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Biomedical subjects

A Ziegler

Publications and source records attributed to A Ziegler.

At least 271 records · Page 15Linked to original sources
PubMed1988

Role of HLA class II and cytokine expression in rheumatoid arthritis.

HLA class II expression is notable in rheumatoid arthritis. We have investigated the mechanism of HLA class II regulation in the joints and found local synthesis, as judged by mRNA levels to be high. The role of antigen presentation in maintaining class II mRNA was explored, and blocking presentation by using monoclonal antibodies to HLA class II inhibited synthesis of mRNA for HLA-DR alpha chain. HLA class II expression is maintained by cytokines and so cytokine production in rheumatoid joints was investigated. It was chosen to use mRNA analysis by slot blotting as a screening assay, and the expression of many cytokines was detected. Levels of these were maintained in culture in the absence of extrinsic stimulation.

Antibody Formation↗
PubMed1988

Association of polyoma virus middle T antigen and pp60src with cytoskeletal elements.

Polyoma virus middle T antigen (mT) as well as pp60v-src, the oncogene product of Rous sarcoma virus, associate with membranes and cytoskeletal structures in virus-infected cells. Furthermore, mT has been shown to be tightly bound to pp60c-src, the cellular homolog of pp60v-src. While the presence of pp60v-src in focal contacts has been demonstrated, the localization of mT and pp60c-src is less clear. We show here that mT is associated with focal contacts and that the phosphorylated protein can be immunoprecipitated with anti-vinculin serum. We suggest that the mT/pp60c-src complex and pp60v-src are tightly bound to vinculin. This interaction may be relevant in the process of cell transformation since disorganization of the actin filament network seems to play an important role in the deregulation of cell growth observed in tumor cells.

Animals↗
PubMed1987

Lack of expression of HLA [corrected] class I and class II molecules on the human oocyte.

The expression of histocompatibility leukocyte antigen (HLA) class I and class II antigens on human oocytes was investigated by the indirect immunofluorescence assay using well-defined monoclonal antibodies. Oocytes were obtained from an in vitro fertilization program or were studied on frozen sections from human ovaries. Neither HLA class I, beta 2-microglobulin, nor HLA class II molecules were detected on cultured oocytes or frozen sections. The zona pellucida also lacked these antigens, but granulosa cells expressed HLA class I molecules. Our results also indicate the presence of certain types of class II molecules on granulosa cells. The present experiments demonstrate that the human oocyte belongs to those few cell types in the human body which are devoid of both types of HLA molecules.

Antibodies, Monoclonal↗
PubMed1987

Serum alpha-tocopherol levels after high-dose enteral vitamin E administration in patients with acute respiratory failure.

Serum levels of tocopherols were measured in 5 healthy volunteers and in 14 patients with acute respiratory failure before and after onset of high-dose enteral vitamin E administration. The initial alpha-tocopherol levels did not differ between both groups (12.1 +/- 2.7 micrograms/ml in the volunteers and 11.3 +/- 3.5 micrograms/ml in the patients; mean +/- SD). After oral administration of 1 g d,l-alpha-tocopherylacetate per day the serum levels more than doubled within 1 day and reached a plateau between 22 and 30 micrograms/ml after 3 days in the volunteers. In contrast, application of even 3 g vitamin E/day by gastric tube in the patients with respiratory failure caused only a delayed increase of the serum levels with values nearly doubling after 5-10 days (6 patients), or there was no increase at all (8 patients). Serum alpha-tocopherol did not rise in patients without accompanying highmolecular weight formula diet and in patients with prolonged hemodynamic insufficiency and metabolic acidosis. The age of the patients, the fact of severe blood losses, hemodialysis and hemofiltration and the final outcome of death or survival appeared to be without influence on the response to enteral vitamin application. Neither in the volunteers nor in the patients with acute respiratory failure were there any detectable amounts of beta-, gamma- or delta-tocopherol or of alpha-tocopherolquinone or alpha-tocotrienol.

