bluuebunny/crossref_metadata_2025 huggingface dataset:
Coagulation Studies in Patients with Acute Infectious Hepatitis
Authors: Gallus A. S. , Lucas C. R. , Hirsh J.
Published: March 2008

Summary

Coagulation studies were performed on 104 hospital inpatients with acute infectious hepatitis. Patients with clinical evidence of liver failure were studied separately from those without liver failure.

A coagulation defect was found in 57 of the 78 patients without liver failure. This consisted of a prolonged prothrombin time and reduced levels of factors V, VII and X, and plasminogen. The defect was mild in most patients and was not associated with bleeding. A severe coagulation defect was found in all 26 patients with liver failure. Factors II, V, VII and X were markedly reduced. Plasminogen was reduced in all patients, and a low plasma fibrinogen concentration and thrombo‐cytopenia were found in half. One third of the patients studied showed an increase in serum fibrin/ fibrinogen degradation products. It is suggested that in some of these patients disseminated intravascular thrombosis contributed to the coagulation defect. Two patients had evidence of increased fibrinolytic activity.

Bleeding occurred in 15 patients with liver failure and required treatment in 10. Fifteen patients with liver failure died. Nine patients with liver failure were treated with exchange transfusions during which a significant improvement of the prothrombin time and a slight reduction in platelet count was observed. Bleeding stopped during exchange transfusions in six of eight patients. It is possible that the improvement of the coagulation defect during exchange transfusions contributed to improved haemostasis.
A Homozygote for the HbGγ Type of Foetal Haemoglobin in India: A Study of Two Indian and Four Negro Families
Authors: Sukumaran P. K. , Huisman T. H. J. , Schroeder W. A. , McCurdy Paul R. , Freehafer John T. , Bouver Nicole , Shelton J. Roger , Shelton Joan Balog , Apell Gerald
Published: March 2008

Summary. The haemoglobin of a 9‐yr‐old boy from the area of Bombay has only haemoglobin F. The γ‐chains of this haemoglobin F are solely of Gγ type, and the child is considered to be a homozygote for hereditary persistence of foetal haemoglobin of the Gγ type. The same kind of haemoglobin F is also present in a second Indian family and in four American Negro families. One Negro family has an appreciably lower percentage of haemoglobin F in heterozygotes than the other five families. In some of the families certain individuals also have haemoglobin E or haemoglobin S in trans to the other condition and haemoglobin A is absent. Although it has been concluded that the hereditary persistence of foetal haemoglobin is present the condition is not expressed uniformly in all these families. Some of them have certain characteristics of F‐thalassaemia. It is possible that two conditions are, in reality, represented: perhaps some families have the hereditary persistence of foetal haemoglobin and others have F‐thalassaemia.
Quantitative Studies on the Release of Platelet Fibrinogen by Thrombin
Authors: Keenan J. P. , Solum N. O.
Published: March 2008

Summary. The effects of varying concentrations of thrombin on the release of fibrinogen from washed human platelets have been examined. A concentration of thrombin which gave adequate release and recovery levels of fibrinogen was used to study the time dependence of release. The small amount of thrombin required and the rapidity of the reaction indicates that the transfer of fibrinogen from intracellular to extracellular phase is due to an active release process.
The Effects of Certain Blood‐Grouping Sera on the Red‐Cell Surface as Seen by the Scanning Electron Microscope
Authors: Longster G. H. , Tovey L. A. D.
Published: March 2008

Summary. The effect of various blood‐grouping antisera on the surface of red cells either possessing or lacking the appropriate antigens were observed using the scanning electron microscope. Certain of these sera produced non‐specific effects on the cell surface and possible causes of these changes were investigated. It was shown that slight contamination of grouping sera with bacteria or chemicals can result in the sera producing similar effects on the red‐cell morphology. The changes produced by proteolytic enzymes used in blood‐group serology on the red‐cell surface were also examined. Each enzyme was shown to have a different effect on red‐cell morphology, but as all the enzymes apparently have the same serological action, it is concluded that the effect of these enzymes on red‐cell morphology and their serological action are not related.
A Direct Method of Determining Red Cell Lifespan Using Radioiron: An Application of the Occupancy Principle
Authors: Dagg J. H. , Horton P. W. , Orr J. S. , Shimmins J.
Published: March 2008

Summary. Existing methods of measuring directly the lifespan of red cells are inconvenient or technically difficult. In the present study, plasma iron clearance and red cell utilization curves were followed after the intravenous injection of radioiron as for routine ferrokinetic measurements; chemical determinations of stable iron in plasma and red cells were also made. The mean red cell lifespan and the flow rate of iron into erythropoiesis were derived from these data by applying the occupancy principle (Orr & Gillespie, 1968).

Using this method, the red cell lifespan in two normal subjects was found to be 104 and 115 days respectively. Five patients with various haematological disorders were also studied; in one of these a normal lifespan of 107 days was obtained, and in four others there were shortened lifespans ranging from 25.8 to 49.6 days. In five of the subjects, the survival of in vitro51Cr‐labelled red cells was also determined. A good correlation was obtained between the red cell lifespan measured by the radio‐iron occupancy method, and estimates of red cell survival using 51Cr‐labelled red cells (P < 0.05). The plasma iron flow rate derived from radioiron occupancy, and the conventional plasma iron transport rate, were also calculated and these are compared in relation to the clinical data.
Gm Types and Antibodies in Multitransfused Haemophiliacs
Authors: Kernoff P. B. A. , Bowell P. J.
Published: March 2008

Summary. The frequency of Gm and Inv factors in a group of 100 multitransfused patients with haemophilia or Christmas disease was found to be similar to that in the normal population. 14 patients were found to have Gm specific antibodies, nine to have non‐specific antibodies and 20 to have a positive latex test for rheumatoid arthritis. 60% of the children aged less than 10 yr had Gm specific antibodies. Only a minority of the patients with antibodies had a positive latex test. Neither specific nor non‐specific antibodies were found in the 17 patients who had been most heavily transfused, and it is suggested that these patients might have developed immune tolerance. Cryoprecipitate and factor‐VIII concentrate contain Gm activity and are probably capable of provoking isoimmunization. The occurrence of Gm specific or non‐specific antibodies was not related to a history of severe transfusion reactions.
Biochemical Changes in the Platelet Energy Transferring System during Concomitant Action of Cephalin and Serotonin
Authors: Pǎuşescu Exacustodian , Chirvasie Rodica
Published: March 2008

Summary. The paper concerns the investigations of the changes in the concentrations of endogenous nicotinamide adenine nucleotides (NAD+, NADH, NADP+ and NADPH) and reduced glutathione (GSH) during the incubation of canine blood platelets with cephalin and/or serotonin. Activity of NADH‐dependent glutathione reductase in this instance was also determined. These investigations have revealed the following findings: (1) platelets maintained constant levels of nicotinamide adenine nucleotides and GSH during incubation in Hanks’ solution; (2) 5‐HT induced a marked immediate increase in the amounts of NAD+, NADH and GSH and a moderate reduction in the amount of NADPH; no significant change was seen in the amount of NADP+ or in the activity of NADH‐dependent glutathione reductase; (3) cephalin had similar effects on NAD+, NADH and GSH, but to a lesser extent; in addition, it induced a significant decrease in the amounts of NADP+ and NADPH and a marked activation of NADH‐dependent glutathione reductase; (4) cephalin in addition to 5‐HT amplified these modifications, except for GSH increase (despite an important cephalin‐induced activation of NADH‐dependent glutathione reductase) and produced a marked fall of NADP+ and NADPH. These findings suggest that: (a) platelet nicotinamide adenine nucleotides and GSH exhibit a high sensitivity to these different substances (a phosphatide and an amine) with implications for platelet function and aggregation; (b) cephalin and 5‐HT, despite their different chemical nature, act somewhat similarly on these compounds.
Evidence that Lithium Induces Human Granulocyte Proliferation: Elevated Serum Vitamin B12 Binding Capacity in Vivo and Granulocyte Colony Proliferation in Vitro
Authors: Tisman Glenn , Herbert Victor , Rosenblatt Seymour
Published: March 2008

Summary. Concentrations of lithium similar to those present in the blood of patients receiving lithium carbonate therapy for manic‐depressive psychosis cause leucocytosis in vivo and proliferation of human granulocyte colonies in vitro. These findings, plus the finding of elevated unsaturated vitamin B12 binding capacity in patients with granulocytosis induced by lithium carbonate, suggests that such therapy produces a true increase in the body granulocyte pool. The possible value of lithium therapy in neutropenic states in man requires exploration.
A Comparison of the Cobalt, Methylene Blue, Zinc, Arsenite and Amino Triazole Effect on Erythropoietin Production
Authors: Thorling E. B.
Published: March 2008

Summary. The possible mechanisms of action of cobalt in stimulating erythropoietin production are considered.

It is demonstrated that although arsenite shares some of its biochemical effects with cobalt, it does not stimulate the production of erythropoietin. It has been claimed previously that methylene blue could prevent the development of erythrocytosis after cobalt. In the present series of experiments, however, methylene blue did not affect the production of erythropoietin after injection of cobalt to rabbits.
Skin Window Macrophages in Malignant Lymphomas
Authors: Ghosh M. L. , Hudson G. , Blackburn E. K.
Published: March 2008

Summary. A modified skin window technique has been used to study macrophages in normal subjects and in patients with Hodgkin's disease and lymphoreticulo‐sarcoma. The cellularity was similar in all cases at 48 hr with over 90% of the cells being macrophages. In malignant lymphoma there was a significant decrease in the number of cytoplasmic inclusions in the macrophages. The results appear consistent with depression of phagocytic activity of skin window macrophages and a further depression by active treatment with chemotherapy or radiotherapy. In the sarcoma patients, significantly more multinucleated forms were present and the maximum number of nuclei seen in a single cell was higher. Macrophage mitosis was noted in a single case in this group.
The Clinical and Haematological Findings in Children Inheriting Two Types of Thalassaemia: High‐A2 Type β‐Thalassaemia, and High‐F Type or δβ‐Thalassaemia
Authors: Kattamis C. , Metaxotou‐Mavromati Anna , Karamboula Katerina , Nasika Evangelia , Lehmann H.
Published: March 2008

Summary. Eleven children who are double heterozygotes for β‐ and δβ‐thalassaemia are described. Of their parents one was always heterozygous for β‐(A2) thalassaemia (increased Hb A2), and the other for the high F variant or δβ‐thalassaemia (increased Hb F). The clinical syndrome resulting from the combination of β‐ and δβ‐thalassaemia shows some heterogeneity, but in general is of intermediate severity. Red cell abnormalities were considerable, Hb F was very high (mean 70.3 ± 12.6%), Hb A2 was low or normal (mean 2.36 ± 1.52%), and Hb A was absent in five patients. Hb F was nearly homogeneously distributed in the red cells of most patients. These findings are explained as the outcome of a mutation which suppresses δ‐ and β ‐chain synthesis which is associated with a genetically determined increased production of γ‐ chains.
Renal Mechanisms Underlying Cyclic AMP Action on Erythropoiesis
Authors: Peschle Cesare , Rappaport Ira A. , D'Avanzo Antonio , Russolillo Silvia , Marone Gianni , Condorelli Mario
Published: March 2008

Summary. Dibutyryl cyclic AMP (dbc‐AMP) was injected into ex‐hypoxic polycythaemic mice either alone or with anti‐erythropoietin (anti‐Ep) serum. Anti‐Ep totally abolishes the wave of erythropoiesis evoked by dbc‐AMP. These results might indicate either that the action of this agent is totally Ep‐dependent, or that a residual amount of endogenous Ep is necessary to allow dbc‐AMP to exert a direct effect at the marrow level. The latter mechanism, however, is precluded by experiments indicating that administration of moderate amounts of anti‐Ep, although abolishing totally the erythroid response to dbc‐AMP, do not induce complete suppression of endogenous Ep activity and erythropoiesis. Furthermore, a significant rise of Ep plasma levels is observed in rats receiving dbc‐AMP. Since this agent does not apparently modify the kinetics of endogenous Ep, it is postulated that dbc‐AMP induces a rise in Ep production. This phenomenon, although unmodified in ureter‐ligated animals, is completely abolished by bilateral nephrectomy. It is therefore concluded that dbc‐AMP induces in vivo a stimulatory effect on erythropoiesis via increased production of Ep, via a renal mechanism possibly represented by elevated levels of the renal erythropoietic factor.
Preparation and Infusion of Cryoprecipitate from Exercised Donors
Authors: van Gastel C. , Sixma J. J. , Borst‐Eilers Els , Leautaud Marlène , Moes Mieke , van der Plas P. M. , Bouma B. N. , Sybesma J. Ph.
Published: March 2008

Summary. Factor‐VIII enriched cryoprecipitate was prepared by exercising donors on a bicycle ergometer. The mean increase in the activity of factor VIII was about 40%. The effect in vivo of post‐exercise cryoprecipitate was studied in patients with haemophilia A. The increment of factor VIII was only perceptible during the first hours after transfusion. This was due to a more rapid disappearance of factor VIII from the circulation, as was apparent by a shortened half‐survival time of the first phase of the biphasic disappearance curve.
The Availability of Food Folate in Man
Authors: Tamura T. , Stokstad E. L. R.
Published: March 2008

Summary. The availability of five different folate derivatives: tetrahydropteroylglutamate (H4PteGlu), 5‐formyltetrahydropteroylglutamate (5‐CHO‐H4PteGlu), 5‐methyltetrahydropteroylglutamate (5‐CH3 ‐H4PteGlu), pteroyltriglutamate (PteGlu3) and pteroylheptaglutamate (PteGlu7) and folates in 12 natural food items: orange juice, romaine lettuce, egg yolk, banana, cooked lima beans (dry and frozen), liver, brewer's yeast, cabbage (raw and cooked), defatted soybean, and wheat germ were measured in human subjects. The method used for this study was based on the measurement of urinary excretion of folate by microbiological assay using Lactobacillus casei (L. casei). Each subject was maintained in a ‘folate‐saturated’ condition by oral administration of 2.0 mg of pure pteroylmonoglutamate (PteGlu) on alternate days and a response curve relating folate intake with urinary folate excretion was established. Urinary folate excretion following administration of synthetic folate derivatives and food samples containing microbiologically assayed quantities of folates were measured and the folates which had been absorbed were estimated by reference to the response curve previously established with PteGlu. We have considered this to be an index of the ‘availability’ of synthetic folates and/or naturally occurring folates in foods. The results indicated that pure synthetic folate derivatives are almost as available as PteGlu. Among the 12 food items, banana, lima beans, liver and bewer's yeast contained relatively highly available folates. Folate availability was poor in orange juice, romaine lettuce, egg yolk, cabbage, defatted soybean and wheat germ.
The Attachment of Heinz Bodies to the Red Cell Membrane
Authors: Winterbourn Christine C. , Carrell R. W.
Published: March 2008

Summary. The binding between Heinz bodies or heat‐precipitated haemoglobin and the red cell membrane was investigated. Ghosts containing Heinz bodies prepared from red cells containing Hb Christchurch and ghosts bound to heat‐precipitated Hb A were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Using this technique, which separated the membrane and Heinz body proteins according to size, no protein bands corresponding to derivatives of haemoglobin covalently bound to a ghost protein were detected. Binding between red cell ghosts and heat‐precipitated Hb A was also studied by density gradient ultracentrifugation, which separated ghosts bound to haemoglobin from pure ghosts and pure heat precipitate. Sulphydryl reducing and blocking agents were found to have no effect on the attachment of the insoluble haemoglobin to the ghosts, and reduction of electrostatic interactions in 2 m‐NaCl was also ineffective.

It is concluded that covalent bonding, and in particular disulphide bonding, is not involved in the attachment of Heinz bodics to the red cell membrane. Hydrophobic bonding is suggested as the likely alternative.
Depression of Bone Marrow Delta‐Aminolaevulic Acid Synthetase Activity in Erythroleukaemia
Authors: Tanaka Masao , Hotta Tomomitsu , Yamada Hideo
Published: March 2008

Summary. Haem synthesis was studied in three patients with erythroleukaemia. Defective synthesis was demonstrated in all cases by a markedly lowered bone marrow δ‐aminolaevulic acid synthetase activity and diminished [14C]glycine and [4C]δ‐aminolaevulic acid incorporation rates into haem. These abnormalities of haem synthesis were improved by blood transfusion.
Studies on the Transcobalamins
Authors: England J. M. , Clarke H. G. M. , Down M. C. , Chanarin I.
Published: March 2008

Summary. Vitamin B12 absorbed from the gut is transported on all the vitamin B12 binding proteins (transcobalamins) and not primarily on Transcobalamin II. Absorbed vitamin B12 can still be detected on the vitamin B12 binding proteins after 10 days suggesting that the very rapid plasma clearance of the TCII‐vitamin B12 complex previously reported was probably due to damage to TCII prior to re‐injection.

Vitamin B12 binder III is part of Transcobalamin I complex showing immunological identity with other binders in tissue fluids (R binders). Heparin given in vivo or in vitro prevented separation of Binder III from TCI and this effect was neutralized by protamine.
Tuberculosis and Blood Disorders
Authors: Coburn R. J. , England J. M. , Samson D. M. , Walford D. M. , Blowers R. , Chanarin I. , Levi A. J. , Slavin G.
Published: March 2008

Summary. Active tuberculous infection was present in 4.6% of patients with haematological diseases as compared to 0.2% of other patients admitted over a similar period of time. There was no evidence either in the literature or in these cases that tuberculosis gave rise to an unusual leukaemoid response. It was more likely that the blood disorder (leukaemia, marrow failure or vitamin B12 deficiency) resulted in loss or diminution of the normal immune response and that this permitted reactivation of an old tuberculous lesion or in a new opportunistic infection.
Characterization of Developing Adult Mammalian Erythroid Cells Separated by Velocity Sedimentation
Authors: Denton M. J. , Arnstein H. R. V.
Published: March 2008

Summary.

By virtue of their different sedimentation rates at unit gravity, different classes of erythroblast have been separated from the bone marrow of the anaemic rabbit. Each class of erythroblast has been characterized by morphological and biochemical criteria. The classes thus characterized form a series of cell types leading from the large immature erythroblast to the marrow reticulocyte. The fractionation procedure permits complete separation between erythroblasts which synthesize RNA and those which are no longer active in RNA synthesis.
The Clinical Features of Sickle‐Cell/β Thalassaemia in Jamaica
Authors: Serjeant G. R. , Ashcroft M. T. , Serjeant B. E. , Milner P. F.
Published: March 2008

Summary.

The clinical and haematological features of 56 Jamaican patients with sickle‐cell /β‐thalassaemia (S/Thal) are reviewed. The two types of S/Thal (with and without Hb A) had distinctive haematological and clinical characteristics. In general, the non‐Hb‐A type had evidence of lower haemoglobin levels, a more rapid haemolytic rate, and a more severe clinical course than the Hb‐A type.
The Treatment of Patients who have Factor‐VIII Antibodies
Authors: Rizza C. R. , Biggs Rosemary
Published: March 2008

Summary.

A new method of measuring factor‐VIII antibodies is described. The application of this method in the study and treatment of patients who have antibodies to factor VIII is discussed.
Red Cell Survival Studies in Patients with Unstable Haemoglobin Disorders
Authors: Bentley S. A. , Lewis S. M. , White J. M.
Published: March 2008

Summary. The survival of mature red cells in one patient with Haemoglobin Hammersmith and in two patients with Haemoglobin Köln (one unsplenectomized) has been measured simultaneously using 51Cr and DF32P. The results indicate that either isotope label gives the same value for mean red cell lifespan. This is discussed in terms of the mechanism of red cell destruction in patients with unstable haemoglobin disorders.
The Effect of Elution on the Reactivity of Antibodies of the ABO System, Including Cross‐reacting Antibodies, as Demonstrated by Use of Red Cells of Various Subgroups of A, and Group B
Authors: Dodd B. E. , Lincoln P. J.
Published: March 2008

Summary. The combining capacity of various A antigens with the corresponding antibodies was investigated. A modified Landsteiner elution technique was the principal method used and eluates were made at various temperatures ranging from 22 to 65° C. The ability of the eluates to agglutinate Ax cells was inversely proportional to the amount of A activity possessed by the cells used for elution. For example, titration values against Ax cells of eluates from A1, A2, A3, Am and Ax cells were 0, 4, 8, 16 and 32 with each type of cell respectively. The highest titre (128) against Ax cells was found in an eluate from B cells, this reaction being entirely due to cross‐reacting antibodies, i.e. antibodies agglutinating both A and B cells, present in the eluate. The results suggest differences in the nature of the combination between anti‐A and the A antigen present in the various A subgroups, and in the combining capacity of the cross‐reacting antibody with cells of group A compared with B. The possibility that alteration of the configuration of the antibody molecules through elution may be responsible for some of the observed results, is discussed.
Acquired Factor‐IX Inhibitor in a Nonhaemophilic Patient with Autoimmune Disease*
Authors: Largo R. , Sigg P. , von Felten A. , Straub P. W.
Published: March 2008

Summary. An acquired inhibitor directed against factor IX was demonstrated in the blood of a patient with autoimmune disease. The inhibitor could be removed from the patient's plasma using PPSB or specific antisera insolubilized by polymerization. It could be recovered from these immunoadsorbents and characterized as an IgG‐immunoglobulin using specific antisera.
‘Autosomal Haemophilia’: A Variant of von Willebrand's disease
Authors: Veltkamp J. J. , van Tilburg N. H.
Published: March 2008

Summary. A patient representing the family with autosomal haemophilia A described elsewhere (Hensen et al, 1965) shows ‘de novo synthesis’ of factor VIII after transfusion with normal and haemophilic cryoprecipitate. Several patients in the family have very low factor VIII‐related antigen levels. These findings are consistent with a diagnosis of von Willebrand's disease but the normal or nearly normal bleeding times and the similarity in factor‐VIII activity levels in all the members of this family are unusual in this condition.

Thus far, three loci involved in factor‐VIII synthesis have been postulated. The locus most frequently occupied by a mutant gene is on the X chromosome and results in haemophilia A, a trait long known to be sex‐linked (for instance in ancient Jewish and Arabian literature; see review by Ikkala, 1960). The effects of mutation in an autosomal locus were first described by von Willebrand (1926, 1931). A third locus involved in factor‐VIII synthesis was postulated by Hensen et al (1965). The effects of this mutant gene have been particularly difficult to study because the features that led to postulate its existence have been reported in only one family. This report deals with the evidence that this condition, originally described as ‘autosomal haemophilia’, is only a variant of von Willebrand's disease.
In Vitro Modifications of Red Cell Acetylcholinesterase Activity
Authors: Herz F. , Kaplan E.
Published: March 2008

Summary. This review summarizes the present knowledge with respect to in vitro modifications of human red cell acetylcholinesterase (ACHE). While the functions of this enzyme in the red cell remain obscure, its physico‐chemical and biochemical properties as well as its position within the red cell membrane are better understood. Of the enzymes recognized in the membrane of the human red cell, alterations in activity associated with pathological conditions are found regularly only with ACHE. Thus, ACHE activity is reduced in paroxysmal nocturnal haemoglobinuria, ABO haemolytic disease of the newborn and occasionally in autoimmune haemolytic anaemia. This review provides a summary of the work from many laboratories concerning the action of exogenous substances on the red cell with special emphasis on the in vitro production of ACHE‐deficient red cells and its relation to other membrane alterations. These substances include proteolytic enzymes, antibiotics, sulphydryl compounds, tannic acid, aldehydes, fluorinated dinitrobenzenes and tetraphenylboron.
Urinary Excretion of Short‐Chain Fatty Acids in Latent Pernicious Anaemia and Related Conditions
Authors: Williams D. L. , Spray G. H.
Published: March 2008

Summary. In 20 hospital control subjects the daily urinary excretion of methylmalonic acid (MMA) was between 17 and 56 mg, of acetic acid between 6.6 and 220 mg, and of propionic acid between o and 14 mg. Thirty‐one patients with latent pernicious anaemia excreted between 6 and 100 mg MMA, 3.5–130 mg acetic acid and o‐11 mg propionic acid per day. The excretion of MMA in latent pernicious anaemia was unaffected by doses of valine given by mouth, whereas in all 17 subjects with megaloblastic anaemia due to vitamin B12 deficiency, valine increased the excretion. Without valine, however, 20% of vitamin B12‐deficient patients excreted normal amounts of MMA, as did every patient with folate deficiency. The mean amounts of acetic and propionic acids excreted by the various groups were not significantly different from the results for control subjects.
Corticosteroid Therapy in Felty's Syndrome and its Effect on Hypersplenic Rats
Authors: Robertson J. H. , Crozier E. H. , Hollinger Mary
Published: March 2008

Summary. A patient with Felty's syndrome was treated with prednisone with resulting improvement in anaemia. This was due to a decrease in an expanded plasma volume; it occurred rapidly and was not associated with any apparent change in the size of the spleen.

A contrasting form of hypersplenism was induced in rats, splenic enlargement being due to storage of methylcellulose in the organ. Corticosteroid treatment of these animals produced haematological changes similar to those in the patient although they occurred much more abruptly. The nature of the changes brought about by steroid therapy was investigated by isotope studies.

It is concluded that corticosteroid therapy can improve the anaemia of hypersplenism by reducing an expanded plasma volume and that this effect may occur without parallel improvement in the other haematological changes of hypersplenism. The decrease in plasma volume does not appear to result from a steroid‐induced lymphoid involution and a reduction in splenic size. Instead, it seems likely that this treatment affects an intermediary mechanism by which plasma volume is increased in hypersplenic states. The possible nature of this is discussed.
Plasma Fibrinogen and its Fragments during Streptokinase Treatment
Authors: Gaffney P. J. , Chesterman C. N. , Allington M. J.
Published: March 2008

Summary. Using immunoprecipitation and sodium dodecyl sulphate (SDS) acrylamide gel electrophoresis, plasma samples were studied from three patients during prolonged streptokinase (SK) infusion (600 000 iu initial dose and 100 000 iu/hr for 3–5 days). During infusion, plasma fibrinogen was degraded to a variety of high molecular weight (mol wt) products, the clottable material from which contained β chains, γ chain dimers, and α chain fragments of about 25 000 mol wt (designation for fibrin sub‐units of the nomenclature subcommittee of the International Committee for Thrombosis and Haemostasis, meeting in Washington, D.C., 1967). The α‐chain polymers (αx) which were present in the fibrin clots before and 14–18 hr after SK treatment, were not present in clots prepared from plasma obtained during SK infusion.

Clottable fibrinogen and serum fibrinogen/fibrin degradation products (FDP) were measured and semi‐quantitative estimates of the high mol wt fragments were obtained. After infusion with SK there was a rapid drop in clottable fibrinogen and a rise in some large mol wt fragments. The variable levels of serum FDPs observed and the nearly complete absence of the fibrin α chain polymers (αx) are discussed in relation to the presence of the different types of the high mol wt fragments. The inability of these fibrinogen fragments to clot efficiently or to form α‐chain crosslinks catalysed by factor XIII offers a partial explanation of the haemostatic defect associated with SK infusion.
A Variant of Factor VIII Related Antigen
Authors: Kernoff P. B. A. , Gruson R. , Rizza C. R.
Published: March 2008

Summary. The factor VIII related antigen in a patient with von Willebrand's disease gave qualitatively different precipitation peaks on electroimmunoassay and showed a faster anodal migration on crossed immunoelectrophoresis than antigen obtained from normal subjects, haemophiliacs and other patients with von Willebrand's disease. In addition, less of the patient's antigen could be recovered from ethanol precipitates and cryoprecipitates of plasma. It is suggested that the patient's plasma contained an atypical form of factor VIII related antigen.
Haemoglobin Inkster (α285 aspartic acid → valineβ2) Coexisting with β‐Thalassaemia in a Caucasian Family
Authors: Reed Robert E. , Winter William P. , Rucknagel Donald L.
Published: March 2008

Summary. Haemoglobin Inkster, a new α‐chain variant, was discovered in a family which also had the gene for β‐thalassaemia. The amino acid abnormality was in αTp‐9 which contains 29 amino‐acid residues. Structural studies were facilitated by cleavage of the abnormal α‐chains with cyanogen bromide followed by tryptic digestion. The substitution was shown to be valine for aspartic acid at position 85 in the α‐chain. Affected individuals had no haematological abnormalities. Individuals with both β‐thalassaemia and Hb Inkster had slightly lower percentages of Hb Inkster than those found in persons heterozygous for the Hb Inkster gene alone. ‘Interaction’ between thalassaemia and variant haemoglobin genes involving different haemoglobin loci has been reported in another family with β‐thalassaemia and an α‐chain haemoglobin mutant, as well as in the converse situation of coexisting β‐thalassemia and a β‐chain haemoglobin mutant. This decrease in the mutant haemoglobin percentage differs from the more common ‘interaction’ of thalassaemia and mutant haemoglobin genes involving the same haemoglobin locus, in which the mutant haemoglobin percentage is increased. The mechanism for the ‘interaction’ is unknown, but the presence of an unusually low percentage of a haemoglobin variant should warrant investigation for coexisting thalassaemia involving a different haemoglobin locus.
Coagulation Activities in Perfused Organs: Regulation by Addition of Animal Plasmas
Authors: Dodds W. Jean , Hoyer L. W.
Published: March 2008

Summary. Production of factor‐VIII and ‐IX activities was studied in isolated rabbit livers and spleens perfused for I hr to release stored coagulation activity and then for another 4 hr. At 30 min of the second perfusion period, 5 ml citrated dog or rabbit plasma from normal animals or from those with congenital or artificially induced coagulation defects was added to the perfusates. Subsequent production of factor‐VIII and ‐IX activities was monitored at intervals for 3.5 hr. Results indicated that following the addition of animal plasmas to perfused organs, production of coagulation activity was inversely proportional to the level of these coagulation factors in the initial perfusate. In addition, development of clotting factor activities in the liver and spleen perfusates was inhibited by puromycin, cycloheximide, and actinomycin D. Several interpretations of the data have been considered, and the results are compatible with regulation by a negative feedback effect on organ protein synthesis and/or release of previously formed molecules.
A New Variant of Sickle‐Cell Disease with High Levels of Foetal Haemoglobin Homogeneously Distributed within Red Cells
Authors: Makler M. T. , Berthrong M. , Locke H. R. , Dawson D. L.
Published: March 2008

Summary. The clinical, biochemical, biosynthetic and genetic properties are described of an unusual variant of sickle‐cell disease occurring in two adult Negro siblings who have resided above 2000 m all their lives. The variant consists of homozygous S disease with elevated levels of Hb‐F homogeneously distributed throughout the red cells. Both parents have Hb‐A and Hb‐S; neither has evidence of thalassaemia nor the gene for hereditary persistence of foetal haemoglobin (HPFH). As these findings cannot be explained by environmental factors or known genetic defects, we postulate the existence of a new F‐gene.
The Effect of Various Cytotoxic Agents on the Erythroid Precursors in Rat Bone Marrow
Authors: Millar J. L. , Blackett N. M.
Published: March 2008

Summary. A comparison of erythroid repopulating ability, erythropoietin‐responsive cells and red cell production after treatment with nitrogen mustard, busulphan, daunorubicin, X‐irradiation, dimethylmyleran, methotrexate and cyclophosphamide is presented. Only some of the observed differences are due to different proliferation rates. This comparison also provides information about the drug sensitivity and proliferation state of the erythropoietin‐responsive cells.
Microangiopathic Haemolytic Anaemia and Experimental Tumour‐Cell Emboli
Authors: Hilgard P. , Gordon‐smith E. C.
Published: March 2008

Summary. The mechanism by which disseminated carcinoma may induce microangiopathic haemolytic anaemia has been studied in rats using intravenous injections of Walker carcinosarcoma‐256 cells. Following the injection of tumour cells there was sequestration of radio‐labelled fibrinogen and platelets in the lungs and a simultaneous fall in peripheral platelet count and rise in free plasma haemoglobin. Anti‐fibrinolytic treatment (EACA) and triamcinolone accentuated the changes whereas heparin abolished the effect. Electron microscopy demonstrated fibrin and platelet deposition around tumour cells. It is concluded that intravascular coagulation around tumour cell emboli is an important mechanism in the production of microangiopathic haemolytic anaemia in disseminated carcinoma.
Abnormal Cells in the Peripheral Blood of Patients with Hodgkin's Disease
Authors: Halie M. R. , Huiges W. , Nieweg H. O.
Published: March 2008

Summary.

The characteristics of large, abnormal cells in the peripheral blood of patients with Hodgkin's disease have been investigated with cytochemical stains. It was possible to distinguish clearly cells of the granulocytic series, megakaryocyte parts, cells of the mononuclear phagocytic system and immunoblasts. These cells, however, are not specific for Hodgkin's disease, for they could also be found in normal subjects, in patients with infectious mononucleosis or cytomegalovirus disease and patients with lympho‐ or reticulosarcoma. Cells considered to indicate dissemination of Hodgkin's disease could only be detected in the peripheral blood of patients with this condition, and not in the other diseases mentioned above. These cells do not react with the periodic acid Schiff stain, Sudan black, peroxidase, non‐specific esterase and sometimes faintly with methyl green pyronin. It is therefore improbable that these cells belong to the categories of the granulocytic or monocytic cells, but a relationship to the lymphoid cells on the one hand or to the reticulum cells on the other could not be excluded on the basis of this morphological investigation.
Functional Cellular Maturation in Cultures of Human Haematopoietic Cells
Authors: Barak Yigal , Shore Nomie A. , Higgins Gussie R. , Vadakan Vibulv.
Published: March 2008

Summary. The capacity of cells grown in colonies derived from human haematopoietic cells to phagocytize bacteria and to reduce nitroblue tetrazolium (NBT) was studied as a measurement of functional maturation. Marrow cells from 12 non‐leukaemic patients, fivc patients with acute non‐lymphocytic leukacmia, and cells taken from a myeloblastic cell line established from a patient with acute myelo‐genous leukaemia (AML) were studied. Cells were cultured in soft agar with normal human leucocyte feeder layers as the source of stimulating factor. While the leukaemic marrows gave rise to fewer colonies than the non‐leukaemic marrows, colony formation by the AML cell line was extensive. In all instances colony formation was completely dependent upon the presence of the leucocyte feeder layers. Suspensions of pooled colonies contained 42% mature granulocytes in non‐leukaemic cultures and 41% in the leukaemic cultures. Granulocytes from these cultures showed active phagocytosis of Staphylococcus aureus and reduction of NBT. In cells taken directly from the liquid suspension culture of the AML cell line, no mature granulocytes nor phagocytosis were noted, whereas 35% and 26% of the cells removed from the colonies formed by these cells were classified as mature granulocytes, or demonstrated phagocytosis and NBT reduction respectively. These observations indicate that granulocytes in soft agar colonies derived from human haematopoietic cells are functionally mature, and that cells derivcd from a human AML cell line have the capacity to form colonies with normal maturation, if they are provided with an appropriate stimulating factor.
Lymphocyte Membrane Markers in Acute Lymphoblastic Leukaemia
Authors: Aiuti F. , Papa G. , Lacava V. , Ciarla M. V. , D'Amelio R. , Garofalo J.
Published: March 2008

Summary. T and B lymphocytes can be detected by specific membrane markers. Spontaneous rosette formation with sheep RBC (E rosette) is a T cell marker, whereas receptors for activated complement component (EAC), for the Fc regions of certain immunoglobulin classes (FcR), and for membrane immunoglobulins (mIg) are specific for B cells. Using these lymphocyte membrane markers we evaluated peripheral blood lymphocytes of 18 patients in different stages of acute lymphoblastic leukacmia (ALL).

Our results indicate that in acute untreated ALL there is no set immunologic pattern; instead there is a variety of selective deficiencies. Patients in remission have normal populations of T and B cells, whereas those in relapse present a rather obscure picture.

The percentage of lymphocytes with membrane markers was compared to the percentage of blast cells and an inverse relation is observed. This indicates that these are abnormal blast cells.

The changes from the untreated acute stage through to remission was followed in one subject, and in two others additional study was performed on bone marrow and spinal fluid lymphocytes.
Endotoxin‐Induced Intravascular Coagulation and Shock in Dogs: The Role of Factor VII
Authors: Garner Robert , Evensen Stein A.
Published: March 2008

Summary. Endotoxin (E. coli 0111; 2.5 mg/kg) was given via an aortic cannula to groups of normal and factor‐VII deficient dogs to determine whether factor‐VII deficiency afforded protection against endotoxin‐induced shock and intravascular coagulation. Normal dogs showed the dramatic fall in blood pressure characteristic of endotoxin shock and became deeply unconscious throughout the 5 hr period of the experiment. The factor‐VII deficient dogs had a niarkedly less dramatic response. The fall in blood pressure was significant but only transitory and the dogs required additional anaesthesia. Endotoxin‐induced intravascular coagulation occurred in both normal and factor‐VII deficient dogs. However, the decrease in factor‐V activity was greater, and the platelets returned to normal levels more slowly, in normal dogs than in factor‐VII deficient dogs. Plasminogen levels fell significantly in normal dogs, but not in the factor‐VII deficient animals. Autopsies revealed marked differences between the groups. Fibrin‐containing thrombi were regularly observed in normal dogs, but in factor‐VII deficient dogs such lesions were absent or minimal. Hereditary factor‐VII deficiency may therefore afford protection against endotoxin‐induced shock and intravascular coagulation. The difference in intravascular coagulation may explain the modified shock response in factor‐VII deficient dogs or vice versa, but convincing evidence for a causal relationship has not yet been collected.
New Kinetic Role for Serum Ferritin in Iron Metabolism
Authors: Siimes Martti A. , Dallman Peter R.
Published: March 2008

