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Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

352 records · Page 20Linked to original sources

Control of blast cell proliferation and differentiation in acute myelogenous leukemia by soluble polypeptide growth factors.

Proliferation of acute myelogenous leukemia (AML) derived blast cells requires the presence in culture of one or more growth factors. In the majority of cases Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate clonogenicity of AML blasts, which can be synergised by Interleukin-6 (IL-6), Interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). In contrast, macrophage colony-stimulating factor (M-CSF) favors deterministic divisions. A substantial part of AML samples have clonogenic cells which, however, proliferate autonomously in vitro. The production by leukemic cells of a variety of growth or synergizing factors including GM-CSF, G-CSF, IL-1, IL-6, and Tumor Necrosis Factor (TNF) has been demonstrated and a fraction of cases will use these molecules to support clonogenic growth in an autocrine or paracrine fashion. However, unlike the situation with retrovirus-induced murine or avian leukemias, the role of production of CSFs and other cytokines by human leukemic cells in the transformational process remains uncertain.

Biological Factors↗

[Dynamic of immune response in primary cytomegalovirus infection and after reactivation of cytomegalovirus in patients with organ allotransplantation].

A total of 44 serum specimens from 7 patients with kidneys or liver transplanted from donors who had antibodies (Ab) to human cytomegalovirus (CMV) were studied. In 4 recipients anti-CMV Ab were found before transplantation and in 3 others they were not detected. It was shown by EIA that IgM and IgG anti-CMV appeared in the sera of primarily infected patients after 1-2 weeks and their titers were 5-10 times lower than in patients with reactivated CMV infection. Immunoblotting of Ab to individual CMV proteins showed a narrower spectrum of Ab during the initial period of primary CMV infection in comparison with the same period of reactivation and delayed production of AB to conformation-dependent determinants. Hence, analysis of anti-CMV Ab during the first 4-6 weeks after organ transplantation by EIA and immunoblotting differentiates primary CMV infection from its reactivation by Ab titers and spectrum. These parameters vary in some patients.

Antibodies, Viral↗

In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6.

Interleukin-6 has been shown to stimulate in vitro synthesis of C-reactive protein (CCRP) in hepatocytes by enhancing the transcriptional rate of the CRP gene. It has also been demonstrated that IL-6 spurs the terminal differentiation of B-cells into immunoglobulin secreting cells when synergizing with IL-3. IL-6 may therefore act as a prime molecule in the acute phase and immune response. We have administered rh IL-3 to cancer patients in a phase I/II clinical trial. Endogenous IL-6 levels increased in a dose-dependent fashion upon i.v. bolus injection of rh IL-3 and continued to be significantly elevated above pretreatment levels when IL-3 was further administered by the s.c. route. Increases of IL-6 levels were associated with enhanced production of CRP in vivo detected after 24 h of injection. At day 14 of rh IL-3 treatment plasma immunoglobulin concentrations were measured and IgM was found to be increased by greater than 2.5 fold above starting levels. These results indicate that rh IL-3 also augments the acute phase response in vivo and contributes to increased synthesis of IgM and that induction of endogenous IL-6 is involved in these events.

Acute-Phase Proteins↗

[Influence of gestational age and postnatal kidney maturation on the kinetics of gentamicin].

The current schedule for gentamicin administration to newborn infants, in doses of 2.5 mg/kg every twelve hours during the first week of life was evaluated in pre-term newborns under 35 weeks of gestational age (GA). Pharmacokinetic studies in steady state conditions were performed at the third and seventh days of therapy (periods A and B respectively) in nine pre-term (GA 30 to 34 weeks) and ten full-term newborns. Minimal gentamicin blood concentrations at period A were 1.96 +/- 0.32 micrograms/ml in term newborns and 2.51 +/- 0.48 micrograms/ml in pre-term infants (p less than 0.005) and, at period B, 1.49 +/- 0.37 micrograms/ml and 2.33 +/- 0.34 respectively (p less than 0.001). Gentamicin excretion showed good correlations with gestational age (r: 0.654; p less than 0.005) and creatinine clearance (r: 0.628; p less than 0.005).

Creatinine↗

Computer-based support for clinical decision making.

Although computers are now commonly used for financial purposes in hospitals and physicians' offices, most physicians do not routinely use them in patient care. And in hospitals where laboratory data are provided on computer terminals, the displays are often difficult to use and programs that offer assistance in interpreting the data are usually unavailable. We have developed decision support programs that are widely used with the clinical computing system at our hospital. This paper describes the programs and how the clinicians use them.

Boston↗

Monokines: stimulatory and inhibitory regulator molecules of myelopoiesis in vitro.

The conditions for monocytes to secrete molecules that are involved in myelopoiesis, i.e. Colony Stimulating Factors (CSFs), Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-alpha) were investigated. Whereas secretion of these molecules by monocytes is negligible in a quiescent state, activation of monocytes with Interferon-gamma (IFN-gamma) results in mRNA accumulation and subsequent protein secretion of CSF for granulocytes (G-CSF) and for monocytes (M-CSF). Under identical conditions mRNA-transcripts of TNF-alpha, IL-1-alpha and IL-1-beta genes were induced. Whereas IFN-gamma induces secretion of TNF-alpha protein, protein secretion of IL-1 by monocytes failed to occur in response to an IFN-gamma stimulus. However, the presence in culture of IFN-gamma in combination with TNF-alpha induced secretion of IL-1. Although IL-1 regulates the production of CSF for granulocytes and monocytes (GM-CSF) by IL-1 receptive T-lymphocytes, and is therefore involved in upregulatory mechanisms of myeloid growth, it may be able to suppress growth of myelopoietic progenitor cells (MPC) as well, when hematopoietic cultures are depleted of cells, that have the potential to secrete CSFs. Similarly, IFN-gamma, although being a major inducer of CSF secretion by monocytes, was shown to inhibit myeloid colony growth when exposed to purified MPC and allowed to synergize with TNF-alpha.

Biological Factors↗