bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA haplotype heterogeneity of β‐thalassaemia in Greece: feasibility of prenatal diagnosis
Authors: Athanassiadou A. , Zarkadis I. , Papahadjopoulou A. , Maniatis G. M. 
Published: July 2010

SummaryWe have carried out DNA haplotype analysis of 69 β‐thalassaemia patients in Greece and 42 of the parents using seven standard polymorphic sites. Our data show a high degree of heterogeneity of the chromosomal background in which β‐thalassaemia occurs in Greece, suggesting a high degree of heterogeneity in the β‐thalassaemia mutations involved. Haplotype I is found here to represent 45% of total β‐thalassaemia mutations detected, a proportion well below the 67% reported in earlier studies with Greek‐American patients. Nine different haplotypes are detected and the ones carrying β+ mutations are the majority, including those which are linked to β+ mutations associated with a thalassaemia intermedia phenotype, and which constitute 11% of all haplotypes. One of these haplotypes (—‐ + + +) has never before been reported to occur in non‐Africans, whether in βthal or βA chromosomes, and it is found here to be of African origin rather than the product of recombination. In 21 families haplotype analysis showed that prenatal diagnosis for a second child was feasible in 81% of the cases. Use of the AvaII‐Ψβ polymorphic site as well as the seven standard ones brought this proportion up to 90%.
Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance
Authors: Kumar S. , Haigh J. R. M. , Tate G. , Boothby M. , Joanes D. N. , Davies J. A. , Roberts B. E. , Feely M. P. 
Published: July 2010

SummaryThere is a discrepancy in the results of reported studies of levels of vitamin K dependent coagulation factors in patients on warfarin therapy. This may have arisen partly because of the problem of assuring compliance with therapy in outpatients. The plasma concentrations of the vitamin K dependent clotting factors II, VII, IX and X were studied in 23 outpatients whose adherence to prescribed warfarin therapy was determined using a pharmacological indicator of complicance. In these patients, who were shown to have consistently good compliance and stable anticoagulant control over a period of 3–6 months, the activities in plasma of the four coagulation factors were not equally suppressed. Factor IX levels were significantly greater than those of factor VII (P<0.0001) which in turn were significantly greater than the levels of factor II (P<0.0001) or factor X (P<0.0001). There was no significant difference between the levels of factors II and X which were depressed to a similar extent. The proportion of variability of the International Normalized Ratio (INR) explained by linear regression was 51–77% and a model was derived to predict the INR from the mean of the levels of the four clotting factors. The concentrations of the coagulation factors II, VII, IX and X are likely to be highly dependent on the degree of compliance with warfarin therapy which should be taken into account when investigating the behaviour of these factors.
Aprotinin reduces cardiopulmonary bypass‐induced blood loss and inhibits fibrinolysis without influencing platelets
Authors: Orchard M. A. , Goodchild C. S. , Prentice C. R. M. , Davies J. A. , Benoit S. E. , Creighton‐Kemsford L. J. , Gaffney P. J. , Michelson A. D. 
Published: July 2010

Summary. Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double‐blind study was carried out comparing aprotinin with placebo in patients undergoing re‐operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss.In the placebo treated group, significant increases were observed, during CPB, in the plasma concentrations of fibrinolytic activity, tissue plasminogen activator antigen. D‐dimer, and β‐thromboglobulin. Platelet counts fell within 5–10 min of the patients going onto CPB, but this could be accounted for by the dilutional effect of the extracorporeal circuit. Inhibition of responsiveness of platelets, as judged by aggregometry. was significant only at the end of bypass when collagen was the agonist and after protamine reversal when ristocetin was the agonist. CPB did not enhance the release, into the circulation, of glycocalicin (a proteolytic fragment of glycoprotein Ib).In the aprotinin‐treated group, the formation of fibrin degradation products as measured by D‐dimer was inhibited. However, aprotinin did not influence the change in platelet count, suppress β‐thromboglobulin release from platelets, prevent the inhibition of platelet function or influence the concentration of plasma glycocalicin during the study period.These observations confirm that CPB leads to a fibrinolytic state and less responsive platelets. This study also indicates that aprotinin‐induced reduction in blood loss is associated with inhibition of plasmin‐mediated fibrin digestion and that the mechanism by which aprotinin reduces blood loss is not via protection of platelets during CPB.
A novel two base pair deletion in the factor V gene associated with severe factor V deficiency
Authors: Montefusco Maria Claudia , Duga Stefano , Asselta Rosanna , Santagostino Elena , Mancuso Giacomo , Malcovati Massimo , Mannucci Pier Mannuccio , Tenchini Maria Luisa 
Published: July 2010

We studied a family in which the proband, a 13‐year‐old boy, had unmeasurable plasma levels of coagulation factor V antigen and activity. Clinical symptoms were severe, with several episodes of haemorrhages in the mucosal tracts (gastrointestinal, nose and urinary) and recurrent haemarthroses that caused permanent arthropathy. Sequence analysis of the factor V gene demonstrated the presence of a novel 2 base pair (bp) homozygous deletion in exon 13 at positions 2833–2834. This mutation, present in the heterozygous state in the asymptomatic mother and absent in the healthy brother, introduced a frameshift and a premature stop at codon 900. This would predict the synthesis of a truncated factor V molecule, lacking part of the B domain and the complete light chain. Because of the existence of a surveillance mechanism that selectively recognizes and degrades mRNA molecules carrying premature termination codons, we analysed the relative abundance of mutant vs. wild‐type mRNA molecules in the platelets of the heterozygous proband's mother. The mutant mRNA was significantly reduced in amount (mutant/wild‐type ratio 0·35). This is the first reported mutation in the factor V gene causing severe factor V deficiency, the effect of which was quantitatively analysed at mRNA level.
High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor‐acute lymphoblastic leukaemia
Authors: Troeger Anja , Gudowius Sonja , Escherich Gabriele , Den Boer Monique L. , Glouchkova Ludmila , Ackermann Birgit , Meisel Roland , Laws Hans‐Juergen , Groeger Marketa , Wessalowski Ruediger , Willers Reinhart , Harbott Jochen , Pieters Rob , Goebel Ulrich , Janka‐Schaub Gritta E. , Hanenberg Helmut , Dilloo Dagmar 
Published: July 2010

SummaryNerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti‐proliferative signals. In spite of its established role in B‐cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor‐acute lymphoblastic leukaemia (BCP‐ALL). p75NTR expression was prospectively studied on primary ALL‐blasts in a cohort of paediatric patients with common ALL (n = 86) and preB‐ALL (n = 34) treated within the Co‐operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06‐97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11–100%). In patients classified as low‐risk at diagnosis, p75NTR expression was significantly higher than in high‐risk patients (P = 0·001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0·038). Accordingly, relapse‐free survival was significantly better in patients expressing high surface p75NTR (P = 0·041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.
Genetic modifiers of the β‐haemoglobinopathies
Authors: Thein Swee Lay 
Published: July 2010

SummaryIdentification of the molecular basis of the β‐thalassaemias and sickle cell disease (SCD) has made it clear that patients with the same β‐globin genotypes can have very variable patterns of clinical expression. Extensive biochemical and pathophysiological studies over the last 50 years have derived two major modifiers – innate ability to produce fetal haemoglobin and co‐inheritance of α‐thalassaemia, subsequently validated by family and population studies. However, these two modifiers do not explain the full clinical spectrum. Genetic studies have been successful in identifying modifiers if the loci have a major clinical effect and if the genetic variants are common. It is possible that additional modifiers could be uncovered using genetic approaches but success will depend on large sample sizes of well‐characterised patients with well‐defined phenotypes. Since some of the complications, such as overt stroke in SCD, are relatively rare events, intermediate end‐points that contribute to the phenotype, such as Transcranial Doppler velocity (a major predictor of stroke in SCD), could be integrated within the genetic analysis. Integrating multiplex genetic testing with clinical and laboratory data to generate predictive models shows potential, but such genetic approaches also require large datasets.
Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis
Authors: FAMULARO G , PROCOPIO A , GIACOMELLI R , DANESE C , SACCHETTI S , PEREGO M A , SANTONI A , TONIETTI G 
Published: July 2010

SUMMARYWe studied the sera of patients with progressive systemic sclerosis (PSS) for elevated levels of soluble interleukin-2 receptor (sIL-2R), interleukin-2 (IL-2) and interleukin-4 (IL-4). We also measured IL-2, IL-4 and B cell growth factor (BCGF) activity in supernatants of peripheral blood mononuclear cells from the same patients. The finding of elevated serum sIL-2R and IL-2, and the increased levels of IL-2, IL-4 and BCGF activity in culture supernatants indicates that T lymphocyte hyperactivity likely play a major role in PSS. The failure to detect under our experimental conditions a direct proliferative effect of recombinant IL-2 on enriched normal B cells might suggest that IL-4 is the cytokine mainly responsible of the BCGF activity recovered in PSS supernatants.
Do infections induce monoclonal immunoglobulin components?
Authors: HAAS H , ANDERS S , BORNKAMM G W , MANNWEILER E , SCHMITZ H , RADL J , SCHLAAK M 
Published: July 2010

SUMMARYThe incidental finding of monoclonal immunoglobulin components (MC) in some infections prompted us to study this phenomenon more systematically. Using isoelectric focusing with immunoblotting (detection limit for MC 0.1 mg/ml), the following infections were studied for the presence of MC: visceral leishmaniasis, cytomegalovirus (CMV) infection, echinococcosis and infectious mononucleosis. MC were found in 16 of 20 leishmania patients and in eight of 18 CMV patients, but in only one of 20 echinococcosis patients and in none of 30 infectious mononucleosis patients. The MC were mostly transient, where tested. A minority of the MC found in the leishmaniasis patients was shown to bind to leishmania antigens. The specificity of the majority of the MC remains unknown. Further study is required to explain the high incidence of MC in CMV infection and visceral leishmaniasis.
Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis
Authors: FRAMPTON G , JAYNE D R W , PERRY G J , LOCKWOOD C M , CAMERON J S 
Published: July 2010

SUMMARY
The interaction of circulating autoantibodies with the endothelium may be an important mechanism in the pathogenesis of systemic vasculitis. In a prospective study, we looked for circulating anti-endothclial cell autoantibodies (AECA) and anti-neutrophil cytoplasm autoantibodies (ANCA) in 80 patients with suspected systemic vasculitis. AECA were measured using an isotype-specific cellular ELISA incorporating human umbilical vein endothelial cells. ANCA activity was determined by indirect immunofluorescence and radioimmunoassay. Sequential studies were performed on sera from four cases with dual positivity, where autoantibody binding was compared with von Willebrand factor (vWF) concentration and disease activity. IgG AECA were significantly higher in the 27 ANCA-positive sera as compared with normal controls (P= 0027) with IgG (P= 0 009) and IgA (P = 0046) AECA isotypes correlating with ANCA positivity; in contrast, no differences were found between AECA levels in the ANCA-negativc sera and the normal controls. Cross-inhibition studies pointed to the co-existencc of two autoantibody populations. An association between autoantibody binding, disease activity and vWF concentration was found for both ANCA and AECA. Some patients with systemic vasculitis have detectable AECA that recognize different epitopes to ANCA and like ANCA. their titre correlates with disease activity and thus they may have a pathogenetic role in these conditions.
Effect of macrophage-derived factor on hypoferraemia induced by Japanese encephalitis virus in mice
Authors: BHARADWAJ M , KHANNA N , MATHUR A , CHATURVEDI U C 
Published: July 2010

SUMMARYDepression of serum iron following Japanese encephalitis virus (JEV) infection was observed in mice. The hypoferraemia was associated with the accumulation of iron in reticulo-endothelial cells in the spleen. Splenectomy (compared with sham-operation) prevented the depression in serum iron concentration after JEV infection. It also prevented the rise in levels of liver iron. The effect of JEV-stimulaled. splenic macrophage-derived factor (MDF) was evaluated in causing hypoferraemia. MDF produced a rapid reduction in the serum iron levels with accumulation of iron in spleen. These observations suggest that MDF plays a key role in the regulation of iron metabolism during JEV infection.
Vascular damage in Wegener’s granulomatosis and microscopic polyarteritis: presence of anti-endothelial cell antibodies and their relation to anti-neutrophil cytoplasm antibodies
Authors: SAVAGE C O S , POTTINGER B E , GASKIN G , LOCKWOOD C M , PUSEY C D , PEARSON J D 
Published: July 2010

SUMMARYTo define mechanisms of vascular injury in Wegener’s granulomatosis and microscopic potyarteritis, anti-endothelial cell antibodies (AECA) were sought in serum from 168 patients, all of whom had anti-neutrophil cytoplasm antibodies (ANCA) detectable by indirect immunofluorescence. Using an ELISA with human umbilical vein endothelial cells (HUVEC), IgG AECA were demonstrated in 59% and IgM AECA in 68% of patients. Pretreatment of HUVEC with tumour necrosis factor (TNF). IL-1 or interferon-gamma (IFN-γ) led to increased binding. Adsorption of AECA/ANCA-containing serum with HUVEC or neutrophils demonstrated that AECA and ANCA recognized different targets, von Willebrand factor (vWf) antigen levels in the patient samples were markedly elevated, with a mean of 3-10+ 1-89 U/ml (control population mean 1-04 + 0-36 U/ml). suggesting widespread endothelial cell damage. Studies using an’ In-labelled HUVEC release assay with 29 AECA-containing sera did not demonstrate complement-mediated cytotoxicity. even following activation of HUVEC with TNF. Four out of 16 AECA-containing sera tested showed antibody-dependent cellular cytotoxicity with unfractionated peripheral blood mononuclear cells. These data suggest that patients with Wegener’s granulomatosis or microscopic polyarteritis can develop AECA to constitutively expressed but cytokine modulated determinants on HUVEC. These antibodies do not appear to support complement-mediated cytotoxicity. but a proportion can support antibody-dependent cellular cytotoxicity, suggesting that they may contribute to vascular injury.
Alveolar macrophages from patients with bronchogenic carcinoma and sarcoidosis similarly express monocyte antigens
Authors: BARBOSA I L , GANT V A , HAMBLIN A S 
Published: July 2010

SUMMARYIt has been shown that bronchoalveolar lavages (BALs) from patients with sarcoidosis and otlher interstitial lung diseases contain abnormally increased numbers of alveolar macrophages (AM) expressing antigens found on monocytes. The aim of this study was to compare the phenotype of AM from patients wilh sarcoidosis with those from patients with non-interstitial lung disease, namely carcinoma. Using a panel of monoclonal antibodies against cells of the mononuclcar phagocytic series and immunohistochemieal staining, we have compared the expression of antigens on AM recovered at BAI, and peripheral blood monocytes from patients wilh sarcoidosis. with similar cell preparations from bronchogenic carcinoma patients and normal volunteers. We have shown that CD14, CR1 (CD35) and CR3 (CD11b, CD18) are expressed on the majority of monocytes from all subjects, but on only a minority of normal AM. In both patients with sarcoidosis and patients with bronchogenic carcinoma increased proportions of AM expressed these monocyte-associated antigcns. Since BALs from the carcinoma patients were derived from lung lobes which were radiologically free of tumour, the accumulation of AM expressing monocytic antigens is not a local response to the tumour. We conclude that infiltration of the lung wilh monocytes is a more general response to lung disease than has hitherto been reported.
Month-related variability in immunological test results; implications for immunological follow-up studies
Authors: VAN ROOD Y , GOULMY E , BLOKLAND E , POOL J , VAN ROOD J , VAN HOUWELINGEN H 
Published: July 2010

SUMMARY
This longitudinal study was originally designed to detect changes in the in vitro immune response of healthy subjects as a result of a psychological intervention. In this study a significant proportion, about 70%, of the immunological variability in the test results was accounted for by the differences in immunological response levels of the subjects. Apart from this between-subject-effect, a significant proportion of the variability in test results was related to the month of data sampling. The month-effect was computed in such a way that the between-subject variation was taken into account. This resulted in a more accurate estimation of the month-effect. Even after correction for the intervention, i.e. the defence of the PhD thesis, the effect of month of data sampling remains significant for mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, percentage of CD4 and CD8 cells, and for the response to the mitogens phytohaemagglutinin, pokeweed mitogen and concanavalin A as well as the results for the mixed lymphocyte culture for one pool out of three. In contrast, no significant month-effect was observed for the whole blood cell counts, for the differential white blood cell counts as determined by monoclonal antibody staining for cell surface markers CD3, GD16, TAG and OKM1, nor for the immunoglobulin IgM and IgG serum levels. Likewise the cell-mediated lympholysis activities measured against three pools of stimulator cells remained unaltered. We discuss the implications for future immunological follow-up studies of the observation that a significant proportion of the variability in immunological test results is related to differences between subjects and to the month of data sampling.
Structural properties of the glycoplasmanylinositol anchor phospholipid of the complement membrane attack complex inhibitor CD59
Authors: RATNOFF W D , KNEZ J J , PRINCE G M , OKADA H , LACHMANN P J , MEDOF M E 
Published: July 2010

SUMMARYCD59, the membrane regulator of aulologous C5b-9 channel formation, exhibits variable sensitivity to cleavage by phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that releases glyco-inositolphospholipid (GPI)-anchored proteins from cell surfaces. To determine whether the GPI-anchor phospholipid of CD59 is similar to that of decay-accelerating factor (DAF) and whether variation in its structure underlies its variable enzyme susceptibility, the GPI anchors of the two proteins expressed on erythrocytes, polymorphonuclear and mononuclear leucocytes were compared in situ and after purification. Flow cytometric analyses of PI-PLC-treated cells showed parallel cell type specific release of both proteins as a function of enzyme concentration. Non-denaturing PAGE analyses of alkaline/hydroxylamine-treated proteins (affinity-purified from [125I]-surface-labelled cells) provided evidence for (i) comparable proportions of GPI-anchor acylation, and (ii) alkali-resistant rather than alkali-sensitive lipid substituents in erythrocytes. These findings argue that the differential C5b-9 sensitivity that distinguishes paroxysmal nocturnal haemoglobinuria II and III erythrocytes does not derive from expression of CD59 molecules with alternative GPI-anchor phospholipid structures.
Hyper-response of serum IgG1 toStaphylococcus aureuspeptidoglycan in patients with hyper-IgE syndrome
Authors: ISHIZAKA A , KOJIMA K , SAKIYAMA Y , MATSUMOTO S , KUWAJIMA K , WAGATSUMA Y , SHIBATA R , JOH K 
Published: July 2010

SUMMARYThe hyper-IgE (HIE) syndrome is characterized by high IgE scrum levels, chronic dermatitis and recurrent infections. To determine whether an impairment of the antibody response to Staphylococcus aureus contributes to infections in this syndrome we measured total serum IgG subclass, specific IgG1 and IgG2 levels against peptidoglycan (PG), the immunodominant cell wall component of S. aureus and serum opsonic activity lo PG. Of the 14 patients with HIE syndrome, nine had increased level of serum IgG1 and six had IgG2 subclass deficiency. In regard to specific response of IgG1 and IgG2 antibodies to PG. patients were divided into live groups related to ages and compared with 10 control subjects for each age cohort. Patients with HIE syndrome had significant high levels of serum-specific IgG1 to PG and significant decreased levels of serum-specific lgG2 lo PG in all five groups. Additionally, serum opsonic activity in patients was significantly higher than that in normal control subjects. It is concluded that IgG2 deficiency or poor IgG2 antibody response to S. aureus is not the explanation of (he abnormal susceptibility to S. aureus infections of HIE patients.