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Biomedical subjects

H Werner

Publications and source records attributed to H Werner.

At least 127 records · Page 7Linked to original sources
PubMed1991

Hypothalamic hormones in milk.

Following a multistep extraction and fractionation of sheep and human milk, immunoreactive and biologically active somatostatin (SS) was demonstrated as a constituent of milk. Milk, in contrast to serum, contains only SS-14-like material and not SS-28. HPLC-purified sheep milk somatostatin was found to inhibit both basal and prostaglandin-induced release of growth hormone from cultured rat pituitary cells. The effect was dose-dependent and similar to that of synthetic SS. In order to determine whether SS or vasoactive intestinal peptide (VIP) can be synthesized by the mammary gland we have looked for SS and VIP messenger RNA in rat glands extracted on different days of lactation. No messages for SS or VIP were detected in the mammary gland, whereas, as expected, hybridization signals for alpha-casein were evident. These results suggest that somatostatin and VIP are not synthesized by the mammary gland and are probably concentrated from blood. In other experiments we have demonstrated that one hour after oral administration of labelled somatostatin to rat pups, about 95% of the neuropeptide, extracted from the stomach, is eluted exactly at the same position as the marker peptide. These results suggest that, in contrast to the adult, somatostatin remains intact in the stomach of the neonate and therefore may be absorbed in a biologically active form.

Animals↗
PubMed1991

Azelastine: a multifaceted drug for asthma therapy.

Azelastine (4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-p hthalazinone hydrochloride), a novel long-acting antiasthmatic/antiallergic drug has been demonstrated to be effective in the treatment both of asthma and of allergic rhinitis. In this paper some selected properties of azelastine are presented which might contribute to its antiasthmatic and antiallergic effect. Azelastine causes a marked inhibition of generation of oxygen radicals in alveolar macrophages. A bronchosecretolytic activity of azelastine is observed which is based on the secretion of a more liquid mucus. Furthermore, the mucociliary clearance is enhanced as demonstrated in a rabbit model. Also IL-1 generation is inhibited in vitro and in vivo. Finally, the possible tissue and cellular accumulation of azelastine in lung and alveolar macrophages resp. is discussed.

Animals↗
PubMed1991

[The effect of sulbactam on the in vitro activity of mezlocillin, piperacillin and cefotaxime].

The in vitro activity of mezlocillin (MZL, CAS 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and cefotaxim (CTX, CAS 63527-52-6) alone and in combination with sulbactam (SBT; CAS 68373-14-8) against mezlocillin-resistant pathogens was determined in a multicenter study. A total of 870 strains were investigated (481 Enterobacteriaceae, 57 Pseudomonas aeruginos, 41 Acinetobaster spp., 194 Bacteroides fragilis, and 97 Staphylococcus spp.). Determinations of MIC were performed according to DIN-guidelines (agar-dilution method for aerobes and microbroth-dilution method for anaerobes). Sulbactam was added in fixed concentrations of 5 mg/l and 10 mg/l. In all sulbactam-combinations examined mean MIC as well as MIC50 and MIC90 were reduced compared to the respective values for the antibiotics alone. Consequently, percentages of susceptible strains increased significantly: i.e. for Enterobacteriaceae: MZL 1% vs. MZL + 10 mg/l SBT 53%; PIP 4% vs. PIP + 10 mg/l SBT 54%; CTX 52% vs. CTX + 10 mg/l SBT 68%. The effect of sulbactam was most pronounced in Bacteroides spp. with an increase in susceptible strains from 2% to 97% for MZL, from 6% to 95% for PIP and from 7% to 98% for CTX. The results indicate that by adding sulbactam the in vitro activity of mezlocillin, piperacillin and cefotaxim against resistant pathogens is augmented significantly. In addition, the spectrum of antibacterial activity is extended to anaerobic pathogens such as Bacteroides spp. The availability of sulbactam as a monosubstance for combination with various beta-lactam-antibiotics thus represents a useful improvement of therapeutic options in bacterial infections.

Acinetobacter↗
PubMed1991

Influence of anticoagulants on growth and vitamin K production of intestinal bacteria.

The influence of anticoagulants on growth and vitamin K production of intestinal bacteria was studied. Bacteroides vulgatus and Escherichia coli were grown in vitro in the presence of increasing amounts of warfarin, phenprocoumon and acenocoumarol. It was found that growth of B. vulgatus was inhibited under anaerobic conditions whereas growth of E. coli under aerobic conditions was not inhibited. A specific inhibition of vitamin K biosynthesis was not observed in either case. It is concluded that therapeutic doses of anticoagulants are unlikely to affect growth or vitamin K production of intestinal bacteria.

Acenocoumarol↗
PubMed1990

Cloning and characterization of the proximal promoter region of the rat insulin-like growth factor I (IGF-I) receptor gene.

We have isolated genomic clones that contain the promoter region of the rat IGF-I receptor gene. A unique transcriptional start site was suggested by the results of primer extension and RNase protection assays, which also defined a 940-base 5'-untranslated region. Despite the single start site, the proximal 415 base pairs of 5'-flanking region were devoid of TATA or CCAAT elements. The region surrounding the start site was, however, similar to a recently described "initiator" sequence that can direct specific transcription initiation in the absence of a TATA element. The 5'-flanking region was GC-rich and contained several possible SP1 sites, but also included potential ETF and AP-2 binding sites. The rat IGF-I receptor gene promoter region appears to have some sequences similar to both "housekeeping" and highly regulated promoters and may be an example of an intermediary class of regulatory region.

Animals↗
PubMed1990

Nonsense suppression in Dictyostelium discoideum.

We describe the generation of Dictyostelium discoideum cell lines that carry different suppressor tRNA genes. These genes were constructed by primer-directed mutagenesis changing a tRNA(Trp)(CCA) gene from D. discoideum to a tRNA(Trp)(amber) gene and changing a tRNA(Glu)(UUC) gene from D. discoideum to a tRNA(Glu)(ochre) as well as a tRNA(Glu)(amber) gene. These genes were stably integrated into the D. discoideum genome together with a reporter gene. An actin 6::lacZ gene fusion carrying corresponding translational stop signals served as a reported. Active beta-galactosidase is expressed only in D. discoideum strains that contain, in addition to the reporter, a functional suppressor tRNA. Both amber suppressors are active in D. discoideum without interfering significantly with cell growth and development. We failed, however, to establish cell lines containing a functional tRNA(Glu)(ochre) suppressor. This may be due to the fact that nearly every message from D. discoideum known so far terminates with UAA. Therefore a tRNA capable of reading this termination codon may not be compatible with cell growth.

Base Sequence↗
PubMed1990

In vitro activity of daptomycin-metronidazole combinations against mixed bacterial cultures: reduced activity of metronidazole against Bacteroides species in the presence of Enterococcus faecalis.

The in vitro activity of daptomycin-metronidazole combinations against mixed cultures of gram-positive facultative cocci and strains of the Bacteroides fragilis group was investigated. Metronidazole did not influence the high activity of daptomycin against strains of Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis in the absence or presence of the co-cultured Bacteroides strains. In contrast, the Enterococcus faecalis isolates protected the co-cultured Bacteroides strains against the killing effect of metronidazole, even at a concentration four- or eightfold the MIC of metronidazole. Killing curve experiments confirmed this protective effect of different isolates of Enterococcus faecalis.

Anti-Bacterial Agents↗
PubMed1990

Are soluble monocyte-derived HLA class II molecules candidates for immunosuppressive activity?

Supernatants of human blood monocyte cultures suppressed PHA responses (IL-2 synthesis, IL-2R expression, DNA synthesis) of autologous and allogeneic lymphocytes. The main suppressive activity was found in the 65-kDa (and 23-kDa) range. It could be incompletely neutralized by mAb specific for a non-polymorphic HLA DR determinant and could also be adsorbed to and eluted from an anti-DR immunoabsorbent column. On blots of monocyte lysates and monocyte culture supernatants, the mAb RoDR recognized antigens of nearly the same Mr. The hypothesis that soluble HLA DR alpha beta heterodimers or beta chains are likely candidates for the suppressor factor was confirmed by analogous effects of purified HLA DR molecules. We favor a model in which soluble MHC class II molecules (in contrast to surface-bound ones) may interfere with the association and cross-linking processes necessary for T cell activation by competing for CD4 binding sites.

Antibodies, Monoclonal↗
PubMed1990

The so-called interleukin-2 inhibitory activity of human serum is largely cytotoxic to mouse cells.

No specific interleukin-2 (IL-2) inhibitor has ever been demonstrated in human, mouse, or any other animal serum. Native mouse serum contains activities which completely inhibit IL-2-dependent and IL-2-independent in vitro proliferation of cells of different animal species by a non-cytotoxic mechanism. The decisive inhibitory component of mouse serum has a molecular weight of about 80,000, is heat-labile and has not been found in other animal sera. Also, native human serum completely suppresses the proliferation of various mouse cell types, predominantly by a cytotoxic effect caused by natural IgM antibodies and complement. Heat-inactivated human serum is no longer cytotoxic to mouse cells, and inhibits the proliferation of mouse cells much less than native serum. There is thus no evidence for a specific IL-2 inhibitor in mouse, human or other serum.

Animals↗
PubMed1990

Chemical modification of cellulosic membranes and their blood compatibility.

Blood compatibility is determined by interactions at the blood-material interface that depend on the material surface chemical structure. Through selective modifications of the chemically reactive hydroxyl groups of cellulose, the aim was to improve the biocompatibility of cellulose membranes. The number of potentially reactive hydroxyl groups on the cellulose membrane surface were reduced through isocyanate cross-links or through the introduction of hydrophilic, hydrophobic, or ionic functionalities by graft copolymerization. To assess blood compatibility, levels of C3a desArg were determined in plasma after membrane contact. Using the electrophoretic mobility test, the release of cytokines were measured after in-vitro incubation of mononuclear cells with membranes. Adsorption of 131J-human fibrinogen was additionally investigated. With respect to the biocompatibility parameters selected, the modified cellulose membranes show improved in-vitro blood compatibility in comparison to unmodified cellulose membranes.

Biocompatible Materials↗
PubMed1990

Regulation of rat brain/HepG2 glucose transporter gene expression by phorbol esters in primary cultures of neuronal and astrocytic glial cells.

We have demonstrated regulation of the rat brain/Hep G2 glucose transporter gene (GT1) by Northern blot analysis with a rat brain glucose transporter cDNA probe. Incubation of both neuronal and glial cells derived from neonatal rats with 12-O-tetradecanoyl-phorbol-13-acetate induced a time- and dose-dependent increase in the steady state levels of GT1 mRNA. In glial cells, this corresponded to an increase in both the level of GT1 protein and glucose transporter activity, as demonstrated by Western blot analysis and [3H]2-deoxyglucose (dGlc) uptake studies. In contrast, in neuronal cells 12-O-tetradecanoyl-phorbol-13-acetate had no effect on either the concentration/level of the GT or [3H]dGlc uptake. These results suggest that phorbol esters regulate dGlc uptake at the transcriptional level in both neuronal and glial cells, but that the increase in expression of the GT1 gene is dissociated from posttranscriptional events involved in dGlc uptake in neuronal cells.

Animals↗
PubMed1990

Liver regeneration is associated with increased expression of the insulin-like growth factor-II/mannose-6-phosphate receptor.

