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Biomedical subjects

K Hartung

Publications and source records attributed to K Hartung.

At least 109 records · Page 6Linked to original sources
PubMed1984

Comparison of in vitro and in vivo modulation of myelopoiesis by biological response modifiers.

In vitro growth and differentiation of granulocyte-macrophage progenitor cells (GM-CFU-C) requires colony-stimulating factors (CSF), and an in vivo role for CSF has also been proposed. Prostaglandins of the E series (PGE) have been reported to serve as negative feedback regulators of myelopoiesis. Here, we report evidence of augmented CSF secretion by mouse peritoneal Mo (macrophages) and bone marrow cells in vitro upon stimulation with various biological response modifiers (BRMs). Optimal induction of CSF secretion occurred after in vitro treatment of peritoneal Mo and mononuclear bone marrow cells with 50 micrograms/ml poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine). 5 micrograms/ml lipopolysaccharide (LPS), or 500 U/ml interferon (IFN alpha,beta) for 2 days. The in vitro stimulation of CSF secretion was paralleled by an increase in PGE secretion by Mo and bone marrow cells. The PGE secretion could, however, be selectively blocked by preincubating the cells for 3 h with indomethacin (10(-7) Mol) leaving CFS production intact. In vivo treatment of mice with either maleic anhydride divinyl ether copolymer (MVE-2; 25 mg/kg) or poly ICLC (2 mg/kg) significantly increased levels of CSF in serum, as well as in culture supernatants of in vivo-treated peritoneal Mo and bone marrow cells. The increase in serum CSF levels and in secretion of CSF by peritoneal Mo and bone marrow cells was followed by a dose-dependent increase in GM-CFU-C, in nucleated bone marrow cells, and in peripheral blood leukocytes. The same BRMs also stimulated the secretion of PGE by in vivo-activated peritoneal Mo, but not by bone marrow cells. Pretreatment of the mice with indomethacin (4 mg/kg) almost completely suppressed PGE secretion by peritoneal Mo, but did not change the CSF secretion by peritoneal Mo or bone marrow cells and had no significant effect on bone marrow cellularity. Therefore, MVE-2 and poly ICLC, in addition to their immunomodulatory activity, can also have stimulatory effects on myelopoiesis, presumably mediated through secretion of CSFs. Protection and/or restoration of bone marrow function could thus either provide the opportunity for more extensive chemotherapy or could increase the number of Mo effector cells available for activation against tumor targets.

Animals↗
PubMed1984

Role of prostaglandin E and interferon in secretion of colony-stimulating factor by murine macrophages after in vitro treatment with biological response modifiers.

We have evaluated the possible role of biological response modifiers (BRMs) in myelopoiesis by investigating BRM modulated secretion of hematopoietic growth factors and inhibitors. Here, we report the evidence of augmented secretion of granulocyte and/or macrophage colony stimulating factors (CSF) by murine resident peritoneal macrophages after in vitro incubation with murine interferons (alpha, beta-mIFN; beta-mIFN; gamma-mIFN), poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine), BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl)-methyl]-aziridine) and lipopolysaccharide (LPS). The secretion of CSF appears to be independent of the ability of the BRMs to induce IFN, as shown by the use of neutralizing antibodies against mIFN. The antiproliferative effects of IFN also did not block the BRM induced effects of CSF. The combination of alpha, beta-mIFN and poly ICLC or LPS and poly ICLC at suboptimal concentrations resulted in additive, but not synergistic effects on CSF secretion by macrophages. Histological examination of the colonies induced indicated the presence of two types of CSF, namely CSF1 and CSF3, which give rise to pure macrophage and granulocyte colonies respectively. In parallel to their effect on CSF secretion, these BRMs also caused a considerable increase in secretion of prostaglandins of the E series (PGE) by macrophages. However, the production of PGE did not interfere or influence CSF secretion, since the inhibition of the enzyme cyclooxygenase with indomethacin (10(-7) molar) 3 h before stimulation with poly ICLC, alpha, beta-mIFN, or LPS, inhibited the secretion of PGE by macrophages without affecting the secretion of CSF. Macrophages, stimulated by one of the active BRMs for 24 h, could not be restimulated by any of these agents to again secrete significant amounts of CSF or PGE, even after a 2 day resting phase. Other drugs tested (diethyldithiocarbamate, maleic anhydride divinyl ether, azimexone) failed to stimulate the in vitro secretion of significant amounts of CSF and PGE. The results presented here indicate that several BRMs can be utilized to stimulate macrophages to secrete the myelopoietic growth factor CSF, thus supporting the concept that these BRMs might be of value in reconstituting or promoting impaired granulocyte and monocyte/macrophage function.

Animals↗
PubMed1984

[Radiography or fluoroscopy. Considerations beyond radiation protection].

A comparison is made between taking radiographs versus fluoroscopy in veterinary medicine. In this evaluation three main features are of importance: financial restrictions, diagnostic quality of x-ray image, radiation protection or radiation hazards. All three aspects show unequivocally that radiography has to be preferred. Fluoroscopy should be the exception and should be used only for special examinations.

Animals↗
PubMed1984

[Possibilities for reducing radiation exposure during radiography of small animals].

Veterinarians may suffer from chronic radiation injuries if exposed consistently to small doses of x-rays over a long period of years. Such injuries can positively be avoided by using accurate techniques. This paper makes suggestions how veterinary radiologists can reduce the radiation exposure by following very simple precautions.

