Search PubMed⌕ Search

Biomedical subjects

U Weber

Publications and source records attributed to U Weber.

At least 163 records · Page 9Linked to original sources

[Osteocalcin and bone histology in osteoporosis].

The decoupling of bone formation and bone resorption causes an insidious bone loss that is responsible for the negative skeletal balance in the frequent form of low turnover osteoporosis. The reduction of bone formation can hardly be verified by clinical methods. Osteocalcin, a non-collagenous bone protein, has proved to be a useful new indicator of bone formation. To establish its predictable value, plasma levels of osteocalcin were compared to conventional serological data of bone turnover and to histomorphometric parameters of iliac crest trabecular bone. In cases of osteoporosis with normal bone turnover activity (as confirmed by histomorphometry) no differences were observed in any of our laboratory data including osteocalcin. However, there was a significant lower mean serum level of osteocalcin in a group of patients with histomorphometrically proven low turnover osteoporosis in comparison to those with normal bone turnover. Serum levels of osteocalcin below 2.0 ng/ml seem to indicate a low turnover in the individual case of osteoporosis while this is unlikely when serum levels above 6.0 ng/ml are measured (according to our RIA).

Adult↗

The white gene as a marker in a new P-element vector for gene transfer in Drosophila.

We describe new vectors suitable for P-element mediated germ line transformation of Drosophila melanogaster using passenger genes whose expression does not result in a readily detectable phenotypic change of the transformed flies. The P-element vectors contain the white gene fused to the heat shock protein 70 (hsp70) gene promoter. Expression of the white gene rescues the white phenotype of recipient flies partly or completely even without heat treatment. Transformed descendents of most founder animals (GO) fall into two classes which are distinguishable by their orange and red eye colours. The different levels of white expression are presumably due to position effects associated with different chromosomal sites of insertion. Doubling of the gene dose in orange eyed fly stocks results in an easily visible darkening of the eye colour. Consequently, the generation of homozygous transformants is easily possible by simple inbreeding due to the phenotypic distinction of homo- and heterozygous transformants. Cloning into these P-element vectors is facilitated by the presence of polylinkers with 8 and 12 unique restriction sites.

Animals↗

Experimental carotenoid retinopathy. II. Functional and morphological alterations of the rabbit retina after acute canthaxanthin application with small unilamellar phospholipid liposomes.

Eight "chinchilla bastard" pigmented rabbits were treated intravenously with sonicated phospholipid liposomes (SUV) consisting predominantly of egg yolk phosphatidylcholine (PC). Four rabbits were treated with canthaxanthin incorporated into PC liposomes in a single injection and fractionated over a period of 19 days. The total amount of PC used was a single dose of 260 mg administered as a 50-ml suspension and 13.7 mg/fraction given as a 5-ml suspension. The total amount of canthaxanthin used was a single 40 mg as a 50-ml suspension and 2.1 mg/fraction as 5-ml suspension. Electroretinography showed that canthaxanthin produced a depression of the a-waves and prolongation of the scotopic a- and b-wave peak latencies. A single high-dose injection of PC and PC plus canthaxanthin resulted in a transitory reduction in ERG amplitudes. A single injection of PC and canthaxanthin also produced hypernormal a-waves within the recovery time. Electron microscopy demonstrated that in contrast to the controls (PC), the canthaxanthin-treated rabbits showed alterations in the RPE/photoreceptor complex, indicating that these layers are the primary site of canthaxanthin effects on the retina.

Animals↗

Experimental carotenoid retinopathy. I. Functional and morphological alterations of the rabbit retina after 11 months dietary carotenoid application.

beta-Carotene, canthaxanthin, and beta-carotene plus canthaxanthin were administered to "chinchilla bastard" pigmented rabbits in their rabbit diet (approximately 200 ppm carotenoid per group). The effect of the carotenoids on retinal function and morphology was tested against a control group in the course of 11 months. Electroretinography showed that in contrast to the control animals, beta-carotene-treated rabbits produced increasing peak latencies of the scotopic b-waves. In the canthaxanthin-treated rabbits, a- and b-waves showed hypernormal amplitudes at low cumulative dosages (approximately 0.5-2 g) and reduced amplitudes at higher dosages (about 5 g). The peak latencies of the scotopic a- and b-waves increased remarkably. This effect was still stronger in the carotenoid combination. Histology and electron microscopy indicated that in contrast to the control animals, canthaxanthin-treated rabbits showed a reduction in retinal thickness in some samples. In particular, they exhibited alterations in the granular layers and a marked diminuation of the photoreceptor outer segments and morphological alterations of the photoreceptor inner segments with massive deposition of electron-dense material. In all animals treated with carotenoids, lipid droplets of the retinal pigment epithelium were enlarged in size and number.

Animals↗

[Significance of an angiogenic factor (in omental lipid) for the vascularization of the cornea].

The existence of an angiogenic factor in the omental lipid was verified by injecting four different test materials in dosages of 50 microliters into the corneas of New Zealand rabbits. The test substances were: 1) phosphate-buffered saline solution; 2) chloroform-methanol solution; 3) phosphate-buffered saline homogenate of the chloroform-methanol extract of the lipid cake from the rabbit omentum. The experimental results show that the modes of neovascularization after injection of lipid and nonlipid materials into rabbit corneas are very similar. For angiogenesis to be stimulated, the noxious substances must be retained in the cornea for several days. One day after injection the phosphate-buffered saline solution is totally resorbed. The other test substances (2-4), are retained within the cornea for days or weeks. Test substance 1 does not induce any corneal vascularization. The injection of test substances 2-4 causes similar corneal neovascularization: the proliferation of vessels always starts from that segment of the limbus closest to the stimulation. Since the extent of vascularization after injection of chloroform-methanol solution alone is similar to that which occurs after injection of an omental lipid extract, the hypothesis of a specific angiogenic factor is not supported. Fluorescein angiography reveals a large outflow of fluid (leakage) out of the neovascularization.

Angiogenesis Inducing Agents↗

[Electrophysiologic and histologic retinal changes after diethylene glycol administration].

The toxic effect of diethylene glycol on the retina was studied in white New Zealand rabbits. In a three-month study diethylene glycol dissolved in water was administered orally to groups of four rabbits at dose levels of 0 (control) and 4%. The ERG revealed a dose-dependent prolongation of the b-wave and a reduction in the photopic amplitudes of the a- and b-waves. In agreement with the electrophysiological findings the histologic study of the retina showed birefringent crystals predominantly in the inner nuclear cell layer. Oxalate seemed to be a metabolite of diethylene glycol, because aggregations of calcium oxalate crystals were deposited in the kidneys and livers of the animals.

Animals↗

Generation of oligomeric insulin receptor forms by intramolecular sulfhydryl-disulfide exchange. Involvement of masked sulfhydryl groups.

Insulin receptors from rat liver membranes were labelled with a 125I-labelled photoreactive insulin analogue or by iodination using lactoperoxidase and analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Under nonreducing conditions different receptor forms with Mr 400,000 (alpha 2 beta 2), 360,000 (alpha 2 beta beta'), 330,000 (alpha 2 beta' beta'), 320,000 (alpha 2 beta), 280,000 (alpha 2 beta'), 240,000 (alpha 2), 210,000 (alpha beta), 165,000 (alpha beta') and 115,000 (alpha) were detected. The subunit composition of these receptor forms was determined by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis in the absence and presence of dithioerythritol. During denaturation in sodium dodecyl sulfate in the absence of reductants, the Mr 400,000 receptor form (alpha 2 beta 2) was converted into the Mr 320,000 (alpha 2 beta) and Mr 240,000 (alpha 2) receptor form. This conversion was prevented either by N-ethylmaleimide, oxidants, or low pH. In contrast, alkylation of the receptor with N-ethylmaleimide under non-denaturing conditions did not prevent the appearance of intermediate-sized receptor forms. Furthermore, the inhibition of receptor cleavage by N-ethylmaleimide during denaturation was also observed when the amount of free sulfhydryl groups was reconstituted by the addition of an unlabelled and non-alkylated receptor sample to the alkylated and photoaffinity-labelled receptor. These results suggest, that the generation of different oligomeric receptor forms detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis is due at least in part to the cleavage of one or both beta-subunits from the insulin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

The nonclassical insulin binding of insulin receptors from rat liver is due to the presence of two interacting alpha-subunits in the receptor complex.

The binding characteristics of the insulin receptor tetramer (alpha 2 beta 2) and dimer (alpha beta) were examined. Unlabelled insulin enhanced the dilution-induced dissociation only of the receptor tetramer-bound 125I-insulin. Furthermore, when both the receptor forms had been preincubated with anti-receptor-antibodies (B9-antiserum), insulin binding only to the receptor tetramer but not to the dimer was inhibited. However, both oligomers are not immunologically distinct since more than 80% of the two forms were immunoprecipitated by the antiserum. These results suggest that both insulin and anti-receptor-antibodies induce cooperative interactions between the two linked alpha-subunits of the receptor tetramer leading to a decrease in insulin binding of this receptor form.

Affinity Labels↗

Characterization of solubilized insulin receptors from rat liver microsomes. Existence of two receptor species with different binding properties.

Insulin receptors were solubilized from rat liver microsomes by the nonionic detergent Triton X-100. After gel filtration of the extract on Sepharose CL-6B, two insulin-binding species (peak I and peak II) were obtained. The structure and binding properties of both peaks were characterized. Gel filtration yielded Stokes radii of 9.2 nm (peak I) and 8.0 nm (peak II). Both peaks were glycoproteins. At 4 degrees C peak I showed optimal insulin binding at pH 8.0 and high ionic strength. In contrast, peak II had its binding optimum at pH 7.0 and low ionic strength, where peak I binding was minimal. For peak I the change in insulin binding under different conditions of pH and ionic strength was due to a change in receptor affinity only. For peak II an additional change in receptor number was found. Both peaks yielded non-linear Scatchard plots under most of the buffer conditions examined. At their binding optima at 4 degrees C the high affinity dissociation constants were 0.50 nM (peak I) and 0.55 nM (peak II). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of peak I revealed five receptor bands with Mr 400 000, 365 000, 320 000, 290 000, and 245 000 under non-reducing conditions. For peak II two major receptor bands with Mr 210 000 and 115 000 were found. The peak II receptor bands were also obtained after mild reduction of peak I. After complete reduction both peaks showed one major receptor band with Mr 130 000. The reductive generation of the peak II receptor together with molecular mass estimations suggest that the peak I receptor is the disulfide-linked dimer of the peak II receptor. Thus, Triton extracts from rat liver microsomes contain two receptor species, which are related, but differ considerably in their size and insulin-binding properties.

Affinity Labels↗