摘要:

Abstract:Proliferation and differentiation of hematopoietic cells are controlled by pleiotropic regulatory molecules. While the sequences of these factors are not related, their membrane receptors are restricted to two gene families with homologous domains. The members of the hematopoietic (or cytokine) receptor family (for erythropoietin, interleukins‐2, ‐3, ‐4, ‐6 and ‐7, granulocyte‐macrophage and granulocyte colony‐stimulating factor) are composed of multiple subunits necessary for high‐affinity binding and cell signalling. Signal transducing mechanisms are largely unknown. The occurrence of variant signal transducers in different tissues could explain the pleiotropy of these regulatory molecules. Members of the receptor tyrosine kinase family bind dimeric forms of macrophage colony‐stimulating factor, stem cell factor and platelet‐derived growth factor leading to kinase activation and phosphorylation of many substrates involved in production of second messengers. Soluble forms (binding proteins) exist for members of both families. These may be proteolytic cleavage products of transmembrane receptors or naturally secreted products. Such binding proteins can potentially function as inhibitors in feedback regulation and in protection and transport of cytokines and would provide a rational therapy when cytokines are produced in excess. Knowledge of signal transduction mechanisms and of the three‐dimensional structure of ligands and receptors can lead to the design of drugs with

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01786.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Neutrophils from patients suffering from severe congenital neutropenia (SCN), who were receiving recombinant human granulocyte colony‐stimulating factor (rhG‐CSF), were investigated in order to analyze the previously described decrease in chemotaxis. This study demonstrated the decreased chemotaxis to five well‐known chemoattractants, FMLP, C5a, IL‐8, LTB4 and PAF. To further investigate this impairment of patients' neutrophils, receptors and receptor turnover for chemoattractants were examined using flow cytometry. We found 1) increased FMLP receptor and decreased C5a receptor expression, 2) a normal expression of intracellular FMLP receptors after incubation with PMA, 3) increased loss and decreased re‐expression of FMLP receptors after incubation with this peptide, 4)normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1 (CD11a/CD18), 5) further signs ofin vivopreactivation: high expression of Fcγ‐RI (CD64) and Fcγ‐RII (CD32), decreased expression of Fcγ‐RIII (CD16), increased expression of CD14, and low expression of HLA‐DR. These data demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is not due: a) to a decrease in the number of intra‐ or extracellular FMLP receptors; b) to a decrease of adhesion molecules. However, the decreased chemotaxis could result from an altered FMLP receptor turnover. The relevance of the altered Fcγ‐receptor pattern for thein vivooccurrence of side‐effects, e.g. the necrotic vasculitis, of G

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01787.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:In this retrospective investigation from Malmö, a city well‐suited for epidemiologic studies, 177 patients (88 males and 89 females) with polycythemia vera (PV) were identified between 1950 and 1984. The incidence rate (number of cases/100 000/yr) in both sexes increased significantly, being 1.0 in 1950–1959 and 2.6 in 1980–1984 (adjusted to the European age‐standardized population). This is the highest rate reported to date. In 1970–1984 the highest age‐specific incidence rates (number of cases/100 000/yr) were found in males ≥ 80 yr and females 70–79 yr of age, being 18.3 and 14.6, respectively. A subgroup of 12 (7%) was identified where the PV diagnosis was not obvious on entry into the study but where it became clear during follow‐up. 16 PV patients (9%) had verified or suspected arterial hypoxemia caused by a concomitant condition. We conclude that the increasing PV incidence rates, mainly confined to older age groups, are probably due to better

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01788.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Langerhans cells originate in bone marrow and probably belong to the monocyte‐macrophage lineage. CD1 is a specific marker of Langerhans cells. By immunofluorescence and immunoelectron microscopy, CD1a antigen and myeloid markers (CD11, CD13, CD14, CD15, CD33, HLA‐DR) were studied in 53 cases of acute myeloid leukemias (AML) and 3 acute lymphoblastic leukemias (ALL). The 11 ANLL without monocytic component were CD1a negative. 2/5 of acute myelomonocytic leukemias (AML4) and 9/37 of acute monocytic leukemias (AML5) were positive. All 3 ALL were negative. No correlation was found between CD1a and myeloid markers. CD1a+ AML did not differ from CD1a‐AML with regard to cytogenetics or response to therapy. The CD1a positive cells may originate from an abnormal proliferation of CD1a positive cells which are present in bone marrow and which may differentiate into Langerhans cell precu

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01789.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Essential thrombocythemia, a myeloproliferative disorder of clonal origin, is often associated with various clinical manifestations resulting from thromboembolic or hemorrhagic complications. The long‐established successful method of treatment with cytotoxic agents or radioactive phosphorus has recently been superseded by interferon alpha. We treated 14 symptomatic patients with 5 times 106IU recombinant interferonα‐2b s.c. daily. 12/14 pts responded within 14–75 days. When platelet counts decreased to below 450 g/l the frequency of administration was reduced stepwise. 7 patients remained in CR during this reduction phase and treatment was stopped in 5 pts after 12–32 months. Until now, 3 of them are still in continuous good PR without any drug therapy and free of symptoms for 3+, 19+ and 36+ months. Continuous response during maintenance was associated with age, initial platelet count and time required to reduce platelet counts to

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01790.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:80 patients with resistant or relapsing multiple myeloma received a combination of vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA) as a second‐line chemotherapy. 27 of them were resistant to primary chemotherapy with alkylating agents, and 53 had relapsed after initially responding to these drugs. An objective response was achieved in 39 patients (49%): in 14 patients who were primarily resistant (52%) and in 25 patients who had a relapse (47%). Of 41 patients relapsing during maintenance chemotherapy 14 (34%) responded, while 11 of 12 patients (92%) treated for a relapse off‐therapy responded. The median duration of response was 22 months. Severe complications, in most cases infections, occurred in 30% of patients, and were fatal in 9% of the cases. According to our experience the five‐drug combination MOCCA is an effective second‐line chemotherapy for myeloma patients primarily resistant to or relapsing after therapy with single alkylating

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01791.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:5 patients with refractory aplastic anemia (AA) received long‐term administration (2–11 + months) of recombinant human G‐CSF (rhG‐CSF) in doses from 250–500 μg/body/day by intravenous infusion or 75–300 μg/body/d by subcutaneous injection. All 5 evaluable patients showed a substantial increase in absolute neutrophil count (ANC) with a recovery of myeloid components in the bone marrow after 1 to 2 months of treatment. Interestingly, 2 out of the 5 patients showed a dramatic improvement in severe anemia after 2 to 4 months of treatment accompanying a recovery of erythroid components in the bone marrow. In addition, there was no serious infection before or during therapy. Long‐term administration of rhG‐CSF was well tolerated because of its minimal toxicity. Clonal assay revealed a recovery of myeloid progenitors in all patients and a recovery of erythroid progenitors in 3 out of the 5 patients. These results suggest that long‐term administration of rhG‐CSF at least mobilizes residual myeloid as well as erythroid progenitor cells and induces a bilineage response in

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01792.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Flow cytometry (FCM) has gained wide use in the determination of clonality in B‐cell lymphoproliferative diseases and many methodological variations exist. We have compared the suitability of a) dual fluorochrome (FITC/PE)‐labelled monoclonal antibodies, b) single fluorochrome (FITC)‐labelled monoclonal antibodies and c) F(ab')2fragments of FITC‐labelled polyclonal antibodies for flow cytometric determination of clonality using commercially available software and a short sample preparation protocol. The FCM method was validated by analysis of immunoglobulin heavy chain and light chain gene rearrangements. We recommend the use of FITC‐labelled monoclonals to obtain three parameters, the k/λ ratio, D and D/S(n) values (Kolmogorov‐Smirnov statistics) instead of the commonly used k/λ ratio and D values only. This allows the use of a rapid sample preparation protocol to blood and bone marrow aspirates without sacrificing sensitivity or specificity obtained by the usu

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01793.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01794.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb01795.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY