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Biomedical subjects

R Mallinger

Publications and source records attributed to R Mallinger.

43 records · Page 3Linked to original sources

In vitro fibrillogenesis of interstitial collagens: electron microscopical studies of long-spacing forms induced by chondroitin sulfate.

Reaggregation behaviour of the three interstitial types of collagen was studied. Pure solutions were prepared and reprecipitation performed by the addition of chondroitin sulfate. The sediments were analyzed in the electron microscope. Classical types of fibrous long spacing collagen could be prepared only from solutions of type I collagen. Segments with an average length of 460 nm and a central overlapping zone of about 120 nm were prepared from solutions of type II collagen. They were termed 'double segment long-spacing collagen' (DSLS). No cross striated fibrils or segments could be obtained from solutions of type III collagen. These results show that there are not only chemical differences between the three interstitial types of collagen but also differences in reaggregation behaviour and in the way of interaction with other macromolecules such as glycosaminoglycans.

Animals↗

[Incorporation of L-azetidine-2-carboxylic acid into collagen of the skin. Structural changes].

As previously shown by two dimensional thin-layer chromatography L-azetidine-2-carboxylic-acid (L-Az) is incorporated into type I skin collagen instead of proline when 3 week old mice are fed with a 0,1% solution of L-Az orally. Ultrastructural investigations did not reveal significant changes in collagen periodicity and on fibril diameter. The collagen fibrils of the upper papillary dermis seemed to be packed more densely, sometimes only one electron dense lamina was seen instead of basal lamina and plasma membrane. The glycosaminoglycane-induced fibrillogenesis was not changed in contrary to the collagen-heat-gelation fibrillogenesis at 37 degrees C, where no gel aggregation could be seen. The reconstruction of native fibres from collagen solutions was disturbed too, several finer precipitated fibrils being detectable. On infrared spectroscopy significant differences in absorption spectra were detected. Correlating with previous results of reduced tensile strength and normal melting point of L-Az collagen we can conclude that L-Az might cause rather intermolecular than intramolecular disturbances of crosslinking.

Animals↗

Studies on a distinct fraction of bovine vitreous body collagen.

We were able to separate pepsin-solubilized collagen of the bovine vitreous body into three distinct fractions by differential salt precipitation with 0.5 M acetic acid containing 0.7 M, 1.2 M, and 2.0 M NaCl, respectively. The 0.7 M NaCl fraction showed an electrophoretic mobility in polyacrylamide gel identical to that of type II collagen, CNBr-derived peptides very similar to type II collagen CNBr-peptides, and a reaggregation behaviour closely related to type II collagen as observed by electron microscopy. Therefore, the fibres of the bovine vitreous body appear to contain a mixture of a collagen very similar to type II collagen precipitable in the presence of 0.7 M NaCl, at least two different collagen types that can be precipitated at 1.2 M, and 2.0 M NaCl concentrations that have not been identified previously.

Animals↗

Ketoprofen-poly(D,L-lactic-co-glycolic acid) microspheres: influence of manufacturing parameters and type of polymer on the release characteristics.

The effect of manufacturing parameters on the size and drug-loading of ketoprofen-containing biodegradable and biocompatible poly(DL-lactic-co-glycolic acid) (PLGA) microspheres prepared by the solvent evaporation method was investigated. For both drug-free and drug-loaded microspheres, smaller microspheres with a narrower size distribution were obtained when the stirring rate or the volume of the organic phase was increased. Incorporation of ketoprofen was found to increase with increasing volume of the organic phase and decreasing pH of the aqueous phase, but was independent of the acidity and the inherent viscosity of the PLGA used. The biphasic release profile of ketoprofen from the microspheres was dependent on the type of PLGA as well as the size and drug-loading, two parameters governed by the manufacturing process. The first burst effect was found to increase with the drug content, reduction of size of the microspheres and increasing inherent viscosity of the matrix, whereas acidity of the PLGA had no effect on the release of this acidic drug. A vigorous first burst effect was associated with reduced sustained delivery of ketoprofen, the rate of the delayed release phase being dependent on the inherent viscosity of the matrix, the size, the payload and the pH during preparation of the microspheres. Thus, by selection of the manufacturing parameters and the type of PLGA, it is possible to design a controlled drug delivery system for the prolonged release of ketoprofen, improving therapy by possible reduction of time intervals between peroral administration and reduction of local gastrointestinal side effects.

Anti-Inflammatory Agents, Non-Steroidal↗

Antigenic changes of the glomerular basement membrane after incorporation of hydroxyproline isomers.

We investigated antigenic changes of murine glomerular basement membrane (GBM) collagen type IV after oral feedings of 3-cis- or 4-cis-hydroxyproline. As shown by thin layer chromatography and gas chromatographic-mass spectrometric studies, 3-cis- and 4-cis-hydroxyproline were incorporated into the GBM collagen instead of the normal trans isomer and led to a considerable reduction of the collagen antibody reactivity on indirect immunofluorescence, passive hemagglutination and radioimmunoassay when compared to GBM collagen of control animals. We speculate that antigen modification due to the incorporation of stereoisomers could serve as a model for basement membrane immunopathology.

Animals↗

Modulation of CD99/MIC2 expression of human AHTO-7 osteoblasts by carcinoma cell line-conditioned media.

BACKGROUND: Prostate cancer metastases induce a predominantly osteoblastic response in bone tissue, resulting in new bone formation and associated morbidity; however, the mechanisms of these tumor-host responses are not fully understood. MATERIALS AND METHODS: Supernatants of prostate (PC3, DU145, LNCaP), breast (BT20, ZR-75-1), colon (SW620, Colo 320DM), pancreatic (ASPC1, Capan-1), renal cell (ACHN) and hepatoma (HepG2) cell lines were tested for their capacity to modulate proliferation, activity of alkaline phosphatase (ALP) and CD99/MIC2 expression in AHTO-7 (large T antigen transfected human trabecular osteoblasts) cells in vitro. RESULTS: Osteoblastic stimulation is not restricted to prostate cancer derived conditioned media CM and high activity is found in CM from Capan-1, HepG2 and ACHN lines. Furthermore these CM down-regulate the expression of the CD99/MIC2 antigen in comparison to medium by AHTO-7 cells as detected by HBA-71 immunofluorescence, with the exception of prostate cancer-derived CM. Induction of the differentiation marker ALP was detected in response to CM derived from Capan-1, BT-20 and Colo320DM. Stimulation of the proliferation of AHTO-7 cells (105-138% of control), induction of ALP (1.17-5.29-fold) and down-regulation of CD99 (13.6-57.5%) exhibited no correlation. CM derived from PC3 and LNCaP metastatic prostate cancer cell lines specifically resulted in the retention/stimulation of the expression of CD99/MIC2 in AHTO-7 cells in contrast to all other cell lines tested. CONCLUSION: The CD99/MIC2 antigen, which is expressed on human osteoblasts and osteosarcoma cells, seems to constitute a new and independent response marker of osteoblasts in the triggering of osteoblastic reaction by prostate cancer cells.

12E7 Antigen↗

Racial variation in lung cancer.

Lung cancer claimed about 153,000 lives in 1994 in the United States. Despite research overall lung cancer survival has still not improved during the last 20 years, with 5-year relative survival remaining about 13%. In addition several epidemiologic and molecular studies showed a difference in the incidence of lung cancer in the three major races. The aim of our study was to investigate the variations of race in lung cancer patients, in order to identify potential risk factors linked to the different racial status. In this light we compared a 10 years lung cancer data of black population from Howard University Hospital, Washington D.C., U.S.A. and a 20 years data of white population from the Vienna University Hospital, Austria. Our results did not show any significant difference in mean age or tumor localization in both groups, but highlighted a remarkable difference in the incidence of the lung cancer histological types also according to the sex. In this respect it could be more successful to consider carcinogenesis like a protracted process of gene function deregulation in response to cell injury from exposure to genotoxic substances with individual specificity.

Adult↗