bluuebunny/crossref_metadata_2025 huggingface dataset:
The myelodysplastic syndrome: analysis of laboratory characteristics in relation to the FAB classification
Authors: May S. J. , Smith S. A. , Jacobs A. , Williams A. , Bailey‐Wood R.
Published: March 2008

Summary

A detailed study of 43 newly diagnosed cases of myelodysplastic syndrome (MDS) shows that many of the morphological features of blood and bone marrow are common to the different FAB groups. In addition, there is no clear distinction between the groups with regard to CFU‐E, BFU‐E or CFU‐GM colony growth in vitro or ferrokinetic assessment of erythropoiesis in vivo. The interrelationships between all the parameters we have studied have been examined and there is little correlation between erythroid colony formation in vitro, the percentage erythroblasts in the bone marrow, erythroid output measured by ferrokinetics and the peripheral blood reticulocyte count, all of which appear to measure different aspects of erythropoiesis. Reduced erythroid colony growth and a high degree of ineffective erythropoiesis in vivo are common in all groups and appear to be an early manifestation of abnormal function. Decreasing marrow iron turnover is more closely related to increasing numbers of marrow blast cells than any other index of erythropoiesis.
Human erythrocyte hexokinase deficiency: a new variant with abnormal kinetic properties
Authors: Magnani M. , Stocchi V. , Canestrari F. , Dachà M. , Balestri P. , Farnetani M. A. , Giorgi D. , Fois A. , Fornaini G.
Published: March 2008

Summary. A 14‐month‐old child who had a haemolytic episode when he was 5 years old, and with psychomotor retardation, was found to have decreased red cell hexokinase activity. The mutant enzyme was characterized by an increased affinity for glucose associated with an increased inhibition constant for glucose‐1,6‐diphosphate. Affinity for Mg ATP2‐, heat stability and pH‐optimum were normal. The isozymic pattern of the red cell enzyme was normal but all the molecular forms were present in reduced amounts. The kinetics of decay of hexokinase during cell ageing was also normal. Glucose consumption of the hexokinase deficient cells was 60–65% of the controls while the amount metabolized through the hexose monophosphate shunt was unchanged. Red cell 2,3‐diphosphoglycerate and glucose‐6‐phosphate levels were normal in the proband but reduced in the erythrocytes of his parents, who were heterozygous for the defect but had normal haematological data. Comparison with the 13 previously reported cases of hexokinase deficiency confirms the broad phenotypic variability that characterizes this disorder.
Differential metabolism of deoxyribonucleosides by leukaemic T cells of immature and mature phenotype
Authors: Sidi Yechezkel , Edwards N. Lawrence , Winkler Charles , Bunn Paul , Mitchell Beverly S.
Published: March 2008

Summary. Experimental evidence has indicated that T lymphoblasts are more sensitive to deoxynucleoside toxicity than are B lymphoblasts. These data have led to the use of purine enzyme inhibitors as selective chemotherapeutic drugs in the treatment of T cell malignancies ranging from T cell acute lymphoblastic leukaemia to cutaneous T cell lymphomas. We have compared the toxicities of 2′‐deoxyadenosine, 2′‐deoxyguanosine, and thymidine for T cell lines derived from patients with T cell acute lymphoblastic leukaemia with those for mature T cell lines derived from patients with cutaneous T cell leukaemia/lymphoma. We have found that both deoxynucleosides are far less toxic to the mature T cell lies than to T lymphoblasts and that the mature cells accumulate much lower amounts of dATP and dGTP when exposed to deoxyadenosine and deoxyguanosine, respectively. Similar studies performed on peripheral blood cells from patients with T cell leukaemias of mature phenotype and on peripheral blood T cells demonstrate similar low amounts of deoxynucleotide accumulation. Measurements of the activities of several purine metabolizing enzymes that participate in deoxynucleoside phosphorylation or degradation do not reveal differences which would explain the toxicity of deoxynucleosides for immature, as compared to mature, T cells. We conclude that deoxynucleoside metabolism in leukaemic T cells varies with their degree of differentiation. These observations may be relevant to the design of chemotherapeutic regimes for T cell malignancies.
A hereditary abnormal c‐fms proto‐oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism
Authors: Verbeek J. S. , Heerikhuizen H. van , De Pauw B. E. , Haanen C. , Bloemers H. P. J. , Van de Ven W. J. M.
Published: March 2008

Summary. A patient with congenital hypothyroidism and acute lymphocytic leukaemia was found to be homozygous for a 0.4 kbp deletion in the c‐fms proto‐oncogene. This was established by studying DNA from the patient's leukaemic cells, from cultured skin fibroblasts of the patient and from normal white blood cells of both parents. The uncertain relevance of this finding to the condition of the patient is discussed.
High‐dose intravenous immunoglobulin for post‐transfusion purpura
Authors: Becker T. , Panzer S. , Maas D. , Kiefel V. , Sprenger R. , Kirschbaum M. , Mueller‐Eckhardt C.
Published: March 2008

Summary. Five patients with post‐transfusion purpura (four due to Zw(a), one presumably due to HLA antibodies) were treated with intravenous immunoglobulin (IgG) at doses of 0.4 g per kg body weight. IgG therapy was immediately effective as indicated by cessation of bleeding and rise of platelet counts in four out of five cases.
Properties and characterization of vesicles released by young and old human red cells
Authors: Snyder L. Michael , Fairbanks Grant , Trainor Jane (Piotrowski) , Fortier Normand L. , Jacobs Jerome B. , Leb Laszlo
Published: March 2008

Summary We have presently demonstrated morphologic differences between young and senescent red cells following 18 h of metabolic depletion in vitro. Young and old red cells both form echinocytes, whereas only young cells demonstrated myelin forms or microspheres. Furthermore, vesicles were released in greater quantities into the cell‐free supernatant from young cells. Isolated vesicles from both young and old red cells contained lipids, intrinsic membrane proteins (especially band 3), and haemoglobin, and they were also enriched in acetylcholinesterase (AChE). Young cells produced more vesicles than old cells but the composition of the low density vesicles was similar except that haemoglobin‐spectrin complex was found exclusively in vesicles from young cells. Oxidation of young red cells prior to metabolic depletion prevented both myelin formation and vesicle release.
Investigations of host defence in patients with sickle cell disease
Authors: Boghossian Seda H. , Wright Geoffrey , Webster A. David B. , Segal Anthony W.
Published: March 2008

Summary Parameters of host defence were investigated in 30 patients with sickle cell disease (SCD). A newly devised perfusion system was used to study the kinetics in whole blood of leucocyte adherence, phagocytosis, killing and solubilization of a mixture of Staph. aureus and Str. pneumoniae, and secretion of lactoferrin. A skin window technique was used to examine the accumulation of leucocytes at inflammatory foci and their subsequent rate of movement through a filter. Serum concentrations of C3, C4, total haemolytic complement and immunoglobulins were also measured.

The rate of neutrophil migration into filters was slightly reduced in patients with SCD. The proportion of monocytes that emigrated from the skin windows and their rate of migration were markedly diminished. The adhesion of neutrophils and their ability to kill staphylococci were also reduced, particularly in patients of the haemoglobin (Hb) SS and Hb S‐β‐thalassaemia genotypes. Neutrophil function was mostly impaired in patients with the greatest frequency of bacterial infection. The rate of clearance of pneumococci was related to the concentration of type specific immunoglobulin G but not M. Serum concentrations of immunoglobulins and complement were normal.

We were unable to define a defect of host defence of sufficient magnitude to explain the susceptibility of these patients to severe infection.
Thrombin increases the adhesion of washed human platelets to collagen
Authors: Sinigaglia F. , Balduini C. L. , Bisio A. , Balduini C.
Published: March 2008

Summary Thrombin stimulates the adhesion of washed human platelets to fibrillar collagen. This phenomenon occurs also when platelets, before thrombin stimulation, are resuspended in the presence of prostaglandin E1 to minimize the release reaction. Enzymatic activity of thrombin is not necessary for the enhancement of platelet adhesiveness, since phenylmethylsulphonylfluoride inhibited thrombin is effective in this respect. Detachment of thrombin from thrombin treated platelets by the use of hirudin restores normal platelet adhesiveness to collagen.
Heterogeneity of Ia antigen expression on myeloblastic leukaemias: correlation with stage of maturation defined by cytochemical markers
Authors: Heumann Didier , Carrel Stefan , Morell Andreas , Gratwohl Alois , Fopp Markus , Schneider Philippe , Barras Catherine , Mach J. P. , von Fliedner V. E.
Published: March 2008

Summary The expression of Ia‐like antigen (la) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS‐D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15–100%); the MS2 group of 14 cases with 10–70% NCAE positive cells (SB: 65–100%) and the MS3 group of 11 cases with 70–100% NCAE positive cells (SB: 89–100%).

Ia expression was determined by complement‐dependent cytotoxicity, immuno‐fluorescence and immunoperoxidase methods. A similar high percentage (80%) of patients from both group MS1 and MS2 expressed Ia on the surface of 32–100% of the cells. Furthermore, individual comparison of all cases from these two groups showed no correlation between Ia, NCAE and SB expression. Only in the 11 cases from the MS3 group, which included nine cases of promyelocytic leukaemias, was there a correlation between very low expression of Ia antigen with the high NCAE expression. Thus, for AML with a low degree of differentiation the expression of Ia seems to be independent of conventional cytochemical markers of cell maturation.
Disproportionate lymphoid cell subsets in thalassaemia major: the relative contributions of transfusion and splenectomy
Authors: Grady Robert W. , Akbar Arne N. , Giardina Patricia J. , Hilgartner Margaret W. , Sousa Maria de
Published: March 2008

SummaryThe relative proportions of T‐cell (OKT3‐positive, OKT4‐positive and OKT8‐positive) and B‐cell (SIg‐positive) populations in peripheral blood obtained from 29 chronically transfused patients withβ‐thalassaemia major were compared with those of 17 healthy controls. Changes attributable to blood transfusion and/or splenectomy are described. The percentage of OKT8‐positive (T‐suppressor) cells found in the thalassaemic patients increased linearly (P< 0.001) with the number of units transfused, irrespective of splenectomy. The percentage of OKT4‐positive (T‐helper) cells varied inversely with increasing transfusion in nonsplenectomized patients while in those who were splenectomized no significant correlation was apparent. Thus, in both groups of patients the T4/T8 ratio declined in a transfusion‐related manner. The splenectomized patients experienced a marked and persistent lymphocytosis due to an increase in the number of both T‐ and B‐cells. When the results were expressed as percentages, the greatest increase occurred in the number of B‐cells, this increase being unrelated to the number of transfusions received. None of the serum parameters usually associated with iron overload or abnormal liver function correlated with the observed increases in T‐suppressor and SIg‐positive cells. These findings corroborate reports that transfusion of blood products may lead to decreased T4/T8 ratios. However, none of the patients studied manifested clinical signs of acquired immune deficiency syndrome (AIDS). Accordingly, studies which define transfusion related AIDS on the basis of analyses with monoclonal antibodies must be viewed with caution.
Prognostic factors in the myelodysplastic syndromes: importance of initial data on peripheral blood counts, bone marrow cytology, trephine biopsy and chromosomal analysis
Authors: Tricot G. , Vlietinck R. , Boogaerts M. A. , Hendrickx B. , Wolf‐Peeters C. De , Van den Berghe H. , Verwilghen R. L.
Published: March 2008

Summary

An analysis of clinical, haematological, histological and cytogenetic data was performed in 85 consecutive patients with myelodysplastic syndromes (MDS). The criteria for diagnosis of refractory anaemia (RA), acquired idiopathic sideroblas‐tic anaemia (AISA) and chronic myelomonocytic leukaemia (CMML) were clearly defined, since the inclusion criteria provided by the FAB co‐operative group are imprecise. None of these patients has received chemotherapy during the follow‐up period. The median survival of the whole group was only 15 months, with less than 10% of the patients surviving after 5 years. Fifteen patients (17.6%) were still alive at time of analysis, 31 (36.5%) have developed acute myeloid leukaemia (AML) and only one of them is still alive; 30 (35.3%) died of infectious and/or haemorrhagic complications. Patients who developed AML had a shorter survival (median survival time 9.5 versus 15 months) but this difference was not significant (P = 0.10). Factors with prognostic value are in order of significance: abnormal localized immature myeloid precursors (= ALIP) in the trephine biopsy. circulating myeloblasts, excess of blasts in the bone marrow smears, age, FAB classification and granulocyte count. In comparison to refractory anaemia with excess of blasts (RAEB), CMML and RAEB in transformation (RAEBt), patients with RA and AISA had a lower incidence of evolution to AML (11% versus 56%), but a higher mortality rate from infections and/or bleeding (59.2% versus 29%). ALIP negative cases were only found among patients with RA and AISA, whereas ALIP positivity was observed in all cases of RAEB and RAEBt. in 10/11 patients with CMML and in almost half the cases of RA and AISA. In RA and AISA patients survival was significantly different between
Reactivity of rat monoclonal antibody CAMPATH‐1 with human leukaemia cells and its possible application for autologous bone marrow transplantation
Authors: Hale G. , Swirsky D. , Waldmann H. , Chan L. C.
Published: March 2008

Summary

The rat monoclonal antibody CAMPATH‐1 recognizes a hitherto undefined antigen present on virtually all normal lymphocytes and monocytes. Its reactivity with 105 samples of fresh leukaemic cells and 13 cell lines was measured by indirect fluorescence and peroxidase staining to define in more detail which stages of differentiation it recognizes. It was found to bind to cells from virtually all cases of lymphoid leukaemia (B cell CLL*, T cell ALL, cALL and the few examples of HCL, PLL, Sezary syndrome and CGL in lymphoid blast crisis). The single case of cALL in relapse and four of six cases of null ALL were negative. Binding to non‐lymphoid leukaemia cells (AML, AMML, AMoL, APL, AEL and CGL in blast crisis) was weaker or undetectable. Binding to established lymphoid cell lines was generally weak compared with fresh cells but some lines (MOLT4, DAUDI and X308) expressed adequate amounts of antigen to be lysed by CAMPATH‐1 with human complement. Because CAMPATH‐1 is very effective at killing lymphocytes in the presence of human complement, it has been used for removal of T cells in allogeneic transplants. The present results suggest that it might also have a role in purging bone marrow of leukaemia cells prior to autologous transplantation for acute lymphocytic leukaemia.
Is the HLA‐linked haemochromatosis allele implicated in idiopathic refractory sideroblastic anaemia?
Authors: Simon M. , Beaumont C. , Briere J. , Brissot P. , Deugnier Y. , Edan G. , Fauchet R. , Garo G. , Ghandour C. , Grolleau J. , Grosbois B. , Krempf M. , Leblay R. , Mignon L. Le , Prise P. Y. Le
Published: March 2008

Summary

In order to assess the previously reported association of HLA‐linked idiopathic haemochromatosis with idiopathic refractory sideroblastic anaemia (IRSA), the prevalence of HLA‐A3 antigen in a group of 22 patients with IRSA was compared to that observed in healthy controls and in patients with homozygous idiopathic haemochromatosis and to that calculated for a population heterozygous for idiopathic haemochromatosis. The prevalence of A3 in patients with IRSA (0.23) was quite similar to that observed in controls (0.29) and significantly different from that observed in homozygous (0.73; P<10−5) and heterozygous (0.57; P<10−3) haemochromatosis. Serum iron, transferrin saturation, serum ferritin and liver iron concentration showed no difference in IRSA patients with or without A3. It is concluded that there is neither systematic association between the haemochromatosis allele and IRSA nor systematic implication of such an allele in the development of iron overload observed in IRSA.
Myelodysplastic syndromes in childhood: three case reports
Authors: Van Wering Elisabeth R. , Kamps Willem A. , Vossen Jaak M. , Van Der List‐Nuver Cathinka J. A. , Theunissen P. M. V.
Published: March 2008

