Search PubMed⌕ Search

Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

At least 73 records · Page 4Linked to original sources
PubMed1991

Biologic effects of recombinant human interleukin-3 in vivo.

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.

Adult↗
PubMed1991

In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders.

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.

Adult↗
PubMed1991

[Is there a drug treatment approach for prevention and therapy of fat embolism syndrome?].

The pathogenesis of fat embolism has been subject to considerable debate ever since it was first described by Zenker in 1864. The clinical course, management and pathophysiology of a typical case are described. As no single causative factor has been implied in the development of fat embolism, its therapy and prevention primarily involves the adequate treatment of shock and of the underlying traumatic lesions.

Adult↗
PubMed1991

Clinical use of recombinant human hematopoietic growth factors (GM-CSF, IL-3, EPO) in patients with myelodysplastic syndrome.

We have conducted several phase I/II clinical studies in a total of 65 MDS patients utilizing recombinant human hematopoietic growth factors including GM-CSF, IL-3, and EPO. Twenty-seven patients with MDS were treated with either continuous i.v. infusion or single daily s.c. injection of rhGM-CSF at dosages from 15 micrograms/m2 to 1000 micrograms/m2. All of them exhibited white cell responses during the treatment cycles, but no sustained rise in reticulocytes or platelets was recorded. In four of the patients, all with > or = 15% blast cells in the bone marrow, the percentage of circulating blast cells increased during treatment with rhGM-CSF (at dosages of 500 micrograms/m2 and 1000 micrograms/m2, respectively), although no leukemic conversion occurred. Of 9 patients treated so far with rhIL-3 at single daily s.c. dosages of 60 micrograms/m2, all exhibited white cell responses; 8 exhibited significant improved platelet and reticulocyte counts. Nineteen further patients received rhEPO for a period of 14 weeks by s.c. (10,000 U five times weekly) or i.v. bolus administration (150-450 U/kg). None of these patients experienced an increase in white cell and platelet counts. A significant increase of the reticulocyte count was recorded in 3 patients only. Another strategy involves the recruitment of leukemic cells into the cell cycle by hematopoietic growth factors followed by treatment with cycle-specific cytostatic agents. Therefore in 10 patients administration of rhGM-CSF (250 g/m2/day x 14, s.c.) was combined with Ara-C treatment (20 mg/m2/day x 14; s.c.). Initial results of this pilot study available in 5 patients indicated that this approach may control leukemic cell proliferation and may increase number of mature myeloid cells in both bone marrow and peripheral blood. A similar approach utilizing rhIL-3 in conjunction with Ara-C is on-going.

Blood Cell Count↗
PubMed1991

Screening for expression of cytokines with hematopoietic growth factor activity by permanent human B-cell lines.

Using colony assays in semi-solid media, several investigators have shown that supernatants (SN) of normal and malignant human B-cells can stimulate the growth of granulocyte-macrophage (GM) progenitor cells. So far macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) have been identified as potential colony-stimulating activity (CSA) present in B-cell SN. However, other CSAs such as GM-CSF, G-CSF, IL-1-beta, IL-3, and IL-4 may also be candidates in this respect. Several human B-cell lines (CL) were screened for the expression of the respective genes at the mRNA and protein level. Constitutive production of GM-CSF was detected in the lymphoblastoid CL Wi-L2-729-HF2 and in the Burkitt line Raji. The signal intensity of specific transcripts and the amount of protein being secreted increased upon exposure to the phorbol ester PMA. The hybridoma line HB-564 also expressed the GM-CSF gene, but required prior stimulation with PMA. 3H-thymidine incorporation of Raji and Wi-L2-729-HF2 cells was unchanged in the presence or absence of a specific neutralizing sheep anti-GM-CSF serum, suggesting that GM-CSF did not serve as an extracellular autocrine growth factor. The expression of the GM-CSF gene was independent of the proliferative state (log phase growth versus plateau phase growth) and of the presence of serum in cultures of the respective CL. The expression of G-CSF, IL-1-beta, IL-3, and IL-4 genes was not detectable in the CL at the mRNA level.

B-Lymphocytes↗
PubMed1991

Expression of leukemia inhibitory factor is regulated in human mesenchymal cells.

A protein variously termed leukemia inhibitory factor (LIF), differentiation-inducing factor, differentiation inhibitory activity or human interleukin for DA cells can control the differentiation and proliferation of hematopoietic cells as well as of several other cellular lineages. In order to further elucidate the spectrum of LIF-producing cells, we examined different cell types for the expression of LIF mRNA using Northern blot analysis. LIF mRNA was detected in activated normal human T-cells and in two T-cell lines but was undetectable in a B-lymphoid cell line, in both resting and activated normal human granulocytes and monocytes and in human myeloid cell lines K562 and HL-60. In human lung fibroblasts and in human umbilical vein endothelial cells, LIF was constitutively expressed and its accumulation was increased in a time-dependent manner following treatment with the phorbol ester TPA and in the presence of the two immediate response cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1-beta. We conclude that mRNA for LIF is not only expressed by T-cells but also in human mesenchymal cells. Expression of LIF transcripts in these cells is constitutive and can be significantly enhanced by phorbol ester, TNF-alpha and IL-1-beta.

Cells, Cultured↗
PubMed1991

Induction of c-jun expression in the myeloid leukemia cell line KG-1 by 1-beta-D-arabinofuranosylcytosine.

c-Jun/AP-1 is a transcription factor commonly induced in mammalian cells by serum, phorbol compounds, or peptide growth factors. We show that c-Jun/AP-1 is inducible as well as coordinately regulated, in the human acute myelogenous leukemia cell line KG-1, by the cytostatic drug 1-beta-D-arabinofuranosylcytosine (Ara-C). Concomitantly with Ara-C treatment, growth inhibition and loss of clonogenic survival of KG-1 cells were observed. Whereas KG-1 cells displayed only barely detectable amounts of c-jun transcripts when cultured in the presence of serum, Ara-C at concentrations of 1 to 50 microM induced c-jun transcripts in a dose-dependent fashion. Time course studies showed that 10 microM Ara-C induced c-jun transcripts 6 hr after initiation of culture. Induction of c-jun mRNA was independent of de novo protein synthesis, because the protein synthesis inhibitor cycloheximide failed to alter Ara-C-induced c-jun mRNA accumulation. Furthermore, cycloheximide did not induce c-jun transcripts, ruling out the possibility of posttranscriptional stabilization of c-jun mRNA by labile proteins, as has been previously reported for a variety of serum-inducible protooncogenes and early response genes. Moreover, nuclear run-on analysis disclosed that c-jun induction by Ara-C in KG-1 cells took place at a transcriptional level. Taken together, these findings indicate that c-jun mRNA, unlike its rapid (within minutes) induction by serum in fibroblasts, is induced by Ara-C in KG-1 cells following a much more prolonged time course and is regulated essentially at a transcriptional level.

Cell Survival↗
PubMed1991

[Cytomorphological and cytochemical studies of experimentally-induced thyroid tumors in the rat].

Carcinomas were induced to the thyroid gland of female rats, using a method originally proposed by Thomas and Bollmann (metachronous application of nitrosomethylurea and methylthiouracil), to establish cytomorphological, histomorphological, cytochemical, and flow-cytophotometric criteria for diagnosis of thyroid carcinoma. Verification was also intended of the diagnostic value of each of the methods involved for differentiation of nodular goitre. Another purpose of the study was to find out, whether chemically induced thyroid tumours in rat were comparable to thyroid neoplasms in man. This provided to the examiners genetically coherent and morphologically comparable biological material at various stages of thyroid tumour growth which included diffuse and adenomatous hyperplasias, adenomas, and, from the 18th to 42nd experimental weeks, papillary as well as follicular carcinomas in 31 to 100% of all experimental animals involved. Cytomorphological comparability of rat thyroid material (imprint specimens) with human material (fine-needle aspiration cytology) was ensured for normal as well as for hyperplastically altered thyroid glands, including adenomatous and carcinomatous changes. Hence, group typing of thyroid cytology, originally devised for human specimens, could be easily adapted to material obtained from rat. Assessment of cytological samples by microscopic criteria yielded an accuracy of 89% in malignoma diagnosis and proved to be an approach of highly informative potential also in the context of rat experiments. Use of additional cytochemical techniques (PAS, toluidine-blue, peroxidase, alkaline and acid phosphatases, gamma-glutamyl transpeptidase) as well as quantitative DNA determination by means of flow-cytophotometry was helpful in casting light at some scattered trends of change from normal for certain stages of proliferation, but it failed to enhance information in cytomorphological diagnosis of the individual case.

Adenocarcinoma↗
PubMed1990

[Blood pressure monitoring in aged hypertensive patients treated with sustained-release nicardipine or nifedipine].

In a double-blind parallel study, 20 elderly hypertensive subjects (mean age 85 years) were treated either by nicardipine or by nifedipine in slow-release form for 7 days. Blood pressure was measured by ambulatory, non-invasive daytime monitoring. Efficacy of both drugs was similar on the seventh day of treatment. However, the hypotensive effect induced by nifedipine was maximal on the first day of treatment, in contrast to the progressive effect induced by nicardipine. In 2 cases, marked hypotension was observed after the first tablet of nifedipine.

Aged↗
PubMed1990

Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts.

We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.

Antibodies, Monoclonal↗
PubMed1990

[Transfer factor].

Explore the source record for details and available documents.

Lymphocyte Activation↗
PubMed1990

Control of tetrahydrobiopterin synthesis in T lymphocytes by synergistic action of interferon-gamma and interleukin-2.

The control of (6R)-5,6,7,8-tetrahydrobiopterin (H4biopterin) synthesis in primed T cells was analyzed by using the human T cell leukemia virus type I (HTLV-I)-transformed T cell line MT-2. In contrast to the slowly progressing induction of H4biopterin synthesis during activation of resting T cells, it is completed during a 59-h period and is directed by a synergism of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). Both GTP cyclohydrolase and (6R)-(1',2'-dioxopropyl)-5,6,7,8-tetrahydropterin synthase activities are induced by IFN-gamma. They are further enhanced by combined treatment with IL-2, which per se is ineffective. Furthermore, the combined treatment synchronizes the time periods of both maximum activities, now extending from 33 to 44 h. This period correlates with high cellular H4biopterin levels. It is preceded by a fast and transient period of H4biopterin increase which depends on the synergistic action of both IFN-gamma and IL-2. It coincides with a transient increase in sepiapterin reductase activity. In contrast to MT-2 cells, HTLV-I-transformed HUT 102 cells constitutively secrete IFN-gamma and express IFN-gamma mRNA. The accumulation of H4biopterin is suppressed by anti-IFN-gamma polyclonal antibody and correlates with constitutive expression of all H4 biopterin-synthesizing enzymes.

Alcohol Oxidoreductases↗
PubMed1990

Effects of recombinant human interleukin-3 in aplastic anemia.

In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained.

Adolescent↗
PubMed1990

Differential regulation of interleukin-6 expression in human fibroblasts by tumor necrosis factor-alpha and lymphotoxin.

The treatment of human diploid fibroblasts with tumor necrosis factor (TNF)-alpha and with lymphotoxin (LT) is associated with induction of interleukin-6 (IL-6) transcripts with TNF-alpha being 10-fold more potent than LT. Here we report on the TNF-alpha/LT-induced signaling mechanisms responsible for the regulation of IL-6 gene expression in these cells. Run-on assays demonstrated that both TNF-alpha and LT increase IL-6 mRNA levels by transcriptional activation of this gene. Stability studies of IL-6 transcripts in fibroblasts showed that TNF-alpha delayed IL-6 mRNA decay but not LT. The induction of IL-6 transcripts by TNF-alpha and LT was not inhibited by the isoquinoline sulfonamide derivative H7. Similarly, depletion of protein kinase C (PKC) by 12-O-tetradecanoyl-phorbol 13-acetate (TPA) did not change the ability of TNF-alpha and LT to induce IL-6 transcripts, demonstrating that stimulation by these agents may not be mediated by activation of PKC. Stimulation of IL-6 transcripts in fibroblasts did also not require new protein synthesis as exposure to the protein synthesis inhibitor cycloheximide (CHX) enhanced accumulation of IL-6 mRNA in the presence or absence of TNF-alpha or LT.

Cells, Cultured↗