Acute Disease↗
PubMed1987

HLA-class II antigens on human hematopoietic progenitors.

A panel of alloindifferent monoclonal antibodies (MAB's) was used in complement-dependent lysis to characterize human myeloid, erythroid and multipotential progenitors (CFU-GM, BFU-E, CFU-GEMM) for their expression of MHC class II HLA-DR, -DP, and -DQ products. 7-16 donors were tested in each system. MAB Tü 34, detecting DR products, caused reduction of CFU-GM by a mean of 89%, whereas BFU-E and CFU-GEMM were reduced by 67% and 66% respectively. 35% of CFU-GM, 27% of BFU-E and 32% of CFU-GEMM were lysed by MAB B7/21, recognizing HLA-DP determinants, while Tü 22, binding HLA-DQ antigens, lysed 32% only of CFU-GM and did not lyse the other progenitors. Employing the "broad" MAB Tü 39, which binds at least DR and DP, inhibition of colony formation by CFU-GM was generally greater than that caused by Tü 34 alone or even by combinations of Tü 34, Tü 22, and B7/21. This suggests that there may be a subset of DR-, DP-, DQ- hematopoietic progenitors, which nonetheless bind MAB Tü 39, previously proposed as a candidate for the recognition of novel class II antigens.

Antibodies, Monoclonal↗
PubMed1987

Role of calcium in the activation of smooth muscle.

Smooth muscle depends to a large extent on the extracellular calcium concentration for activation of its contractile proteins. Calcium influx via voltage-dependent or receptor-operated channels is thought to supply the cell with Ca2+ for contractile activation. If this is so, the inhibition of transmembranal calcium influx will prevent mechanical activation. A blockade of transmembranal calcium influx has been proposed as a mode of action for calcium antagonists. This suggestion seems to be supported by experiments in which tissue was incubated in 45Ca-containing solutions for 2-3 min and thereafter transferred for 40-60 min to ice-cold calcium-free or lanthanum-containing solutions. The amount of remaining 45Ca in the tissue at the end of the wash-out phase is taken as a measure of calcium influx during the labelling period. However, procedures involving rather long-lasting wash-out periods cannot yield information on Ca2+ influx, since the calcium store relevant for contractile activation adapts rapidly to changes in extracellular Ca2+ concentration.

Adaptation, Physiological↗
PubMed1987

Effects of gallopamil, nifedipine, Ni2+, and La3+ in guinea pig atria after a sudden increase in extracellular Ca2+ concentration.

In isolated left atria of guinea pigs, we investigated the effects of four different calcium antagonists on the adaptation of force of contraction, action potential duration (APD), and calcium (Ca) content to a sudden change in the extracellular Ca2+ concentration ([Ca2+]0) from 0.9 to 3.6 mM. Under control conditions (rate of stimulation, 1 Hz), force of contraction rapidly adapted to an increase in [Ca2+]0 from 0.9 to 3.6 mM, reaching a transient maximum within 5 min ("hypercontractility"). The accompanying prolongation in APD also had a biphasic time course, but only when [Ca2+]0 was increased within the 1st hour of an experiment. The Ca antagonists investigated were gallopamil (0.2 microM), nifedipine (75 nM), Ni2+ (0.5 mM), and La3+ (1 mM). The negative inotropic effect of La3+ was complicated by an increase in resting tension after prolonged exposure (greater than 30-60 min). With the exception of Ni2+, the Ca antagonists depressed the maximum and the steady-state force of contraction after the increase in [Ca2+]0. The biphasic nature of force adaptation was attenuated by gallopamil, Ni2+, and La3+, but not by nifedipine. Gallopamil and La3+ slowed the time course of adaptation. The Ca content of the tissue was determined with the 45Ca method. Gallopamil, nifedipine, and Ni2+ had no effect on the Ca content nor on the time course of Ca uptake after the increase in [Ca2+]0, but La3+ profoundly slowed the time course of Ca uptake. Although inhibition of the Ca current by Ca antagonists modifies the functional adaptation to elevated [Ca2+]0, the Ca antagonists with the exception of La3+, do not influence the change in total Ca content. It is concluded that calcium channels are not the only pathway by which calcium is taken up by the tissue when [Ca2+]0 is increased.

