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Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

At least 109 records · Page 6Linked to original sources
PubMed1990

Interleukin-4 regulates mRNA accumulation of macrophage-colony stimulating factor by fibroblasts: synergism with interleukin-1 beta.

We demonstrate that macrophage-colony stimulating factor (M-CSF) is expressed in human fibroblasts at the mRNA and protein level. Following activation with both interleukin (IL)-1 beta and IL-4, fibroblasts synthesized M-CSF transcripts detectable by Northern blot analysis with peak expression occurring at 8 h and 12 h, respectively. Exposure of fibroblasts to both cytokines resulted in M-CSF protein release at 60 h of c. 500 U/ml (for IL-1 beta) and 1000 U/ml (for IL-4), relative to a control preparation of recombinant human M-CSF in a murine bone marrow colony assay. Both interleukins synergized to enhance M-CSF mRNA accumulation and their ability to induce M-CSF transcripts could be abolished by treatment with specific neutralizing antibodies. These observations provide support for the idea that fibroblasts may control monocyte/macrophage development and function, and that IL-1 beta and IL-4 are involved in the regulation of this process.

Blotting, Northern↗
PubMed1990

Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration.

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.

Aged↗
PubMed1990

Effect of interleukin 3 on cytosine arabinoside-mediated cytotoxicity of leukemic myeloblasts.

The concept of biologic modification of proliferation and differentiation of myeloid leukemia cells has attracted much attention over the past years. One promising strategy involves the recruitment of leukemic cells into the cell cycle by hematopoietic growth factors in combination with cycle-specific cytotoxic drugs. Because cytosine arabinoside (Ara-C), which targets only cells in S-phase of the mitotic cell cycle, is included in most chemotherapeutic regimens for the treatment of acute myelogenous leukemia, we explored the hypothesis that the recruitment of quiescent immature leukemic blasts into the cell cycle by the early acting growth factor interleukin 3 (IL-3) can increase the efficacy of Ara-C for kill of leukemic stem cells. We show that IL-3 increases the fraction of blasts in S-phase, as assessed by DNA histogram analysis with propidium iodide staining, leading to an enhancement of kill of clonogenic blast cells when combined with Ara-C. Expression of the protooncogenes c-myc, c-fms, and c-fos, known to be linked to cellular proliferation and differentiation, was also altered by IL-3 in Ara-C-treated cultures, further substantiating the role that IL-3 plays as an enhancer of the cytotoxicity of Ara-C.

Antigens, CD↗
PubMed1990

Hematopoietic growth factors in bone marrow transplantation.

Preliminary clinical results demonstrate the activity of recombinant human granulocyte (rHuG) and granulocyte/macrophage (rHuGM) colony stimulating factors (CSFs) in enhancing bone marrow engraftment after autologous and allogeneic bone marrow transplantation (BMT). In several analyses of prospective, controlled clinical trials of rHuG- and rHuGM-CSF, reduced morbidity and cost, as well as improved survival have been observed. There is reason to hope that more profound understanding of the in vivo biology of these and other cytokines will lead to further reduction in morbidity and mortality associated with both autologous as well as allogeneic BMT. These advances could significantly broaden the spectrum of diseases amenable to treatment by BMT.

Bone Marrow↗
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↗