris E. , Crosbie James , Crozier Dan , Conrad Marcel E.
Published: March 2008

Summary. Monkeys infected with the Asibi strain of yellow fever virus developed multiple coagulation abnormalities 3–4 days after viral inoculation. These coagulation abnormalities occurred almost simultaneoulsy with the development of fever, clinical illness and pathologic changes in the liver. The haemorrhagic manifestation of yellow fever and the rapid development of multiple coagulation abnormalities cannot be explained solely by impaired production of coagulation proteins and suggested that there was accelerated intravascular coagulation. Heparin therapy in one group of infected animals decreased the severity of coagulation abnormalities but did not prolong the life of these animals.
Effects of Dietary Methionine and Vitamin B12 Deficiency on Folate Metabolism
Authors: Vitale Joseph J. , Hegsted D. Mark
Published: March 2008

Summary. Glutamate formimino transferase activity (GFA) and liver folic acid and vitamin B12 levels were decreased in rats fed diets deficient in methionine and vitamin B12. The addition of either methionine or vitamin B12 resulted in a rise in GFA and in liver folate levels. However, L. casei serum folate was not affected by the dietary level of vitamin B12 or methionine, but the S. faecalis serum folate decreased as the level of dietary methionine and vitamin B12 was increased. The results of these studies do not appear to support the concept that vitamin B12 deficiency results in a ‘pile‐up’ of N5‐methyl folate but suggests that it induces folate deficiency. Also the results suggest that the effect of vitamin B12 on folate metabolism may be mediated via methionine metabolism.
A New Sickling Disorder Resulting from Interaction of the Genes for Haemoglobin S and α‐Thalassaemia
Authors: Weatherall D. J. , Clegg J. B. , Blankson J. , McNeil J. R.
Published: March 2008

Summary. A new abnormal haemoglobin syndrome is described resulting from homozygosity for the sickle‐cell gene in association with two α‐thalassaemia genes. This type of disorder is probably quite common in populations like those in Saudi Arabia where there is a relatively high frequency of both the sickle‐cell and α‐thalassaemia genes. In Saudi Arabia both sickle‐cell anaemia and α‐thalassaemia are associated with higher levels of foetal haemoglobin production than in other racial groups examined to date. This finding may account, at least in part, for the remarkable differences in the clinical manifestations of the sickling disorders in Saudi Arabia as compared with those observed in African populations.
The Effects of Whole Body Irradiation on Serum Colony Stimulating Factor and in Vitro Colony‐Forming Cells in the Bone Marrow
Authors: Hall Barbara M.
Published: March 2008

Summary. Using in vitro cultures of mouse bone marrow cells, levels of colony stimulating factor were assayed in serum from mice following whole body irradiation. No significant differences from control levels were noted in the period 1–32 days following 50, 150, 250 or 450 rads. A dose of 250 rads caused a sharp fall in the level of colony‐forming cells in the bone marrow followed by regeneration between 6 and 16 days following irradiation.

Six to 8 hours following whole body irradiation, blood polymorphs and serum colony stimulating factor levels were consistently elevated. Splenectomy did not affect this response.

The results suggest that serum colony stimulating factor is unlikely to be the major regulator determining regeneration of in vitro colony‐forming cells in the bone marrow following irradiation.
A Random Sample from Wales
Authors: Jacobs A. , Entwistle C. C. , Campbell H. , Waters W. E.
Published: March 2008

Summary. The prevalence of antibodies to parietal cells, intrinsic factor and thyroid cytoplasm in the Welsh population has been estimated. Women had a higher prevalence of these antibodies than men and their frequency shows a significant increase with age. There is a significant association between the presence of thyroid and gastric autoantibodies in women but not in men. Parietal‐cell antibodies are more common in men with low haemoglobin levels. Three out of 506 women were found to have intrinsic‐factor antibody.
A Quantitative Study of Blood and Bone Marrow Eosinophils in Severe Hypoxia
Authors: Grant J. B. F. , Hudson G.
Published: March 2008

Summary.

Quantitative methods have been employed to study the eosinophil granulocytes in the blood and bone marrow of guinea‐pigs following continuous exposure to a simulated altitude of approximately 20,000 feet (6096 m.) for periods of between 1 and 12 days. Striking changes were observed on the first day and persisted for the whole period of observation. The blood eosinophils were increased in number, while the marrow eosinophil compartments showed marked depletion, the compartment of late (band and segmented) forms being particularly affected. The marrow neutrophils and basophils showed a much less dramatic reduction in numbers. There was a ‘shift to the right’ in the blood eosinophils.

In interpretation of the findings, it is suggested that, in addition to the loss of large numbers of mature and nearly‐mature eosinophils from the marrow in the earlier stages of severe hypoxia, there was a decrease in the proliferative activity of the marrow eosinophils, together with a decrease in the turnover of eosinophils in the blood. Factors which might contribute to such changes are discussed.
Some Variations in the Normal Haemoglobin Concentration
Authors: Cruickshank J. M.
Published: March 2008

In a study of the haemoglobin concentrations of 408 male and 789 female blood donors aged 18–65, it was found that in both sexes the haemoglobin level, except for a peak in the middle of the third decade, remained constant until the fifth decade. From this period to the age of 65, there was a progressive and significant decrease of haemoglobin concentration in men and a progressive and significant increase of haemoglobin concentration in women. An initial difference in haemoglobin level, between men and women, of almost 2 g/100 ml in the early twenties was reduced to just over 1 g/100 ml in the middle sixties. Possible reasons for the above differences were discussed with emphasis on the effects of hormonal environment and iron deficiency.
The Effect of Neomycin on Iron Absorption in Germfree Rats
Authors: Geever E. F. , Crowley L. V. , Levenson S. M.
Published: March 2008

Studies of radioiron absorption were performed on two groups of adult male germfree and open animal room rats which had been raised under special conditions. The latter were housed in germfree type isolators and shielded from further external bacterial exposure from weanling to adult life. Both groups were given a 5 day course of neomycin treatment and 1 day later radioiron was administered by intragastric instillation. Both groups showed an increase in radioiron absorption and total serum iron level over controls at death 7 days following intragastric instillation. Our findings suggest that the neomycin effect on iron absorption is a complex one which may operate in the absence of living bacteria.
In Vitro Studies of Red Cell Metabolism in Haemoglobin H Disease
Authors: Scott G. L. , Rasbridge M. R. , GRIMES A. J.
Published: March 2008

Summary. A study has been made of glycolysis and some membrane abnormalities in the red cells of six patients with haemoglobin H disease. Haemoglobin H has been shown to be thermolabile and this property was used to determine the amount present in blood samples. Fresh red cells have increased anaerobic glycolysis and hexose monophosphate pathway activity in accord with the low MCHC of the cells and the young red cell population present in blood samples. However, red cell ATP was low in three of four patients studied and GSH was low in four of six patients. Red cell phospholipid was abnormally high in the four patients studied. Following incubation in vitro, red cell phospholipid, AChE activity, ATP and GSH decreased in an abnormal manner not attributable to the abnormal degree of lysis that occurred. Studies with young and old red cell fractions indicated that whilst GSH was significantly low in older cells hexose monophosphate pathway activity tended to be high. The significance of these results is discussed
The Assay of Human Factor VII by Means of Modified Factor VII Deficient Dog Plasma
Authors: Garner R. , Conning D. M.
Published: March 2008

Summary. An inbred group of beagle dogs deficient in factor VII has been used to provide a reagent for the assay of factor VII in human plasma. Dilutions of human plasma were tested in a one‐stage system with beagle dog plasma, brain extract and calcium chloride. It was found that, if the concentration of factor V in the beagle dog plasma was reduced and a dilute human brain extract used, log clotting time was directly related to log concentration of factor VII. Assays using beagle dog plasma and human plasma deficient in factor VII gave comparable values. A range of factor‐VII activity is reported for normal human plasma samples.
Molecular Forms of Antihaemophilic Globulin in Plasma, Cryoprecipitate and after Thrombin Activation
Authors: Weiss Harvey J. , Kochwa Shaul
Published: March 2008

Summary. Sedimentation characteristics of factor VIII were investigated by ultracentrifugation in 10–40% w/v sucrose gradient in pH 7.2 imidazole buffered saline at 65 000 rpm for 6 hr. Following dialysis of fractions for 12 hr against buffered saline, the factor‐VIII activity was assayed by a one‐stage method and other proteins were identified by immunological techniques. In human citrated plasma, two regions of factor‐VIII activity were detected, a main fast sedimenting activity in the region ofγM macroglobulin and a minor slow sedimenting activity in the region of fibrinogen. Cryoprecipitate activity was all of the fast type, while the activity in its supernatant was of the slow type. When plasma was fractionated in a sucrose gradient prepared in 0.4 or 1 M NaCl, the factor‐VIII activity was found in the slow fraction, suggesting that fast‐sedimenting factor VIII is a non‐covalently bound polymer. Incubation of plasma with thrombin (0.035 u/ml for 10 min at 37°C) markedly increased the factor‐VIII activity, all of which appeared in the slow fraction. Although this suggests the possibility that the fast fraction represents a factor VIII‐fibrinogen complex, immunological analysis of this fraction failed to reveal the presence of any fibrinogen. Alternatively, the fast fraction may be composed of sub‐units of factor VIII which are both released and activated by thrombin.
Megakaryocytopoiesis in Splenectomized and ‘Hypersplenic’ Rats
Authors: Rolovic Zoran , Baldini Mario
Published: March 2008

Summary. Megakaryocytopoiesis was studied in splenectomized, in normal and in ‘hypersplenic’ rats in order to evaluate the role of the spleen on platelet kinetics. Bone marrow autoradiography after injection of tritiated thymidine was utilized in this investigation. The splenectomized rats were studied 6 weeks after the operation when their platelet count was stable at a level of 23% higher than before splenectomy. Splenomegaly was produced by repeated intraperitoneal injections of methylcellulose and was associated with a 52% lowering of the platelet count.

