摘要:

AbstractCD45, a transmembrane tyrosine phosphatase, is found on almost all nucleated hematopoietic cells and plays a crucial role in lymphocyte activation and differentiation. We recently achieved isolation of the human LSM‐1 (hLSM‐1) gene, whose product is a possible substrate for CD45, and we raised antibodies against the hLSM‐1 protein. hLSM‐1 expression in hematopoietic cells was examined with Northern and Western blot, fluorescence‐activated cell sorter, and immunocytochemical analyses. It was found that in the lymphoid lineage, T and B lymphocytes as well as NK cells expressed LSM‐1, whereas terminally differentiated plasma cells did not. As for the myeloid lineage, immature myeloid cells expressed LSM‐1, whereas terminally differentiated granulocytes and monocytes did not. In the erythroid lineage, normal erythroblasts expressed very low levels of LSM‐1, while erythroid cell lines (K562 and HEL) did not. Megakaryocytes did not express LSM‐1. Both CD34+/CD33−and CD34+/CD33+hematopoietic progenitor cells weakly expressed LSM‐1. These results showed that LSM‐1 is expressed in a lineage‐ and differentiation stage‐specific fashion. Am. J. Hematol. 54:1–11

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<1::AID-AJH1>3.0.CO;2-1

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractCerebrovascular accidents in patients with sickle cell anemia are among the most devastating complications of the disease. It has recently been demonstrated that some patients have a hypercoagulable state on the basis of the presence of an abnormal factor V molecule, factor V Leiden. We undertook this study to evaluate the presence of factor V Leiden in sickle cell patients with stroke. Eighty‐two patients with either Hgb SS, Hgb SC, or Hgb Sβ+‐thalassemia comprised the study population. Of the 82 patients in the study, 19 of them had a history of stroke. In our study population, none of the stroke patients possessed the factor V Leiden mutation. One of the non‐stroke patients was a heterozygote for the mutation (P= 1.00). The overall frequency of the factor V Leiden allele in our population is 0.6%. The estimated prevalence for this mutation is reportedly between 3 and 7% in Caucasian populations. We conclude that the gene frequency for factor V Leiden is less common in Africa Americans with sickle cell disease. Furthermore, factor V Leiden does not appear to be responsible for the development of stroke in sickle cell patients. Am. J. Hematol. 54:12–15, 1997. © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<12::AID-AJH2>3.0.CO;2-7

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractMolecular analysis was performed on 95 Israeli patients with thalassemia intermedia, representing 60 families of Arab (Moslem and Christian), Jewish, Druze, and Samaritan origin. There was a wide range of phenotypic severity, with baseline hemoglobin levels ranging from 5.5 to 10.7. Eighteen thalassemia mutations were found (29 genotypes), which were subdivided into groups, according to the severity of mutations. A consistently mild phenotype (10 families) was caused by compound heterozygosity for a silent mutation, such as −101 C‐T or by coexistence of triplicated α‐globin genes with thalassemia trait. In 39 thalassemia intermedia families, the genotype which was found was one which led to severe thalassemia intermedia, or, in other families, was associated with thalassemia major. Elevated hemoglobin F ameliorated the disease in some patients with a severe genotype. We did not find a beneficial effect of concurrent α‐thalassemia in any of the families studied. In 11 families, only one β‐thalassemia allele was identified. One was a dominant thalassemia intermedia allele. Three additional families with heterozygous β‐thalassemia had excess α‐globin genes (5 or 6 total). In 7 of these heterozygotes, no explanation was found for the thalassemia intermedia phenotype. Our results suggest a substantial influence of as yet unknown genetic modifiers. These findings have important implications for prenatal diagnosis and for the genetic counseling of families with thalassemia intermedia. Am. J. Hematol. 54:16–22, 1997 ©

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<16::AID-AJH3>3.0.CO;2-7

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractDifferent parameters of fibrinolytic systems like t‐PA, PAI, D‐dimer, and inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and antithrombin III (AT‐III), have been studied in cases of acute malaria due toPlasmodium falciparumandplasmodium vivaxinfection, and these patients were followed up. It was observed that the plasma PAI‐1 was very high in cases ofP. falciparummalaria infection as compared to normal controls andP. vivaxinfection. The changes in complicated cases ofP. falciparumwere remarkable as compared to uncomplicated ones. The PC, PS, and AT‐III levels were also low inP. falciparum, particularly so in complicated cases, and were normal inP. vivaxinfection. The factor VIII R:Ag levels were invariably high in acute malaria. On follow‐up of some of these cases the values came back to normal after the antiparasite treatment. The monocyte procoagulant activity was found to be significantly higher inP. falciparuminfection as compared to that ofP. vivaxinfection. All these findings therefore contribute towards the production of a hypercoagulable state inP. falciparuminfection and partly explain the complications ofP. falciparuminfection like cerebral malaria. Am. J. Hematol. 54:23–29, 1997 © 1997 W

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<23::AID-AJH4>3.0.CO;2-6

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractHS‐26, the mouse homologue of HS‐40, is the major regulatory element of the mouse α‐globin gene locus. Like HS‐40, HS‐26 is located within an intron of a house‐keeping gene; comparison of the nucleotide sequences of HS‐26 and HS‐40 reveals conservation of the sequences and positions of several DNA binding motifs in the 5′ regions of both elements (3 GATA, 2 NFE‐2, and 1 CACCC sites) and the absence in HS‐26 of three CACCC sites and one GATA site that are present in the 3′ region of HS‐40, suggesting that the two elements might not be identical. We report here that when HS‐26 is linked to a 1.5 kb Psti human α‐globin gene fragment, it has a weak enhancer activity in induced MEL cells and in transgenic embryos, and it does not have any detectable activity in adult transgenic mice. This suggests that HS‐26 does not have Locus Control Region (LCR) activity but can act as an enhancer during the embryonic life when integrated at a permissive locus. To further test the importance of HS‐26 at its natural locus, we have generated embryonic stem cells and chimeric animals in which 350 bp containing HS‐26 have been replaced by a neomycin resistance gene by homologous recombination. The sizes of the chimeras' red cells were then estimated by measuring forward scattering on a FacsScan apparatus in hypotonic conditions. This revealed that a fraction of the chimeric animals' red cells were smaller than normal mouse red cells and were very similar to cells from mice heterozygous for α‐thalassemia. Density gradient analysis also suggested the presence of thalassemic cells. These results indicated that despite its lack of LCR activity, HS‐26 is important for the regulation of the mouse α‐globin gene locus. Am. J. H

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<30::AID-AJH5>3.0.CO;2-5

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractVariation in the level of fetal hemoglobin (HbF) accounts for much of the clinical heterogeneity observed in patients with sickle cell disease (SCD). The HbF level has emerged as an important prognostic factor in both sickle cell pain and mortality, and a % HbF of 10–20% has been suggested as a threshold level for diminished clinical severity. The number of erythrocytes that contain HbF (termed F cells) may also be critically important, as F cells resist intravascular sickling and have preferential in vivo survival. Since F cells can be enumerated with high accuracy using flow cytometry methods, we prospectively studied a cohort of 242 children with SCD. Children with HbS and hereditary persistence of fetal hemoglobin (S/HPFH) had essentially 100% F cells. In contrast, children with homozygous sickle cell anemia (HbSS), HbS/β0thalassemia, or HbS/β+thalassemia had significantly lower mean % F cell values (55.9, 61.6, and 51.3%, respectively;P<0.001), and children with HbSC had even fewer F cells (27.0%;P<0.001). There was a highly significant correlation between the % F cells and the log (% HbF), which was observed for the total population of children (r = 0.95,P<0.001), as well as for each of the individual subgroups of children with HbSS (r = 0.94,P<0.001), HbSC (r = 0.89,P<0.001), or HbS/β0thalassemia and HbS/β+thalassemia (r = 0.95,P<0.001). This logarithmic correlation between % F cells and % HbF has not been previously described and has important implications for the pharmacologic manipulation of HbF in patients with SCD. Am. J. Hematol. 54:40–46, 1997 © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<40::AID-AJH6>3.0.CO;2-4

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

Abstract“Autonomous” development of erythroid colonies in erythropoietin (EPO)‐free semi‐solid culture has been used as an in vitro assay for diagnosis of polycythemia vera (PV). These colonies, however, are small and poorly hemoglobinized, rendering the assay in many cases unreliable. We report here on the use of a novel assay; it combines a modified culture procedure that maximizes the growth of EPO‐independent erythroid cells, and immunofluorescence flow cytometry for their detection and quantitation. Peripheral blood mononuclear cells are cultured for 2–5 days in the presence of a combination of growth factors. During this phase, early erythroid committed progenitors, burst forming units (BFUe), proliferate and differentiate into colony forming units (CFUe)‐like progenitors. In the second phase, the latter cells, in the presence of stem cell factor, hemin, and iron‐saturated transferrin, continue to proliferate and mature into hemoglobin (Hb)‐containing orthochromatic normoblasts. Neither phases contained EPO. The culture produced large, pure, and synchronized erythroid cell populations. The cells were then dually labeled with fluorescent probes, nuclear DNA with thiazole orange and intracellular hemoglobin (Hb) with phycoerythrin‐conjugated monoclonal antibodies against human Hb. Cells positive for both labels were assigned as Hb‐containing nucleated precursors. The presence of such cells in EPO‐free cultures indicated “autonomous growth.” None of the EPO‐free cultures derived from normal donors or patients with secondary polycythemia contained such cells. Cultures derived from PV patients contained from 5 to 92% “autonomously‐grown” cells. These culture and analysis methods should minimize false negative results with PV patients and provide objective and quantitative data. Am. J. Hematol. 54

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<47::AID-AJH7>3.0.CO;2-4

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractSignificant advances in identification of etiologies of inherited thrombosis have been recently reported. A point mutation in coagulation factor V (factor V Leiden) results in resistance to activated protein C and probably represents the most common genetic risk factor for venous thrombosis. A metabolic disorder, homocysteinemia, is now known to be an important risk factor for both arterial and venous thrombosis. Many patients with recurrent thrombosis will have more than one genetic risk factor identified. Recognition of these new disorders should permit a diagnosis to be achieved in at least half of patients evaluated for inherited thrombosis. Am. J. Hematol. 54:53–60, 1997 © 1997 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<53::AID-AJH8>3.0.CO;2-3

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractVarious clinical observations have implicated T cells in the control of chronic myeloid leukemia (CML). These observations have in recent years been supported by laboratory results indicating the presence of CML‐specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease‐bearing patients. Both MHC‐unrestricted and MHC‐restricted immune effector mechanisms are involved. Donor lymphocyte infusion has produced encouraging GvL effects. However, future adoptive immunotherapy may depend on the isolation and generation of leukemia‐specific T cells. Although many proteins may potentially act as leukemia antigens in CML for MHC‐restricted cytotoxicity, the bcr‐abl fusion protein has been most extensively investigated. There is now much evidence to suggest that the bcr‐abl junctional peptides are capable of eliciting both CD4 and CD8 responses in normal healthy donors and CML patients. Furthermore, the T‐cell lines generated react with autologous or HLA‐matched fresh CML cells, suggesting that the bcr‐abl fusion protein can be processed in vivo so that the joining segment is bound to HLA molecules in a configuration and concentration similar to those of the immunizing peptide for antigen recognition by the antigen‐specific T‐cell receptor. These results also indicate that the bcr‐abl junctional peptides may be used for immunotherapy of CML. Other strategies available for immunotherapy of CML include immunologically or genetically manipulated donor T‐cell infusion, the use of cytokines, adoptive immunotherapy with leukemia‐reactive T‐cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore play an important adjuvant role in future in the management of patients with CML. Am. J. Hematol.

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<61::AID-AJH9>3.0.CO;2-2

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractSome patients with systemic light chain amyloidosis develop bleeding complications that can be caused by vascular infiltration with amyloid or by alterations of the coagulation or fibrinolytic systems. Factor X deficiency is the most common cause of bleeding manifestations, although deficiencies of other clotting factors, a disruption in the conversion of fibrinogen to fibrin, and circulating heparin‐like anticoagulants have also been reported. Deficiency of factor X is a well‐recognized cause of bleeding manifestations in patients with light chain amyloidosis. This acquired disorder appears to be secondary to adsorption of factor X to the amyloid fibrils. Previous studies have shown that infusion of plasma into patients with acquired factor X deficiency and amyloidosis induces a transitory improvement of the coagulation tests. However, there is a rapid return to pretransfusion levels. In this manuscript we report the clinical application of plasma exchange in the management of a patient with systemic light chain amyloidosis with acquired factor X deficiency. Am. J. Hematol. 54:68–71, 1997 © 1997 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199701)54:1<68::AID-AJH10>3.0.CO;2-6

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY