bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary stomatocytosis: phenotypical expression of sodium transport and band 7 peptides in 44 cases
Authors: And A. Kanzaki , Yawata Y. 
Published: March 2008

Summary The clinical heterogeneity and the role of red cell membrane protein band 7 in membrane transport were studied in 44 patients with hereditary stomatocytosis with normal red cell membrane lipids. These patients were arbitrarily categorized into three phenotypes, based on the extent of sodium influx: hereditary stomatocytosis Type I: with markedly increased Na influx (8.90±3.39 mmol/lRBC/h); Type II: with moderately increased Na influx (2.10±0.79) and Type III with normal Na influx (1.31±0.13). The three groups of patients were compared with normal controls (1.29±0.14). The extent of anaemia and jaundice was almost identical in the three groups in the presence of nearly the same degree of stomatocytosis (I: 54.8±10.7%, II: 38.8±12.8, and III: 40.2±10.8). Approximately one third of the cases (14/44) with hereditary stomatocytosis showed no overt haemolysis even with marked stomatocytosis. Cell hydration was abnormal in Type I (MCV 119.6±8.5 fl, MCHC 29.3±1.8%) but normal in Types II and III (MCV 98.2±11.7, 94.1±8.5; MCHC 34.4 ± 2.1, 34.5 ± 2.2). These results indicate that there was no correlation between the extent of Na influx and either the degree of stomatocytosis or the extent of overt haemolysis.The role of band 7 in membrane transport was also studied. Three components (30 kD, 28 kD and 26 kD polypeptides) of band 7 were analysed by SDS‐PAGE and NEPHGE/SDS‐PAGE, and the content of these polypeptides were expressed as the ratio to band 5. The 30 kDa polypeptide in the three groups was nearly identical to that in normal controls (12.3 ±4.0), except for non‐haemolysing patients in Type II. The 28 kD peptide was also decreased in five out of nine cases of Type II (25.7 ± 5.6) as compared with normal controls (32.9 ± 3.6) and cases of Type I (35.8±2.8) and Type III (32 ± 7 ± 2.9). No deficiency of this peptide was noted in Type I patients. No correlation was observed between the content of the 28 kD polypeptide and Na influx (r=0.416), but the 26 kD polypeptide tended to be elevated in cases with overt haemolysis. These results suggest that band 7 may not be essentially involved in the formation of stomatocytic changes, although the presence of subtle defects in band 7 structure and function may not be ruled out. The present findings provide an important starting point to initiate further extensive investigations.
Antibodies to plasma proteins: an association with platelet transfusion refractoriness
Authors: Heal J. M. , Cowles J. , Masel D. , Rowe J. M. , Blumberg N. 
Published: March 2008

Summary. We hypothesized that antibodies to HLA‐linked polymorphic plasma proteins could be involved in platelet refractoriness by an‘innocent bystander’or immune complex mechanism. Employing a kinetic enzyme‐linked immunosorbant assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti‐plasma protein antibody could be eluted from platelets of refractory patients.The development of anti‐plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion > 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.
Inhibition of thrombin generation by heparin and low molecular weight (LMW) heparins in the absence and presence of platelet factor 4 (PF4)
Authors: Padilla Ana , Gray Elaine , Pepper Duncan S. , Barrowcliffe Trevor W. 
Published: March 2008

Summary. The ability of several low molecular weight (LMW) heparins and unfractionated heparin (UFH) to inhibit thrombin generation, and their anti‐Xa and anti‐IIa activities, were measured in the absence and presence of platelet factor 4 (PF4).The LMW heparins studied were 2–5 times less potent, on a weight basis, than UFH as inhibitors of thrombin generation in platelet‐poor plasma: the inhibition of thrombin generation by LMW heparins correlated better with their anti‐IIa activity (r= 0–98) than with their anti‐Xa activity (r= 0–69). At low concentrations of PF4. the activity of LMW heparins in the thrombin generation test was neutralized less than that of UFH. but at higher PF4 concentrations all their activities could be neutralized except in anti‐Xa assays.These observations support the hypothesis that anti‐IIa activity is important for inhibition of thrombin generation by LMW heparins in vitro. However, when all the anti‐IIa activity of LMW heparins was neutralized by PF4. considerable inhibitory activity remained in thrombin generation and anti‐Xa assays, indicating that a portion of the anti‐Xa activity of LMW heparins also contributes towards inhibition of thrombin generation.
Mechanisms of inhibition of T cell IL‐2 secretion by factor VIII concentrates
Authors: Wadhwa Meenu , Dilger Paula , Tubbs Jill , Barrowcliffe Trevor , Mahon Bernard , Thorpe Robin 
Published: March 2008

Summary. We have continued our previous study of the inhibitory effects of factor VIII concentrates on IL‐2 secretion by T cells. Experiments with an extended range of products confirm our previous conclusion that some but not all low, intermediate and high purity concentrates possess inhibitory activity on IL‐2 secretion. The inhibition occurs almost immediately after addition of factor VIII concentrate and it was not possible to adsorb inhibitory activity with activated or non‐activated cells; this suggests that the mechanism of inhibition involves interference with early T cell activation events rather than simple blocking of cell surface components by inhibitory molecules.The inhibitory components were shown to reside in different molecular weight fractions of concentrates. A strongly inhibitory component of approximately 200 kD and a minor species of approximately 60 kD were identified in strongly inhibitory concentrates. Some products contained a dialysable inhibitory substance which is most likely a salt as it was also present in some formulation buffers. The proportions of the inhibitory components varied widely between products.We have found that the pattern of inhibition using in vitro systems reflects that observed using a mouse in vivo antigen challenge method. In addition we have shown that the previously reported concentrate mediated inhibition of lectin induced low affinity IL‐2 receptor (CD25) is mainly a consequence of diminished IL‐2 secretion rather than a ‘direct’ effect on CD2 5 expression.Considering the wide variation between products of the same purity group, caution should be exercised in drawing conclusions concerning the immunosuppressive effects of a particular type of concentrate in haemophilia patients from study with only one product from that group.
Book Reviews
Authors: Roberts B. E. , van den Berghe H. 
Published: March 2008

Advances in Chronic Lymphocytic Leukaemia: Proceedings from the 5th International Workshop on Chronic Lymphocytic Leukaemia, Sitges (Barcelona), Spain, April 1991. Edited by Aaron Polliack and Emilio Montserrat The Leukaemic Cell, 2nd edn. Edited by D. Catovsky
Lymphoid subsets and prognostic factors in multiple myeloma
Authors: Miguel J. F. San , González M. , Gascón A. , Moro J. , Hernández J. M. , Ortega F. , Jiménez R. , Guerras L. , Romero M. , Casanova F. , Sanz M.A , Sanchez J. , Portero and J.A. , Orfao A. 
Published: March 2008

Summary.In a uniform series of 170 untreated myeloma patients (MM) we investigated the distribution of T cell subsets in peripheral blood (PB) and their relationship with the most relevant disease characteristics, including survival. CD4 cells were significantly decreased both in percentage and absolute numbers (P< 0.0001). On the other hand, the CD8 cells only showed a slight increase in relative numbers. Upon correlating the abnormalities in the distribution of T cells with other clinical and biological disease characteristics the most remarkable correlation was with survival. A low number of CD4 cells (< 700 × 106/1) was associated with both an advanced clinical stage and a shorter survival (20 v. 43 months,P= 0.01). Moreover, a significant correlation also exists between the decrease in CD4 cells and both high β2‐microglobulin (β2M) levels and anaemia. On the other hand, no relationship was found with the type of M‐component nor with the plasma cell phenotype. Finally multivariate analysis showed that the number of CD4 cells add independent prognostic information to other well‐established tests for the assessment of disease outcome in patients with multiple myeloma.
A new lupus anticoagulant neutralization test based on platelet‐derived vesicles
Authors: Arnout Jef , Huybrechts Erwin , Vanrusselt Marleen , Vermylen Jos 
Published: March 2008

Summary.We here present an easily standardizable and reproducible procedure which clearly separates lupus anticoagulants (LA) from coagulation factor inhibitors. This new LA neutralization test makes use of platelet‐derived micro‐vesicles which were prepared as follows: gel‐filtered platelets (4 × 105/μl) were incubated with 60 μM of the calcium ionophore A23187 for 20 min at 37°C. The vesicles were separated from the platelet aggregates by centrifugation at 1000 g for 10 min. The vesicle containing supernatant was then spun down at 15000 g for 15 min, lyophilized and stored at −20°C until used. The vesicles were resuspended in plasma from normal individuals, from patients with LA activity, from patients with factor VIII inhibitors, from patients with congenital factor deficiencies and from patients receiving oral anticoagulants or intravenous heparin. A kaolin clotting time was performed in the absence (KCT) or presence of these vesicles (KCTves) and the ratios of these times to their respective mean normal times were calculated. Segregation of LA patients from all remaining patients except heparinized ones could be made with a high degree of accuracy. A thrombin time was needed to separate LA from heparinized patients. The method was highly reproducible and only minor (negligible) differences in potencies were observed between different vesicle preparations. Both the intra‐batch and the inter‐batch coefficients of variations on the KCTves were lower than 6%.
Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy
Authors: Cuthbert R.J. G. , Ludlam C.A. , Steel C. M. , Beatson Dianne , Peutherer J. F. 
Published: March 2008

Summary.Immunological studies were performed on a group of 44 haemophilia A and 15 haemophilia B patients who were treated exclusively with blood products manufactured by the Scottish National Blood Transfusion Service (SNBTS). All patients were HIV seronegative throughout the study.Of the haemophilia A patients 14 (32%) had CD4 + lymphocyte subset counts ≤ 0.5 × 109/l, compared with one (6%) haemophilia B patient and four (8%) controls. The percentage of activated T cells was greater than 5% in 19/33 (57%) with haemophilia A, 5/9 (55%) haemophilia B and 14/50 (28%) of control subjects. β2 microglobulin values ≥2.0 mg/l were observed in 19 (43%) haemophilia A and four (26%) haemophilia B patients, compared with one (2%) control. No significant increases in serum interleukin‐2 receptor concentrations were observed in 15 haemophilia A and one haemophilia B patients. Significantly elevated levels of IgG, IgM and IgA were observed in the haemophilia A group, but elevation of immunoglobulins was restricted to the IgG class in the haemophilia B group. Of the haemophilia A patients 16/30 (53%) and 6/11 (54%) haemophilia B patients had depression of cell‐mediated immunity (CMI) as assessed by delayed‐type hypersensitivity responses to intra‐dermally injected recall antigens. There was no correlation between factor VIII or factor IX usage and changes in lymphocyte subsets, β2 microglobulin, and immunoglobulin levels. There was, however, a strong correlation between annual factor VIII usage and the degree of depression of CMI for those with haemophilia A but not for those with haemophilia B. No correlation between alterations in the immune parameters and disturbance of liver function tests was observed in either haemophilia A or haemophilia B patients.We conclude that alloantigen or non‐HIV viral exposure due to repeated administration of factor concentrates brings about alterations in the immune response, and that these changes are more marked following exposure to intermediate purity factor VIII compared with factor IX concentrate.
Identification of an extensive ζ‐α globin gene deletion in a Chinese individual
Authors: Waye John S. , Eng Barry , Chui David H. K. 
Published: March 2008

Summary.We describe a novel α‐thalassaemia‐1 deletion that removes the entire ζ‐α globin gene cluster. A Chinese couple were referred for counselling after two consecutive pregnancies ended with fetal hydrops. Gene mapping was used to demonstrate that the mother is heterozygous for the South‐east Asia α‐thalassaemia‐1 deletion (ζζα/ζζ—SEA), while the father carries an α‐thalassaemia‐1 deletion of more than 100 kilobases (ζζα/—). This newly discovered deletion extends for unknown distances 3’ and 5’ of the ζ‐α globin gene cluster and has been designated (—HW).
Short‐term study of chimaerism after bone marrow transplantation for severe aplastic anaemia
Authors: Socié G. , Landman J. , Gluckman E. , Devergie A. , Raynal B. , Esperou‐Bourdeau H. , Brison O. 
Published: March 2008

Summary.Chimaerism was studied early (2 weeks to 3 months) during haematopoietic reconstitution after bone marrow transplantation in 18 severe aplastic anaemia patients (acquired SAA: 14 patients; Fanconi anaemia: four patients). Fourteen patients received marrow from an identical sibling donor, one from the phenoidentical father and three from a matched unrelated donor. Peripheral blood cell DNA was first analysed by Southern blotting with a multilocus minisatellite probe (33.6.3) or a Y chromosome specific probe (pHY2.1). For all 14 patients grafted with a genotypically identical sibling donor, the post‐graft DNA profile strictly matched the respective donor profile (minisatellite probe) or disclosed the Y chromosome specific band in the case of female patients grafted with a male donor. In contrast, for the one patient grafted in a mismatched situation and for two out of three patients grafted with a matched unrelated donor, the results indicated autologous bone marrow recovery. This difference between patients grafted with an identical sibling donor and those grafted in other situations is statistically significant (P < 0.01). The 15 patients with circulating cells of donor origin were then studied by polymerase chain reaction amplification of the DNA samples. The three male patients with a female donor were studied by amplification of a Y chromosome specific sequence (DYZ1), allowing the detection of one male cell in 104 female cells. In all three cases, residual male nucleated celts were detected. The analysis was performed by amplification of the 33.6.3 minisatellite sequence for the 12 remaining patients. No residual recipient cells were detected within the sensitivity limit of the method which is 1% in that case. This suggests that detection of residual host cells depends on the sensitivity of the technique used.
Cytomorphology of childhood lymphoblastic leukaemia: a prospective study of 2000 patients
Authors: Lilleyman J. S. , Hann I. M. , Stevens R. F. , Richards S. M. , Eden O. B. , Chessells J. M. , Bailey C. C. 
Published: March 2008

Blast cell morphology of children with lymphoblastic leukaemia (ALL) entering two national multicentre trials was prospectively reviewed by three haematologists to define the clinical importance of (a) French–American–British (FAB) classification, (b) the presence of cytoplasmic vacuoles, and (c) the presence of ‘hand‐mirror’cells.Of 2135 evaluable children, 1907 (89%) had FAB L1 morphology and 228 (11%) L2. (L3 patients were not eligible for the trials in question). L2 patients more frequently had residual disease 14 d after starting treatment and had a significantly inferior disease‐free survival, but not if the analysis was stratified for age, sex and diagnostic white cell count (WBC), 627 (29%) had blast cells with cytoplasmic vacuoles, and showed a significant survival advantage over the remainder. Vacuoles were positively associated with a low WBC, age range 1–6 years and blast cell positivity for CD10, but their benign influence was apparent even when these variables were taken into account. ‘Hand‐mirror’(HM) cells were only studied in UKALL X, and were noted in 316/1402 (23%) children. There appeared to be an inverse correlation between HM cells and cytoplasmic vacuoles and a weak association with T‐cell immunophenotype, but no prognostic significance was evident.FAB classification appears to be of less prognostic importance than has previously been supposed, though L2 disease is more resistant to current remission induction regimens. Hand‐mirror cells may be more common in T‐ALL, but are seen in all types and are not related to prognosis. Cytoplasmic vacuoles are predictive of a good response to current therapeutic schedules even allowing for other prognostic variables, and are the single most important morphological feature relating to prognosis in childhood ALL.
Interferon‐α therapy during pregnancy in chronic myelogenous leukaemia and hairy cell leukaemia
Authors: Baer Maria R. , Ozer Howard , Foon Kenneth A. 
Published: March 2008

Summary.Interferon‐α is an effective agent in the treatment of chronic myelogenous leukaemia and hairy cell leukaemia. Because interferon‐α does not inhibit DNA synthesis, we have used it to treat these diseases during pregnancy. We report here two patients with chronic myelogenous leukaemia and two patients with hairy cell leukaemia managed with interferon‐α during pregnancy. Tnterferon‐α was well tolerated, and the pregnancies proceeded without complications. All four infants were apparently normal at birth, and all four have enjoyed normal growth and development. Interferon‐α may represent relatively safe therapy during pregnancy, because of its lack of inhibition of DNA synthesis. Nevertheless, recommendations regarding the use of interferon‐α to treat chronic leukaemias during pregnancy must await further experience with this agent in this setting.
A randomized study of intermediate versus conventional‐dose cytarabine as intensive induction for acute myelogenous leukaemia
Authors: Schiller Gary , Gajewski James , Nimer Stephen , Territo Mary , Ho Winston , Lee Myung , Champlin Richard 
Published: March 2008

Summary.The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100–200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara‐CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional‐dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate‐dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional‐dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate‐dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age >60 assigned to conventional‐dose cytarabine and 10/17 assigned to intermediate‐dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P=0.004). Actuarial 4‐year disease‐free survival for patients assigned to conventional‐dose cytarabine was 20.16% versus 28.17% for patients assigned to intermediate‐dose cytarabine (P=0–9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.
The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP)
Authors: Basso G. , Putti M. C. , Cantú‐Rajnoldi A. , Saitta M. , Santostasi T. , Santoro N. , Lippi A. , Comelli A. , Felici L. , Favre C. , Mancuso G. Russo , Guglielmi C. , Paolucci P. , Biondi A. , Rondelli R. , Pession A. 
Published: March 2008

Summary.A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1; 6–12 months: group 2; 13–18 months: group 3). There were three cases of T‐ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre‐B ALL in 15 patients (13.3%), pre‐pre‐B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%).In non‐T ALL, positivity to CD10 (corresponding to C‐ALL and pre‐B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre‐pre‐B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event‐free survival (EFS) by statistical analysis. A better outcome in CD10‐positive ALL than in CD01‐negative ones (48% v. 25% of long‐term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg‐negative than in MyAg‐positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10‐negative, MyAg‐positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.