Animal Diseases↗
PubMed1983

Prostaglandin E synthesis and release by murine macrophages and human monocytes after in vitro treatment with biological response modifiers.

Prostaglandins of the E series (PGE), produced by mononuclear phagocytes, have many biological activities and are involved in the regulation of myelopoiesis and of the cytotoxic activities of macrophage (M phi) and natural killer (NK) cells. Since one of the possible effects of biological response modifiers (BRMs) on immune regulation might be modulation of PGE production, resident peritoneal murine M phi (mM phi) and elutriated human blood monocytes (hM) were incubated with BRMs and the supernatants were then assayed for PGE. Control mM phi produced about 4.9 ng PGE/10(5) mM phi over a 24 hr period. Lipopolysaccharide (LPS, 1-5 micrograms/ml), polyinosinic-polycytidylic acid complexed with poly-L-lysine (Poly ICLC, 0.1-10 micrograms/ml) and murine alpha, beta-interferon, (IFN, 10-1000 U/ml) all caused a highly significant increase in PGE-secretion. BM41.332, a 2-cyanoaziridine (25-50 micrograms/ml), was found to be less stimulatory, whereas the pyran copolymer MVE-2 (25-50 micrograms/ml), and Azimexone (25-50 micrograms/ml) had marginal effects on PGE-production. Kinetic studies showed that the plateau of PGE-production by mM phi occurred during the first 24 hr of incubation, and mM phi which were washed after a 24 hr incubation period could not be restimulated to produce more PGE. PGE release by hM was increased after stimulation with LPS, Poly IGLC and BM41.332, whereas human IFNs (alpha and beta) induced a slight decrease in PGE production. As in the murine studies, Azimexone and MVE-2 had no detectable effect. The ability of some BRMs to augment PGE-secretion by mM phi and hM may contribute to their negative effects on host responses, such as suppression of NK cell activity.

Adjuvants, Immunologic↗
PubMed1982

Properties of a Ca2+ activated K+ conductance in Helix neurones investigated by intracellular Ca2+ ionophoresis.

1. Membrane current responses produced by intracellular ionophoretic injection of Ca2+ ions into voltage clamped Helix neurones were investigated. 2. The Ca2+ activated current depends on the intensity and duration of the Ca2+ injection as well as on the membrane potential. The current-voltage relation is non-linear and shows strong outward rectification. 3. The Ca2+ activated current reverses near the equilibrium potential for K+ ions and the associated current fluctuations disappear at the K+ reversal potential, which indicates a single current source, probably activation of K+ channels. 4. The Ca2+ activated K+ conductance is voltage dependent and changes e-fold per 31 mV membrane depolarization. 5. Extracellular tetraethylammonium, gallamine and quinidine block the Ca2+ activated K4 current. Extracellular 4-aminopyridine has no blocking effect. 6. Sustained injection of high amounts of Ca2+ irreversibly suppresses the outward current. 7. The K+ outward current evoked by repeated Ca2+ injection exhibits summation and facilitation.

Animals↗
PubMed1981

Pharmacokinetics of 14C-activity after the administration of 14C-azimexone in rats.

The pharmacokinetics of 14C-activity were studied in male Sprague-Dawley rats over 24 and 288 h periods after oral i.v. administration respectively. After oral administration rapid and complete absorption of azimexone occurred. The elimination of radioactivity from plasma after i.v. administration could be best described by an open four-compartment-system yielding a terminal half-life of 74.45 h indicating the existence of deep compartment for azimexone or its metabolites. The renal clearance of 14C-activity decreased considerably after i.v. administration with progressing time. This points to an extensive metabolism of azimexone. Fifty-seven and sixty-seven per cent of the given 14C-activity could be recovered in urine within 24 h after i.v. and p.o. administration respectively and in both cases less than 1% of the doses in feces. Studies on the distribution of the labelled substance 24 h after i.v. administration showed highest concentration in gastric contents, spleen thyroid gland and bone marrow. Twelve days after i.v. administration the ratio of the 14C-content in organ/plasma was greatly increased for spleen, thymus, lung, bone marrow and thyroid gland as compared with the conditions 24 h after administration. Thus it can be assumed that the target organs for the immunomodulating activity of the drug belong to the deep compartment of azimexone or its metabolites.

Adipose Tissue↗
PubMed1980

The effect of sodium ions on the light-induced 86Rb release from the isolated crayfish retina.

The effect of low external Na+ concentrations on the light-induced K+ release from crayfish photoreceptor cells was tested by labelling intracellular K+ with the isotope 86Rb. The amount of isotope released per light stimulus is roughly proportional to the external Na+ concentration if the osmolarity is kept constant by replacing Na+ with Tris, choline or sucrose. When sucrose is used to replace the depleted Na+ the light-induced K+ release is a linear function of the external Na+ concentration and is reduced by approx. 95% at an external Na+ concentration of 5 mmol/l. For choline and Tris substitutions the relationships are less clear but at Na+ concentrations less than or equal to 56 mmol/l it seems that in comparison with sucrose the light-induced K+ release is smaller in a Tris solution and larger in a choline solution. It is suggested that the light-induced K+ release is due mainly to an activation of voltage sensitive K+ channels.

Animals↗