bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in Ty Lymphocytes in B‐Cell Chronic Lymphocytic Leukaemia
Authors: Catovsky D. , Lauria F. , Matutes Estela , Foa R. , Mantovani V. , Tura S. , Galton D. A. G.
Published: March 2008

Summary. The proportion of Tγ and Tμ lymphocytes was studied in 40 cases of B‐chronic lymphocytic leukaemia (B‐CLL) and six of B‐prolymphocytic leukaemia (B‐PLL). The significant increase in Ty cells, previously reported in two small B‐CLL series, was confirmed and shown to be directly correlated with the clinical stages of the disease (P < 0.01 to < 0.001). The normal Tμ: Tγ ratio (2.3:1) was reversed in B‐CLL (1:1.4) and B‐PLL (1:1.9). The proportion of Tμ cells was decreased but was not related to stage.

Our findings suggest that the increase in Ty cells may be responsible for the hypogammaglobulinaemia of B‐CLL. This is supported by two sets of observations. First, serum Ig levels were more often normal in cases in Stages 0 and 1 than in Stages II‐IV (P < 0.05), while the levels of two or three Ig classes were below normal in Stages II‐IV twice as frequently. Secondly, splenic irradiation in one case was followed by a fall in the absolute number of Ty lymphocytes, a reversion to normal of the TμW: Tγ ratio and an improvement in serum Ig levels. Thus, the imbalance in the regulatory T‐cell subsets may provide an important clue to understand the pathogenic mechanism of the immunodeficiency in the chronic B‐cell leukaemias.
Factor VIII:C and VIII:CAg Response in Patients with Haemophilia A and von Willebrand's Disease after Administration of Different Factor VIII Concentrates or Plasma
Authors: Holmberg Lars , Borge Lise , Nilsson Inga Marie
Published: March 2008

Summary. Factor VIII procoagulant activity (VIII:C) and factor VIII procoagulant antigen (VIII:CAg) were studied in seven patients with haemophilia A after administration of three different factor VIII concentrates or plasma. The in vivo recovery of VIII:CAg was less than that of VIII:C and the disappearance rate of VIII:CAg was much higher either when concentrates or plasma were given. The half‐life of VIII:C was thus about 12 h but of VIII:CAg only about 3 h or less. Six patients with von Willebrand's disease were studied after administration of AHF‐ Kabi. In contrast to haemophilia A the discrepancy between VIII:C and VIII:CAg disappearance rates was not present in von Willebrand's disease, since both VIII:C and VIII:CAg showed a typical progressive increase. We conclude that factor VIII:C given to haemophilia patients does not behave like native VIII:C, not even when fresh plasma is used. Patients with von Willebrand's disease are capable of forming a normal VIII:C when appropriately stimulated.
Prognostic Importance of Morphology (FAB Classification) in Childhood Acute Lymphoblastic Leukaemia (ALL)
Authors: Miller Denis R. , Leikin Sanford , Albo Vincent , Sather Harland , Hammond Denman
Published: March 2008

Summary.The French‐American‐British (FAB) classification has been proposed as a useful and uniform method of defining morphologic subsets of acute leukaemias. As part of a prospective study designed to identify subsets of children with high risk of early relapse (CCG 141), submitted bone marrow slides from 765 of 883 patients entered on study were reviewed by two morphologists blinded as to prognostic factors and treatment regimen. L1, L2and L3acute lymphoblastic leukaemia (ALL) comprised 85·1%, 14·1% and 0·8%, respectively, of the total population. Children with > 25% L2lymphoblasts had a significantly higher relapse rate and significantly poorer survival. Results of this study indicate that as a single variable, lymphoblast morphology is a very significant predictor of survival, haematologic remission, and complete continuous remission. Multivariate analyses show that lymphoblast morphology is again significant in determining duration of survival (P=0·048), and is of borderline statistical significance (P=0·089) in predicting length of complete continuous remission. The FAB classification, with minor modifications, is reproducible, useful, and prognostic in childhood ALL.
Haemolytic Disease of the Newborn and Chronic Anaemia Induced by γβ Thalassaemia in a Dutch Family
Authors: Oort M. , Heerspink W. , Roos D. , Flavell R. A. , Bernini L. F.
Published: March 2008

Summary. Severe haemolytic anaemia with hyperbilirubinaemia and erythroblastaemia was observed in nine newborn infants belonging to one large family. One infant was still‐born, two died shortly after birth, five recovered after receiving one or more exchange transfusions and one improved without transfusional therapy. In four out of six newborns whose bilirubin levels were determined, a mixed hyperbilirubinaemia was found with high concentrations of both free and conjugated bilirubin. At the end of the first year of life the surviving children, although in satisfactory general condition, showed a mild microcytic hypochromic anaemia with decreased red cell osmotic fragility and morphological abnormalities of the erythrocytes consisting of microcytosis, anisopoikilocytosis and target cells. The serum iron levels were normal. The same haematological picture was also present in those parents of the affected children that are members of this family; these adults had normal levels of Hbs A2 and F.

Incorporation of [3H]leucine into the globin chains of two adults with this syndrome revealed a reduced β‐chain synthesis (β/α ratio of 0.49 and 0.53, respectively). In the two infants available for this investigation, reduced γ‐chain production was found shortly after birth. In parallel with the switch from fetal to adult haemoglobin, the deficient γ‐chain production was replaced by a similar reduction of β‐chain synthesis. These results suggested, therefore, a combined deficiency of γ and β‐chain production. The normal levels of Hb A2 were compatible with a defective δ‐chain synthesis as well. Analysis with restriction enzymes had shown previously a large deletion, comprising γ and δ genes, in one of the chromosomes of the affected individuals. The same procedure had established that, in spite of the defective β‐chain production, the β‐globin structural gene is intact.
Genetic Heterogeneity of Factor XIII Deficiency: First Description of Unstable A Subunits
Authors: Castle S. , Board P. G. , Anderson R. A. M.
Published: March 2008

Summary. In previously reported cases, congenital deficiency of coagulation factor XIII has been found to result from the absence of the cnzymatically active A subunits. In the family reported here two members were found to be heterozygous for an unstable A subunit which, in the homozygous state, or in the heterozygous state with the previously described null allele, would be expected to result in factor XIII deficiency. The implications that this new variant has on heterozygote screening are discussed.
Red Cell Membrane Response to Hydrogen Peroxide‐Sensitivity in Hereditary Xerocytosis and in Other Abnormal Red Cells
Authors: Snyder L. M. , Sauberman N. , Condara H. , Dolan J. , Jacobs J. , Szymanski I. , Fortier N. L.
Published: March 2008

Summary. Osmotically resistant red cells associated with some haemolytic anaemias, including hereditary xerocytosis, sickle‐cell disease and β thalassaemia minor, are more sensitive than normal red cells to exogenous in vitro hydrogen peroxide (H2O2). This sensitivity is manifested by a rapid loss of intracellular potassium, shape change, protein aggregation, and methaemoglobin formation at lower concentrations of H2O2 (225 μm.) than are required to induce similar effects in normal red cells (450 μm). Malonyldialdehyde (MDA) formation occurs later than the other effects and can be inhibited by the antioxidant, butylated hydroxytoluene (BHT), without affecting protein aggregation or potassium leak. Incubation of normal red cells directly with MDA induces protein aggregation, but only after 1 h of incubation. Although nystatin‐sucrose treated normal cells which are dehydrated with altered cation content, and therefore osmotically resistant, do not display abnormal H2O2 hypersentitivity as manifested by excessive potassium permeability, they do show an increase in methaemoglobin formation and protein aggregation similar to xerocytes. These data indicate that membrane protein cross‐linking occurring immediately following H2O2 exposure seems independent of either the sulfhydryl or MDA mechanisms, and that the membrane permeability of the abnormal red cells predisposes them to oxidative damage.
Red Cell Size and the Clinical and Haematological Features of Homozygous Sickle Cell Disease
Authors: Serjeant G. R. , Foster Karen , Serjeant B. E.
Published: March 2008

Summary. The contribution of red cell size (mean cell volume) to the clinical and haematological manifestations of homozygous sickle cell (SS) disease has been investigated by comparing the features of two groups of patients with low (≤80 fl) and high (>95 fl) MCV values after matching for age, sex and fetal haemoglobin level. The microcytic group manifested significantly higher Hb, PCV, RBC and HbA2 levels and significantly lower reticulocyte and irreversibly sickled‐cell counts. Clinical features were not less severe in the microcytic group, splenomegaly persisting for longer and painful crises were more common although the latter difference did not reach significance. The milder haematological picture associated with decreased intravascular sickling was not reflected in a more mild clinical course. It is postulated that the higher viscosity accompanying the higher haemoglobin levels in microcytic patients may offset the rheological advantages of decreased intravascular sickling.
The Preparation and Properties of Monoclonal Antibodies against Human Granulocyte Membrane Antigens
Authors: Zola H. , McNamara P. , Thomas Miriam , Smart I. J. , Bradley J.
Published: March 2008

Summary. A series of four monoclonal antibodies has been prepared by hybridization of mouse myeloma cells with spleen cells from mice immunized with human blood granulocytes. The four antibodies all react specifically with granulocytes, failing to stain lymphocytes and other blood cells. Lymphocytic leukaemia cells are not stained, whereas myeloid leukaemia cells give a varied reaction with the antibodies. Studies on marrow, leukaemic cells and cell lines suggest that the four antibodies react with distinct differentiation antigens which are absent from myeloblasts, appear at the promyelocyte, myelocyte or metamyelocyte stage (depending on the antibody in question) and are expressed on all mature granulocytes.
Splenic Irradiation in B‐Prolymphocytic Leukaemia
Authors: Oscier D. G. , Catovsky D. , Errington R. D. , Goolden A. W. G. , Roberts P. D. , Galton D. A. G.
Published: March 2008

Summary.

Twelve patients with B‐cell prolymphocytic leukaemia (PLL) were treated with splenic irradiation at a weekly dose of 100 cGy to a maximum total dose of 1000 cGy. There was no morbidity associated with this treatment. Seven patients responded. Three achieved a good response and four a partial response. Two of the patients who had a partial response have subsequently died of unrelated causes. Four of the five patients who failed to respond have died as a result of their disease. When more than 25% of the prolymphocytes formed rosettes with mouse red blood cells (MRBC) the patients appeared to respond better to splenic irradiation. There was no correlation between response and the initial white cell count or the size of the spleen.
Comparative Studies on Human Activators of Plasminogen
Authors: Mackie Michael , Booth Nuala A. , Bennett Bruce
Published: March 2008

Summary. Agents activating human plasminogen have been prepared from a variety of human sources, namely plasma, blood vessel endothelium and tissue. Their physical and functional properties have been found to differ from that of the urinary activator, urokinase. Antiserum to urokinase, while it quenched the activity of urokinase itself, had no effect on the activity of the plasma, endothelial or tissue activators.
The Use of Factor IX Concentrates in Man: a 9‐Year Experience of Scottish Concentrates in the South‐East of Scotland
Authors: Prowse C. V. , Cash J. D.
Published: March 2008

Summary. During the last 9 years, two factor IX concentrates produced in Scotland, PPSB and DEFIX, have been used for the treatment of haemophilia B and acquired coagulation disorders, including those due to liver disease, coumarin therapy, neonatal immaturity and post‐operative bleeding. During the period of study 112 batches of DEFIX and 40 batches of PPSB were used in the Edinburgh and South‐East Scotland Region. Data were analysed from 575 non‐haemophilic patients, receiving 968 treatment episodes, as well as 24 haemophiliacs. Serial coagulation studies and analysis of retrospective data showed that both concentrates corrected the coagulation deficiencies in all the above patient groups; in no case was there any evidence of intravascular coagulation resulting from concentrate infusion.
HLA Antigens and Childhood Acute Lymphocytic Leukaemia
Authors: Davey Frederick R. , Lachant Neil A. , Dock Nancy L. , Hubbell Charlene , Stockman James A. , Henry John B.
Published: March 2008

Summary. HLA‐A and ‐B antigens were determined for 94 children with acute lymphocytic leukaemia (ALL) and for 376 normal controls. Sixty‐four of these 94 patients were typed for lymphocyte surface markers and 59 were defined as ‘null cell’ ALL. There was no difference in the distribution of the HLA‐A or ‐B locus antigens between the control group and the entire group of patients with ALL or the ‘null cell’ subgroup. Patients with HLA‐A9 determinants had a significant increase in early, first remission duration compared to patients without HLA‐A9. This was particularly evident in the ‘null cell’ ALL subgroup. In addition, HLA‐A9 appeared to be an independent factor affecting the length of first remission since there was no correlation between known prognostic factors such as patient age, sex or WBC and the presence or absence of the HLA‐A9 antigen. Survival for the first 12–18 months was also greater in the HLA‐A9 group than in the non‐HLA‐A9 population. Thus, the presence of HLA‐A9 appears to be associated with some protective effect among patients with ALL.
Hereditary Antithrombin III Deficiency in an English Family
Authors: Scully M. F. , Haas H. De , Chan P. , Kakkar V. V.
Published: March 2008

Summary. A family including four members with decreased antithrombin III (ATIII) measured by a biological and an immunological method is described. Immunologically measured levels of other coagulation inhibitors were normal. In the antithrombin III deficient family members there was a history of thrombotic disease. Turnover of 125I‐antithrombin III in a deficient individual showed the lower plasma levels probably to be due to a deficiency in the rate of synthesis rather than to an increased catabolic rate.
Immunoradiometric Assay of Factor VIII: Coagulant Antigen using Four Human Antibodies. Study of 27 Cases of Haemophilia A
Authors: Girma Jean‐Pierre , Lavergne Jean‐Maurice , Meyer Dominique , Larrieu Marie‐Josea
Published: March 2008

Summary. Immunoradiometric assay (IRMA) of VIII:C antigen was performed using either IgG or monovalent Fab fragments from four antibodies arisen in polytransfused haemophilia A patients (titre between 100 and 1500 U/ml). Using IgG isolated by a solid or a liquid phase system, only the high titre (1000 U/ml) antibodies could be used for IRMA, with a sensitivity of 0.2% VIII:CAg. Using Fab fragments isolated by liquid phase, high and low (150 U/ml) titre antibodies could be used and the IRMA was significantly improved with a 10‐fold higher sensitivity. The affinity of the antibodies for VIII:CAg, studied by displacement curves using a modification of the IRMA, was found not to depend upon the titre of the antibody. Comparative levels of VIII:C and VIII:CAg in 27 cases of haemophilia A emphasize the heterogeneity of this disorder, two types of severe and three types of mild haemophilia being observed.
A Radial Immunodiffusion Method for the Assay of Factor VIII:C Antigen (VIII:C Ag) in Plasma
Authors: McLellan D. S. , Devlin J. D. , Groom P. , Aronstam A.
Published: March 2008

Summary. A method has been developed for the immunological quantitation of factor VIII:C Ag using a medium titre (50 new Oxford units) factor VIII:C antibody arising in a severe multitransfused haemophiliac. The method, which utilizes clotting inhibition in an agarose gel medium, gave close and significant correlation with the two‐stage factor VIII:C procoagulant assay (r= 0.83, P < 0.01) for 54 normal subjects. Similar or higher values were found in 19 mild, moderate and severe haemophiliacs with 2–30% average normal plasma levels of factor VIII:C (r= 0.72, P < 0.01). Four mild von Willebrand patients gave similar results by immunoassay and procoagulant assay methods. A previously identified patient with cross reacting material (CRM+) gave an immunoassay within the normal range (66%) with only 4% VIII:C activity detectable. The method offers a simple, sensitive and apparently reliable procedure for the assay of plasma factor VIII:C Ag which may prove useful in the further investigation of factor VIII:C Ag and antibody heterogeneity. The procedure offers an alternative to immunoradiometric assay and may be of potential use in the assessment of the haemophilia carrier state and possibly the early detection of thrombosis.
An Evaluation of Chromogenic Substrates in the Control of Oral Anticoagulant Therapy
Authors: Latallo Z. S. , Thomson Jean M. , Poller L.
Published: March 2008

