摘要:

AbstractActivation of malignant B cells can lead to extensive morphological changes of these cells. A combination of PMA and TNF‐α can induce adherence of purified B‐CLL cells, which acquire a dendritic cell‐like appearance. This phenomenon that we have termed spreading, is accompanied by upregulation of expression of both β1 and β2 integrin molecules. Spreading was inhibited by the addition of antibodies against CD18 or CD11c. In other B cell malignancies (HCL and NHL), morphological changes could be induced by PMA in the absence of TNF‐α. Culturing in the presence of prednisolone resulted in an inhibition of spreading, most likely mediated via a down regulation of CD18 and CD11c expression. These data indicate that the CD11c/CD18 complex might be important for the adhesive properties of B cells. © 1993 Wil

ISSN:0361-8609    

DOI:10.1002/ajh.2830440402

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to improve erythropoiesis in patients with anemia due to myelodysplastic syndromes (MDS). We treated 13 patients first with recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) for 6 weeks, then with recombinant human erythropoietin (rhEpo) and rhGM‐CSF for the next 12 weeks. Five patients had refractory anemia (RA), 3 refractory anemia with ringed sideroblasts (RAS), and 5 refractory anemia with excess of blasts (RAEB). Ten patients were transfusion‐dependent at the time of inclusion. Eleven patients completed this phase II study. Five responded with an increase in hemoglobin level (3 patients) or a reduction in transfusion requirement (2 patients). We registered no response in the remaining 6 patients during treatment. Patients responding to combined treatment had relatively low concentrations of plasma Epo and plasma ferritin before treatment with rhEpo and a normal karyotype throughout the study. Long‐term bone marrow cultures did not predict the response. Still, responders seemed to have a higher number of colony‐forming progenitors than non‐responders. In conclusion, combined therapy with rhGM‐CSF and rhEpo may stimulate hematopoiesis and correct or improve anemia in some patients with MDS. © 19

ISSN:0361-8609    

DOI:10.1002/ajh.2830440403

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

年代:1993

数据来源: WILEY

摘要:

AbstractTo determine whether warm‐antibody autoimmune hemolytic anemia (AIHA) responds to treatment with intravenous gammaglobulin (IVGG), we conducted separate pilot studies at three institutions enrolling a total of 37 patients. We combined these results with a review of 36 cases of AIHA treated with IVGG reported in the literature. Sixteen clinical variables were examined to determine associations with response to IVGG. Overall, 29 of 73 patients (39.7%) responded to IVGG therapy. Two variables were strongly related to a good response to IVIG: the presence of hepatomegaly (with and without splenomegaly) and a low pre‐treatment hemoglobin. A trend towards a better response was observed in the 11 children. Overall, IVGG provided acute benefit in only 1/3 of patients and therefore cannot be recommended as standard therapy for AIHA. It may, however, be useful as adjunctive treatment in selected cases, such as in those with a pre‐treatment hemoglobin<6–7 gm/dl or those with hepatomegaly, and in clinical settings where the toxicity of other treatments may be an important consideration. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830440404

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

年代:1993

数据来源: WILEY

摘要:

AbstractA thrombotic etiology has been suggested as the cause of idiopathic avascular necrosis of the hip, although the underlying pathophysiological mechanisms are unknown. Transient osteoporosis of the hip has also been suggested to represent bone marrow edema that may be related to ischemia. We evaluated four patients with idiopathic avascular necrosis and one patient with transient osteoporosis of the hip for thrombotic potential placing a special emphasis on the fibrinolytic system. All five patients had identifiable abnormalities of fibrinolysis. Four patients had elevated levels of plasminogen activator inhibitor (PAI‐1) and one patient had an inadequate increase in tissue plasminogen activator (tPA) post venous occlusion. Serum triglycerides were increased in three of the patients. These findings suggest an association between decreased fibrinolytic potential and the subsequent development of avascular necrosis and transient osteoporosis of the hip. These patients should have an evaluation of the fibrinolytic system with tPA and PAI‐1 levels as well as a lipid profile. © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830440405

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have recently demonstrated that azidothymidine (AZT) elevates the levels of circulating platelets in mice made immune deficient by infection with LP‐BM5 murine leukemia virus (MAIDS mice). In an attempt to elucidate the mechanisms of the AZT platelet elevating effect, we examined the number of splenic and bone marrow megakaryocyte colony‐forming cells (CFU‐mk) and the ploidy of megakaryocytes derived from CFU‐mk using fluorescence cytophotometric methods. Two other dideoxynucleosides (ddN) 2′3′‐dideoxyinosine (ddL) and 2′3′‐dideoxycytidine (ddC) were assessed to determine the specificity of the effect of AZT. MAIDS mice were given ddN in drinking water for 15 days. AZT was the only ddN that significantly increased circulating platelet levels in MAIDS mice. AZT significantly increased splenic CFU‐mk in MAIDS mice, but bone marrow CFU‐mk were not affected. ddL and ddC failed to change either platelet levels or the numbers of splenic or bone marrow CFU‐mk. The ploidy of megakaryocytes derived from splenic and bone marrow CFU‐mk were examined by first identifying CFU‐mk by staining for acetylcholinesterase, followed by nuclear staining with propidium iodide. The fluorescence of individual cells was then measured using a Perceptics image analysis system. Modal ploidy of CFU‐mk megakaryocytes derived from spleen cells of AZT‐treated immunodeficient mice was shifted upwards from 16N to 32N. Similarly, AZT treatment changed the modal ploidy number of colony megakaryocytes derived from bone marrows of immunodeficient mice from 16N to 32N. The ploidy distribution was also significantly shifted. ddL and ddC failed to significantly alter either modal ploidy number or distribution of megakaryocytes derived from splenic or bone marrow CFU‐mk. These findings suggest that AZT may affect physiological processes that lead to platele

ISSN:0361-8609    

DOI:10.1002/ajh.2830440406

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

年代:1993

数据来源: WILEY

摘要:

AbstractA study of 565 Puerto Rican patients with storage pool deficient (SPD) Hermansky‐Pudlak syndrome (HPS) demonstrated that most HPS patients had minor bleeding episodes while others had repeated, severe hemorrhagic episodes requiring transfusion. The severity of bleeding in these latter patients could not be attributed to their SPD alone. As swine with SPD platelets and low von Willebrand factor antigen (vWF:Ag) have more severe hemorrhages than pigs with either defect alone, 146 albino patients and 46 normally pigmented patients were examined for their level of vWF:Ag. The risk of SPD HPS patients having severe, repeated bleeding episodes increased when vWF:Ag fell below 70 U/dL. Family studies indicated that low vWF:Ag levels were more frequently associated with O blood group than from a gene suppressing production or release of vWF1. HPS patients should be tested for vWF:Ag levels. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830440407

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI‐1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI‐1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI‐1 activity was significantly greater in patients (P<0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P= 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI‐1 activity but also by reduced total uPA concentration. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830440408

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

年代:1993

数据来源: WILEY

摘要:

AbstractSeveral studies have reported increased von Willebrand factor (vWF) levels in plasma of uremic patients, with a normal multimeric pattern. Two recent studies, however, have shown a reduction of the larger multimers of plasma vWF and one has also found low levels of platelet vWF in uremic patients with prolonged bleeding time (BT). We have measured plasma and platelet vWF and analyzed its multimeric pattern in 20 uremic patients, 11 with a prolonged BT and 9 with a normal BT. For Plasma vWF, no difference for vWF:Ag, RiCof, and ristocetin‐induced platelet agglutination was found between the two groups with normal and prolonged BT. The multimeric pattern of plasma vWF, as evaluated by densitometric scanning of the electrophoretic gels, was normal in both groups. For platelet vWF, vWF:Ag and RiCof content was similar in the two groups. The multimeric pattern was indistinguishable from that of normal platelets. In conclusion, our study does not confirm the presence of a structural defect of plasma vWF and the reduction of platelet vWF content in uremia. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830440409

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have identified a severely unstable hemoglobin variant through sequencing of amplified DNA involving the α1‐globin gene; the mutation is located in codon 59 (CCG CAG) andresults in a Gly—Asp replacement. This amino acid substitution concerns a glycine residue at an internal position in the E helix, which is in close contact with a glycine residue of the B helix; introduction of the larger and charged aspartic acid residue greatly affects the stability of the molecule. This variant was present in association with a common α‐thalassemia‐1 deletion [‐(α)20.5 kb] in two adults and caused a severe type of Hb H disease with anemia, low levels of Hb A2, increased → chain, and Hb Bart's. In vitro chain synthesis in reticulocytes showed a high specific activity of the variant α chain. Only a minute quantity of Hb H was present but instead about 10% of Hb Bart's was observed. The increased synthesis of γ chains was likely due to specific characteristics of a chromosome with haplotype #3, which was present in both patients. The same family was studied 18 years ago [1]; the improved methodology presently available has led to a corrected diagnosis for these patients. © 199

ISSN:0361-8609    

DOI:10.1002/ajh.2830440410

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

年代:1993

数据来源: WILEY

摘要:

AbstractQuantitative changes of hemostatic molecular markers were studied in patients with nephrotic syndrome. The plasma levels of fibrinopeptide A (FPA), thrombin‐antithrombin III complex (TAT), products of thrombin activation, and fragment F1 + 2 (F1 + 2), a product of prothrombin activation, were measured by enzyme immunoassay in 21 patients with nephrotic syndrome and in 16 normal controls. The mean value of FPA was 17.5 ± 7.5 ng/ml (mean ± SD) in nephrotic patients and 4.5 ± 0.3 ng/ml in normal controls (P<0.02); F1 + 2 concentration was 1.4 ± 0.3 ng/ml in nephrotic patients and 0.5 ± 0.1 ng/ml in normal controls (P<0.001); TAT level was 1.0 ± 0.3 μg/l in nephrotic patients and 0.2 ± 0.1 μg/l in normal controls (P<0.05). These data indicated intravascular hemostasis activation. Based on these results, we propose that low antithrombin III level in nephrotic patients may be due to both urinary loss and intravascular consumption. © 1993 Wile

ISSN:0361-8609    

DOI:10.1002/ajh.2830440411

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

年代:1993

数据来源: WILEY