bluuebunny/crossref_metadata_2025 huggingface dataset:
Anabolic Agents and Relative Polycythaemia
Authors: Verwilghen R. , Louwagie A. , Waes J. , Vandenbroucke J.
Published: March 2008

after the administration of testosterone an increase in the haemoglobin concentration may occur, and the difference in haemoglobin concentration between males and females has been ascribed to this hormonal influence. This hypothesis has been confirmed experimentally by Kennedy (1962). An increase in the haemoglobin concentration has also been brought about by the administration of ‘anabolic’ drugs (Booij and Kuypers, 1962; Everse and Van Keep, 1962). Both testosterone and anabolic drugs have induced remissions in congenital and acquired aplastic anaemia (Kennedy and Gilbertson, 1957; Shahidi and Diamond, 1959, 1961; Kennedy, 1962). These authors also reported polycythaemia in some cases following treatment with androgens or anabolic drugs. Gardner and Pringle (1961) have described polycythaemia in a woman suffering from a tumour of the adrenal cortex. Booij and Kuypers (1962) reported two cases of polycythaemia after prolonged administration of Nandrolone‐phenylpropionate (Durabolin) at high dosage, and they also demonstrated that this drug had an erythropoietic action in rats. But, like most other workers they based their observations only on measurements on peripheral blood and they made no blood volume determinations. Thus they were unable to distinguish between an increase in haemoglobin concentration due to a decrease of the plasma volume and an absolute increase of the whole red cell mass. Kennedy (1957), however, observed a return to normal values of the red cell mass during treatment of breast cancer with testosterone and even an increase exceeding the normal values in some of the patients. Unfortunately no plasma volume determinations were made.

The results in three patients with clinical signs of polycythaemia after prolonged administration of anabolic drugs are reported. Examination of the peripheral blood showed an increase in haemoglobin concentration and packed cell volume. However, determination of the plasma and red cell volume showed that these changes were due to a decrease of the plasma volume.
Sites of Red Cell Destruction in the Haemolytic Anaemia of Adoptively Immunized NZB Mice
Authors: Barnes R. D. S. , Tuffrey Maureen
Published: March 2008

autoimmune haemolytic anaemia in the NZB strain of mice was first described by Bielchowsky, Helyer and Howie (1959) and a positive direct Coombs test (D.C.T.) in this condition was first reported by Holmes, Gorrie and Burnet (1961). The presence of another red‐cell autoantibody which cross‐reacts with human red cells (A.H.R.) has recently been observed in these mice (Holborow, Barnes and Tuffrey, 1965). It seems likely that the spleen also plays a part in this disease process. Splenomegaly has been noted and, in addition, splenectomy in young animals seems to reduce haemolysis in spontaneously diseased NZB mice (Helyer and Howie, 1963). Diminution of the effects of haemolytic disease following splenectomy in young male animals has been confirmed by Holmes and Burnet (1963). We have recently succeeded in inducing the formation of both D.C.T. and A.H.R. antibodies in young NZB mice by adoptively immunizing these animals with spleen cells from older animals possessing these antibodies. It appears that in such animals, the occurrence of the A.H.R. antibody enhances the increased red‐cell destruction associated with a positive D.C.T. (Barnes and Tuffrey, 1966).

Using a 51Cr labelled red‐cell method in such an experimental model, we have now tried to relate the occurrence of these two antibodies to the haematological disturbance, paying particular attention to the role of the liver and spleen in the haemolytic process.
The Aplastic Anaemia–Paroxysmal Nocturnal Haemoglobinuria Syndrome
Authors: Lewis S. M. , Dacie J. V.
Published: March 2008

Seven patients are described who suffered from the aplastic anaemia‐paroxysmal nocturnal haemoglobinuria syndrome. All had been first diagnosed as having aplastic anaemia. In one case the bone marrow became repopulated but the patient developed severe intravascular haemolysis and died of liver failure due to intrahepatic venous thrombosis. Two patients died of marrow aplasia; haemolysis was minimal and was only a laboratory phenomenon. Another patient also died of marrow aplasia but in his case haemolysis had contributed significantly to his illness. In three patients the bone marrow became repopulated completely or partially and the patients have recovered clinically despite the persistence of a small proportion of PNH red cells.

The relationship between aplastic anaemia and PNH is discussed. It seems likely that the link between the diseases is the development of an abnormal clone of haemopoietic cells in a regenerating, previously aplastic, marrow.

The effect of the superimposition of the PNH defect on the prognosis in aplastic anaemia is discussed. In five cases haemolysis had little or no influence on the course of the disease; but in two patients intravascular haemolysis was severe and was undoubtedly harmful.

The influence of splenectomy on the course of the disease was studied. It was performed in four of the patients, but in only one did it seem to have a beneficial effect.
Regulation of Platelet Production: ‘Hypersplenism’ in the Experimental Animal
Authors: Gabriele Geswalda de , Penington D. G.
Published: March 2008

The distribution and survival of 51Cr‐labelled platelets in normal, splenectomized and ‘hypersplenic’ rats together with calculation of the total body platelets demonstrate that the influence of the spleen on the circulating platelet count is primarily due to pooling of platelets, the size of the pool being related to splenic size. In states of normal platelet production splenic enlargement would be associated with reduction in the circulating platelet count.
The Platelet Destruction Site in Thrombocytopenic Purpuras
Authors: Najean Y. , Ardaillou N. , Dresch C. , Bernard J.
Published: March 2008

The site of sequestration of 51Cr‐labelled platelets has been studied in 465 subjects, of whom 317 suffered from idiopathic thrombocytopenic purpura. The validity of the method was demonstrated in several ways: a given subject usually showed the same site of platelet sequestration when investigated more than once even after a long interval; there were characteristic and very different platelet sequestration curves in the thrombocytopenias due to bone marrow hypoplasia, hypersplenism or ITP; and there was a correlation between the preoperative in vivo results and the radioactivity found in the spleen after splenectomy.

In ITP the destruction of labelled platelets was more often splenic in children and in patients whose thrombocytopenia responded to steroid therapy. There was a perfect correlation between the site of platelet destruction and the platelet rise immediately after splenectomy. There was a good correlation between the site of platelet destruction and the long‐term effectiveness of splenectomy.
The Esterase Activity in Megaloblasts, Leukaemic and Normal Haemopoietic Cells
Authors: Rozenszajn L. , Leibovich M. , Shoham D. , Epstein J.
Published: March 2008

Summary. Esterase activity was investigated in blood cells of peripheral blood and bone marrow in healthy subjects and in various pathological conditions. As substrates were used: α‐naphthyl acetate, naphthol AS‐D acetate and naphthol AS‐D chloroacetate. Fast blue B and fast garnet G. B. C. were used as coupling agents.

The distribution of AS‐D acetate esterase in different blood cells was described. Strong α‐naphthyl acetate esterase activity was found in monocytes, reticulum cells, megakaryocytes and in monoblasts in cases of monocytic leukaemia. Weak activity was shown in thrombocytes, and in lymphocytes.

With naphthol AS‐D chloroacetate as substrate strong enzymatic activity was demonstrated in the cells of the neutrophilic myelocytic series. The activity was strong in the more mature cells. Blasts from acute myelocytic leukaemia showed enzymatic activity.

The use of α‐naphthyl acetate and naphthol AS‐D chloroacetate as substrates proved to be of help in differentiating between the three types of acute leukaemia.

In cases with megaloblastic erythropoiesis only strong α‐naphthyl acetate esterase activity was demonstrated in the megaloblasts. Successful treatment of pernicious anaemia with B12, resulted in disappearance of megaloblasts and cessation of the strong esterase activity. There seems to be a correlation between strong naphthyl acetate esterase activity and the presence of megaloblasts. An explanation of this phenomenon is suggested.
The Differential Ferrioxamine Test in Rheumatoid Disease, Neoplastic and Other Haematological Disorders
Authors: Wardle E. N. , Israëls M. C. G.
Published: March 2008

Summary The chelatable body iron test shows that one‐third of patients with rheumatoid disease have a high body iron in the face of low serum iron values. This may reflect an altered reactivity of the reticulum cell related to the activity of the disease process, resulting in increased iron in the reticulum cells of the marrow, liver and spleen and possibly in the synovium of the diseased joints. The test may be clinically useful to predict the response of the rheumatoid patient to iron, and in particular to detect those with genuine iron deficiency anaemia. High chelatable body iron values are also found in advanced cases of reticulosis and carcinoma at the same time as a lowering of the serum iron and an increase of the serum mucoprotein.
Absence of Intrinsic Factor from Human Portal Plasma during 57CoB12 Absorption in Man
Authors: Cooper B. A. , White J. J.
Published: March 2008

Summary The 57CoB12 activity in blood obtained from the portal vein during 57CoB12 absorption did not have the biological or the immunological features in vitro of intrinsic factor from normal human gastric juice.

This indicates that 57CoB12 probably is not absorbed from the intestine with intrinsic factor.
The Metabolism of Iron‐Dextran Given as a Total‐Dose Infusion to Iron Deficient Jamaican Subjects*
Authors: Wood J. K. , Milner P. F. A. , Pathak U. N.
Published: March 2008

Summary The movements of iron‐dextran, following a total dose infusion of up to 2550 mg. iron in six severely iron deficient patients, have been studied using a 59Fe tagged complex. The preparation is removed from the plasma in 8–10 days. Fifty per cent of the iron was incorporated into haemoglobin in 3–4 weeks and the iron stores replenished rapidly.

Using organ scanning, the liver was confirmed as the site of primary plasma clearance, but accumulations of iron were also detected in the spleen and bone marrow. Only minute quantities of radioactivity appeared in the urine. No untoward effects on iron metabolism have been detected, but reduction of the serum iron and total iron binding capacity to low levels 6 weeks post infusion is of interest. An attempt has been made to interpret the findings to elucidate the ferrokinetics of this method of treatment.
Post‐Transfusion Survival of Red Cells Stored in Liquid Nitrogen
Authors: Morrison F. S. , Mollison P. L. , Robson D. C.
Published: March 2008

Summary In 13 cases in which red cells were stored in a PVP‐ACD mixture at 4°C. for not more than 24 hours before being frozen in liquid nitrogen and were then stored in liquid nitrogen vapour (−150°C.) for periods up to 486 days, post‐transfusion 51 Cr survival at 24 hours varied from 57 to 83.5 per cent with a mean of 69.8 per cent. There was no evidence that the period of storage at −150°C. had any influence on survival. On the other hand, minor variations in the method of labelling the cells with 51 Cr did appear to affect the results; there was some evidence that repeated washing of the cells in PVP‐plasma had an unfavourable effect.

In a further 14 cases in which red cells were stored in PVP‐plasma at 4°C. for up to 48 hours before freezing and for 1–32 days after thawing, evidence was obtained first, that storage for more than 24 hours before freezing was deleterious and, second, that storage for up to 12 days probably had no adverse effects and, thirdly, that storage for 15 days or more after thawing was very deleterious.

In two experiments in which cells were labelled both with DF32P and with 51Cr it was found that Cr did not elute at an abnormal rate from red cells which had been frozen and thawed after being mixed with PVP. Accordingly, standard corrections for Cr elution may be applied and it may be concluded that the true 24‐hour survival of red cells frozen and thawed in liquid nitrogen averages about 73.5 per cent.
The Passage of Vitamin C across the Erythrocyte Membrane
Authors: Hughes R. E. , Maton S. C.
Published: March 2008

Summary In all the species examined dehydroascorbic acid entered the erythrocyte considerably more rapidly than ascorbic acid (vitamin C). The uptake was pH‐dependent but did not appear to be influenced by enzyme inhibitors. The rate of uptake of the dehydroascorbic acid appeared to be influenced by the activity of an erythrocyte DHAA‐reducing system. Dehydro‐iso ascorbic acid (dehydro‐d‐araboascorbic acid) entered the erythrocyte considerably less rapidly than DHAA. Ascorbic acid was released from the erythrocyte at a comparatively slow rate.
Occlusion of Plasma Proteins by Human Fibrin: Studies using Trace‐Labelled Proteins
Authors: Regoeczi E.
Published: March 2008

Summary The occlusion of 13 different proteins by human fibrin has been investigated using radioactive techniques. Each of the proteins examined exhibited different tendencies to be retained by clots. For a satisfactory demonstration of this, studies of the effects of varying protein and fibrinogen concentration were required and are reported here.

With normal plasma, the contamination of the syneresed and washed fibrins with albumin and transferrin was negligible whereas significant quantities of β‐lipoproteins, haptoglobin‐haemoglobin complex, free haemoglobin and IgG‐globulins were trapped. Substantial contaminations were noted with macroglobulins (IgA, IgM and α2‐macroglobulin), and above all with plasminogen, of which more than 50 per cent was adsorbed to the fibrin. Bence Jones proteins were also occluded by fibrin, Type K more so than Type L, whereas iodinated thrombin showed no affinity for fibrin.

Some effects of clotting conditions on occlusion are also reported, and it is shown that in dilute plasmas occlusion is reduced and in covalently bound fibrin it is enhanced.
A Study of the Interdependence of Red Cell and Bone Marrow Stem Cell Populations
Authors: Orr J. S. , Kirk J. , Gray Kathleen G. , Anderson J. R.
Published: March 2008

Haemolytic anaemia was produced in rabbits by the administration of a regular course of incompatible red cell iso‐antibody. A greatly increased rate of red cell production was observed but haemoglobin and reticulocyte counts exhibited vigorous and continuing fluctuations with, in the adult rabbits, a regular periodicity. The effects of steroids and splenectomy on this antibody‐mediated red cell destruction were found to be virtually unobservable, and the implications of this with regard to the haemolytic anaemias of man resulting from red cell destruction by iso‐ or auto‐antibodies are discussed.

The significance of the fairly regular oscillations was analysed on the basis of evidence on the various parts of the haemopoietic system. The nature of these and other oscillations observed led to the suggestion that they could be understood in terms of interactions of a four‐component system: the stem cell population; a stem cell specific mitotic inhibitor, termed chalone, which is produced in proportion to the stem cell population and catabolized in proportion to its own level; the differentiated cell population; and erythropoietin. The features of the various oscillations in terms of the four‐component system, and the effects of the parameters on these features, are discussed.
The Measurement of Iron Clearance from the Skin
Authors: Beamish M. R. , Jacobs A.
Published: March 2008

Iron clearance from the skin was measured in 10 normal subjects and two patients with iron‐deficiency anaemia. Some of the iron injected into the skin is probably bound to transferrin in the interstitial fluid whilst the remainder is rapidly removed into the blood stream. Approximately two‐thirds of the bound iron is cleared with a half‐life of about 1 day, the remainder disappearing slowly with a half‐life of about 60 days.
Relationship between Membrane Function and Permeability II. THE INTERRELATIONSHIP OF COPPER ATTACHMENT, GLYCEROL TRANSPORT AND THROMBOPLASTIN AVAILABILITY IN THE INTACT HUMAN ERYTHROCYTE
Authors: Cohen Phin
Published: March 2008

Glycerol in trace amounts appears to enhance exponentially the attachment of trace amounts of copper to human erythrocytes, while its own penetration of the erythrocytes is unaffected. At higher concentrations of glycerol its effect in enhancing copper attachment is abolished. At higher concentrations of copper, glycerol transport is delayed as shown by the PF‐3 availability test in which glycerol is used as the probing agent and the erythrocytes as the source of PF‐3 activity. The copper effect on the glycerol‐induced PF‐3 availability may be surmounted by a surfeit of glycerol.

Using these findings, along with some assumptions based upon other data in the literature, a new theory interrelating glycerol and copper transport and thromboplastin availability in the intact erythrocyte has been presented.
Transferrin Synthesis in the Rat: A Study Using the Fluorescent Antibody Technique
Authors: Lane R. S.
Published: March 2008

The fluorescent antibody technique has been used to investigate transferrin synthesis in rats. The alteration in hepatic transferrin content has been noted in rats suffering from acute blood loss, chronic iron deficiency before and after treatment with iron, iron loading and localized hepatic sepsis. Marked changes in the transferrin content in the rat liver can be correlated with changes in erythropoietic rate, plasma transferrin concentration and the associated variation in catabolic rate of transferrin in these different situations. Rapid increases in hepatic transferrin content are considered to represent a synthetic response and are associated with elevation of plasma transferrin concentration. The synthesis response follows an extreme reduction in liver transferrin content; after acute blood loss and treatment of chronic iron deficiency anaemia with iron, a transferrin synthesis response coincides with the onset of erythropoiesis. The injection of iron‐dextran into normal rats appears to be associated with a suppression of transferrin synthesis during the period of peak hepatic ferritin formation. It is thought that iron influences transferrin synthesis through its regulatory effect on erythropoietic rate.
Regulating Factors in the Transfer of Iron across the Rat Placenta
Authors: Lane R. S.
Published: March 2008

The effect of maternal blood loss on the iron uptake of the foetectomized placenta has been studied. Normal pregnant rats were used as controls. It is suggested that the rate of maternal blood flow and plasma iron concentration primarily controls placental iron uptake independent of the presence of a foetus. Starch gel electrophoresis and fluorescent antibody techniques have been employed to investigate foetal rat synthesis of transferrin. The onset of synthesis at the commencement of the last third of gestation is probably important in creating a viable system for foetal plasma iron turnover which, under the control of the foetal erythroid marrow, is responsible for the high rate of iron transfer from the placenta to the foetus.
The Effect of Phytohaemagglutinin on Human Foetal Cells Grown in Culture
Authors: Pegrum G. D. , Ready Doreen , Thompson Elizabeth
Published: March 2008

Cell suspensions of foetal thymus, liver, spleen and bone marrow have been grown in cell culture and the effect of adding PHA observed. 3H thymidine uptake by the cells after exposure for a measured time was quantitated by autoradiographic counts performed on the initial suspensions and following culture. The initial unstimulated liver and thymic cell suspensions had a high level of 3H thymidine uptake, while that of the spleen and bone marrow cells was low. After 3 days culture the unstimulated cells from the liver, thymus and bone marrow showed very little 3H thymidine uptake, while that of the spleen was slightly increased. Foetal thymic and splenic cells responded to PHA while liver and bone marrow cells did not. The findings suggest that foetal cells of similar morphology may have different origins in the reticulo‐endothelial system.
Increased Agglutinability by Anti‐i of Red Cells in Sideroblastic and Megaloblastic Anaemia
Authors: Cooper A. G. , Hoffbrand A. V. , Worlledge S. M.
Published: March 2008

Agglutinin titres have been performed using anti‐I and anti‐i cold antibodies on red cells from patients with sideroblastic, iron deficiency and megaloblastic anaemias, as well as on normal adult and cord blood red cells.

Raised i antigen titres were found using the red cells of 13 of 15 patients with sideroblastic anaemia and of seven of eight patients with megaloblastic anaemia but in none of eight patients with iron deficiency anaemia and in one of 17 patients with megaloblastic anaemia in remission. Those patients who had an elevated i antigen titre usually also had an elevated I antigen titre.

The raised i and I antigen titres of the red cells of a patient with pernicious anaemia were shown to decrease markedly within 3 months of the onset of B12 therapy, indicating that the alteration probably persists for the life‐span of the red cell but that the cause of the alteration is reversible once the underlying blood disorder is corrected.

It is believed that disordered erythropoiesis results in membrane alterations which lead to the increased agglutinability, but the cause is not known. It does not appear that a shortened red cell maturation time is a necessary factor.
The Effect of Iron Stores on Gastric Acid Secretion by Rats
Authors: Murray M. J. , Stein Nell
Published: March 2008

Tissue iron deficiency as measured by liver non‐haem iron levels was produced in rats by iron‐poor diets and bleeding. Studies on gastric secretion with the Shay technique revealed significant changes in pH, total acid and acid concentration in the iron deficient rats when compared with control normals and control anaemic animals.
Bone Marrow Involvement in Burkitt's Tumour
Authors: Wright D. H. , Pike P. A.
Published: March 2008

The bone marrow aspirates from 100 cases of Burkitt's tumour have been analysed. Eight of these showed diffuse massive infiltration with Burkitt tumour cells and eight showed very scanty tumour cells. A leuco‐erythroblastic blood picture with occasional or no tumour cells was commonly found in those cases with diffuse massive bone marrow infiltration. This type of bone marrow involvement carries a poor prognosis, the mean survival time of the eight cases in this series being 33 days. The percentage of lymphocytes in the marrow smears of 20 children with Burkitt's tumour, without tumour cells in their bone marrow, was found to be less than that in the bone marrow smears from 20 control children. This may reflect an impaired immune mechanism in children with Burkitt's tumour.
The Mechanism of Action of Human Placental Lactogen on Erythropoiesis
Authors: Jepson J. H. , Friesen H. G.
Published: March 2008

A purified preparation of human placental lactogen (HPL) increased the incorporation of 59Fe into erythrocytes of polycythaemic mice, an effect which was abolished by its incubation with anti‐HPL but not with anti‐sheep erythropoietin (anti‐ESF).

The erythropoietic‐stimulating capacity of HPL was abolished by increasing the endogenous concentration of anti‐ESF prior to injection of HPL into plethoric mice, indicating that some ESF was required for the effect of HPL to become apparent. The main action of HPL appeared to be through an augmentation of the erythropoietic effect of ESF in intact and hypophysectomized plethoric and nonplethoric mice through its specific and general anabolic action on erythropoiesis. A similar effect may occur during human pregnancy.
The Site of Abnormal Erythrocyte Destruction during Experimental Fever
Authors: Karle Hans
Published: March 2008

Measurement of the 51Cr activity in the whole body, blood, and reticulo‐endothelium system organs in rabbits, exposed to a period of fever by injection of bacterial pyrogen after labelling of the erythrocytes, showed:

(1) 51 Cr, liberated by normal or abnormal erythroclasis, is temporarily deposited in an extravascular site. Under normal conditions the spleen and bone marrow are the main organs where the deposition occurs.

(2) The abnormal erythrocyte breakdown during fever immediately gives rise to an increased excretion of 51Cr in the urine. Simultaneously, there is a significant increase in the activity in the spleen. Five days after a 5‐day period of fever, about 40 per cent of the abnormal 51Cr loss from the blood was recovered in the spleen. There were no signs of intravascular haemolysis.

(3) The presence of increased haemoglobin in the splenic tissue of the fever‐exposed rabbits and the absence of abnormal erythrocyte loss during pyrexia in splen‐ectomized rabbits indicate that the spleen plays a direct role in the abnormal loss. The pathogenesis of the cell loss is discussed.
Observation of Four Age‐Related Parameters in the Red Cells of Various Disease States
Authors: Sabine Jean C. , Kwok Lillian W.
Published: March 2008

Simultaneous determinations of anaerobic glycolysis, hexokinase activity (HxK), glucose‐6‐phosphate dehydrogenase activity (G6PD) and acetyl‐cholinesterase activity (AChE) were made in the whole red cell populations of patients and of healthy subjects, and in the layers of the centrifuged cell packs of selected patients to give regression lines for each parameter plotted against each of the others. Apparently normal interrelationships were found in blood loss and in haemolytic disease of various origins.

Abnormalities were revealed which would escape notice if a single parameter were assayed. These were relative, not absolute, deficiency of anaerobic glycolysis in a case of congenital nonspherocytic haemolytic disease with no deficiency of G6PD, HxK or pyruvate kinase; of HxK in a case of unexplained anaemia; and of AChE in a case of Coombs positive haemolytic disease.

In a case of paroxysmal nocturnal haemoglobinuria AChE was severely deficient while glycolysis, HxK and G6PD were extraordinarily high and appeared normally interrelated. The patient had been transfused just before these studies, and calculations based on the enzyme data led to the hypothesis that in this case the donor cells were rapidly destroyed.

Observations in normal blood showed that values for G6PD and AChE occur as two independent normal distributions. The same was true for glycolysis and AChE. Glycolysis and G6PD were correlated but did not approach a perfect functional relationship.

There is evidence that high G6PD unrelated to red cell age occurs in malignant disease, but it is not conclusive.
Polycythaemia Vera: Differential Diagnosis by Ferrokinetic Studies and Treatment with Busulphan (Myleran*)
Authors: Brodsky Isadore , Benham Kahn S. , Brady Luther W.
Published: March 2008

Summary. Twenty‐two patients with polycythaemia Vera, six with benign polycythaemia or relative polycythaemia and six with secondary (hypoxaemic) polycythaemia were compared by means of ferrokinetic studies and measurement of bone‐marrow iron stores. In polycythaemia Vera a poor correlation was noted between the haemoglobin (Hb), packed cell volume (PCV) and total red‐cell mass (TRBC). Reliance on the Hb and PCV alone is frequently misleading in the differential diagnosis of the polycythaemic states. A rapid 59Fe T1/2 (< 30 minutes) was found in 85 per cent of patients with polycythaemia Vera, and was associated with absent marrow iron stores in 21 of 22 patients. In benign polycythaemia and relative polycythaemia the 59Fe T1/2 was normal and stainable iron was present in the marrow. Similar findings were noted in secondary polycythaemia.

Fifteen of the 22 patients with polycythaemia Vera were treated with busulphan. This treatment was effective in controlling leucocytosis and thrombocytosis. Dosage, toxicity and indications for the use of busulphan in the treatment of polycythaemia Vera are discussed.
Hormonal Regulation of Pre‐natal Haemoglobin Synthesis by Erythropoietin
Authors: Cole R. J. , Hunter Janne , Paul J.
Published: March 2008

Summary. Developmental changes in the response of mouse, rat and rabbit foetal liver cells and of rat foetal spleen cells to erythropoietin have been investigated in vitro.

Liver cells from 101/2‐141/2‐day mouse foetuses and 12–13‐day rat foetuses show little haemoglobin synthesis in vitro but marked response to erythropoietin. This is followed, in the mouse, by a brief period in which the rate of synthesis on explantation is high and cannot be increased by erythropoietin. In the rat from 14 to 16 days the rate of synthesis on explantation increases progressively while the response to erythropoietin persists. Liver cells from later foetuses of both animals show variable haemoglobin synthesis and are not erythropoietin sensitive. 14–18‐day foetal rabbit liver cells and 18–19‐day foetal rat spleen cells are also sensitive to erythropoietin. It is suggested that development of sensitive stem cell populations precedes erythropoietin production in vivo so that critical population numbers are reached which enable feedback controls to be established.

Isotopically labelled haenioglobins produced in vitro by rat and mouse foetal liver cells were electrophoretically characterized. Erythropoietin caused increased production of a haemoglobin type already present.
Red‐Cell Density in Paroxysmal Nocturnal Haemoglobinuria
Authors: Lewis S. M. , Vincent P. C.
Published: March 2008

Summary. Density distribution of red cells has been measured in twelve patients with PNH by centrifuging blood with phthalate‐ester mixtures of varied specific gravity. Results have been compared with findings in other blood diseases and in normal subjects. The PNH red cells have an abnormally low density but normal osmotic fragility. The reason has not been established.

The lightest cells had in general a greater phospholipid content than the heavier cells from the same blood sample; but not more so than in normal blood, and there did not appear to be significant variation in the phosphatide composition of the excessively light PNH cells.

By the technique described it is possible to separate a limited fraction containing only the lightest 10 per cent of the cell population. This fraction contains a concentration of cells which are most susceptible to lysis in vituo; it provides a means for increasing the sensitivity of laboratory tests on PNH blood, and it has enabled a diagnosis to be made in an obscure case when the standard in‐vitro lysis tests on whole blood have been negative.
Cell Population Kinetics of the Erythroid System in the Rat. The Response to Protracted Anaemia and to Continuous γ‐Irradiation
Authors: Tarbutt R. G.
Published: March 2008

Estimates have been obtained of the parameters defining the cell population kinetics of the erythroid system in rats subjected to protracted anaemia and to continuous γ‐irradiation at 43 rad/day.

The inflow of cells to the proerythroblast compartment and the outflow of erythrocytes to the circulation have been measured by 55Fe autoradiography. In the anaemic rats, the ratio of the outflow to the inflow is normal, indicating that the precursors undergo the normal number of divisions during maturation from proerythroblast to erythrocyte. In the continuously irradiated rats, the outflow is normal but the inflow is decreased by a factor in the range 2–4, so that the ratio of the outflow to the inflow is increased by this factor, and the cells undergo more divisions than normal during maturation.

The cell proliferation parameters of the various maturation stages of the erythroid system have been determined in anaemic rats, using 3H‐TdR autoradiography. The number of divisions undergone during maturation through each stage is normal, but the maturation times and cycle times are considerably reduced. Less information is available on the proliferation parameters in the continuously irradiated rats, but the 55Fe experiments indicate that the transit times of the proerythroblasts and of the non‐dividing stages of the system are increased in response to this stress.
Serum Blood Group Substances and ABO Haemolytic Disease
Authors: Denborough M. A. , Downing H. J. , Doig A. G.
Published: March 2008

The passage of incompatible maternal anti‐A and anti‐B isoagglutinins across the placenta can cause haemolysis of foetal erythrocytes. This occurs almost entirely in group A or B infants born to a group O mother, but only one in five such infants shows evidence of a mild haemolytic disease. This suggests that there must be factors protecting the foetal red cells against incompatible maternal antibody. The investigation described here suggests that one such factor is the presence of blood group substances in foetal serum.

In an investigation of the amount of A‐substance present in the cord blood of group A infants, significantly greater amounts were found in secretors than in non‐secretors. Also, in group A secretor infants, the amounts of A substance in the cord blood of infants with group O mothers was diminished in comparison with those with group A mothers. These findings are compatible with the idea that some of the A‐substance in the serum of the group A infants with O mothers had combined with maternal anti‐A agglutinin and had been removed from the circulation. This supports the suggestion that blood group substances in cord serum protect the foetal erythrocytes from incompatible maternal antibodies.
The Incidence of Anti‐A and Anti‐B Isoagglutinins in Cord Blood and Maternal Saliva
Authors: Denborough M. A. , Downing H. J.
Published: March 2008

The distribution of anti‐A and anti‐B isoagglutinins varies in individuals of different ABO groups in two distinct ways. Individuals of group O differ from those of group A in that anti‐B agglutinins are found more commonly in saliva and in milk. This is probably due to differences in the local synthesis of IgA anti‐B in the appropriate glands. Mothers of group O also differ from those of groups A and B in transmitting larger amounts of IgG anti‐A and anti‐B to the circulation of their foetus. This is probably explained by the fact that individuals of group O tend to produce more 7S isoagglutinin than those of groups A and B.
Hypersegmented Neutrophilic Granulocytes in Iron Deficiency Anaemia
Authors: Beard Michael E. J. , Weintraub Lewis R.
Published: March 2008

Neutrophil hypersegmentation and giant metamyelocytes have been demonstrated in iron‐deficiency anaemia in which an associated deficiency of exogenous vitamin B12 or folate has been excluded. In each case treatment with iron returned the lobe average to within the normal range.
The Incorporation of Delta Aminolaevulinic Acid and Glycine into Faecal Stercobilin and Coproporphyrin in Man
Authors: Yamamoto Toshio , Fujii Masahiro , Inuki Taira , Wakisaka Gyoichi
Published: March 2008

The incorporation of [4‐14C]ALA and [2‐14C]glycine into haem, faecal coproporphyrin and stercobilin was studied in patients with various disorders. After the administration of [4‐14C]ALA, the specific activities of isolated faecal copropor‐phyrin and stercobilin increased and declined quickly within 3–4 days. These changes were associated with each other, and this relationship suggests that they arise from a common source. Incorporation of the labelled precursor into haem was minimal. When [2‐14C]glycine was the precursor, the rise and fall of faecal Coproporphyrin activity was independent of that of stercobilin and the stercobilin activity maintained a plateau for several days after the fall of faecal Coproporphyrin activity. This was associated with incorporation of the precursor into red cell haem. The activity peak in stercobilin which appeared at the end of red cell life span was not associated with faecal Coproporphyrin activity. These findings are consistent with the presence of two components of early‐labelled bilirubin. The first of these is associated with faecal Coproporphyrin activity and independent of erythropoiesis and the second is unassociated with faecal Coproporphyrin and closely related to erythropoiesis.

Faecal Coproporphyrin activity was not related to red cell destruction, but correlated with hepatic production of bilirubin, and is thought to be hepatic in origin.
Serum Valine and Methionine Levels in Pernicious Anaemia under Treatment
Authors: Parry T. E.
Published: March 2008

The serum levels of the amino acids, valine and methionine have been determined by a quantitative microbiological method in 17 cases of pernicious anaemia both before and on successive days after treatment. The results have been compared with the serum levels of the two amino acids in 16 normal subjects under similar conditions.

The serum valine level is normal in pernicious anaemia in relapse. It falls sharply during the first 48 hours following treatment, thereafter rising gradually to reach about two‐thirds the pretreatment level by the fifth day. This confirms the fall in valine level in whole blood and marrow previously reported in pernicious anaemia under treatment.

The serum methionine level is subnormal in pernicious anaemia in relapse. It rises to normal in 48 hours after treatment.

Both vitamin B12 and folic acid are effective in lowering the serum valine and elevating the serum methionine.

The rise in serum methionine can be explained in terms of the known actions of vitamin B12 and folic acid. The fall in serum valine cannot at present be explained but several possibilities are discussed.
The Absorption of Pteroylglutamic (Folic) Acid in Rats
Authors: Hefner G. W.
Published: March 2008

Absorption of crystalline folic acid (pteroylglutamic acid—PGA) was studied in rats, using tritiated PGA and an in vivo absorption technique. Increasing doses of PGA were introduced into the jejunum and ileum: the percentage absorption fell with increasing doses in the jejunum, suggesting the presence of an active transport mechanism, whereas percentage absorption in the ileum remained constant for all doses, suggesting that absorption occurred by passive diffusion. Phenytoin and methotrexate put into the jejunum immediately before PGA partly inhibited its absorption, as did subcutaneous methotrexate given 3 hours before the PGA was administered. Methotrexate had no effect on the ileal absorption of PGA, nor on the absorption of D‐xylose in the jejunum.
Anomalies of Blood Group Antigens and Erythrocyte Enzymes in Two Types of Chronic Refractory Anaemia
Authors: Dreyfus B. , Sultan C. , Rochant H. , Salmon Ch. , Mannoni P. , Cartron J. P. , Boivin P. , Galand C.
Published: March 2008

Blood‐group antigens and erythrocyte glycolytic enzyme activities were studied in II cases of refractory anaemia consisting of seven cases of refractory anaemia with excess of myeloblasts in bone marrow and four cases of acquired sideroblastic anaemia. Some significant modifications of the amounts of A, A1, B, H, I and i antigens were found in 10 cases. Some enzyme deficiencies involving pyruvate kinase, 2–3‐diphosphoglycerate mutase and phosphofructokinase were observed. In addition, several populations of pathological red cells showing distinct antigenic abnormalities were demonstrated in one patient. A new type of anaemia with acquired multiple and varied enzyme anomalies of the red‐cell series has therefore been defined. Its links with acute leukaemia are discussed.
Changes in Factors V and VIII after Administration of Adrenaline to Normal and Splenectomized Rats
Authors: Pudlaak P. , Farská I. , Deimlová E.
Published: March 2008

Changes in Factors V and VIII were studied in normal, unilaterally nephrectomized, and splenectomized rats. Adrenaline in a dose of 3 or 6 μg. per 200 g. body weight subcutaneously induced a significant but not very large increase in the activity of Factors V and VIII. A similar increase occurred in splenectomized and unilaterally nephrectomized rats. However, after unilateral nephrectomy an injection of adrenaline did not further raise the concentration of Factor VIII; and in Splenectomized rats a decrease in Factor VIII was found after adrenaline. The level of Factor V was not further significantly altered in either operated group after giving adrenaline.

The mechanism of these changes is discussed but remains to be elucidated.
Postulated Gastric Factor Enhancing Iron Absorption in Haemochromatosis
Authors: Smith Paul M. , Studley Frances , Williams Roger
Published: March 2008

A variety of everted gut sac techniques have been used to determine if there is a factor in neutralized gastric juice from patients with haemochromatosis and iron deficiency which will potentiate iron absorption, as suggested by Murray (1968). No such effect was found and iron uptake by the sacs did not correlate with measurements of iron absorption in the patients with haemochromatosis using a whole body counter.

Peak iron uptake was found to occur from between 12 to 24 cm. from the rat pylorus, in the jejunum. Ascorbic acid enhanced iron transfer from the mucosal to the serosal surface but no evidence for an active transport system was found.
Effect of a Natural Phosphatidyl Serine Fraction on Blood Coagulation, Platelet Aggregation and Haemostasis
Authors: Nishizawa E. E. , Hovig T. , Lotz F. , Rowsell H. C. , Mustard J. F.
Published: March 2008

The intravenous infusion of a phosphatidyl serine fraction into pigs or dogs caused prolonged bleeding from transected vessels. This effect appeared to be due to inhibition of blood coagulation and of platelet aggregation induced both by collagen and by thrombin. This influence on the effect of thrombin and collagen on platelets may be attributed to suppression of the release of platelet constituents, including ADP, for the phosphatidyl serine fraction does not inhibit ADP‐induced aggregation.
Induction of Intravascular Coagulation and Renal Cortical Necrosis in Rabbits by Simultaneous Injection of Thorotrast and Endotoxin
Authors: Seeler Ruth A. , Forman Edwin N. , Bolger Jane F. , Abildgaard Charles F. , Schulman Irving
Published: March 2008

Preparation of rabbits with 6 ml./kg. of Thorotrast, administered intravenously, permits the induction of intravascular clotting and the production of renal cortical necrosis with simultaneous injections of E. coli endotoxin. With this dose of Thorotrast, a dose‐response relationship was observed between the fall in fibrinogen after 4 hours and doses of endotoxin ranging from 5 to 50 μg./kg. body weight. With such preparation, renal cortical necrosis occurred in 46 per cent of animals receiving 100μg./kg. of endotoxin and increased to 80 per cent in animals receiving 100 μg./kg. Thorotrast preparation with 3 ml./kg. permits intravascular clotting to occur with a single injection of endotoxin administered simultaneously. However, no relationship between endotoxin dose and fibrinogen depletion was observed and renal cortical necrosis developed only with relatively high doses of endotoxin. An efficient and predictable experimental model for studying both intravascular clotting and renal cortical necrosis is described by these observations.
Generalized Shwartzman Reaction: Role of the Granulocyte in Intravascular Coagulation and Renal Cortical Necrosis
Authors: Forman Edwin N. , Abildgaard Charles F. , Bolger Jane F. , Johnson Christine A. , Schulman Irving
Published: March 2008

The protective effect of nitrogen mustard‐induced neutropenia on the development of the GSR was studied. No coagulation defect was found in neutropenic rabbits and simultaneous administration of Thorotrast and endotoxin did not produce intravascular coagulation or renal cortical necrosis. Infusion of neutropenic rabbits with suspensions of viable granulocytes derived from peritoneal exudates reinduced susceptibility to both intravascular coagulation and renal cortical necrosis. It is concluded that the presence of granulocytes is essential for the production of intravascular coagulation by endotoxin.
The May–Hegglin Anomaly. A CASE REPORT AND CHROMOSOME STUDIES
Authors: Gausis Nina , Fortune D. W. , Whiteside M. G.
Published: March 2008

The May‐Hegglin anomaly was observed in a patient admitted to hospital on account of bruising and foetal death in utero. The patient's son was also found to have the anomaly and chromosomal studies on both were normal.
Two Types of Haemophilia (A+ and A−): A Study of 48 Cases
Authors: Denson K. W. E. , Biggs Rosemary , Haddon M. E. , Borrett R. , Cobb Kathryn
Published: March 2008

Summary. The inhibitor‐neutralizing ability of plasma and Factor‐VIII concentrates from a group of 48 haemophilic patients and 30 normal persons has been studied. Factor‐VIII inhibitors were neutralized by the material from four of the haemophilic patients and all the normal subjects. The material from the larger group of 44 haemophilic patients showed no significant inhibitor‐neutralizing ability. The former group have been designated Haemophilia A+ because of the presence of material antigenically related to Factor VIII, and the latter group Haemophilia A− because of the lack of such material.
Sites of Red Cell Destruction in the Anaemia of Experimental Burns*
Authors: Bhargava Manorama , Agarwal K. N. , Kumar Sharad
Published: March 2008

Summary. There are mainly two sites for red‐cell destruction following thermal burn injury in albino rats. Intravascular haemolysis as well as hepatic destruction of red cells account for the elimination of red cells from the circulation during anaemia observed as early as 24 hours following burns. The anaemia that occurs on the 6th day of burns is associated mainly with splenic sequestration of red cells. Prednisolone was found to be ineffective in inhibiting the splenic sequestration of red cells, but splenectomy almost completely prevents the progression of anaemia.
Clinical and Laboratory Studies on the Action of Desferrioxamine
Authors: Cumming R. L. C. , Millar J. A. , Smith J. A. , Goldberg A.
Published: March 2008

Summary. Most of the published literature on the iron chelating agent desferrioxamine (DFA) relates to urinary excretion of iron following its administration. In the present study, six patients suffering from various iron storage diseases were maintained on a fixed dietary intake of iron and a basal value for faecal iron excretion was obtained. In all cases the faecal iron content rose significantly after treatment with desferrioxamine (P <0.05). The increase in faecal iron after DFA was between 30 and 50 per cent (mean 40 per cent) of the total increase in both urinary and faecal iron excretion. This finding has a relevance to the correct interpretation of tests using DFA for the assessment of body iron stores.

The serum ferritin levels of another group of patients suffering from various iron storage diseases, but also including one patient with iron deficiency, were measured before and after DFA administration. In all cases the serum ferritin levels increased significantly (I) <0.001) 2 hours after administration of DFA.

Quantitative studies on the ferritin protein and ferritin iron content of liver, spleen, kidney and intestinal mucosa in rats showed that DFA causes significant reductions in both these substances in liver and spleen. It was calculated that over 70 per cent of the iron removed by DFA emanated from liver and that the amount of ferritin protein released from rat liver after DFA was sufficient to bind all the iron removed. Thus the major source of the iron excreted after DFA therapy is probably liver ferritin iron.
Oxymetholone in Refractory Anaemia
Authors: McCredie K. B.
Published: March 2008

Summary. Three cases of aplastic anaemia, one of Fanconi's anaemia and one of a myeloproliferative disorder responded to therapy with oxymetholone. Seven cases of chronic renal failure and one of refractory sideroblastic anaemia were treated without success. Oxymetholone appears to be effective in those diseases which have a high level of erythropoietin but not in the anaemia of chronic renal failure.