The results revealed identical patterns of megakaryocytopoiesis in splenectomized and normal rats indicating that post‐splenectomy thrombocy tosis was not the consequence of an increased rate of megakaryocyte maturation. On the contrary, megakaryocytopoiesis in the ‘hypersplenic’ rats was stimulated, although slightly so. This demonstrated that thrombocytopenia in the rats with splenomegaly could not be ascribed to the functional inhibition of megakaryocyte maturation.

These findings support the view that in normal conditions the role of the spleen lies only in the distribution of the circulating platelet mass with a higher concentration of platelets in the spleen, and are consistent with the suggestion that in ‘hyper‐splenism’ the thrombocytopenia occurs because of excessive pooling of the platelets in the enlarged spleen, while the bone marrow provides a larger than normal number of platelets.
The Factor‐X Defect: Recognition of Abnormal Forms of Factor X
Authors: Denson K. W. E. , Lurie A. , Cataldo F. De , Mannucci P. M.
Published: March 2008

Summary. Six patients with the ‘Factor‐X defect’ have been investigated. At least five different forms of the defect were recognized by the use of the following laboratory tests: the kaolin cephalin clotting time as a measure of intrinsic clotting, the factor‐X assay employing either brain extract or Russell's viper venom, and the neutralization of a factor‐X antibody as a measure of the presence of factor‐X antigen. It is suggested that different forms of the defect are the result of a variety of genetic mutations.
Intestinal Absorption of Reduced Folate Compounds in Man
Authors: Perry Janet , Chanarin I.
Published: March 2008

Summary. Oral administration of folate compounds was followed by a rise in L. casei active factors in blood. This was due to reduction and methylation of the folate compounds in the small gut and this was demonstrated by the use of dihydropteroylglutamic acid labelled with tritium.

Parenteral administration of tritium‐labelled folate analogues was followed by a rapid exchange with unlabelled L. casei active folate from tissues.
The Haemoglobin Constitution of Infants with the Haemoglobin Bart's Hydrops Foetalis Syndrome
Authors: Weatherall D. J. , Clegg J. B. , Boon Wong Hock
Published: March 2008

Summary. The haemoglobin constitution of 14 infants with the haemoglobin Bart's hydrops syndrome has been examined. Thirteen of the infants were stillborn or lived only a few minutes after delivery, but in one case an exchange transfusion was performed and the pattern of globin chain synthesis examined by an [H3]leucine incorporation experiment utilizing umbilical cord blood. These studies indicate that the syndrome results from a total deficiency of α‐chain production. Furthermore, it has been possible to exclude the presence of fragments of α‐chain longer than II residues in the cells of these infants.

In each infant a small quantity of haemoglobin was found which consisted of normal γ‐chains in association with chains of unique constitution. A similar component was found in trace amounts in normal umbilical cord blood. This haemoglobin may be identical with haemoglobin Portland. It is suggested that the non‐γ‐chain of this haemoglobin is the product of a normal foetal haemoglobin locus which produces very small amounts of gene product in normal infants but which is capable of increased activity in the presence of a partial or total deficiency of α‐chains.
Idiopathic Heinz Body Anaemia: Hb‐Bristol (β67 (E11) Val→Asp)
Authors: Steadman J. H. , Yates A. , Huehns E. R.
Published: March 2008

Summary. It is shown that the haemolytic anaemia in the original patient with ‘idiopathic Heinz body anaemia’ is due to the presence of 36% unstable haemoglobin: Hb‐Bristol (β67 (E11) Val→Asp). This haemoglobin has a low oxygen affinity which accounts for the normal development of this patient in spite of the presence of permanent severe anaemia. The relative rates of synthesis of βBristol‐ to βA‐chains were identical, indicating that the reduced amount of Hb‐Bristol found in the haemolysate is due to precipitation of the abnormal protein. The inability to separate this haemoglobin by electrophoresis is due to interaction of the abnormal aspartic acid with the adjacent histidine at β63 (E7).
Megakaryocytes in States of Altered Platelet Production: Cell Numbers, Size and DNA Content
Authors: Penington D. G. , Olsen T. E.
Published: March 2008

Summary. Megakaryocytes have been studied in rats using objective methods, with assessment of numbers of cells, cell diameter and DNA content. Stimulation and suppression of platelet production have been shown to be accompanied by changes in cell diameter, and in numbers of megakaryocytes in the bone marrow and spleen. A method is described permitting measurement of DNA content of the cells under these conditions, using Feulgen staining and an integrating micro‐densitometer. It has been demonstrated that alteration in size is secondary to alteration in ploidy value. The reduction in ploidy following transfusion of platelets was apparent morphologically as a decrease in the number of lobes in the nucleus, but following stimulation of platelet production, an increase in ploidy occurred which was not associated with a discernible increase in nuclear lobulation. Microdensitometry provides the only certain method of objective assessment of megakaryocyte ploidy. It is concluded that the system regulating megakaryocyte proliferation governs DNA replication in both megakaryoblast and stem cells.
Adrenergic Mechanisms in the Systemic Plasminogen Activator Response to Adrenaline in Man
Authors: Cash John D. , Woodfield D. G. , Allan A. G. E.
Published: March 2008

Summary. The effect of propranolol, ICI 50172 and a combination of propranolol and phentolamine, on the plasminogen activator response to a 30 mm intravenous infusion of adrenaline hydrochloride (0.1 μg/kg/min) has been studied in five healthy subjects. Plasma factor VIII, serum free fatty acids, blood glucose and pulse rate changes were also monitored to confirm the efficacy of adrenergic blockade. Propranolol blocked the plasminogen activator response by a factor of 29% whereas ICI 50172 had no effect. The addition of phentolamine to propranolol failed to influence further the degree of blockade already present with propranolol alone. It is postulated that the plasminogen activator response to adrenaline is derived from two separate components, and that the relatively minor one may be secondary to vasoactive changes whereas the second and major component is quite independent of this phenomenon. It is also proposed that both components may share a common adrenergic receptor site.
Exchange between Parenteral and Tissue Folate in Man
Authors: Chanarin I. , Perry Janet
Published: March 2008

Reduced folate compounds (dihydro‐ and tetrahydro pteroylglutamic acid) given intravenously in man exchange rapidly and completely with tissue 5‐methyltetrahydrofolate which accumulates in plasma. Following an intravenous dose and before exchanging with tissue methylfolate the reduced compounds are altered to a heat stable form of folate, probably pteroylglutamic acid, in the plasma of control subjects. This does not take place in the plasma of patients with untreated pernicious anaemia where the injected folate remains in the reduced state until exchanged with tissue folate.
The Abnormal Haemoglobins in Homozygous α‐Thalassaemia
Authors: Todd D. , Lai M. C. S. , Beaven G. H. , Huehns E. R.
Published: March 2008

Summary The red cells from Chinese stillborn infants with erythroblastosis foetalis due to homozygous α‐thalassaemia contain about 80% Hb‐γ4, the second haemoglobin always present does not contain α‐chains and has the structure Hbγ2X2 identical to Hb‐Portland 1. Hb‐A, Hb‐F, or Hb‐A2 were not detected.
The Thalassaemia Syndromes in Nigeria
Authors: Esan G. J. Folayan
Published: March 2008

Summary The β‐thalassaemia trait was found in 23 out of 3002 random blood donors in an indigenous population of Western Nigerians. The haematological manifestations are described, and the inheritance was studied in selected families. In the same population 52 out of 1151 babies were found to have low levels (1–5.4%) of haemoglobin Bart's at birth. It is suggested that this may be a transient developmental abnormality, rather than a manifestation of α‐thalassaemia.
Inactivation of ‘Arvin’ by Plasma Proteins
Authors: Pitney W. R. , Regoeczi E.
Published: March 2008

Summary The coagulant activity of Arvin is neutralized by incubation with normal human serum. Coagulation experiments, and chromatographic and electrophoretic studies using radioactive Arvin, indicate that Arvin interacts with at least two serum proteins. One of these is α2 macroglobulin and the other may be antithrombin III. Although these proteins inactivate thrombin also, the mechanisms of neutralization of Arvin and thrombin are not identical. In addition, considerable amounts of radio‐active Arvin are trapped in the fibrin mesh when fibrinogen is clotted with Arvin. Serum samples from patients clinically resistant to Arvin showed complexing of Arvin with a γ globulin fraction, confirming the antibody nature of Arvin resistance.
Platelet Glycolytic Enzymes: Effect of Cellular Disruption Procedures on Activity
Authors: Doery J. C. G. , Hirsh J. , Gruchy G. C. de
Published: March 2008

Summary The activities and cellular distribution of the following glycolytic enzymes were determined in human platelets: hexokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, triosephosphate isomerase, glyceraldehyde 3‐phosphate dehydrogenase, 3‐phosphoglycerate kinase, phosphoglyceromutase, enolase, pyruvate kinase, lactate dehydrogenase and glucose 6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase.

The effect of four different methods of cellular disruption on platelet ultrastructure and enzyme activity was determined. Freezing and thawing was found to inactivate phosphofructokinase markedly, and to inactivate hexokinase and glucose‐6‐phosphate dehydrogenase slightly. In addition, glucose‐6‐phosphate dehydrogenase was rapidly inactivated in cell lysates irrespective of the method of lysis. This process, which was considerably greater at room temperature than 4°C, was prevented by addition of 0.2 mM‐NADP to the medium before disruption of the platelets. Spontaneous loss of activity of phosphofructokinase, triosephosphate isomerase and pyruvate kinase in cell lysates was decreased by the presence of the reducing agent, dithiothreitol.

Hexokinase was found in both the soluble and particulate fraction. The proportions of the enzyme distributed between these two fractions depended on the disruption procedure used.
Metabolic and Biosynthetic Features of Lymphocytes from Patients with Diabetes Mellitus: Similarities to Lymphocytes in Chronic Lymphocytic Leukaemia
Authors: Brody Jerome I. , Merlie Katherine
Published: March 2008

Summary This study assayed glucose utilization via the hexose monophosphate (HMP) shunt and Embden‐Meyerhof pathways in lymphocytes from patients with diabetes mellitus (DM) and chronic lymphocytic leukaemia (CLL) employing the quantitative evolution of 14CO2 and production of radioactive glycolytic intermediates from [1‐14C]glucose as respective experimental endpoints. In addition, DNA synthesis, as reflected by [14C]thymidine incorporation by the same cells in tissue culture, was measured. Most diabetic lymphocytes displayed depressed absolute and proportional glucose metabolism through the direct oxidative pathway and also demonstrated decreased incorporation of radioactive thymidine, particularly when the lymphocytes were stimulated by phytohaemagglutinin (PHA). The lymphocytes in chronic lymphocytic leukaemia showed the same abnormalities. Moreover, in all lymphocytes assayed, a correlative, semiquantitative relationship was present between the amount of glucose passing through the HMP pathway, which generates NADPH, and the synthesis of DNA, a process requiring this enzyme for reduction of oxyribonucleotides to deoxyribonucleotides. It is postulated that normal antigenic recognition and satisfactory initiation of the immune responses, as mediated by the lymphocyte, may have a metabolic basis, and that this function appears to be abnormal in most patients with diabetes mellitus in this particular study group.
The Relationship between Serum Iron Levels and Ascorbic Acid Stores in Siderotic Bantu
Authors: Wapnick A. A. , Bothwell T. H. , Seftel H.
Published: March 2008

Summary The concentrations of serum iron and of leucocyte ascorbic acid were measured in 35 adult Bantu subjects and were compared with the marrow gradings of storage iron. Ascorbic acid depletion was almost uniformly present in the 18 subjects with increased iron stores, but was uncommon in those with normal stores. On the other hand, there was no significant correlation between the serum iron levels and the marrow iron gradings.

After therapy for 7 days with ascorbic acid the mean serum iron level rose significantly in the siderotic group but was unchanged in the group with normal stores. At this time there was a highly significant correlation between the levels of serum iron and the marrow iron gradings.

It is concluded that the serum iron can be used as an index of iron overload in the Bantu only after repletion with ascorbic acid.
The Effect of Prostaglandin E1 on Platelet Function in Vitro and in Vivo
Authors: Kinlough‐Rathbone R. L. , Packham M. A. , Mustard J. F.
Published: March 2008

Summary Low concentrations of prostaglandin E1 (PGE1) inhibit ADP‐induced aggregation in pig and rabbit citrated platelet‐rich plasma and in suspensions of washed platelets. Higher concentrations also inhibit the initial change in shape induced by ADP and the release of platelet ATP, ADP and serotonin caused by stimuli such as collagen, thrombin, antigen‐antibody complexes and gamma‐globulin‐coated polystyrene particles. PGE1 is not taken up by platelets and its effects can be removed by resuspending platelets in fresh medium. Immediately following an intra‐arterial injection, ADP‐induced platelet aggregation is suppressed, but after 5 min the response returns to normal. PGE1 inhibits haemostasis in rabbits when given as a continuous infusion. It is concluded that the effect of PGE1 on haemostasis involves inhibition of the release of ADP from platelets exposed to collagen and thrombin, and inhibition of ADP‐induced aggregation.
Enzymatic Diagnosis of Megaloblastic Anaemia
Authors: Winston R. M. , Warburton F. G. , Stott A.
Published: March 2008

Summary A comparison of the lactate dehydrogenase (LDH) isoenzyme pattern found in the red cells from patients with megaloblastic anaemia, with that of normal human red cells, and the red cells from patients with iron deficiency and haemolytic anaemias, has shown that megaloblastic anaemia, whether due to vitamin B12 deficiency, folate deficiency, or a mixed deficiency of both vitamins, causes a characteristic reversal in distribution of the faster moving isoenzymes LDH‐1 and LDH‐2. In normal red cells and those present in other anaemias, LDH‐2 activity is always greater than LDH‐1 activity, but in all cases of megaloblastic anaemias examined, LDH‐1 was consistently greater than LDH‐2 activity. This reversed LDH isoenzyme pattern is also present in the serum in megaloblastic anaemia, and is almost certainly derived from intramedullary destruction of megaloblastic precursor cells, with very little contribution from the circulatory red cells. It is well known that a feature of megaloblastic anaemia is a raised serum LDH activity, and it has been shown that a simple chloroform inhibition test made on either serum showing a raised serum LDH of over 900 units, or on the red cells, will give 2 good indication that this reversed pattern is present.
The Use of Reticulocytes with High Non‐haem Iron Pool for Studies of Regulation of Haem Synthesis*
Authors: Poňka P. , Neuwirt J.
Published: March 2008

Summary One‐hour incubation of reticulocytes with 10−2m isonicotinic acid hydrazide (INH) and transferrin‐bound 59Fe changes the normal distribution of radioiron inside the cell. About 10% of 59Fe is found in haem and 90% is present in the non‐haem iron pool. The accumulated non‐haem radioiron may be utilized for haem synthesis. This is demonstrated by the reincubation of washed reticulocytes with a high non‐haem radioiron pool induced by INH under optimal conditions. The incorporation of radioiron from intracellular non‐haem pool into haem is used as a method for the estimation of the rate of haem synthesis in the presence of various inhibitors. INH reduces haem synthesis from non‐haem iron to a greater extent than that from transferrin iron. On the other hand, haemin, which inhibits the incorporation of 59Fe from transferrin into haem, does not significantly decrease the utilization of intracellular non‐haem iron for haem synthesis. These results are considered as further evidence for the inhibitory effect of haem on the membrane transport of iron. Cells with an artificially increased non‐haem iron pool incorporate more [2‐14C]glycine into haem than normal reticulocytes. These results are in accordance with the possibility that the supply of iron to the critical sites of haem synthesis may be a limiting factor controlling the rate of haem synthesis.
Erythrocyte Glutathione‐Peroxidase Deficiency
Authors: Necheles Thomas F. , Steinberg Martin H. , Cameron Dorothy
Published: March 2008

