bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Antiplatelet Antibody Specificities in Immune Thrombocytopenic Purpura
Authors: DONNELL R. L. , Mcmillan R. , Yelenosky R. J. , Longmire R. L. , Lightsey A. L.
Published: March 2008

SUMMARY It is generally accepted that patients with immune thrombocytopenic purpura (ITP) produce antibody against platelet‐associated antigens; however, it is not known if these antiplatelet antibodies are directed towards the same or different antigenic sites. In the present studies, quantities of antiplatelet antibody from different ITP patients, sufficient to saturate platelet antigenic sites, were simultaneously incubated with normal platelets and the quantity of platelet‐binding IgG (PBIgG) was determined. In each of the five comparisons made, the amount of PBIgG bound after incubation of normal platelets with saturating quantities of two ITP antibodies approximated to the sum of the PBIgG bound after incubation with the antibodies separately. These data suggest that the antiplatelet antibody from these ITP patients differed in antigenic specificity.
The Interaction of α‐Thalassaemia and Haemoglobin G Philadelphia
Authors: Rieder R. F. , Woodbury D. H. , Rucknagel D. L.
Published: March 2008

An American Negro woman was found to have HbH disease in association with HbG Philadelphia (α68‐asnlys). Starch gel electrophoresis failed to reveal the presence of any HbA or HbA2 and studies of globin chain synthesis indicated absence of αA production. The αG/β synthesis ratio was 0.63. The woman's son and her two half‐sibs had α‐thalassaemia trait with no HbH and α/β synthesis ratios of 0.84, 0.84 and 0.76. The data indicate that there is no functioning αA gene linked to the αG gene. The absence of αA synthesis by the propositus also indicates that the α‐thalassaemia gene trans to the αG gene completely suppresses α chain production, the first evidence for such a gene in Negroes.
Erythropoiesis and Carbon Monoxide Production in Hodgkin's Disease
Authors: Cavallin‐Starhl Eva , Mercke C. , Lundh B.
Published: March 2008

Endogenous production of carbon monoxide (V co), red cell survival and iron kinetics were studied in 15 subjects with Hodgkin's disease. The subjects were divided into two groups, namely: eight patients with anaemia (group A, haemoglobin (Hb) concentration less than 11.5 g/dl) and seven patients without anaemia (group B, Hb concentration greater than 11.5 g/dl). Red cell survival was not significantly different in the two groups being 91 ± 40 days (mean± 1 SD) in group A and 111 ± 54 days in group B. Relative V co (μmol/mmol total body haem (TBH)/d) was, however, significantly higher (0.010.001) in group A (20.7±4.7) compared to group B (12.0±3.8). When absolute V co (μmol/d) was compared to the daily turnover of circulating red cell haemoglobin haem (V haem‐c), the V co/V haem‐c quotient was 2.1 ± 0.9 in group A and 1.2±0.3 in group B. Erythron turnover of iron (ET, μmol Fe/mmol TBH/d) was calculated through subtraction of the non‐erythron turnover (NET) from the total plasma iron turnover (PIT). ET was significantly higher (0.05>P>0.01) in group A (39±21) than in group B (20±8). The conclusion drawn from the finding of significant increases in V co and ET without any concomitant significant decrease in red cell survival in the anaemia group is that ineffective erythropoiesis, i. e. bone marrow haemolysis, seems to play an important role in the anaemia of Hodgkin's disease.
The Morphological Classification of Red Cells using an Image Analysing Computer
Authors: Bentley S. A. , Lewis S. M.
Published: March 2008

Image analysis provides a potential method for automation in the examination of blood films. In order to assess the applicability of this technique to red cell morphology, a scheme has been defined for the classification of red cells into six categories, namely, round cells, elongated cells, tear drop poikilocytes, helmet cells, irregular cells and spherocytes. A study was carried out to determine the consistency with which observers classified red cells according to this scheme. Measurements of area, perimeter, maximum diameter and integrated optical density of fixed, Romanowsky‐stained red cells were made using an image analysing computer. A multivariate classifier based on parameters derived from these measurements, namely cell area and the quotients of integrated density over area, area over the square of perimeter and perimeter over maximum diameter was also used to classify red cells into the above categories. It was found that the inherent error of the machine‐based classifier was of the same order as the degree of inconsistency encountered between trained observers. The significance of these findings is discussed.
βs Chain Turnover in Reticulocytes of Sickle Trait Individuals with High or Low Concentrations of Haemoglobin S
Authors: Shaeffer Joseph R. , Kleve Lois J. , DeSimone Joseph
Published: March 2008

Reticulocytes, isolated from the blood of sickle cell trait donors with either low (25–30%) or high (40–42%) haemoglobin S (Hb S) concentrations, were incubated with [3H]leucine for various times from 1.25 to 60 min. Samples of the total soluble fractions of the cells were denatured with urea and mercaptoethanol. The mixtures were analysed by electrophoresis on cellulose acetate strips. The specific radioactivities (dpm/mg) of the separated βs and βA globin chains were determined. The βs/βA ratios of globin chain specific radio activities in the reticulocytes of the ‘low Hb S’ donors decreased gradually from initial values higher than 1.30 to values near unity. These data suggested that faster turnover of some of the soluble, newly synthesized βs chains compared to the newly synthesized βA chains could explain part, but not all, of the disparity in concentrations of Hbs S and A in these people. When reticulocytes from ‘high Hb S’ donors were 3H‐labelled for times longer than 5 min, the βS/βA specific radioactivity ratios remained at or near unity. This result suggested that newly synthesized βS chains were not turning over selectively in these cells. Instead, there was a relative decrease in βS chain synthesis proportional to the difference in blood concentrations of Hb S and Hb A. Additional calculations suggested that the more rapid turnover of newly synthesized βS chains in the ‘low Hb S’ reticulocytes could explain the difference in Hb S concentrations between ‘high and low Hb S’ people. These results are consistent with previous reports that an α‐thalassaemia gene, present in ‘low Hb S’ but absent in ‘high Hb S’ donors, may be responsible for the selective turnover of βS chains.
Erythrocyte Vitamin B12 Activity in Healthy Indian Lactovegetarians
Authors: Inamdar‐Deshmukh A. B. , Jathar V. S. , Joseph D. A. , Satoskar R. S.
Published: March 2008

