Biomedical subjects

I Rollinger-Holzinger

Publications and source records attributed to I Rollinger-Holzinger.

6 recordsLinked to original sources

PubMed2000

LST1: a gene with extensive alternative splicing and immunomodulatory function.

The gene of the leukocyte-specific transcript (LST1) is encoded within the TNF region of the human MHC. The LST1 gene is constitutively expressed in leukocytes and dendritic cells, and it is characterized by extensive alternative splicing. We identified 7 different LST1 splice variants in PBMC; thus, 14 LST1 splice variants (LST1/A-LST1/N) have been detected in various cell types. These isoforms code for transmembrane as well as soluble LST1 proteins characterized by two alternative open reading frames at their 3' end. We demonstrate the presence of the transmembrane variant LST1/C on the cell surface of the monocytic cell lines U937 and THP1. Recombinant expression of LST1/C permitted its profound inhibitory effect on lymphocyte proliferation to be observed. In contrast, the alternative transmembrane variant LST1/A, the extracellular domain of which shows no amino acid sequence homology to LST1/C exerted a weaker but similar inhibitory effect on PBMC. These data demonstrate the protein expression of LST1 on the cell surface of mononuclear cells, and they show an inhibitory effect on lymphocyte proliferation of two LST1 proteins although they have only a very short amino acid homology.

Adjuvants, Immunologic↗

PubMed1999

Endogenous FLT-3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) caused by a clonal hematopoietic stem cell disorder progress to either overt leukemia or cytopenia, which leads to lethal infection or bleeding. Although several clinical trials have attempted to reverse cytopenia by using hematopoietic growth factors (HGF), success has been limited due in part to a limited understanding of the role of HGF in MDS progression. The FLT3 ligand, which binds to and activates the FLT3 receptor, does not have a stimulatory effect on hematopoietic cells, but can synergize with other HGF to support the expansion of both immature and committed progenitors. Using ELISA technology we measured endogenous serum levels in 93 patients with MDS: 29 RA, 1 RARS, 31 RAEB, 23 RAEBt, 9 CMML. 48.3% of RA patients' sera had significantly elevated FLT3 ligand levels ranging from 404 to 5735 pg/ml, whereas none of the RAEB, RAEBt, or CMML patients sera had levels different from controls. No significant correlation was found between FLT3 ligand levels and peripheral blood counts, bone marrow cellularity, age, cytogenetic abnormalities, or survival. Our data suggest that FLT3 ligand levels can be upregulated early in the course of MDS, which may represent an appropriate response to a decreased number of normal progenitors, or alternatively a dysregulated HGF system.

Adolescent↗

PubMed1998

Expression and regulation of the thrombopoietin receptor variants MPLP and MPLK in PBMC.

The human c-mpl proto-oncogene encodes the receptor for thrombopoietin (TPO), which plays a central role in magakaryopoiesis and platelet production. Recent results showed that c-mpl mRNA expression is restricted to CD34(+) cells, megakaryocytes, and platelets. The authors analysed mRNA expression by reverse transcription and PCR (RT-PCR) of the transmembrane Mpl variants, MPLK and MPLP, in magakaryocytic cell lines, peripheral blood mononuclear cells (PBMC), lymphocytes, and monocytes. Transcription of both Mpl variants was detected in freshly isolated PBMC and the megakaryocytic cell line, DAMI, whereas none could be detected in the megakaryocytic cell line Meg-01. The cytokines TPO, interleukin 11 (IL-11), erythropoietin (EPO), and stem cell factor (SCF), which are known stimulators of megakaryopoiesis, but not interleukin3 (IL-3), increased MPLP mRNA detection in PBMC during 96 h of incubation. However, concomitantly the detection of MPLK transcripts decreased in these cells. MPLP was also detected in monocytes, B-lympocyte and T cell populations. In contrast, MPLK mRNA expression was low in monocytes, B and T cells, and no clear increase in transcription detection was observed during stimulation of these cells.

B-Lymphocytes↗

PubMed1998

Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes.

Prognosis in patients with myelodysplastic syndromes (MDS) is closely correlated with cytopenia. To date, no factor is available which is able to reliably stimulate megakaryopoiesis in vivo. Recently, the ligand of the mpl receptor was cloned and found to be thrombopoietin (TPO). We measured endogenous TPO serum levels in 69 patients suffering from MDS using an TPO receptor-based ELISA. Twenty-six of the patients suffered from refractory anemia (RA), 12 from RA with excess of blasts (RAEB), 25 from RAEB in transition (RAEBt), and six from chronic myelomonocytic leukemia (CMML). This assay uses a chimeric molecule consisting of the human TPO receptor fused to the Fc portion of human IgG as the capture reagent. Biotinylated antibody to TPO IgG was used for detection and the lower detection limit in serum was found to be 160 pg/ml. Samples obtained from healthy individuals with a normal platelet number were shown to be below detectable levels. In patients with RA, high endogenous serum TPO concentrations correlated with low platelet count and significantly elevated TPO concentrations were only found when megakaryopoiesis was absent or decreased in the bone marrow. This correlation was not detected in RAEB and RAEBt patients and no detectable TPO serum concentrations were found in six CMML patients whether they showed decreased or normal platelet count. Our data show that endogenous TPO production is upregulated by decreased circulating platelet count only in patients with refractory anemia. In the more advanced stages of MDS where the leukemic clone has further progressed, an inadequate TPO response occurs, possibly due to overexpression of the mpl receptor by the malignant clone.

Adult↗

PubMed1997

Spontaneous or interferon-gamma-induced T-cell infiltration, HLA-DR and ICAM-1 expression in genitoanal warts are associated with TH1 or mixed TH1/TH2 cytokine mRNA expression profiles.

The purpose of the study was to investigate the cytokine gene expression patterns and immunohistochemical characteristics of genitoanal warts in order to obtain a clue as to the immunological mechanisms possibly relevant for wart regression or persistence. We analysed surgically removed warts from 11 patients, 2 of whom were immunosuppressed. Lesions of five of the nine otherwise healthy individuals were additionally treated with intralesional interferon-gamma (IFN gamma) prior to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1 expression on keratinocytes were found in two otherwise healthy patients and were intensified by intralesional IFN gamma in four of five patients. The mRNA expression patterns in seven of eight non-recurrent warts were compatible with a predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant warts of three patients (one healthy, two immunocompromised) histological signs of immunore-activity and TH1-like cytokine mRNA expression were not detected. In recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was repeatedly found suggesting a predominant TH2 response. In conclusion, immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM-1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine mRNA expression profile.

Adult↗

PubMed1996

In vitro stimulation of erythropoiesis by stem cell factor alone in myelodysplastic syndrome patients with elevated endogenous erythropoietin serum levels.

Anemia remains a therapeutic problem in patients with myelodysplastic syndrome (MDS). In view of the recently reported potential of stem cell factor (SCF) in restoring erythropoiesis in combination with erythropoietin (Epo), we first aimed to define a correlation between SCF serum levels and anemia in MDS. Endogenous SCF levels in 50 MDS patients were determined by using a quantitative sandwich enzyme immunoassay. Broad interindividual variations were observed, but SCF serum levels were in the normal range with no correlation to peripheral blood count. A soft agar culture system was used to further define the role of SCF for stimulation of erythroid growth. Bone marrow mononucleated cells of 20 MDS patients (4 refractory anemia, 5 refractory anemia with excess of blasts, 7 refractory anemia with excess of blasts in transition, and 4 chronic myelomonocytic leukemia) were investigated, and SCF plus Epo was able to stimulate burst-forming unit-erythroid significantly more than SCF or Epo alone independent of French-American-British group. When mononucleated cells from six MDS patients (two refractory anemia, two refractory anemia with excess of blasts, and 2 refractory anemia with excess of blasts in transition) with elevated serum Epo levels were incubated in the presence of SCF and autologous serum, a significant dose-dependent stimulation of burst-forming unit-erythroid number and cells per colony was detected. Erythroid differentiation was further enhanced by adding serum with high colony-stimulating activity obtained from patients with severe aplastic anemia. Our data suggest that in MDS patients with high endogenous Epo serum levels SCF alone might be effective in stimulating erythropoiesis in vivo.

Adult↗