Summary Glutathione peroxidase deficiency is the most recently described erythrocyte enzyme abnormality. This enzyme occupies a critical position in the pathways leading to the decomposition of peroxides in the erythrocyte. On the basis of our studies of patients with GSH‐P deficiency, it appears that a spectrum of disease quite similar to that found in G‐6‐PD deficiency is present; this includes compensated haemolytic disease, drug‐induced haemolysis and neonatal jaundice.
Hereditary Defect in the Platelet Release Reaction Caused by a Deficiency in the Storage Pool of Platelet Adenine Nucleotides
Authors: Holmsen Holm , Weiss Harvey J.
Published: March 2008

Summary A large family has recently been described in which impaired platelet aggregation was attributed to defective release of the ADP present, although in decreased amounts, in their platelets (Weiss et al, 1969). It was postulated that these patients might lack the storage, or non‐metabolic, pool of ADP which is selectively released from specialized granules during the platelet release reaction and studies on three affected members of this family were undertaken to test this hypothesis. Citrated platelet‐rich plasma (PRP) was incubated with [8‐14C]adenine for 2 hr at 37°C and the specific activity of platelet nucleotides was determined. The release reaction was then induced by shaking the PRP with collagen fibres. The labelling patterns in the patients' platelets were distinctly abnormal. The specific activities of their platelet ADP following incubation with [14C]adenine were 4–6 times those of similarly treated normal platelets and were similar to those obtained in the normal platelets after they had been depleted of their non‐metabolic (unlabelled) ADP by treatment with collagen. The findings are consistent with the hypothesis that the patients' platelets contain a normal amount of metabolically active ADP, but are deficient in the storage pool. Similar conclusions were reached for ATP. Incubation of the patients' platelets with collagen was accompanied by a normal disappearance of radioactive ATP and accumulation of radioactive IMP and hypoxanthine. Thus the abnormality in the platelet release reaction in these patients appears to be the result of a diminished storage pool of nucleotides rather than a block in the pathway which may provide the energy for this reaction.
Successful Immunosuppressive Treatment of Erythroid Aplasia Appearing after Thymectomy
Authors: Safdar Shabbir H. , Krantz Sanford B. , Brown Elmer B.
Published: March 2008

Summary. A unique case of red cell aplasia appearing 2 yr after removal of a thymoma and a transient episode of myasthenic crisis is presented. When the marrow cells of this patient were incubated in vitro a marked increase in haem synthesis occurred, suggesting that the marrow had been freed from an inhibitor of erythroid function. An antibody to erythroblast nuclei was also present. The patient failed to respond to an initial course of immunosuppressive therapy, but after splenectomy he had a second course of immunosuppressive treatment which was followed by a complete haematologic remission. Guidelines for the future therapeutic use of immunosuppressive agents in pure erythroid aplasia are presented.
The Role of Slowly Proliferating Cells in Rat Bone Marrow during. Regeneration following Hydroxyurea
Authors: Bohne F. , Haas R. J. , Fliedner T. M. , Fache I.
Published: March 2008

Summary. Rats were labelled with 3H‐thymidine (3H‐TdR) in utero and for 6 weeks after birth to obtain 100% labelling of all the cells in the animals. 6 weeks after the last 3H‐TdR injection only cytokinetically resting cells were still labelled. In bone marrow these were cells of the bone marrow matrix and a fraction of small bone marrow lymphocytes. At this time the effect of hydroxyurea (HU) on bone marrow and especially on the resting cells of this organ was studied.

Animals which had received 4x 500 mg HU/kg at 6 hr intervals showed a destruction of all proliferating cells of the bone marrow. Regeneration started 4 days after HU‐treatment and was not completed before 10 days afterwards. The resting matrix cells did not change in number or labelling intensity which shows that they were neither destroyed nor stimulated to proliferate during regeneration. In contrast, the resting small bone marrow lymphocytes showed a dilution of labelling intensity, and after an initial increase, a decrease of their number during recovery of bone marrow. At the same time a new class of labelled cells which was identified as undifferentiated blast cells appeared, and later on labelled erythroid and myeloid precursor cells could be observed. The labelling of these cells disappeared c 6 days after HU‐treatment. Animals which received a single injection of the total dose of 2000 mg/HU/kg showed essentially the same effects but a markedly smaller response to the drug.
Splenomegaly and Haematologic Disorders of the Gunn Rat
Authors: Lozzio B. B. , Mcdonald T. P. , Lange R. D. , Cawein M. J. , Chernoff A. I.
Published: March 2008