Summary. A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and four modified amidolytic assays in the assessment of laboratory control of oral anticoagulant administration in short‐term and long‐term patients. The results were also correlated with the APTT and specific assays for factors VII and X based on established coagulation techniques. The chromogenic substrate assays did not give as close agreement with the BCT as the clotting assays for factors VII and X. A combination of the amidolytic factor II and X results did not improve the correlation. Agreement with the BCT was better in long‐term patients with the substrates but there was no obvious advantage between the factor II and X amidolytic methods in this group. The development of a specific amidolytic assay for factor VII should be considered based on the evidence of this study although its reliability for oral anticoagulant control would need to be validated by clinical trial. In the interim, it may be anticipated that thromboplastins showing less sensitivity than BCT to factor VII would give a better correlation with the amidolytic assays.
Defective Neutrophil Mobility in the May‐Hegglin Anomaly
Authors: Cabrera J. R. , Fontaan G. , Lorente F. , Regidor C. , Fernaandez M. N.
Published: March 2008

Summary. A case of May‐Hegglin anomaly is reported in which functional studies of PMN cells showed abnormalities consisting of impairment of chemotactic and chemokinetic responses, random mobility being otherwise normal. These abnormalities seem unrelated to microtubule system dysfunction or to abnormal cell deformability, since no defect was observed in the concanavalin A (Con A) surface receptors and no improvement of directional movement resulted when filters of larger pore size were used in the assays. Other possible mechanisms of the functional defect, such as abnormal membrane receptors to kinetic signals or metabolic abnormalities cannot be excluded. PMN function should be studied in additional cases in order to ascertain if these findings are a constant feature in the May‐Hegglin anomaly, a syndrome in which undue susceptibility to infection has not been reported.
In Vitro Assay of Erythropoietin in Fetal Mouse Liver Cultures
Authors: Brandan N. C. , Cotes P. M. , Espada J.
Published: March 2008

Summary. Iron bound to human transferrin but not apotransferrin, increases the effect of erythropoietin in stimulating incorporation of H‐thymidine into DNA in fetal mouse liver cells in vitro. The effect of erythropoietin, with or without transferrin‐iron is blocked by pre‐incubation of the erythropoietin with rabbit anti erythropoietin serum. Human sera contain factors in addition to erythropoietin and transferin‐iron which may modify the stimulation of incorporation of H‐thymidine into fetal mouse liver DNA induced by erythropoietin. Heat treatment of sera at 56°C for 30 min does not necessarily destroy these factors. Acid heat treatment of sera (pH 5.5 and 100°C for 5 min) may destroy inhibitory factors and can result in an apparent increase in serum erythropoietin activity assessed in this fetal mouse liver system.
An Assessment of an Amidolytic Assay for Factor VII in the Laboratory Control of Oral Anticoagulants
Authors: Poller L. , Thomson Jean M. , Bodzenta Anna , Easton Ann C. , Latallo Z. S. , Chmielewska Joanna
Published: March 2008

Summary. A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and a chromogenic substrate assay for factor VII in the assessment of laboratory control of oral anticoagulants in short‐term and long‐term patients. Opportunity was also taken to compare the findings with parallel results obtained with the venous Thrombotest technique and a specific clotting assay for factor VII. There was good agreement between the amidolytic factor VII assay, using a method modified from Seligsohn et al (1978) with the Quick test using BCT and Thrombotest in 60 long‐term patients. Tests in 53 patients within the first 3 weeks of starting oral anticoagulant administration gave less satisfactory agreement between the above amidolytic method and the conventional tests. In contrast, there was a good correlation between the two conventional tests in both groups and also between the clotting and amidolytic factor VII method. Although the results are an improvement on previous, less satisfactory correlations between the BCT prothrombin time method and amidolytic assays for factor II and X, the present study indicates the limitations of a specific clotting assay versus a broad spectrum extrinsic clotting test in oral anticoagulant control. While not warranting the routine use of the chromogenic assay for factor VII in place of the prothrombin time using BCT, the factor VII amidolytic assay offers a limited but dependable guide to dosage in long‐term patients. The complexity of the technique in its present form militates against its adoption for routine anticoagulant control in hospital laboratories.
Contact Activation of Factor XI
Authors: Jacobs Aaron , Mannhalter Christine , Margalit Ruth , Schiffman Sandra
Published: March 2008

Summary. Factor XI is a circulating trace plasma protein composed of two similar or identical chains of about 80 000 daltons which upon activation undergo proteolytic cleavage. Recently, we have shown that trypsin activation leads to an active factor XI (factor XIa) which, on reduction, yields three chains of 46 000, 37 000 and 26 000 daltons. Herein, we re‐evaluate the effect of contact activation of factor XI at an activating surface both in normal human plasma and in a mixture of purified factors XI, XII, and high molecular weight kininogen (HMWK). Mixtures were analysed by coagulant activity and by reduced sodium dodecyl sulphate polyacrylamide gel electrophoresis using [125I] factor XI. In the purified system, fully activated factor XI on reduction yielded chains of 46 000, 37 000 and 23 000 daltons. In contrast, factor XI activated by surface contact in plasma yielded on reduction only chains of 46 000 and 37 000 daltons in addition to some uncleaved 80 000 chain. We propose that factor XIa containing only 46 000 and 37 000 chains be designated factor XIaα, and that factor XIa containing the third chain of 23 000 daltons be designated factor XIaβ. Sequential elution of contact activated plasma factor XI revealed that factor XIa was attached to the glass surface through the 46 000 dalton chain.
Diurnal Levels of Immunoreactive Erythropoietin in Normal Subjects and Subjects with Chronic Lung Disease
Authors: Miller Marilyn E. , Garcia Joseph F. , Cohen Ruth A. , Cronkite Eugene P. , Moccia Giuseppe , Acevedo Julio
Published: March 2008

Summary. Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20‐60 years, to establish a control value for Ep of 18·5±5·0 (x̄ SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17‘normal’volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects with chronic lung disease. These patients, in contrast to normal subjects, exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P <0·02).
Biochemical Studies on Cryopreserved Granulocytes: Possible Explanations for the Defects Induced
Authors: McCarthy D. M. , Goldman J. M. , Peters T. J.
Published: March 2008

Summary. The functional capacity of normal human granulocytes has been studied after cryopreservation by two different methods with dimethylsulphoxide as cryoprotectant. Both methods resulted in substantial disruption of organelle membranes and impaired cell function. Similar organelle disruption could be induced without cryopreservation following the addition of dimethylsulphoxide to cells, but the extent of this disruption was dependent on the temperature at which the dimethylsulphoxide was diluted out. The loss of cellular function also depended on the temperature and rate of dilution.

We suggest that disruption of membrane organization is the mechanism underlying the loss of cell function induced by cryopreservation. Pending development of more successful methods of cryopreserving granulocytes, it is recommended that optimal preservation of functional activity would be obtained if the cryopreserved cells are thawed directly at 37°C and the cryoprotectant diluted carefully and slowly.
The Aplastic Presentation of Childhood Leukaemia: a Feature of Common‐ALL
Authors: Breatnach F. , Chessells J. M. , Greaves M. F.
Published: March 2008

Summary. Transient pancytopenia preceded the onset of acute leukaemia in eight of 360 (2%) of children with acute lymphoblastic leukaemia (ALL) but did not occur in 70 cases of acute non‐lymphoblastic leukaemia. The patients developed overt leukaemia within 5—38 weeks of first presentation with features of marrow failure. Immunological classification of blast cells was performed in six of the eight patients and all had the phenotype of common‐ALL (c‐ALL). We conclude that the syndrome of pre‐leukaemia aplasia in childhood is a feature of c‐ALL.
Antibodies against Platelet Membrane Glycoproteins II. INFLUENCE ON ADP‐ AND COLLAGEN‐INDUCED PLATELET AGGREGATION, CROSSED IMMUNOELECTROPHORESIS STUDIES AND RELEVANCE TO GLANZMANN'S THROMBASTHENIA
Authors: Jenkins C. S. P. , Ali‐Briggs ELIZABETH F. , Clemetson K. J.
Published: March 2008

Summary. In Glanzmann's thrombasthenia glycoproteins IIb and IIIa are missing or strongly reduced and aggregation to ADP, collagen and thrombin is impaired. Antibodies against glycoproteins IIb and IIIa did not entirely induce a thrombasthenia‐like state in normal platelets. However, they did strongly inhibit collagen‐induced aggregation and inhibited the second wave of aggregation induced by ADP.

Crossed immunoelectrophoresis studies using Triton X‐100 extracts of whole platelets with these antibodies gave a single immunoprecipitate. This immuno‐precipitate was absent when similar studies were carried out with thrombasthenic platelets.

Platelet antibodies gave a number of immunoprecipitates with normal platelets and differences were observed with thrombasthenic platelets, the most notable of which was a marked reduction in one of the major immunoprecipitates.

These results provide further evidence that glycoproteins IIb and IIIa are involved in the later stages of platelet aggregation.
Post‐transfusion Purpura: a Serological and Immunochemical Study
Authors: Pegels J. G. , Bruynes E. C. E. , Engelfriet C. P. , Kr.von dem Borne A. E. G.
Published: March 2008

Summary. By applying the platelet suspension immunofluorescence test (PSIFT), platelet‐specific alloantibodies responsible for post‐transfusion purpura were detected in eight patients within a period of 2 years. All patients were female and had previously received blood or had been pregnant. The platelet‐specific alloantibodies had the specificity anti‐Zwa in all the patients, who were all Zw(a ‐). In two patients the platelets were tested in the acute phase of the disease and found to be coated with IgG. In one patient an ether eluate was prepared from the platelets that reacted strongly with Zw(a +) platelets, but weakly with platelets from Zwb‐homozygous individuals. The sera of these two patients, and of two others whose platelets were not directly tested, taken in the acute phase of the purpura, reacted strongly with Zwa‐positive platelets. The four sera also reacted, however weakly, with Zwa‐negative platelets, with autologous platelets taken during remission and with platelets from patients with Glanzmann's disease.

It is postulated that Zwa‐anti‐Zwa complexes, present in the eluate and the sera, caused the reaction with Zwa‐negative platelets and the patients’own platelets. Immunochemical characterization of the post‐transfusion purpura antibodies showed that in all patients these were IgG, in two combined with IgM antibodies. Antibodies of the sub‐class IgG1 were found in all patients, sometimes together with IgG3. In the indirect immunofluorescence test with anti‐complement serum, the PTP antibodies in only four sera were able to fix complement. In only two of these sera were these complement‐binding antibodies detectable in the 51Cr‐lysis technique and then in a much lower titre than in the immunofluorescence technique.
Specific Enhancement of Mouse CFU‐E by Mouse Transferrin
Authors: Rich Ivan N. , Sawatzki Gunter , Kubanek Bernhard
Published: March 2008

