摘要:

Abstract:Platelets and megakaryocytes have been characterized in a Bernard‐Soulier syndrome (BSS) kindred with respect to glycoprotein (GP) membrane receptors and measurements of thrombocytopoiesis. The index patient exhibited lifelong bleeding tendency, moderate thrombocytopenia (35 × 109/1), giant platelets (mean platelet volume 12.5 μm3compared to 7.5 ± 1.5 μm3in normals), absent ristocetin‐induced platelet agglutination and absent binding of von Willebrand factor (vWF). Flow‐cytometric analysis revealed absent platelet binding (0–2%) of monoclonal antibodies (mAb, LJ‐P3, LJ‐Ibl and LJ‐Ibl0) directed against distinct epitopes on membrane GPIbα of the GPIb‐IX complex, and normal binding of LJ‐P4 mAb directed against GPIIb/IIIa complex (relative to increased platelet surface area). Marrow megakaryocytes also failed to express GPIb‐IX complex, but demonstrated normal expression of GPIIb/IIIa. Among 6 asymptomatic family members, the patient's mother and 2 of his 4 children exhibited approximately 50% binding of anti‐GPIbα mAb to their platelets by both flow cytometry and direct binding studies using125I‐vWF,125I‐LJ‐Ibl and125I‐LJ‐Ibl0 mAb. Marrow megakaryocytes were increased in the average cell volume and cytoplasmic granularity with a corresponding increase in ploidy (46%>16N compared to 22 ± 5% in normal individuals), a pattern typical of megakaryocytes stimulated by thrombocytopenia. Autologous111In‐platelet life span was shortened to 4.1 days (compared with 9.5 ± 0.5 days in normal subjects), and the turnover of platelet mass in the circulation was near normal. The data directly demonstrate that the platelet membrane GPIb‐IX defect in BSS originates in megakaryocytes at all levels of cell maturation, and exclude the possibility that the receptor abnormality is acquired during cell maturation or after platelets are released into the circulation. Since marrow megakaryocytes exhibited cellular changes consistent with stimulated megakaryocytopoiesis, these results also suggest that thrombocytopenia in this kindred of BSS is a consequence of both decreased platelet s

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00645.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:We analyzed the surface phenotype of CD34‐positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34*** cells (45.8%, 37.8%, respectively) (both p<0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony‐stimulating factor (G‐CSF) was significantly higher than that of those without G‐CSF. Most of the PB CD34+ cells possessed the HLA‐DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt‐1. The administration of G‐CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p<0.01). This G‐CSF mobilization also resulted in an increased number of CD 13‐34+ and CD33‐34+ cells and all types of colony‐forming cells. On the other hand, macrophage colony‐stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G‐CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid diff

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00646.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:To investigate the role of protein phosphorylation in the early phase of EPO‐mediated signal transduction, we EPO‐stimulated a murine erythroid cell line ELM‐I‐1 transformed by plasmids comprised of the c‐fos enhancer/promoter linked to the luciferase gene. Using this reporter gene system, we previously showed that EPO‐induced activation of the c‐fos promoter can be detected rapidly and sensitively as an elevation of cellular luciferase activity. In this study, we first examined the role of protein tyrosine phosphorylation. The tyrosine phosphatase inhibitor orthovanadate not only induced luciferase activity by itself but enhanced the action of EPO. On the other hand, the tyrosine kinase inhibitors erbstatin and herbimycin suppressed the effect of EPO. Next, the role of protein kinase C (PKC) in the EPO response was assessed. The PKC activator phorbol myristate acetate (PMA) not only induced luciferase activity by itself but enhanced the action of Epo. On the other hand, the PKC inhibitor 1‐(5‐isoquinolynyl‐sulfonyl)‐2‐methylpiperazine (H7) suppressed the effect of Epo and PMA, whereas a nonspecific protein kinase inhibitor, N‐(2‐Guanidinoethyl)‐5‐Isoquinolinesulfornamine (HA1004) inhibited the action of neither Epo nor PMA. Another known PKC inhibitor staurosporine (STSP) did not inhibit but rather enhanced the effect of Epo. This action of STSP was blocked by H7but not by HA1004. These results suggest that the EPO‐mediated early signal transduction pathway leading to c‐fos expression involves protein‐tyrosine phosphorylation, is modulated by tyrosine phosphatase activi

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00647.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Fifty‐three patients affected with B‐cell chronic lymphocytic leukemia (CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico‐hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B‐CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population. Sex distribution, mean peripheral lymphocyte count, platelet count, distribution among Rai's and Binet's stages, total tumor mass (TTM) score, histological pattern of bone marrow infiltration and lymphocyte doubling time (LDT) were similar to a series of 201 CLL cases older than 50 years. Only hemoglobin mean level was significantly higher in younger patients (13.1 ± 2.1 vs 12.2 ± 2.6 g/dl; p<0.01). The overall median survival was 7.1 years. Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of “smoldering” CLL, had a very long survival (75% survival probability at 16 years). Life‐expectancy of younger patients was significantly longer than that of older ones (median survival, 7.1 versus 4.1 years; p<0.05). However, when the background mortality due to non‐CLL related deaths (i.e., cardiovascular complications, epithelial cancers) was removed, survival advantage of young cases disappeared. In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well‐defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive the

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00648.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23–48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the deceased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma‐exchange and pharmacologic ther

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00649.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Tissue deficiency of vitamin B12and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B12and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B12and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B12or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B12with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty‐four percent of patients with a low serum vitamin B12and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost‐effective process than sHcy assay in most instances to determine the presence of tissue deficie

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00650.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Up to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are refractory to standard therapy with corticosteroids and splenectomy. The treatment of refractory ITP is barely effective, but promising results of interferon therapy were reported recently. In a prospective study 21 refractory ITP patients were treated with interferon alpha 2B at 3 million Units three times a week for a period of 4 weeks. Ten out of 21 patients had a response, of whom 2 had a complete response of 3.5 and 7 months duration, after which both relapsed. One other patient retreated after relapse has a complete response of 24 + months. The characteristics of the responding patients were not different from the non‐responding patients. Adverse effects were minimal. Short treatment with interferon in refractory ITP patients may be justified and the results reported here challenge us to elucidate the mechanism of action of interfero

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00651.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Thirteen patients withde novoacute non‐lymphocytic leukaemia (ANLL) refractory to standard chemotherapy for remission induction and 12 patients with ANLL in relapse were treated with low‐dose cytosine arabinoside (LD ara‐C) 10 mg/m2subcutaneously every 12 hours for 21 days. Five of 13 patients (38%) and 6 of 12 patients (50%), respectively, obtained a complete remission (CR). Of these, 7 patients subsequently relapsed after 2–76 months, while 4 patients remain in CR after 7–131 months. Compared to standard intensive regimens treatment with LD ara‐C was rather non‐toxic, requiring platelet transfusions and antibiotics in only 6 and 13 cases, respectively. Three patients (12%) died during induction therapy with LD ara‐C; 2 had a cerebral haemorrhage and 1 developed anuria following a staphylococcol septicaemia. In conclusion, therapy with LD ara‐C may be preferable to more intensive and toxic regimens in the treatment of patients with relapsed o

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00652.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00653.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1994.tb00654.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY