Recombinant human erythropoietin: a multipotential hemopoietic growth factor in vivo and in vitro.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
K Lechner
Publications and source records attributed to K Lechner.
Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia.
The prognostic significance of the expression of surface membrane antigens on the blasts of 123 consecutive patients with de novo acute myeloblastic leukemia (AML) was evaluated. For this purpose, reactivity of monoclonal antibodies (mAbs) CLB-ERY3 (antiblood-group H antigen), VIM-D5 (CD15), WT1 (CD7), MY7 (CD13), MY9 (CD33), VID-1 (antihuman leukocyte antigen locus DR [anti-HLA DR]), VIM-2 (CDw65L), VIM-13 (CD14), 63D3 (CD14) and anti-TdT with leukemic blast cell populations was prospectively analyzed with respect to the rates of complete remission (CR), continuous complete remission (CCR), and survival. The overall rate of CR was 65%, the 6-year rates of overall CCR and survival were 23% and 13%, respectively (median period of patient observation, 30 months). Of all Abs tested, four (CLB-ERY3, MY7, anti-TdT, and VIM-D5) were found to be of prognostic value. Reactivity of CLB-ERY3, MY7, and anti-TdT was predictive for CR (CLB-ERY3+, 43% v CLB-ERY3-, 73%, P less than .02; MY7+, 59% v MY7-, 91%, P less than .003; TdT+, 28% v TdT-, 71%, P less than .001, respectively) and probability of survival (significantly lower survival rates: CLB-ERY3+, P less than .02; MY7+, P less than .03; and TdT+ cases, P less than .001, respectively). Reactivity of VIM-D5 was significantly associated with a higher probability of CCR (P less than .01). Our results confirm earlier reports on the prognostic significance of expression of CD13 and TdT in AML and indicate CLB-ERY3 (antiblood-group H antibody) and VIM-D5 (CD15) as further markers predictive for the clinical outcome in patients with de novo AML.
Adolescent↗
Diagnosis of carriers of haemophilia A by RFLP analysis: Austrian results.
RFLP analysis with extragenic and intragenic probes was performed in 25 Austrian families with haemophilia A for the purpose of carrier diagnosis. Diagnosis could be established in 22 families, in 7 families with intragenic and extragenic probes, in 15 families with extragenic probes only. The remaining 3 families were not informative. During routine diagnosis we found three interesting cases which are described in the following paper. Firstly, we identified one deletion with Bcl I/p 114.12. Secondly, we observed an additional polymorphic band (5.2 kb) with Xba I/probe A. Thirdly, we saw one case where Bcl I/p 114.12 and Bgl I/1.8 were not in linkage disequilibrium.
Austria↗
Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies.
Sera from 32 bone marrow allograft recipients were screened for the presence of autoantibodies 4-61 months post-graft. Sera from 12 of 19 patients with extensive chronic graft-versus-host disease (c-GVHD) stained the nucleolar region strongly in immunofluorescence, indicating the presence of specific antinucleolar antibodies. In contrast, none of three patients with limited and none of 10 patients without c-GVHD had antinucleolar antibodies. Antibodies reacting with nuclear constituents other than nucleoli were found in five of the 12 antinucleolar positive patients. The appearance of antinucleolar antibodies coincided with early clinical symptoms of c-GVHD. We conclude that the appearance of antinucleolar antibodies after bone marrow transplantation is specific for patients with extensive c-GVHD. Furthermore, the development of extensive c-GVHD is paralleled by the emergence of these antinucleolar antibodies.
Adolescent↗
Thromboxane A2 and prostacyclin generation in the microvasculature of patients with atherosclerosis--effect of low-dose aspirin.
Generation of thromboxane A2 (TxA2) and prostacyclin (PGI2) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time was investigated in 7 patients with atherosclerosis (angiographically verified obstructions of the femoral arteries) and in 7 normal control subjects apparently free of atherosclerotic lesions. Similar amounts of TxA2 (measured as thromboxane B2, TxB2) were generated at the site of plug formation in the patients with peripheral vascular disease (PVD) and in the control subjects. Significantly lower levels of PGI2 (measured as 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha) were found in blood from an injury of the microvasculature in the patients compared with the controls. These data do not suggest a major role of the platelet prostaglandin metabolism in the development of atherosclerosis. However, decreased synthesis of PGI2 by endothelial cells might contribute to the development and/or progression of atherosclerotic lesions. In the patients with PVD, low-dose aspirin (50 mg/day for 7 days) resulted in a greater than 90% inhibition of the TxB2 production at the site of plug formation. Following low-dose aspirin 6-keto-PGF1 alpha levels were below 20 pg/ml (limit of sensitivity of our radioimmunoassay procedure) in the majority of the samples. We therefore conclude that in patients with PVD a decreased synthesis of PGI2 by endothelial cells might contribute to the progression of atherosclerosis. Furthermore, low-dose aspirin treatment results in a similar inhibition of the platelet prostaglandin generation as recently observed in healthy subjects.
6-Ketoprostaglandin F1 alpha↗
High risk of acquired immune deficiency syndrome (AIDS) and of AIDS related complex (ARC) in hemophiliacs seropositive for more than 5 years.
A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 patients have developed the lymphadenopathy syndrome, 9 patients AIDS and 11 patients ARC (CDC IV C 2). 6/9 cases of AIDS and 10/11 cases of ARC have occurred only after 1985. Patients, who subsequently became symptomatic, had significantly higher IgG levels in 1983, otherwise no predictive laboratory tests were identified. Patients with T4 counts above 500/microliters became symptomatic later, but after 5 years the incidence of AIDS was comparable in patients with original T4 counts of more than or below 500/microliters.
AIDS-Related Complex↗
Interleukin-3 is a differentiation factor for human basophils.
The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF-alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8-). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.
Antibodies, Monoclonal↗
Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes.
The immunologic surface marker profile of human mast cells (MCs) was established using a combined toluidine/immunofluorescence staining procedure [49 monoclonal antibodies (MoAbs) tested]. Ascites (n = 9) MCs as well as enzymatically dispersed MCs from all organs tested (lung n = 11, skin n = 7, intestinum n = 10) exhibited an identical marker profile. MCs were recognized by MoAbs clustered as CD9 (anti-gp24), CD33 (anti-gp67), and CD45 (anti-gp220) as well as by MoAbs directed against membrane-bound IgE. MoAB YB5B8 (anti-gp145) selectively recognized MCs. Most significantly, however, MCs were stained by MoAbs MAX1 (anti-gp65), MAX3 (anti-gp68), MAX11 (anti-gp65), and MAX24 (anti-gp65). These antibodies bind to surface membrane antigens associated with a late stage of monocyte/macrophage differentiation. Thus, our results provide definite evidence that MCs share surface membrane markers with mononuclear phagocytes. In contrast, MCs are stained neither by lymphatic markers (CD1-8, 10, 19-24) nor by myelomonocytic markers (CD11-17). MCs also lack the interleukin-2 (IL-2) receptor (CD25), the T10 antigen (CD38), and most of the myelocytic markers expressed on peripheral blood (PB) basophils. Thus, MCs displayed a unique phenotype within the hematopoietic system. This new approach enabled us to enrich human lung MCs to a purity greater than 95% by means of negative selection with complement-mediated cell lysis. Purified MCs were subsequently stained with MoAbs and analyzed by flow cytometry, which confirmed the results obtained from the double-staining experiments. We next examined cultured metachromatic cells derived from bone marrow (BM) and peripheral blood colony-forming units (CFU). These metachromatic cells previously could not be classified by morphologic criteria alone and have therefore been termed basophil-like/MC-like cells. In this study, toluidine blue-positive cells obtained from either pooled multipotential colonies (day 14-CFU-GEM) or pooled myelocytic colonies (day 16/17-CFU-GM/G/M) were recognized by MoAbs MY7 (CD13), VIM12 (CD11b), and VIM2, as well as by an anti-IgE MoAb, after preincubation with IgE. In contrast, CFU-derived metachromatic cells were not stained by MoAb YB5B8. This marker profile corresponds to the immunologic phenotype of blood basophils and excluded a detectable formation of mature MCs in colonies derived from cultured hematopoietic stem cells.
Antigens, Surface↗
Anticardiolipin antibodies are elevated in HIV-1 infected haemophiliacs but do not predict for disease progression.
Levels of anticardiolipin antibodies (ACA) were measured in 55 patients with haemophilia A in serum samples obtained in 1983 and in 1987. Twenty-one patients were negative for anti HIV-1 antibodies in 1983 and remained negative in 1987; 34 patients had anti HIV-1 antibodies in 1983; 17 of these latter patients remained asymptomatic, whereas 17 patients developed ARC or AIDS during the 4 years follow-up. Thirteen anti HIV-1 negative patients had elevated ACA levels in 1983; subsequently, a significant decrease was observed in all these subjects (p less than 0.001). All anti HIV-1 positive patients had elevated ACA levels in 1983; normal values were found in 9 patients in 1987. Yet, these changes were not significant (p greater than 0.05). ACA levels were significantly higher in HIV-1 infected patients than in those without anti HIV-1 antibodies (p less than 0.05). There was no difference of ACA levels between the two anti HIV-1 positive patient groups, be it in 1983 or be it in 1987 (p greater than 0.05). There was no correlation of ACA levels with serum IgG concentrations, CD4+ lymphocytes, or the consumption of factor VIII concentrates.
Acquired Immunodeficiency Syndrome↗
Identification of the target platelet glycoprotein in autoimmune thrombocytopenia occurring after allogeneic bone marrow transplantation.
We report the case of a patient who developed autoimmune thrombocytopenia after allogeneic bone marrow transplantation from her HLA-identical sister. An IgG autoantibody was detected that bound to the platelet glycoprotein IIb/IIIa and to the HLA class I proteins. Immunoprecipitation studies with radiolabeled platelets revealed additional antibody binding sites on proteins of 214 kDa molecular weight under nonreduced conditions and 65 and 56 kDa molecular weight under reduced conditions.
Adult↗
Organization and nucleotide sequence of a transcriptional unit of Methanococcus vannielii comprising genes for protein synthesis elongation factors and ribosomal proteins.
By a chromosome walking strategy the DNA region from Methanococcus vannielii flanking the genes for protein synthesis elongation factor (EF) 1 alpha and EF-2 was cloned and sequenced. A gene organization of 5' - beta' - open reading frame (ORF) 1 - ORF2 - S12 - S7 - EF-2 - EF-1 alpha - S10 - ORF3 - ORF4 - 3' was found where beta', S12, S7, S10, EF-2, and EF-1 alpha represent gene products with sequences similar to the beta' subunit of RNA polymerase, ribosomal proteins S12, S7, and S10, and EF-G and EF-Tu from Escherichia coli, respectively. ORF1-4 represent gene products with no known eubacterial counterparts. Northern blot analysis of transcripts and nuclease S1 mapping showed that transcription initiates between beta' and ORF1 and terminates at the 3' side of the S10 gene and that the genes from ORF1 to S10 are cotranscribed. Apart from the presence of two additional ORFs, ORF1 and ORF2, and of the gene for S10, this organization is identical to that of the eubacterial "streptomycin operon." ORF1 displays sequence similarity to rat liver ribosomal protein L30 and may represent one of the "additional" ribosomal proteins of Methanococcus. The sequenced part of the beta' gene and the EF-2 and EF-1 alpha gene products from Methanococcus are more similar to their eukaryotic than to their eubacterial counterparts. It appears, therefore, that the genetic organization of the translational components resembles the situation in eubacteria, whereas their primary structures are more eukaryotic in nature.
Amino Acid Sequence↗
Interleukin 3 activates human blood basophils via high-affinity binding sites.
Pure populations of human basophilic granulocytes were obtained from chronic myeloid leukemia (CML) blood by negative selection using a mixture of monoclonal antibodies and complement. 125I-radiolabeled recombinant human interleukin 3 (rhIL-3) bound to purified basophils in a specific manner. Quantitative binding studies and Scatchard plot analyses performed on samples from two donors revealed the presence of a single class of high-affinity IL-3 binding sites (500 and 2100 sites per cell; dissociation constant at equilibrium, 230 and 160 pmol/liter, respectively). Purified CML basophils maintained in suspension in the presence of rhIL-3 (100 units/ml) incorporated up to 12 times more [3H]thymidine than basophils in control cultures. Furthermore, after preincubation in vitro with rhIL-3 (100 units/ml) for 30 min, normal blood basophils released 2- to 3-fold more histamine than basophils pretreated with control medium when exposed to various concentrations of an anti-IgE antibody. Together, these results show that rhIL-3 binds to a specific receptor on blood basophils and is a regulator of basophil function.
Antibodies, Monoclonal↗
Immune thrombocytopenia more than a year after allogeneic marrow transplantation due to antibodies against donor platelets with anti-PlA1 specificity: evidence for a host-derived immune reaction.
We report on a male patient transplanted from his HLA-matched sister for Ph1-chromosome positive chronic myelogenous leukaemia who developed immune thrombocytopenia more than 1 year after transplantation. The platelet antibody reacted with the platelet specific antigen PlA1 on donor platelets, and also on recipient platelets after engraftment. A presumed host-versus-donor induced thrombocytopenia was supported by Southern blot analysis using a Y-chromosome specific probe demonstrating residual host-origin cells in the patient's excised spleen.
Adult↗
Oral cyclosporin-A is effective treatment for untreated and also for previously immunosuppressed patients with severe bone marrow failure.
16 patients with transfusion-dependent, life-threatening bone marrow failure (14 with severe aplastic anaemia, 1 with systemic lupus erythematosus and 1 with pure red cell aplasia) were treated with cyclosporin-A (Cy-A) after either lack of response to conventional immunosuppression with antithymocyte-globulin/high-dose methylprednisolone for 95 to 1190 days (median 186.5) (group I, 8 patients) or as a primary treatment due to ineligibility for conventional immunosuppression (group II, 8 pat.). Cyclosporin-A was given orally to maintain trough levels of 200 to 300 ng/ml (RIA). In group I, 6 out of 8 patients responded 30 to 480 d (median 53) and are currently alive 627 to 1482 d (median 731) after initiation of Cy-A, respectively. In 3 of the responders Cy-A has been withdrawn, without relapse. In group II, 5 of 8 patients responded 26 to 170 d (median 63) and are currently alive 142 to 697 (median 420) d following initiation of Cy-A, respectively. These data indicate a place for cyclosporin-A in the management of patients with life-threatening bone marrow failure in whom a) immunosuppressive therapy with antithymocyte-globulin and high-dose methylprednisolone had failed and b) who are not candidates for vigorous immunosuppression or bone marrow transplantation, for medical or other reasons.
Administration, Oral↗
Gene organization and structure of two transcriptional units from Methanococcus coding for ribosomal proteins and elongation factors.
Two transcriptional units coding for ribosomal proteins and protein synthesis elongation factors in Methanococcus vannielii have been cloned and analysed in detail. They correspond to the "streptomycin operon" and "spectinomycin operon" of the Escherichia coli chromosome. The following general conclusions can be drawn from comparison of the nucleotide and the derived amino acid sequences of ribosomal proteins from Methanococcus with those from eubacteria and eukaryotes. (i) Ribosomal protein and elongation factor genes in Methanococcus are clustered in transcriptional units corresponding closely to E. coli ribosomal protein operons with respect to both gene composition and organization. (ii) These transcriptional units contain, in addition, a few open reading frames whose putative gene products share sequence similarity with eukaryotic 80S but not with eubacterial, ribosomal proteins. They may correspond to "additional" ribosomal proteins of the Methanococcus ribosome, there being no functional homologues in the eubacterial ribosome. (iii) Methanococcus ribosomal proteins and elongation factors almost exclusively exhibit a higher sequence similarity to eukaryotic 80S ribosomal proteins than to those of eubacteria. (iv) Many Methanococcus ribosomal proteins have a size intermediate between those of their eukaryotic and eubacterial homologues. These results are discussed in terms of a hypothesis which implies that the recent eubacterial ribosome developed by a "minimization" process from a more complex organelle and that the archaebacterial ribosome has maintained features of this ancestor.
Amino Acid Sequence↗
Lymphokine overproduction in severe aplastic anemia is not related to blood transfusions.
The production of interferons (IFNs), IFN-gamma, tumor necrosis factors (TNFs) and TNF-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMNCs) of untransfused and transfused, but otherwise untreated patients with severe aplastic anemia (SAA) was determined using bioassays and immunoassays. In untransfused and pretransfused SAA patients, spontaneous and lectin-induced production of these cytokines by PBMNCs was strongly enhanced. Cytokine production in untransfused SAA patients did not differ from that in pretransfused patients. Similar relative frequencies of activated (HLA-DR+) lymphocyte subpopulations present in the PBMNCs demonstrated cytokine overproduction per cells. Cytokine production was studied in three SAA patients before and after blood cell transfusions. Spontaneous and lectin-induced production of these cytokines was abnormally high and unaffected by blood transfusions. In another patient exhibiting abnormal cytokine production, the hematopoietic response to cyclosporin-A in vivo was accompanied by normalization of cytokine production in vitro. We conclude that overproduction of IFN-gamma and TNF-alpha by lectin-stimulated PBMNCs is an intrinsic abnormality of SAA unrelated to blood transfusions. Normalization of production of IFN-gamma and TNF-alpha accompanying a clinical response to cyclosporin-A may cautiously be taken as further evidence suggesting a pathogenetic role of cytokine overproduction in SAA.
Anemia, Aplastic↗
Recombinant human erythropoietin and hematopoietic progenitor cells in vivo.
Explore the source record for details and available documents.
Bone Marrow↗
Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure.
The formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the alpha-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is--at least partially--due to an acquired defect of the platelet alpha-granule release and an increased generation of PGI2 in the microvasculature.
6-Ketoprostaglandin F1 alpha↗