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H Engler

Publications and source records attributed to H Engler.

85 records · Page 5Linked to original sources
PubMed1980

Dissociation between interferon production induced by phytohemagglutinin and concanavalin A in spleen cell cultures of nude mice.

Spleen cells of homozygous nude mice did not react with lymphoproliferation to both phytohemagglutinin (PHA) and concanavalin A (Con A), and there was no detectable interferon production in response to Con A. However, PHA-induced interferon production was equal in spleen cells of nu/nu mice and nu/+ mice. One possible explanation for these findings is that a subset of T cells responds to PHA with interferon production different from that responding to Con A with interferon production.

Animals↗
PubMed1980

The effect of atropine and metiamide on pepsin secretion of the rat.

The inhibition of pepsin secretion by metiamide and atropine was studied by perfusing the stomach lumen of anaesthetized rats. Atropine was more effective than metiamide in the inhibition of pepsin secretion induced by pentagastrin or carbachol. Perfusion of the stomach with a weak acid solution stimulated pepsin secretion, which was only abolished by atropine. Metiamide was ineffective. It is postulated that (1) hydrogen ions probably stimulate pepsin secretion, (2) a cholinergic-like reflex may be involved in this stimulation, (3) anticholinergics are direct and strong inhibitors of pepsin secretion, (4) histamine H2-receptor antagonists probably inhibit pepsin secretion indirectly via reduction of acid output.

Animals↗
PubMed1980

Interferon production in cocultures between mouse spleen cells and tumor cells: possible role of mycoplasmas in interferon induction.

Interferon production was measured in the murine mixed lymphocyte tumor cell interaction (MLTI) using spleen cells of three inbred mouse strains and a number of in vitro grown lymphoma cells. No difference in interferon production was observed when syngeneic or allogeneic combinations were compared. Interferon was not detectable during the first 6 h of culture and reached its maximum after 12--24 h. In contrast, natural killer cell activity of spleen cells against one of these lymphoma lines (YAC-1) was already high after 4h. A cell line that was not susceptible to natural killing (MDAY-D2) induced the same amount of interferon as YAC-1. These findings suggest that natural killer cell activity and interferon induction in the MLTI are not correlated. Several lymphoma cell lines induced interferon in the MLTI whereas some others did not. All lines that were inductive were found to contain mycoplasmas. Furthermore, even the cell-free supernatants of inducing lines contained mycoplasmas and induced interferon. Purified mycoplasmas and membranes thereof were able to induce interferon production in mouse spleen cells. Our data strongly suggest that interferon production in the MLTI is caused by mycoplasmas. This artifact is the relevance for three reasons. First, cocultures between lymphoma cells and lymphocytes are widely studied in immunology. Secondly, contamination with mycoplasmas is extremely common and often goes unnoticed in immunological laboratories. Thirdly, interferon is known to affect profoundly a number of in vitro functions of immunocompetent cells.

Animals↗
PubMed1979

Production of interferon in the murine mixed lymphocyte culture. II. Interferon production is a T cell-dependent function, independent of proliferation.

Interferon production occurs after two days of culture in murine mixed lymphocyte cultures (MLC). This was demonstrated in various combinations of mouse spleen cells differing at the major histocompatibility (H-2) locus. Interferon production could be demonstrated in one-way MLC when F1/parent combinations were used and in reactions in which one partner was treated by puromycin. After treatment of both cell populations with mitomycin C, interferon production occurred in the absence of lymphoproliferation. Interferon production in response to alloantigen did not occur in spleen cell cultures of nude mice and in cultures treated by anti-theta antiserum plus complement indicating that interferon production is a T cell-dependent function.

Animals↗
PubMed1979

Low molecular weight intracellular iodocompounds with long intrathyroidal half-life: remnants of thyroglobulin hydrolysis?

In this paper additional information on low molecular weight, soluble, intrathyroidal iodocompounds with slow metabolic rate is provided. These compounds have previously been localized autoradiographically within the follicular cells. Radioiodide was administered to rats on a normal iodine intake (6--7 microgram/day) for 80 days to approach isotopic equilibration of the intrathyroidal iodine with the dietary radioiodide. When the isotope was omitted from the diet the intrathyroidal radioiodine was released with an apparent half-life of approximately 12 days. When the individual soluble components carrying radioiodine were analyzed after separation on Sephadex G-200, different apparent half-lives were found, the half-life of thyroglobulin (Tgb) being roughly 10 days and that of the low molecular weight iodocomounds being in the order of 60 to 100 days or more. In addition to the soluble low molecular weight iodocompounds, the radioactivity in the particulate fraction increased by 100% during the tracer washout when compared to Tgb and the total soluble fraction. The soluble slow turnover iodocompounds contained a higher percentage of carbohydrate and total iodine than Tgb, while the relative amounts of each sugar analyzed (hexoses, fucose, hexosamine and sialic acid) were close to those in Tgb. Sephadex G-25 chromatography of the low molecular weight iodocompounds obtained after Sephadex G-200 separation resulted in the separation of 4 peaks. Two peaks identified as iodopeptides could be further analyzed. The carbohydrate composition of these peptides was similar to that of 2 glycopeptides obtained after in vitro enzymatic hydrolysis of purified Tgb with pronase. Slow equilibration with radioiodine, long apparent intrathyroidal half-life and carbohydrate content similar to that of Tgb, taken together with previously published data on intracellular localization of soluble intrathyroidal iodocompounds, suggest that the low molecular weight iodocompounds are products of in vivo hydrolysis of engulfed Tgb droplets.

Animals↗
PubMed1979

[Synthesis and H2-antihistaminic activity of ring methylated metiamide analogues. 4th communication: H2-antihistaminic agents (author's transl)].

In studies on structure-activity relationships of histamine H2-receptor antagonists, the influence of different imidazole ring methylation on the H2-antagonist activity was investigated. 2-Methyl-, 5-methyl-, 2,5-dimethyl- and unsubstituted analogues of metiamide were prepared and tested. While 5-methyl- and unmethylated analogues with a thiourea group proved to be quite active, the 2-methyl- and 2,5-dimethyl-derivatives, as well as those with a urea group, had only low H2-antihistaminic activity.

Animals↗
PubMed1979

[The secretory action of various C-5-alkylsubstituted histamines and N alpha-methyl-histamines on anaesthetized cats with Heidenhain pouches (author's transl)].

In particular, the action of N alpha-methyl-histamine has to be considered since its secretory response is approximately 1.5 times greater than that of histamine and its secretion lasted for a longer period of time. After C-5-alkylsubstitution, both 5-methyl-histamine and N alpha,5-dimethyl-histamine showed secretory action comparable to that of histamine; the agonistic activity, however, decreased with increasing chain length.

Animals↗
PubMed1978

Transformation of normal follicles into thyrotropin-refractory "cold" follicles in the aging mouse thyroid gland.

Autoradiographs of thyroid glands of aging mice demonstrate the gradual appearance of "cold" follicles which fail to iodinate the intraluminar iodoproteins even after intense exogeneous or endogeneous TSH stimulation. "Cold" follicles first appear at the age of 5 months. They may account for 80% of all thyroid follicles in 13-month-old mice. Morphologically, the "cold" follicles are characterized by a larger than normal colloid volume and a comparatively flat epithelium for any given follicle size. Old thyroids are twice as large as young ones. They contain twice as much normally iodinated thyroglobulin/mg wet weight. The total number of cells per gland remains constant throughout the life time. This is probably also true for the total number of follicles. The iodide pump, as judged by the tissue to serum ratio, remains normal and TSH-responsive. Yet, it is not established whether this is due to a higher activity of the pump in normal follicles or to preservation of inorganic iodide transport in "cold" follicles. Pinocytosis is defective in "cold" follicles and is poorly responsive to TSH stimulation. Furthermore, diffusion of iodocompounds is severely impaired in the colloid of "cold" follicles. It is suggested that the primary defect in the pathogenesis of "cold" follicles in old mice is the gradual failure of endocytosis to respond to normal TSH stimulation. Because exocytosis and iodination would first proceed normally, the follicular lumina would become overdistended up to a point where the apical membrane is functionally impaired. With this sequence of events, "cold" follicles would have impaired iodination while being metabolically as active as hot ones. Thus, several puzzling reports on high metabolic activity of "cold" tissue could possibly be interpreted.

Aging↗
PubMed1975

Autoradiographic localization of slow turnover iodocompounds within the follicular cells of the rat thyroid gland.

In addition to thyroglobulin, several low molecular wt iodinated glycopeptides are present in the thyroid gland. Some of these compounds are considered to be slowly metabolized remnants of intracellular lysis of engulfed colloid droplets. In this paper we present autoradiographic evidence obtained by light microscopy, suggesting that breakdown products of thyroglobulin digestion can indeed be located within the thyroid cells. The thyroid glands of rats were labeled with 125I to approach isotopic equilibrium. The tracer was then withdrawn from the otherwise unchanged high-iodine diet, and thyroidal radioactivity was washed out for 80 days. Autoradiographs of glands containing 10% or less of the tracer present at equilibrium showed the bulk of 125I within the follicular cells while the colloid was only slightly labeled. An additional finding was the presence of dense radioactive inclusions in the lumina of many follicles. They are assumed to represent clusters of thyroglobulin molecules not readily available to pinocytosis. In addition to autoradiographic evidence, the identity of intracellularly located radioactivity with slow-turnover enzyme-resistant iodocompounds is supported by double labeling experiments, using 125I as the "old" tracer, accumulating within the cells, and 131I as the "new" label representing intraluminal 19 S thyroglobulin. Experimental manipulations which tended to deplete the thyroid of thyroglobulin, increased the 125I/131I ratio in the gland as predicted by the working hypothesis. Thus, this paper describes a new kind of autoradiographic ring reaction due to a hitherto barely considered intracellular organic iodine pool.