Plasma and erythrocyte vitamin B12 was measured in apparently healthy Indian lactovegetarians and compared with the healthy non‐vegetarians from the same population. Comparison of the mean values for routine haematological parameters revealed no significant difference in various dietetic groups. The plasma vitamin B12 levels were distinctly lower in the lactovegetarians than in the non‐vegetarians. However, the mean erythrocyte vitamin B12 levels in different dietetic groups showed no significant difference.
Measurement of the Mean Cell Volume using Electronic Particle Counters
Authors: England J. M. , Down M. C.
Published: March 2008

Under carefully controlled conditions electronic cell counters, for example the Coulter Counter, Model FN, and Channelyzcr, may be calibrated to give MCV values down to as small as 20 fl which agree with those derived from the centrifugation PCV (corrected for plasma trapping) and the red cell count.

The MCV values will be too high if the instrument uses a high cell concentration, has a fixed lower threshold, no effective upper threshold and no edit facility. This may partly explain why the Coulter Counter, Model S, when standardized with 4C cell control gives higher MCV values than the Model FN linked to the Channelyzer. The difference is, on average, 2 fl with normal blood samples and 5 fl in cases of microcytic anaemia. It is suggested that standards of low MCV should be used together with those of normal MCV when calibrating the Model S.
The Role of Membrane Bound Complement in the Aggregation of Mammalian Platelets by Collagen
Authors: Chater B. V.
Published: March 2008

Platelets from dogs decomplemented with purified Cobra Venom Factor (CVF) lose the ability to aggregate in response to collagen stimulation. In vitro in man, dog and rabbit, and in vivo in the dog, CVF abolishes the collagen response of platelets, the effect being dose‐related. Resuspension of CVF inactivated platelets in plasma containing complement resulted in a total return of sensitivity to collagen. Examination of CVF inactivated platelets with the electron microscope failed to show any marked difference from control platelets. Serotonin granules were still present and the platelets retained a discoid appearance. Incubation of platelets with antibodies to C1, C3 and C5 resulted in inhibition of the collagen response: this effect was dose‐related. Light microscopy indicated that CVF does not affect the adhesion of platelets to collagen but appears to prevent subsequent aggregation. It is suggested that the complement system is involved in the induction of the platelet release reaction by collagen, and that inhibition by CVF and anticomplement antibodies is the result of a blocking of the release reaction.
The Diurnal Rhythm of Enzymes in Human Red Cells
Authors: Brok‐Simoni Frida , Ashkenazi Yisrael E. , Ramot Bracha , Holtzman Fanny
Published: March 2008

The activities of glucose‐6‐phosphate dehydrogenase (D‐glucose‐6‐phosphate: NADP oxidoreductase, G6PD), 6‐phosphogluconate dehydrogenase (6‐phospho‐d‐gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D‐hexose 6‐phosphotransferase, HK), lactic dehydrogenase (L‐lactate: NAD oxidoreductase, LDH) and aspirate aminotransferase (L‐aspartate: 2‐oxoglutarate aminotransferase, Asp. T) were determined in red blood cells of 11 healthy individuals. The determinations were carried out on samples drawn every 4 h over a 24 h period. The activities of G6PD, 6PGD, LDH and Asp. T exhibited a semi‐circadian rhythm, namely, two peaks of activity during 24 h while HK activity demonstrated a true circadian rhythm. In addition a polymorphism of the G6PD and LDH activity patterns was observed. The implications of a biological clock in enucleated cells are discussed.
Relation between the Inhibition of Aggregation and the Concentration of cAMP in Human and Rat Platelets
Authors: Michel Huguette , Caen J. P. , Born G. V. R. , Miller R. , DAuriac Ghislaine Angles , Meyer P.
Published: March 2008

Summary.

Adenosine inhibits the aggregation of human but not of rat platelets whereas both are inhibited by prostaglandin E1 or by the pyrimido‐pyrimidine compound RA233. In human platelets all three agents increase adenosine‐3′,5′‐cyclic monophosphate (cAMP). If the inhibition of aggregation depended on this increase, adenosine might be expected not to increase cAMP in rat platelets. Under conditions in which adenosine inhibited aggregation and increased cAMP in human platelets, adenosine caused a similar increase in cAMP in rat platelets without inhibiting their aggregation. The aggregation of rat platelets was inhibited as effectively as that of human platelets by PGE1 or RA233 at concentrations which caused greater increases in cAMP than did the highest concentrations (2.8 × 10‐4m) of adenosine it was possible to use. When the increase of cAMP in rat platelets by PGE1 was limited to that produced by adenosine, PGE1 like adenosine failed to inhibit aggregation. Therefore, the difference in the inhibitory effectiveness of adenosine on rat and human platelets was quantitative rather than qualitative and apparently depended on the inability of adenosine to increase cAMP sufficiently in rat platelets. When cAMP had been increased by adenosine, PGE1 or RA233, the addition of ADP caused cAMP to decrease rapidly in both human and rat platelets to between +22 and 18% of control values, except that the decrease in rat platelets was to +40% after RA233 had been present for 0.5 min before ADP. The increase in cAMP produced in rat platelets by adenosine at 5 × 10‐6 to 2.8 × 10‐4m for 3 min was associated with a small increase in aggregation velocity. It is suggested that the comparative ineffectiveness of adenosine as an inhibitor of platelet aggregation, particularly with rat but less so also with human platelets, is because, unlike PGE1 or RA233, adenosine has two opposing actions on aggregation; one being inhibition by activating adenylate cyclase and increasing cAMP, and the other being potentiation by uptake. This hypothesis accounts for the present results as well as for the earlier observation that dipyridamole which prevents the uptake of adenosine potentiates its inhibitory effect on the aggregation of human platelets.
A Standardized Bioassay for Platelet Factor 3 Released by Kaolin
Authors: Pérez‐Requejo J. L.
Published: March 2008

Summary.

The test for platelet factor 3 described by Hardisty & Hutton (1975) has been modified to conform to the usual design for a parallel‐line bioassay. Manchester Comparative Thromboplastin has been used as assay Standard, allowing an arbitrary unit of activity to be adopted. However, experiments suggested that the platelet activity measured was different from tissue factor activity. Platelets are tested as platelet‐rich plasma diluted in a standardized mixture of plasma and fibrinogen, so that differences between the clotting factors of the test samples are eliminated, as verified by experiments on haemophiliacs and patients on anticoagulant treatment. Sonication and repeated freezing and thawing of platelet‐rich plasma showed that approximately 15% of the PF3 is released by kaolin. In vivo, a single dose of 600 mg of aspirin reduced the PF3‐release to half the previous value in 2 h; initial values were regained in 5–8 days.
In Vivo Behaviour of Homologous Urea‐Soluble 131I‐Fibrin and 125I‐Fibrinogen in Rabbits: the Effect of Fibrinolysis Inhibition
Authors: Müller‐Berghaus G. , Mahn I. , Köveker G. , Maul F.‐D.
Published: March 2008

Summary.

The in vivo behaviour of urea‐soluble fibrin monomer (FM) was compared with that of fibrinogen in rabbits. Purified rabbit 125I‐fibrinogen was injected into 36 unanaesthetized rabbits. Three days later the rabbits received either purified rabbit 131I‐FM 1 mg/kg body weight, which corresponds to c 1% of the circulating plasma fibrinogen pool or 131I‐fibrinogen, or buffered urea only. The distribution volume of FM was 43.4±6.9 ml/kg and of fibrinogen 43.5±7.7 ml/kg (mean±SD). The elimination curve of urea‐soluble FM as represented by the clottable 131I‐radioactivity, plotted on a semi‐logarithmic paper, consisted of an initial steep decay within the first 6 h and a slow flattening of the slope 6 to 24 h after injection of FM. Although a terminal single‐exponential slope, as observed in fibrinogen elimination, could not be computed for the 24 h following FM injection the mean half‐life time of the last segment of the clottable‐radioactivity curve, between 12 h and 24 h, was 12 h. Within 24 h a mean of 83.5% of the injected FM were removed from the circulating blood. The elimination characteristics of fibrinogen were not influenced by the injected FM. Control experiments showed that buffered 3.0 M urea, the solvent of FM, does not influence distribution volume and elimination of 125I‐fibrinogen. The distribution of 131I as well as 125I‐radioactivities in organs representing FM and fibrinogen respectively did not differ from each other. Elevated levels of 131I‐radioactivity, however, were found in the urine after FM injection suggesting an accelerated elimination of FM in comparison to fibrinogen. Fibrinolysis inhibition with high doses of aprotinin did not significantly reduce the urinary excretion of 131I‐radioactivity representing breakdown of FM. Furthermore, inhibition of the fibrinolytic system had no influence on the elimination characteristics of either fibrinogen or FM. In order to explain the results obtained in this study the following theory is proposed. Intravenously injected FM forms complexes with fibrinogen and fibrinolytic degradation products. The complexes continuously increase in size until they dissociate into fibrin oligomers and carrier proteins. The oligomers are eliminated whereas the carrier proteins recycle.
Surface Sulphydryl Groups and Hexose Monophosphate Pathway Activity in Resting Human Polymorphonuclear Leucocytes
Authors: Tsan Min‐Fu , Newman Burlina , Chusid Michael J. , Wolff Sheldon M. , McIntyre Patricia A.
Published: March 2008

Summary. The role of surface ‐SH groups on the hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes was studied. Endotoxin, taurocholic acid and concanavalin A stimulated [1‐14C]glucose oxidation to a greater degree than [6‐14C]glucose oxidation. The stimulation of glucose‐1‐C oxidation by endotoxin, taurocholic acid and concanavalin A could be prevented by p‐chloromercurybenzene sulphonic acid, an inhibitor of surface ‐SH groups. In contrast, polymorphonuclear leucocytes from four patients with chronic granulomatous disease failed to show stimulation of glucose‐1‐C oxidation by endotoxin, taurocholic acid or concanavalin A.
Three Approaches to the Radioimmunoassay of Human β‐Thromboglobulin
Authors: Bolton A. E. , Ludlam C. A. , Moore S. , Pepper D. S. , Cash J. D.
Published: March 2008

Summary. Three radioimmunoassays for the measurement of β‐thromboglobulin are described. The standard method, using antiserum in solution, could be used to measure plasma concentrations of β‐thromboglobulin with the results available after 2–3 d. The use of a greater dilution of antiserum and tracer, with delayed addition of tracer, resulted in a more sensitive assay suitable for measuring β‐thromboglobulin in urine. The use of a solid‐coupled antiserum under non‐equilibrium conditions allowed the measurement of plasma levels of β‐thromboglobulin after an assay incubation time of 1 h. These three radioimmunoassay systems for β‐thromboglobulin cover the likely clinical requirements for the measurement of this platelet specific protein.
The Efffects of Acute Bleeding on Acid–Base Balance, Erythropoietin (Ep) Production and in Vivo P50 in the Rat
Authors: Miller Marilyn E. , Rörth M. , Stohlman F. , Valeri C. R. , Lowrie G. , Howard D. , McGilvray Norah
Published: March 2008

Summary. The mechanism of erythropoietin (Ep) production after acute haemorrhage has been thought to be due to a reduction in blood volume and tissue perfusion leading to tissue hypoxia. In the present study we have evaluated the effect of acute haemorrhage in the rat on the acid‐base status, the red cell affinity for oxygen in vivo, and Ep production. Within a few hours after acute blood loss there was a respiratory alkalosis with an increase in blood pH, a decrease in pCO2 and an increase in the red cell affinity of Hb for oxygen in vivo that was temporally related to an increase in Ep production. Within 24 h after the acute haemorrhage, the blood pH and pCO2, red cell affinity for oxygen in vivo, and Ep level returned towards normal. The decrease in in vivo red cell affinity for oxygen was associated with an increase in red cell 2,3‐DPG levels and a decrease in Ep production.
Biological Variation in the Heterogeneous Distribution of Haemoglobin F among Erythrocytes
Authors: Bhattacharya Syama P. , Anyaibe Stephen I. O. , Headings Verle E.
Published: March 2008

Summary. The development of highly specific fluorescent labelled antibodies against haemoglobin F presented an opportunity to investigate variables which might influence distribution of this haemoglobin among individual erythrocytes. Earlier investigations revealed heterogeneous distribution within healthy individuals and in individuals with sickle cell disease and other haemoglobinopathies. The current study demonstrates quantitatively that there are normal biological determinants of variability in the frequency of F‐containing erythrocytes in individuals who have a haemoglobin A electrophoretic phenotype. It also is shown that the frequency of F‐containing erythrocytes during the early recovery phase of sickle cell crisis is significantly higher than when there is no recent history of crisis. The mean quantity of haemoglobin F per F‐containing erythrocyte appears to be lower after a crisis than in individuals without recent history of crisis. This suggests that following a crisis there may either be biochemical constraints on haemoglobin F synthesis per erythrocyte precursor cell or else there is limited opportunity for selective removal of low F‐containing erythrocytes from the circulation.
The Abundance of Ferritin in Yolk‐Sac Derived Red Blood Cells of the Embryonic Mouse
Authors: Theil Elizabeth C.
Published: March 2008

Summary. Circulating red blood cells formed early in development have several distinctive properties which include retention of the nucleus (mammals), large size and characteristic haemoglobin type (mammals, birds, amphibia). The primitive or embryonic red cells of early development are replaced by the definitive red cells which contain fetal or adult haemoglobin; a second developmental change occurs in the haemoglobin of some mammals (man, cattle, sheep) but does not involve a cell replacement. Circulating yolk‐sac derived red cells from embryonic mice are siderocytes; elevated ferritin levels are associated with the circulating red cells of bullfrog tadpoles, but not with those of the adult frog, again indicating that red cell iron metabolism can change during development. In order to extend the observations made on an amphibian to a mammal, the ferritin content of circulating red cells from embryonic mice was determined and found to be 0.65 mg/100 mg of soluble protein; no ferritin (≤ 0.007 mg/100 mg of soluble protein) was detected in adult mouse red cells. Elevated ferritin levels appeared to be specifically associated with the yolk‐sac derived population of red cells since a decline in red‐cell ferritin content coincided with the replacement of yolk‐sac derived red cells by definitive red cells derived from the liver. Fractionation of mixtures of yolk‐sac derived and liver derived red cells showed that fractions rich in the definitive red cells contained less ferritin than the mixture. The results suggest that elevated ferritin levels may be a general characteristic of the circulating, haemoglobinized red cells formed early in development.
Iron Mobilization in the Pregnant Rat
Authors: Hershko C. , Cohen H. , Zajicek G.
Published: March 2008

Summary. Iron exchange in the pregnant rat was quantitated by repeated determinations of plasma iron turnover (PIT), transferrin iron distribution and measurements of storage iron and food iron utilization employing selective radio‐iron probes. Despite a sixfold increase in PIT, intestinal absorption of iron accounted for 40% of the PIT throughout pregnancy, with variations not exceeding ±5%. Increased fetal requirements were efficiently compensated for by the mobilization of iron from maternal tissue stores and by increased absorption, and there was no subsequent reduction in iron supply to maternal tissues. Enhancement of iron absorption occurred in the absence of a reduction in serum iron levels or the size of iron stores. In view of the close correlation between PIT and rates of absorption it is postulated that iron absorption in the pregnant rat is regulated by PIT which in turn is determined by the rate of plasma iron clearance by the placenta and the maternal erythroid marrow.
HL‐A Groups in Pernicious Anaemia
Authors: Chanarin I. , Knight Stella , O'Brien Jacqueline , James D.
Published: March 2008

