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Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

At least 235 records · Page 13Linked to original sources
PubMed1990

Gamma-interferon interrupts growth stimulation in chronic myelogenous leukemia established by endogenous granulocyte colony-stimulating factor.

We have previously shown that maturing neoplastic cells from patients with stable phase chronic myelogenous leukemia (SP CML) constitutively produce granulocyte colony-stimulating factor (G-CSF) and are also receptive for this molecule. G-CSF functions as an endogenous growth factor in SP CML, and thus is responsible for divisions in maturing leukemic cells leading to an expansion of the compartment of mature cells. In the investigations to be reported below, the effects of various hematopoietic inhibitor molecules on the expression of the G-CSF gene by SP CML bone marrow cells enriched for promyelocytes/myelocytes were examined at the mRNA and protein level. We show that exposure of SP CML bone marrow promyelocytes/myelocytes to recombinant human (rh) interferon (IFN)-gamma but not to rh IFN-alpha, rh tumor necrosis factor (TNF)-alpha, and rh lymphotoxin (LT) leads to downregulation of G-CSF expression and interruption of the G-CSF-mediated endogenous growth stimulation. The action of G-CSF takes place at the posttranscriptional level and involves an acceleration of decay of steady-state levels of G-CSF transcripts in the malignant cell population.

Bone Marrow↗
PubMed1990

Synergistic effect of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D-arabinofuranosylcytosine (Ara-C) on proto-oncogene expression and induction of differentiation in human U 937 cells.

The in vitro action of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D arabinofuranosylcytosine (ara-C) was studied on the human leukemia cell line U 937. Parameters investigated included monitoring of transcript levels of the proto-oncogenes C-MYC, C-FOS, and C-FMS, and analysis of nitroblue tetrazolium (NBT) reduction and of surface expression of the C3 bi receptor. Furthermore clonal proliferation of U 937 cells was assessed in soft agar cultures. The results indicate that both agents have only little effects on U 937 cells when acting alone. When combined in culture, however, they synergize to induce monocytic differentiation of U 937 cells as disclosed by significant increase of cells capable of reducing NBT and displaying surface C3 bi receptor that was accompanied by reduction of clonogenicity in colony assays. Induction of differentiation and inhibition of proliferation of U 937 cells was preceded by downregulation of transcript levels of C-MYC, increase of C-FOS mRNA, and induction of accumulation of C-FMS mRNA. By sequential use of LIF and ara-C we also demonstrate that the basis of synergism of both agents does not involve mechanisms at the level of receptor ligation but that synergism may be initiated by complementary intracellular metabolic cascades.

Cell Differentiation↗
PubMed1990

Retrospective analysis of ras gene activation in myeloid leukemic cells.

Ras genes are activated by point mutations at critical sites of their coding regions. Activated N-ras genes with transforming ability have been detected in patients with myelodysplastic syndromes (MDS), acute myelogenous leukemia (AML) and in human myeloid cell lines. We used polymerase chain reaction (PCR), differential oligonucleotide hybridization and direct DNA sequencing to retrospectively analyze the N-ras gene of blast cells from the same patient (a) at time of diagnosis of MDS, (b) after the patient had developed AML. Two types of archival tissue samples served as a source of cells. Different passages of the KG-1 myeloid cell line which had been established from leukemic blasts of this patient were also analyzed. We found that native blast cells isolated at either of the two disease stages did not carry an N-ras mutation, and neither did early passage KG-1 cells. However, direct DNA sequencing of PCR-amplified DNA from nude mice transformants induced by DNA from late passage of the KG-1 cell line revealed two linked mutations involving both the second nucleotide of codon 12 and the third nucleotide of codon 15 of N-ras. The nucleotide substitution at codon 15 did not result in an amino acid substitution (silent mutation). The mutations probably occurred during prolonged passaging of the KG-1 cells and might have been overlooked by oligonucleotide hybridization assay.

Animals↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce surface expression of interleukin-2 receptor p55-chain and CD4 by human eosinophils.

In this report it is shown by immunofluorescence analysis, biochemical analysis and mRNA hybridization that human eosinophils express surface CD4 and interleukin-2 receptor (IL-2R) (CD25) when exposed to eosinophil activators granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3. Although the functional role of eosinophil CD4/CD25 expression has to be elucidated, it will be of interest in further studies to investigate whether in vivo induction of these molecules occurs in association with certain disease processes such as the hypereosinophilic syndrome or in immunological responses during allergic and helminthic parasitic diseases.

Blotting, Northern↗
PubMed1990

In vivo recruitment of GM-CSF-response myelopoietic progenitor cells by interleukin-3 in aplastic anemia.

Previous studies have indicated that colony-stimulating factors may stimulate myelopoiesis and thus increase the number of circulating white blood cells in patients with hematopoietic failure including aplastic anemia. However, long-term administration of the factor was required to maintain its response. In the present article we report on a patient with severe aplastic anemia undergoing treatment with recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF). After an initial response, the patient became refractory to GM-CSF. However, treatment with interleukin (IL)-3 restored responsiveness to GM-CSF, suggesting that IL-3 may have replenished the bone marrow with myelopoietic progenitor cells sensitive to the action of GM-CSF. This observation suggests the value of application of sequentially acting hematopoietic growth factors in aplastic anemia patients.

Anemia, Aplastic↗
PubMed1990

Stimulation of granulopoiesis in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor: assessment of two routes of administration.

We administered Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor to 61 patients with malignancy, 36 of whom had normal peripheral blood counts and 25 of whom had peripheral cytopenia due to underlying bone marrow disease, to compare the efficacy of two different routes of administration to stimulate the in vivo granulopoiesis: i.e., continuous i.v. infusion and s.c. injection. Three well-tolerated dose levels were investigated. Application of granulocyte-macrophage colony-stimulating factor resulted in dose-dependent increases in circulating neutrophils, eosinophils, and monocytes and an increase in bone marrow cellularity, irrespective of route of administration. In some patients, mild side effects, including bone pain, dyspnea, flu-like symptoms, and a decrease of platelet counts, were recorded, but they were less pronounced when the hormone was administered subcutaneously.

Adolescent↗
PubMed1990

Hematopoietic growth factors in oncology.

Hematopoietic growth factors, or hemopoietins, are peptide hormones produced by peripheral blood cells, bone marrow stroma, as well as several other cell types, such as endothelial cells and fibroblasts. Hemopoietins play a central role in regulating peripheral blood cell number and function. By recombinant DNA technology, several of these factors, also called colony-stimulating factors (CSF) or interleukins, are now available in such quantities to allow clinical evaluation. First experiences in clinical trials show that these peptides are capable of stimulating production of various cell types of the peripheral blood by stimulation of bone marrow progenitor cells without significant toxicity for the patient under treatment. Treatment of renal anemia by erythropoietin and reduction of chemotherapy-induced myelosuppression by G- and GM-CSF are already defined indications for these hemopoietins. Further studies are under way to test the indication of these factors in other clinical situations as well as studies investigating the biology, pharmacology, and clinical efficacy of interleukin 3 (IL-3).

Hematopoietic Cell Growth Factors↗
PubMed1990

[Beyond normal values--practical experiences with the standard deviation score (SDS) for the assessment of lung function measurements in acute bronchial asthma].

Expressing results of pulmonary function tests as a percentage of the subject's predicted value (% predicted) has been widely adopted. This method has some serious disadvantages: The range of values % predicted in the reference population depends on the body height and varies from index to index. An alternative is to use the standard deviation score (SDS), which is derived by dividing the difference between the recorded and predicted value by the standard deviation of the residuals (SDS = (recorded-predicted)/SD).

Acute Disease↗
PubMed1989

[Low T3 syndrome and chronic inflammatory rheumatism].

For the clarification of pathogenesis and clinical relevance of decreases of the triiodothyronine (T3) level in patients with chronic inflammatory rheumatism in a group of 63 patients with clinically, paraclinically and roentgenologically diagnosed rheumatoid arthritis (59 times) and with SLE (4 times), respectively, parallel were determined parameters of the thyroid gland function and of the rheumatic activity as well as a subtile drug anamnesis for the medication of antirheumatic drugs was established. In 33 of the 63 patients who were included into the study decreases and low normal values, respectively, for the total T3 (TT3 less than 1.5 nmol/l) were found. In comparison to the remaining 30 patients with normal TT3 a typical constellation of paraclinical parameters of the thyroid gland with distinct reduction of TT3 and free T3 (FT3), low normal total T4 (TT4), slight increase of the reverse T3 (rT3), moderate decrease of the basal and stimulated TSH and an only very small restriction of the binding capacity of the thyroid hormone (TBG) were found. A clinically relevant hypothyroidism is thus to be excluded with certainty. Antirheumatic drugs, in particular steroidal ones (glucocorticoids) may on principle also induce such paraclinical constellations, related to the thyroid gland. In our investigations a therapy with antirheumatic drugs is causally scarcely considered, since both in the group of patients with decrease of T3 and without decrease comparable quantities of antirheumatic drugs including glucocorticoids were administered and the cortisol values in the plasma do not differ. The investigations confirm our already formerly expressed supposition that also in rheumatics a "low-T3-syndrome" is existing as it is otherwise described in consumptive extrathyroidal diseases (NTI).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Changed thyroid function parameters in severe extrathyroidal diseases].

Patients with critical non-thyroidal illnesses (NTI) often show decreased serum levels of thyroid hormones. We find the so-called low T3-syndrome and the low T3-low T4-syndrome in cases of severe liver- or kidney-diseases, inflammation, metabolic disorders and in emergency situations with danger to life. A strong decrease of the serum-T4-level signals a bad prognosis. In spite of the relative low concentrations of thyroid hormones and a possible disturbance in pituitary regulation, the patients are clinically in an euthyroid situation. There is no hypothyroidism in the common sense, but possibly an adaptation to the morbid situation of the organism with effects on protein- and energy-economy. Therefore the substitution of thyroid hormones is not indicated. In such cases of NTI the diagnosis of real disturbances of thyroidal function is often difficult. The employment of more sensitive TSH-assays may improve this situation.

Diagnosis, Differential↗
PubMed1989

[Changes in the blood picture in hyperthyroidism].

On the basis of a retrospective study about 276 clinically and paraclinically ascertained cases of hyperthyroidism in 34% of the patients above all mild anaemias could be proved which under thyreostatic therapy with thiamazol which after repeated incidence of an euthyroid metabolic situation vastly normalized themselves also without an anaemia-specific additional medication. Leukocytopenias (5.8%) and thrombocytopenias (3.3%) had only a low frequency in untreated hyperthyroidism. Nevertheless an unequivocal parallelity of the haematologic changes was to be observed in erythro-, granulo- and thrombopoiesis. There was a clear correlation between the activity of hyperthyroidism, measured at the T3- or T4 level, and anaemia and haemocytopenia, respectively. Lacking substance deficiency conditions and signs of haemolysis let us first of all think of a causal thyrotoxic bone-marrow damage on account of the dependence of the haematologic changes on the activity of hyperthyroidism and their immediate influencibility by aimed thyrostatic therapy. A relatively low dosed thiamazol therapy has influence on haematopoiesis and peripheral blood picture only at a very small percentage, in which cases the changes mostly are fully reversible. Thereby the initial haematologic situation before the therapy does not provide any predictability for perhaps appearing haematotoxic or allergic side-effects under thyreostatic treatment. The thiamazol therapy does not show any recognizable side-effects in the dosage administered on the investigated leukocytic functions agglomeration, adhesion and phyagocytosis. Only for the adhesion of leukocytes was proved a significant functional disturbance of leukocytes, which was, however, reversible with normalization of metabolism and with high probability was also directly thyreotoxically induced.

Adolescent↗
PubMed1989

[The effect of cytokines on myelopoiesis. Origin, regulation of secretion and biological activity].

Recombinant DNA technology has been central in answering some of the most relevant questions in research of the regulation of the functional status of hematopoietic progenitor cells and their progney. This article focuses on recent results that have emerged from studies utilizing recombinant growth factor molecules regulating hemopoietic blood cell development and activation. The following points are considered: biological characteristics of hemopoietic growth factors and synergizing factors, their role in the regulation of hemopoiesis and activation of normal and leukemic cells, their cellular origin, and regulation of production.

Biological Factors↗
PubMed1989

[The importance of the SCC antigen in the diagnosis and follow-up of cervix carcinoma. A cooperative study of the Gynecologic Tumor Marker Group (GTMG)].

SCC (squamous cell carcinoma) antigen is a subfraction of tumour antigen TA-4 isolated from cervical squamous cell carcinomas. Serum concentrations of SCC antigen were measured by radioimmunoassay in 382 control subjects, 70 women with cervical intraepithelial neoplasia (CIN), 517 with cervical carcinoma and 203 with other gynaecological carcinomas. Elevated SCC antigen levels (greater than 2.5 ng/ml) were found in 4% of normal controls, in 7% of women with CIN I-III, in 2%-23% with various forms of genital adenocarcinomas, in 55% with primary and in 76% of those with recurrent cervical squamous cell carcinoma. The positivity rate of the antigen was correlated with tumour stage (FIGO) and lymph node involvement of primary cervical squamous cell carcinomas. During long-term follow-up serum levels of SCC antigen were found to be concordant with tumour activity in 74% of cases. Patients with still elevated marker levels after therapy had twice the recurrence rate of women with normal serum values. Routine determination of SCC antigen during follow-up of cervical cancer is recommended.

Antigens, Neoplasm↗
PubMed1989

Functional consequences of monocyte IL-2 receptor expression. Induction of IL-1 beta secretion by IFN gamma and IL-2.

The generation of an immune response involves the interaction of monocytes and T cells, but the events which regulate this interaction are not well understood. Culture of human peripheral blood monocytes in vitro induces low level surface expression of the p55 protein of the IL-2R and the expression of this receptor can be enhanced significantly by exposure to IFN-gamma. The addition of IL-2 to IFN-gamma-treated monocytes was shown to augment subsequent IL-1 beta secretion in the presence or absence of LPS. These effects could be partially blocked by anti-p55-IL-2R mAb. Nuclear "run on" assays and Northern analysis to probe for IL-1 beta transcripts showed enhanced IL-1 beta gene transcription and mRNA accumulation by monocytes treated with IFN-gamma and IL-2 but not in cultures that were obtained from monocytes treated with IL-2 alone. These results suggest that the T cell lymphokines IFN-gamma and IL-2 may act in a sequential fashion on monocytes to amplify the immune response by establishing a positive feedback circuit.

Adjuvants, Immunologic↗
PubMed1989

Production of macrophage-, granulocyte-, granulocyte-macrophage- and multi-colony-stimulating factor by peripheral blood cells.

The specific cell sources and signals for induction of various colony-stimulating factors (CSF) in peripheral blood mononuclear cells (PBMC), purified T lymphocyte and monocyte (Mo) populations have been investigated. In the absence of exogenous activating stimuli, human PBMC, T cells and Mo failed to produce stable cytoplasmic mRNA for CSF for macrophages (M-CSF or CSF-1), for granulocytes (G-CSF), for granulocytes and macrophages (GM-CSF) and for multilineage CSF [multi-CSF, interleukin (IL) 3] and thus failed to release CSF proteins. However, after stimulation with phorbol myristate acetate and phytohemagglutinin, M-, G-, GM- and multi-CSF mRNA became detectable in PBMC, resulting in the secretion of the respective proteins. Identical culture conditions resulted in synthesis of only G- and M-CSF by purified Mo, whereas purified T lymphocytes produced GM-CSF and multi-CSF only. When Mo or T lymphocytes were exposed to recombinant human interferon-gamma or were stimulated by triggering the epitopes recognized by the monoclonal antibodies anti-Tll2 and Tll3, respectively, again disparate CSF expression patterns were found to be associated with both cell species. Moreover, IL2-receptive T lymphocytes showed the same distinct pattern of CSF secretion when activated by recombinant human IL2.

Colony-Stimulating Factors↗
PubMed1989

Role of colony-stimulating factors in the biology of acute myelogenous leukemia.

A high proportion of acute myeloid leukemias (AML) recently investigated for their capacity to synthesize biologically active bioregulatory molecules was found to accumulate messenger (m) RNA and to produce membrane-bound or -secreted forms of stimulating factors for granulocyte, macrophage and mixed granulocyte-macrophage colony growth. Blast cells have also been found to secrete interleukin 1, tumor necrosis factor-alpha, interleukin 6, and to express receptors for various growth factors as well. However, growth factors like interleukin 2 and interleukin 3 have not been identified as AML products, and several other factors including interleukin 4, interleukin 5, etc. need further evaluation. Responsiveness of clonogenic leukemic cells to exogenous growth-promoting factors in vitro suggests a possible role of these biomolecules in the course of these disorders. Important evidence for the crucial role of growth factors, at least in some subtypes of AML, has been provided by demonstrating constitutive growth factor production by leukemic cells and their autonomous in vitro growth which is dependent on autocrine secretion of a specific growth factor. The concert of mechanisms providing stimulatory and inhibitory signals for hematopoiesis, which is adapted to the various physiological requirements of the organism, may have multiple defects in AML. This leads to successive steps of malfunctioning of cells, which finally express a fully malignant phenotype. In addition, these derangements also lead to defects in accessory cells on the level of mediator communication. However, there is evidence for autonomous growth promotion of AML blast by constitutive production of growth factors active in an autocrine fashion (GM-CSF, G-CSF, interleukin 6) and by recruitment of accessory cells to increase CSF supply (GM-CSF, G-CSF) via molecules such as interleukin 1 and TNF-alpha in a paracrine fashion. Molecular analysis of transformed hematopoietic cells has revealed changes of the genome, e.g., insertion of viral genetic information or cytogenetic fractures at DNA sites controlling growth factor gene activation. These events appear to be crucial in the induction of uncontrolled growth factor expression promoting oncogenic transformation of hematopoietic progenitor cells.

Colony-Stimulating Factors↗