bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiliaemophilic Factor (Factor VIII): An a‐2 Globulin
Authors: Barkhan P. , Lai M. , Stevenson M.
Published: March 2008

Little is known of the molecular size or structure of antihaemophilic factor (AHF)‐also known as Factor VIII or antihaemophilic globulin (AHG). It is generally assumed to be a protein and has been characterized electrophoretically as a B‐2 globulin (Spaet and Kinsell, 1953; van Creveld, Hoorweg, den Ottolander and Veder, 1956). Hardisty and Pinniger (1956) found that it migrated with the B‐globulin fraction.

In the course of using the method of starch‐block electrophoresis for the separation of clotting factors from human plasma we have found the AHF activity in the a‐2 globulin region, and have failed to detect similar activity in any of the B‐globulin fractions. In this paper we report and discuss these findings.
The Incidence and Types of Thalassaemia‐Trait Carriers in Israel
Authors: Ramot B. , Abrahamov Ayalah , Frayer Z. , Gafni D.
Published: March 2008

The Israeli population has been found to be heterogeneous by the use of a number of genetic markers (Ramot, Duvdevani‐Zikert and Kende, 1962; Szeinberg, Sheba and Adam, 1958; Sohar, Pras, Heller and Heller, 1961; Sheba, Ashkenazi and Szeinberg, 1962; Gurevitch, Hasson, Margolis and Poliakoff, 1954). The presence of thalassaemia among Buchara and Kurdish Jews has been previously described by Schieber (1945) and by Matoth, Shamir and Freundlich (1955).

This study was undertaken to determine (a) the frequency of thalassaemia among different Jewish ethnic groups, and (b) the frequency of an increase in haemoglobin A2 among thalassaemia carriers in our population.
Hereditary Sideroblastic Anaemia
Authors: Losowsky M. S. , Hall R.
Published: March 2008

Cases of sideroblastic anaemia without an obvious underlying cause and with other members of the family affected by what is clearly the same condition are few in the literature, and in most reports the family study has not been sufficiently extensive to establish the type of inheritance or even to ensure that the cause is hereditary rather than environmental.
Sideroblastic Anaemia: A Commentary
Authors: Goldberg A.
Published: March 2008

I would like to make a few comments in an attempt to correlate with known biochemical mechanisms of haem biosynthesis some of the observations which have been described in the preceding papers, for it is clear that there is a disorder in haem formation in the sideroblastic anaemias. There are several phases in haem biosynthesis which may be affected. In the pyridoxine‐responsive types, the fault presumably lies prior to the formation of δ‐aminolaevulic. acid, for the combination of glycine and succinyl Co‐A is brought about by a system requiring pyridoxal or pyridoxal phosphate. In addition, however, Cooper, Webster and Harris (1963) have recently suggested that pyridoxal phosphate is also necessary for the mobilization of iron from mitochondria.
The Effect of Temperature on Folic Acid Metabolism
Authors: Panders J. T. , Rupert Marijke S. E.
Published: March 2008

Megaloblastic changes of the bone marrow in febrile patients have been described by Miesch, Baxter and Levin (1957), Maclver (1960), Maclver and Went (1960), Hilkowitz (1960), Luhby and Cooperman (1961), Chanarin, Burman and Bennett (1962), Lindenbaum and Klipstein (1963), Lecocq and Harper (1963), Chanarin, Barkhan, Peacock and Stamp (1964) and Chanarin and Davey (1964). In experiments on monkeys, May, Stewart, Hamilton and Salmon (1952) established that megaloblastic changes of the bone marrow occurred in association with sterile abscesses produced by injections of turpentine, and in association with infectious diseases.
Studies on Fibrinogen Fractions Isolated from Human Plasma by Precipitation with Cold Ether
Authors: Eisen V.
Published: March 2008

Mackay, Maycock, Silk and Combridge (1965) have shown that human fibrinogen preparations isolated by cold ether from freshly collected plasma (fraction HAHG, rich in Factor VIII), or from outdated plasma (fraction ETF), generate, when incubated at 37°C., traces of kinin (2–30 μmg. of bradykinin per ml. of fraction in 60 minutes). Activation of the plasminogen in the two fractions enhances the kinin formation in HAHG (30–117 μmg./ml. per 60 minutes), but not in ETF. Longer incubation did not increase the kinin yield.

With larger transfusions, the amounts of kinin which develop in activated HAHG could be sufficient to produce pharmacological effects, and consequently clinical reactions (Mackay et al., 1965). However, there is no evidence that the plasminogen in transfused HAHG is activated in the body. Even if this were the case, the action of this enzyme on the kinin‐yielding substrate (kininogen) in HAHG is so slow that the resulting kinin would be destroyed in vivo by the normal blood kininase (a carboxypeptidase), before effective levels could develop. The present work suggests that the occasional reactions to transfusions (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) could be due to the presence in HAHG and ETF of already active kalli‐krein which rapidly forms kinin by interacting with the high kininogen concentration in the recipient's plasma (cf. Fig. 1 in Mackay et al., 1965). The fractions also contain a factor capable of activating the kallikreinogen in the patient's plasma.

The nature of the enzymic contaminant in HAHG and ETF, which hydrolysed p‐tosyl‐l‐arginine methyl ester (TAMe) even when the plasminogen in the two fractions had not been activated (Mackay et al., 1965), was also investigated in the present study.
The Action of the First Component of Complement on Cells Sensitized with Blood Group Antibody
Authors: Stratton F. , Rawlinson Violet I.
Published: March 2008

We have always experienced difficulties in the past in treating cells sensitized with blood group antibody with the first component of complement so that they became strongly active following such treatment. Such cells, prepared as described by other workers (Harboe, Müller‐Eberhard, Fudenberg, Polley and Mollison, 1963) have always proved to be insufficiently active for our experiments.

We therefore explored a number of alternative methods, and found that a pellet obtained by ultracentrifugation of human serum (Naff, Pensky and Lepow, 1964) could be used for this purpose. The object of this paper is to describe the treatment of cells sensitized with blood group antibodies with this pellet and to describe the reactions of the cells so prepared.
Granulocytopoiesis in the Rat Thymus
Authors: Sin Yoke Min , Sainte‐Marie G.
Published: March 2008

This work is a quantitative analysis of the pure and mixed islands of neutrophilic and eosinophilic cells present in the rat thymus and described in the preceding paper (Sin and Sainte‐Marie, 1965). Its purpose is to determine the number of generations of each of the 10 previously defined cell types (A‐J) formed during granulocytopoiesis (Sin and Sainte‐Marie, 1965).
Iron in the Anaemia of Kwashiorkor
Authors: Adams E. B. , Scragg J. N.
Published: March 2008

Anaemia in kwashiorkor has been reported as normocytic or slightly macrocytic, hypoplastic or megaloblastic (Altmann and Murray, 1948; Van der Sar, 1951; Trowell, Davis and Dean, 1952; Adams, 1954; Lien‐Keng and Tumbelaka, 1960; Adams and Scragg, 1962; Walt, Taylor, Magill and Nestadt, 1962; Neame and Simson, 1964), and all these varieties have been observed in one series (Walt, Taylor and Robertson, 1961). There is no clear evidence that hypochromic anaemia, when it occurs, is due to iron‐deficiency. In this paper we record some observations on hypochromia and the role of iron in kwashiorkor.
Platelet Survival Studies in Man with Diisopropylphosphorofluoridate (DF32P). SOME OBSERVATIONS IN PATIENTS WITH HYPOCOAGULABILITY, ‘HYPERCOAGULABILITY’ AND PLATELET DISORDERS*
Authors: Barkhan P.
Published: March 2008

Diisopropylphosphorofluoridate (DF32P) acts as a cell label by combining irreversibly with esterases in the cell membrane. It was first used in man for tagging red cells (Cohen and Warringa, 1954) and later for platelets (Leeksma and Cohen, 1956) and leucocytes (Athens, Mauer, Ashenbrucker, Cartwright and Wintrobe, 1959). Since DF32P allows platelets to be labelled directly in vivo it has obvious advantages over the 51Cr method (Aas and Gardner, 1958) which necessitates removal of platelets from the body for labelling and subsequent re‐injection.

The precise form of the normal platelet survival curve in man and the relative importance of intrinsic factors such as cell age, and extrinsic factors such as variations in the concentration of plasma coagulation factors, remains to be established. As part of an investigation into some of these factors, DF32P has been used in a small comparative study of platelet survival in some hypocoagulable and some ‘hypercoagulable’ states. During the course of this study the opportunity arose to apply the method to patients with qualitative and quantitative platelet abnormalities. These studies are presented and discussed in this paper.
Studies on Neutrophil Function I. Physiological and Pharmacological Aspects
Authors: Penny R. , Galton D. A. G. , Scott J. T. , Eisen V.
Published: March 2008

During inflammation, the circulating neutrophil adheres to the altered venular endothelium (Marchesi, 1964; Cotran, 1965), and emigrates between the endothelial cells into the tissue towards its prey. Both phenomena were first observed by Dutrochet in 1824 in the small blood vessels of the tail of the frog tadpole. Accurate observations on the margination and emigration of leucocytes in inflammation were made between 1833 and 1850 by Wagner, Waller, Addison and Wharton–Jones, and later by Cohnheim and Adami. The history of the early work is reviewed by Grant (1965). The amoeboid locomotion of leucocytes was studied by Metchnikoff at the end of the 19th century. He introduced the term phagocytosis and was the first to recognize it as a defence reaction (1893), his contemporaries including Klebs, Koch, Waldeyer and Virchow having regarded leucocytes as a source of dissemination of the bacteria they had observed within them.

Pseudopodia form and enclose the particles to be phagocytosed within a phagocytic vacuole into which are discharged the enzyme‐rich contents of the neutrophil granules (Senda, 1962; Zucker‐Franklin and Hirsch, 1964; Zatti, Rossi and Meneghell, 1965). This process requires the participation of intrinsic neutrophil mechanisms and of extrinsic serum and tissue components. The biochemical aspects of neutrophil function at rest and in action have been investigated, (Karnovsky, 1962; Rossi and Zatti, 1964; Ohta, 1964a, b; Perry, 1964; Zatti et al., 1965) but recently more attention has been directed towards the extracellular components concerned in leucocyte emigration (Hurley, 1964), adhesiveness (Rabinowitz, 1964), chemotaxis (Boyden, North and Faulkner, 1965; Ward, Cochrane and Müller‐Eberhard, 1965), phagocytosis (Tullis and Surgenor, 1950; Nelson and Lebrun, 1956; Boyden, 1963; Gerlings‐Petersen and Pondman, 1964; Vaughan, 1965), and the post‐phagocytic phase (Li, Mudd and Kapral, 1963; Archer, 1964; Boyden et al., 1965).

In the present study, adhesiveness and phagocytosis were the two aspects of neutrophil function assessed in vitro under physiological and pharmacological conditions (I) and in pathological states (II), in the hope of casting light on the causes of disturbed function in a variety of pathological states.
Observations on the in vitro Growth of Peripheral Leucocytes from Patients with Myeloproliferative Disorders
Authors: Pegrum G. D.
Published: March 2008

In 1960 Moorhead, Nowell, Mellman, Battips and Hungerford described a method for obtaining chromosome preparations by culturing peripheral blood leucocytes. This work has provoked intensive studies of human chromosomes in many disorders. Studies on leukaemia and related conditions were not long in appearing, and in 1960 Nowell and Hungerford described an abnormality of one of the small acrocentric chromosomes in two male patients with chronic myeloid leukaemia. The abnormal chromosome was later found to occur in the majority of patients with chronic myeloid leukaemia and was named the Philadelphia (Ph1) chromosome. In the first studies this chromosome was sometimes absent from the peripheral blood cultures stimulated with phytohaemagglutinin but present in the marrow. However, there are cases of chronic myeloid leukaemia where no Ph1 chromosome can be found (Tough, Jacobs, Court‐Brown, Baikie and Williamson, 1963; Krauss, Sokal and Sandberg, 1964).

Studies on non‐leukaemic myeloproliferative disease indicated no constant chromosomal abnormality (Sandberg, Ishihara, Crosswhite and Hauschka, 1962; Goh and Swisher, 1964). While carrying out chromosome studies on patients with myeloproliferative disorders it was noticed that there was considerable variation in the number of cells in mitosis when cells from different patients were grown in vitro (Pegrum, 1965). An investigation has therefore been carried out on the growth of cells from 28 patients with myeloproliferative disorders, using 15 blood donors as controls, in an attempt to evaluate these differences. The cells synthesizing DNA prior to division were identified at intervals of 3, 5 and 7 days by autoradiography following exposure to tritiated thymidine.
Platelet Aggregation and the Availability of Platelet Factor 3
Authors: Hardisty R. M. , Hutton R. A.
Published: March 2008

We have previously shown (Hardisty and Hutton, 1965, 1966) that kaolin makes platelet factor 3 (PF3) available in platelet‐rich plasma (PRP) by a reaction which involves platelet aggregation and which is inhibited by antagonisis of adenosine diphosphate (ADP), such as adenosine and related compounds. Using the kaolin clotting time system, we were not able to detect a significant effect of ADP on PRP in the absence of kaolin, and we therefore concluded that adhesion of platelets to an activating surface was also necessary for optimal effect, and that ADP aggregation alone did not make PF3 available. This conclusion was at variance with those of Mustard, Hegardt, Rowsell and MacMillan (1964) and Castaldi, Larrieu and Caen (1965), who used different clotting systems and found evidence of increased clotting activity in platelets after ADP aggregation. We therefore decided to reinvestigate the effect of platelet aggregation on PF3 availability, using the ‘Stypven time’ in order to eliminate the need for simultaneous activation of the earlier stages of the intrinsic coagulation process. Spaet and Cintron (1965) have already used this system to demonstrate the effect of kaolin and connective tissue on PF3 availability.
Studies on Thalassaemia‐like Anaemias in Pregnant Immigrants in London*
Authors: Beaven G. H. , Dixon G. , White J. C.
Published: March 2008

It is increasingly recognized that the thalassaemia trait is extremely variable in all its manifestations, and that its geographical distribution is very widespread. For this reason it may be expected to be found in many of the immigrant groups in the United Kingdom. The requisite haematological and biochemical study over a sufficient period of time can conveniently be carried out during antenatal attendance, and the possible influence of this condition on the haematological status during pregnancy is itself of considerable interest. The same immigrant groups also contain numerous examples of the easily definable traits for the common abnormal haemoglobins (Hb‐S, Hb‐C), as well as diverse anaemias and others which are essentially due to iron deficiency. In such groups all these conditions may also be complicated by parasitic infestations, particularly hookworm.

The present report deals specifically with a group of thalassaemia‐like anaemias, which are compared with a group of iron‐deficiency anaemias. The recognition of the thalassaemic state is based on: (a) consistently reduced MCHC or microcytosis, (b) reduced osmotic fragility of the red cells before or after incubation, (c) presence of stainable iron in the stores and erythroblasts of the bone marrow, and (d) quantitative studies of the Hb‐A2 and Hb‐F levels in haemolysates.

The occurrence of Hb‐γ4 (Hb‐Bart's) in the cord bloods at delivery has also been studied. Parallel observations have been made on the subjects with iron‐deficiency anaemias of pregnancy.
Effects of Human Plasma on Thrombelastographic Patterns Produced by Fibrinolytic Agents in Fibrin Clots
Authors: Egeblad Klas , Astrup Tage
Published: March 2008

A comparative study is presented of the thrombelastographic patterns produced by, and the curves correlating concentration and activity of, fibrinolytic agents incorporated in a bovine fibrin clot containing various amounts of human plasma. Except for a delay of lysis the thrombelastographic patterns produced by plasmin in the simple fibrin clot are in principle retained in the presence of plasma. An interference of plasmin with clot structure is revealed by a decreased maximum amplitude. The slopes of the plasmin correlation curves are considerably increased in the presence of plasma.

Urokinase and SK‐activator (streptokinase+ human globulin) produced the same thrombelastographic pattern in the simple fibrin clot as in the presence of plasma except that at low concentrations of SK‐activator a prolongation of the end phase occurred. This was even more pronounced when SK‐resistant plasma was used. In this case also the correlation curves became steep. With urokinase and plasmin the SK‐resistant plasma showed the patterns produced by normal plasma.

Platelets interfere strongly with clot formation and final clot structure. There is a large increase in maximum amplitude. The antifibrinolytic effect of platelets is mainly directed against plasmin.
New Anticoagulant from Lysed Fibrinogen
Authors: Triantaphyllopoulos E. , Triantaphyllopoulos D. C.
Published: March 2008

Once fibrinogenolysis had been initiated, few, if any fibrinogen molecules remained unaffected. Even the fraction which could still be precipitated by 0–25 per cent ammonium sulphate saturation showed differences from intact fibrinogen. Its solubility decreased very early, its coagulability gradually disappeared and the fraction itself acquired anticoagulant properties.

The ability of the 0–25 per cent fraction to prolong the thrombin clotting time of intact fibrinogen varied with incubation in a way similar to that of the 25–50 per cent fraction (AFIF). It was, however, less potent and it disappeared after heating at 60° C. for 15 minutes. The two anticoagulant fractions could be differentiated by the electrophoretic and thermo‐stable protein patterns, the degree of precipitability by ether, the effect of alkaline pH buffers and the effect of fraction concentration on the inhibitory activity.

The main electrophoretic component of the 0–25 per cent fraction, responsible for the bulk of the inhibitory effect at 100 per cent CP, had a slightly slower mobility and lower specific activity than the main component of the 25–50 per cent fraction.

Purified thrombin liberated acid soluble protein fragments from the 0–25 per cent fraction equal to about 1.5 per cent of the total protein.
The Factor‐VIII Activity in Fresh and Stored Plasma
Authors: Preston A. E.
Published: March 2008

An investigation into the Factor‐VIII activity in fresh and stored plasma is reported and the present methods of production at the Oxford Regional Blood Transfusion Centre described.

Simple methods for increasing the Factor‐VIII activity of therapeutic plasma are suggested.

Special equipment and methods did not prevent the loss of activity which occurs following the freezing, storage and thawing of fresh frozen plasma.

A comparison between plasma stored at 4° C. for less than 18 hours is made with fresh frozen plasma and the use of the former is suggested for routine treatment of minor injuries when fresh frozen plasma is not available.
Spontaneous Lymphocyte Transformation in vitro: Negative Evidence from a Study of Thymidine Uptake
Authors: Caron G. A.
Published: March 2008

Studies of the uptake of tritiated thymidine by human peripheral lymphocytes cultured in autologous plasma or, after washing, in foetal calf serum have failed to provide evidence for the occurrence of spontaneous blastoid transformation during 1–7 days in vitro.

Repeated washing of peripheral lymphocytes caused an inconstant reduction in their ability to respond to stimulation with PHA.

The accuracy and sensitivity of the technique of measuring the degree of in vitro transformation activity of lymphocyte cultures by their uptake of radioactively labelled thymidine is increased by partially removing polymorphonuclear leucocytes from the leucocyte suspensions and by restricting exposure of the cultures to the radioactive thymidine to the final 1 hour of culture.
Vitamin B12 Absorption by Inhalation
Authors: Shinton N. K. , Singh A. K.
Published: March 2008

Cyanocobalamin in the form of an aerosol was inhaled by normal subjects, patients with pulmonary diffusion defects and patients with vitamin B12 deficiency. In all groups there was a rapid increase in serum B12 levels suggesting that absorption had occurred by diffusion through the lung alveoli.

Six patients with pernicious anaemia given daily inhalations showed complete clinical and haematological remission and a group of six patients with B 2 deficiency were maintained in remission for 12 months. While effective, this method of administration of vitamin B12 is not regarded as superior to that of injections and is therefore considered to have no therapeutic application. The possibility of inducing pulmonary damage is considered.
The Effect of Age on the Creatine in Red Cells
Authors: Griffiths W. J. , Fitzpatrick Margaret
Published: March 2008

The creatine in packed red cells was estimated by the diacetyl‐i‐naphthol technique. The error due to the presence of other guanidino compounds in the cells was found to be small.

The mean value for creatine in the packed red cells of normal females was found to be 5.6 (S.D. ± 1.3) mg. per 100 ml., and in normal males 4.4 (S.D. ± 1.5) mg. per 100 ml. The sex difference is statistically significant.

When red cells were segregated according to age by centrifugation the young red cells contained more creatine than the old cells. The creatine in the mixed population of red cells of patients under treatment for anaemia in whom there was increased erythropoiesis was greatly elevated; values as high as 50 mg. per 100 ml. were observed. With a decline in marrow activity and reticulocytosis there was a persistence of the high red‐cell creatine for a long time, suggesting that the loss of creatine from the cells with age is a gradual process.

It is concluded that the level of creatine in the circulating red cells is a sensitive parameter of the mean age of the population.
Regulation of Platelet Production: ‘Thrombopoietin’
Authors: Gabriele Geswalda de , Penington D. G.
Published: March 2008

Plasma from thrombocytopenic animals induces thrombocytosis in normal recipients. Thrombocytopenia induced by platelet antiserum or bleeding is followed by a reactive thrombocytosis and animals in this phase of increased platelet count provide a more sensitive system for the demonstration of ‘Thronibopoietin’. This humoral factor may be inactivated or removed by viable platelets suggesting the mode of operation of the thrombopoietic ‘feed‐back’ mechanism.
Separation of Lymphocytes of Rat Bone Marrow by Combined Glass‐Wool Filtration and. Dextran‐Gradient Centrifugation
Authors: Morrison J. H.
Published: March 2008

The two‐step separation of rat bone marrow involving glass‐wool filtration combined with dextran‐gradient centrifugation yields viable cell suspensions composed predominantly of lymphocytes with a minimum of contamination by granulocytes (less than 10 per cent). Because filtration of rat bone marrow through glass wool removes the larger marrow cells and most of the immature forms of the red cell series, it is useful as a first step in the separation of lymphocytes from bone marrow.

Density‐gradient centrifugation of the glass‐wool filtrate serves to differentially settle out lymphocytes and granulocytes when dextran solutions of appropriate densities are used. The middle or layer 2 (density 1.0600) of the dextran gradient yields the greatest absolute numbers of lymphocytes. Small numbers of transitional and blast cells are also present in this layer.

The separation procedure results in excellent preservation of cell morphology as evidenced by Jenner‐Giemsa staining. A high level of viability of the separated cells is indicated by dye exclusion, characteristic fluorescence in the presence of acridine orange, and capacity for oxygen consumption. In vivo viability of the separated cells is also indicated by their capacity to confer protection following their infusion into lethally irradiated rats.
The Nature and Significance of Platelet Products in Human Plasma
Authors: Wolf Peter
Published: March 2008

Fresh plasma freed of intact platelets can be shown to contain minute particulate material (platelet‐dust) which can be separated by ultracentrifugation. Much of this material is rich in phospholipid and shows coagulant properties resembling those of Platelet Factor 3. The supernatant plasma, freed of these particles, shows a corresponding deficiency in Platelet Factor 3 activity.

Electron microscopic studies suggest that the lipid‐rich particles may originate from the osmophilic granules of platelets and that they are extruded on storage of platelets, even in the absence of coagulation. It is suggested that the liberation of this material is the basis of the process of ‘activation’ of platelets known to occur with storage.

When clotting occurs, coagulant particulate material is released from platelets, considerably in excess of what is required for thrombin generation and it can be detected in serum. Its presence accounts for the platelet‐like activity of serum.

The material can be distinguished from intact platelets, red cell stroma and chylomicra. It was observed that chylomicra, freed of platelet‐dust, were inactive in a thrombin generation test, which thus appeared responsive only to platelet type lipid. Both chylomicra and platelet‐dust were effective in a Stypven time test. Attention is drawn to possible errors of interpretation which may arise from the use of the latter test as an index of Platelet Factor 3 activity.

Preliminary immunological investigation of platelets revealed the presence of fibrinogen and at least three other constitutents which appear to be primarily platelet components.
Histochemical Studies on Leucocyte Alkaline Phosphatase in Non‐Leukaemic Granulocytosis: Effects of Anticoagulants and Role of Zinc and Magnesium
Authors: Perillie P. E. , Finch S. C.
Published: March 2008

Studies were performed to determine the effects of a variety of anticoagulants on the increased granulocyte alkaline phosphatase activity present in patients with non‐leukaemic granulocytosis and to determine the metallic requirements of the phosphatase activity present in the cells of such patients. The results indicated that although the anticoagulant ethylene‐diamine tetra‐acetic acid produced varying degrees of inhibition of LAP in the majority of patients studied, the degree of inhibition did not result in levels of LAP that could be confused with those observed in chronic granulocytic leukaemia. It is concluded that anticoagulated blood can be used for the histochemical evaluation of LAP without detracting from the clinical usefulness of the procedure.

In all patients studied the addition of zinc resulted in almost complete restoration of EDTA inhibited LAP.
The Effect of Cortisol on the Rate of Autohaemolysis of Red Cells Incubated in vitro
Authors: Morley A. A.
Published: March 2008

Evidence is presented for a direct effect of cortisol on the rate of red cell lysis in vitro. It is suggested that this effect is due to the mineralocorticoid action of cortisol. The finding may be relevant to certain disease states especially paroxysmal nocturnal haemoglobinuria, in which the rate of haemolysis is inversely related to plasma steroid levels.
Potentiation of Purified Erythropoietin with Serum Proteins*
Authors: Gardner E. , Wright C.‐S. , Lewis J. P. , Moores R. R.
Published: March 2008

Non‐neutralizing antiserum, normal rabbit, human and mouse sera potentiate the erythropoietic activity of anaemic human urinary Fraction II + III. This substantiates the concepts introduced by Kuratowska, Lewartowski and Lipinski.

Orosomucoid (alpha‐1 acidic‐glycoprotein) similarly potentiates the erythropoietic activity of anaemic human urinary Fraction II + III.

The erythropoietic activity of Standard B was not enhanced by the addition of serum proteins.

The erythropoietic activity of human urinary concentrates was enhanced by the addition of normal serum proteins and suggestive enhancement of anaemic human serum and plasma was noted.
Atypical Hereditary Spherocytosis: Biochemical Studies and Sites of Erythrocyte Destruction
Authors: Zail S. S. , Krawitz P. , Viljoen E. , Kramer S. , Metz J.
Published: March 2008

A family with hereditary spherocytosis has been investigated and found to have the following unusual features: atypical pre‐ and post‐incubation red cell osmotic fragility and absence of splenic sequestration of red cells. Ouabain, an inhibitor of active cation transport, was found not to inhibit the corrective effect of glucose on the rate of autohaemolysis of whole blood, a finding present in some cases of known hereditary spherocytosis, but not in others. The red cells of the propositi showed evidence of increased A.T.P.‐ase activity as well as increased utilization of A.T.P. for purposes other than for active cation transport, and are metabolically similar to hereditary spherocytic cells in this respect. The reason for the absence of splenic sequestration of red cells was not established.
Hormonal Control of Erythropoiesis during Pregnancy in the Mouse
Authors: Jepson Joanne , Lowenstein Louis
Published: March 2008

Summary. Increased plasma erythropoietic activity was observed during pregnancy in the mouse, first appearing on the 5th day. Reticulocytosis, increase of red‐cell volume, decrease of plasma iron and increase of the total iron binding capacity appeared on the 10th day. The major increase of red‐cell volume and plasma volume occurred during late pregnancy as the reticulocytes and plasma iron progressively decreased. Suppression of endogenous erythropoietin production in pregnant mice by hyperoxia did not completely abolish either plasma erythropoietic activity or the rise of the red‐cell volume observed in unexposed pregnant mice. Placental lactogen was found to have some erythropoietic activity and increased the plasma volume. Ovarian hormones were erythropoietically ineffective and, in fact, oestrogen appeared to inhibit the activity of placental lactogen.
Effects of Halides on Binding of Trace Concentrations of Mercury to Human Erythrocytes
Authors: Azen Edwin A. , Jensen Lorene
Published: March 2008

Summary. Trace concentrations of mercury (in the range of 10‐‐6 M) in the presence of 0.144 M‐NaCl or NaBr bind to erythrocytes to a limited degree, whereas mercury in the presence of 0.144 M‐NaI under similar conditions is completely bound by erythrocytes. The limited binding of mercury to erythrocytes in the presence of bromide and chloride is due to the presence of substances in the incubation fluid that bind mercury. Little of the mercury in iodide solution is bound by these extracellular substances, whereas most of the mercury in bromide and chloride solution is bound to these substances. The erythrocyte membrane appears to function like a dialysis membrane by permitting the unbound fraction (small mercury‐halide complexes) to enter erythrocytes for intracellular binding while excluding the bound fraction of mercury (large molecules). The high concentration of binding substances in the erythrocytes results in binding of mercury that would not bind to dilute extracellular substances. Cellulose dialysis tubing mimics many of the properties of the erythrocyte system because of the presence of binding sites for mercury on the tubing. The data are best explained by the increasing affinity of chloride, bromide and iodide ions for mercury and the reciprocally related ease with which halides can be displaced from mercury‐halide complexes to form ‘active’ positively charged mercury ions for binding to receptor sites. The factors demonstrated in this system may be relevant to the accumulation of other metals within cells.
In vitro and In vivo Studies with Trasylol, an Anticoagulant and a Fibrinolytic Inhibitor
Authors: Dubber Anne H. C. , Mcnicol G. P. , Uttley D. , Douglas A. S.
Published: March 2008

Summary Trasylol is a competitive inhibitor of plasminogen activation by streptokinase and urokinase. The proteolytic activity of plasmin and trypsin is inhibited non‐competitively and the esterolytic activity of urokinase is inhibited in a mixed competitive and non‐competitive manner. These inhibitory effects are observed at high substrate concentrations. At low substrate concentrations, the inhibitory effects of Trasylol are relatively increascd. Trasylol is considerably more effective in vitro as an inhibitor of fibrinolytic activity than tranexamic acid and EACA: and in contrast to these amino acid inhibitors, Trasylol is more effective as an inhibitor of formed plasmin than of plasminogen activation.

Trasylol possesses anticoagulant effects probably due to inhibition of prothrombin conversion and of intrinsic thromboplastin formation.

Irt vivo in high dosage Trasylol imparts antifibrinolytic, anticoagulant and anti‐tryptic effects to plasma. It may accelerate platelet aggregation in vivo.

In one patient with hypofibrinogenaemia, its administration was associated with a fall in the platelet count. In another patient there was evidence of a rise in fibrinogen Factor V, antihaeinophilic globulin (Factor VIII) and in the platelet count.

An initial dosage of 100,000 units as a single injection or as an infusion given over 1 hour followed by maintenance dosage of 50,000 units/hr. seems appropriate in the treatment of pathological fibrinolysis. For the therapy of intravascular coagulation, higher dosage may be required, possibly 100,000 units/hr. This latter dosage would also be required in the treatment of systemic proteolysis due to trypsin.
Experimental Iron Deficiency in the Rat THE USE OF 51Cr, DF32P AND 59Fe TO DETECT HAEMOLYSIS OF IRON‐DEFICIENT CELLS
Authors: McKee L. C. , Wasson Marie , Heyssel Robert M.
Published: March 2008

Summary Dietary iron deficiency in the rat results in marked normoblastic hyperplasia of the bone marrow, peripheral blood reticulocytosis, the presence of nuclear remnants in red cells and a haeinolytic process. Haemolysis of the red cells was not detected using the 51Cr label. DF32P did detect moderate shortening of red cells but to a lesser degree than would be expected by the degree of reticulocytosis. Cohort labelling of red cells using 59Fe indicated an early rapid destruction of newly formed cells. These findings are at variance, in part, with the observations in human iron deficiency where reticulocytosis is minimal.
Metabolism of 5‐MethyItetrahydrofolate in Pernicious Anaemia
Authors: Chanarin I. , Perry Janet
Published: March 2008

Summary 5‐Methyltetrahydropteroylglutamic acid was given intravenously to control subjects and to patients with untreated megaloblastic anaemia. The rate of clearance of this substance from the plasma and excretion into the urine after an intravenous dose of 5 μg./kg. of body weight was followed.

The rate of clearance was faster in patients with folate deficiency as compared to control subjects. In pernicious anaemia the clearance was either within the normal range or more rapid than normal if there was associated folate deficiency. No support was obtained for the hypothesis that in pernicious anaemia there is a failure to utilize 5‐methylfolate.
The Haemoglobin Picture in Cooley's Disease
Authors: Silvestroni E. , Bianco I. , Graziani B.
Published: March 2008

Summary The haemoglobin picture has been studied in 38 patients with Cooley's anaemia, all homozygous for β‐microcythaemia. In 10 of the patients Hb A1 was completely absent, in the remaindcr it was present on agar gel electrophoresis in amounts varying from minute traces to a rather abundant quota.

In 34 of the Cooley's patients studied Hb A2 was present in amounts comparable to those found in normal non‐microcythaemic subjects. In the rest it was raised as in heterozygous carriers of β‐microcythaemia. There was no correlation between the haemoglobin picture and the severity of clinical findings.

The genetic significance of the different types of haemoglobin picture found in Cooley's patients is discussed.
The Autohaemolysis Test: Appraisal of the Method for the Diagnosis of Pyruvate Kinase Deficiency and the Effect of pH and Additives
Authors: Grimes A. J. , Leets Irene , Dace J. V.
Published: March 2008

Summary

The autohaemolysis test has been compared in its original form with a modified procedure in which the blood is mixed continuously throughout the 48‐hour period.

Continuous mixing of blood from ten PK‐deficient subjects yielded values unequivocally outside the normal range. Two of these subjects gave autohaemolysis results within the normal range when tested by the original method.

Glucose added to the PK‐deficient blood did not significantly reduce the autohaemolysis values by whichever method was used.

Normal or PK‐deficient blood incubated at different pH values with lactic, hydrochloric and orthophosphoric acid, or in phosphate buffer, gave minimum haemolysis at pH 6.7–7.1.

Adenosine triphosphate added to normal or PK‐deficient blood does not sustain glycolysis and its effectiveness in diminishing autohaemolysis is considered to be partly due to pH.

Adenosine, inosine and guanosine added to normal blood maintain glycolysis, which explains their beneficial effect upon autohaemolysis.
Interrelationship of Pyrrole and Globin Metabolism in β‐Thalassaemia *
Authors: Kreimer‐Birnbaum Martha , Bannerman R. M.
Published: March 2008

Detailed metabolic studies in a case of β‐thalassaemia intermedia following 14C‐2‐glycine administration demonstrate some of the interrelationships of pyrrole pigments and haemoglobins, and some secondary effects of a β‐thalassaemia mutation.

Marked increase in the early‐labelled fraction of faecal bile pigment was confirmed; labelling rose to a maximum at 5 days, in advance of the haem peak, and was approximately three times greater than maximum haem labelling.

Urinary coproporphyrins were increased in quantity, thus allowing complete serial determinations of radioactivity, which was at its maximum within 24 hours. The urine also contained a brown pigment, probably a dipyrrole, which had a labelling pattern resembling that of the urinary coproporphyrins, with maximum activity in the first sample. It is suggested that the ‘dipyrrole’may arise by early destruction of redundant haem associated with α‐chains.

At all times, haemoglobin F was more highly labelled than haemoglobin A in both the haem and the globin moieties. Mean cell survival estimated graphically from the various curves was approximately 32 days. Haem/globin ratios were similar to those reported previously in normal subjects and in thalassaemia.
Estimation of Haemopoietic Stem Cells with Erythropoietin: A Consideration of Dose—Response Curves
Authors: Byron J. W. , Lajtha L. G.
Published: March 2008

The validity of results using the erythropoietin test to estimate the haemopoietic stem cell population has been based upon accepting several assumptions regarding cell kinetics under erythropoietin stimulation. These studies show that these assumptions may not always be valid. Hence, doses of erythropoietin giving maximal stem cell response more correctly estimate the state of the stem cell population at any time following injury. Full dose‐response studies furnish information with respect to the effect of agents on the kinetics of erythropoietin‐stimulated cells. After 150 rad TBR there is (a) an initial depression of the stem cell population, followed by (b) a post‐irradiation dip, and (c) a return to normal values but with no overshoot at 14 days post‐irradiation.
The Effects on Iron Absorption of Gastro‐intestinal Secretions from Patients with Iron‐Deficiency Anaemia and Haemochromatosis
Authors: Murray M. J. , Stein Nell
Published: March 2008

We have investigated the effects of gastric and intestinal secretions from normal human subjects and those with iron‐deficiency anaemia and haemochromatosis on the in vitro uptake of 59Fe by everted rat gut segments. Whereas gastric secretions from normal subjects did not potentiate the uptake, intestinal secretions did. This effect was more marked with gastric and intestinal secretions obtained from patients with iron‐deficiency anaemia and haemochromatosis, but it disappeared with prior heating. These findings suggest that gastric and intestinal secretions play a role in the regulation of iron absorption.
Marrow‐Suppressing Factors in the Blood in Pure Red‐Cell Aplasia, Thymoma and Hodgkin's Disease
Authors: Field E. O. , Caughi M. N. , Blackett N. M. , Smithers D. W.
Published: March 2008

1. A stem cell suppressing factor has been found in the serum of a patient with Hodgkin's disease, a thymic tumour and pure red‐cell aplasia. This factor disppeared when active erythropoiesis returned following radiotherapy to the tumour.

2. The suppressing activity was assayed in mice by measuring the capacity of their bone marrow to restore erythropoiesis in heavily irradiated recipients.