Action Potentials↗
PubMed1987

Calcium, cell membrane, and excitation-contraction coupling.

Skeletal muscle, heart muscle, and smooth muscle differ with respect to morphology, function, and Ca metabolism. For the actual coupling between excitation and contraction, three different sources of Ca2+ supply are conceivable: release from intracellular organelles, release from plasmalemmal binding sites, and transmembranous influx. Considerable experimental evidence favors the membranes of the sarcoplasmic reticulum as the source of coupling Ca2+ in skeletal muscle, whereas in cardiac and smooth muscles the Ca store from which coupling Ca2+ is released has to be in intimate contact with the extracellular Ca2+ concentration. In order to distinguish between the two remaining possibilities for the source of coupling Ca2+, i.e., transmembranous Ca influx and Ca release from the plasmalemma, Ca antagonist--widely accepted tools for detecting Ca influx--were used. Ca antagonists did not have any influence on Ca exchange or Ca uptake either in cardiac or in smooth muscles. These findings may be interpreted as follows: Ca antagonists do not act by inhibiting the Ca2+ influx, although they reduce the amount of coupling Ca2+. This conclusion conflicts with current ideas concerning the mode of action of Ca antagonists. We feel, however, that the experimental support for the Ca-channel hypothesis is rather vague. This leads us to favor the plasmalemma as the main source of coupling Ca2+ in cardiac and smooth muscles.

Animals↗
PubMed1987

Critical remarks on the Ca-flux determinations in smooth and cardiac muscle.

The commonly used methods of determining Ca fluxes in smooth and cardiac muscle are scrutinized for their appropriateness. These methods include an incubation of the tissue in 45Ca, followed by a washout period either in ice-cold EGTA-containing Ca-free solutions or in lanthanum-containing Ca-free solutions. The amount of 45Ca remaining in the tissue at the end of the washout phase is taken as Ca2+ influx during the labeling period. Procedures including longer washout periods cannot yield information on Ca2+ influx, since the Ca store relevant for contractile activation rapidly adapts to changes in the extracellular Ca2+ concentrations.

Animals↗
PubMed1987

Assignment of the TCP1 locus to the long arm of human chromosome 6 by in situ hybridization.

TCP1, the human homolog of the Tcp-1 locus in the mouse, which is part of the murine t complex and codes for an abundant testicular germ-cell protein, has been mapped within the human genome by in situ hybridization. Using a cDNA probe for TCP1, pB1.4 hum, we assigned TCP1 to human chromosome region 6q23----qter, with the most likely localization being 6q25----q27.

Animals↗
PubMed1987

[Binding of drugs to artificial plasma substitutes].

The binding of different drugs to plasma proteins as well as the binding to other structures (e.g. dialysis membranes, i.v. delivery sets) is well documented and of therapeutic importance. Colloid solutions of macromolecules are widely used as plasma substitutes and plasma expanders. A possible binding of drugs to these macromolecules was investigated by means of equilibrium dialysis. Benzodiazepines, beta-blockers, cardiac glycosides, local anesthetics, non steroidal antiinflammatory drugs, glibenclamide, phenobarbitone and phenprocoumon (10(-7) in 50 mM tris buffer, pH 7.4) were dialyzed against tris buffer diluted (1:5) commercially available plasma substitutes consisting of hydroxyethyl starch (HES), dextran, gelatine and polyvinylpyrrolidone (PVP). Binding to plasma substitutes was observed with the highest values for penbutolol and oxypolygelatine (41%), digitoxin and HES 200 (35%), phenprocoumon and PVP (43%). It is concluded that the binding of drugs to plasma substitutes is in most cases negligible and not of clinical relevance. Since some drugs seem to bind to some extent to different macromolecules this should be borne in mind and could be of some influence e.g. in perfusion experiments with isolated organs.

Chemical Phenomena↗