bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alloimmunization to the PIA1 platelet antigen: results of a prospective study
Authors: Blanchette Victor S. , Chen Lily , De Friedberg Zofia Salomon , Hogan Victoria A. , Trudel Elise , Décary Francine 
Published: March 2008

SummaryThe natural history of alloimmunization to the PlA1 platelet antigen is uncertain. We followed 50 PlA1‐negative pregnant women during pregnancy and for 6 months post‐partum in order to determine this natural history. The cohort of PlA1‐negative women was obtained by PlA1 typing 5000 women. Three PlA1‐negative women formed anti‐PlA1 antibodies during this prospective study, two in pregnancy and one in the immediate post‐partum period. All three PlA1 antibody producers were HLA‐DR3 positive, a histocompatibility phenotype that is strongly associated with alloimmunization to the PlA1 antigen. One of the three infants delivered to these mothers was thrombocytopenic (platelet count 9 x 109/1). The remaining two infants had normal platelet counts at birth (160 and 174 x 109/1). The HLA‐A1, ‐B8, ‐DR3 and ‐DRw52 phenotype frequencies in the group of PlA1‐negative women who did not form PlA1 antibodies (n= 47) was similar to that found in their husbands, and that expected in a normal Caucasian population. From our data we estimate that alloimmunization to the PlA1 antigen occurs in approximately one out of every 1000 pregnancies in a Caucasian population. It is important to recognize that not all pregnancies in which a mother has formed PlA1 alloantibodies will result in the delivery of a thrombocytopenic infant. These findings are relevant to programs designed to either prevent alloimmunization to the PlA1 antigen (through passive administration of anti‐PlA1 immunoglobulin to at‐risk PlA1‐negative mothers), or to identify women at risk of delivery of thrombocytopenic infants (by antenatal screening to detect women alloimmunized to the PlA1 antigen).
Infant acute lymphoblastic leukaemia with t(11;19)
Authors: Gibbons B. , Katz F. E. , Ganly P. , Chessells J. M. 
Published: March 2008

SummarySeven cases of infant acute lymphoblastic leukaemia with t(11:19) (q23;p13) are described. They are characterized by a high white cell count, organomegaly, early central nervous system (CNS) disease, and a poor prognosis. Blasts are usually of an immature early B‐cell lineage although monocytoid features are present in some cases. The characteristics of infant acute leukaemia with t(11;19) are very similar to those found with t(4;11), and the presence of t(11;19) may indicate the same poor prognosis.
Monoclonal antibody ratios in malignant myeloid diseases: diagnostic and prognostic use in myelodysplastic syndromes
Authors: Kristensen Josrgen Schosler , Hokland Peter 
Published: March 2008

SummaryBased on a 6 1/2 year study of bone marrows (BM) from 74 consecutive adult patients with newly diagnosed primary myelodysplastic syndromes (MDS), we have evaluated the role of immunophenotyping (IP) for subclassification purposes with a selected panel of monoclonal antibodies (Mab). Compared to normal BM IP revealed increased numbers of Mab‐defined immature myeloid cells (defined by Mab MY7 [CD13] and MY9 [CD33] (P<0.05). Furthermore, decreased numbers of mature myeloid cells (defined by Mab NAT‐9 II:3F‐6F [NAT‐9])(P<0.001) were demonstrated in all French‐American‐British (FAB) subtypes except refractory anaemia with sideroblasts (RA‐S).Since expression of CD13 and CD33 antigens on immature myeloid cells is variable, IP based on a single Mab was often found to be non‐informative. However, the construction of myeloid antibody ratios (MAR), designed to give higher figures with increasing numbers of immaturfe myeloid cells and/or decreasing numbers of mature myeloid cells in the BM, disclosed increasing mean ratio values with progressing FAB subtypes. More significant however, was that different prognostic subgroups based on the MAR could be identified independently of the FAB classification. We conclude that the use of IP—especially when MAR is included—is useful in prognostic scoring systems in MDS.
Molecular characterization of β‐thalassaemia in 174 Greek patients with thalassaemia major
Authors: Kattamis C. , Hu H. , Cheng G. , Reese A. L. , Gonzalez‐Redondo J. M. , Kutlar A. , Kutlar F. , Huisman T. H. J. 
Published: March 2008

SummaryThe mutations producing β‐thalassaemia in 174 Greek patients with thalassaemia major were investigated by dot‐blot hybridization of oligonucleotide probes to genomic DNA amplified by the polymerase chain reaction procedure, by direct sequencing of amplified DNA, and by gene mapping. β‐thalassaemia in Greeks was found to be very heterogeneous at the molecular level as 17 different mutations were observed; 86.6% of the β‐thalassaemic genes, however, could be identified with five probes: IVS‐I‐110 (G→A) (42.5%), codon 39 (C→T) (17%), IVS‐I‐1 (G→A) (13.2%), IVS‐I‐6 (T°C) (7.2%) and IVS‐II‐745 (C→G) (6→9%). Several mutations which had not previously been reported in the Greek population and which occurred at an incidence of 2% or lower were observed in this study. The information obtained will facilitate the prenatal diagnosis of β‐thalassaemia in Greece.
Non‐invasive quantitation of liver iron‐overload by magnetic resonance imaging
Authors: Kaltwasser J. P. , Gottschalk R. , Schalk K. P. , Hartl W. 
Published: March 2008

SummaryA standard magnetic resonance imaging (MRI) system allowing spin echo times of 10 ms was used to quantitate liver iron concentration in nine healthy normal subjects and 13 patients with various grades of iron overload. Body iron status was estimated by measuring the serum ferritin concentration. In 11 subjects (two normal healthy controls, eight patients with HLA‐related hereditary haemochromatosis and one patient with thalassaemia major) non‐haem hepatic iron concentration was determined chemically in biopsy specimens (dry weight), in parallel to serum ferritin and MRI‐T2 relaxation times. A moderate correlation (r=0.79) was obtained for the correlation of the T2‐relaxation rate (1/T2) and serum ferritin of the 22 subjects investigated. A much closer correlation (r= 0.98) was observed for the 1/T2 liver iron relationship in the 10 subjects analysed by liver biopsy. It is concluded from these preliminary observations, that MR‐imaging may provide a useful non‐invasive tool for the quantitative determination of liver iron in iron overload‐syndromes.
Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature POSSIBLE EXISTENCE OF A NEW CLINICAL ENTITY ORIGINATING FROM THE THIRD LINEAGE OF LYMPHOID CELLS
Authors: Imamura Nobutaka , Kusunoki Yoichiro , Kawa‐Ha Keisei , Yumura Keiko , Hara Junichi , Oda Kenji , Abe Kazuhiro , Dohy Hiroo , Inada Tominari , Kajihara Hiroki , Kuramoto Atsushi 
Published: March 2008

SummaryThe morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non‐T, non‐B natural killer cell leukaemia/lymphoma (ANKL/L) are described. The leukaemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, OKIa1 and NKH‐1 (CD56) monoclonal antibodies on their cell‐surface, and also showed natural killer (NK) activity. In addition, these ANKL/L belonged to neither T‐ nor B‐cell lineage, proved by studying clonal gene rearrangement for the Tβ, Tγ and Tδ receptors, and immunoglobulin.After comparing them with the seven cases of ANKL/L reported in other institutions, with regard to immunophenotype, genotype and function, we conclude that ANKL/L originating from a third lineage of lymphoid cells is a distinct clinical entity.
Enhanced growth of clonogenic cells from acute myeloblastic leukaemia by erythropoietin
Authors: Motoji Toshiko , Hoshino Shigeru , Ueda Masatsugu , Takanashi Minoko , Masuda Michihiko , Nakayama Keiko , Oshimi Kazuo , Mizoguchi Hideaki 
Published: March 2008

SummaryThe effect of erythropoietin (Epo) on colony formation by blast progenitors in acute myeloblastic leukaemia other than erythroleukaemia was studied using a blast colony assay. Epo alone did not induce colony formation, but when it was used together with phytohaemagglutinin‐stimulated leucocyte‐conditioned medium (PHA‐LCM) the number of leukaemic colonies significantly increased in nine out of 12 cases studied. Preincubation of Epo with anti‐Epo antibody completely abolished this enhancement, indicating that the increase in colony numbers was caused by Epo itself. Cell surface phenotype analysis of colonies produced by Epo plus PHA‐LCM showed no increase in percentages of erythroid and megakaryocyte lineages. The addition of Epo also increased the self‐renewal capacity of leukaemic blast cells. Fresh leukaemic cells did not express Epo receptors, but they were induced after incubation with PHA‐LCM. The present study thus showed that the proliferative response to Epo is not restricted only to the erythroid lineage, but also extends to AML blast cells other than those in erythroleukaemia in the presence of colony stimulating factors.
Demonstration of platelet antigens that bind platelet‐associated autoantibodies in chronic ITP by direct immunoprecipitation procedure
Authors: Tomiyama Y. , Take H. , Honda S. , Furubayashi T. , Mizutani H. , Tsubakio T. , Kurata Y. , Yonezawa T. , Tarui S. 
Published: March 2008

