ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01930.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe deoxyuridine suppression test (dUST) was used to evaluate human immunodeficiency virus type 1 positive (HIV‐1) patients with low serum levels of vitamin B12and/or low red cell folate and to assess any possible interferences of azydothymidine (AZT) in this test. The dUST was studied in 29 HIV‐1 positive patients, 18 without low serum vitamin B12or low red cell folate and 11 with low serum vitamin B12(6 patients), low red cell folate (4 patients) and 1 case with both. The role of AZT was studied using different concentrations (0.2, 2.5 and 10 μM/ml) in 2 groups: 1 group of 5 patients with vitamin B12and/or folate deficiency and another group consisting of 13 healthy subjects. Methotrexate (MTX) (50 μg/ml) was added to induce a folate megaloblastic pattern in the latter group. Results of the dUST in the HIV‐1 group without low levels of serum vitamin B12fell within the health‐related reference interval values. A vitamin B12deficiency was only detected in 1 case in the HIV‐1 group with low serum vitamin B12, although a folate deficiency pattern was observed in the 4 patients with low red cell folate. In the healthy subjects AZT induced a dose‐dependent decrease of the MTX‐induced folate megaloblastic pattern. The pattern was also observed in the group of patients with vitamin B12or folate deficiency, although AZT did not entirely interfere with the dUST. The effect of AZT on the dUST was attributed to a decrease in the incorporation of the isotope in the absence of deoxyuridine. The dUST is useful in differentiating vitamin B12deficient patients from HIV‐1 infected patients with low levels of

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01931.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe purine nucleoside analogues fludarabine (Fl) and chlorodeoxyadenosine (2‐CdA) are considered to be cell cycle specific agents which require DNA synthesis for cytotoxicity. However, their efficacy in the treatment of CLL, an indolent lymphoid malignancy suggests additional mechanisms of action. Like cytosine arabinoside (AraC), Fl and 2‐CdA gain access to the cell via a specific nucleoside transporter (NST) protein. To investigate the mode of action of these drugs in CLL, we used a fluorescent ligand for the NST (5‘‐(SAENTA‐ x 8)‐fluorescein) and 3‐colour flow cytometry to determine NST expression on CD5+/CD19+B‐cells from the peripheral blood (PB) of patients with CLL. NST levels on these cells was found to be not significantly different from normal control lymphocytes (mean = 485±425) vs. (mean = 553±178). Exposure to varying concentrations (0, 3 μM and 30 μM) of Fl and 2‐CdA, however, resulted in an upregulation of NST (mean = 1552±775 with 30 μM FL; mean = 3392±2197 with 30 μM 2‐CdA) after 48 h. “Large” lymphoid cells (not present in normal PB) were found to express significantly more NST (mean = 2540±2861) and have a higher proliferative capacity than “small” cells (mean = 357±517 NST/cell). Incubation of CLL cells with Fl (n= 6) and 2‐CdA (n= 8)in vitroover 48 h also resulted in an increase in the proportion of cells in S‐phase (0 μM = 0.2±0.1; 30μM FL = 2.4±2.0; 30 μM 2‐CdA = 3.3±1.3) and a significant increase in morphologically identifiable apoptosis. Apoptosis was confirmed by flow cytometric DNA analysis (0 μM = 13±8%; 30 μM FL = 40±20%; 30 μM 2‐CdA = 48±11%).In situhybridization using a biotinylated cDNA bcl‐2 probe demonstrated that bcl‐2 mRNA expression was markedly decreased in treated cells after 24 h. These studies have demonstrated that: (1) NST expression on CLL lymphocytes is low; (2)in vitroexposure to the analogues increases both the level of NST expression and the % cells in S‐phase; (3) exposure to the a

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01932.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The fate of polymorphonuclear neutrophilic granulocytes (PMN) after their mobilization from the bone marrow of healthy individuals is not clearly understood. It has been suggested that there is a continuous utilization of these cells in widespread, subclinical inflammatory foci, where they are ultimately degraded. The goal of the present experiments was to determine whether an alternative ecotaxis (“homing”) exists, namely sequestration and degradation of PMN by mononuclear phagocytes exposed to the bloodstream in the liver, spleen and bone marrow. Blood PMN were collected from donor rats, labelled with51Cr, and injected i.v. into 2 syngeneic rats, one of them having an induced sterile peritonitis. After various time intervals up to 18 h, the rats were killed and exsanguinated. As expected, we found cell‐bound radioactivity in the inflamed peritoneal cavities, and also a high amount of radioactivity in liver, spleen, and bone marrow. The bone marrow uptake of PMN appeared to be much lower in the inflammation rats than in the normal controls. These findings were confirmed in PMN transfer experiments using PVG rats congenic for theRT7alloantigenic system. Here, transfused blood leukocytes were traced with fluorescent, monoclonal HIS41 antibodies and flow cytometry. A possible corticosteroid effect on the bone marrow sequestration could not be substantiated. Uptake and degradation of PMN takes place in organs containing phagocytes exposed to the bloodstream. Sequestration of PMN in the bone marrow is apparently down‐regulated in inflammatory states, perhaps increasing the PMN availability to inflamed

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01933.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractAnti‐cardiolipin antibodies (ACLA) have been suggested to play a role in the pathogenesis of thrombocytopenia. When sera from 40 patients with chronic idiopathic thrombocytopenic purpura (ITP) were analyzed for ACLA, these autoantibodies were present in 12 (30%). In 4 sera the antibody activity was restricted to the IgG or IgM isotype, respectively, while 4 of the samples contained both IgG and IgM antibodies. To elucidate the interaction between platelets and ACLA, we studied the reactivity of sera from non‐ITP patients with ACLA, with fragmented platelet membranes. None of them had a concurrent platelet deficiency, but sera from 8 (67%) of them showed increased IgG‐binding to platelet membranes. Absorbtion with cardiolipin reduced membrane binding in 6 (50%). C3 levels were normal, while low C4 values occurred in both groups with significantly lower levels in ACLA‐positive patients (p<0.05). Circulating immune complexes (CIC) were common in both groups.AbstractConclusion: The prevalence of ACLA is increased in ITP and sera from non‐ITP patients with ACLA react with fragmented platelet membranes. This reactivity is often decreased by absorption with cardiolipin, suggesting that ACLA bind to phospholipid epitopes on platelet

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01934.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Infection is a common adverse event after therapy with nucleoside analogs, including 2‐chlorodeoxyadenosine (CdA). However, the incidence of CdA‐related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6‐month period before CdA to their incidence during the 6 months after initiating therapy. Ninety‐five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre‐CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre‐CdA period and a diagnosis of chronic lymphocytic leukemia or of non‐Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections (1 vs. 8 episodes,p= 0.04) and of fever of unknown origin (6 vs. 17 episodes,p= 0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on th

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01935.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe studied the expression of the receptor of interleukin (IL)‐4, one of the T cell growth factors, on fresh peripheral blood leukemic cells from adult T‐cell leukemia (ATL) patients. Flow cytofluorometric analysis with a monoclonal antibody to the IL‐4 receptor (IL‐4R) were used to investigate whether expression of IL‐4R on ATL cells is different from that on normal lymphocytes and other types of leukemic cells. Leukemic cells from acute type ATL patients synthesize IL‐4R without stimulation, at levels much higher than normal resting lymphocytes and other types of leukemic cells. Furthermore, leukemic cells from acute type ATL showed higher IL‐4R expression than that of chronic type ATL or human T‐cell leukemia virus type I carriers. In addition, there was correlation between expression of IL‐4R on the cell surface and the proliferative response to IL‐4. Both IL‐4 and IL‐2 induced upregulation of IL‐4R on activated normal T cells but not on ATL cells. These results suggest that abnormal expression of IL‐4R may display different biological activities in ATL compared with other types of leukemia. Furthermore, the high expression of IL‐4R in ATL may be involved in the proliferation of leukemic cells and the l

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01936.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Sera of 104 patients with haematological diseases, transfused with platelets and sometimes also with red cells, were prospectively investigated in: the lymphocytotoxicity test (LCT), the platelet suspension immunofluorescence test (PSIFT) and the monoclonal antibody immunobilization of platelet antigens (MAIPA) technique. All tests on admission were negative. The overall incidence of alloantibodies after transfusions was 30.8%. Platelet‐specific antibodies were, however, detected much more rarely (9.6%) than anti‐HLA (21.3%). The specificity against HPA antigens was defined in 4 (3.9%) patients: anti‐HPA‐1a, 2b, 3a and 5b. In the remaining 6 (5.7%) cases only the glycoproteins on platelets were identified (GPIb and GPIIIa) which gave positive reaction with the antibodies. Our observations indicate a rather low incidence of platelet‐specific antibodies after tra

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01937.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01938.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01939.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY