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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 199 records · Page 11Linked to original sources
PubMed1990

Suicide risk in suicidal versus nonsuicidal depressed inpatients.

Depressed patients seem to be the prototype of patients with a higher suicide risk. Therefore, it is important for clinicians in psychiatric hospitals dealing with depressed inpatients as well as with depressed schizophrenic or alcoholic patients, to get a clear idea of the nature of suicide proneness among these inpatients. Results from different studies done by the Weissenau Depression Treatment and Research Group concerning the special issue of suicide proneness in depressed patients show that a "suicidal depressive syndrome" can best be described on a cognitive level by feelings of worthlessness, anxiety, and depressive delusions, and also by more sleep disorders and more past suicidal behavior.

Crisis Intervention↗
PubMed1990

[Effects of estrogen treatment on the antiviral properties of murine Kupffer cells].

Adult female mice were administered 17 beta-oestradiol at pharmacological dosages by subcutaneous injections. Histopathological examination revealed an increase in cells of the mononuclear lineage infiltrating the sinusoids of the liver. In vitro culture of Kupffer cells demonstrated that the treatment did not alter their antiviral properties but did rather induce an activation of their non-specific immune properties. This activation might be beneficial or deleterious for the infected host and must be discussed in each particular pathological process.

Animals↗
PubMed1990

[The question of the transmissibility of the results of subcutaneous tests of biomaterials from animals to humans].

The histologic estimation of the subcutaneous connective-tissue reaction at implants forms an important part of the biocompatibility test. The connective-tissue capsulae around titanium implants in man, guinea-pig, and Wistar-rat were analysed by a special test system because of the question concerning the transmission of results of animal experiments on the man. The subsidence process of the thickness of the connective-tissue capsule and of the cell count per measuring fields were represented in dependence on the time. The findings showed the fundamental similar course of wound healing in man, guinea-pig, and Wistar-rat by the influence of an implant.

Animals↗
PubMed1990

Slow accumulation of cyclosporin metabolites as measured by specific and nonspecific cyclosporin RIA.

Blood cyclosporin concentrations were measured by radioimmunoassay (RIA) using nonspecific polyclonal and specific monoclonal antibodies in 32 kidney transplant patients. Kinetics of cyclosporin concentrations after transplantation (day 0-2) and after long-term dosage (day 7-month 6) were evaluated by nonlinear regression analysis. Elimination and accumulation kinetics were linear and in agreement with one- or two-compartment kinetics. Only in 3 cases were saturable Michaelis-Menten kinetics observed (Vm = 23 ng/ml h-1, Km = 636 ng/ml). Bioavailability was 0.72 as estimated from first-pass extraction. The median values (5-95% CI) for the elimination half-life of nonspecific RIA concentrations increased from 5 h (2.5-6.2) on day 2 after transplantation to 10 h (9.2-11) after long-term dosage. The specific monoclonal antibody data revealed an elimination half-life of 6.4 h (5.6-7.7) for parent cyclosporin, which was unchanged after multiple dosing. After month 6, the elimination half-life of specific monoclonal antibody data was significantly shorter (p = 0.03) than elimination half-life of nonspecific RIA concentrations (6.6 vs 9.1 h). In relation to blood concentrations measured by nonspecific polyclonal antibody RIA, the fraction of parent cyclosporin significantly decreased from 84 percent (49-90) to 30 percent (24-52) after long-term dosage as measured by specific monoclonal antibody (p = 0.01). It is concluded that metabolites of cyclosporin accumulate in a slow compartment and, after long-term cyclosporin administration, nonspecific RIA blood concentrations are mainly contributed by cyclosporin metabolites.

Adult↗
PubMed1990

Changes in the distribution of proteinpolysaccharide complexes within the articular cartilage in experimental osteoarthrosis.

The quantity and type of proteinpolysaccharide complexes in the matrix determine up to a great extent the mechanical properties of articular cartilage. It is the purpose of this study to evaluate the changes in the mentioned matrix components against the background of experimentally induced osteoarthrosis. As shown by electron microscopic and morphometric studies, the changes in the superficial layer are promptly occurring and clearcut, whereas those in the deep layers are recorded in late observation terms only. A reduction of proteoglycan quantity is noted with a simultaneous differentiation of their fine structure in the various stages of osteoarthrosis development. Initially the alteration in the cell organization of chondroblasts is associated with occurrence of differences in proteoglycan content, and subsequently--in the collagen structures of the matrix too.

Animals↗
PubMed1990

[Estimation of the healing process of denatured orthotopic bone implants in an animal model. I. Measurements with polarization microscopy].

The paper gives in a series of 3 parts a survey, quantitative statements and conclusions on the healing process of denatured orthotopic osteoresections with the initial bone obtained by, polarization optical measurements (this first part), morphological evaluation method (part II), (in these cases the collagen polymorphism served as indicator for the regeneration course) and, semiquantitative method of observation after conventionally histological treatment as well (part III). The investigations were carried out on the mandible of pigs depending on the treatment of the resected bone parts (chemical or hyperthermal denaturation in comparison with the native state). Samples of osteoreimplantions were taken in intervals of one week up to the 70th postoperative day. Histological sections were used from the different regions (contact region, gap region, border and internal regions of the resections) and investigated by the methods mentioned above. The results of the first part (polarization microscopical measurements) revealed the regular course of differentiation in the bone regeneration process: The resection is fully integrated into the initial bone after a mean duration of 112 +/- 25 days. The fastest regeneration takes place in the contact region, the slowest is found within the resection (in the case of chemical denaturation investigated).

Animals↗
PubMed1989

Pore-forming protein from Entamoeba histolytica forms voltage- and pH-controlled multi-state channels with properties similar to those of the barrel-stave aggregates.

Pore-forming protein from Entamoeba histolytica forms cation-selective channels in planar bilayers. With increasing potentials, the open-state probability of these channels decreases, and channel aggregates collapse (Young, J.D.-E. and Cohn, Z.A. (1985) J. Cell. Biochem. 29, 299-308). In this communication we report the following observations: (i) incorporation of the pore in black-lipid membranes was stimulated by membrane potential, (ii) pores were rectifying, (iii) breakdown of pores resulted in a continuous spectrum of subconductance states, (iv) the open-state probability increased strongly with pH. This pattern of behaviour is similar to that of the barrel-stave aggregates (alamethicin and related toxins). We therefore conclude that the amebal pores, like those of the barrel-stave class, may consist of complexes involving variable numbers of membrane-spanning subunits.

Animals↗
PubMed1989

Cyclosporin drug monitoring: comparison of four immunoassays and HPLC.

Cyclosporin blood trough levels were measured with four different immunoassays and high-performance liquid chromatography in 12 patients receiving low-dose steroids and CsA after kidney transplantation. These patients represent a selection with an uncomplicated posttransplant course and received no drugs with a known influence on CsA pharmacokinetics. The use of specific antibodies against the parent drug yielded levels comparable to those detected by HPLC. CsA levels measured with nonspecific antibodies exceeded those measured with specific ones by a factor of two to three. All immunoassay-detected CsA levels correlated significantly with the HPLC-determined CsA levels. In addition, blood levels of the CsA metabolites 1, 17, 18, and 21 were determined by HPLC. In one additional patient, who was under tuberculostatic treatment and had a transitory deterioration of liver function, levels of nonspecific-antibody-determined CsA rose, as confirmed by rising levels of metabolite 17, while those of the parent drug fell. We conclude that routine drug monitoring should include at least one immunoassay with a specific antibody detecting the unchanged CsA, and a supplementary immunoassay with a nonspecific antibody detecting a composition of cross-reacting metabolites plus the unchanged substance. If available, HPLC should be used to confirm levels of CsA and its metabolites in patients with suspected alteration of their CsA metabolism.

Administration, Oral↗
PubMed1989

Nerve growth factor increases in adult rat brain after hypoxic injury.

Brain injury increases the synthesis of many growth and trophic factors. We have measured nerve growth factor (NGF) content in brain of adult rats with bilateral carotid artery occlusion exposed to 7% O2. Five days after hypoxia the NGF content was increased in neostriatum, hippocampus and cerebral neocortex, areas exhibiting focal neuronal degeneration and inflammation. The increase was not related to changes in choline acetyltransferase activity that was only reduced in heavily damaged cortex. The findings may indicate that the increase in NGF content was due to enhanced NGF synthesis by inflammatory cells including stimulated glia.

Animals↗
PubMed1989

Muscarinic receptors on cultured cells of rat hippocampus: cholinergic regulation and presence of subtypes.

Muscarinic acetylcholine receptors in intact, cultured explants of rat hippocampus were investigated in binding experiments with tritiated quinuclidinyl benzilate ([3H]QNB) as ligand. Dissociation constants (Kd) were determined to 320-575 pM and maximal binding capacity (Bmax) to 67-87 fmol/explant. The KdS obtained in kinetic experiments were very similar. Hippocampal explants cultured alone contained more muscarinic receptors than hippocampal explants reinnervated by cholinergic fibers from co-cultured septal explants. Pretreatment of hippocampal explants with carbachol resulted in a down-regulation of receptor number which was counteracted by the simultaneous addition of atropine. Atropine added alone had no effect on receptor number in hippocampal explants cultured alone whereas it occasionally caused an up-regulation in co-cultured hippocampus. Displacement experiments with scopolamine and oxotremorine as competitors, showed that hippocampal explants cultured alone contain multiple types of muscarinic receptors. With atropine, pirenzepine and AF-DX 116, only one class of receptors could be detected.

Animals↗
PubMed1989

Saturable first-pass kinetics of propranolol.

Reduced bioavailability (F) due to hepatic first-pass extraction of an oral dose (D) is a well-known pharmacokinetic phenomenon. An integrated solution for Michaelis-Menten kinetics of the first-pass effect is derived from the maximal metabolic rate (Vm), volume of distribution (Vd), first order absorption rate constant (ka), Michaelis constant (Km), and liver blood flow (Q). F = 1 - VmVd/kaD ln (1 + kaD/QKm) This equation for single dosage can also be extended to steady state kinetics after multiple dosing in which the amount of a drug present in the hepatic circulation is considered. According to the literature, the bioavailability of a single 80 mg oral dose of propranolol (F = 0.22) increases after multiple doses Fss = 0.36). Based on the first pass equations for single dosage and multiple dosing, the maximal metabolic rate (Vm = 0.043 mg l-1 h-1) corresponding to 310 mg per day and the Michaelis constant (Km = 0.10 mg/l) were calculated for propranolol. Incorporation of nonlinear plasma protein binding in this concept may explain the lack of threshold phenomenon for a single dose of less than 40 mg propranolol. Zero order absorption kinetics could explain why cumulation kinetics seem linear even at an excessive dosage of 960 mg propranolol per day. From these derivations it may be concluded that multiple dosing, increase in plasma protein binding, high absorption rate, and increased portal venous blood flow will increase bioavailability, whereas slow release formulations, fractional drug dosage, and saturable absorption kinetics will decrease bioavailability of first-pass drugs like propranolol.

Absorption↗
PubMed1989

Quinine dosage in severe malaria with renal failure necessitating haemodialysis.

For therapy of severe malaria with renal failure, a 2/3 reduction in the usual intravenous dose of quinine is recommended (600 mg per 24 h instead of 600 mg per 8 h). Two patients with severe malaria and renal failure requiring dialysis have been treated. The half-life was not prolonged (15 h). Quinine proved to be nondialysable. It was shown that this dose of quinine tended to lead to a low level in blood (under 10 mg.l-1). A normal dose of quinine (2 x 15 mg/kg per day) is therefore recommended for malaria therapy, even in cases with renal failure requiring haemodialysis, in order to attain the desired plasma level (5 to 15 mg.l-1).

Chromatography, High Pressure Liquid↗
PubMed1989

Developmental and regeneration-associated regulation of the limbic system associated membrane protein in explant cultures of the rat brain.

In the present study we have examined the topographic and temporal patterns of expression of the limbic system associated membrane protein by light and electron microscopic immunocytochemistry in organotypic cultures of the rat brain. The regional, cellular and subcellular distribution of staining in young cultures was similar to that in the intact brain of corresponding age. Since the tissue in vitro is isolated both from afferents and targets, short-term protein expression appears to be regulated by factors intrinsic to the neuron. In culture, the protein was present on the surface of neurons which are physiologically interconnected, such as neurons belonging to the septohippocampal system (cholinergic neurons in the septum and pyramidal and granule cells in the hippocampus). It was also present on the surface of axons and growth cones during process outgrowth. Thus, the limbic system associated membrane protein is expressed in an appropriate spatial and temporal pattern for mediating interactions between growing axons and their targets. The expression of the protein in culture showed some important differences as compared to the intact brain. With increasing age, there was an increasing scattering and disappearance of immunoreactivity in cultures fixed with paraformaldehyde/glutaraldehyde. The decreased immunoreactivity in aged cultures does not appear to reflect decreased protein synthesis, because unfixed and acetone-fixed explants continued to show immunostaining. Furthermore, dot-blot assays showed similar amounts of immunoreactivity in culture as in the intact brain of corresponding age. Thus, the age-dependent decrease of immunoreactivity may reflect altered insertion of the protein into the membrane or a modification of the epitope recognized by the antibody. There was a rapid increase (within 1 hour) of immunostaining on the surface of sprouting processes following mechanical lesion of mature, unstained axons. The altered distribution after tissue injury could be a means of ensuring specificity of connectivity during nerve fiber regeneration. On the basis of the reported findings, we suggest that system-specific membrane proteins, including the limbic system associated membrane protein, may mediate the formation of specific connections in the brain. Furthermore, we suggest that the reinnervation processes taking place after central nervous system injury may exhibit a similar molecular basis to the development of neural pathways.

Animals↗
PubMed1989

A membrane glycoprotein associated with the limbic system mediates the formation of the septo-hippocampal pathway in vitro.

The ability of a neuronal surface glycoprotein to mediate the formation of neuronal connections was tested in an explant culture system. A monoclonal antibody against the limbic system-associated membrane protein (LAMP) was used in co-cultures containing cholinergic neurons of the septum and their hippocampal target neurons. Antibody treatment had no effect on general axon outgrowth, but significantly diminished the ability of septal cholinergic axons to invade and collateralize in the hippocampus. The results suggest that factors regulating general axon outgrowth may be distinct from those regulating the patterns of outgrowth that define the formation of neural circuits.

Animals↗