Summary. Erythrocyte values, leucocyte counts, haemoglobin components and erythropoietin levels were determined in Wistar and Gunn rats. Spleen and bone marrow examinations were also performed. Erythrocyte values and leucocyte counts in Gunn rats were lower than in Wistar rats. Females of both strains of rats showed lower haematocrit values, haemoglobin concentrations, erythrocyte counts, and erythropoietin levels than did the males. Female Gunn rats also had leucopenia when compared with the males. The leucopenia disappeared after castration. The erythrocyte abnormalities were particularly marked in homozygous female Gunn rats which manifested anaemia, shortened erythrocyte survival time and splenomegaly. After splenectomy and/or ovariectomy, the erythrocyte survival time became normal and the anaemia improved. However, ovariectomy alone did not influence the splenomegaly nor the enhanced splenic sequestration of erythrocytes. Microscopic examination of the bone marrow of Gunn rats revealed normal overall cellularity. In contrast, hyperplasia of the white and red pulp was observed in the spleens of Gunn rats of both sexes. These findings suggest that the anaemia of homozygous female Gunn rats is caused by enhanced sequestration of erythrocytes in the spleen and by a possible disturbance of oestrogen metabolism.
A Controlled Trial of Oral Contraceptives in Haemophilia
Authors: Beck Peter , Bloom A. L. , Giddings J. C. , Sweetnam P. M.
Published: March 2008

Summary. A controlled trial of an oral contraceptive in the treatment of haemophilia is reported. No significant change in the frequency or duration of bleeding episodes or in factor‐VIII levels was found. The incidence of side effects was high. It is concluded that oral contraceptives do not appear to be of benefit in the management of haemophilia.
Platelet Volume: Density Relationships in Normal and Acutely Bled Dogs
Authors: Minter F. M. , Ingram M.
Published: March 2008

Summary.

The relationship between platelet volume and platelet density was studied in normal dogs and in dogs subjected to acute blood loss.

Frequency distribution histograms of platelet densities were obtained by centrifuging diluted whole blood over a series of 13 silicone solutions varying in specific gravity from 1.007 to 1.065 and determining the percentage of platelets that remained in the supernatants above the silicone after centrifugation for 2 min at 9500 g. Frequency distribution histograms of platelet volumes were obtained using the Model B Coulter Counter with the Coulter Model H particle size analyser.

Platelets of normal dogs have a skewed distribution of densities. The mean density is approximately 1.020 but the plateau region on the cumulative distribution of platelet densities is not reached until specific gravity 1.045‐1.050. Mean platelet volume increases as density increases.

When platelet production was increased following acute blood loss, both mean density and mean volume increased abruptly, but the change in density histograms was more prolonged as well as more striking than change in mean density. Results of serial observations suggest that the large dense platelets produced following acute blood loss represent an aberrant population and that these platelets do not decrease in volume as they age.
A New Technique for the Quantitative Estimation of Fibrinolysis using In Vivo [125I]Fibrinogen
Authors: Hickman J. A.
Published: March 2008

Summary.

A technique for the quantitative measurement of the fibrinolytic activity of blood is described, based on the rate of release of radioactivity in vitro from clotted blood obtained from patients previously receiving [125I]fibrinogen. The accuracy of the technique was assessed by comparison of the release of radioactivity with the appearance of fibrin degradation products, by observation of the effects of fibrinolytic inhibitors and by comparison of the initial fibrin content of the clot with the measurement of radioactivity released after total lysis.

The measurement of fibrinolysis with this technique correlated well with the dilute blood clot lysis time in samples with a normal fibrinogen concentration, but the correlation was poor when the fibrinogen concentration was elevated. Since the measurement of fibrinolysis by this new technique is likely to be largely unaffected by the fibrinogen concentration, it is suggested that this technique is of particular value when the fibrinogen concentration is outside the normal range and, further, will allow significant comparison of fibrinolytic activity between blood samples of differing fibrinogen concentration.
Studies on the Regulation of Granulopoiesis
Authors: Morley A. , Monette F. C. , Rizzoli V. , Howard D. , Stohlman F.
Published: March 2008

Summary.

Tritiated thymidine autoradiography was used to study the control of granulocyte production and release using the irradiated leg shielded mouse as an experimental model. Neutropenia resulted in a shortening of 24–36 hr in the mean transit time through the non‐proliferating granulocyte compartment. There was little difference between neutropenic and control animals in labelling indices of the cells in the proliferative granulocyte compartments, which suggests that the granulocytic hyperplasia observed in the neutropenic mice was predominantly due to differentiation of morphologically unrecognizable precursor cells rather than increased proliferation of morphologically recognizable cells. The persistence of a labelling index of approximately 60% in the myeloblast‐promyelocyte compartment 24 hr after injection suggests that these precursor cells were rapidly proliferating.
Iodine‐Labelled Fibrinogen: A Review
Authors: Regoeczi E.
Published: March 2008

