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Biomedical subjects

N Weber

Publications and source records attributed to N Weber.

96 records · Page 6Linked to original sources

Pulmonary deposition of monodisperse aerosols in patients with chronic obstructive pulmonary disease.

In order to improve patient convenience and drug availability for patients with alpha 1-protease inhibitor deficiency, the administration via the inhalation route has been considered. This study investigated if it is possible to obtain high values of peripheral aerosol deposition by using optimized and controlled inhalation conditions. Therefore, peripheral deposition was studied in 10 patients with alpha 1-protease inhibitor deficiency (phenotype PiZ) and moderate to severe chronic obstructive pulmonary disease by measuring the 24-hour Clearance of radiolabeled inert iron oxide particles with diameters of 2 microns, 3 microns, and 4 microns. Patients inhaled a large volume of aerosol (1000 to 2000 cm3), which was normalized to the individual lung function, with a flow rate of 200 cm3/S. Due to this breathing pattern, peripheral deposition was for all particle sizes above 50% of the inhaled aerosol. The highest peripheral deposition (68%) was found for 3-microns particles.

Administration, Inhalation↗

Radioactive labelling of lipids in rat neurosarcoma by intravenous injection of [1-14C]-octadecenol.

Radioactivity from cis-9-[1-14C]octadecenol, injected intravenously into rats bearing neurosarcoma, is incorporated to a significantly greater extent into tumor than into muscle. In the lipids of both tissues, radioactivity is incorporated predominantly into the acyl moieties, rather than into the alkyl or alk-1-enyl moieties, of diradylglycerophosphocholines, diradylglycerophosphoethanolamines, and triradylglycerols.

Animals↗

Specific positional distribution of acyl moieties in phospholipids is not generally deleted in neoplastic cells.

The distribution of acyl moieties at sn-1 and sn-2 positions of cholinphosphoglycerides (CPG) and ethanolaminephosphoglycerides (EPG) has been determined for neurosarcoma, sarcoma 180 and leukemia L 1210. In all the three samples, the positional distribution of acyl moieties in the two major classes of phospholipids is found to be similar to that in cellular phospholipids of most mammalian tissues. The saturated acyl moieties are located predominantly at sn-1 and polyunsaturated acyl moieties at sn-2, whereas the monounsaturated acyl moieties are randomly distributed between these two positions. Apparently, a disruption of specific positioning of acyl moieties in phospholipids, which hitherto has been considered to be a general metabolic deletion in neoplasia, does not exist in an all neoplastic cells.

Acylation↗

Fatty acid alteration of plastidic and extra-plastidic membrane lipids in metribuzin-resistant photoautotrophic Chenopodium rubrum cells as compared to wild-type cells.

The fatty acid compositions of plastidic and extra-plastidic membrane lipids of two metribuzin-resistant cell lines L4 and L7 of Chenopodium rubrum were determined after growth in the absence and in the presence of the herbicide and compared with those of wild type cells. Fatty acid biosynthesis was markedly affected in all cell lines by metribuzin treatment. In the absence and in the presence of metribuzin alterations of the fatty acid composition of the various lipid classes were, as compared to wild type cells, generally lower in the highly resistant L4 cells than in the less resistant L7 cells. The two resistant cell lines demonstrated a higher degree of unsaturation within the plastidic monogalactosyldiacylglycerols (L4 cells also within plastidic digalactosyldiacylglycerols) and, particularly, within the predominantly extra-plastidic phosphatidylcholines (L7 cells also within the predominantly extra-plastidic phosphatidylethanolamines), whereas the degree of unsaturation was slightly altered in the plastidic phosphatidylglycerols. Within the two metribuzin-resistant cell lines, the highly resistant L4 cells differed from the less resistant L7 cells by increased alpha-linolenic acid/palmitic acid ratios in both the plastidic and extra-plastidic membrane lipids suggesting that particularly in L4 cells higher proportions of linolenate are formed as a result of selection pressure. On the other hand, the proportion of linoleate was increased predominantly in extra-plastidic membrane lipids of both L4 and L7 cells which explains a raise in linoleic acid/palmitic acid ratios in both cell lines as compared to wild-type cells. Moreover, in the absence of metribuzin decreased proportions of trans-3-hexadecenoic acid were found in phosphatidylglycerols of L4 and, particularly, of L7 cells as compared to the wild type cells. It is suggested that L4 and L7 cells--having multiple mutations in the psbA gene as observed earlier--are additionally characterized by increased degree of unsaturation of acyl moieties in various polar lipids, e.g. linoleoyl moieties in L4 and L7 cells as well as linolenoyl moieties particularly in highly resistant L4 cells. This increase gives rise to a change in membrane fluidity and may finally lead to increased metribuzin resistance.

Drug Resistance↗

Biologically active ether lipids: incorporation of long-chain precursors into 1(3),2-diacylglycero-3(1)-O-4'-(N,N,N-trimethyl)homoserines and other lipids of Chlorella fusca.

The lipids of Chlorella fusca are composed of the ester lipids typical of photosynthetically active cells. In addition, there occurs a class of less common ether lipids, the biologically active 1(3),2-diacylglycero-3(1)-O-4'-(N,N,N- trimethyl)homoserines, at a level of about 1.3% of total lipids. The acyl moieties of the total lipids include saturated as well as mono-, di- and tri-unsaturated species with chain lengths of 16 and 18 carbon atoms, the major constituents being palmitic and oleic acids. In both the diacylglycerophosphocholines, i.e., the major class of ester phospholipids, and the diacylglycero-4'-O-(N,N,N-trimethyl)homoserines palmitic acid is located predominantly at position 1 of the glycerol backbone, whereas oleic acid is almost equally distributed between positions 1 and 2; palmitoleic and polyunsaturated fatty acids are esterified preferentially at position 2. Incubation of C. fusca cultures with 14C-labeled fatty acids leads to their rapid incorporation into various lipid classes. Oleic and palmitic acids are incorporated at a faster rate than stearic acid (18:1 greater than 16:0 much greater than 18:0). 1,2- and 1,3-Diacylglycerols are the most prominent intermediates of early metabolism of the exogenous fatty acids. In the course of time, a steady decrease of radioactive 1,2-diacylglycerols is observed that is accompanied by an increase in labeled triacylglycerols, diacylglycerophosphocholines, and diacylglycero-O-(N,N,N-trimethyl)homoserines. The stereospecific distribution of acyl moieties in the diacylglycero-O-(N,N,N-trimethyl)homoserines in C. fusca indicates that these ether lipids are derived from 1,2-diacylglycerol intermediates. This notion is supported by the finding that during incubation with radioactively labeled fatty acids the formation of diacylglycero-O-(N,N,N-trimethyl)homoserines parallels the biosynthesis of both diacylglycerophosphocholines and diacylglycerophosphoethanolamines, two classes of phospholipids which are known to be derived from 1,2-diacylglycerols. The mechanism of the formation of the ether bond, however, is as yet unknown. Incubation of C. fusca cultures with 14C-labeled fatty acids or alcohols leads to the formation of fair proportions of wax esters that are labeled in both the acyl and the alkyl moieties, indicating that in these algae fatty acids and alcohols are interconverted. 14C-Labeled long-chain alcohols are not incorporated into the alkyl moieties of ether lipids, whereas labeled 1-O-alkylglycerols are used, though to a very small extent, as precursors of ether phospholipids.

Chlorella↗