bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of the Homozygous States for Gγ and GγAγδβ Thalassaemia
Authors: Amin A. B. , Pandya N. L. , Diwin P. P. , Darbre P. D. , Kattamis C. , Metaxatou‐Mavromati A. , White J. M. , Wood W. G. , Clegg J. B. , Weatherall D. J.
Published: March 2008

Summary. One Arabic and two Indian patients with thalassaemia intermedia produce only Hb F of the Gγ type. Haemoglobin synthesis studies and genetic analysis indicate that they are homozygous for Gγδβ thalassaemia. The findings in these patients and their heterozygous relatives are compared with those in an individual homozygous for GγAγδβ thalassaemia. From this analysis, and from previously reported data on GγAγδβ thalassaemia, the phenotypic expression of the two varieties of δβ thalassaemia is defined. The relationship between the clinical expression and molecular pathology of these forms of δβ thalassaemia is discussed.
Ultrastructural Localization of Peroxidases in ‘Undifferentiated’Blasts during the Blast Crisis of Chronic Granulocytic Leukaemia
Authors: Marie J. P. , Vernant J. P. , Dreyfus B. , Breton‐Gorius J.
Published: March 2008

Summary. Twelve cases of Philadelphia chromosome positive chronic granulocytic leukaemia (CGL) in blast transformation have been investigated using ultrastructural peroxidase detection. In all cases, the leukaemic blasts were negative for myeloperoxidase on the basis of standard cytochemistry. In nine cases a variable proportion of blasts contained peroxidase activity detectable only by electron microscopy, permitting definition of their myeloid nature. By their distinct characteristics and localization, different peroxidase activities were recognized. Thus, several types of blasts were identified: megakaryoblasts (MKB), basophil promyelocytes (BPM), myeloid blasts with small granules containing peroxidase (MyB), and proerythroblasts (ProE). MKB were predominant in two cases and present in four cases, mixed with other myeloid blasts. BPM were abundant in one case and present in seven cases. MyB were identified as a majority in four cases. Three cases remained without any peroxidase. It is concluded that ultrastructural detection of peroxidases is of value for the identification of early myeloid blasts. Their high incidence and the simultaneous presence of several myeloid precursors suggest that during the blast crisis the target cell is frequently a pluripotent myeloid stem cell.
SV40 T‐Antigen Expression in Acute Non‐lymphocytic Leukaemia
Authors: Lubiniecki A. S. , Blattner W. A. , Dosik H. , Fraumeni J. F.
Published: March 2008

Summary. Susceptibility to SV40 virus infection has been suggested as an in vitro marker of predisposition to leukaemia and possibly other cancers in man. To evaluate this relationship, sporadic as well as familial cases of acute non‐lymphocytic leukaemia were tested. Among skin fibroblast lines from 22 patients without family history of leukaemia, eight had values above the 95% confidence limit for the normal control population. In four leukaemia‐prone families, elevated T‐antigen expression was found in all four patients tested and in three‐quarters of 36 blood relatives. In addition, elevated values were found in two of three cases of acute myelogenous leukaemia associated with constitutional cytogenetic anomalies, and in all three cases with preleukaemic haematologic disorders. Since SV40 T‐antigen expression was elevated in most persons prone to acute non‐lymphocytic leukaemia, as well as over one‐third of sporadic cases, heritable risk factors may be involved in both groups.
Granulecyte‐specific Alloantigen Loss in Chronic Granulocytic Leukaemia
Authors: Reijden H. J. v. d. , Von Dem Borne A. E. G. Kr. , Verheugt F. W. A. , Floor‐van Gent A. B. , Melief C. J. M. , Engelfriet C. P.
Published: March 2008

Summary. The granulocytes of 23 patients with chronic granulocytic leukaemia were examined in the indirect immunofluorescence test and some also in the microleucoagglutination test, with specific alloantisera against the NA1, NA2, NB1, and ND1 antigens and a specific granulocyte xenoantiserum. In 10 cases a complete loss of alloantigens was detected. In one patient a partial loss was found. A significant correlation was established between this loss and an accelerated activity (impending blast crisis) of the disease.
Neutrophil Marrow Profiles in Patients with Rheumatoid Arthritis and Neutropenia
Authors: Dancey J. T. , Brubaker L. H.
Published: March 2008

Summary. Neutrophil marrow cellularity was determined in 14 neutropenic patients with rheumatoid arthritis (RA) from measurements of neutrophilnormoblast ratios in marrow biopsies and ferrokinetic estimates of marrow normoblasts. A marrow profile was developed for each patient comprising the numbers of promyelocytes and myelocytes, of metamyelocytes and bands, and of segmented neutrophils in whole marrow. In each case a maturation ratio was calculated by dividing the number of metamyelocytes and bands by the number of promyelocytes and myelocytes. The physiologic marrow response to loss of neutrophils from circulation was assumed to be an increase in promyelocytes and myelocytes due to proliferation and influx, a reduction in segmented cells due to early release, and a normal maturation ratio. The results were interpreted in the light of the 95% confidence limits for data previously obtained from 13 normal subjects: in patients with neutropenia reduced or basal numbers of promyelocytes and myelocytes were interpreted as absence of the anticipated proliferative response; increased numbers of marrow segmented cells were attributed to failure of release; a low maturation ratio was assessed to reflect intramedullary cell loss. The pattern in two patients with Felty's syndrome was consistent with a physiological response to neutrophil destruction. The other 12 patients had neutrophil marrow abnormalities. Seven patients with Felty's syndrome and four patients without splenomegaly had absolute or relative hypoplasia of neutrophil marrow or low maturation ratios. One patient with a normal spleen size had an increased number of marrow segmented cells yet failed to mobilize cells normally in response to dialysis coil‐activation of C3. Abnormalities of neutrophil marrow may contribute to neutropenia in RA irrespective of the presence of splenomegaly. Recognition of neutrophil marrow abnormalities in these patients may be of value in prognosis and management.
Transplacental Transport in the Rabbit of Vitamin B12 Bound to Human Transcobalamins I, II and III
Authors: Fernandes‐Costa Francisco , Metz Jack
Published: March 2008

Summary. Transcobalamins I, II and III (TCI, TCII, TCIII) were purified from human serum, saturated with 57Co‐vitamin B12 (57Co‐B12), and injected into pregnant rabbits. Whole body retention of the 57Co‐B12 averaged 91% and was similar for each of the three vitamin B12 binders. A maximum of 62% of the injected 57Co‐B12 was found in fetal tissues when the vitamin was injected bound to TCII, but only 6–7% when bound to TCI or TCIII. Thus TCII is responsible for the delivery of vitamin B12 to the fetus.
Mean Cell Volume in a Working Population: the Effects of Age, Smoking, Alcohol and Oral Contraception
Authors: Chalmers D. M. , Levi A. J. , Chanarin I. , North W. R. S. , Meade T. W.
Published: March 2008

Summary. The effects on mean cell volume (MCV) of age, smoking habit, alcohol consumption, menopausal status, and use of oral contraceptives have been studied as appropriate in 1596 white men and 892 white women in working populations in North‐West London. In men, increasing age, smoking and alcohol consumption each make an independent contribution to MCV. In women, the effect of smoking is similar to that in men; the effect of alcohol is less obvious, possibly because of the low stated alcohol intake in women. The effect of alcohol on MCV in the population studied is not as marked as in hospital patients who admit to excessive alcohol consumption; this may partly be due to differences in methods of eliciting intake. There is a small increase in MCV following the menopause. Women on oral contraceptives show a rise in MCV with increasing age; this is not seen in women not on oral contraceptives. There is a strong inverse association between MCV and red blood cell count, which may be part of a mechanism to ensure constant oxygen carrying capacity.
Prostaglandins as Inhibitors of Human Platelet Aggregation
Authors: Minno G. Di , Silver M. J. , Gaetano G. de
Published: March 2008

Summary. The potencies of prostaglandins (PG) I2, PGD2 and PGE1 as inhibitors of human platelet aggregation induced by threshold concentrations of four aggregating agents were determined in platelet‐rich plasma from normal individuals who had not ingested aspirin. The order of activity against ADP, adrenaline and collagen was always PGI2 > PGD2 > PGE1. However, PGD2 and PGE1 were almost equipotent with PGI2 when tested against arachidonic acid (AA). The threshold inhibitory effects of PGD2, PGE1 and PGI2 could be overcome by increasing the concentrations of the aggregating agents AA, collagen or ADP. Adrenaline was found to be different from the other aggregating agents. It could overcome inhibition of platelet aggregation by PGD2 but could not overcome inhibition by PGI2 or PGE1. These facts support the hypothesis that platelet receptors for PGI2 and PGE1 are similar to each other and different from the receptor(s) for PGD2.

PRP obtained from normal subjects after the ingestion of aspirin exhibited only one wave of aggregation in response to ADP, adrenaline or collagen. PGI2, PGD2 and PGE1 were all powerful inhibitors of this single wave of aggregation. The inhibitory activity of all three prostaglandins at threshold concentrations was overcome by increasing the concentration of ADP or collagen but not by increasing the concentration of adrenaline.
New Translocations in Chronic Granulocytic Leukaemia: t(X;22) (p22;q11) and t(15;22) (q26;q11)
Authors: Hossfeld D. K. , Köhler S.
Published: March 2008

Summary. Two cases of Ph1‐positive chronic granulocytic leukaemia with hitherto undescribed translocations are presented. In case 1 the deleted part of chromosome number 22q‐ was translocated to the short arm of the X chromosome, t(X;22)(p22;q11). Pronounced basophilia, trisomy 19 in the majority of metaphases, and a partial cytogenetic normalization of the bone marrow during busulphan induced remission were additional remarkable features of this case. In case 2 a translocation t(15;22)(q26;q11) was found. In this case the disease was characterized by an increase of unusually small megakaryocytes, thrombocytosis, and an accelerated course.
Interaction of Alpha and Beta Thalassaemia Genes in Two Sardinian Families
Authors: Furbetta M. , Galanello R. , Ximenes A. , Angius A. , Melis M. A. , Serra P. , Cao A.
Published: March 2008

Summary. Our paper describes two Sardinian families with α‐β thalassaemia interaction. In the first (family S), the propositus, whose haemoglobin pattern at birth consisted of about 25% Hb Bart's and 75% Hb F, successively developed a clinical and haematological picture typical of Cooley's anaemia. Haematological and globin chain synthesis studies together with these findings suggest that he is homozygous for β0 thalassaemia and heterozygous for α thalassaemia‐1 and α thalassaemia‐2. This conclusion is further substantiated by the finding of various combination of α and β thalassemia among his family members.

In the P family two twins whose haemoglobin pattern and synthesis data at birth were similar to those of the proband of family S died in the neonatal period. The mother was assumed to be a compound heterozygte for α thalassaemia‐2 and β0 thalassaemia and the father for α thalassaemia‐1 and β0 thalassemia. The homozygous state for β0 thalassaemia in association with the α thalassaemia 1 and α thalassaemia 2 genes results in a severe clinical picture similar to that of a homozygous β0 thalassaemia. The interaction between the heterozygous state for β0 thalassaemia and the α thalassaemia 1 or α thalassaemia 2 genes, or the combination of both, results in a haematological picture similar to that of a β thalassaemia heterozygote.
Two Populations of Factor VIII‐Related Antigen in a Family with von Willebrand's Disease
Authors: Armitage Helen , Rizza C. R.
Published: March 2008

Summary. The factor VIII‐related antigen in a patient with von Willebrand's disease showed increased anodal mobility on two‐dimensional immunoelectrophoresis. However, the antigen present in several of this patient's relatives showed two distinct peaks, one in the normal position and one similar to that of the patient. Very little of the patient's antigen could be recovered from ethanol precipitates or cryoprecipitates of whole plasma. Only the slower component could be recovered from the precipitates prepared from plasma of these family members showing two populations of antigen, the faster moving antigen remaining in the supernatant. This antigen of increased mobility corresponds very closely to that remaining in the supernatant of normal plasma, following similar fractionation procedures. It is suggested that the factor VIII‐related antigen in some variant forms of von Willebrand's disease is a normal component of plasma, present in increased amounts.
Absence of Tight Junctions in Endothelium of Marrow Sinuses: Possible Significance for Marrow Cell Egress
Authors: Tavassoli Mehdi , Shaklai Matityahu
Published: March 2008

Summary. The nature of contact between endothelial cells in rat marrow sinuses was studied. Colloidal lanthanum permeated freely into the interendothelial space. Moreover, using freeze‐fracture technique, we failed to show junctional structures where these endothelial cells came into contact. With thin sectioning electron microscopy, we observed occasional submembranous densities but the interendothelial distance measured 20 nm and no membrane fusion was seen. Absence of tight junctions between endothelial cells of marrow sinuses may serve a function in marrow cell egress by permitting these cells to slide over each other, thereby changing the luminal size. Within the fixed volume of marrow, an increase in luminal size results in displacement of haemopoietic cells into the lumen.
Patterns of Globin Chain Synthesis in Erythroid Colonies Grown from Sheep Marrow of Different Developmental Stages
Authors: Darbre Philippa D. , Adamson J. W. , Wood W. G. , Weatherall D. J. , Robinson J. S.
Published: March 2008

Summary. Erythroid colonies were grown from fetal sheep bone marrow at different stages of development and from adult marrow. Colony numbers increased with erythropoietin concentration, but fetal erythroid cells were more sensitive to the hormone than adult cells. Haemoglobin synthesis was characterized in the colonies and compared to that in control marrow incubations. No β chain synthesis was detectable in marrow incubations or erythroid colonies form fetal marrow at 87–96 d gestation. Incubations of 115–120 d marrow showed 5%β chain synthesis while erythroid colonies synthesised up to 20%β chains. Incubations and erythroid colonies from 125 d marrows showed about 27%β chain synthesis, despite a similar increase in colony numbers with erythropoietin as the other marrows. Later in gestation, β chain synthesis was lower in erythroid colonies than in marrow incubations and declined further in erythroid colonies as erythropoietin concentration increased. Adult marrow showed no detectable γ chain synthesis but erythroid colonies produced up to 12%γ chains, the identity of which was confirmed by peptide mapping. All changes in globin synthesis in vitro were correlated with colony numbers. In adult marrow, the maximal level of γ chain production was inversely related to the cloning efficiency of the marrow samples studied. Potential uses of this model for studying globin gene expression are discussed.
The Determination of Antithrombin III by Radioimmunoassay and its Clinical Application
Authors: Chan Vivian , Chan T.K. , Wong Vivian , Tso S. C. , Todd D.
Published: March 2008

Summary. A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 μ/dl. AT III‐RIA level and biological activity (anti‐Xa) was significantly correlated (r=0.737, P<0.001). Plasma levels in 36 healthy males (mean ± SD, 19.9±2.5 mg/dl) and 21 healthy females (19.1 ± 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lowere levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post‐operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.
In Vitro DNA Synthesis by Bone Marrow Cells and PHA‐stimulated Lymphocytes. Suppression by Nonradioactive Thymidine of the Incorporation of 3H‐Deoxyuridine into DNA: Enhancement of Incorporation when Inadequate Vitamin B12 or Folate is Corrected
Authors: Das Kshitish C. , Manusselis Cathy , Herbert Ictor
Published: March 2008

Summary.

Previous studies demonstrated that excess deoxyuridine (dU) added to short‐term bone marrow and PHA‐stimulated lymphocyte cultures, blocks the incorporation of radioactive thymidine into DNA via the salvage pathway. In the current study, we investigated the effects of added thymidine (TdR) in varying concentrations (10−6to 1 μmol) on the incorporation of 3H‐dU into thymine‐DNA, i.e. we executed ‘thymidine suppression tests.’Increasing concentrations of exogenous TdR caused progressive inhibition of 3H‐dU incorporation into DNA, and decreasing 3H‐dU incorporation was parallelled by increasing incorporation of added 14C‐TdR. These findings demonstrate reciprocity of the salvage and the de novo pathways of thymine‐DNA synthesis, presumably mediated by thymidine‐triphosphate (dTTP), the common end product of both pathways, via feedback inhibition. In patients with folate and/or vitamin B12 deficiency, the addition of appropriate vitamins to marrow and lymphocyte cultures enhanced the incorporation of 3H‐dU into DNA. As predicted, this was not observed in normal subjects. The enhancing effect of these vitamins on in vitro incorporation of 3H‐dU into DNA by deficient cell systems was similar to their correcting effect on abnormal dU suppression. These findings support the theoretical concept that the dU suppression test defines biochemical megaloblastosis due to deficiency of folate and vitamin B12.
γ Chain Composition in Five Italian Newborns Heterozygous for Hb F Malta Gγ117 His → Arg
Authors: Mazza U. , Meloni T. , David O. , Pich P. G. , Camaschella C. , Saglio G. , Ciocca Vasino M. A. , Guerrasio A. , Ricco G.
Published: March 2008

Summary.

The percentage of Hb F Malta Gγ117His Arg and the γ chain composition have been evaluated at birth and at different times after birth in five Italian newborns heterozygous for this variant. The percentage of Hb F Malta ranged at birth from 24% to 31% of the total Hb F, while the average Gγ/Aγ chain ratio was about 7/3, overlapping the values observed in normal newborns. Tγ chains were detected in three out of five newborns, with a percentage of about 10% of the total Hb F. After birth the Hb F Malta declined faster than the total Hb F; thus, the Hb F decrease during the first 45 d of life is mainly due to the switch‐off of the Gγ locus containing the Hb F Malta gene.
Congenital Dyserythropoietic Anaemia (CDA) with Severe Gout, Rare Kell Phenotype and Erythrocyte, Granulocyte and Platelet Membrane Reduplication: a New Variant of CDA Type II
Authors: Lowenthal R. M. , Marsden K. A. , Dewar C. L. , Thompson G. R.
Published: March 2008

Summary.

A 43‐year‐old man with lifelong anaemia showed features which indicate him to have a previously undescribed variant of congenital dyserythropoietic anaemia (CDA), type II. The main clinical features—of which the first two are unique or very unusual in CDA—have been severe tophaceous gout, massive splenomegaly, gall stones necessitating cholecystectomy and haemosiderosis affecting the liver and probably the heart. At age 41 he sustained a spontaneous retinal detachment. In the peripheral blood there were large numbers of nucleated red blood cells and marked macrocytosis; otherwise the picture was typical of CDA type II. The bone marrow contained many bi‐ and multi‐nucleated erythrocyte precursors. There were increased levels of a number of red cell enzymes and a slightly raised level of HbF. Uncharacteristically, the red cells failed to lyse with acidified normal serum. The cells were strongly agglutinated by anti‐i and were of the rare Kpb‐negative phenotype. Plasma lipid analysis showed very low levels of cholesterol and vitamin E. Lipid peroxidation was markedly increased. Ultrastructural studies showed reduplication of the erythrocyte, granulocyte, and platelet cell membranes.
HLA Haplotypes and Long Survival in Childhood Acute Lymphoblastic Leukaemia Treated with Transfer Factor
Authors: Bruyère M. De , Cornu G. , Heremans‐Bracke T. , Malchaire J. , Sokal G.
Published: March 2008

Summary.

Association between HLA haplotypes and a long survival was investigated in 116 children with acute lymphoblastic leukaemia. It was found that patients with A2 B12 and/or A2 B40 haplotypes survived longer than patients without these two haplotypes. Since all children were treated with transfer factor obtained from their relatives, it is suggested that children possessing A2 B12 or A2 B40 haplotypes may respond better to this type of immunotherapy.
Lymphocyte, Granulocyte and Platelet Contamination of Blood Frozen by the Low‐Glycerol Liquid Nitrogen Technique
Authors: Amer K. A. , Pepper D. S. , Urbaniak S. J.
Published: March 2008

Summary.

The residual leucocyte and platelet content of blood frozen in 20% (v/v) glycerol was assessed by several methods. The final red cell suspension contained 6–12% of the original leucocytes in the form of intact lymphocytes, whilst intact polymorphonuclear cells and platelets could not be detected. The lymphocytes were nonviable as assessed by trypan blue dye exclusion but there was a low response to phytohaemagglutinin stimulation in culture.

Using 125I cell‐surface labelling it was found that 39·5 ± 7% (SD) of the labelled lymphocyte surface material, 25·8 ± 6·6% of the granulocyte material and 2·6 ± 0·4% of the platelet surface membrane material remained in the final product after processing. The level of the remaining leucocyte derived material could be lowered by removing the buffy coat after the centrifugal wash steps and by passage through a 40 μan micropore filter; however, this was at the expense of a loss of approximately 25% of red cells.

The intact lymphocytes which remained were non‐antigenic in vitro as assessed by the one‐way mixed lymphocyte reaction using the recovered cells as stimulators. However, when the antigen status of the frozen blood as a whole was studied in vivo by injection into laboratory animals, this blood stimulated lymphocytotoxic antibody production, although the levels of antibody were lower and appeared later than those induced by the infusion of a comparable volume of fresh blood. The antibody levels could be diminished further by passing the blood through a 40 μm micropore filter prior to injection.
An Agarose Plate Method for Detecting Alloantisera to Coagulant Factor IX and Factor IX Antigen
Authors: Reisner Howard M. , Strand Elizabeth A. , Chung Kuo‐San , Roberts Harold R.
Published: March 2008

Summary.