Clinical interest in labelled fibrinogen outgrew the existing narrow channels of supply some time ago, and to meet the continuously increasing demand, possibilities of establishing a central source for this material are now being seriously considered in the United Kingdom. If, as it is widely hoped, these plans succeed, many new users will find themselves confronted with a variety of questions as how to make the best use of radioactive fibrinogen. The present article was conceived first of all with those in mind who lack personal experience with this protein. Its purpose is not so much to describe techniques in detail, but more to elucidate the underlying physicochemical principles.
Prothrombal: A New Concentrate of Human Prothrombin Complex for Clinical Use
Authors: Bruning P. F. , Loeliger E. A.
Published: March 2008

Summary. There is a great need for a concentrate containing coagulation factors II, VII, IX and X, suitable for the prevention or treatment of haemorrhage due to a deficiency of these factors. This paper describes a routine method for the production of such a concentrate (called Prothrombal), the properties of the material and its clinical use. The method has the following advantages: simplicity, suitability for small‐scale application in any blood bank, and the use of standard human ACD plasma as starting material, the other components of the blood remaining available for clinical use. In the adsorption‐elution procedure aluminum hydroxide was a suitable adsorbent.

Administration of Prothrombal to patients was tolerated very well. Safe haemostasis was obtained in a patient with severe haemophilia B using Prothrombal to cover several extensive orthopaedic operations. The recovery in vivo of coagulation factor activity was satisfactory and reliable and was assessed for factor IX at about 25%. The results of giving Prothrombal on nine occasions to patients with a severe deficiency of factor IX (haemophilia B), factor II, factor VII, or a combination of factors II, VII, IX and X, are described and discussed.
Studies on Adrenaline‐induced Leucocytosis in Normal Man
Authors: French E. B. , Steel C. M. , Aitchison W. R. C.
Published: March 2008

Summary. The influence of an α and β blocking agent (phenoxybenzamine and propranolol) on the leucocyte response to adrenaline has been studied in three healthy male subjects. Blood pressure and pulse rate measurements established that effective α and β blockade of the cardiovascular effects of adrenaline was achieved. There appeared to be a biphasic cardiovascular effect within the first hour after adrenaline injection. Neither agent produced any marked alteration in the pattern of adrenaline‐induced leucocytosis, but when given in combination the subsequent white cell response to adrenaline was substantially diminished. Our findings do not substantiate the view that the leucocytosis provoked by adrenaline results from mobilization of intravascular marginated cells as a direct consequence of alterations in blood flow. The receptors involved appear to be equally sensitive to the α and the β properties of adrenaline, without discriminating between them.
Folate Analogues in Normal Mixed Diets
Authors: Perry Janet
Published: March 2008

Summary. The folate present in a mixed Western type diet consisted largely of reduced methyl forms (60%), all but 4% of these being polyglutamates of varying chain length. Formyl folates (30%), principally 5, formyltetrahydrofolate polyglutamates, comprised the next largest group, while pteroyglutamic acid itself contributed only 1.5% of the total folate activity, a figure well within the range of experimental error of the techniques employed.
Clonal Origin of the Philadelphia Chromosome and Chronic Myeloid Leukaemia: Evidence from a Sex Chromosome Mosaic
Authors: Fitzgerald P. H. , Pickering Alison F. , Eiby Jenny R.
Published: March 2008

Summary. A male patient aged 69 yr with chronic myeloid leukaemia was a constitutional XY/XXY sex chromosomal mosaic as indicated by a positive sex chromatin in neutrophils and cytogenetic studies of lymphocytes cultured with phytohaemagglutinin. He was of normal phenotype and intelligence. In a bone‐marrow aspirate taken when the patient was in the acute phase of leukaemia the 46, XY cell line carried the Ph1 chromosome, whereas the 47, XXY cell line did not. Two further cell lines were considered to have been derived by clonal evolution of the 46,XY,Ph1‐positive line, although one of them possessed ambiguous features. The results support a clonal origin of the Ph1 chromosome, and presumably also of chronic myeloid leukaemia. An interesting feature of the bone marrow was that the 46, XY, Ph1‐positive cell line had apparently replaced the normal 46, XY cells but not the 47, XXY cells.
Haemoglobin, Vitamin B12 and Folate Levels in the Elderly
Authors: Elwood P. C. , Shinton N. K. , Wilson C. I. D. , Sweetnam P. , Frazer A. C.
Published: March 2008

Summary. Community‐based surveys of a representative sample of 533 subjects aged 65 yr and over were conducted in a mining valley and a seaside town in South Wales. Haemoglobin level, PCV, serum vitamin B12, plasma and red‐cell folate were measured and several simple tests of learing and memory were applied. The results give no evidence to suggest that anaemia is common and although low levels of vitamin B12 and folate occurred no evidence of an associated impairment of health was detected.
Rapid Identification of Hepatitis Associated Antigen and Antibody by Counter‐Immunoelectroosmophoresis
Authors: Das P. C. , Hopkins R. , Cash J. D. , Cumming R. A.
Published: March 2008

Summary A modification of the counter‐immunoelectroosmophoresis method is described which will allow rapid identification of hepatitis associated antigen and antibody within 2 hr by producing a reaction of identity with known reference materials. The specificity of the reaction is established by the demonstration of non‐identity and partial identity by this technique.