SummaryPlatelet antigens that bind platelet‐associated autoantibodies in chronic idiopathic thrombocytopenic purpura (ITP) were demonstrated using a direct immunoprecipitation procedure. ITP platelets, with bound autoantibodies, were radiolabelled and solubilized, and then platelet antigen‐antibody complexes adsorbed to protein A‐bearing Staphylococcus aureus were analysed by 7.5% sodium dodecyl sulphate, polyacrylamide gel electrophoresis (SDS‐PAGE). Direct immunoprecipitation demonstrated the presence of platelet‐associated autoantibodies against glycoprotein (GP) IIb/IIIa in four of six ITP patients with an intensive band corresponding to platelet‐associated IgG. These results were confirmed by indirect immunoprecipitation using ether eluates from two ITP patients. In addition, only direct immunoprecipitation demonstrated the presence of autoantibodies against an unidentified protein having a molecular mass of 56 kDa in three of the six patients. These three ITP patients having autoantibodies against GP IIb/IIIa and against the 56 kDa protein were studied after splenectomy. Two patients, showing disappearance of autoantibodies against these antigens, attained a complete remission, and one patient, with autoantibodies against the 56 kDa protein despite splenectomy, attained only partial remission. These data suggest that autoantibodies against GP IIb/IIIa and against the 56 kDa protein may play a role in platelet destruction in some ITP patients.
Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit
Authors: Voss R. , Matthias F. R. , Borkowski G. , Reitz D. 
Published: March 2008

SummaryDisseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t‐PA), tissue plasminogen activator inhibitor (PAI), D‐dimer, euglobulin‐clot‐lysis‐time (ECLT), plasminogen, α2‐antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II‐score).An increase in D‐dimer and t‐PA‐antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t‐PA‐activity was not detectable, PAI‐function was elevated, the ECLT was prolonged and α2‐antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t‐PA‐antigen, PAI‐function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II‐score of the patients.We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, α2‐antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.
Protein C and protein S levels in two patients with acquired purpura fulminans
Authors: Madden Renee M. , Gill Joan Cox , Marlar Richard A. 
Published: March 2008

SummaryPurpura fulminans (PF) is a cutaneous manifestation of a dramatic and deadly syndrome of systemic disseminated intravascular coagulation (DIC). It is characterized by microvascular thrombosis in the dermis followed by perivascular haemorrhage. Since two other related syndromes involve the protein C (PC) system, we undertook a serial study to investigate the levels of PC and protein S (PS) in two patients with acquired PF. Laboratory findings were consistent with DIC, and both patients were treated with blood replacement and heparin therapy. The levels of PC activity were very low during the initial 24–36 h after onset and gradually increased until returning to normal levels. The total and ‘free’PS were also abnormal during the initial onset of PF. The total and free PS increased to normal after 4–6 d. Although the pathogenesis is not fully understood, the infection and sepsis appears to consume PC and PS selectively during the PF and DIC phase. Acquired PF appears to selectively involve the PC system in a similar fashion to two other syndromes of PF‐like lesions.
Primary polycythaemia: positive diagnosis using the differential response of primitive and mature erythroid progenitors to erythropoietin, interleukin 3 and alpha‐interferon
Authors: Dudley J. M. , Westwood N. , Leonard S. , Eridani S. , Pearson T. C. 
Published: March 2008

