摘要:

Abstract:Cytokines presently known to be involved in systemic bacterial infection are tumour‐necrosis factor (TNF), interleukin (IL)‐1, IL‐6, IL‐8 and interferon‐gamma (IFN‐γ) and the counterregulatory molecules soluble TNF receptor (sTNFR) and IL‐1 receptor antagonist (IL‐1 Ra). In animal models TNF, IL‐1 and IFN‐γ mediate organ damage, low blood pressure and fatality, whereas IL‐6 is involved in infection‐related manifestations, like the production of acute‐phase protein and fever, and IL‐8 is chemotactic to granulocytes. TNF and IL‐1 increase expression of adhesion molecules on endothelial cells and influence a number of components of the haemostatic system in favour of coagulation. The presence of cytokines in the circulation is characterized by sequential releases of TNF, IL‐1 and IL‐6/IL‐8; however, many variations of this pattern exist during human infection. In experiments as well as in human infection TNF, IL‐1, IL‐6, IL‐8 and IFN‐γ have been detected, and levels of TNF, IL‐6 and IL‐8 have been found to be associated with the severity of the disease. Collectively, TNF, IL‐1 and IFN‐γ emerge as mediators of systemic infection and septic shock whereas IL‐6 and IL‐8 are related to other manifestations of infection. Counteracting molecules like sTNFR are released after somewhat of a delay following TNF and IL‐1Ra is released concomitantly with IL‐1. Probably these factors modulate the cytokine effect although their true potency in natural infection has yet to be clarified. In granulocytopenic infections TNF, IL‐1, IL‐6 and IL‐8 can be detected in scrum, and levels of TNF and IL‐6 are even higher than in the normal situation in experimental animals. Antibodies to TNF inhibit bacteria‐induced fatality in granulocytopenic mice. Altogether, few data related to the granulocytopenic situation are available. However, it is reasonable to believe that the altered development of granulocytopenic infections is due to chang

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00156.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:We have studied the effects of interferons gamma (IFN‐γ) and alpha (IFN‐α), and tumour‐necrosis factor‐alpha (TNF) on circulating 14‐day erythroid progenitor cell (BFU‐E) growthin vitrofrom patients with non‐leukaemic myeloproliferative disorders (MPD) compared with normal controls. IFN‐γ (1000 U/ml) inhibited BFU‐E growth in all controls studied (mean growth ± SE = 61 % ± 6%, n = 10). In 7 of 11 MPD studied there was no inhibition, and in some cases clear enhancement of BFU‐E growth by IFN‐γ. When cultured in the presence of recombinant erythropoietin (rEpo) 1 U/ml, both IFN‐α and TNF (at 100 and 1000 U/ml) produced a similar degree of inhibition of BFU‐E growth in MPD and controls. The inhibition by 100 U/ml IFN‐α was abrogated, partially in controls but completely in MPD, by increasing the dose of rEpo to 5 U/ml. Similarly, the increase in rEpo dose enhanced BFU‐E growth in cultures with 100 U/ml TNF, but had little effect on cultures containing 1000 U/ml of either IFN‐α or TNF. The aberrantin vitroresponse to IFN‐γ demonstrated in some of these patients may be of relevance to the pathophysiology of MPD. These results fail to demonstrate a differentialin vitroeffect for IFN‐α on MPD BFU‐E growth compared with controls and suggest that thein vitrosuppression of haemopoiesis by

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00157.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Human parvovirus B19 (B19) has a remarkable tissue‐tropism for erythroid elements ‐ from erythroid precursors (BFU‐E, CFU‐E) to erythroblasts. B19 is thought to be incapable of propagating in cells other than erythroid progenitors. Leukocytopenia and thrombocytopenia sometimes occur in addition to erythrocytopenia in patients with B19 infection. We retrospectively investigated the possible cause of thrombocytopenia by B19 infection in 23 patients with thrombocytopenia admitted to our hospital in the past 5 years. Two patients were found to be infected by B19. Mild thrombocytopenia in both cases was thought to be an early event in B19 in

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00158.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Sixty‐four untreated patients with non‐Hodgkin lymphomas (NHL) were analyzed with respect to fraction of S‐phase cells in tumor material and serum lactic dehydrogenase (LD) levels. A significant correlation between the two variables was found in the low‐grade (LGM) (r = 0.44, p4%) (p<0.001) as well as for patients with elevated LD values (≥ 7.5 μkat/l) (p<0.001). A multivariate analysis showed clinical stage (p<0.001), S‐phase fraction (p = 0.002) and age (p = 0.002) to be independent prognostic factors. For serum LD a borderline value (p = 0.05) was found, whereas morphology and B‐symptoms were non‐significant. LD level, but not fraction of S‐phase cells, added prognostic information for LGM lymphomas (p<0.001). For HGM lymphomas, the clinical stage was the strongest factor for prediction of prognosis. We conclude that the fraction of S‐phase cells describes the biological behavior in a more reliable way than morphology (HGMvsLGM) and better identifies lymphomas with poor or good prognosis. The strong additional prognostic information obtained by serum LD within LGM lymphomas is assumed to be due to an associati

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00159.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thromboxane B2 (TXB2) synthesis in response to thrombin stimulation in human megakaryocytesex vivo.Human megakaryocytes were purified by Counterflow Centrifugal Elutriation from bone marrow punctures, taken from volunteers before and 2 hours after ingestion of one dose of 500 mg (n = 4), 80 mg (n = 4) or 40 mg (n = 2) aspirin. Subsequently, megakaryocytes were purified before and 12 h after ingestion of 80 mg (n = 3) aspirin twice daily for 1 week and 12 h after 500 mg (n = 3) aspirin. On average, 140 ± 102 × 103(mean ± 1 SD) megakaryocytes were recovered. We found that aspirin inhibits megakaryocyte cyclooxygenase in a dose‐dependent manner. Two hours after 500 mg of aspirin, TXB2 synthesis in megakaryocytes was inhibited by 96.8 ±2%, whereas one dose of 80 and 40 mg aspirin showed an inhibition of 79.4 ± 13.7% and 80 ± 6.2% respectively. However, the inhibition of TXB2 synthesis seems not to be long‐lasting since, 12 h after the ingestion of aspirin, an increase of megakaryocyte TXB2 production could be observed which reached significance after the 500 mg aspirin dosage (p<0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspirin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygenase, but this inhibition is incomplete and megakaryocyte cyclooxygenase seems to recover within 12 h after ingestion o

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00160.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Fifty‐two patients with chronic myelogenous leukemia (CML) who underwent bone marrow transplantation (BMT) at Huddinge Hospital were analyzed retrospectively regarding type of graft‐versus‐host disease (GvHD) prophylaxis. With T‐cell depletion (TCD) (n = 13) the incidence of grade II—IV acute GvHD was 8% compared to 27% among patients given short course methotrexate (MTX) + cyclosporin (CSA) (n = 23) (ns) and 60% in patients who received MTX or CSA alone (n = 16) (p = 0.006vsTCD and 0.03vsMTX + CSA). The incidence of chronic GvHD was 56%, 31% and 75%, in the three groups, respectively (p = 0.02 combinationvsmonotherapy). Probability of relapse differed significantly, with most relapses in the TCD group, 62% compared to 20% in the MTX + CSA group (p = 0.02) and no relapse in the monotherapy group (p = 0.01 TCDvsmonotherapy). Patient survival at 6 years was 54%, 59% and 38%, in the three groups, respectively (ns). Relapse‐free survival was 23% in the TCD group, 55% in the combination group (p = 0.06) and 38% in the monotherapy group (ns). We conclude that TCD in patients with CML is correlated with an increased risk of relapse and a tendency towards a decreased long‐term relapse‐free survival compared to patients receiving other kind of G

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00161.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:W/Wvand Sl/Sldmice with macrocytic anemias are a potential model for human inherited pure red cell anemia, called Diamond‐Blackfan anemia (DBA). The W mutation involves the gene for c‐kit, and the SI mutation the gene for the kit ligand, called mast cell growth factor, steel factor, or stem cell factor. Since many children with DBA respond to treatment with corticosteroids, we administered steroids to these genetically anemic mice, to determine whether they might provide a model for the human disease. There was no improvement in the murine anemia, consistent with other evidence suggesting that mutations inkitorsteelmay not be involved in Diamond‐Blackfan a

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00162.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Multidrug resistance, mediated by the overexpression of an energy‐dependent transport protein, P‐glycoprotein, has been one of the major targets of interest in solving the mechanisms of clinical drug resistance of malignant cells. To evaluate the correlation between P‐glycoprotein overexpression and the response to chemotherapy, we analysed cytospin preparations of gradient‐separated blood or bone marrow mononuclear cells from 79 patients with acute leukaemia by means of the P‐glycoprotein‐directed monoclonal antibody JSB‐1 and immunocytochemistry using the alkaline phosphatase‐antialkaline phosphatase technique. P‐glycoprotein expression was detected in all disease phases of acute leukaemia. Thirteen out of 51 patients at diagnosis, 10/29 patients in relapse or during residual disease and 8/27 patients in remission overexpressed P‐glycoprotein. Seven out of the 8 positive remission samples were collected between the cycles of consolidation treatment. Our results suggest that increased P‐glycoprotein expression in samples collected between the cycles of consolidation treatment during remission may be induced in normal leukocytes by cytotoxic drug treatment, infections, or by some physiological mechanisms related to the disease. Patients older than 45 years of age were significantly more often P‐glycoprotein‐positive (11/25) at diagnosis than younger patients (2/26). P‐glycoprotein expression at diagnosis was significantly correlated with a low remission rate after the first cycle of induction therapy. Of 34 P‐glycoprotein‐negative patients, 25 achieved remission after the first cycle as compared to 4/12 of the P‐glycoprotein‐positive patients. Our results indicate that the method used is specific and sensitive enough for the analysis of P‐glycoprotein expression and that the expression at initial presentation is inversely correlated

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00163.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:A patient who represented acute hemolytic crisis was studied. Analysis of the erythrocyte membrane proteins by SDS‐PAGE revealed a deficiency of band 4.2. In the family, the sister of the patient who had been clinically normal was also shown to be deficient in band 4.2. Binding studies showed that the propositus' membranes were able to bind normal band 4.2 protein as much as control. It was suggested that the binding sites for the protein were prepared on the membrane. We analyzed the band 4.2 cDNA of the propositus and detected a mutation that changes a codon for alanine to one for threonine at residue 142. Band 4.2 exon III of genomic DNA which included the mutation site was amplified and sequenced directly in the family members, and it was revealed that only the homozygotes of the mutation allele manifested band 4.2 deficiency and the parents, who were heterozygotes, showed normal amounts of band 4.2. Recently, the same mutation was reported as Protein 4.2NIPPONin another 4 cases (Bouhassira et al. Blood 1992: 79: 1846–1854). This study supports the hypothesis that this mutation is the pathogenetic cause of band 4.2 deficiency and not a polymorph

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00164.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Fludarabine monophosphate (FAMP) has been shown to be highly effective against low‐grade malignant B‐cell lymphoproliferative diseases. Because some opportunistic infections were observed in patients treated with FAMP, we investigated the influence of this drug on several parameters of immunocompetence. For 17 consecutive patients treated with FAMP for CLL or low‐grade malignant lymphoma we studied T‐cell subpopulations during and after therapy by flow cytometry and our findings were correlated with the clinical course of their disease. A pronounced decrease in the various T‐cell subpopulations was seen in all cases, that for CD4+ cells was still present 11–13 months after the end of the therapy. In 7 patients a severe opportunistic infection developed; the outcome was fatal in 2 cases. Only 5 patients did not experience any serious infection. These results show that FAMP therapy in a dose of 25 mg/m2/day for 5 d every 4 weeks might be too toxic for patients with very advanced disease. However, in view of the efficacy of FAMP, the possibility of less intensive schedules for these advanced cases should

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00165.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY