摘要:

The role of bone marrow stromal cells of the hematopoietic microenviron-ment in ionizing-irradiation leukemogenesis is a focus of current investigation. Evidence from recent in vitro and in vivo experiments suggests that damage by slowly proliferating cells of the hematopoietic microenvironment contributes to the sustained survival of irradiation-damaged hematopoietic progenitor cells/stem cells and can contribute to the selection and proliferation of a malignant clone. The molecular mechanism of the interaction of irradiated stromal cells with attached hematopoietic cells has been difficult to evaluate. Irradiated bone marrow stromal cell line D2XRII demonstrated altered patterns of fibronectin splicing and increased expression of several transcrip-tional splice variants of macrophage-colony-stimulating factor. Differential display has revealed specific radiation-induced gene transcripts which persist after irradiation of stromal cells in vitro or in vivo. In recent experiments, we demonstrated that irradiation of mouse bone marrow stromal cell line D2XRII induces release of significant levels of transforming growth factor (TGF)- β into the tissue culture medium despite the lack of a detectable increase in TGF-β mRNA. Since TGF-β is known to induce reactive oxygen species (ROS), we tested how a target hematopoietic cell line, responsive to ROS by up-regulation of a transgene for an antioxidant protein, responded to cocultivation with irradiated bone marrow stromal cells. Bone marrow stromal cell line GPIa/GBL, derived from long-term bone marrow culture of a C57BL/6J-GPIa mouse, was irradiated in vitro and then cocultured with the interleukin (IL)-3-dependent hematopoietic progenitor cell line 32D cl 3, or with each of several subclonal lines expressing a transgene for human manganese superoxide dismutase (MnSOD). Cobblestone island formation, as a measure of adherence and proliferation by 32D-MnSOD clones in the presence or absence of IL-3, was increased with irradiated compared to control GPIa cells. Furthermore, using a fluorescent dye which detects ROS, hematopoietic cells cocultivated with irradiated stromal cells demonstrated higher levels of intracellular ROS than cells cocultivated and forming cobblestone islands on nonirradiated stromal cells. Since ROS are known to induce mutations in hot spots in the p53 gene, it appears worthwhile to investigate a potential mechanism for irradiated stromal cell induction of hematopoietic stem cell transformation through ROS-induced mutations. The present cell culture and molecular biology techniques provide new methods to analyze the effects of irradiated stromal cells on closely attached hematopoietic stem cells during irradiation leukemogenes

ISSN:0001-5792    

DOI:10.1159/000203708

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The mechanisms accounting for the impaired natural killer cell activity (NKa) in B-cell chronic lymphocytic leukaemia (B-CLL) were investigated in 34 B-CLL patients. We found that patients with B-CLL have indeed very low NKa which may be increased in the presence of recombinant human interferon-α or recombinant human interleukin-2. Patients had also very low mitogen-induced cellular cytotoxicity. Their absolute numbers of peripheral blood CD 16+, CD57+, CD3+, and CD8+ cells were significantly increased. Patients’ NK cells had a normal tumour cell binding capacity but failed to release sufficient amounts of soluble cytolytic molecules upon stimulation with K562 cells or activation with phytohaemagglutinin (PHA). However, B-CLL NK cells released tumour necrosis factor-α (TNF-α) following stimulation with PHA. We concluded that defective NKa in B-CLL patients is probably the result of an impairment in the production and/or release of soluble cytolytic mediators, but not of TNF-α by NK cells. Further studies on the production and release of other cytolytic molecules, such as perforin and granzymes, as well as studies on the possible inability of NK cells to activate the apoptotic mechanisms in the target cells are in progress in our labor

ISSN:0001-5792    

DOI:10.1159/000203709

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied serum lipid and lipoprotein changes before and after induction treatment in 25 acute nonlymphocytic leukemia (ANLL) and in 18 acute lymphocytic leukemia (ALL) patients in order to investigate their relationship with disease activity and their prognostic relevance. ANLL at diagnosis is associated with significantly low levels of all lipid parameters, the same applies to ALL patients apart from plasma triglycerides and very-low-density-lipoprotein cholesterol (VLDL-C) which are significantly higher than in the normal population. In ANLL responders, after effective chemotherapy, a significant increase of total cholesterol, low-density-lipoprotein cholesterol (LDL-C) and apolipoprotein B levels, without changes of high-density-lipo-protein cholesterol (HDL-C) values, is observed. A further decrease of total cholesterol and LDL-C was found in nonresponders and in ANLL responders treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), known for its cholesterol-lowering action; in fact after the completion of GM-CSF therapy, these parameters returned progressively toward normal values. In ALL responders an increase of total cholesterol, HDL-C and apolipoprotein Al with a simultaneous decrease of triglycerides and VLDL-C is evident; no variation was found in the nonresponder group. These results suggest a close correlation between serum lipids and acute leukemia: total cholesterol and LDL-C in ANLL, and HDL-C and VLDL-C in ALL may be considered reliable markers of complete remission and may be useful in the follow-up of leukemic patients.

ISSN:0001-5792    

DOI:10.1159/000203710

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Using the IgG fraction of an antiserum against cord red blood cell (RBC) membranes (F-IgG), antigenic properties of RBC of newborns (n = 24) and patients suffering from anemia (n = 46) [either due to β -thalassemia intermedia (n = 37) or hemorrhage (n = 9)] as compared to those of normal adults (n = 18) were examined with fluorescence microscopy, flow cytometry and radio-immunoassays (RIA). With fluorescence microscopy and flow cytometry 1.01 ± 0.31 and 0.82 ± 0.28% (mean ± SD), respectively, of cord RBC and 0.79 ± 0.31 and 0.53 ± 0.28% of RBC from anemic patients reacted with F-IgG. RBC of normal adults showed virtually no F-IgG reactivity. In anemic patients there was a good correlation between the percent of F-IgG-reactive cells and the percent of reticulocytes, although the former were only two thirds of the latter; the ratio of F-IgG-reactive cells to reticulocytes was higher in posthemorrhagic anemia than in thalassemia. Moreover, double stainings revealed that the majority of F-IgG-reactive RBC were at the reticulocyte stage (80%), and coexpressed transferrin receptor (96%). Furthermore, the F-IgG-positive RBC correlated inversely with Hb levels. When RIA was employed, F-IgG binding to RBC of anemic patients and newborns was similar and considerably and significantly higher than that to RBC from healthy adults. The results demonstrate the reappearance in certain forms of anemia of F-IgG-reactive RBC, which are likely to represent a subpopulation of reticulo

ISSN:0001-5792    

DOI:10.1159/000203711

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Twenty-eight patients (14 with relapsing and 14 with refractory non-Hodg-kin’s lymphoma; NHL) were treated with a combination of CACE chemotherapy (cytosine arabinoside, carboplatin, and etoposide) and recombinant granulocyte colony-stimulating factor (G-CSF) to investigate the efficacy and adverse effects of this regimen. Twenty-eight NHL patients (16 men and 12 women, median age 52 years) received intravenous infusions of cytosine arabinoside (100mg/m2) on days 1-7, carboplatin (250mg/m2) on day 1, and etoposide (70 mg/m2) on days 1-3, as well as the subcutaneous administration of G-CSF (2 μg/kg) beginning on day 9. Eleven of 28 (39.3%) patients achieved complete remission (CR) and 10 patients (35.7%) partial remission (PR). Therefore, a total response rate of 75% was achieved. Nine patients with relapsing disease and 2 with refractory NHL achieved CR. Of the 28 patients 51.5% were alive at 3 years, while the 3-year survival rate for those who achieved CR was 87.5%. The 50% disease-free survival duration was 20.8 months. Adverse effects included leukopenia (2 × 109/1) in 4 patients (14.2%) and thrombocytopenia (50 × 109/1) in 18 patients (64.3%). Although the efficacy of the CACE regimen was demonstrated for treatment of relapsing NHL, the efficacy of CACE was not satisfactory for the treatment of refractory NHL. Further study is required to determine the value of the CACE regimen as therapy for the refractory

ISSN:0001-5792    

DOI:10.1159/000203712

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Pleural effusion in chronic lymphocytic leukemia (CLL) is a relatively rare phenomenon. We report a case of a pleural effusion associated with B-cell CLL but with predominantly reactive T lymphocytes in the effusion. A cell surface phenotype study showed that T lymphocytes predominated in the pleural effusion, although B lymphocytes were predominant in the peripheral blood. Genotypic analysis of the cells in the peripheral blood, bone marrow, lymph node, and pleural effusion showed the same rearrangement pattern of the immunoglobulin heavy chain genes consistent with a B-lymphocytic neoplasm (CLL). A pleural biopsy demonstrated diffuse infiltration of lymphoid cells. Most of the cells demonstrated T cell markers, although some cells revealed B cell markers by immunologic staining. These results suggested that the pleural involvement by B-CLL may have caused a reactive T-lymphocyte proliferation in the pleura and pleural effusion. To our knowledge, this is the first published case indicating that genotypic analysis of immunoglobulin heavy chain gene rearrangement may be useful in the diagnosis of a pleural effusion associated with B-cell CLL.

ISSN:0001-5792    

DOI:10.1159/000203713

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Ki-1 anaplastic large cell lymphoma (Ki-1 ALCL) is a recently recognized entity. Primary presentation in the bone is very rare. Very few cases of primary bone presentation have been reported. All previous reported patients were children and young adults, usually with multiple bone involvement. We report a case of a 60-year old man who presented with extensive mixed blastic and lytic lesions in one tibia, simulating osteogenic sarcoma radiographically, with regional lymphadenopathy. Further studies showed this tumor to be a B cell Ki-1 ALCL. Tumor cells stained positive for Ki-1 antigen (CD30), leukocyte common antigen (CD45), vimentin, and L26 (CD20), negative for cytokera-tin, SI00, Leu Ml (CD 15). The patient was treated with combination chemotherapy and local radiation, with an excellent initial response.

ISSN:0001-5792    

DOI:10.1159/000203714

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We report on a morphologic variant of multiple myeloma, identified in a 39-year-old man, with osteolytic lesions in two ribs and three lumbar vertebrae. Serum electrophoresis was normal and immunofixation of serum and urine was negative. Histologic examination of a resected rib revealed a homogeneous population of neoplastic plasma cells with granular and eosinophilic cytoplasm. Immunohistochemical stains showed monoclonality for λ light chain and negativity for all heavy chains. At the ultrastructural level, the cytoplasm of the neoplastic plasma cells was almost totally occupied by round and elongated mitochondria, pushing the rough endoplasmic reticulum to the periphery. To the best of our knowledge, only two similar cases have been reported in the literature so far. The usefulness of obtaining a clinicopathologic correlation for the behaviour of this extremely rare variant of multiple myeloma is discussed

ISSN:0001-5792    

DOI:10.1159/000203715

出版商:S. Karger AG    

年代:1996

数据来源: Karger