bluuebunny/crossref_metadata_2025 huggingface dataset:
GγAγ(δβ)°‐thalassaemia and a new form of γ globin gene triplication identified in the Yugoslavian population
Authors: Efremov G. D. , Filifcče V. , Gjorgovski I. , Juričič D. , Stojanovski N. , Harano T. , Nakatsuji T. , Kutlar A. , Kutlar F. , Bakioglu I. , Huisman T. H. J.
Published: March 2008

Summary

Among several hundred apparently healthy Yugoslavian adults with slightly elevated levels of fetal haemoglobin, we have identified two distinct abnormalities, (a) A GγAγ(δβ)°‐thalassaemia heterozygosity with an ∼ 15 kb deletion which involves part of the δ globin gene and the β globin gene. This deletion is probably the same as that seen among Italians (Ottolenghi et al, 1982; Carèet al, 1984). (b) A nondeletion form of hereditary persistence of Hb F which is caused by a γ globin gene triplication of the (+)Gγ mD (+)Gγ mD Aγ type. It is characterized by the presence of some 5% Hb F in the heterozygote containing nearly 100%Gγ chains. The C→T mutation at position — 158 5’to the Gγ chain [(+)Gγ], identified through analyses of Xmn I digests, was present at both Gγ globin genes. This mutation is known to be associated with increased Gγ chain production (Gilman & Huisman, 1985), and thus is responsible for the increased Gγ chain production in these heterozygotes. The condition is different from the (+)Gγ mD (+)Gγ nondeletion type of HPFH which has been observed in heterozygotes of two Black families, and is associated with the presence of 3–4% Hb F (with mainly Gγ chains) in heterozygotes.
Pure red cell aplasia: lymphocyte inhibition of erythropoiesis
Authors: Abkowitz Jamis L. , Kadin Marshall E. , Powell Jerry S. , Adamson John W.
Published: March 2008

Summary

The pathogenesis of pure red cell aplasia (PRCA) was studied in a patient who had no evidence of malignancy. In marrow culture, no erythroid colonies (from late erythroid progenitors [CFU‐E]) but normal numbers of well‐haemoglobinized erythroid bursts (from early erythroid progenitors [BFU‐E]) were found, indicating that BFU‐E existed in the patient but that their subsequent in vivo differentiation was inhibited. Autologous coculture studies suggested that inhibition was mediated by the patient's ER+ lymphocytes. After remission was induced with cyclophosphamide, autologous ER + cells no longer suppressed in vitro erythropoiesis. However, cryopreserved ER + cells, obtained with anaemia, suppressed BFU‐E growth from remission marrow. An expanded population of large granular lymphocytes (LGL) with ER +, Fcγ+. T3 +, T8 +, HNK‐1 +, Ia —, M1 — phenotype and no functional natural killer (NK) cell activity was noted during PRCA that reverted to normal with remission. For this patient, both in vivo and in vitro evidence demonstrates a cellular inhibition of erythropoiesis at the level of differentiation between BFU‐E and CFU‐E.
Chronic idiopathic and secondary neutropenia: clinical and serological investigations
Authors: Van der Veen J. P. W. , Hack C. E. , Engelfriet C. P. , Pegels J. G. , Kr. vondem Borne A. E. G.
Published: March 2008

Summary

Clinical data on 49 patients with chronic idopathic neutropenia (CIN) and 42 patients with neutropenia secondary to a well‐defined immuno‐logical disorder (SN) were collected and related to serological parameters. In 47% of the patients with CIN and 53% of those with SN, a positive direct immunofluorescence test was obtained with granulocytes from the patients. In the sera from the patients in the two groups, antibodies against donor granulocytes were detected by the indirect immunofluorescence test, the leucoagglutination test and/or the granulocytotoxicity test in 15%, 19% and 15%, respectively. The results of the above tests could not be correlated with any clinical or haematological parameter.
Adult‘fetal‐like’erythropoiesis characterizes recovery from bone marrow transplantation
Authors: Weinberg R. S. , Schofield J. M. , Lenes A. L. , Brochstein J. , Alter B. P.
Published: March 2008

Summary

The transient fetal‐like erythropoiesis which appears during recovery from bone marrow transplantation has now been examined at the level of erythroid progenitor cells. A 7‐year‐old boy with β+‐thalassaemia major was studied during engraftment from his β‐thalassaemia trait sister. Hb F and i antigen rose as expected. Macrocytosis never developed, but red cell size distribution became very heterogeneous. Bone marrow CFU‐E and BFU‐E were detected by 30 d, prior to the appearance of reticulocytes. Marrow erythroid progenitor cell numbers were normal by 146 d, while those in the blood became normal by 360 d. After transplantation globin synthesis ratios in erythroid colonies were diagnostic of thalassaemia trait, indicating engraftment. Individual erythroid colonies derived from both blood and marrow at all times during reconstitution showed no correlation of Gγ and γ. Thus the fetal‐like stress erythropoiesis of marrow expansion following transplantation was derived from adult and not fetal progenitor cells.
Thrombocytopenia associated with gold therapy: a drug‐induced autoimmune disease?
Authors: Kr. Von Dem Borne A. E. G. , Pegels J. G. , Van Der Stadt R. J. , Van Der Plas‐Van Dalen C. M. , Helmerhorst F. M.
Published: March 2008

Summary

We studied 13 patients with rheumatoid arthritis (RA) and gold‐induced thrombocytopenia. Platelet‐specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocyto‐penic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet‐specific autoantibodies, and that gold‐induced thrombocytopenia is a drug‐induced autoimmune disease.
An acute leukaemia augured before clinical signs by blood group antigen abnormalities and low levels of A and H blood group transferase activities in erythrocytes
Authors: Lopez M. , Bonnet‐Gajdos M. , Reviron M. , Janvier D. , Huet M. , Salmon Ch.
Published: March 2008

Summary

A mixed field agglutination pattern with anti‐A reagents and very low levels of A and H blood group antigen specific transferase activities were found in the erythrocytes of a 4‐year‐old girl who presented no clinical signs of haematological disease. Blood and marrow examination displayed some features consistent with a moderate dysmyelopoietic state. 18 months later an acute myeloblastic leukaemia confirmed the suspected haematological malignancy.
Progesterone inhibits proliferation of human marrow colony forming cells (CFU‐GM) through increased prostaglandin production by marrow macrophages
Authors: Smith M. A. , Lucie N. P. , Ferguson M. M. , Mairs R. J. , Smith J. G.
Published: March 2008

Summary

Progesterone inhibited proliferation of granulocyte/macrophage progenitor cells (GFU‐GM) in human bone marrow cultured in methylcellulose; the inhibition ranged from 8% at 3 x 10‐9 M, 22% at 3 x 10‐8 M to 38% at 3 x 10‐7 M progesterone in 14 non‐malignant marrows.

Depletion ofmarrow monocytes/macrophages with a monoclonal antibody MO2, abolished the inhibitory effect of progestrone. However, production of colony stimulating activity (CSA0 did not appear to be affected, either in PHA stimulated peripheral blood or in bone marrow. indomethacin, a prostaglandin synthetase inhibitor, greatly reduced the degree of inhibition and the addition of prostaglandin E1 (PFE10 to culture in concentrations as low as 10‐12 M completely removed any additional inhibitory effect of progesterone. PGE1 is known to inhibit only those CFU‐GM bearing the Ia antigen; we observed that depletion of Ia positive CFU‐GM by either 24 h incubation or by monoclonal (I2) treatment, reduced or abolished progresterone mediated inhibition. this confirms that the mechanism of progesterone inhibition of CFU‐GM is mediated through increased PGE production by marrow macrophages, and subsequent inhibition by PGE of ia positive CFU‐GM.
The role of platelet membrane glycoproteins Ib and IIb‐IIIa in platelet adherence to human artery subendothelium
Authors: Sakariassen Kjell S. , Nievelstein Patricia F. E. M. , Coller Barry S. , Sixma Jan J.
Published: March 2008

Summary

Platelet adherence to human artery subendothelium in blood from eight normal subjects, four patients with Glanzmann's thrombasthenia (deficiency of platelet membrane glycoproteins IIb and IIIa: GPIIb‐IIIa), two patients with Bernard‐Soulier syndrome (deficiency of platelet membrane glycoprotein Ib: GPIb) and one patient with von Willebrand's disease (VWD subtype III, deficient in factor VHI‐von Willebrand factor: FVIII‐VWF) was compared at various wall shear rates (300, 500, 1000, 1800 and 2500 s‐1).
Serum sickness and haematopoietic recovery with antithymocyte globulin in bone marrow failure patients
Authors: Bielory Leonard , Gascon Pedro , Lawley Thomas J. , Nienhuis Arthur , Frank Michael M. , Young Neal S.
Published: March 2008

Summary

We have evaluated 3 3 patients with various bone marrow dyscrasias treated with horse antithymocyte globulin (ATG) (Upjohn) to determine the relationship of haematopoietic response to the occurrence of serum sickness. Patients received ATG intravenously over 10 or 28 d at a dose of 15 mg/kg/d. Total or partial haematological responses were noted in 12 of 33 patients. Twenty‐eight patients developed clinical signs of serum sickness 6–14 d after the first infusion of ATG, while five patients did not. Twenty‐five of these patients were evaluated by immunochemical assays for circulating immune complexes (Clq‐binding assay) and 21 patients for serum complement (C3, C4 and CH50 assay) levels. There was a direct correlation between increases in immune complex levels, decreases in serum complement levels, and the development of the clinical signs and symptoms and serum sickness. Twenty‐one of 28 patients who developed serum sickness failed to show haematological improvement. However, haematopoietic recovery occurred in all five patients who did not manifest serum sickness (P <0.05) and in four patients who failed to develop immune complexes. These findings indicate that the development of serum sickness is not required for a haematopoietic response with ATG and may indeed impair recovery.
Liberation of surface and internal platelet‐associated IgG (PA‐IgG) during platelet activation
Authors: Pfueller Sharron L. , David Rosemary
Published: March 2008

Summary

The relationship between platelet‐associated IgG (PA‐IgG) of intact platelets to that of lysed platelets has been studied using a competitive ELISA. In platelets from 20 normal individuals mean surface PA‐IgG constituted 3 5% of mean total PA‐IgG and showed a significant linear relationship with total PA‐IgG. In platelets from 61 patients with various forms of thrombocytopenia including that with immune causes, 38 showed a similar proportion of PA‐IgG on the surface after storage at 2°C, as seen in normal platelets, while in 23, levels of surface and total PA‐IgG were equal. Normal platelets activated with thrombin or calcium ionophore A2 318 7, also had levels of surface PA‐IgG close‐to total PA‐IgG. Supernatants of platelet suspensions activated with aggregating agents contained increased amounts of IgG and when the platelets were washed, both total and surface PA‐IgG were decreased. Liberation of IgG from platelets was slower than that of [14C]serotonin but was decreased by release reaction inhibitors. Platelets treated at 2°C with soluble heat‐aggregated IgG, which binds to the Fc γ receptor, showed increased surface PA‐IgG, but, after incubation at 37°C, although [14C]serotonin was released, PA‐IgG levels were no longer increased.
Sickle cell anaemia among Eti‐Turks: haematological, clinical and genetic observations
Authors: Aluoch J. R. , Kilinç Y. , Aksoy M. , Yüregir G. T. , Bakioglu I. , Kutlar A. , Kutlar F. , Huisman T. H. J.
Published: March 2008

Summary. Haematological and genetic observations have been made on 71 SS Eti‐Turk patients and their relatives from Çukurova (southern Turkey) and of immigrant families in The Netherlands. Similar data were collected for 2 5 Black patients and their relatives from Surinam, Netherlands Antilles, and Kenya. Haematological and clinical results were the same for both groups; the haemolytic anaemia in the Turkish patients was as severe as in the others. Haplotyping, involving nine restriction sites, identified haplotype 19 (Antonar‐akis et al, 1984) as the major type among the Eti‐Turks; this chromosome has previously primarily been observed among SS patients from West Africa. The suggestion that the βS‐chromosome among Eti‐Turks originates from that area is supported by a relatively high incidence of α‐thalassaemia‐2 (the 3.7 kb deletion), also frequently present in the Black population of West Africa, and by the absence of other major haplotypes, such as types 20 and 3, characteristic for the βS‐chromosome in the population of Central Africa and Kenya, and in Senegal, respectively. The Saudi Arabian type of βS chromosome in association with the haplotype 19 βS chromosome was present in only one Eti‐Turk patient; this 30‐year‐old female was mildly affected and exhibited a high level of fetal haemoglobin.
Organization of the ζ‐α genes in Chinese
Authors: Chan Vivian , Chan T. K. , Cheng M. Y. , Kan Y. W. , Todd D.
Published: March 2008

Summary. Analysis of α and ζ genes in 101 healthy normals and hospitalized patients with non‐haematological diseases revealed a 3% incidence of α thalassaemia in the local Chinese population of Hong Kong. Triple α genes were found in only one person while triple ζ genes were more prevalent, occurring in 13 subjects. Studies of 28 unselected patients with Hb H disease indicated a predominance of the rightward χ gene deletion. The extent of α gene deletion in homozygous α thalassaemia 1 was at least 18.1 kb, beginning from the BamH I site 3’to the ζ1 gene and includes the Φα, α2 and α1 genes. Nineteen of the 20 chromosomes bearing the α thalassaemia 1 deletion had identical ζ‐intergenic hypervariable region suggesting a common origin of this mutation. The co‐inheritance of α thalassaemia in β thalassaemia subjects was 8%, but did not ameliorate the clinical features of those with homozygous β thalassaemia
Expression of two G‐6‐PD genes in an XX phenotypic male
Authors: Steinberg Martin H. , Gill Frances , Emanuel Beverly S.
Published: March 2008

Summary. The glucose‐6‐phosphate dehydrogenase (G‐6‐PD) gene is located on the X‐chromosome. Normal males have a single gene and produce a single G‐6‐PD type, while normal XX females may be heterozygotes for two different G‐6‐PD genes. We report the case of a phenotypic male who was found to be heterozygous for two G‐6‐PD enzymes. Cytogenetic analysis showed that he was a 46.XX male.
Recovery of immurioglobulin isotypes following T‐cell depleted allogeneic bone marrow transplantation
Authors: Brenner M. K. , Wimperis J. Z. , Reittie J. E. , Patterson J. , Asherson G. L. , Hoffbrand A. V. , Prentice H. G.
Published: March 2008

Summary. After conventional bone marrow transplantation serum IgG, IgM and IgA levels fall from pre‐transplant levels and may not return to normal for 3–12 months. In contrast IgE may rise to supranormal levels, an event that may be associated with graft‐versus‐host disease. We have investigated the recovery of immunoglobulin isotypes in the recipients of allogeneic marrows depleted of T‐cells to prevent graft‐versus‐host disease. We find that pre‐transplant IgG, IgM and IgA levels are maintained throughout the post‐transplant period but that there is a short‐lived rise in IgE about 3 weeks after transplantation: this rise occurs in the absence of clinically detectable graft‐versus‐host disease. We conclude that specific T‐cell depletion does not impair and may actually enhance the functional recovery of B cells after allogeneic BMT.
Effect of intensified chemotherapy on the pluripotent haematopoietic progenitor cells CFU‐GEMM in adult acute lymphoblastic leukaemia
Authors: Ganser A. , Hoelzer D.
Published: March 2008

Summary. In order to analyse the short‐term and long‐term effects of intensified induction chemotherapy, the frequency, cellular composition and proliferative state of the pluripotent haemopoietic progenitor cells CFU‐GEMM was investigated in a total of 35 patients with acute lymphoblastic or acute undifferen‐tiated leukaemia at diagnosis, as well as during and after therapy. At diagnosis, the number of CFU‐GEMM/ml bone marrow aspirate was significantly reduced to 12.1 (95% confidence interval 2.1–70) as compared to healthy controls (50.4/ml; 95% confidence interval 66–3846/ml). While immediately after the end of induction therapy, the respective values for CFU‐GEMM were still decreased (30.4/ml; 95% confidence interval 8.4–108); values not significantly different from normal were reached within the following 4 weeks. During and after cessation of maintenance therapy again no significant deviation from normal values was observed. Immunological analysis of single colonies revealed that during the early phase after remission induction only 60 ± 7% of mixed colonies contained megakaryocytic cells (normal 86 ± 3%; P<0.01) while normal values were found during and after maintenance therapy. Cell cycle analysis disclosed highly increased proliferative activity of pluripotent progenitor cells during marrow regeneration after induction therapy as well as during maintenance therapy, but a return to the resting state after cessation of maintenance therapy. It is concluded that this intensive chemotherapy regimen does not result in any apparent long‐term damage to the pluripotent haemopoietic progenitor cells.
Chronic lymphoid leukaemia and hairy cell leukaemia due to chronic exposure to benzene: report of three cases
Authors: Aksoy Muzaffer
Published: March 2008

Three cases of chronic leukaemia, two with chronic lymphoid and one with hairy cell leukaemia are reported. These three leukaemic patients belonged to a series of 58 leukaemic patients with chronic exposure to benzene. The low percentage of chronic leukaemias in this series is discussed.
Sensitive methods for determining subclasses of IgG anti‐A and anti‐B in sera of blood‐group‐O women with a blood‐group‐A or ‐B child
Authors: Brouwers H. A. A. , Overbeeke M. A. M. , Gemke R. J. B. J. , Maas C. J. , van Leeuwen E. F. , Engelfriet C. P.
Published: March 2008

The determination of the subclasses of IgG antibodies against blood groups A and B is important in order to improve our understanding and predict haemolytic disease of the newborn due to IgG anti‐A or ‐B. We describe two techniques that circumvent the problem of the agglutination of A and B red cells by the corresponding IgG antibodies in saline: an antiglobulin consumption test and a modified solid‐phase micro‐immunofluorescence test. The results of the two techniques are compared with the results obtained in the indirect antiglobulin test beyond the saline agglutination titre in a microplate technique. The solid‐phase micro‐immunofluorescence test was the most sensitive for the determination of the subclasses of IgG anti‐A and ‐B. Usually sera contained IgG2 anti‐A, B in a higher titre than antibodies of other subclasses.
A myeloproliferative disease in two infants associated with eosinophilia and chromosome t(1;5) translocation
Authors: Darbyshire P. J. , Shortland D. , Swansbury G. J. , Sadler J. , Lawler S. D. , Chessells J. M.
Published: March 2008

Two children are described who presented at the age of 5 and 7 months with anaemia, a high white cell count with eosinophilia and thrombocytopenia. Both children had an identical balanced translocation t(1;5)(q23;q33) and no evidence of a constitutional abnormality. The response to treatment of one child was poor, the other remains well on therapy. This translocation has not been previously reported and is likely to represent a subclass of myeloproliferative disorder analogous to the monosomy 7 syndrome, although less common. The previous literature of acquired chromosome abnormalities involving chromosomes 1 and 5 is reviewed.
Response to therapy in 37 patients with HIV‐related thrombocytopenic purpura
Authors: Oksenhendler Eric , Bierling Philippe , Farcet Jean‐Pierre , Rabian Claire , Seligmann Maxime , Clauvel Jean‐Pierre
Published: March 2008

Thirty‐seven patients belonging to the major AIDS‐risk groups and with serum antibodies to the human immunodeficiency virus (HIV), were evaluated and treated between 1983 and 1986 because of profound chronic thrombocytopenia with clinical bleeding. Fifteen out of 26 patients achieved a significant response while on prednisone therapy. Six of them sustained their platelet count above 50 × 109/1 following cessation of steroids. High dose intravenous immunoglobulin therapy gave a satisfactory initial response rate in 12 of 17 patients. Only two of 18 patients responded to danazol. Splenectomy was successful in 10 of 14 patients.
Relationship between platelet aggregating factor and von Willebrand factor in thrombotic thrombocytopenic purpura
Authors: Murphy William G. , Moore Jane C. , Barr Ronald D. , Pai Mohan K. R. , Kelton John G.
Published: March 2008

The pathophysiology of the platelet thrombotic disorder, thrombotic thrombocytopenic purpura (TTP), is not well understood. Two apparently unrelated laboratory abnormalities have recently been described in patients with TTP: a platelet aggregating factor and abnormalities in von Willebrand factor (vWF). Although an interaction between these two abnormalities has been postulated to participate in the disease, this has not been proved. In this report we describe studies on a patient with relapsing TTP. These studies demonstrate that a consistent relationship exists between the platelet aggregating factor present in the patient's serum and vWF. The patient had chronic low‐grade thrombocytopenic and schistocytic haemolytic anaemia that could be temporarily cured by infusions of plasma and certain other blood products. During acute exacerbations of the illness, a platelet aggregating factor was detectable in the patient's serum and this was associated with the loss of the larger multimers of vWF. During remissions of the illness, abnormally large multimers of vWF were present. The results of this study support the concept that a platelet aggregating factor plus large multimers of vWF participate in the acute platelet thrombi that characterize TTP.
Characterization of a new α° thalassaemia defect in the South African population
Authors: Vandenplas S. , Higgs D. R. , Nicholls R. D. , Bester A. J. , Mathew C. G. P.
Published: March 2008