An agarose plate method for detecting human alloantibodies (inhibitors) to coagulant factor IX has been developed. The assay is based on the ability of such antisera to inhibit the coagulation of a mixture of haemophilia B plasma, normal plasma and platelet substitute in an agarose matrix. The agarose plate method was also adopted to measure levels of FIX antigen (IX:Ag) in plasma. Using this technique, 12 of 17 obligate carriers of haemophilia B demonstrated reduced levels of IX:Ag. Three of the five carriers with normal IX:Ag levels were members of kindred in which affected individuals had normal or near normal levels of IX:Ag.
Familial Haemostatic Defect Associated with Reduced Prothrombin Consumption
Authors: Parry D. H. , Giddings J. C. , Bloom A. L.
Published: March 2008

Summary.

Ten individuals from three unrelated families suffered from an unusual inherited haemorrhagic disorder. The defect was associated with reduced prothrombin conversion as shown by a grossly abnormal prothrombin consumption index. All known plasma coagulation factors were present in adequate concentrations but in the two families tested the results were consistent with a defect of the interaction between plasma and platelets or phospholipid. Some of the affected family members exhibited a mild bleeding tendency characterized by post‐operative or post‐partum haemorrhage but none suffered spontaneous bleeding. In therapeutic trials in one of the patients both plasma and platelet transfusions were needed in order to correct the abnormality. This finding together with in vitro and other in vivo studies indicated that the abnormality is associated with an inhibitor of the interaction between plasma and phospholipid during blood coagulation. The results suggest the possibility of an abnormality of the γ‐carboxyglutamic acid residues of one or more vitamin K dependent coagulation factors but immunological and electrophoretic studies have so far failed to detect this. The findings underline the importance of a test of prothrombin conversion in screening procedures for an otherwise unexplained bleeding disorder.
Studies of Lymphocyte Proliferation in Hairy Cell Leukaemia: Activity in Mixed Lymphocyte Reaction and Responses to Mitogens
Authors: Davey Frederick R. , Dock Nancy L. , Wolos Jeffrey A.
Published: March 2008

Summary. Subpopulations of splenic lymphocytes from patients with hairy cell leukaemia (HCL) were compared with similar subpopulations of lymphocytes from reference individuals for their ability to respond to mitogens and to participate in allogeneic and autologous mixed lymphocyte reactions. T cell enriched subpopulations were obtained by double passage of mononuclear cells through nylon wool columns. Non‐T cell subpopulations were collected by eluting adherent cells from nylon wool columns and by incubating them with sheep erythrocytes followed by density gradient centrifugation. Unfractionated mononuclear cells, T enriched and non‐T subpopulations were compared. Enriched T cell subpopulations from HCL and reference patients responded similarly to allogeneic antigens and phytohae‐magglutinin. Splenic non‐T cells from reference patients produced a stronger stimulus in the allogeneic mixed lymphocyte reaction than did the unfractionated or the T enriched cells. In contrast, the non‐T subpopulations from patients with HCL produced a reduced response compared to that of reference splenic cells when mixed with allogeneic lymphocytes. In addition, non‐T cells from HCL patients failed to respond to pokeweed mitogen. Neither reference nor HCL splenic cells produced a significant response in the autologous mixed lymphocyte reactions. The data suggest that splenic non‐T cells from patients with HCL either suppress the stimulatory capacity of normal B lymphocytes or fail to stimulate allogeneic lymphocytes in the mixed lymphocyte reactions.
Evaluation and Modification of Whole Blood Filtration in the Measurement of Erythrocyte Deformability in Pregnancy and the Newborn
Authors: Buchan Peter C.
Published: March 2008

Summary. SUMMARY. This study was designed to investigate the deformability of erythrocytes from pregnant women and full‐term newborn infants, with healthy female adults as a comparison, using a whole blood filtration method. Delay in measurement, white cells, haematocrit, plasma viscosity, temperature and pH all significantly affected the rate of whole blood filtration and could thereby obscure or exaggerate changes in erythrocyte deformability.

A new method was developed which eliminated or minimized these sources of error and the study was completed. Fetal erythrocytes were found to be significantly less deformable than adult erythrocytes which were in turn found to be significantly less deformable than erythrocytes from pregnant women. These differences appear to be related to the varying plasma fibrinogen concentrations in the three groups of subjects. The significance of these findings in the special haemodynamic situations found in the neonate and during pregnancy are discussed.
Studies on Circulating Soluble Fibrin: Separation of 125I‐Des‐AB Fibrin and 131I‐Fibrinogen by Gel Filtration
Authors: Kröhnke Isa , Mahn I. , Krell W. , Müixer‐Berghaus G.
Published: March 2008

Summary. The behaviour of labelled des‐AB fibrin in plasma was studied by gel filtration after it had been injected into rabbits. Purified rabbit [125I]des‐AB fibrin was prepared by clotting of [125I]fibrinogen by thrombin and solubilizing the formed clot in buffered 3 M urea. Gel filtration of this material on urea‐equilibrated columns showed a single peak identical to the elution profile of fibrinogen. This indicated the existence of monomeric des‐AB fibrin. When plasma from rabbits injected with monomeric [,25I]des‐AB fibrin and [,31I]fibrinogen was gel‐filtered through plasma‐equilibrated columns, two separate peaks of radioactivities were obtained. The first peak eluted mainly with the void volume and contained [I25I]des‐AB fibrin whereas the second peak eluting within the fractionation range contained [131I]fibrinogen. Identical elution profiles were obtained in in vitro studies when monomeric [125I]des‐AB fibrin was mixed with plasma containing [131I]fibrinogen and gel‐filtered through plasma‐equilibrated columns. We conclude from these studies that monomeric des‐AB fibrin formed high‐molecular weight aggregates or changed its conformation posing as a larger molecule than fibrinogen when injected into rabbits. No complex formation between des‐AB fibrin and fibrinogen was observed as [131I]fibrinogen was not incorporated into des‐AB fibrin aggregates. Thus, soluble des‐AB fibrin can circulate in the blood without forming fibrin–fibrinogen complexes.
Sequential Changes in Factor VIII and Platelets Preceding Deep Vein Thrombosis in Patients with Spinal Cord Injury
Authors: Rossi Ennio C. , Green David , Rosen Joel S. , Spies Stewart M. , Jao James S. T.
Published: March 2008

Summary. The relationships between factor VIII associated activities, platelet function, and venous thrombosis were studied in 18 patients with lower limb paralysis following acute spinal cord injury (SCI). Deep vein thrombosis (DVT) was detected in 13 patients (72%). Eight of the 13 thromboses were documented between 6 and 8 d following injury while the other five episodes were noted on days 11 (two), 13,18 and 22. The detection of thrombosis was preceded by marked increases in VIIIR:Ag and VIII:RCoF whereas VIII:C was only marginally increased. The platelet aggregation response to collagen was hyperactive by the sixth day while the platelet aggregate ratio (PAR) did not become abnormal until after DVT was detected. These studies suggest a chronology in the series of events leading to DVT in patients with lower limb paralysis following SCI. Initial elevations in VIIIR:Ag and VIII:R‐CoF are followed in sequence by increased platelet responsiveness to collagen, the occurrence of DVT, and the appearance of circulating platelet aggregates. Conceivably, VIIIR:Ag elaborated by endothelial cells alters platelet reactivity and provides an important determinant for venous thrombosis.
Subclassification of Acute Lymphoblastic Leukaemia in Children: Analysis of the Reproducibility of Morphological Criteria and Prognostic Implications
Authors: Viana Marcos B. , Maurer Helen S. , Ferenc Christine
Published: March 2008

Summary

. Stained smears of aspirated bone marrow obtained at time of diagnosis from 223 children with acute leukaemia were reviewed independently by three observers in a double‐blind fashion in order to assess the reproducibility and clinical significance of the French—American—British Cooperative Group Classification. In 170 cases of acute lymphoblastic leukaemia (ALL), triple agreement of 69.4% was reached in the subclassification into L1, L2 and L3 types. The closest degree of agreement between two observers was 86.8%.

In children with blasts classified as L1, 57 of 61 patients (93.4%) remained in haematological remission after 12 months, as compared with 14 of 20 (70%) in children whose blasts were typed as L2 morphology, a difference which was statistically significant (P < 0.05). There was no difference when these groups were compared after 24 or 36 months. Children older than 7 years had an increased incidence of L2 type (P < 0.05).

We conclude that although there may be significant variation in individual interpretations of the criteria utilized for classification, blast morphology may nevertheless be a useful prognostic factor.
Phenotypic Characterization of a Virus Producing Line Established from a Patient with Leukaemia/Lymphoma: Comparison with T‐Lymphoblastic and Myeloblastic Lines
Authors: Karpas A. , Worman C. P. , Khalid G. , Neumann H. , Hayhoe F. G.J. , Newell D. , Stewart J. W.
Published: March 2008

Summary

. The properties have been studied of a haemic cell line established from a patient with longstanding non‐Hodgkin's lymphoma after transformation to acute leukaemia. The cells are EBNA, Fc, C3 and SmIg and la‐like antigen negative. The continuous in vitro proliferation and karyotype abnormalities suggest malignancy. The cells contain only the lymphoid type of alkaline phosphatase and a high level of terminal deoxynucleotidyl transferase and as they formed E‐rosettes during the first year in culture they may be of T‐cell lineage. Since the patient's leukaemic cells have not been studied it is impossible to know whether the cultured cells represent an in vitro proliferation of the patient's malignant cells or an outgrowth of a subpopulation of cells. In the cytoplasm of many cells inclusion bodies containing virus‐like particles, similar to those observed in fresh human leukaemia cells, were often seen. As this new virus is biologically active, infection of the cells by virus may explain their continuous proliferation in vitro.
Autoimmune Thrombocytopenia in Pregnancy
Authors: Minchinton R. M. , Dodd N. J. , O'Brien H. , Amess J. A. L. , Waters A. H.
Published: March 2008

Summary. The laboratory diagnosis of autoimmune thrombocytopenia has only recently become more satisfactory. In this study a fluorescein‐labelled antiglobulin technique was used to investigate the immunochemical properties of the platelet antibody detected in a pregnant woman with severe thrombocytopenia. The antibody was autoimmune and appeared to have specificity for platelet antigens. It had both IgG and IgM components and did not fix complement. Steroids had a beneficial effect indicated by a return to normal of the platelet count, a falling antibody titre and the disappearance of detectable antibody on the patient's own platelets. Studies on the baby showed that the antibody had not crossed the placenta in detectable amounts.
A Comparison of Methods for the Study of Platelet Hyperfunction in Thrornboembolic Disorders
Authors: Chen Yao‐Chang , Wu Kenneth K.
Published: March 2008

Summary.

To gain insight into the interrelationship of various methods for the study of platelet hyperfunction, we compared plasma β‐thromboglobulin (β‐TG), circulating platelet aggregates (CPA), and ADP‐induced platelet aggregation in 119 patients with thromboembolic disorders and 28 control subjects. CPA correlated fairly well with β‐TG, suggesting that both methods measure similar in vivo platelet activation and aggregation. CPA had an excellent correlation with platelet survival half‐time. In contrast, there was a poor correlation between in vitro platelet aggregation and CPA or β‐TG. These results confirm the notion that both CPA and β‐TG procedures are suitable for determination of in vivo platelet activation whereas platelet aggregation technique has serious limitations to test in vivo platelet activity. In order to have an accurate assessment of platelet hyperfunction, a battery of tests are needed.
Patterns of Factor‐VIII Related Antigen on Crossed Immunoelectrophoresis and Large Pore Polyacrylamide Gel‐Crossed Immunoelectrophoresis in von Wilkbrand's Disease
Authors: Fukui H. , Mikami S. , Takase T. , Fujimura Y. , Nishino M. , Yoshioka A.
Published: March 2008

Summary.

Plasma samples from patients with various types of von Willebrand's disease were subdivided into six patterns according to the electrophoretic mobility and shape of VIIIR: Ag on crossed immunoelectrophoresis (CIE): pattern 1 no precipitation arc, pattern 2 normal mobility with low arc, pattern 3 intermediate mobility with low arc, pattern 4 faster anodal mobility with low arc, pattern 5 normal mobility with normal arc height, pattern 6 faster anodal mobility with normal arc height. Of 62 patients, 14 had pattern 1, 6 pattern 2, 16 pattern 3, 12 pattern 4, 9 pattern 5, and 5 pattern 6.

Large pore polyacrylamide‐agarose gel‐crossed immunoelectrophoresis (PAAG‐CIE) of crude factor VIII fraction from cryoprecipitate revealed no arcs in patients with pattern 1, three arcs of reduced height in the patients with patterns 2 and 3, four arcs very similar to normal control in patients with pattern 5, and two arcs with fast anodal migration in the patients with patterns 4 and 6. Crude factor VIII fractions from normal cryosupernatant showed one low fast anodally migrating arc corresponding to the fourth arc of normal cryoprecipitate. No peak was seen in patients with pattern 1, and one low fast anodal arc similar to normal control was present in the patients with patterns 2, 3, 4, 5 and 6.
Binding and Release of Factor VIII/von Willebrand's Factor by Human Endothelial Cells
Authors: Wall Robert T. , Coums Richard B. , Harker Laurence A. , Striker Gary E.
Published: March 2008

Summary.

The uptake and release of factor VIII/von Willebrand's protein by cultured human umbilical vein endothelial cells have been examined using highly purified 125I‐factor VIII poswssing von Willebrand's factor activity. 125I‐factor VIII/vWF was taken up by the cells, reaching maximum binding within 4 h with a tl‐2 of binding of 15 min. Endothelial cell binding of 125I‐factor VIII/vWF reached saturation at a concentration of 1.5 mg/l. Binding was inhibited by coincubation of excess unlabelled factor VIII/vWF. Most of the cell‐associated radioactivity was released by treatment of the cells with trypsin. Internalization of bound protein was evidenced by the incorporation into the cells of radioactivity which could not be released by trypsin. Human vascular smooth muscle cells did not bind 125I‐factor VIII/vWF. Addition of 0.1 μm epinephrine to the 125I‐factor VIII/vWF labelled endothelial cultures induced the release of cell bound, protein‐associated radioactivity into the medium. Propranolol inhibited completely epinephrine‐induced release, whereas phenylephrine had no effect.

Endothelial cells maintained in medium partially depleted of factor VIII/vWF by tricalcium citrate cellulose treatment of plasma did not release factor VIII antigen into the culture medium during subsequent incubation. Although [3H]proline was incorporated into proteins released by endothelial cells under these experimental conditions, specific incorporation of label into factor VIII/vWF antigen was not detectable by a sensitive solid‐phase immunoradiometric assay. We conclude that factor VIII/vWF binds to endothelial cells and that this cell‐bound protein is mobilized by epinephrine through beta‐adrenergic stimulation.
C‐Group Chromosome Abnormalities in Bone Marrow Cells of Three Children with Dyshaematopoiesis of Unknown Origin
Authors: Hagemeijer A. , Hählen K. , Smit E. M. E. , Zanen G. E. van
Published: March 2008

Summary.

Clinical and cytogenetic findings in three children with dyshaematopoiesis and bone marrow aneuploidy are described. Monosomy 7 was found in immature cells of one 10‐year‐old boy with myelofibrosis following a 3 years evolution of severe thrombocytopenia and anaemia. Trisomy 8 was found in 80% of the bone marrow metaphases of a 5 1/2year‐old girl with aplastic anaemia and Australia antigen positivity. During a 3 year observation period the number of cells with trisomy 8 regressed and eventually disappeared. Improvement of her clinical condition is present but still limited. Trisomy 8 was also found in all bone marrow cells of an 8‐year‐old girl with an undefined myeloproliferative disorder. Her disease was apparently related to collagen‐vascular disorders like periarteritis or other necrotizing angiitis and presented bvith periods of exacerbation and periods of chronic evolution. Periods of exacerbation were accompanied by excessive myeloid proliferation. Repeated bone marrow cytogenetic analysis during the acute and chronic phases showed trisomy 8 in all the metnphases analysed. During the last episode of acute illness, further clonal evolution was observed, characterized by a translocation (8; 17).
Binding of Serum Ferritin to Concanavalin A: Patients with Hornozygous β Thalassaemia and Transfusional Iron Overload
Authors: Worwoon M. , Cragg S.J. , Jacobs A. , McLaren C. , Rickeits C. , Economidou J.
Published: March 2008

Summary.

Serum ferritin concentrations have been measured in 124 patients with homozygous β thalassaemia who were between 2 and 21 years old, had received 11–504 units of blood but had not undergone splenectorny. There were highly significant correlations between serum ferritin concentration and both the amount of blood transfused and alanine amino‐transferase (ALT) activity. However, multivariate analysis showed that units of blood and ALT activity together only accounted for about 30% of the variation in serum ferritin concentration. Little of the remaining variation could be explained by other variables related to iron nietabolism or liver damage. The concentration of concanavalin A binding ferritin increased rapidly with the number of units of blood up to 100 units but thereafter showed no further increase with number of transfusions. The concentration of non‐binding ferritin was more closely related to transfusion load. These results suggest that the secretion of glycosylated ferritin from rcticuloendothelial cells reaches a maximum with increasing iron accumulation, perhaps reflecting a maximum rate of synthesis. Ferritinaemia in patients with transfusional iron overload therefore seems to be the result of the combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells. A simple relationship between serum ferritin and iron stores cannot be assumed when ferritin concentrations exceed 4000 μg/l or in patients who have received more than 100 units of transfused blood.
Management of Relative Polycythaemia: Studies of Cerebral Blood Flow and Viscosity
Authors: Humphrey P. R. D. , Michael J. , Pearson T. C.
Published: March 2008

Summary.

Cerebral blood flow has been shown to be reduced in a group of patients with high packed cell volume due to a reduced plasma volume (relative polycythaemia). 500 ml of intravenous Dextran 40 resulted in a significant fall in PCV and whole blood viscosity with a concomitant rise in cerebral blood flow (CBF). This effect, however, lasted less than 24 h. Oral fludrocortisone therapy (0.2 mg daily) resulted in no definite change in either PCV, viscosity or CBF. Venesection brought about a significant fall in PCV and whole blood viscosity with a significant rise in CBF. Of the methods used, venesection was the only practical long‐term method of lowering PCV in this group of patients.
ADCC (K‐Cell) Lysis of Human Erythrocytes Sensitized with Rhesus Alloantibodies III. COMPARISON OF IgG ANTI‐D AGGLUTINATING AND LYTIC (ADCC) ACTIVITY AND THE ROLE OF IgG SUBCLASSES
Authors: Urbaniak S. J. , Greiss M. Ayoub
Published: March 2008

Summary.

Conventional manual (enzyme and antiglobulin titres) and Auto‐Analyser quantitation of anti‐D sera were compared with the ability of the same sera to mediate lysis of Rh(D) positive red cells in an ADCC assay. Auto Analyser (AA) quantitation correlated significantly with manual titration methods, although there were wide discrepancies between individual sera. The ADCC activity of the anti‐D sera did not correlate with any of the conventional assays (AA, enzyme, antiglobulin). There were significant differences between anti‐D sera obtained from females immunized during pregnancy and male volunteers immunized by deliberate injection. The female sera contained significantly less anti‐D when assessed by AA, yet were significantly more active in ADCC activity at equivalent concentrations. These functional differences in anti‐D activity could not be attributed to the absence of IgG subclasses (IgG1 and IgG3) known to induce ADCC. However, there was a relationship between ADCC and IgGI/IgG3 titres in that high ADCC activity was seen where the IgG3 titre was higher than the IgG1 titre. In the male anti‐D sera IgGl titres were ≥ IgG3 titres and ADCC activity was very low.
Drug Dependent Red Cell Antibodies and Intravascular Haemolysis Occurring in Patients Treated with 9 Hydroxy‐Methyl‐Ellipticinium
Authors: Criel A. M. , Hidajat M. , Clarysse A. , Verwilghen R. L.
Published: March 2008

Summary.

Eleven patients were treated weekly with a new cytostatic drug, 9 hydroxy‐methyl‐ellipticinium (9 HME). Eight were treated for longer than 4 weeks and three of these developed a drug dependent antibody reacting with normal red cells. In two of these patients acute intravascular haemolysis occurred, one with oliguric renal failure; in the third patient the drug was stopped as soon as the antibody was detected. In all three patients the antibody developed after 4 weeks of treatment. It was IgM, agglutinated normal red cells and bound complement only in the presence of the drug. No antibodies could be detected in the patient's serum reacting with normal platelets in the presence of the drug. The incidence of haemolysis with this drug is much higher than seen with other drugs causing immune‐complex haemolysis. Studies done with closely related substances suggest that the antigenic site of the drug is related to the group attached to carbon atom 9.
Globin Chain Synthesis in Haemoglobin New York (β 113 Valine→Glutamic acid
Authors: Todd D. , Chan Vivian , Schneider Rose G. , Dozy Andree M. , Kan Y. W. , Chan T. K.
Published: March 2008

Summary.

The presence of Hb New York was confirmed in a Chinese family in which affected members have occasional red cells with Hb H‐like inclusions and a relative decrease in α chain synthesis, suggestive of a coexisting α thalassaemia trait. However, globin gene mapping and DNA hybridization revealed no deletion of the α genome. Timed‐incubation experiments showed that the rate of synthesis of βNY chain was greater than that of normal β chain in the early periods. Chromatographic separation of Hb NY and Hb A before chain analysis revealed preferential binding of newly synthesized α chains to βNY, with a four‐fold increase in specific activity of the αHbny chains. It is concluded that βNY chain is being synthesized more rapidly and its increased turnover may account for this presentation of apparent a chain deficiency.