Summary. There is a significant association with HL‐A3 type and pernicious anaemia. In addition there is a negative association with HL‐A2. There is no association between HL‐A type and the presence or absence of immunity to intrinsic factor.
Preparation and Storage of Platelet Concentrates: II. STORAGE VARIABLES INFLUENCING PLATELET VIABILITY AND FUNCTION
Authors: SLICHTER S. J. , HARKER L. A.
Published: March 2008

Summary. Factors affecting the viability and function of stored platelet concentrates have been investigated in a blood component programme. It was found that platelets could be maintained for up to 72 h without bacterial contamination under the following conditions: (1) surgical skin preparation at venipuncture site; (2) blood collection in CPD or ACD anticoagulant in a closed bag system; (3) centrifugation of PRP at 3000 g for 20 min; (4) storage in Fenwal PL‐146, Cutter CL‐2383, or McGaw plastic bags; (5) resuspension of the platelet pellet in 70 ml residual plasma; (6) storage at 22± 2°; and (7) constant gentle mixing throughout storage. Platelet viability as determined by recovery and survival is largely maintained, as is platelet function measured by template bleeding time. Both viability and function of concentrated platelets stored at 4° are severely compromised.
Terminal Deoxynucleotidyl Transferase Measurements in the Differential Diagnosis of Adult Leukaemias
Authors: HUTTON J. J. , COLEMAN MARY SUE
Published: March 2008

Summary. Terminal deoxynucleotidyl transferase (TDT) is an unusual DNA polymerase that does not use template information to synthesize new strands of DNA. It is normally found in high concentration in thymus (50 u/108 cells) and in low concentration in bone marrow (< 5 u/108). We report TDT measurements in the marrow and/or peripheral blood of 51 adult patients, 28 of whom had leukaemia. TDT is present in very high levels (> 50 u/108 cells) in leukaemic lymphoblasts and in low levels in leukaemic myeloblasts (< 9 u/108 cells). Of two patients who developed lymphosarcoma‐cell leukaemia following treatment of poorly differentiated lymphocytic lymphoma, one had high and one low levels of TDT in the leukaemic blast cells. Leukaemic cells from three of seven patients with chronic myeloid leukaemia in blast crisis had TDT levels within the range expected of acute lymphoblastic rather than acute myeloid leukaemia. High TDT in leukaemic cells probably marks them as derivatives of lymphoid progenitor, thymic or pluripotential stem cells. Quantitative assay of TDT may provide information useful in classifying haematological neoplasms.
Quantitative Studies of Splenic Erythropoiesis in Polycythaemia Vera and Myelofibrosis
Authors: PETTIT J. E. , LEWIS S. M. , WILLIAMS E. D. , GRAFTON C. A. , BOWRING C. S. , GLASS H. I.
Published: March 2008

Summary. A quantitative scanning method employing cyclotron‐produced 52Fe has been developed to assess splenic erythropoiesis in patients with myeloproliferative disorders. In 12 patients with myelofibrosis splenic uptake of 52Fe was from 5.0% to 48% of the injected dose. Although a single patient with classical polycythaemia vera had a minor uptake of 2.8% six other patients with this diagnosis showed no concentration of isotope in the splenic area. The fraction of 52Fe in the spleen of four patients with ‘transitional’myeloproliferative disorders characterized by a high red cell mass, hypercellular bone marrow and a leucoerythroblastic blood film varied from 5% to 41%. No clear relationship was noted between the degree of splenic erythropoiesis as defined by this technique and the level of haemoglobin, the degree of splenomegaly, the effectiveness of erythropoiesis or traditional 59Fe surface counting. If splenectomy is considered in patients with myelofibrosis splenic 52Fe quantitation will provide more precise data on the contribution of splenic erythropoiesis than 59Fe surface counting alone.
Annotation: BONE MARROW TRANSPLANTATION
Authors: KAY H. E. M.
Published: March 2008

Summary. There are now about 100 people alive whose haemopoietic function has been dependent for 1 year or longer on a bone‐marrow graft. We can be certain that virtually all would, but for their graft, have succumbed to bone marrow aplasia, acute leukaemia or combined immunity deficiency. It is an appropriate moment to examine the current bone marrow transplant prospectus.
Two Biochemical Markers in Lymphocyte Subpopulations
Authors: HUANG ANDREW T. , LOGUE GERALD L. , ENGELBRECHT HELEN L.
Published: March 2008

Summary. Human blood lymphocytes can be separated into two populations according to the presence of surface complement receptors. Lymphocytes containing complement receptors (CR+) were found to have a high rate of RNA synthesis or turnover accompanied by increased protein synthesis. Lymphocytes not containing complement receptors (CR—) while maintaining a low profile in RNA synthesis, had a 10–12‐fold greater activity in adenosine deaminase enzyme which is believed to be related to lymphocyte‐immune responses and cell‐mediated immunity. These two biochemical characteristics can be useful tools for future studies in lymphocyte functions. By using these two biochemical markers, we found that CLL lymphocytes were predominantly of the CR+ type, had high active RNA synthesis, and very low adenosine deaminase level. Lymphocytes from two patients with X‐linked agammaglobulinaemia showed a picture opposite to that of CLL.
Platelet Antithrombins: Role of Thrombin Binding and the Release of Platelet Fibrinogen
Authors: Watanabe Kiyoaki , Chao Francis C. , Tullis James L.
Published: March 2008