A new a thalassaemia defect has been detected in the South African population. Restriction mapping of the α globin gene cluster in affected individuals has established that the defect is associated with the removal of 22·8·23·7 kb of DNA, including the pSα1, pSα1, pSα2, α2, and α1 globin genes. The 5’endpoint of the deletion has been localized between the 2 and pSα1 globin genes, and the 3’endpoint lies 4–5 kb 3’to the α1 globin gene. We have called the deletion ––SA in order to distinguish it from α° thalassaemia defects described in other populations.
The haematology of steady state homozygous sickle cell disease: interrelationships between haematological indices
Authors: Maude G. H. , Hayes R. J. , Serjeant G. R.
Published: March 2008

Summary. The interrelationships between steady state haematological variables in 825 patients with homozygous sickle cell (SS) disease have been examined. On simple correlation coefficient analysis HbA2 correlated negatively with both HbF and MCV, red cell count (RBC) correlated positively with total haemoglobin and negatively with MCV and reticulocytes, and MCV correlated positively with reticulocytes. Less consistent were positive correlations between HbA, and RBC, between HbF and both MCV and haemoglobin, between MCHC and MCV, and a negative relationship between haemoglobin and reticulocyte count. Partial correlation coefficient analysis clarified some of these relationships. In principal component analysis, the first component weighted positively on Hb and RBC and negatively on reticulocytes and possibly reflected the haemolytic rate. The second component weighted positively on HbF and MCV and negatively on HbA2 and may be related to alpha thalassaemia status. The third component weighted almost exclusively on MCHC and may relate to the degree of intracellular polymerization of HbS. These three components accounted for approximately 75% of the total variation in the haematological data.
Antiglobulin serum mediated phagocytosis of normal senescent and oxidized RBC: role of anti‐IgM immunoglobulins in phagocytic recognition
Authors: Leb L. , Snyder L. M. , Fortier N. L. , Andersen M.
Published: March 2008

Summary. Fresh human monocytes usually do not recognize normal RBCs: however, in our newly developed assay antiglobulin‐opsonized normal RBCs were phagocytized. Both anti‐IgG and anti‐IgM fractions present in the antiglobulin serum were involved but the major opsonin was anti‐IgM. The anti‐IgM opsonized mainly senescent RBCs and therefore could be used to discriminate young from senescent RBCs. The antiglobulin serum and monospecific anti‐IgM increased opsonization of in vitro oxidized and desialylated RBCs, whereas trypsin‐treatment of RBCs decreased phagocytosis. The material removed by trypsin from the RBCs surface inhibited the antiglobulin and monospecific anti‐IgM phagocytic assay supporting the view that membrane associated elements crossreacted with anti‐IgM. These results suggest that both internal cellular events and external removal of sialic acid play a role in the emergence of non‐IgG covered epitopes on the surface of senescent and oxidized erythrocytes.
Erythroid and myeloid maturation patterns related to progenitor assessment in the myelodysplastic syndromes
Authors: Dörmer P. , Schalhorn A. , Wilmanns W. , Hershko C.
Published: March 2008

Summary. Patterns of erythropoiesis and granulopoiesis were studied in 15 patients with myelodysplastic syndromes and in one with smouldering leukaemia by correlating CFU‐C, BFU‐E and CFU‐E cloning efficiency with erythroid and myeloid maturation indices derived from quantitative 14C‐autoradiography and with ferrokinetics. Maturation index of a cell lineage was defined as the ratio of cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. The myeloid maturation index was reduced in all cases, but CFU‐C progenitor frequency was increased by a factor of 3. Erythroid maturation index was also reduced in most cases, and BFU‐E progenitor frequency was reduced by a factor of 2. Similarly, CFU‐E cloning efficiency corrected for the erythroid maturation index was 2.5–10‐fold lower than normal. Comparison of the erythroid maturation index with ferrokinetics revealed a constant ratio of ineffective erythropoiesis with a maturation disturbance in the proliferative pool twice that in the non‐proliferative pool.

These findings indicate basic qualitative and quantitative abnormalities and a difference in the patterns of production of erythroid and myeloid cells in the myelodysplastic syndromes: Myeloid progenitors are increased in number but their maturation is grossly abnormal. On the other hand, the apparent reduction in erythroid progenitors and the reduced erythroid maturation index are attributable to both premature cell death of the more mature erythroblasts and an increased proerythroblast proliferation, i.e. extra divisions in the proerythroblast compartment at the expense of maturation.
Bone marrow transplantation in patients with leukaemia previously transfused with blood products from family members
Authors: Ho Winston G. , Champlin Richard E. , Winston Drew J. , Feig Stephen A. , Gale Robert Peter
Published: March 2008

Summary. Transfusions are withheld, whenever possible, from patients with aplastic anaemia who are potential bone marrow transplant recipients because of the increased risk of graft failure associated with transfusions prior to transplantation. Family members are specifically excluded as blood product donors to reduce the likelihood of sensitizing the recipient to antigens shared by the blood and bone marrow donor. This policy of not using family members, particularly the HLA‐matched bone marrow donor, to provide blood products prior to transplantation has been extended to leukaemia as well.

To evaluate this policy we reviewed the outcome of bone marrow transplantation in 18 patients with leukaemia transfused prior to transplantation with platelets and/or leucocytes from related family members. In 15 cases in which the outcome could be evaluated, engraftment was rapid and graft failure did not occur. Transfusion of blood products from related family members to patients with leukaemia prior to transplantation does not appear, therefore, to increase the risk of graft rejection.
An in vitro model for the study of acute release of von Willebrand factor from human endothelial cells
Authors: Booth F. , Allington M. J. , Cederholm‐Williams S. A.
Published: March 2008

Summary. An in vitro model is described which utilizes human umbilical vein endothelial cells cultured on plastic microcarrier spheres and perfused with serum‐free medium. This model was used to study the acute release of von Willebrand factor following stimulation of the cells with putative agonists. Thrombin, plasmin and interleukin‐1 were found to release von Willebrand factor. Adrenaline and bradykinin also stimulated release but only at high dosage. 1‐desamino‐8‐d‐arginine vasopressin (DDAVP) was inactive.
Evaluation of splenectomy in large granular lymphocyte leukaemia
Authors: Loughran Thomas P. , Starkebaum Gordon , Clark Eoward , Wallace Paul , Kadin Marshall E.
Published: March 2008

We performed splenectomy in four patients with severe neutropenia (<0.5 × 109/1), recurrent infections, and splenomegaly associated with large granular lymphocyte leukaemia. Prior to splenectomy, elevated levels of neutrophil‐reactive IgG were detected in sera of all three patients tested. In all patients, enlargement of the spleen was due to a characteristic lymphoid infiltration of red pulp cords. Splenectomy resulted in an increased neutrophil count >0.5 × 109/l in all patients; this response was sustained in two patients who benefited clinically by a dramatic reduction in frequency of infections. Poor clinical response was associated with elevated levels of antineutrophil antibody post‐splenectomy. All four patients had an increase in number of circulating large granular lymphocytes post‐splenectomy; one patient who had attained a sustained neutrophil response died of an accelerated lymphoproliferative disorder 19 months post‐splenectomy. We conclude that splenectomy may be of value in correcting severe neutropenia and reducing infections in some patients with large granular lymphocyte leukaemia. However, splenectomy appeared to be of no value in treatment of the underlying lymphoproliferative disorder.
Mechanisms and prognostic value of cell kinetics in the myelodysplastic syndromes
Authors: Dörmer P. , Hershko C. , Wilmanns W.
Published: March 2008

Cell kinetics were studied by quantitative autoradiography in 29 patients with myelodysplastic syndromes (MDS) and in four with smouldering leukaemia (SML) in a prospective 6–year study. Cellular turnover in all FAB groups was characterized by reduced labelling index and prolonged DNA synthesis time indicating reduced proliferative activity. Two more parameters were derived from the measurements. (1) The relative cell production rate, which is increased in proerythroblasts and myeloblasts in most cases. This could be attributed to an increased number of divisions in early recognizable precursors in the absence of maturation, and (or) an increased influx from the progenitor compartments. (2) The maturation index of a cell lineage was determined by the ratio of relative cell production rate increase from the first to the last proliferative compartment over the corresponding normal value. It showed a high degree of abnormality in all FAB subgroups, indicating premature cell death in the bone marrow. None of the kinetic parameters proved to be of value in predicting the evolution of leukaemia. In contrast, an excellent correlation was found between the myeloid maturation index and survival (P<0.0001). No correlation, however, was found between survival and the erythroid maturation index, which was relatively normal in the worst prognostic group. These findings indicate that althoughin vitrocell kinetic studies can not predict the evolution of overt leukaemia, the myeloid maturation index is a useful predictor of survival in patients with MDS and SMI.
Quinine‐ and quinidine platelet antibodies can react with GPIIb/IIIa
Authors: Christie Douglas J. , Mullen Patrick C. , Aster Richard H.
Published: March 2008

Quinine‐ and quinidine‐dependent antiplatelet antibodies are generally believed to bind to the membrane glycoprotein complex, GPIb/IX. However, we and others have found that some drug‐dependent antibodies bind to platelets from patients with the Bernard‐Soulier syndrome which lack these glycoproteins. We therefore studied the reactions of a group of these antibodies with normal and Bernard‐Soulier platelets and their membrane proteins.

As indicated by rosette formation of the sensitized platelets around protein A‐Sepharose beads, two quinine‐ and two quinidine‐dependent antibodies reacted with both normal and Bernard‐Soulier syndrome platelets at a high (300 μM) concentration of drug. At a pharmacologic drug concentration (10 μM), all four antibodies reacted with normal platelets, but only the two quinine‐induced antibodies reacted with Bernard‐Soulier platelets.

Immunoprecipitation studies with solubilized, tritiumlabelled normal platelets, at both high and low drug concentrations, showed that each of the four antibodies precipitated proteins corresponding to GPIb and GPIX. Fainter bands corresponding to glycoproteins IIb and IIIa, which do not label well with tritium, were also detected. With radioiodinated normal platelets, it was found that each of the four antibodies was capable of precipitating GPIIb/IIIa, but only in the presence of drug.

The four antibodies also promoted drug‐dependent precipitation of GPIIb and GPIIIa from lysates of radioiodinated Bernard‐Soulier platelets. The two quinine‐dependent antibodies precipitated these glycoproteins at both high and low drug concentrations, while the quinidine‐dependent antibodies reacted much more strongly at the higher drug concentration. Precipitation of GPIb/IX was not observed with BSS platelets.

Absorption of a quinine‐induced antibody with Bernard‐Soulier platelets in the presence of drug eliminated its ability to precipitate GPIIb and GPIIIa. However, the absorbed antibody retained the ability to precipitate GPIb from solubilized normal platelets. Thus, at least two drug‐dependent antibodies were present, one specific for GPIb/IX and the other for GPIIb/IIIa.

These findings indicate that glycoproteins IIb and/or IIIa, in addition to the GPIb/IX complex, can serve as targets for drug‐dependent antibodies in both intact and detergent‐solubilized platelet preparations.
Dose—effect relationship between smoking and blood rheology
Authors: Ernst E. , Matria A. , Schmölzl Ch. , Magyarosy I.
Published: March 2008

Summary. Five groups of male blood donors were investigated. The first group had never smoked, the second were ex‐smokers, the third smoked between 10 and 20 cigarettes per day, the fourth between 21 and 40. and the fifth more than that. Haematocrit, white cell count, plasma and native blood viscosity, blood cell filterability and aggregation, plasma colloid oncotic pressure as well as fibrinogen were measured. Results show that smoking is associated with a progressive significant deterioration of the above haemorheologic variables. These changes are interpreted as an absolute and a relative polycythaemia possibly in conjunction with a chronic inflammatory process. It is concluded that smoking induces a dose‐related increase in viscosity of blood among young men which is reversible by abstention.
Gerbich reactivity in 4.1(—) hereditary elliptocytosis and protein 4.1 level in blood group Gerbich deficiency
Authors: Sondag Danièle , Alloisio Nicole , Blanchard Dominique , Ducluzeau Marie‐Thérèse , Colonna Pierre , Bachir Dora , Bloy Christian , Cartron Jean‐Pierre , Delaunay Jean
Published: March 2008

The membrane polypeptide composition and the blood group Gerbich phenotype of red cells from 4.1(–) hereditary elliptocytic patients and from Gerbich‐negative donors, who display two unrelated genetic abnormalities, were compared. In homozygous 4.1(–) hereditary elliptocytosis where the primary defect was presumably the absence of the membrane skeletal protein 4.1, there was approximatively a 70% reduction in the minor sialoglycoproteins β and γ. This was associated with a severe reduction of blood group Gerbich reactivity as determined with both murine monoclonal and human anti‐Gerbich antibodies. In the heterozygous state in the presence of one haploid set of protein 4.1 gene there was only a modest decrease in glycoproteins β and γ and the Gerbich serological reactivity was within normal limits.

In homozygous Gerbich‐negative red cells which lack glycoproteins β and γ but do not display elliptocytic red cells, the levels of protein 4.1 was repeatedly found within or just below the lowest values of normal controls. In the heterozygous Gerbich‐negative conditions, glycoproteins β and γ were present in reduced amounts but the blood group Gerbich reactivity fell within normal limits since the anti‐Gerbich reagents used were unable to detect a dosage effect. The amount of protein 4.1 was normal.

These results add further support to the view that protein 4.1 and the sialoglycoproteins β and γ are physically linked in vivo which in some way serve to maintain red cell shape and integrity. Of interest was the finding that absence of protein 4.1 had a greater influence on the level of membrane glycoproteins β and γ than did the absence of β and γ glycoproteins on band 4.1.
Anti‐granulocyte opsonic activity in sera from patients with systemic lupus erythematosus
Authors: Hadley A. G. , Byron M. A. , Chapel H. M. , Bunch C. , Holburn A. M.
Published: March 2008

Neutropenia is common in patients with systemic lupus erythematosus (SLE) but mechanisms of cell depletion remain obscure. To investigate the possible autoimmune aetiology of neutropenia in SLE, sera from 31 patients with this disorder were tested for anti‐granulocyte activity. Granulocyte‐binding immunoglobulins were detected by indirect immunofluorescence, and the ability of patient sera to opsonize granulocytes was determined by measuring the chemiluminescent response of human monocytes to granulocytes sensitized by test sera.

Sera from 22 of the 31 patients bound IgG to granulocyte cell membranes and/or to nuclei, but only membrane‐binding antibodies opsonized the cells for recognition by monocytes. There was no correlation between neutrophil count and the level of granulocyte‐binding IgG as measured by indirect immunofluorescence. In contrast, opsonic activity and neutrophil count were inversely correlated (r= 0·5; P < 0·05). However, opsonic activity was present in sera from most non‐neutropenic patients. In patients with SLE, impaired reticuloendothelial system function may allow sensitized granulocytes to remain in the circulation.
Platelet acquired defect in PDGF and β thromboglobulin content in hairy cell leukaemia: improvement after interferon therapy
Authors: Dupuy E. , Sigaux F. , Bryckaert M. C. , Tobelem G. , Castaigne S. , Flandrin G. , Degos L. , Caen J. P.
Published: March 2008

To investigate the platelet contribution to the development of myelofibrosis in hairy cell leukaemia (HCL), we have studied two platelet α granule components in 15 patients with HCL before chemotherapy: mitogenic activity was measured by 1H thymidine incorporation in BALB/C 3T3 cells and β thromboglobulin (βTG) assayed by radioimmunoassay (RIA). Platelet mitogenic activity and βG content were significantly decreased in the patients as compared to the control subjects. The nine patients who were treated with recombinant human interferon (IFNαA) were restudied after 4 months of therapy. The levels of both mitogenic activity and βG platelet content were significantly increased after IFNα‐treatment with a complete response in five of the nine treated patients, a partial response in two and no response in the two others. HCL seemed therefore to be responsible for an acquired platelet α granule defect. As in the grey platelet syndrome a relationship between this abnormal platelet granule storage and the development of myelofibrosis is suggested in HCL.
Risk factors for acute graft‐versus‐host disease
Authors: Gale Robert Peter , Bortin Mortimer M. , van Bekkum Dirk W. , Biggs James C. , Dicke Karel A. , Gluckman Eliane , Good Robert A. , Hoffmann Raymond G. , Kay Humphrey E. M. , Kersey John H. , Marmont Alberto , Masaoka Tohru , Rimm Alfred A. , van Rood Jon J. , Zwaan Ferdinand E.
Published: March 2008

Summary. Acute graft‐versus‐host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA‐identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2‐year actuarial probability was 54% (95% confidence interval 52–56%) for absent or mild and 46% (44–48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex‐match (female→male greater than others, relative risk 2.0, P<0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P<0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P<0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female→male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P<0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.
Normal membrane function of abnormal β‐related erythrocyte sialoglycoproteins
Authors: Reid M. E. , Anstee D. J. , Jensen R. H. , Mohandas Narla
Published: March 2008

Summary. Red cells totally deficient in β and γ sialoglycoproteins (the Leach type of Gerbich‐negative) are elliptocytic and have altered membrane physical properties as evidenced by marked decreases in both membrane mechanical stability and membrane deformability. Red cells from individuals who are of the Gerbich and Yus phenotypes of Gerbich‐negative are also deficient in β and γ sialoglycoproteins, but possess abnormal β‐related sialoglycoproteins. In order to determine if these β‐related sialoglycoproteins can functionally substitute for normal sialoglycoproteins, we measured membrane deformability and stability of red cells of the Gerbich and Yus phenotypes. In contrast to the red cells of the Leach phenotype, cells of Gerbich and Yus phenotypes were found to have normal membrane deformability and stability. Moreover, flow cytometric analysis using a monoclonal anti‐β antibody revealed that the Gerbich and Yus phenotype red cells expressed the β‐related sialoglycoprotein to the same extent as its normal counterpart on normal cells. Based on these data, we suggest that the abnormal β‐related sialoglycoproteins can functionally substitute for normal β and γ sialoglycoproteins.
Red cell 3‐phosphoglycerate level as a diagnostic aid in pyruvate kinase deficiency
Authors: Lestas A. N. , Kay L. A. , Bellingham A. J.
Published: March 2008

Summary. A case of pyruvate kinase (PK) deficiency is described in which the diagnosis was aided by measurement of the 3‐phosphoglycerate (3PG) concentration. Review of the literature on the levels of red cell metabolites in 52 families with PK deficiency confirmed that a rise in 3PG is a valuable indicator of a functional deficiency of PK. Estimation of 3PG is relatively easy (and accurate). Furthermore, reticulocytosis, which sometimes makes the diagnosis of PK deficiency more difficult, has minimal effect on the level of 3PG in comparison with all other glycolytic intermediates or PK activity.
Immunohistochemical determination of growth fractions in human permanent cell lines and lymphoid tumours: a critical comparison of the monoclonal antibodies OKT9 and Ki‐67
Authors: Pileri Stefano , Gerdes Johannes , Rivano Maria , Tazzari Pier Luigi , Magnani Monica , Gobbi Marco , Stein Harald
Published: March 2008

OKT9 and Ki‐67 monoclonal antibodies have recently been proposed as useful tools for evaluating the growth fraction in malignant tumours, with special reference to non‐1 Hodgkin's lymphomas. In particular, while the former is commonly thought to detect a transferrin receptor present on the cytoplasmic membrane of proliferating cells, the latter recognizes a nuclear antigen, which is expressed in Gl, S, G2 and M phase of continuously cycling elements.

To further verify their reliability. OKT9 and Ki‐67 were applied to seven permanent cell lines (four myeloid and three B‐lymphoblastoid) and 100 lymphoid tumours (70 non‐Hodgkin's and 30 Hodgkin's lymphomas) phenotypically characterized on frozen sections.

The results obtained showed that OKT9 and Ki‐67 cannot be employed as equivalent means in assessing the growth fraction. In fact, OKT9 is directed to a transferrin receptor which is not only expressed by proliferating cells, but also by some resting elements. On the other hand. Ki‐67 provides a nuclear, easily detectable positivity which is restricted to proliferating cells only. Therefore, it seems to represent the only monoclonal which can confidently be employed in the assessment of the growth fraction.

Furthermore, the present study underlines that the immunocytochemical analysis of the proliferation rate in tumours gives similar information to the radionucleide uptake assay, while it represents a more sensitive method than the cytofluorimetric evaluation of the DNA content.
Superoxide dismutase, glutathione peroxidase and catalase in the red cells of patients with malignant lymphoma
Authors: Bewick M. , Coutie W. , Tudhope G. R.
Published: March 2008

Erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities have been measured in patients with untreated malignant lymphomas. Marked deficiencies of superoxide dismutase (P<0.001) and glutathione peroxidase (P<0.001) were found, whereas catalase levels were normal. There was no apparent difference in enzyme activities between the different histological types of lymphoma.