摘要:

AbstractPlatelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c‐sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patient

ISSN:0361-8609    

DOI:10.1002/ajh.2830350302

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe have recently described a new two‐phase liquid culture that supports the development of human erythroid progenitors (Fibach et al.,Blood73:100, 1989). The procedure separates the erythroid burst‐forming units (BFUe) from the erythroid colony‐forming units (CFUe) stage and enables quantitation of the proliferation and differentiation of BFUe into CFUe. In the present study we have utilized this system to study erythroid progenitors in polycythemia vera (PV). The abnormality of the erythroid series in PV has been shown to be associated with an increased responsiveness of the progenitors to the hormone erythropoietin (Epo). A basic question in this clonal stem cell disorder is at what developmental stage this abnormality of the PV clone is phenotypically expressed. We have studied this question by comparing the development of Epo‐dependent and Epo‐independent CFUe from peripheral blood BFUe of the PV patient during the BFUe to CFUe transition in the liquid culture. The results indicated that both types of CFUe are generated and that in all cases tested the ratio of Epo‐independent progenitors at both the BFUe and CFUe stage was similar indicating no preferential development of Epoindependent CFUe. These results suggest that the abnormality of the PV erythroid progenitors is expressed only at the CFUe level. Moreover, since the liquid culture did not contain Epo, the results also support the conclusion that BFUe do not require Epo for proliferation or differentiatio

ISSN:0361-8609    

DOI:10.1002/ajh.2830350303

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

年代:1990

数据来源: WILEY

摘要:

AbstractTwo proteins, p70 and p80, were found in chemically crosslinked complexes with class II MHC molecules and Iiafter 3–12 hr labelings with [35S]methionine. Two‐dimensional, nonreduced/reduced SDS gel electrophoresis of immunoprecipitated complexes revealed 1) endogenous disulfide linkages between Ii‐Iiand Ii‐p70 and 2) chemically crosslinked, nearest neighbors of α‐β, α‐Ii, Ii‐p70, and α‐p80. Although such nearest neighbors within multimeric complexes were identified as dimers in nonreduced/reduced 2D gels, stoichiometries could not be determined in the high molecular weight complex(es), which included α, β, Ii, p70, and p80, and were not separated in the first dimension. p80 was not the chondroitin‐sulfate form of Ii(Ii‐CS) because it was not electrophoretically heterogeneous and was not sensitive to chondroitinase ABC. p70 was not hsp72/74 detected with C92 or N27 mAbs, and p80 was not BiP detected with its respective mAb. While only these two proteins associated prominently with class II MHC antigens and Iilate after synthesis, th

ISSN:0361-8609    

DOI:10.1002/ajh.2830350304

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

年代:1990

数据来源: WILEY

摘要:

AbstractEvidence of activation of the clotting system in individuals with sickle cell anemia (SCA) has been observed by several investigators. It has been suggested that the clotting and fibrinolytic systems may play a role in the pathophysiology of vaso‐occlusion in SCA. We reported previously evidence of abnormal fibrinolytic activity as reflected in decreased releasable tissue plasminogen activator (t‐PA) using a functional assay. We have examined the mechanism of the decreased functional releasable t‐PA in individuals with SCA. We studied 12 patients with respect to releasable t‐PA, fast acting inhibitor to t‐PA (or PAI‐1), and immunoreactive or antigenic t‐PA. These SCA individuals were at their baseline states and not taking medications known to interfere with the fibrinolytic or clotting systems. We found that the mean releasable t‐PA for the SCA individuals was 0.01 IU/ml of plasma with a standard error of mean (SEM) of 0.01. The mean releasable t‐PA of 118 healthy normal controls was 0.70 IU/ml with SEM 0.10 (P<0.001). The mean level of fast‐acting inhibitor to t‐PA in unoccluded circulation of the SCA patients' plasma was 16.5 IU/ml with SEM of 3.54. The mean plasma levels of fast‐acting inhibitor to t‐PA in 56 healthy controls was 2.56 IU/ml with SEM of 0.29 (P<0.0001). The SCA patients had a mean baseline t‐PA antigen level of 5.98 ng/ml with SEM of 1.72. The mean level of t‐PA antigen of 78 healthy controls using the same technique was 4.3 ng/ml with SEM of 2.7 (not significant). The mean baseline functional t‐PA for SCA individuals was 0.15 IU/ml with SEM 0.01 and the mean baseline functional t‐PA for 118 controls was 0.17 IU/ml with SEM 0.10. These data suggest that the mechanism of decreased releasable t‐PA in sickle cell anemia is related to an elevation of fast‐acting inhibitor to t‐PA and that antigenically t‐PA is present in normal quantities

ISSN:0361-8609    

DOI:10.1002/ajh.2830350305

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

年代:1990

数据来源: WILEY

摘要:

AbstractHemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly (P<0.001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co‐stored with ATP, is unaltered. Analysis of the CRF‐derived platelets reflects a selective acquired storage pool defect with significantly (P<0.001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different (P<0.02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times (P<0.001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patie

ISSN:0361-8609    

DOI:10.1002/ajh.2830350306

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HMW‐F) of plasma, separated by an Evaflux® 2A fractionator, improved the patient's thrombocytopenia as the plasma infusion, and maintained its beneficial effect for about 2 weeks during early pregnancy. Though an occurrence of a toxemia‐like syndrome responded to repeated plasma infusion, the dose of plasma required to improve the thrombocytopenia gradually increased and reached 5,040 ml by the 20th week of pregnancy. Thus, instead of periodic infusions of whole plasma, periodic infusions of the HMW‐F of plasma were used. Under this regimen the platelet count remained above 10.0 × 104/μl during late pregnancy, and the total dose (2,600 ml) of HMW‐F of plasma that was administered until delivery at full term was less than the dosage of whole plasma that was used during early pregnancy. In this manner we were able to obtain a healthy baby by controlling the patient's TTP during pregnancy. This method of preventing thrombocytopenia appears to be safer with respect to volume loading during pregnancy in the T

ISSN:0361-8609    

DOI:10.1002/ajh.2830350307

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

年代:1990

数据来源: WILEY

摘要:

AbstractFour commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R‐500A® and the PALL RC50® were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100® which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The Imugard IG‐500® had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50® to 92.2% for the Sepacell

ISSN:0361-8609    

DOI:10.1002/ajh.2830350308

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

年代:1990

数据来源: WILEY

摘要:

AbstractIn a 2‐yr old girl a hemolytic anemia was present since birth requiring multiple blood transfusions. Pyruvate kinase deficiency was suspected on the basis of a marginal enzyme activity, but could not be established due to the presence of massive numbers of donor cells in her peripheral blood. However, by density fractionation we succeeded in the isolation of a small fraction of the patient's own cells, in which a severe pyruvate kinase deficiency could be detected. In contrast hexokinase and glucose‐6‐phosphate dehydrogenase activities were extremely high, which is indicative that a very immature cell population is present in this fraction.In immunofluorescence studies a clear crossreaction was apparent with anti M2‐type pyruvate kinase antibodies, whereas only a faint reaction with anti L‐type could be detected. Despite the presence of a slight amount of L‐type immunoreactive material, the residual activity in the patient's cell fraction could only be attributed to M2‐type pyruvate kinase as was shown by cellulose acetate el

ISSN:0361-8609    

DOI:10.1002/ajh.2830350309

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

年代:1990

数据来源: WILEY

摘要:

AbstractDuring the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high‐dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high‐dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non‐cross‐resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early

ISSN:0361-8609    

DOI:10.1002/ajh.2830350310

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe report a Japanese newborn who developed alloimmune thrombocytopenia by the antibodies to the newly discovered platelet antigen Yuka. The infant recovered uneventfully in 10 days without specific treatment. Antiplatelet ailoantibodies in the patient were IgG class detected by mixed passive hemagglutination (MPHA). Family study showed that Yukaantigen was inherited as an autosomal dominant trait. Cases with Yuka‐associated alloimmune thrombocytopenia are reviewe

ISSN:0361-8609    

DOI:10.1002/ajh.2830350311

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

年代:1990

数据来源: WILEY