The nature of platelet antithrombin was elucidated by comparison of thrombin binding and antithrombin activities of intact platelets and by purification of antithrombin from platelet lysates using glycerol osmotic lysis, ethanol precipitation and Sephadex gel filtration techniques. The major portion of the antithrombin and thrombin binding activity of intact platelets is lost after brief sonication. The antithrombin activity in destroyed platelets is found to be due to platelet fibrinogen. Treatment of platelets with PGE1 (100 μg/ml) markedly inhibits (>80%) the release of platelet fibrinogen induced by thrombin. However, the PGE1 treatment produced slight (<30%) but significant decrease of antithrombin activity of intact platelets, whereas the binding of thrombin to platelets was not affected by PGE1 treatment. The amounts of thrombin bound to and inactivated by PGE1‐treated platelets at the same cell concentration are identical. The above results suggest that platelets contain at least two antithrombin activities. One, which accounts for the major portion of platelet antithrombin is mediated by thrombin binding to platelets. The other, which attributes to a lesser extent to platelet antithrombin activity, is due to the release of platelet fibrinogen. Also, antithrombin is readily demonstrated in a plasma medium indicating physiological significance of platelet antithrombin.
Mucosal Iron‐Binding Proteins in Mice with X‐Linked Anaemia
Authors: Valberg Leslie S. , Sorbie Janet , Ludwig John
Published: March 2008

The mouse with X‐linked anaemia (sla) has a defect in iron absorption which can be temporarily reversed by feeding a low iron diet. Duodenal non‐haem iron was significantly higher in the sla than in the normal mouse on an iron supplemented diet but non‐haem iron was reduced to minute amounts when the mice were fed a low iron diet. Gel chromatography on Sephadex G‐200 of the particle‐free supernatant of pooled mucosal homogenates revealed the presence of three proteins binding 59Fe. Fraction I (mol wt 450 000) resembled ferritin and was present in both normal and sla mice fed an iron supplemented diet. Fraction II (mol wt 78 000) eluted in a similar position to transferrin and was evident in both normal and sla mice fed an iron deficient diet. Fraction III (mol wt less than 15 000) contained equivalent amounts of radioiron in normal and sla mice fed the iron deficient diet, whereas this fraction contained less radioactivity in sla animals in two of three experiments in which the animals were fed an iron supplemented diet. The iron transport defect in sla mice does not appear to reside in the iron‐binding proteins in the supernatant fraction of the intestinal mucosa and the cause of the defect in iron absorption remains to be elucidated.
Combined T and B Lymphocyte Marker Test in Lymphoproliferative Disorders
Authors: Chapel Helen M. , Ling N. R.
Published: March 2008

The combined T and B lymphocyte marker test of Mendes et al (1974) has been developed to provide an easy, reproducible test for clinical practice. It has been used to study subpopulations of peripheral lymphocytes in patients with lymphoid malignancies. Significant increases in the numbers of lymphocytes which bind both sheep erythrocytes (E) and the fixed, third component of complement (C3) have been found using this test, in the peripheral blood of all untreated lymphosarcoma (L/SA) patients and T cell acute lymphoblastic leukaemia (ALL) patients. Such increases were not found in blood from patients with chronic lymphatic leukaemia (CLL), other non‐lymphoid malignancies, null‐cell ALL or normal individuals. These mixed E and C3 receptor bearing cells may be Fc receptor positive and represent a separate subpopulation of lymphocytes.
Evidence for Rapid Loss of Newly Synthesized Haemoglobin S Molecules in Sickle Cell Anaemia and Sickle Cell Trait
Authors: Desimone J. , Adams J. G. , Shaeffer J.
Published: March 2008

The present study indicates that newly completed haemoglobin S molecules rather than free βS‐chains are preferentially bound to the reticulocyte stroma of individuals with sickle cell trait and sickle cell anaemia. Reticulocytes from individuals with HbAA, AS and SS were incubated with [3H]leucine from 1.25 min to 120 min. Unlike the stroma‐free haemolysates, the stroma of all individuals contained an excess of labelled β‐chains relative to α‐chains after short incubation times. In haemoglobin AA and AS individuals, the stromal βA radioactivity was 1–2% of the total cellular βA radioactivity. In haemoglobin AS and SS individuals, the stromal βS radioactivity was 3–5% and 10–20% of the total cellular βS radioactivity, respectively. All of the stroma β‐chain radioactivity was associated with completed haemoglobin molecules. Because of the unlabelled free α‐chain pool found in reticulocytes, after short incubation times newly completed haemoglobin molecules have predominantly labelled β‐chains and unlabelled α‐chains. These findings suggest that part of the discrepancy between the stroma and stroma‐free haemolysate α/β radioactivities seen in HbAS and HbSS individuals may result from normal labelling kinetics.

A pulse chase experiment performed on an individual with HbSS revealed that completed HbS molecules, in addition to being associated with the stroma, were lost from the cell.
A Circadian Variation of Melphalan (L‐Phenylalanine Nitrogen Mustard) Toxicity to Murine Bone Marrow: Relevance to Cancer Treatment Protocols
Authors: Simpson H. W. , Stoney P. J.
Published: March 2008

The toxicity of Melphalan to murine bone marrow was assessed by automated Coulter counts of femoral marrow nucleated cells. A significant dose‐response slope (P0.001) was shown and also a significant variation along the 24 h scale. With food available ad libitum and light from 06.00 to 18.00 hours, the minimum marrow depression occurred around 16.00 hours. Extrapolating these findings to human chemotherapy it would appear that prescription of the drug during the early part of the activity span (usually breakfast) will minimize marrow depression. This differs from a human study in which Melphalan was given at ‘bedtime’as an adjuvant to mastectomy in breast carcinoma and in which there was leucopenia at some stage of treatment in all 103 patients.

It is recommended that in future cancer therapy protocols test for circadian variability of white cell depression by varying treatment times systematically along the 24 h scale.
Stimulation of Human Haemopoietic Cells by Colony Stimulating Factors: Adherent Cell Dependent Colony Stimulating Activity in Human Serum
Authors: Francis G. E. , Berney J. J. , Hoffbrand A. V.
Published: March 2008

The number of granulocyte‐macrophage clones formed in agar culture of bone marrow is dependent on levels of colony stimulating activity (CSA) a proposed in vivo haemopoietic regulator. A dose‐response relationship for stimulation of human haemopoietic cells by CSA is demonstrated, which could be explained by thresholds of stimulation to cell division following a normal distribution. A simple method for the comparison of activities of test and control sources of CSA is presented. The apparent potentiating effect of the addition of two sources of CSA is explained by this dose‐response relationship. Haemopoietic cells from patients with chronic granulocytic or acute myeloid leukaemia showed the same dose‐response relationship. CSA levels in normal human sera were greatly reduced by assay in the absence of adequate numbers of bone marrow ‘adherent cells’(cells adherent to nylon or plastic) or peripheral blood leucocytes, suggesting the presence of two kinds of CSA in human serum, one dependent on the presence of bone marrow adherent cells and one effective in their absence. Reduction of numbers of nonspecific esterase positive cells in the bone marrow sample correlated with reduction in the stimulating effect of serum. In all sera tested, adherent cell dependent CSA was the major component.
Comparison of Haematological Features of the β0 and β+ Thalassaemia Traits in Jamaican Negroes
Authors: Millard Doreen P. , Mason Karlene , Serjeant Beryl E. , Serjeant Graham R.
Published: March 2008

Haematological characteristics have been compared in 29 subjects with heterozygous β0 thalassaemia and in 33 subjects with heterozygous β+ thalassaemia, identified by the type of sickle cell‐β thalassaemia among close relatives, in a Jamaican Negro population. Total haemoglobin, MCV and MCH were significantly lower in the β0 type but the level of Hb A2 was not significantly different. Individual values for MCV, MCH and Hb A2 in the β+ type occasionally overlapped those in the normal population casting doubt on the adequacy of these criteria in identifying all cases of heterozygous β+ thalassaemia. The haematological differences are those which would be expected on theoretical grounds. The inability to confidently differentiate the two types of heterozygous β thalassaemia has implications for genetic counselling. The inability to distinguish heterozygous β+ thalassaemia from normals on any single haematological index suggests that surveys depending on estimations of Hb A2 or on MCV alone may have underestimated the prevalence of the β+ thalassaemia gene.
Reduced Ferrochelatase Activity: a Defect Common to Porphyria Variegata and Protoporphyria
Authors: Becker D. M. , Viljoen J. D. , Katz J. , Kramer S.
Published: March 2008

Erythroid ferrochelatase activity has been studied in the normoblasts of patients with porphyria variegata and protoporphyria. Two methods were used for the investigation: one using intact cells and the other lysed cells, each measuring the amount of haem synthesized by normoblasts. In patients with porphyria variegata, ferrochelatase activity estimated by both methods was approximately 50% of the normal, and in protoporphyria the ferrochelatase activity was normal in intact normoblasts but was 20% of the normal in sonicated normoblasts (marrow lysates). It is suggested therefore that in porphyria variegata a dominantly inherited structural gene mutation results in an active ferrochelatase whereas in protoporphyria the genetic mutation results in an unstable ferrochelatase. The mechanism of the enzyme instability is not known though a number of postulates are discussed.
Haematological Changes Associated with the McLeod Phenotype of the Kell Blood Group System
Authors: Wimer B. M. , Marsh W. L. , Taswell H. F. , Galey W. R.
Published: March 2008

The McLeod phenotype is inherited as an X‐linked characteristic. The red cells have weak antigenicity in the Kell blood group and lack Kx, a precursorlike substance that appears to be necessary for proper biosynthesis of Kell antigens. Kx antigen is also required for establishment of normal cell morphology. Absence of Kx antigen causes a membrane abnormality, in which the most prominent feature is acanthocytosis, and a compensated haemolytic state.

The X‐linked gene that determines normal Kx production is called X1 k. Inheritance of a variant allele at the Xk locus is responsible for lack of Kx synthesis and the McLeod phenotype. The Xk locus is inactivated by the Lyon effect, and female carriers of the variant gene exhibit blood group mosaicism in the Kell system and have a dual red cell population of acanthocytes and discocytes.
Development of Neutrophilia by Serially Increasing Doses of Dexamethasone
Authors: Mishler John Milton , Emerson Pauline M.
Published: March 2008

Dexamethasone (4‐8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4‐6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2‐6 h. Dexamethasone‐induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.
Metabolism and Function of Human Platelets Washed by Albumin Density Gradient Separation
Authors: Walsh Peter N. , Mills David C. B. , White James G.
Published: March 2008

A method for washing platelets by albumin density gradient separation, originally designed for the study of platelet coagulant activities, has been modified for platelet aggregation and metabolic studies. Platelets are sedimented into a continuous density gradient of isosmolar albumin containing apyrase to protect them from clumping and physical injury and are resuspended in calcium‐free Tyrode's solution. The mean recovery of platelets after two separations relative to plateletrich plasma (PRP) was 90.3%. When small amounts of plasma were added to washed platelet suspensions, aggregation and release of [14C]5‐hydroxytryptamine (5HT) in response to adenosine diphosphate (ADP) or 5HT were similar to results obtained with PRP. When fibrinogen was substituted for plasma, ADP‐induced aggregation occurred but was feeble. Without added plasma or fibrinogen, platelets were refractory to ADP and insensitive to the cyclic endoperoxide analogue U44619. When both ADP and U44619 were added simultaneously, in low concentrations, to washed platelets without added plasma or fibrinogen, aggregation occurred immediately. Washed platelets were not aggregated by adrenaline, which potentiated ADP‐induced aggregation. Several biochemical measurements which are sensitive indicators of cellular damage were normal in washed platelets, including [14C]adenine uptake, adenylate energy charge, hypoxanthine formation and the response of adenylate cyclase to stimulation by PGE1 or PGD2. Platelet coagulant activities were not made available and heparin‐neutralizing activity (HNA) was not spontaneously released by the washing procedure, but the washed platelets responded normally to appropriate agents by developing coagulant activities and releasing HNA. The ultrastructure of washed platelets was similar to those in control PRP. Inclusion of apyrase in the first albumin gradient had a beneficial effect on platelet morphology, aggregation and metabolism, but washing at 37deg;C compared with 25deg;C did not. Albumin density gradient separation is a useful method for isolating platelets for aggregation and metabolic studies.
An Unusual Form of Chronic Neutropenia in a Father and Daughter with Hypogammaglobulinaemia
Authors: Mentzer William C. , Johnston Richard B. , Baehner Robert L. , Nathan David G.
Published: March 2008

Chronic neutropenia, with an abundance of mature neutrophils in the bone marrow, was discovered in a father and daughter who also had common variable hypogammaglobulinaemia. Under the stress of infection or following the administration of typhoid vaccine, release of neutrophils from the marrow was enhanced sufficiently to abolish neutropenia temporarily. Although their morphology was abnormal, the function of neutrophils in vitro was normal. Thus, the increased susceptibility to infection that characterized these patients appeared to be due primarily to their defect in humoral immunity rather than their neutropenia.
The Philadelphia Chromosome (Ph1) in Adults Presenting with Acute Leukaemia: a Comparison of Ph1+ and Ph1‐ Patients*
Authors: Bloomfield C. D. , Peterson L. C. , Yunis J. J. , Brunning R. D.
Published: March 2008

To evaluate the frequency and clinical significance of the Philadelphia chromosome (Ph1) in adult acute leukaemia, bone marrow chromosomes were studied in 15 adults with acute lymphocytic leukaemia (ALL) and 55 with acute nonlymphocytic leukaemia (ANLL). Morphology, clinical findings, therapeutic response and survival were compared in patients with and without the Ph1. The Ph1 was found in six newly diagnosed adults presenting with ALL. Adults with Ph1+ ALL differed from those with Ph1–ALL in being older, in having more frequent lymphadenopathy and splenomegaly and in demonstrating higher initial leucocyte counts and more peripheral blasts. Complete remissions were obtained in all nine adults with Ph1‐ALL but in only three of six with Ph1+ALL. Adults with Ph1–ALL survived significantly longer. Four adults with ANLL were Ph1+. They did not respond to treatment and survived significantly shorter periods than adults with Ph1–ANLL. No clinical or morphologic features indicated which patients with acute leukaemia would have the Ph1. Since the presence of the Ph1 in acute leukaemia has therapeutic and prognostic significance, marrow chromosome studies should be performed in adults presenting with acute leukaemia, especially ALL.
Occurrence of Acute Leukaemia in Myeloproliferative Disorders
Authors: Rosenthal David S. , Moloney William C.
Published: March 2008

In a series of 306 cases of myeloproliferative disorders followed over a period of 21 years, 18 cases of well‐documented acute leukaemia were encountered. Leukaemias were either acute myeloblastic or myelomonocytic and occurred from 6 months to 20 years after the initial diagnosis. Onset was relatively abrupt and the course rapidly fatal with a median survival of 4 weeks. Due to the prolonged preleukaemic phase, it was possible to carry out a variety of clinical and laboratory observations. While no consistent features were noted, dysplastic haemopoiesis, a fall in leucocyte alkaline phosphatase activity, presence of Pelger‐Hüet anomaly and other abnormalities suggest a disturbance in granulocytic maturation. These findings suggest that, following an initial injury to a pleuripotential haemopoietic stem cell, a prolonged ‘latent’period occurs and, due to exposure to additional injurious agents or to a lack of cell regulating factors, acute leukaemia develops.
Lymphocyte Abnormalities in Myeloma
Authors: Sewell R. L.
Published: March 2008

Summary. Lymphopenia and monocytosis were found in one third of untreated myeloma patients but there was no correlation between the two. Half of the patients studied had an increase in medium basophilic lymphoid cells, and eight had a raised PAS score. Lymphocytes from the majority of untreated myeloma patients failed to respond to antigenic stimulation in vitro compared with age matched controls. Three patients were immunized but showed no increase in immunoblasts or rise in antibody titre. The findings strongly suggest that abnormal lymphocytes are present in the blood in myeloma. The failure of lymphocytes to respond to antigen provides an explanation for the lack of normal plasma cells and depressed antibody responses in myeloma.