3. Failure to demonstrate a raised erythropoietin level, as well as the finding that IgA and IgM immunoglobulins were reduced, suggested that autoimmune processes might be involved. However, it appeared unlikely that the factor was an autoantibody since suppressing activity was destroyed by storage at −20° C.

4. The sera of nine other patients, one with a thymoma associated with erythroid and megakaryocyte aplasia, three with anterior mediastinal tumours and five with secondary marrow aplasia, were assayed. Three of these showed mild suppressing activity, but this could have been due to non‐specific causes, the nature of which is discussed.
Thrombopoietin Activity in Idiopathic Thrombocytopenic Purpura
Authors: Choi Sun I. , McClure P. D. , Vranic Magda
Published: March 2008

In this study we have attempted to measure thrombopoietic activity in patients with idiopathic thrombocytopenic purpura. The activity was more readily detectable in serum than in urine. When a high level of thrombopoietic activity was found, it was often followed within a few days by a rise in platelet count. Activity was significantly elevated only in acute and recurrent ITP, although a suggestive increase was found in chronic ITP. Patients with iron deficiency had no thrombopoietic activity in this assay, even though many of them had elevated platelet counts.
Thrombopoietin and Erythropoietin Levels in Idiopathic Thrombocytopenic Purpura and Iron‐Deficiency Anaemia
Authors: McClure P. D. , Choi Sun I.
Published: March 2008

Erythropoietin activity was elevated in some patients with iron‐deficiency anaemia but in none with idiopathic thrombocytopenic purpura. Thrombopoietin was elevated only in patients with idiopathic thrombocytopenic purpura. No correlation existed between erythropoietin and thrombopoietin activities measured on the same serum sample. Although erythropoietin activity bore some relationship to the degree of anaemia, thrombopoietin could not be related. The finding suggests that erythropoietic and thrombopoietic activities are different factors.
Creatine and Phosphocreatine in the Human Red Cell
Authors: Griffiths W. J.
Published: March 2008

In vitro experiments showed that the concentration of creatine in a mixed population of normal red cells was either unchanged or slightly diminished during incubation at 37° C. for 48 hours in plasma or a buffered medium. If young cells were present there was always a fall in creatine during the early stages of incubation. Creatine lost in this way appeared in the cell‐free supernatant fluid. The ability of the red cell to retain some creatine throughout its life span is due to the relative impermeability of the cell membrane to this substance.

Traces of phosphocreatine and creatine phosphokinase were detected in a population of young cells but not in mature cells. It is unlikely, therefore, that creatine takes part in energy transformations in the non‐nucleated red cell, although it may do so in an earlier phase of its development. The origin of the red‐cell creatine is obscure. Synthesis of creatine by young, non‐nucleated, red cells was not detected in vitro and its derivation from plasma creatine is considered unlikely because of the impermeability of the cell membrane. It is suggested that the creatine is acquired by the cell at some stage in its development from nucleated precursors.
Review of Fifty‐Four Subjects with Monoclonal Gammopathy
Authors: Axelsson Uno , Hällén Jan
Published: March 2008

Of 6995 persons examined in a population study, 64 were found to have M‐components in the serum. One of these was diagnosed as having myelomatosis and another as having asymptomatic chronic lymphatic leukaemia. Two‐and‐a‐half years later 52 of the 62 subjects who were considered to have benign monoclonal gammopathy were re‐examined. The M‐components were still demonstrable in all subjects in similar concentrations to those observed at the first examination. This, together with the subjects’clinical condition, strongly supports the original diagnosis of benign monoclonal gammopathy. Myelomatosis was excluded in two subjects in whom it had originally been suspected. Of the ten patients not re‐examined, one had left the district, four refused re‐examination and five had died. In none was there any evidence of myelomatosis or Waldenström's macro‐globulinaemia.

The results lend further support to the view that benign monoclonal gammopathy is more common than myelomatosis or Waldenström's macroglobulinaemia.
Ham‐positive Red Cells Induced In vitro by N‐Acetylcysteine or D‐Penicillamine
Authors: Sandre G. De , Vettore L. , Corrocher R. , Cortesi S. , Perona G.
Published: March 2008

Red cells incubated with N‐acetylcysteine or D‐penicillamine in appropriate concentrations become sensitive to lysis by acidified normal human serum, i.e. become PNH‐like cells and give a positive Ham test. At the same time the cells lose some of their acetylcholinesterase activity. Substances active in this way share a common chemical grouping:
A Cytochemical Study of Marrow Enzymes in Megaloblastic Anaemia
Authors: Stuart J. , Skowron Pryma N.
Published: March 2008

A cytochemical study of the enzyme content of megaloblasts compared with normoblasts under comparable conditions of erythroid hyperplasia has shown an increased activity of representative enzymes of the Embden‐Meyerhof pathway, pentose phosphate shunt and tricarboxylic acid cycle in individual megaloblasts at all stages of maturation. The finding of a mixed population of cells with regard to enzyme content in late megaloblasts may be related to reported variations in prolongation of the intermitotic period at an earlier stage of maturation in megaloblasts. An increased cell content of soluble, NAD‐linked, α‐glycero‐phosphate dehydrogenase in the megaloblast contrasts with reports of a selective decrease of this enzyme in homogenate studies of human and animal tumours which has been claimed to be a specific metabolic change in neoplastic cells.

It is concluded that the increased serum lactate dehydrogenase levels in megaloblastic anaemia are derived from the intramedullary destruction of large numbers of megaloblasts containing an increased amount of this enzyme.