Summary

Three children with myelodysplastic syndromes (MDS) are described following the diagnostic criteria proposed by the FAB‐cooperative group. Two of the children were of Turkish origin. Two cases fit the criteria for ‘refractory anaemia with excess of blasts in transformation’. The other one is most consistent with ‘chronic myelomonocytic leukaemia’. The patients received ‘ANLL type’ induction. One died during induction, two were grafted, of whom one survives.
Relationships between blood product exposure and immunological abnormalities in English haemophiliacs
Authors: Lee C. A. , Bofill M. , Janossy G. , Thomas H. C. , Rizza C. R. , Kernoff P. B. A.
Published: March 2008

Summary

Amongst 160 English haemophiliacs treated with clotting factor concentrates, abnormalities of T lymphocyte subset distribution (characterized by low T4/T8 ratios and high total T8 counts), low in vitro phytohaemagglutinin stimulation and raised serum IgG levels, were more common in patients with haemophilia A than B, in patients who had received heavier blood product exposure, and in adults rather than children. A slight reduction in lymphocyte and platelet counts was found in 26% and 17% of patients. In the sample of patients tested, serum α1‐thymosin levels were often raised, but β2‐microglobulin levels were usually normal. Fractionation procedures used to prepare clotting factor concentrates, and the amounts of concentrate used, are more likely to be causally related to these immunological abnormalities than the origins of source donor plasmas.
Persistence of host Langerhans cells following allogeneic bone marrow transplantation: possible relationship with acute graft‐versus‐host disease
Authors: Perreault Claude , Pelletier Micheline , Belanger Robert , Boileau Jacques , Bonny Yvette , David Michele , Gyger Martin , Landry Diane , Montplaisir Serge
Published: March 2008

Summary

Langerhans cells (LC) are bone marrow‐derived dendritic antigen‐presenting cells found in the epidermis. In an effort to determine the origin (host versus donor) of LC at different intervals following bone marrow transplantation, we performed skin biopsies in 16 recipients of sex‐mismatched marrow. LC were identified using monoclonal antibody OKT6 in an indirect immunoperoxidase assay and their donor or host origin determined according to the presence or absence of Y body. The presence of Y‐positive (donor) LC could be demonstrated in all (6/6) skin biopsies of female recipients of male marrow tested between days 39 and 730 post‐transplant. Persistence of host LC in male recipients of female marrow was documented in all (6/6) recipients studied on day 39 and in two out of seven patients tested on day 120 post‐transplant. From day 365 onward, no residual host LC could be detected, suggesting that by this time all epidermal LC are donor‐derived. Our study demonstrates that host LC usually persist for 39 and up to 120 d following bone marrow transplantation. The relevance of this observation to the possible role of LC and other host dendritic antigen‐presenting cells in the graft‐versus‐host reaction is discussed.
A genetic marker for elevated levels of haemoglobin F in homozygous sickle cell disease?
Authors: Wainscoat J. S. , Thein S. L. , Higgs D. R. , Bell J. I. , Weatherall D. J. , Al‐Awamy B. H. , Serjeant G. R.
Published: March 2008

Summary

Ten patients with sickle cell (SS) disease from a Jamaican family were found to have unusually high levels of haemoglobin F for this population. Each of them has inherited one sickle cell gene on a chromosome characterized by an arrangement of restriction fragment length polymorphisms (haplotype) which is very rare in the Jamaican population. Genetic analysis of the family suggests that there is a determinant linked to the β‐globin gene cluster, characterized by this haplotype, which is responsible for increased haemoglobin F production in response to anaemia. Interestingly this particular haplotype appears to be common in patients with SS disease in eastern Saudi Arabia in whom a high level of haemoglobin F is the rule rather than the exception. Hence it is possible that this haplotype (++–++) acts as a genetic marker for elevated levels of haemoglobin F in sickle cell disease.
Thalassaemia genes in Peninsular Arabs
Authors: White J. M. , Byrne M. , Richards R. , Buchanan T. , Sheik‐Yousouf I. , White Y. S. , Frost B.
Published: March 2008

Summary

The haematological indices of Peninsular Arabs (United Arab Emirate Nationals, Yemeni and Omani) have been examined. The most outstanding feature, seen in 40–50% of all subjects, was one of hypochromia, microcytosis associated with erythrocytosis. In approximately 5% the hypochromia was severe (MCH 19–22 pg) and 20% of these were found to have β thalassaemia trait. In 10% of subjects the hypochromia was moderate (MCH 23–24 pg) and β thalassaemia was confirmed in only 10%. The remaining 25% had a mild hypochromia (MCH 25–27 pg) and no β thalassaemia was detected. The cause of the hypochromia in subjects with a normal Hb A2 (30% of the total population) is probably α thalassaemia, firstly because in those patients with an MCH of 19–24 pg the other haematological parameters are statistically the same as those with proven β thalassaemia and, secondly, in those with an MCH of 25–27 pg iron deficiency is not common (6% of the population). The degree and pattern of the distribution of hypochromia of the three major ethnic groups of the Peninsular Arabs could be explained either by different α and β thalassaemia genes being operative or by different degrees of inbreeding of the same genes.
Marrow cell necrosis in anorexia nervosa and involuntary starvation
Authors: Smith Robert R. L. , Spivak Jerry L.
Published: March 2008

Summary

Marrow specimens from six patients with anorexia nervosa and three with involuntary starvation were examined for the presence of gelatinous transformation and marrow cell necrosis. Five of the patients had pancytopenia. Acanthocytes were present in the circulation of all nine. In only two patients was marrow cellularity adequate. Gelatinous transformation was present in every marrow specimen and was of a marked degree in eight. Marrow cell necrosis was identified in all nine marrow specimens. The necrosis was extensive in one specimen, focal in the others and limited to the areas of gelatinous transformation. Severe malnutrition was the single element common to all the patients.
Unclassified type of congenital dyserythropoietic anaemia (CDA) with prominent peripheral erythroblastosis
Authors: Bethlenfalvay N. C. , Hadnagy Cs. , Heimpel H.
Published: March 2008

