bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Pure Red Cell Aplasia: VIII. MAINTENANCE THERAPY WITH IMMUNOSUPPRESSIVE DRUGS
Authors: Zaentz S. D. , Krantz S. B. , Brown E. B.
Published: March 2008

Summary.

Two patients with pure red cell aplasia, whose marrow cells were capable of increasing their rate of haem synthesis when incubated in vitro with erythropoietin concentrate, had a complete remission associated with the administration of cyclo‐phosphamide and prednisone. Both patients relapsed when the drugs were withdrawn. The patients again went into remission when therapy was reinstituted. Maintenance of normal erythropoiesis was dependent on the continued administration of these drugs. This study provides additional evidence for a causal relationship between immunosuppressive therapy and the resumption of erythropoiesis in patients with this disease and demonstrates the value of this therapy for the maintenance of a remission.
Surface Sulphydryl Groups and Phagocytosis‐Associated Oxidative Metabolic Changes in Human Polymorphonuclear Leucocytes
Authors: Tsan Min‐Fu , Newman Burlina , McIntyre Patricia A.
Published: March 2008

Summary. The role of surface sulphydryl (‐SH) groups of human polymorphonuclear leucocytes on phagocytosis and. phagocytosis‐associated oxidative metabolic changes was studied. p‐Chloromercurybenzene sulphonic acid, a surface ‐SH group inhibitor, had no effect on phagocytosis, superoxide production during phagocytosis, or killing of S. aureus by the leucocytes, while it inhibited phagocytosis‐associated stimulation of hexose monophosphate pathway activity and H2O2 production. In contrast, N‐ethylmaleimide, which inhibits both intracellular and surface ‐SH groups, inhibited phagocytosis and phagocytosis‐associated oxidative metabolic changes. p‐Chloromercurybenzene sulphonic acid also inhibited the stimulation of hexose monophosphate path‐way activity by exogenous H2O2, suggesting a regulatory role of plasma membrane on the pathway's activity in human polymorphonuclear leucocytes. The results also suggest that: (1) superoxide production is the primary event of oxidative metabolic changes during phagocytosis, (2) superoxide plays an important role in the killing of S. aureus, and (3) the hexose monophosphate pathway plays a primary role in producing NADPH for H2O2 production from superoxide.
Activation of Intravascular Coagulation by Endotoxin: the Significance of Granulocytes and Platelets
Authors: Müller‐Berghaus Gert , Bohn Elisabeth , Höbel Wilfried
Published: March 2008

Summary. The importance of granulocytes and/or platelets in endotoxin‐induced generalized intravascular coagulation was studied in neutropenic as well as thrombocytopenic rabbits. Neutropenia and thrombocytopenia were induced by oral administration of busulphan. Generalized intravascular coagulation, as indicated by renal glomerular microclot formation, was initiated by two intravenous injections of endotoxin. Granulocyte counts before the second injection of endotoxin were most significantly related to activation of intravascular coagulation whereas platelet counts either before the first or second injection of endotoxin were not definitely related to the activation process. Renal glomerular microclots occurred in rabbits after two injections of endotoxin even when the platelet counts were between 500 and 5000/μl. These experiments indicated that granulocytes but not platelets are essential to the activation of endotoxin‐induced intravascular coagulation.
Immunoradiometric Assay of Factor VIII Related Antigen, with Observations in 32 Patients with von Willebrand's Disease
Authors: Ruggeri Z. M. , Mannucci P. M. , Jeffcoate S. L. , Ingram G. I. C.
Published: March 2008

Summary. A solid phase non‐competitive immunoradiometric assay (IRMA) has been developed which allows measurement of factor VIII related antigen (VIIIR: AG) levels in normal plasma as low as 2.5 × 10−4 U/ml. The assay is based on the extraction of VIIIR: AG from test plasma by means of polystyrene tubes coated with a specific unlabelled anti‐VIIIR: AG rabbit antiserum and subsequent labelling of the extracted antigen with 125I‐labelled anti‐VIIIR: AG rabbit IgG. The amount of radioactivity retained by the tubes (percentage bound) is proportional to VIIIR: AG concentration and a linear correlation is observed when logs of plasma dilutions (from 1 in 300 to 1 in 4000) are plotted against logits of percentage bound. The IRMA is technically simple, specific and reproducible. In 32 normal persons there was a highly significant correlation (r= 0.94) between IRMA and rocket electro‐immunodiffusion assay (EIA) of VIIIR: AG plasma levels using the same antibody. IRMA has also been used to investigate 32 patients with von Willebrand's disease (vWd) in whom VIIIR: AG plasma levels were below the lowest measurable concentration using EIA (< 0.10 U/ml). In 17 patients with an autosomal recessive mode of inheritance and unusually severe symptoms, the markedly abnormal laboratory findings were consistent with the homozygous state. In 11 of these VIIIR: AG was < 2.5 × 10−4 U/ml and was extremely low in the remaining 6 (1.3 × 10−2 to 4 × 10−3 U/ml). In 15 patients the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity; the IRMA or VIIIR: AG ranged between 1.2 × 10−1 and 4 × 10−2 U/ml. The assay thus appears a useful tooi in the investigation of vWd and helps to identify two different types of the disease.
Studies on the Liberation of β‐Thromboglobulin from Human Platelets in Vitro
Authors: Ludlam C. A. , Cash J. D.
Published: March 2008

Summary. A platelet specific protein, β‐thromboglobulin, is liberated during the preparation of platelet poor plasma. Using combinations of different anticoagulant and anti‐platelet compounds, this release can be significantly reduced. The best results were obtained when native blood was collected as soon as possible into a mixture of EDTA, prostaglandin E1 and theophylline and maintained and processed at a temperature between 0 and 4°C. These technical innovations have permitted the use of a radioimmunoassay for β‐thromboglobulin on plasma samples in clinical practice.
Disseminated Intravascular Coagulation Caused by the Carpet Viper (Echis carinatus): Trial of Heparin
Authors: Warrell David A. , Pope Helen M. , Prentice Colin R. M.
Published: March 2008

Summary. Heparin has been advocated for the treatment of poisoning by Echis carinatus, a snake whose venom causes disseminated intravascular coagulation. Fourteen patients with proven E. carinatus bite who had incoagulable blood were treated with specific Echis antivenom, Seven of them were also given low‐dose heparin, initially 50 units/kg body weight by i.v. injection, followed by 10 units/kg/h by i.v. infusion for 22 h. Response to treatment was assessed clinically and by repeated tests of blood coagulation. All patients showed a rapid return to normal blood coagulability after treatment and the heparinized group were not significantly different in any respect from the group given antivenom alone. Heparin did not reduce the local effects of envenoming. There appears to be no place for heparin in the treatment of E. carinatus poisoning provided that potent antivenom is available. The in vivo results were supported by in vitro studies in which it was found that Echis‐induced thrombin was less sensitive to the inhibitory effect of heparin than physiological thrombin.
Haemolytic Anaemia due to Glucose‐6‐Phosphate Dehydrogenase (G6PD) Deficiency: Demonstration of Two New Biochemical Variants, G6PD Hamm and G6PD Tarsus
Authors: Gahr M. , Bornhalm D. , Schröter W.
Published: March 2008

Summary. Two new variants of erythrocytic glucose‐6‐phosphate dehydrogenase have been found in one German patient and in another patient of Turkish origin. The enzymes were partially purified 165‐fold and 111‐fold respectively. Both revealed reduced activity, increased thermolability and a pH‐optimum in the alkaline region (8.5 and 9.0). One variant (G6PD Hamm) had a low Km‐value for glucose‐6‐phosphate, the other (G6PD Tarsus) exhibited an increased affinity for glucose‐6‐phosphate and a reduced affinity for NADP+. This enzyme showed an increased inhibitor constant for NADPH with respect to NADP+. Electrophoretic mobility was normal in both cases. 2‐Desoxy glucose‐6‐phosphate was utilized to an increased rate by both variant enzymes (46% and 33%). Also galactose‐6‐phosphate (29% and 25%) and deamino‐NADP+ (230% and 261%) gave increased utilization rates. The mothers of both patients could be identified as heterozygous for this enzyme deficiency.
Haemopoietic Progenitor Cells in Prenatal Congenitally Anaemic ‘Flexed‐Tailed’ (f/f) Mice
Authors: Cole R. J. , Regan T.
Published: March 2008

Summary. The incidences of erythroid colony forming cells (CFUe) and granulocyte‐macrophage colony forming cells (CFUC) have been measured in 11–18 d prenatal livers of mice of genotype f/f and nearly congenic +/+ controls. In normal fetal livers numbers of CFUe (cells able to form colonies of 16 or more cells after 72 h in vitro) rise to a maximum on day 14 of gestation and represent c 1% of total fetal liver cells. In f/f fetal livers, peak values for numbers and proportions of CFUe are 50% of normal. They f/f lesion does not reduce the numbers of CFUc in fetal liver. Since this deficiency in CFUe parallels deficiencies of similar magnitude in spleen‐colony forming units (CFUs) and erythroblasts in the liver, and erythrocytes in the blood, of f/f fetuses it is concluded that the f/f lesion is expressed at an early stage of haemopoietic development in prenatal life. The possibility that restricted haem synthesis is the primary effect of the f/f genotype and responsible for disturbances of both haemopoietic cellular proliferation and haemoglobin synthesis is examined.
T Cell Variant of Chronic Lymphocytic Leukaemia with Chromosome Abnormality and Defective Response to Mitogens
Authors: Nowell P. , Jensen J. , Winger L. , Daniele R. , Growney P.
Published: March 2008

Summary. Lymphocytes from a patient with chronic lymphocytic leukaemia, in whom therapy was ineffective, were defined as thymus‐derived (T) cells by membrane markers (sheep erythrocyte rosettes, complement rosettes, surface immunoglobulin). The lymphocytes responded weakly to two mitogens, phyto‐haemagglutinin and the calcium ionophore A23187, but not to concanavalin A. Cytogenetic studies of leukaemic cells from unstimulated and mitogen‐stimulated cultures revealed an abnormal karyotype with 45 chromosomes and multiple rearrangements. The T cell variant of classical chronic lymphocytic leukaemia is relatively rare; additional reports are needed to determine if the clinical course is typically less benign than in the common B cell variety, or whether this patient simply represented a late, unresponsive phase of the disease.
Platelet Density and Size: the Interpretation of Heterogeneity
Authors: PENINGTON D. G. , LEE N. L. Y. , ROXBURGH A. E. , MCGREADY J. R.
Published: March 2008

Summary. Platelets have been separated according to buoyant density using a colloidal silica‐polyvinylpyrrolidone system and subjected to electronic sizing. All density populations were found to be heterogeneous in size, the most dense platelets ranging from less than 3 fl to greater than 21 fl in both man and rat. Light platelet fractions contained no platelets greater than 13 fl in either species. Cohort labelling with [75Se]selenomethionine showed no indication of significant change in platelet buoyant density with ageing; greater specific activity found in young, dense platelets appears to be related to increased protein synthetic activity shown in vitro and likely to occur also in their precursor megakaryocytes.

It is postulated that dense, intermediate and light platelets are released synchronously by the three different ploidy classes of megakaryocyte, that varying density indicates differing structural characteristics and presumably differences in function. The present findings do not deny the possibility that platelets decrease in size with ageing but if such occurs, it is not associated with a significant change in platelet buoyant density.
Preparation and Storage of Platelet Concentrates: I. FACTORS INFLUENCING THE HARVEST OF VIABLE PLATELETS FROM WHOLE BLOOD
Authors: SLICHTER S. J. , HARKER L. A.
Published: March 2008

Summary. Factors affecting the yield and viability of concentrated platelets have been investigated in a blood component programme. It was found that 86± 1% of the platelets from a unit of whole blood can be concentrated without loss of viability by processing ACD or CPD anticoagulated blood at room temperature. The steps are initial centrifugation at 1000 g for 9 min to harvest platelet‐rich plasma; centrifugation of the platelet‐rich plasma at 3000 g for 20 min to pack the platelets; and resuspension of the platelet pellet in residual plasma after 11/2 h.
Solubilization, Partial Purification and Radioassay for the Intrinsic Factor Receptor from the Ileal Mucosa
Authors: COTTER R. , ROTHENBERG S. P.
Published: March 2008

Summary. A macromolecule which binds intrinsic factor saturated with vitamin B12 has been solubilized from the guinea‐pig ileum by homogenization followed by mechanical disruption without organic solvents or detergents. This intrinsic factor ‘receptor’was further purified by precipitation with 30% saturated ammonium sulphate, centrifugation at 105 000 g, and filtration through Sephadex G‐200. Failure to precipitate the receptor following centrifugation at 105 000 g for 3 h and filtration of the receptor with the included volumes through Sepharose 4B and 6B was evidence that it was solubilized.

The purification of the receptor was monitored by a radiometric assay where the intrinsic factor‐[57Co]vitamin‐B12 complex coupled to the solubilized receptor precipitated at 15% sodium sulphate while intrinsic factor‐[57Co]B12 alone remained soluble at this salt concentration. This radioassay also permitted the in vitro study of the interaction of the solubilized receptor and intrinsic factor saturated with [57Co]B12. The receptor did not bind intrinsic factor‐[57Co]B12 below pH 5 while binding was observed topH 9.0. Binding was equivalent at 37° and 25°, but was markedly reduced at 4° and 56° and was destroyed at 100°. The receptor resisted 60 min of digestion by trypsin, chymotrypsin, pronase and subtilisin. After 180 min digestion, pronase and subtilisin inactivated 90% and 41% of the receptor respectively, whereas trypsin and chymotrypsin inactivated only 21% and 23%. Trisodium EDTA inhibited the binding of intrinsic factor‐[57 Co]B12 to the receptor and this inhibition could be reversed by the addition of excess Ca2+. Mg2+ and Mn2+ were less effective than Ca2+ for the activity of the receptor. Kinetic analysis of the reaction indicated a maximum velocity of 0.083 nmole IF bound B12/min with a Km of 1.36 x 10‐10 M. The solubilized receptor had a greater affinity for intrinsic factor bound to vitamin B12 than for intrinsic factor free of vitamin B12.

The solubilization of this intrinsic factor receptor without chemicals suggests that it is not an integral component of the microvillus membranes hydrophobically bonded to the lipid matrix, but rather a peripheral protein weakly associated with the membrane by non‐covalent interaction.
Folic Acid Metabolism in Normal, Folate Deficient and Alcoholic Man
Authors: LANE F. , GOFF P. , MCGUFFIN R. , EICHNER E. R. , HILLMAN R. S.
Published: March 2008

Summary. Folate metabolism was studied in normal, folate‐deficient and alcoholic man by tracer measurements of plasma clearance, urinary excretion, tissue storage and release of folate using both [3H]pteroylglutamic acid (3H‐PteGlu) and 14C‐methyl‐H4PteGlu. Alcohol ingestion did not adversely affect tissue uptake of folates. Whether in normal or folate deficient subjects, the relative clearance rates of 3H‐PteGlu and 14C‐methyl‐H4PteGlu were maintained in the face of alcohol ingestion and there was no evidence of increased urinary loss of intact vitamin or labelled breakdown products. As measured by the flushing technique, the rate of storage or tissue binding of 3H‐PteGlu was not influenced by folate deficiency, folate store depletion or alcohol ingestion. However, alcohol may retard the release of methyl‐H4PteGlu from tissue stores to plasma. A significantly greater recovery of 14C‐methyl‐H4PteGlu with flush was observed in those normal subjects who ingested alcohol for 6 d. A partial block in the rate of release of tissue folate stores would be a possible mechanism behind the rapid depression in serum methyl‐H4PteGlu levels and early induction of megaloblastic erythropoiesis which has been observed following acute alcohol ingestion.
Autoimmune Haemolytic Anaemia in Children
Authors: ZUPANASKA B. , LAWKOWICZ W. , GÓRSKA B. , KOZLOWSKA J. , OCHOCKA M. , ROKICKA‐MILEWSKA R. , DERULSKA D. , CIEPIELEWSKA D.
Published: March 2008

Summary. Forty‐four children with autoimmune haemolytic anaemia (AIHA) are described: 31 had acute, subacute or chronic disease with warm autoantibodies and 13 had acute or chronic anaemia with cold autoantibodies. The commonest forms were the acute and subacute types with warm autoantibodies and these were more frequent in young children, while chronic AIHA occurred mainly among children at puberty. In about 16% the anaemia was accompanied by a chronic disorder but in over 50% the anaemia was preceded by an acute infection or immunization. The former gave rise mainly to chronic anaemia, but the latter was associated with the acute and subacute forms. In general the prognosis was good and death was never caused by anaemia per se. The prognosis was worse in patients with clinical features of thrombocytopenia and bleeding and with the immunological findings of free autoantibodies in the serum and a positive direct antiglobulin test. In acute and subacute forms, treatment with corticosteroids and sometimes with blood transfusions was effective. In chronic forms of the disease it was often necessary to give additional immunosuppressive drugs or/and to perform a splenectomy.
Serum ‘Uracil+Uridine’Levels in Pernicious Anaemia
Authors: PARRY T. E. , BLACKMORE J. A.
Published: March 2008

Summary. The serum ‘uracil+ uridine’level, expressed as uracil, has been measured in 21 cases of vitamin B12 deficiency, in which the serum folate was normal, and compared with the level in 97 normal subjects. The level in the vitamin B12 deficient group (11.9 μmol/l.) was significantly lower than in the controls (15.7 μmol/l., P< 0.005). Nine of the former were complicated by systemic illness but the clinical and haematological features in the remaining 12 were consistent with the diagnosis of pernicious anaemia in relapse. The serum uracil level in this group was even lower (10.21 μmol/l., P< 0.01). This finding is unexpected in view of the generally accepted indirect role of vitamin B12 in the methylation of deoxyuridine mono‐phosphate to deoxythymidine monophosphate. Reasons are given for not accepting these results as reflecting the main biochemical lesion in vitamin B12 deficiency. Although they do not give direct support to an impairment in the methylation of deoxyuridine monophosphate, they do not exclude it as they test only one possible metabolic pathway and moreover they could represent the result of more than one action of vitamin B12 on uracil metabolism. They do show, however, that some aspect of uracil metabolism other than methylation is affected in vitamin B12 deficiency in man.
Indium Chloride Scintigraphy: An Index of Severity in Patients with Aplastic Anaemia
Authors: MCNEIL BARBARA J. , RAPPEPORT JOEL M. , NATHAN DAVID G.
Published: March 2008

Summary. [111In]Indium chloride scans of the bone marrow were performed in 22 patients with idiopathic aplastic anaemia before therapeutic intervention. In 20 patients there was a marked reduction in the uptake of indium chloride by the marrow, and in two patients the uptake of indium chloride was normal. Nineteen of the 20 patients with reduced marrow uptake of indium chloride, who underwent bone marrow transplantation, died or failed to improve. One of the two patients with normal scans improved and the other has remained stable. Four patients studied both pre and post successful bone marrow transplantation had minimal marrow uptake before transplantation and normal scans after transplantation. Failure of indium‐111 chloride marrow uptake correlates with poor prognosis in idiopathic aplastic anaemia.
Ferrokinetics and Erythropoiesis in Man: An Evaluation of Ferrokinetic Measurements
Authors: Ricketts C. , Cavill I. , Napier J. A. F. , Jacobs A.
Published: March 2008

The plasma iron clearance half‐time and plasma iron turnover have usually been interpreted as measures of total erythroid activity and the red‐cell utilization of 59Fe has been equated with effective red‐cell production. Erythrocyte iron turnover has sometimes been calculated as the product of plasma iron turnover and percentage utilization. We have assessed these measurements as estimates of erythroid activity by comparing them with total marrow iron turnover and red‐cell iron turnover determined by the method of Ricketts et al (1975) in 10 normal subjects and 51 patients with an uncomplicated haematological disorder. The results show that the plasma iron clearance half‐time does not reflect erythroid activity and that plasma iron turnover can be particularly misleading in patients with reduced marrow activity. Red‐cell utilization and erythrocyte iron turnover give a distorted reflection of effective erythropoiesis except in patients with erythroid hypoplasia. Marrow iron turnover and red‐cell iron turnover provide more realistic and generally applicable assessments of the degree and effectiveness of erythroid activity.
Factor‐VIII Activity and Antigen, Platelet Count and Biochemical Changes after Adrenoceptor Stimulation
Authors: Ingram G. I. C. , Jones R. Vaughan , Hershgold E. J. , Denson K. W. E. , Perkins J. R.
Published: March 2008

Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI and XII, platelet count, lactate, pyruvate, potassium and free fatty acids. Factor VIII was studied by clotting assays, by reactions with two rabbit antisera and two human antibodies, and by desulphated agarose chromatography. At the rate at which they were administered, all three drugs increased the pulse rate by 20–40 beats/min. Factor VIII rose c. 2.5 x with adrenaline but only c. 1.5 x with isoprenaline and salbutamol; but other clotting factors did not alter. Chromatography provided no evidence of a change in the size of the molecule carrying factor‐VIII clotting activity. The rate of clearance of the heightened plasma activity could not be shown to differ from that of ‘ordinary’factor VIII infused into haemophiliacs. The platelet count rose after adrenaline, fell after salbutamol and did not change significantly after isoprenaline. Among the biochemical responses, the only significant difference between the drugs was that lactate rose after adrenaline and salbutamol but did not change after isoprenaline.

The rise in factor‐VIII clotting activity after adrenaline is considered to represent a real increase in blood concentration, presumably by release of additional factor VIII from stores. The evidence suggests that this could be classified as a β2 effect; and that the quantity which can be released is unrelated to the current plasma level. The rise in platelet count produced by adrenaline may be the resultant of an α‐mediated rise due to contraction of the exchangeable splenic pool and a β2‐mediated fall, the α effect predominating.
Haematologic Profile of Natural Populations: Red Cell Parameters
Authors: Kelly Anthea , Munan Louis
Published: March 2008

Age‐sex specific reference values and frequency distribution of erythrocyte parameters were derived from a representative sample of a natural population consisting of 1094 men and 1284 women between 10 and 96 years of age. Some differences have been found between previously reported reference values and those presented here, the importance of which lies not so much in their magnitude as in the fact that the latter are based upon a probability sample of a natural population unselected as to disease and are presented as percentile distributions by age and sex rather than as the more frequently used normal distribution. These results are intended for use as reference data both for clinical and for population estimates of haematological parameters.
Haemoglobin Radcliffe (α2β299(G1)Ala): A High Oxygen‐Affinity Variant Causing Familial Polycythaemia
Authors: Weatherall D. J. , Clegg J. B. , Callender S. T. , Wells R. M. G. , Gale R. E. , Huehns E. R. , Perutz M. F. , Viggiano G. , Ho C.
Published: March 2008

Three members of an Oxfordshire family have polycythacmia. In each case their whole‐blood oxygen affinity is increased. This is due to a previously undescribed haemoglobin variant which has been named haemoglobin Radcliffe (α2β299(G1)Ala). In addition to having a high oxygen affinity haemoglobin Radcliffe shows virtually no haem‐haem interaction and a diminished Bohr effect. It is synthesized at the same rate and is as stable as haemoglobin A. X‐ray analysis indicates that crystals of deoxyhaemoglobin Radcliffe are isomorphous with those of deoxyhaemoglobin A. Solutions of haemoglobin Radcliffe were also studied by high‐resolution proton nuclear magnetic resonance spectroscopy. The structure/function relationships of haemoglobin Radcliffe are discussed in the light of these studies.
Reversal of Ineffective Erythropoiesis in Pernicious Anaemia following Vitamin B12 Therapy
Authors: Samson Diana , Halliday D. , Chanarin I.
Published: March 2008

Ineffective erythropoiesis was quantitated in a series of patients with pernicious anaemia at different times in relation to vitamin B12 therapy by measuring the incorporation of [15N]δ aminolaevulinic acid and [15N]glycine into early labelled bilirubin. Prior to therapy ineffective erythropoiesis was grossly increased but this was reversed within 24 h of giving vitamin B12, suggesting that most of the existing megaloblasts are enabled to mature into circulating red cells.
Effect of Hypertransfusion on Granulopoiesis in Bone Marrow Depression: Studies in the Irradiated Mouse
Authors: Firkin Frank C. , Hays Esther F. , Cline Martin J.
Published: March 2008

The response of granulopoietic activity in bone marrow depression to a reduction in the demand for erythropoiesis has been examined by means of hypertransfusing C57B mice which had been exposed to sublethal whole body irradiation. Multiple intraperitoneal injections of 0.5 ml packed red cells from irradiated donors were employed to maintain the haematocrit sufficiently above the normal range to produce significant suppression of erythropoietic activity for the duration of the bone marrow depression. This was associated with elevation above control values of 32‐102% in the blood granulocyte count, 22‐78% in total cells of the granulocytic series per femur, and up to 44% in total agar colony forming units per femur. Restoration of essentially normal values occurred 13 d after irradiation in contrast to 17‐18 d in controls. Single transfusions which produced less suppression of erythroblast numbers per femur resulted in an intermediate degree of improvement in these parameters. Such changes in the granulocyte compartment indicate improved granulopoietic capacity in the hypertransfused group. It is suggested that this effect reflects increased production of granulocyte progenitors due to the reduction in competing demands on the compromised multipotential stem cell compartment for progenitors of the erythroid series. The findings raise the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis in human bone marrow depression.
Bone Marrow Culture Studies in Refractory Cytopenia and ‘Smouldering Leukaemia’
Authors: Milner Gillian R. , Testa Nydia G. , Geary C. G. , Dexter T. M. , Muldal S. , Maciver J. E. , Lajtha L. G.
Published: March 2008

As an adjunct to conventional haematological and cytogenetic data, 22 cases of refractory cytopenia, and five with chronic myelomonocytic leukaemia, (CMML) were studied by bone marrow culture.

Cultures from 11 such patients without an excess of marrow myeloblasts usually showed low, or undetectable, numbers of cells capable of giving rise to colonies of granulocytes and/or macrophages (CFUC) but near‐normal numbers of cluster‐forming cells and cells capable of forming erythroid colonies (CFUE).

Those with similar blood pictures, but in whom the marrow contained a slight excess of myeloblasts (11 cases), showed a more profound defect in growth patterns: low or undetectable numbers of CFUC, clusters and CFUE, results similar to those found in acute myeloblastic leukaemia, into which three of this group evolved. The patients with CMML gave comparatively normal CFUC, cluster and CFUE growth patterns.
Defective Platelet Lipid Peroxidation in Myeloproliferative Disorders: A Possible Defect of Prostaglandin Synthesis
Authors: Keenan J. P. , Wharton J. , Shepherd A. J. N. , Bellingham A. J.
Published: March 2008

Platelet lipid peroxidation induced by the sulphydryl blocking reagent n‐ethylmaleimide (NEM) was measured by production of malonyldialdehyde (MDA). Lipid peroxidation was decreased in five of 10 patients with proven myeloproliferative disease. The low levels of lipid peroxidation correlated well with in vitro and in vivo tests of platelet function and the bleeding and bruising problems. The reduction in lipid peroxidation with NEM may be due to one or more of the following: (i) an aged platelet population; (ii) an abnormal cell line; (iii) a reduction of the cyclo‐oxygenase enzyme activity in the platelet prostaglandin synthetic pathway; (iv) a reduction of the substrate for platelet prostaglandin synthesis, Arachidonic acid; and (v) an abnormality of phospholipase A activation.
Analysis of Treatment in Childhood Leukaemia
Authors: Waller C. A. , Maclennan I. C. M. , Campbell A. C. , Festenstein M. , Kay H. E. M. ,   and the Medical Research Council's Working Party on Leukaemia in Childhood
Published: March 2008

Lymphopenia induced by treatment for acute lymphoblastic leukaemia is analysed and discussed in relation to the type and incidence of infection occurring in those patients during complete remission.

Blood lymphocytes can be placed into three largely independent groups: (1) those lymphocytes susceptible to long‐term depletion following irradiation; (2) those lost from the blood during and for a short period after maintenance chemotherapy with methotrexate and 6‐mercaptopurine; and (3) the remainder which are not depleted by irradiation or maintenance chemotherapy.

The number of cells in each compartment varies from child to child and probably with age but on average is about 1.2 × 109/1. for group 1, 0.7 × 109/1. for group 2 and 0.4 x 109/1. for group 3. Conventional lymphocyte typing crosses these barriers in that: Group 1 consists mainly of E‐rosetting cells and cells which show a mitotic response to phytohaemagglutinin; Group 2 also contains E‐rosetting cells but contains a major proportion of blood lymphocytes with surface immunoglobulin and essentially all antibody dependent cytotoxic lymphocyte (K‐cell) activity; Group 3 comprises E‐rosetting cells and a few immunoglobulin‐staining cells.
The Anaemia of Chronic Disorders: Studies of Iron Reutilization in the Anaemia of Experimental Malignancy and Chronic Inflammation
Authors: Zarrabi Mohammad Hosein , Lysik Rita , Distefano John , Zucker Stanley
Published: March 2008

The purpose of this study was to evaluate the contribution of defective reutilization of iron in the pathogenesis of the anaemia of chronic disease (ACD). Normal rats with or without splenectomy and rats with Walker 256 carcinosarcoma with or without splenectomy were studied. The reutilization of 59Fe labelled heat‐damaged red cells (59Fe DRBC), the sequestration of 59Fe DRBC in major organs, red cell mass, 51Cr red cell survival, serum iron, plasma erythropoietin and routine haematological parameters were measured.

Three weeks after tumour implantation in rats a moderate degree of anaemia was noted. The maximum 59Fe reutilization in the tumour group and tumour with splenectomy group (63 ± 6% and 56 ± 9%, respectively) was not significantly different than observed in the normal group (64 ± 6%) or normal with splenectomy group (53 ± 7%). Excessive iron sequestration in liver and spleen was not observed in animals with cancer. Red cell survival in the tumour group was slightly decreased as compared to normal. Plasma erythropoietin levels were appropriately increased for the degree of anaemia in rats with cancer. This type of experiment was repeated in a second group of anaemic animals with turpentine induced abscesses. Reutilization of 59Fe DRBC in rats with inflammation was normal.

These results indicate that adult rats with anaemia of malignancy or chronic inflammation do not have a decreased reutilization of red cell iron. Thus RE blockade of iron is not a major factor in anaemia of chronic disease in this experimental model. Furthermore, these experiments confirm the importance of decreased red cell production in the anaemia of malignancy.
An Investigation into the Development and Fate of Neutrophil Giant Metamyelocytes using the Techniques of Electron Microscopy and High Resolution Autoradiography
Authors: Wickramasinghe S. N. , Bush Valerie
Published: March 2008

The neutrophil giant metamyelocytes present in vitamin B12‐ and folate‐deficient patients were studied using the techniques of electron microscopy and electron microscope autoradiography. The ultrastructural features of the cytoplasm of a proportion of these cells resembled those of promyelocytes and myelocytes, particularly with respect to the types of neutrophil granules present. This finding suggests that the giant metamyelocytes result from an abnormal type of development in promyelocytes and myelocytes which have been arrested or retarded in their progress through the cell cycle. The hypothesis that giant metamyelocytes eventually die within the marrow was supported by the observations that a significant proportion of these cells contain intracytoplasmic autophagic vacuoles, that some giant metamyelocytes suffer from a marked depression of RNA and protein synthesis and that degenerating giant metamyelocytes can be recognized within the cytoplasm of some bone marrow macrophages.
Acid Esterase in Human Lymphoid Cells and Leukaemic Blasts: a Marker for T Lymphocytes
Authors: Kulenkampff J. , Janossy G. , Greaves M. F.
Published: March 2008

A non‐specific acid alpha‐naphthyl‐acetate esterase activity was investigated in human lymphoid cell populations from tonsils, blood, thymus and in different leukaemias. Four patterns have emerged. (i) The vast majority of T lymphocytes (peripheral blood, tonsils) showed a localized, intense reaction product (‘T‐like’). (ii) A thymocyte subpopulation expressed faint, localized enzyme activity (‘Thy‐like’) but the majority of thymocytes showed no esterase activity. Some cells from acute lymphoblastic leukaemias with thymocyte surface characteristics had a ‘Thy‐like’appearance. (iii) Most B lymphocytes and cells from chronic lymphocytic leukaemias were esterase negative. No activity was seen in mitogen activated peripheral blood T and B lymphoblasts from peripheral blood and in leukaemic blasts from the common form of childhood acute ‘lymphoblastic’leukaemia. (iv) Myeloid cells, including peripheral blood monocytes, and blast cells from acute myeloblastic and chronic granulocytic leukaemias showed an intense, diffuse reaction product (M‐like).

It is concluded that the modified esterase technique is a convenient marker for small mature human T lymphocytes in tissue sections and smears. It may also be helpful in the differential diagnosis of acute lymphoblastic leukaemia with T characteristics, the common form of acute ‘lymphoblastic’leukaemia and acute myeloblastic leukaemia.
Autologous Bone Marrow Repopulation following High Dose Cyclophosphamide and Allogeneic Marrow Transplantation in Aplastic Anaemia
Authors: Territo M. C. ,   for the UCLA Bone Marrow Transplantation Team
Published: March 2008

Two patients are described who received allogeneic bone marrow transplantation for aplastic anaemia. Both patients rejected their grafts but subsequently repopulated their marrow with autologous haematopoietic cells. The significance of this phenomenon and its relationship to the possible pathogenesis and therapy of aplastic anaemia are discussed.
Intravascular Phagocytosis in the Rabbit Bone Marrow: A Possible Fate of Normal Senescent Red Cells
Authors: Tavassoli Mehdi
Published: March 2008

Perisinal macrophages in the rabbit bone marrow can penetrate the sinus wall and phagocytose circulating red cells intraluminally. Serial sectioning reveals that the penetration occurs through the cytoplasm of a single endothelial cell. This phenomenon may provide an effective mechanism for monitoring the circulation and removing normal senescent red cells.
Mechanisms of Red Cell Destruction Mediated by Non‐Complement Binding IgG Antibodies: the Essential Role in Vivo of the Fc Part of IgG
Authors: Kr. von dem Borne A. E. G. , Beckers Do , Engelfriet C. P.
Published: March 2008

Summary: F(ab′)2G anti‐D was prepared by limited digestion of IgG anti‐D with pepsin. Conditions of digestion were chosen in order to obtain a nearly complete conversion of the anti‐D antibody molecules as tested by immunochemical and serological techniques. The F(ab′)2G anti‐D was not capable of inducing adherence of rhesus D positive red cells to monocytes in vitro or of eliminating such cells in vivo in normal volunteers. These findings are compatible with a role of the Fc‐receptor‐mediated adherence to cells of the macrophage system in vivo in the destruction of erythrocytes by non‐complement binding IgG antibodies.
Proliferation of Erythroid Colonies in Semi‐Solid Agar
Authors: Horland A. A. , Wolman S. R. , Murphy M. J. , Moore M. A. S.
Published: March 2008

Summary. Growth of human erythroid cells in soft‐agar culture with no added erythropoietin was demonstrated. This growth was particularly marked in patients with diseases such as myelofibrosis (MF) in which patients had a previous history of polycythaemia vera (PV) characterized by excessive red cell production. A rapid assessment of the proportion of erythroid colonies was obtained by directly staining the culture with benzidine. Fixed and stained preparations of these agar‐grown cells revealed elements in all stages of erythroid maturation. The morphology of these erythroid colonies was characteristic of ‘erythroblastic islands’ containing central, iron‐containing macrophages, surrounded by erythrocytic precursors, with the more mature erythrocytes found at the periphery of the colony. These observations document that erythropoiesis may be maintained in agar cultures, and suggest that this technique may be of diagnostic value in disease states characterized by abnormalities of red cell production.
Transferrin Receptors in Developing Murine Erythroid Cells
Authors: Nunez M. T. , Glass J. , Fischer S. , Lavidor L. M. , Lenk E. M. , Robinson S. H.
Published: March 2008

Summary. Techniques of cell separation were used to isolate murine erythroid cells at different stages of maturation. The number of transferrin receptors in these cell populations was assayed by measuring binding of 125I‐labelled transferrin. Nearly 23 times as many receptors were found in the least mature cells, chiefly pronormoblasts, as in reticulocytes. Iron transport, determined by measurement of the rate of 59Fe uptake from 59Fe‐labelled transferrin, was proportional to the number of receptors at all stages of differentiation. Electron microscope radioautographic studies of the interaction of 125I‐labelled transferrin with erythroid precursor cells demonstrated that 15–35% of cell associated transferrin was intracellular in erythroid precursors.
Iron Deficiency in Pregnant Women in Ibarapa District of Western Nigeria
Authors: Oluboyede O. A. , Topley Elizabeth , Ogunbode O.
Published: March 2008

Summary. Ninety‐nine pregnant women with anaemia (haematocrit <0.30) were detected by antenatal screening in Ibarapa District. Studies on 23 anaemic women and 17 non‐anaemic women from the same clinic on the same day showed that eight out of 23 anaemic women had a transferrin saturation of less than 15%. The mean level (19.5%) for the anaemic patients was significantly less than that found in the nonanaemic controls: mean 33.0% (P<0.01). Bone marrow studies on 32 anaemic women revealed megaloblastic change and absent iron in 27 of the 32 patients.

In a trial of parenteral iron treatment in 66 patients the mean haematocrit of Imferon treated patients rose from 0.27 to 0.32 in 6 weeks but remained at 0.28 or less in the controls. There was a significant difference between the iron‐treated group and the comparable group receiving no imferon (P<0.001 at 6 weeks).

The method of using parenteral iron treatment to make a diagnosis of iron deficiency anaemia is discussed together with the possible advantages and disadvantages of giving iron.
The Detection of Granulocyte Alloantibodies with an Indirect Immunofluorescence Test
Authors: Verheugt F. W. A. , Kr. von dem Borne A. E. G. , Décary F. , Engelfriet C. P.
Published: March 2008

Summary. An indirect immunofluorescence technique for the detection of alloantibodies against granulocytes was developed. A major problem was the unspecific fluorescence of granulocytes, due to unspecific adherence of immunoglobulins to the cell membrane. This could be suppressed by the prefixation of the granulocytes with paraformaldehyde. The developed test proved to be specific and sensitive and to have a high reproducibility. Strongly positive reactions were obtained with antisera containing granulocyte‐specific agglutinins or granulocyte‐cytotoxins, but also with some sera that did not react in either the agglutination or the cytotoxicity test.

HLA antisera also gave positive reactions, but strong anti‐A, anti‐B or anti‐D sera did not react. With this technique leucocyte antibodies can be detected in a higher percentage of patients with febrile transfusion reactions.
Microvascular Occlusive Lesions in Primary Thrombocythaemia
Authors: Singh A. K. , Wetherley‐Mein G.
Published: March 2008

Summary. Although haemorrhagic manifestations are common in primary thrombocythaemia, microvascular occlusive lesions often leading to peripheral gangrene are frequent and can be the sole clinical manifestation of the disease.

Twenty‐seven patients were followed for periods of 6 months to 14 years. The microvascular occlusive group of nine patients presented with distal gangrene of toes, a purple mottled appearance of the skin resembling lesions of livedo reticularis pain aggravated by warmth and erythromelalgia. These ischaemic lesions appearing without demonstrable arterial disease indicate a primary role of the platelets in the occlusive process. None of these patients presented with haemorrhagic symptoms but many later showed abnormal post‐traumatic bleeding. The ischaemic lesions including the gangrenous toes were completely reversed by treatment and did not recur.

Ten patients presented with characteristic features of primary haemorrhagic thrombocythaemia. The haemorrhagic manifestations ranged from small, recurrent and multiple ecchymoses to recurring gastro‐intestinal blood loss, massive spontaneous haematoma and excessive post‐operative bleeding.

An asymptomatic group of six patients were diagnosed during routine investigation of other disorders. In none of them did a causal relationship seem possible. The miscellaneous group consisted of two patients with the characteristic clinical and haematological features of primary thrombocythaemia who when successfully treated, developed polycythaemia.

Busulphan was shown to be effective in controlling the proliferative process in all groups.
The Measurement of Red Cell Lifespan Using 59Fe
Authors: Ricketts C. , Cavill I. , Napier J. A. F.
Published: March 2008

Summary. Red cell lifespan has been measured using 51Cr and 59Fe in 19 patients. 59Fe can be used to give results which agree closely with those obtained using 51Cr provided that the plasma 59Fe clearance curve is properly defined and the data analysed correctly. In some patients elution of 51Cr may be more than three times the normal level and the use of 59Fe may provide the only reliable estimate of red cell lifespan.
Immunological Evidence that Human Factor VIII is Composed of Two Linked Moieties
Authors: Koutts Jerry , Lavergne Jean‐Maurice , Meyer Dominique
Published: March 2008

Summary. the relationship between the three measurable components of the factor VIII complex, procoagulant activity (VIII:C), Ristocetin cofactor (VIIIR:WF) and factor VIII related antigen (VIIIR:AG), has been investigated using a solid phase immunoadsorption system in which homologous antibodies specific for VIII:C are insolubilized onto Sepharose beads. The VIII:C component of partially purified factor VIII can be completely separated from the Willebrand factor (VIIIR:WF/VIIIR:AG) by this technique. The loss of VIII:C has no detectable effect on the molecular size, antigenicity or electrophoretic mobility of the original molecule. The Willebrand factor (WF) recovered from these immunoadsorption columns was used to absorb heterologous antisera to factor VIII. A specific heterologous antiserum to VIII:C, which no longer neutralized VIIIR:WF nor precipitated VIIIR:AG, was obtained. Heterologous antisera to WF were prepared which potently neutralized VIIIR:WF and precipitated with VIIIR:AG, but also weakly neutralized VIII:C (titre 1 u/ml). This study is compatible with the theory that VIII:C and VIIIR:WF/VIIIR:AG are two different but linked entities.
Acute Folate Deficiency Associated with Intravenous Nutrition with Aminoacid‐Sorbitol‐Ethanol: Prophylaxis with Intravenous Folic Acid
Authors: Wardrop C. A. J. , Lewis M. H. , Tennant G. B. , Williams R. H. P. , Hughes L. E.
Published: March 2008

Summary. Preoperative folate levels were initially normal in 30 patients with gastrointestinal tract disease but fell within 48 h by 60–95% in 20 patients who received intravenous nutrition for 6–12 d with aminoacid‐sorbitol‐ethanol (ASE). This depression persisted in patients not given folate supplements. Folate levels in 10 control patients not given ASE showed only minimal decline. Haematological changes were reduced to a minimum in 10 patients given 0.5 mg i.v. folic acid daily whilst eight unsupplemented patients showed evidence of megaloblastic haemopoiesis. Three of these eight patients developed thrombocytopenia and/or leukopenia which was fatal in one patient.
Erythroid Hypoplasia in Myelofibrosis: a Feature Associated with Blastic Transformation
Authors: Bentley S. A. , Murray K. H. , Lewis S. M. , Roberts P. D.
Published: March 2008

Summary. Four cases of myelofibrosis have shown a pattern which is usually found only where there is erythroid hypoplasia and in none of these was there evidence of extramedullary erythropoiesis. Three of these cases terminated in a blastic phase. The findings suggest that the occurrence of erythroid hypoplasia in myelofibrosis may be associated with blastic transformation—whether as a predisposing factor or as a secondary event is still speculative. This phenomenon is discussed in relation to the natural history of niyelofibrosis.