Summary. Pure human and mouse transferrins were prepared by a chromatographic procedure and their effect on the growth of early (BFU‐E) and late (CFU‐E) erythropoietic precursors in mouse bone marrow is described. In the presence of optimal erythropoietin concentrations mouse bone marrow cells have a greater specificity for mouse transferrin (950 CFU‐E colonies/105 cells) than human transferrin (650 CFU‐E colonies/105 cells). Optimal transferrin concentrations for both human and mouse transferrins were 1.3 × 10−13 M and 1.3 × 10−10 M corresponding to between 7.8 × 107 and 7.8 × 1010 molecules/ml of culture. These concentrations are in excess of that calculated on a theoretical basis. Neither erythropoietic burst nor granulocyte/macrophage colony formation exhibited a dose dependent relationship for any of the transferrins employed, although higher colony numbers were obtained with mouse transferrin compared to human transferrin.
Terminal Transferase Expression in Relapsed Acute Myeloid Leukaemia
Authors: Bradstock K. F. , Pizzolo G. , Papageorgiou E. S. , Cetto G. L. , Prentice H. G. , Ganeshaguru K. , Prentice A. G. , Smith A. , Chilosi M. , Ambrosetti A. , Hoffbrand A. V.
Published: March 2008

Summary. In three cases of acute myeloid leukaemia marked increases in expression of the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), were observed during disease relapse. The first case was heterogeneous at diagnosis, consisting of subpopulations of large TdT− myeloblasts and small TdT+ blasts; however, at relapse there was complete replacement by TdT+ lymphoblasts. The other cases at diagnosis were both typical acute myeloid leukaemia, TdT−; at relapse, one showed a mixture of TdT− myeloblasts and TdT+ lymphoblasts, while in the other, TdT was demonstrated on a subpopulation of myeloblasts. No chromosomal abnormalities were found. It is suggested that in the first two cases these phenomena may have been due to leukaemic involvement of a pluripotential stem cell, or that sub‐clones with different properties may have coexisted. In the third case at relapse, TdT was expressed aberrantly by malignant myeloid cells.
Antenatal diagnosis of haemoglobinopathies by Biorex chromatography of haemoglobin
Authors: Blouquit Y. , Beuzard Y. , Varnavides L. , Chabret C. , Dumez Y. , John P. N. , Rodeck C. , White J. M.
Published: March 2008

Summary. Biorex chromatography of haemoglobin has been compared to the standard chromatographic separation of radioactive globin chains in 60 fetal blood samples obtained for the antenatal diagnosis of haemoglobinopathies. Biorex chromatography of haemoglobin permitted two measurements, the optical density at 418 nm and the radioactivity incorporated into fetal and adult haemoglobin. The two measurements were highly correlated (r2= 0.96) and enabled a distinction between homozygous from heterozygous states of the diseases to be made, particularly in β thalassaemia. A single column was used for 50 analyses. This fast and very sensitive method is proposed for the antenatal diagnosis of haemoglobinopathies using fetal blood.
Immuno‐histological analysis of bone marrow involvement in lymphoproliferative disorders
Authors: Pizzolo G. , Chilosi M. , Cetto G. L. , Fiore‐Donati L. , Janossy G.
Published: March 2008

Summary. Cryostat sections from bone marrow biopsies submerged in gum‐sucrose solution and snap‐frozen can be stained with various antisera to detect both the membrane and cytoplasmic antigens on normal and malignant populations in their tissue environments. This technique seems to be the method of choice to analyse the degree of BM involvement in cases of non‐Hodgkin's lymphoma where conventional histology provides equivocal results. The uniform expression of only one type of light chain in B lymphoma and the analysis of the T cell infiltrate in T‐CLL using monoclonal antibodies is demonstrated.
The IgG binding function of the normal red cell plasma membrane: identification of integral polypeptides that bind IgG
Authors: Victoria Edward J. , Mahan Lawrence C. , Masouredis S. P.
Published: March 2008

Summary. Non‐immune IgG binds to red cell integral membrane proteins obtained by mild alkaline extraction of ghosts. Detergent gel chromatography and electrophoretic analyses of IgG‐membrane protein complexes obtained by nonionic detergent solubilization and affinity binding to protein A indicate that three polypeptides participate in the binding of IgG. These have apparent molecular weights of 90 000, 44 000 and 22 000 and are present in a 1:3:0.9 stoichiometry. Evidence obtained indicates that the major sialoglycoproteins are not involved in this type of binding.
Uncontrolled thrombocytosis in chronic myeloproliferative disorders
Authors: Kessler Craig M. , Klein Harvey G. , Havlik Richard J.
Published: March 2008

Summary. A retrospective study was performed to examine the natural course of uncontrolled thrombocytosis associated with chronic myeloproliferative disorders. Thirty‐eight patients with polycythaemia rubra vera (PV), myelofibrosis/myeloid metaplasia (MM), chronic myelogenous leukaemia (CML) or essential thrombocythaemia (ET) had platelet counts greater than 1000 × 109/1 and were followed closely for a total of 246 patient years. Eleven of the patients experienced haemorrhagic episodes. Bleeding was twice as frequent in patients over 59 years old as in those younger and no bleeding occurred in those less than 51 years of age. There was no correlation between frequency of bleeding and extent of thrombocytosis. Bleeding events occurred concurrently with use of anti‐inflammatory agents in 32% of episodes. The gastrointestinal tract was the most frequent site. Documented thrombotic events occurred in three patients, two of whom had PV with haematocrits greater than 53%. This study suggests that the thrombocytosis of myeloproliferative processes may pose a less serious threat than originally thought and that aggressive lowering of the platelet count may not be indicated in all cases.
Fractionation of mammalian bone marrow by counterflow centrifugation‐elutriation using a continuous albumin gradient: analysis of granulocyte‐macrophage colony‐forming units
Authors: Jemionek John F. , MacVittie Thomas J. , Byrne Patrick J. , Schein Philip S. , Walden Dane A.
Published: March 2008

Bone marrow cells from murine, canine, primate and human donors were fractionated by counterflow centrifugation‐elutriation (CCE) using a continuous albumin gradient. Fractionation of 9 × 108 nucleated bone marrow cells (without prior removal of the erythrocytes) can be done in less than 1.5 h with 92% nucleated cell recovery, depending on donor species. Murine bone marrow cell recovery after fractionation averaged 52% whereas cell recoveries for canine, primate and human donors averaged 85%, 92% and 89%, respectively. The fractions were evaluated for total nucleated cell counts and granulocyte‐macrophage colony‐forming units (GM‐CFC). Each species studied presented a unique profile for nucleated cell recovery and associated GM‐CFC activity. These profile variations may suggest significant differences in the modes of GM‐CFC expression in the individual species that may depend on cell‐to‐cell interactions. Although CCE is unable to isolate a single population responsible for GM‐CFC activity, CCE does permit a rapid, reproducible fractionation of large numbers of cells with minimal manipulation of sample. This makes the isolated sample ideal for further purification of progenitor cell populations.
The role of the enterohepatic cycle in folate supply to tumour in rats
Authors: Steinberg Stephen E. , Campbell Caryl L. , Hillman Robert S.
Published: March 2008

SUMMARY. The importance of the folate enterohepatic cycle in governing the supply of folate to implants of a rapidly‐growing tumour were studied in a new animal model. Following enteric administration of tritiated pteroylglutamic acid, [3H]PteGlu1, tumour uptake of labelled folate was limited to CH3[3H]H4PteGlu1 produced by the gut mucosal cells during absorption or subsequently recirculated through the enterohepatic cycle. 50% of the labelled folate reaching the tumour nodules in the first 6 h after enteric administration first circulated through the enterohepatic cycle. In addition, labelled folate taken up by tumour was immediately incorporated into a polyglutamyl folate pool. There was no evidence for a release of labelled folate from tumour for recirculation to the liver. Therefore the liver and folate enterohepatic cycle appear to play a major role in regulating the supply of folate to rapidly proliferating tissues such as tumour by acutely storing folate from the diet and then secreting it into bile for reabsorption and transport to tissue.
Changes in the mean corpuscular red cell volume in women with β‐thalassaemia trait during pregnancy
Authors: Lewis D. , Stockley R. J. , Chanarin I.
Published: March 2008

Thirty‐eight women with β‐thalassaemia trait and thirty‐five normal Asian women were studied retrospectively during normal pregnancies. The red cell size increased in both groups, with a mean increase of 2.3 fl (SD 2.3) in the women with β‐thalassaemia trait and a significantly higher increase of 4.3 fl (SD 2.1) in the normal Asian women. The rise in red cell size during pregnancy which is a physiological change, is thus impaired by defective globin‐chain synthesis as well as by iron deficiency.
PLASMIN‐α2‐ANTIPLASMIN COMPLEX AS AN INDICATOR OF IN VIVO FIBRINOLYSIS
Authors: BOOTH N. A. , BENNETT B.
Published: March 2008

α2‐Antiplasmin is the principal plasma inhibitor of plasmin, with which it rapidly and irreversibly forms a complex. The simple technique of crossed immunoelectrophoresis against antiserum to α2‐antiplasmin has been applied to detect plasmin‐α2‐antiplasmin complex in plasma. The presence of this complex is demonstrated in patients in whom overactive fibrinolysis was the only or major contributor to severe haemorrhagic disorders arising spontaneously.
Thiamine responsive anaemia: a study of two further cases
Authors: Haworth Catherine , Evans D. I. K. , Mitra J. , Wickramasinghe S. N.
Published: March 2008

A brother and sister of Pakistani origin suffered from sensorineural deafness, diabetes mellitus and a macrocytic anaemia. Their bone marrows showed megaloblastic erythropoiesis and contained many ringed sideroblasts. Electron microscope studies of the bone marrow revealed (1) iron‐laden mitochondria in many erythroblasts, (2) non‐specific abnormalities indicative of dyserythropoiesis in some erythroblasts, and (3) evidence of ineffective erythropoiesis. The deoxyuridine suppression test indicated that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. Studies of nucleic acid synthesis in the bone marrow cells showed that the rate of incorporation of [3H]thymidine into DNA was increased and that the rates of incorporation of [14C]glycine and [14C]adenine into both DNA and RNA were essentially within the normal range. The anaemia did not respond to therapy with hydroxocobalamin, folic acid or pyridoxine but responded to 25 mg thiamine, daily, by mouth. In one of the cases a post‐thiamine marrow aspirate showed a considerable improvement in both the megaloblastic and sideroblastic changes.
Assessment of the sites of red cell destruction using quantitative measurements of splenic and hepatic red cell destruction
Authors: Ferrant A. , Cauwe F. , Michaux J. L. , Beckers C. , Verwilghen R. , Sokal G.
Published: March 2008

Red cell survival, surface counting indices, the splenic and hepatic contribution to red cell destruction and the rate of splenic and hepatic red cell destruction were measured in 29 patients. Splenectomy was performed in 14. No correlation could be found between the splenic excess count index and both the amount and rate of red cell destruction in the spleen, but the rate of splenic and hepatic red cell destruction was related to the rate of disappearance of red cells from the circulation. The mean fractions of red cell destruction in spleen and liver were 46.1%± 20.5 (SD) and 11.7%± 4.2 (SD) respectively. After splenectomy, the haematocrit returned to normal in all patients despite fractions of red cell destruction in the spleen not exceeding 60%. Although the measurements of the splenic red cell destruction rate and of the fraction of red cell destruction in the spleen provide more precise information on the role of the spleen in red cell destruction, their prognostic value in patients who underwent splenectomy was not obvious.
Post‐transfusion purpura: response to steroids and association with red blood cell and lymphocytotoxic antibodies
Authors: Slichter Sherrill J.
Published: March 2008

An unusual patient with post‐transfusion purpura is described who had a rapidly rising platelet count with high dose steroid treatment in the presence of an increasing anti‐PlA1 antibody titre. A platelet autoantibody could not be detected by a radioactive platelet antiglobulin test, but autologous platelet survival data indicated a compensated thrombolytic state in the recovery period. Thus in spite of the failure to demonstrate a platelet autoantibody, the rapid response to steroids in association with a reduced platelet survival is compatible with an autoimmune platelet destructive process. In addition to PlA1 platelet antibodies, this patient had an associated anamnestic recall of multispecific red cell and lymphocytotoxic antibodies.
Deoxycoformycin‐induced response in chronic lymphocytic leukaemia: deoxyadenosine toxicity in non‐replicating lymphocytes
Authors: Kefford R. F. , Fox R. M.
Published: March 2008

The occurrence of severe immunodeficiency disease in children with inherited adenosine deaminase deficiency, and reports of remission induction in T‐cell acute lymphoblastic leukaemia with the adenosine deaminase inhibitor deoxy‐coformycin, prompted a study of the effects of deoxyadenosine on resting peripheral blood lymphocytes (PBL) and chronic lymphocytic leukaemic (CLL) lymphocytes in short‐term culture. In the presence of an inhibitor of adenosine deaminase, micromolar concentrations of dAdo caused elevation of deoxyadenosine‐5′‐triphosphate (dATP) pools and in vitro lysis of non‐dividing PBL and CLL lymphocytes. This death of non‐replicating cells indicates a mechanism of deoxyadenosine toxicity independent of DNA replication and ribonucleotide reductase inhibition. Similar changes occurred in vivo in a patient with advanced CLL who responded to treatment with deoxycoformycin, 0.1 mg/kg, days 1‐5, with a fall in the WCC from 102.0 × 109/l to 6.8 × 109/l over 21 d. Therapeutic blockade of deoxyadenosine catabolism deserves further investigation both in the treatment of lymphoproliferative disease and as a method of lympholytic immunosuppression.
Intracellular lactic dehydrogenase and phosphohexose isomerase activity in leukaemia and malignant lymphoma
Authors: Ho Anthony D. , Fiehn Walter , Hunstein Werner
Published: March 2008

Intracellular activities of total lactic dehydrogenase (LDH) and phosphohexose isomerase (PHI) were investigated in the leukaemic cells of 14 patients with acute myeloid leukaemia (AML), five with chronic myeloid leukaemia (CML), seven with acute lymphoblastic leukaemia (ALL), 19 with chronic lymphocytic leukaemia (CLL), 16 with leukaemic non‐Hodgkin's lymphoma (NHL) and in the lymphocytes of 14 normal persons. Intracellular total LDH‐activity of the blasts of AML and ALL was in the same range as the normal lymphocytes. Patients with CLL and NHL had significantly lower levels (P<0.01) of total intracellular LDH than the controls. Intracellular PHI activity was consistently lower in the lymphoid malignancies (ALL, CLL, NHL) than in normal lymphocytes (P<0.05), or in leukaemic myeloblasts (P<0.01). The intracellular LDH/PHI index of the leukaemic lymphoblasts was significantly elevated as compared to lymphocytes from normal subjects (P<0.0001) or to leukaemic cells from patients with AML (P<0.001), with CLL (P< 0.0001) or with NHL (P< 0.001). The patients with CLL and NHL, on the other hand, had significantly lower levels of LDH/PHI ratio than the normal subjects (P<0.0001 and P<0.025 respectively).
A new familial variant of antithrombin III: ‘Antithrombin III Paris’
Authors: Wolf M. , Boyer C. , Lavergne J. M. , Larrieu M. J.
Published: March 2008

Summary. A 59‐year‐old woman presented a recurrent history of thromboembolism. A qualitative defect of antithrombin III (AT III) was suggested by the discrepancy between a normal amount of AT III antigen and a decreased heparin cofactor activity. Six members of the same family showed a similar defect although clinically asymptomatic. The qualitative abnormality of AT III was confirmed by two‐dimensional immunoelectrophoresis. In the absence of heparin, a single peak was obtained with both control and patients' plasmas. In the presence of heparin, two peaks of AT III were observed in the patients' plasmas: the mobility of one peak was similar to that of the control, whereas the other showed a decreased mobility, suggesting a lack of binding to heparin. The two populations of AT III were separated by affinity chromatography on heparin‐agarose. 50% of the patients' AT III bound to the agarose beads. The remainder, recovered in the supernatant, migrated in two‐dimensional immunoelectrophoresis as a single peak with the same mobility in the presence or absence of heparin, and was devoid of heparin cofactor activity. This familial AT III variant characterized by a reduced affinity for heparin is tentatively named ‘Antithrombin III Paris’.