Summary

Two unrelated cases of congenital dyserythropoietic anaemia (CDA) are described. They show striking similarities which could not be attributed to one of the well‐known types of CDA or any other congenital disease of the erythroid system. Both patients were followed for many years before and after splenectomy. There was a long‐lasting, prominent post‐splenectomy erythroblastosis, suggesting impairment of red cell denucleation. The type of heredity is unknown, and the enzymatic or molecular basis of the changes observed is not understood.
Endothelial cell proliferation in myelofibrosis
Authors: Reilly J. T. , Nash J. R. G. , Mackie M. J. , McVerry B. A.
Published: March 2008

Summary

The distribution of laminin and collagen type IV in normal human bone marrow appeared to be limited to a small number of capillary and sinusoidal basement membranes. Cellular elements including megakaryocytes showed a negative staining reaction. In contrast, myelofibrotic bone marrow showed markedly increased quantities of both laminin and collagen type IV. This was consistent with a proliferation of endothelial cells within the marrow as confirmed by factor VIII RAG staining. It is suggested that in myelofibrosis in addition to a marked fibrous reaction proliferation of vascular elements is also prominent.
The red cell antigens A, B, D, U, Ge, Jk3 and Yta are not detected on human granulocytes
Authors: Gaidulis Laima , Branch Donald R. , Lazar Gary S. , Petz Lawrence D. , Blume Karl G.
Published: March 2008

Summary

We report the inability to detect the following red blood cell antigens on human granulocytes: A, B, D, U, Gerbich (Ge), JkaJkb (Jk3) and Cartwright (Yta). To study each antigen, granulocytes were purified on density gradients, fixed in glutaraldehyde, and the uptake of specific antisera measured using two direct immunological techniques: 125I‐staphylococcal protein A (125I‐SPA) binding and avidin‐biotin‐complex (ABC) immunoperoxidase staining. Glutaraldehyde fixation was shown not to affect the antigenicity when the antisera were tested using red blood cells. Using three anti‐A, three anti‐B and three anti‐A,B antisera, our 125I‐SPA results of 47 tests with granulocytes from group A individuals and 39 tests with granulocytes from group B individuals indicate that A or B antigens are not expressed on human granulocytes. Tests using ABC were also negative with 37 and 36 granulocytes from group A or B individuals, respectively. In addition, no positive results using 125I‐SPA were obtained with granulocytes from individuals having antigen positive red cells when tested with two anti‐D (number of tests performed (n= 22), three anti‐Ge (n= 22), three anti‐U (n= 20), two anti‐Jk3 (n= 17), and three anti‐Yta (n= 25); control anti‐NA1 or ‐NB1 antisera were invariably positive. Also, using these antisera, no positive results were obtained by ABC except with one anti‐Yta antiserum which was positive with one of seven granulocytes tested. This anti‐Yta was also positive with three of 10 granulocytes by 125I‐SPA. This activity was shown to be due to a granulocyte‐specific antibody; adsorption of the antiserum with human granulocytes removed all activity against granulocytes but did not reduce the activity against red cells. Thus, our results are in agreement with recent reports which demonstrated the absence of the A, B and D antigens on human granulocytes. However, we have been unable to confirm previous reports which indicated the
The importance of thrombin inhibition for the expression of the anticoagulant activities of heparin, dermatan sulphate, low molecular weight heparin and pentosan polysulphate
Authors: Ofosu F. A. , Blajchman M. A. , Modi G. J. , Smith L. M. , Buchanan M. R. , Hirsh J.
Published: March 2008

Summary

The effects of standard heparin, three low molecular weight derivatives of heparin, dermatan sulphate and pentosan polysulphate on the intrinsic coagulation pathway were compared in order to evaluate the contributions of the anti‐factor Xa and anti‐thrombin activities to their anticoagulant activities. The anticoagulant potency was measured by the ability of each sulphated polysaccharide to inhibit the generation of thrombin activity in plasma. Similarly, the ability of the six sulphated polysaccharides to enhance the rates of inactivation either factor Xa or thrombin in defibrinated plasma containing calcium chloride and cephalin were also determined. Standard heparin was the only sulphated polysaccharide that could equally inhibit thrombin generation and enhance the inactivation of factor Xa and thrombin by plasma. Dermatan sulphate and pentosan polysulphate were more effective as inhibitors of thrombin generation than potentiators of factor Xa inactivation. The two smallest derivatives of heparin, which had high anti‐factor Xa (but low antithrombin) activity, were the poorest inhibitors of thrombin generation. Our results therefore suggest that only sulphated polysaccharides that enhance the inactivation of thrombin by plasma and/or inhibit the generation of thrombin activity in plasma are good anticoagulants. These two activities of sulphated polysaccharides appear to be good predictors of the relative antithrombotic potency in vivo.
Simple monosomy 7 and myelodysplastic syndrome in thirteen patients without previous cytostatic treatment
Authors: Michiels J. J. , Mallios‐Zorbala H. , Prins M. E. F. , Hählen K. , Hagemeijer A.
Published: March 2008

Summary. Thirteen patients with simple monosomy 7 presented with pallor in 11, easy bruisability in five, splenomegaly in four, no infections, refractory anaemia in all, granulocytopenia in seven, monocytosis in three, leucocytosis in four and thrombocytopenia in eight. Peripheral blood and bone marrow findings were consistent with myelodysplastic syndrome (MDS) type I in three, type II in two, type III in two, type IV in three and acute myelofibrosis in three patients. Transformations to acute leukaemia in seven patients were M2 in one, M4 in four, megakaryoblastic in one and undifferentiated in one. Lack of chromosome 7 in 12–85% of analysed cells at initial presentation of MDS progressed to nearly 100% during blastic transformation. At that time an additional change in the long arm of chromosome 3 was seen in two patients and trisomy 8 in 6% of analysed cells in a third case. The median survival time was 12 months for MDS and 3 months for acute leukaemia. Simple monosomy 7 appears to be largely confined to young children and elderly people.
The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia
Authors: Melo Junia V. , Wardle Jane , Chetty Margaret , England John , Lewis S. M. , Galton David A. G. , Catovsky Daniel
Published: March 2008

Summary. The peripheral blood WBC size distribution was assessed by morphological and volume measurements in 73 patients with B‐cell chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL). Patients with typical CLL, with ≤10% prolymphocytes, had a homogeneous major population of small cells which could be recognized both by morphology and volume (median volume 211.5 ±32.5fl). In PLL, the volume of the main cell component was significantly larger than in CLL: in two‐thirds of cases the major cell population was distributed in a first lognormal fitted curve of the volume histogram, with median volume 281.8±38.0 fl; in the remaining cases the main cell component showed a larger median volume (353.5±71.9 fl) contained within the second lognormal curve which was preceded by a minor peak. CLL patients with 11.55% prolymphocytes (CLL/PL) had characteristic cell volume histograms in which two lognormal curves could always be fitted: in 80% of cases the main cell component was located in a first curve with median volume of 257.9 ±28.6 fl; in the remaining cases the major population was represented by cells with median volume of 349.0 ± 83.9 fl distributed in a second peak. Although in both CLL and CLL/PL the majority of cells was defined morphologically as small, the median volume of these lymphocytes was significantly larger in CLL/PL than in CLL. The degree of concordance in the assessment of cell size between morphology and volume measurements was high in CLL, whereas in CLL/PL and PLL morphology underestimated the cell
Insulin stimulates cord blood erythroid progenitor growth: evidence for an aetiological role in neonatal polycythaemia
Authors: Perrine Susan P. , Greene Michael F. , Lee Phillip D. K. , Cohen Ruth A. , Faller Douglas V.
Published: March 2008

Summary. Polycythaemia in the neonate is a serious pathologic entity which occurs particularly in infants of diabetic mothers (IDM) and srnall‐for‐gestational age (SGA) infants. Both of these conditions are associated with fetal hyperinsulinaemia. Cultures of cord blood mononuclear cells from polycythae‐mic IDM showed increased growth of late erythroid progenitor colonies, compared to cord blood mononuclear cells from non‐polycythaemic infants, reflecting a possible expansion of this progenitor population in the polycythae‐mic fetus. No changes were observed in early erythroid progenitor populations. Biosynthetic human insulin at physiological levels characteristic of IDM stimulated growth in culture of late erythroid progenitors in cord blood from premature, term and IDM infants. Three out of five polycythaemic infants had elevated cord blood plasma levels of insulin C‐peptide at birth, whereas no infant with a haematocrit of less than 65% had high insulin C‐peptide measurements. These data suggest that the polycythaemia noted in infants of diabetic mothers may be secondary, in large part, to a stimulatory effect on erythroid progenitor growth by the hyperinsulinaemic environment in which they develop in utero.
Multilineage expression of haemopoietic precursors with an abnormal clone in idiopathic myelofibrosis
Authors: Sato Yuko , Suda Toshio , Suda Junko , Ohsaka Akimichi , Kubota Kazuo , Saito Masaki , Miura Yasusada
Published: March 2008

Summary. To clarify the lineage involvement of haemopoietic progenitor cells in idiopathic myelofibrosis (MF), simultaneous analysis of morphology and chromosomes were performed on single colonies from a 70‐year‐old Japanese woman with typical presentation of MF. The cytogenetic analysis of unstimu‐lated peripheral blood cells revealed three cell lines 47.XX, −6, +9, +der(6)t (1;6)(lqter→1q21::6p21→6qter), 46,XX, −6, +der(6) and 46.XX. Of 91 metaphases examined, the numbers of each cell line were 43, 41 and 7, respectively. Blood mononuclear cells were plated at 2 × 103 or 1 × 104/ml in methylcellulose medium containing phytohaemagglutinin‐stimulated leucocyte conditioned medium and erythropoietin. On days 10,12 and 14 of culture, 47 individual colonies were lifted and served for morphological and cytogenetic examination. Morphological examination revealed that the colonies contained neutrophils (n), macrophages (m), basophils (b), erythrocytes (E) and megakaryocytes (M). Twenty‐two of the 47 colonies had analysable metaphases, yielding totally 158 metaphases. Twelve colonies contained three or more metaphases. Eight colonies (3bE, IE, 2b, InEM, IbEM) were of the abnormal cell line 46,XX, − 6, + der(6), and four colonies (2E, IbE, ImE) were of the karyotypically normal cell line 46,XX. The other abnormal cell line 47.XX, −6, +9, +der(6) was not detected in any of the metaphases obtained from single colonies. These results provided direct evidence that the pluripotent stem cells were involved in MF.
ABO and Rhesus phenotyping of fetal erythrocytes in the first trimester of pregnancy
Authors: Gemke R. J. B. J. , Kanhai H. H. H. , Overbeeke M. A. M. , Maas C. J. , Gravenhorst J. Bennebroek , Bernini L. F. , Engelfriet C. P. , Van't Veer M. B.
Published: March 2008