Animals↗
PubMedDate not supplied

The effect of tasuldine, a bronchosecretolytic agent, on mucus rheology and clearability and the interaction with acetylcholine in ferrets.

Tasuldine (Ts) is an orally active bronchosecretolytic agent shown to be clinically effective in human studies. Tasuldine decreases the sialomucin content of the mucus and, in animal studies, this modulation of the glycopeptide correlates with decreased mucus viscosity. The aim of this study was to evaluate the effect of tasuldine on mucus viscoelasticity and correlate the rheological changes to mucociliary and cough clearability. Tracheal mucus samples were collected from anaesthetized adult ferrets by a modification of the cytology brush technique. Mucus was collected prior to and following administration of either vehicle (normal saline) or Ts (10 mg/kg i.v.), and followed by acetylcholine (ACH) challenge (ca. 4 ml of 10(-2)M i.v., slow infusion). The analysis included magnetic microrheometry to measure the viscosity and elasticity of microlitre quantities of mucus. Mucociliary transportability (NFPTR) was measured by means of the frog palate assay and mucus collection rates (mg/min) were used as an indirect measure of secretion rate. The principal index of mucus rigidity, log G*, decreased with tasuldine infusion (P = 0.014) and further decreased with ACH (P = 0.002). In simple terms, the mucus became less rigid or more deformable with tasuldine administration, thus benefiting clearability based on predictions from model studies. The changes observed with acetylcholine alone were consistent with a classic secretagogue response--the outputting of a large volume of watery mucus. NFPTR increased with tasuldine treatment, and even further with acetylcholine; however, the combination of Ts and ACH resulted in a decrease in NFPTR close to baseline, which was likely due to the fact that the resulting mucus was too liquid for maximal mucociliary efficiency. The index of mucus flux (mg/min) was very much elevated with ACH compared with control; this was not the case with Ts. This indicates that tasuldine, despite improving the rheological properties of the mucus, did not stimulate hypersecretion, as was the case for acetylcholine. The changes in mucus rheology with infused tasuldine can be considered beneficial with respect to their effects on predicted mucociliary and cough clearability, supporting the clinical effectiveness of this type of mucolytic therapy in airway diseases such as chronic bronchitis. The study also illustrates the potential danger of overliquification of mucus.

Acetylcholine↗
PubMedDate not supplied

Effects of sodium salicylate on elimination kinetics of indomethacin and bile production in dogs.

We investigated the effects of sodium salicylate on the elimination kinetics of indomethacin in bile duct-cannulated beagles. Indomethacin and metabolites were quantified by HPLC in plasma, bile, and urine. Indomethacin was administered as iv bolus injection and iv infusion to yield a steady-state plasma concentration of approximately 1 microgram/ml. Following sodium salicylate, given either iv (25 mg/kg) or via duodenal fistula (50 mg/kg), the indomethacin plasma level dropped instantaneously by 60-70%. Concomitantly, total systemic clearance from the plasma and biliary clearance were increased significantly. In addition, a reduced plasma protein binding of indomethacin and a significant increase in the volume of distribution were observed. The amount of indomethacin, excreted as free and conjugated drug in bile, was significantly increased temporarily by sodium salicylate. The total amount eliminated in bile (approximately 70% of the dose), however, was not changed by sodium salicylate co-administration. The bile flow was significantly enhanced for at least 4 hr. Both phase 1 metabolism and renal excretion of indomethacin remained practically unaffected by sodium salicylate treatment.

Animals↗
PubMedDate not supplied

A recombinant adenoviral vector expressing full-length human retinoblastoma susceptibility gene inhibits human tumor cell growth.

As a prelude to considering retinoblastoma (RB) gene therapy for cancer, a series of human tumor cell lines with either full-length, mutated, or undetectable RB protein were treated with recombinant adenovirus encoding RB (ACNRB). Both RB protein expression and the cytotoxic and antiproliferative effects of ACNRB treatment were evaluated. While the transgene expression of a reporter virus encoding the beta-galactosidase enzyme (rAd-beta-gal) varied among cell lines, the reintroduction and expression of the RB gene resulted in a pronounced inhibition of cellular proliferation in RB-altered cell lines. An antiproliferative response was observed with control adenovirus treatment in some cell lines. ACNRB treatment did not cause detectable cytotoxicity in either RB+ or RB-altered cells. Dose-dependent cytostasis was observed in RB- cell lines. In vivo tumor suppression was observed in a breast xenograft model subsequent to the treatment of established tumors with ACNRB. These data support a role for RB gene therapy of tumors with RB mutations and provide a basis for the further evaluation of ACNRB gene therapy of human cancer.

Adenoviridae↗