Summary. The role of the iron in serum ferritin was investigated with regard to iron kinetics. Serum (or plasma) was fractionated on a sucrose gradient by ultra‐centrifugation to separate iron in ferritin from other iron‐containing components in serum. After injection of heat‐treated [59Fe]RBC in rats, detectable labelling of the serum ferritin fraction was brief, between 20 and 40 min. The labelling of other iron components in the serum was maximal between 1 and 2 hr. No labelling of the serum ferritin fraction was detected after intravenous administration of [59Fe]‐transferrin in man and in the rat, or after [59Fe]haemoglobin‐haptoglobin or oral [59Fe2+]citrate in the rat. These results indicate that iron in serum ferritin originates in part from the degradation of haemoglobin in senescent red cells and that this labelled ferritin is cleared from the serum rapidly.

In normal rats, [59Fe]ferritin, purified from rat liver and injected intravenously, disappeared from the serum at an exponential rate with a half‐disappearance time (HDT) of 4 min. After 1 hr 97% of the label had accumulated in the liver. After a delay of 24 hr, increasing amounts of label appeared in the RBC to an estimated maximum of 70–80% at 5 days. Conditions which increased or decreased rates of synthesis of haemoglobin altered the percentage of [59Fe]ferritin incorporated into haemoglobin, but these conditions did not change the rate of removal of [59Fe]ferritin from the serum by the liver. These results indicate that the iron in serum ferritin is cleared from the serum much more rapidly than transferrin‐bound iron. The data are consistent with the passage through serum ferritin of a major portion of the iron that is released from the degradation of red cell haemoglobin in the RE system.
Haemoglobin Content of Individual Erythrocytes in Normal and Abnormal Blood
Authors: James V. , Goldstein D. J.
Published: March 2008

Summary. Procedures were developed for the measurement of the haemoglobin content of individual unstained human erythrocytes in blood smears, using a Vickers M85 scanning and integrating microdensitometer. Possible errors due to instrumental factors were investigated. Spatial distribution error was found to be unimportant when using a flying spot 1.8 μm diameter in the specimen plane. Measurements of an oxyhaemoglobin solution adhered to Bouguer's Law (i.e. absorbance was proportional to pathlength); microdensitometric results obtained at a given wavelength and with a given monochromator bandwidth could be corrected to correspond to λmax and minimal bandwidth by multiplication by an empirical constant.

Seventy cells in each of nine control and 10 pathological blood samples were measured. Microdensitometric estimates of the MCH correlated well with those obtained by conventional methods, although the former were slightly higher.

The mean coefficient of variation of the haemoglobin contents of the control samples was 14.1%, considerably higher than the instrumental uncertainty (under 4%). Seven of the nine control samples exhibited statistically normal distributions without significant skewness or kurtosis (skewness referring to an asymmetrical distribution around the mean, and kurtosis referring to an excess or deficit of observations in the flanks of the distribution curve); the remaining two samples may not have been completely normal in the biological sense. Seven of the 10 pathological samples had significant skewness and/or kurtosis, and only one pathological sample showed no abnormal parameter (MCH, coefficient of variation, skewness or kurtosis). Bimodal distributions appeared to be present in some cases.

Microdensitometry of individual erythrocytes yields information not otherwise obtainable, and may prove valuable in the research investigation of a variety of blood conditions.
Erythropoietin‐Stimulated Proliferation of Human Red Cell Precursors in Vitro
Authors: Golde David W. , Schooley John C. , Cline Martin J.
Published: March 2008

Summary. A liquid culture system is described that supports human erythropoiesis in vitro. Replication and maturation of red cell precursors in bone marrow from normal subjects and from patients with various disturbances of haemopoiesis were sustained in culture for periods up to 2 weeks. Added erythropoietin stimulated erythroid precursor DNA synthesis and cell replication. The erythropoietin effect was inhibited by a rabbit antibody to human erythropoietin. The culture system provides a means to study directly normal and abnormal human erythropoiesis in vitro.
The Population of Cells in Paroxysmal Nocturnal Haemoglobinuria of Intermediate Sensitivity to Complement Lysis: Significance and Mechanism of Increased Immune Lysis
Authors: Rose W. F. , Adams J. P. , Thorpe A. M.
Published: March 2008

Summary. The red cells in paroxysmal nocturnal haemoglobinuria (PNH) are of three sorts: population I in which the cells appear to be normal, population II in which the cells are 3–5 times more sensitive to complement (C) lysis than normal and population III in which the cells are 10–15 times more sensitive to complement. In all previously reported patients, two or three populations were present. Two patients were found to have only cells of population II. These cells are like those of population I (normal cells) and population III in fixation of antibody and the first and fourth components of complement. The cells of populations II and III fix larger amounts of the third component than normal. The amount of lysis obtained for a given amount of fixed C3 is much less for cells of population II than for cells of population III.