Summary. Determination of fetal red blood cell antigens in early pregnancy can be important in cases with a history of severe haemolytic disease of the newborn. From chorionic villus biopsies (CVB) between the 8th and 12th week of gestation a small number of fetal red blood cells was obtained, inevitably highly contaminated with maternal blood cells. Two techniques were used to demonstrate the minor (fetal) cell population with a blood group antigen differing from the major (maternal) cell population: (1) a solid‐phase microfluor‐escence technique (introduced in this paper) which was compared with (2) the mixed agglutination technique. In series of artificial mixtures of erythrocytes it was shown that with the microfluorescence technique the ABO and Rhesus phenotypes of minor cell populations could be determined at a ratio of 1 in 4000 erythrocytes of the major population, making this technique 4 times as sensitive as the mixed agglutination technique. We further investigated the reliability of the microfluorescence technique to demonstrate antagonistic fetal blood groups in the first trimester of pregnancy. Of 18 women undergoing CVB prior to therapeutic abortion, blood group antagonism (ABO and Rhesus systems) was demonstrate in all 11 cases in which it was present. Therefore, it seems that CVB can be reliably used for the prenatal diagnosis of (recurrent) blood group antagonism.
Prolonged thrombocytopenia in post‐transfusion purpura (PTP) associated with changes in the crossed immunoelectrophoretic pattern of von Willebrand factor (vWF), circulating immune complexes and endothelial cell cytotoxicity
Authors: Lillicrap David P. , Ford Peter M. , Giles Alan R.
Published: March 2008

Summary. A 39‐year‐old multigravida presented with a platelet count of 2 × 109/l 12 d after a blood transfusion. The clinical presentation was typical of post‐transfusional purpura (PTP). She was successfully managed with intensive plasma exchange with plasma replacement. Replacement with albumin saline was unsuccessful. Elevated levels of immune complexes were detected on presentation but were reduced to normal levels by plasma exchange but were elevated again during relapse. Raised levels of circulating platelet aggregates and platelet‐aggregating activity were found during relapse but were absent during remission. Crossed immunoelectrophoresis of vWF showed a left shift suggesting the presence of abnormally high molecular weight multimeric forms. In contrast, multimeric assay of the same samples were within normal limits suggesting that the shift noted on crossed immunoelectrophoresis may have resulted from complexing of vWF with some other components. Immunological studies demonstrated the presence of endothelial cell cytotoxicity and lymphocytotoxicity in the patient's serum. It is concluded that the thrombocytopenia observed in PTP may not occur as a direct result of the immunological event initiating the disorder but rather indirectly via the release of vWF consequent upon endothelial cell damage which, either alone or in combination with another factor, possibly immune complexes, induces intravascular platelet aggregation and sequestration. There were significant
Toxoplasmosis in hairy‐cell leukaemia
Authors: Knecht Hans , Rhyner Kaspar , Streuli Rolf A.
Published: March 2008

Summary. Toxoplasma serology was performed in 28 patients with hairy‐cell leukaemia and was positive in eight patients (29%). In two patients (7%) reactivated toxoplasmosis was proven by either isolation of Toxoplasma gondii or by significant antibody titre rise with generation of specific IgM‐antibodies. In four patients (14%), a clinical diagnosis of active toxoplasmosis was based on signs and symptoms, serologic tests, and response to specific treatment. The high proportion of patients in which active toxoplasmosis was proven or probable (six; 21%) may be related to the presence of severe monocytopenia. In patients with hairy‐cell leukaemia developing fever of unknown origin and myositis, toxoplasma serology should be performed, particularly because treatment of active toxoplasmosis usually is successful.
Survival of 111‐Indium platelet subpopulations of varying density in normal and post splenectomized subjects
Authors: Watson H. H. K. , Ludlam C. A.
Published: March 2008

Summary. The present study was designed to investigate the survival of platelets of differing densities in normal and post‐splenectomized subjects. Autologous platelets, labelled with 111In‐oxine, were reinjected into normal subjects (n = 12); 63% were recovered in the circulation and their survival curve was linear with a T1/2 of 4·5 d. When the platelets were layered onto a continuous Percoll gradient, they formed a band extending between 1·040 and 1·080 g ml−1. After fractionation of the gradient the specific radioactivity of 111In platelets recovered was measured. The specific activity of low density platelets (average 1·050 g ml−1) decreased rapidly with a T1/2 of 2·0 d, whilst medium density platelets (average 1·060 g ml−1) survived with a T1/2 of 4·5 d; high density platelets (average 1·073 g ml−1) exhibited a T1/2 > 5·0 d. This latter population of high density platelets also showed a significant increase in specific activity on the first day following injection. In post‐splenectomy subjects a similar relationship between density and 111In associated activity was observed but no increase in the specific activity of the dense platelets on day 1 was observed. We conclude that high density autologous 111In‐platelets are preferentially retained in the spleen and have a more prolonged survival than those of lower density.
Studies on immunological assay of vitamin K dependent factors.
Authors: Mikami S. , Tuddenham E. G. D.
Published: March 2008

Summary. A radioimmunoassay (RIA) for factor VII was developed using 125I‐factor VII, anti‐factor VII rabbit serum and anti‐rabbit IgG goat serum. The lower limit of sensitivity in normal reference plasma was 3 × 10−3 units/ml. Although the level of factor VII antigen (VII:Ag) in normal plasma samples (= 20) 0.944·0.176 units/ml. correlated with that of factor VII coagulant activity (r= 0.89), VII:Ag level in paired normal sera showed a higher value (1.469 0.376 units/ml).

The level of antigen according to RIA of factor VIIa activated by factor Xa increased 2.5‐fold compared with that of unactivated factor VII. It is suggested that the polyclonal anti‐factor VII produced in a rabbit had higher affinity for factor VIIa than for factor VII.

In two out of seven patients with congenital factor VII deficiency, VII:Ag was detectable (0.04, 0.31 units/ml, respectively) whereas VII:C was less than 0.01 units/ml.

In 12 warfarin‐treated individuals, VII:C showed a lower level (0.121 0.063 units/ml) that that of VII:Ag (0.518 0.186 units/ml). During 4 weeks observation after stopping warfarin, VII:C and VII:Ag reached normal levels in 1 week. However, VII:C did not reach equivalence with VII:Ag until 4 weeks had elapsed.
Different types of plasminogen activator inhibitors in plasma and platelets in pregnant women
Authors: Nilsson Inga Marie , Felding P. , Lecander Ingegerd , Lennér Christina , Åstedt B.
Published: March 2008

Summary. The content of tissue plasminogen activator inhibitor (‐PA‐1), and of specific pregnancy plasma‐PA‐I reacting with antibodies to placental‐PA‐I, was measured in platelet‐poor plasma (PPP), platelet‐rich plasma (PRP), serum and platelet lysates, both from pregnant women and healthy non‐pregnant (male or female) controls. Inhibitory activity was much higher in PPP from pregnant women than in PPP from controls, though it was comparable in platelet lysates both from pregnant women and from controls. The specific pregnancy Plasma‐PA‐I was present in high concentration in pregnancy PPP, but absent in PPP from the controls and also absent in platelet lysates from both pregnant women and controls. The results show that the specific pregnancy plasma‐PA‐I is not identical to either the PA‐I in platelet lysate or to the PA‐I in PPP from non‐pregnant controls.
Quantitative assessment of erythropoiesis in bone marrow expansion areas using 52Fe
Authors: Ferrant A. , Rodhain J. , Leners N. , Cogneau M. , Verwilghen R. L. , Michaux J. L. , Sokal G.
Published: March 2008

Summary. Quantitative 52Fe scans were performed in 180 patients. Expansion of bone marrow was observed in 70. This bone marrow expansion was a nearly constant feature in haemolytic anaemia and in sideroblastic anaemia. It occurred in a third of the patients with myelofibrosis. In patients with polycythaemia rubra vera, expansion was noticed in only two out of seven. Erythropoiesis in expansion areas occurred despite persistence of fat in the iliac crest bone marrow biopsy. It could exist with a slight increase in erythropoiesis and might develop only after a long period of erythropoietic stimulation.Increased marrow activity can take place without erythropoietic expansion in long bones. The fraction of iron uptake in expansion areas did not exceed a third of total marrow iron uptake. With increasing erythropoiesis, the increase in iron uptake in expansion areas was less marked than the increase in the central areas. Erythropoiesis in expansion areas was usually not of major quantitative importance but could nevertheless reach the erythropoiesis of a normal adult.
The significance of host haemopoietic cells detected by cytogenetic analysis of bone marrow from recipients of bone marrow transplants
Authors: Walker Helen , Singer C. R. J. , Patterson Janet , Goldstone A. H. , Prentice H. G.
Published: March 2008

Summary. Bone marrow from 39 patients who received a bone marrow transplant (BMT) from a matched donor of different sex were studied by chromosome analysis for evidence of mixed haemopoietic chimaerism (MC). Recipient metaphases were detected in the bone marrow of 10 patients after BMT. Patients in whom MC was detected within 6 weeks of BMT did not all have a poor outcome. Two of seven are disease‐free survivors at > 470 and > 632 d. All three patients in whom MC was diagnosed more than 6 weeks after BMT subsequently relapsed. Four factors appear to be important in determining the probability of relapse when MC is detected in a patient after BMT: the timing of detection of residual recipient cells; the proportion of these cells in the bone marrow; persistence of these cells in increasing proportions; and the karyotype of the recipient metaphases detected. Cytogenetic assessment may provide the earliest indication of relapse in these patients. In addition, this study provides further evidence that cyclophosphamide and total body irradiation, as used in these patients, may be inadequate conditioning therapy for BMT.
Feasibility of prenatal diagnosis of β thalassaemia by DNA polymorphisms in an Italian population
Authors: Wainscoat J. S. , Work S. , Sampietro M. , Cappellini M. D. , Fiorelli G. , Terzoli S. , Weatherall D. J.
Published: March 2008

Summary. A feasibility study of prenatal diagnosis of β thalassaemia in a northern Italian population has been carried out. Twenty‐five families have been studied, each consisting of two parents and a homozygous β thalassaemia child, thus enabling linkage analysis of restriction fragment length polymorphisms (RFLPs) to the normal and the thalassaemic chromosomes. Using seven standard RFLPs, 19/25 families could be offered prenatal diagnosis; inclusion of the recently described Ava IIΨβ polymorphism increased this figure to 23/25 (92%) of the families.