SummaryForty adult subjects were studied with the aim of establishing positive diagnostic criteria in primary proliferative polycythaemia (polycythaemia vera, PPP). These comprised 14 patients with PPP, eight secondary polycythaemia (SP), five idiopathic erythrocytosis, and 13 normal subjects, classified under standard criteria following comprehensive investigation for causes of SP. Erythroid colony formation from peripheral blood in a serum‐free system was assayed with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or α‐interferon (α‐IFN). The differential sensitivity of primitive and mature progenitors (BFU‐E) was assessed by counting the number of clusters (‘sub‐colonies’) comprising each erythroid burst. ‘Endogenous’erythroid colonies were found in both PPP (56%) and controls (17%). In Epo containing cultures, the mean number of clusters per burst was lower in PPP than controls, and the percentage of small (≦ 8 clusters) bursts was higher. In PPP primitive BFU‐E demonstrated greater dependence on IL3 than controls, and mature BFU‐E greater inhibition by α‐IFN. These findings suggest an abnormal response to several growth factors, rather than dysfunction of a single growth factor receptor. Regression analysis of these data defined a discriminant of high diagnostic sensitivity and specificity. This discriminant accurately predicted diagnosis in a further nine polycythaemic patients.
Clinical significance of the presence of myeloid associated antigens in acute lymphoblastic leukaemia
Authors: Urbano‐Ispizua Alvaro , Matutes Estela , Villamor Neus , Ribera Josep Maria , Feliu Evarist , Montserrat Emilio , Grańtena Albert , Vives‐Corrons Joan‐Lluis , Rozman Ciril 
Published: March 2008

SummaryWe have analysed the immunological characteristics of blasts from 89 acute lymphoblastic leukaemia (ALL) cases (62 adults and 27 children), by using a panel of antilymphoid and myeloid associated monoclonal antibodies (McAb) and the APAAP method, which detects membrane and cytoplasmic expression of antigens.The McAb CD19 was the marker most consistently expressed in B lineage ALL, being positive in 100% of cases, compared to CD24 and CD22 expressed in 82% and 79%, respectively. Similarly, for the T lymphoid lineage, the McAb CD3 was the most reliable and specific marker, being expressed in all T‐ALL cases including those with an early thymic phenotype (CD7 +, TdT+).Lymphoblasts from eight adults (12.9%) and three children (11.1%) expressed one to four myeloid associated antigens recognized by CD13, CD14, CD33 and anti‐myeloperoxidase. There were no substantial clinical and morphological differences between the two ALL groups with or without myeloid associated markers. However, the presence of myeloid associated markers in adult ALL was associated with a significantly lower complete remission (CR) rate (P=0.05) and with a shorter survival (P= 0.001): this variable was independent of advanced age and high WBC. It is concluded that immunophenotypic analysis in ALL should include myeloid markers for its probable, prognostic implications.
Reversal of drug‐resistance by cyclosporin‐A in a patient with acute myelocytic leukaemia
Authors: Sonneveld Pieter , Nooter Kees 
Published: March 2008

SummaryThe emergence of resistant leukaemia in a patient with acute myeloid leukaemia (AML) was evaluated during clinical progression of the disease. At relapse, a decrease of the intracellular accumulation of daunorubicin (DNR) as determined by real time flow cytometry was associated with a relative overexpression of RNA encoding for the multidrug resistance phenotype (MDR1), and by a decreased in vitro sensitivity to DNR of clonogenic AML cells (IC50 0.8‐3.4 μm). Intracellular DNR accumulation and in vitro DNR sensitivity could be completely restored by adding cyclosporin‐A (3 μm) to the cells. At progressive relapse the patient was treated with re‐induction therapy (DNR 30 mg/m2 x 3. cytarabine 200 mg/m2 x 7) to which cyclosporin‐A was added (Cy‐A 4 mg/kg twice daily for 3 d, 2.5 mg/kg twice daily for 2 d). which resulted in elimination of the MDR1 positive AML cells with restoration of the original DNR accumulation and in vitro sensitivity. After 12 weeks the resistant clone reappeared in the blood and bone marrow.
A past mutation at Isoleucine397 is now a common cause of moderate/mild haemophilia B
Authors: Bottema Cynthia D. K. , Koeberl Dwight D. , Ketterling Rhett P. , Bowie E. J. W. , Taylor Sherryl A. M. , Lillicrap David , Shapiro Amy , Gilchrist Gerald , Sommer Steve S. 
Published: March 2008

SummaryOf the factor IX sequence changes that we have identified in 65 consecutive males with haemophilia B, 11 (17%) are the same mutation. This mutation is a T→C transition at base 31311 which substitutes threonine for isoleucine397 (ile397) in the factor IX molecule. The 11 patients are of Western European descent and have the same haplotype: Hinf1 (‐), Xmn1 (‐), Taq1 (‐), BamH1 (+), Malmö allele = thr148. The frequency of this haplotype was estimated and the probability of the same mutation occurring independently 11 times in this haplotype was miniscule. We conclude that these patients have a common ancestor despite the lack of overlapping pedigrees.The clinical symptoms of the disease were consistently moderate/mild in these 11 patients, whereas factor IX coagulation values obtained from the medical records varied more than sixfold between individuals. However, when plasma from five individuals was assayed by the same laboratory concurrently, the values varied less than twofold. Thus, in routine practice, clinical severity may correlate better with the presence of a given mutation than the factor IX coagulant activity.The high frequency of the mutation at ile397 indicates that carrier testing in families of Northern European descent with moderate/mild haemophilia B can be expedited by first determining whether this particular mutation is present. We demonstrate here that the technique of polymerase chain reaction (PCR) amplification of specific alleles (PASA) can be used to rapidly perform carrier testing in families with the ile397 mutation.
Platelet concentrates irradiated with ultraviolet light retain satisfactory in vitro storage characteristics and in vivo survival
Authors: Pamphilon D. H. , Potter M. , Cutts M. , Meenaghan M. , Rogers W. , Slade R. R. , Saunders J. , Tandy N. P. , Fraser I. D. 
Published: March 2008

SummaryWe have previously reported that platelet concentrates (PC) may be irradiated with ultraviolet light (UVL) in a cryostorage pack such that mixed lymphocyte reactions (MLR) are abolished whilst satisfactory platelet function is retained during subsequent storage using Fenwal PL‐1240 containers. We have now studied both platelet structure and function after irradiation in DuPont Stericell bags which are both UV‐permeable and biocompatible. The irradiation dosage was 3000 Joules/m2 of UVL at a mean wavelength of 310 nm; a dose previously shown to abolish MLR. No detriment to platelet function was observed when compared to control as measured by aggregation responses to adenosine diphosphate (ADP), collagen and ristocetin, hypotonic shock response and pH during 5 d of storage. Lactate levels were significantly higher (P<0.01) and glucose levels lower (P<0.01) in UV‐treated PC, although in the majority the lactate level did not exceed 20 mmol/l. Betathromboglobulin and platelet factor 4 levels were higher during storage in the UV group, the latter reaching significance (P<0.05). When whole platelets and platelet membranes were stained with Coomassie blue or Periodic Acid‐Schiff s reagent after electrophoresis in polyacrylamide gels no obvious alterations to major membrane constituents were observed on days 1 and 5 of storage. Paired in vivo autologous studies in healthy volunteers using 111Indium‐labelling were performed at the end of 5 d of storage. The UV‐treated platelets gave satisfactory and equivalent results for recovery, half life and survival when compared to controls. We conclude that PC irradiated with UVL and stored for 5 d in DuPont Stericell containers appear suitable for transfusion and may prove to be non‐immunogenic. Further in vivo studies of haemostatic efficacy and recipient alloimmunization are now warranted.
Frequencies of Band 3 variants of human red cell membranes in some different populations
Authors: Ranney Helen M. , Rosenberg Gwen H. , Morrison Martin , Mueller Thomas J. 
Published: March 2008

SummaryA variant of Band 3, the major protein of the erythrocyte membrane, was observed by Mueller and Morrison in 1977 in 6–7% of healthy blood donors on sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS–PAGE) of erythrocyte membranes treated with pronase. Pronase treated red cells containing this first recognized variant [here designated ‘Band 3‐Memphis (m)’]§ had two bands of about 63000 and 60000 Mr while pronase treated normal cells had only the lighter Mr band. The present study includes data on the frequency of variants resembling Band 3‐Memphis in patients of different ethnic groups and on random donors obtained earlier in Memphis. These variants were detected by the original method of Mueller and Morrison and were not associated with recognized clinical or haematological abnormalities. Significantly higher gene frequencies for the variants of the (m) type were observed in American Indians, African Americans and Filipinos than in Caucasians: putative heterozygotes and homozygotes were identified among each of these groups. The frequency of silent Band 3 polymorphisms in different populations should be considered in the interpretation of clinical findings associated with the presence of Band 3 variants.