The process of liver regeneration involves the concerted action of certain growth factors, which stimulate hepatocyte proliferation, and other antiproliferative factors, which prevent uncontrolled growth of this organ. Some of the biological actions of insulin-like growth factor-II (IGF-II), a mitogenic polypeptide closely related to insulin, may be mediated by the IGF-II receptor. This receptor consists of a single chain extracellular domain and a very small cytoplasmic domain, and can bind lysosomal enzymes that contain mannose-6-phosphate (M-6-P) residues. Since these enzymes may be involved in remodelling processes in certain tissues, we measured the expression of the IGF-II/M-6-P receptor in the liver after subtotal hepatectomy. Binding of [125I]IGF-II to crude plasma membranes from regenerating liver was maximal 2 days after hepatectomy (4.9% specific binding/60 micrograms protein) and subsequently decreased. Both control livers (livers removed at the time of operation) and sham-operated control livers demonstrated specific [125I]IGF-II binding of 1.1% throughout the experimental period. This increase in binding in regenerating liver was shown to be associated with an increase in the concentration of IGF-II receptor protein by means of Western blot analysis using a polyclonal anti-IGF-II/M-6-P receptor antiserum (3637). Similarly, steady state levels of IGF-II/M-6-P receptor mRNA, measured by solution hybridization/RNase protection assays, were significantly increased in the regenerating liver (2.0-fold over the control value 2 days after hepatectomy). Five and 10 days postsurgery, the levels of IGF-II receptor mRNA were markedly reduced, and they were even lower than the levels in control livers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression.

To investigate the potential role(s) of the insulin-like growth factors (IGFs) in embryogenesis, we have used in situ hybridization histochemistry to localize mRNAs for IGF-I, IGF-II, and the type I IGF receptor during an early period in rat embryonic development (embryonic days 14 and 15). IGF-I and IGF-II mRNAs were found in distinctly different patterns of cellular distribution. IGF-I mRNA was particularly abundant in undifferentiated mesenchymal tissue in the vicinity of sprouting nerves and spinal ganglia, and in circumscribed regions of the developing face that corresponded to the target zones of the trigeminal nerve. IGF-I mRNA was also found in aggregations of mesenchyme surrounding, but not in developing muscle and cartilage. IGF-I mRNA was selectively concentrated in areas of active tissue remodeling, such as the cardiac outflow tract, and was undetectable in liver, pituitary, and nervous system at this early stage of organogenesis. IGF-II mRNA was abundant in developing muscle, cartilage, and vascular tissue, and in the embryonic liver and pituitary. IGF-II mRNA was also conspicuous in areas of vascular interface with the brain, such as the choroid plexus and the organum vasculosum of the lamina terminalis. Messenger RNA for the type I IGF receptor was widely distributed in embryonic tissues, but the highest level were seen in the ventral floorplate of the hindbrain, where specialized neuroepithelial cells act as guides for axonal targeting. In conclusion, the different cellular patterns of expression of genes for IGF-I and IGF-II indicate that these two IGFs are differently regulated and, thus, may have significantly different roles in the process of embryonic development. Furthermore, the early and widespread expression of the type-I IGF receptor gene, in contrast to the relatively limited and localized pattern of IGF-I gene expression, is consistent with the view that this receptor may mediate the effects of IGF-II as well as IGF-I during embryogenesis.

Animals↗
PubMed1990

Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney.

Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study.

Animals↗
PubMed1990

[Electrochemical examinations to the influence of mechanical treatment of surfaces on the corrosion on different dental amalgams. 2: Measurements of potentiodynamic polarization with high polarization rate].

In a cell with artificial saliva the electrochemical behaviour of amalgam specimens of Germadent, Duragam and ANA 2000 are characterized in dependence of different mechanical treatments of surfaces using cycling voltimetry. In the beginning the influence of roughness on the corrosion is evident, but increasing the influence of chemical composition dominant. Duragam-amalgam is most resistant to corrosion. The content of copper in Duragam has a better effect than the high content of copper in ANA 2000.

Copper↗