摘要:

AbstractThis study was designed to identity the β‐thalassemia mutations in an Argentine population. Seventy‐one pediatric patients and 101 available relatives were studied (85 chromosomes). Diagnosis of β‐thalassemia was made by conventional hematological procedures. Molecular studies were carried out by dot‐blot and restriction endonuclease analysis on amplified DNA to detect the eight most frequent mutations in the Mediterranean area. We were able to identify 95.3% of the β‐thalassemia mutations in the subjects under study. The four common defects (C‐39, 47%; IVS‐I nt 110, 22.4%; IVS‐I nt 1, 9.4%; and IVS‐I nt 6, 5.9%) account for 84.7% of the β‐thalassemia alleles. The alleles and their distributions showed a close similarity to the spectrum of alleles in Italy. The differences might represent the influence of other immigrations, especially from Spain. We conclude that β‐thalassemia in Argentina originated mainly from Italian immigrants. This study will enable us to design an adequate approach to genetic counseling and/or prenatal diagnosis for couples at risk. Am. J. Hematol. 54:179–182,

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<179::AID-AJH1>3.0.CO;2-T

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

年代:1997

数据来源: WILEY

摘要:

AbstractFrequency of painful episodes in sickle‐cell disease is considered to be related to clinical severity and possibly to other aspects of the disease. Measurements of frequency often include only hospital‐related or more severe, longer‐lasting episodes. Since painful episodes, however, may regularly occur in nonhospital settings or be shorter‐lasting with possible different pathologic effects, we measured all painful episodes in 10 adults with sickle‐cell disease for 1.0–3.8 years, using a daily questionnaire. The results were related to other indices of disease severity and to possible precipitating factors, such as cold weather and menses. Sixty‐one percent (on average) of the total number of episodes (243) were nonhospital‐related, and 33% (on average) were shorter‐lasting. Episode frequencies, whether determined as total, hospital‐related, nonhospital‐related, or shorter‐lasting, were not related to each other or to other indicators of disease severity. The highest incidence of episode frequency occurred in the winter. The association of episodes with menses was moderately close in individual patients. The findings suggest that nonhospital‐related painful episodes and shorter‐lasting episodes may contribute significantly to episode frequency. Measurement of frequency of all painful episodes would require consideration when evaluating episode frequency and its relationship to disease severity, to possible precipitating factors of episodes, and to treatment of the disease, and for study of the natural course of the disease. Am. J. Hematol. 54:183–188

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<183::AID-AJH2>3.0.CO;2-S

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

年代:1997

数据来源: WILEY

摘要:

AbstractThe MDM‐2 oncoprotein exists in an autoregulatory feedback loop with the tumor suppressor protein p53. Therefore, intracellular levels of these two proteins may play important roles in cell proliferation and tumorigenesis. Several MDM‐2 proteins (Mr 35–100 Kd) have been demonstrated in human cell lines. We report here the expression profile of MDM‐2 and p53 proteins in 87 cases of chronic lymphocytic leukemia (CLL) as detected by immunoblot analysis. The MDM‐2 proteins (p57, p59, p67, and p90) were found to be overexpressed in different combinations in 56/87 (64%) of cases of CLL when compared with normal volunteers. The MDM‐2 protein p57 was predominantly overexpressed 46/87 (53%) in CLL. In 22/87 (25%) cases of CLL p57 was overexpressed alone, and in 24/87 (28%) cases it was co‐overexpressed with other MDM‐2 proteins p59/p67/p90. Six of the 87 cases of CLL showed overexpression of the tumor suppressor protein p53 by immunoblot analysis, and five of those cases also co‐overexpress MDM‐2 protein p57. No statistically significant correlation of MDM‐2 protein overexpression to clinical disease stage and history of previous chemotherapy of CLL patients has been found. However, considering the oncogenic potential of overexpressed MDM‐2 proteins, a possible role of MDM‐2 proteins in the promotion of CLL disease remains to be evaluated. Am. J. Hematol. 54:189

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<189::AID-AJH3>3.0.CO;2-S

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

年代:1997

数据来源: WILEY

摘要:

AbstractRecent reports indicate that antibodies associated with heparin‐induced thrombocytopenia and thrombosis (HITP) are specific for complexes formed between heparin and the heparin‐binding, platelet alpha granule protein, platelet factor 4 (PF4). As with other disorders mediated by immune complexes (IC), the characteristics of the involved immunoglobulins could affect the ability of IC to cause symptoms. We therefore studied the class, subclass, and potency of antibodies specific for heparin:PF4 complexes formed by two groups of patients: one with severe thrombocytopenia, with or without thrombosis, and a positive serotonin release assay (SRA) (Group 1) and another with mild or absent thrombocytopenia, absence of thrombosis, and a negative SRA despite having formed antibodies reactive with heparin:PF4 complexes (Group 2).IgG antibodies were more common in the Group 1 patients (100%) than in Group 2 (46%), whereas IgM antibodies were more common in Group 2 (81%) than in Group 1 (42%) (P= 0.009). About half of each group formed IgA antibodies. In each group, the IgG antibodies were predominantly IgG1 (82%); 42% were IgG3. Only one IgG2 antibody was identified in a total of 52 antibody formers. Antibodies of the IgG class were consistently of higher titer in Group 1 patients than in Group 2 patients (P<0.001).Recent reports suggest that the H131 form of the FcγRII receptor, which binds preferentially to IgG2 Fc, is found with greater than expected frequency in patients with HITP. Identification of only one IgG2 antibody among 38 antibodies of the IgG class argues against a unique role for antibodies of this subclass in the pathogenesis of HITP. The finding that titers of antibodies in Group 1 patients were a significantly higher titer than in Group 2 patients suggests that development of the full‐blown HITP syndrome may require the formation of antibodies of unusually high titer. Am. J. Hematol. 54:196–201 © 1997 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<196::AID-AJH4>3.0.CO;2-R

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

年代:1997

数据来源: WILEY

摘要:

AbstractAutologous transplantation using bone marrow stem cells (BMSC) or peripheral blood stem cells (PBSC) is widely used for non‐Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). We report a randomized, comparative trial comparing BMSC vs. nonmobilized PBSC for responsive NHL or HD. Patients randomized to BMSC (n = 13) vs. PBSC (n = 15) had more rapid neutrophil recovery (median 23 vs. 30 days), RBC independence (25 vs. 62 days), platelet independence (24 vs. 54 days), and shorter hospital stay. However, neither relapse, overall survival, nor relapse‐free survival were different receiving BMSC vs. PBSC (allP>.7). Concurrently, 54 others (34 BMSC, 20 PBSC) were assigned non‐randomly because of resistant disease or marrow unsuitable for harvest and similar patterns of engraftment favoring BMSC over PBSC were observed. In the entire group, BMSC transplantation (n = 47) led to quicker neutrophil recovery (P= .02), RBC (P= .06), and platelet independence (P= .04) and earlier hospital discharge (P= .02) vs. PBSC (n = 35). No difference in relapse, overall, or relapse‐free survival were observed using BMSC vs. PBSC. These data suggest that non‐mobilized PBSC are a satisfactory alternative to BMSC in patients with unsuitable marrow; however, transplantation with non‐mobilized PBSC was associated with slower hematologic recovery, and longer hospital stay. No difference in tumor recurrence rates was observed between the PBSC or BMSC recipients. Unprimed PBSC transplantation offered no clinical advantage to BMSC. Am. J. Hematol. 54:202–208, 1997 © W

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<202::AID-AJH5>3.0.CO;2-#

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

年代:1997

数据来源: WILEY

摘要:

AbstractAnnexin V has a calcium‐dependent binding affinity for anionic phospholipids and activated platelets, and prevents prothrombinase activity. We investigated the clinical significance of IgG anti‐annexin V antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG anti‐annexin V antibodies by ELISA. IgG anti‐annexin V antibodies were detected in 27 of 140 patients (19%). Significantly higher incidences of arterial or venous thrombosis, intrauterine fetal loss, and prolonged activated partial thromboplastin time were found in patients with anti‐annexin V antibodies than in those without anti‐annexin V antibodies. Three patients with thrombosis were found not to have anticardiolipin antibodies, but to show sustained serological reactions for anti‐annexin V antibodies, irrespective of prednisolone administration. These results indicated the clinical characteristics of SLE patients with anti‐annexin V antibodies, and that these antibodies may be associated with the pathogenesis of thrombotic events. Am. J. Hematol. 54:209–213, 1997

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<209::AID-AJH6>3.0.CO;2-#

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

年代:1997

数据来源: WILEY

摘要:

AbstractA single point mutation of the factor V (FV) gene, leading to the substitution Arg506GIn in the FV molecule (FV‐Leiden) and hence resistance to its breakdown by activated protein C (APC), is the most prevalent risk factor for venous thrombosis in the Caucasians. A ratio determined by activated partial thromboplastin time (APTT) of test plasma in the presence or absence of exogenous APC (the APC ratio), is the method widely used to screen individuals with this risk factor for thrombosis. Because of functional defects of vitamin K‐dependent clotting factors in patients on oral anticoagulant therapy, this method cannot be applied to those patients without modification. One modification is to mix test plasma (1:5 or 1:10) with FV‐deficient plasma so that 80–90% of functioning vitamin K‐dependent factors are supplied by the FV‐deficient plasma. Even with 10–20% of FV in the mixture, APC‐resistance still can be demonstrated. In this report, we present our results of the modified APC‐sensitivity assay using FV‐deficient plasma from different commercial sources. APC ratios determined by the original method in which test plasma is not mixed with FV‐deficient plasma can be significantly different from those determined by the modified method in which test plasma is diluted 1:5 with FV‐deficient plasma. This difference between methods was observed not only in normal individuals, but also in FV‐Leiden positive individuals, and in patients on warfarin therapy. Further, APC ratios varied significantly depending on the commercial source of the FV‐deficient plasma. The modified method is apparently suitable to identity APC‐resistance in patients on warfarin therapy, as well as in individuals not receiving anticoagulant treatment. However, one must be aware that APC‐resistance ratios obtained with the modified method are likely to be different from those established with the original method, and the source of FV‐deficient plasma can be a factor influencing the ratios in the former cases. Am. J. Hematol. 5

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<214::AID-AJH7>3.0.CO;2-Z

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

年代:1997

数据来源: WILEY

摘要:

AbstractThe plasma level of soluble E‐selectin (sE) reflects the activation of endothelial cells induced by cytokines such as tumor necrosis factor‐α and interleukin‐1 in vitro. These cytokines are important in the development of coagulation abnormalities in patients with sepsis. We compared the plasma levels of sE in patients with infections suspected of having disseminated intravascular coagulation (DIC) (n = 33) and in patients with underlying disorders other than infections, including solid tumors (n = 28), obstetric disorders (n = 13), hematologic malignancies (n = 13), and liver disease (n = 9), to clarify the involvement of cytokines in the development of coagulation abnormalities in patients with sepsis. Plasma levels of sE in patients with infection were significantly higher than in patients with the other underlying disorders. The plasma level of sE was also significantly higher in patients with infection with DIC (114.6 ± 77.9 ng/ml, n = 21) than in patients with infection without DIC (54.5 ± 53.1 ng/ml, n = 12,P<0.02). There was no significant difference in sE level between patients with the other underlying disorders with and without DIC. The plasma level of sE was significantly correlated with the serum level of FDP(E) in patients with infection. The plasma level of sE was significantly higher in patients with infection with organ failure compared to patients without organ failure. There was no significant difference between patients with the other underlying disorders with and without organ failure. Plasma levels of tumor necrosis factor‐α and interleukin‐6 were detected in only 12.1% and 20.0% of patients with infections, respectively. These observations strongly suggest that plasma levels of sE reflect the activation of endothelial cells induced by cytokines, which may lead to DIC and organ failure in the presence of sepsis. Furthermore, determination of plasma level of sE may be useful for detecting the endothelial activation induced by cytokines in the pathologic conditions of sepsis, even when plasma levels of cytokines cannot be detected. Am. J. Hematol. 54:219–224, 1997 © 1997

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<219::AID-AJH8>3.0.CO;2-Z

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

年代:1997

数据来源: WILEY

摘要:

AbstractThrombopoietin (TPO) is the primary physiologic regulator of platelet production. The effect of TPO on platelet function, both alone and in combination with other hematopoietic growth factors, adenosine diphosphate (ADP), and epinephrine, was investigated using fluorescent‐labeled antibodies to the activation‐dependent antigen CD62 (P‐selectin) and flow cytometry. TPO stimulated CD62 expression on normal human platelets, and this expression was completely inhibited by the soluble extracellular domain of the TPO receptor, MPL. The growth factors granulocyte colony‐stimulating factor (G‐CSF) and erythropoietin (EPO), but not interleukin‐3 (IL‐3) or stem‐cell factor (SCF), also stimulated platelet activation. The combination of EPO, SCF, ADP, and epinephrine with TPO were synergistic for platelet CD62 expression. These data further support a role for TPO in modulating platelet function. Am. J. Hematol. 54:225–232, 1997 © 19

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<225::AID-AJH9>3.0.CO;2-Y

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

年代:1997

数据来源: WILEY

摘要:

AbstractNondominant hereditary spherocytosis (ndHS) is a disorder characterized in some patients by severe hemolytic anemia and marked deficiency of erythrocyte spectrin. This report describes the identification of a variant spectrin chain, α‐spectrin Bughill or αBH, that is associated with this disorder in a number of patients. Tryptic maps of spectrin from affected individuals revealed an acidic shift in isoelectric point of the αll domain peptides at 46 kD and 35 kD. A point mutation at codon 970 of the α‐spectrin gene (GCT→GAT), that changes the encoded amino acid from an alanine to an aspartic acid, was identified in genomic DNA of affected patients. The αBHvariant was present in 8 patients with ndHS from five different kindreds but was absent in 4 patients from two other kindreds. The 8 ndHS patients with the αBHvariant appeared to be homozygous for the αBHvariant by analysis of peptide maps of limited tryptic digests of erythrocyte spectrin. However, following genomic DNA analysis, only 2 of these patients were true homozygotes, whereas 6 were found to be doubly heterozygous for the αBHallele and a second, presumably abnormal, α‐spectrin gene. These results suggest that, in these 6 patients, the second α‐spectrin allele is in fact associated with one or more genetic defect(s), causing decreased accumulation of α‐spectrin. The pattern of transmission of the αBHallele in certain families suggests that the αBHamino‐acid substitution is not itself responsible for ndHS but is more likely a polymorphic variant that, in some but not all cases, is in linkage disequilibrium with another uncharacterized α‐spectrin gene defect that itself is a cause of ndHS. Am. J. Hematol. 54:233–2

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199703)54:3<233::AID-AJH10>3.0.CO;2-E

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

年代:1997

数据来源: WILEY