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Biomedical subjects

N Weber

Publications and source records attributed to N Weber.

At least 19 recordsLinked to original sources

Biosynthesis of storage lipids in plant cell and embryo cultures.

The biosynthesis of storage lipids in plant cell and embryo cultures is discussed in the light of their significance in the breeding of agriculturally important oil seed crops. After a short introduction to the biosynthesis of storage lipids, i.e. triacylglycerols and wax esters, this review covers the occurrence and biosynthesis of storage lipids in plant cell and embryo cultures. Plant cells in culture generally contain low levels of both unusual fatty acids and triacylglycerols indicating that these cells are quite different from cells of oil storage tissues. There are a few exceptions to this rule which demonstrate that induction of genes involved in the expression of fatty acid modification and triacylglycerol assembly is possible in plant cell cultures. Such biosynthetically active plant cells may be of particular interest in future studies of storage lipid assembly. Both somatic and gametophytic embryos of oil plants exhibit high capacities for storage lipid biosynthesis and accumulation in vitro compared to cultured plant cells. Above all, the microspore-derived embryo system is recommended to both plant breeders and plant biochemists for the selection and multiplication of plants of superior quality.

Agriculture

Stereoselectivity of lipases: esterification reactions of octadecylglycerol.

Stereoselectivity of several triacylglycerol lipases (EC 3.1.1.3) has been investigated in the enzymatic esterification of rac-1-O-octadecylglycerol with oleic acid in the presence of organic solvents, such as hexane. X-1(3)-O-Octadecylmonooleoylglycerols were the only products formed with most lipases; considerable proportions of X-1(3)-O-octadecyldioleoylglycerols were also formed with the lipase from Candida cylindracea. The mixtures of unesterified enantiomeric substrates, i.e., X-1(3)-O-octadecylglycerols were converted to their 3,5-dinitrophenylurethane derivatives and subsequently resolved into sn-1 and sn-3 enantiomers by HPLC on a chiral stationary phase (Sumichiral OA 2100). The data on enantiomeric excess (ee) and enantiomeric ratio (E) in the unesterified substrate revealed for the lipases from porcine pancreas, Rhizopus sp., Pseudomonas sp., Candida cylindracea, Chromobacterium viscosum and Penicillium cyclopium a distinct preference for 1-O-octadecyl-sn-glycerol over its enantiomer indicating stereoselectivity for the sn-3 position. For the lipase from Rhizomucor miehei a slight stereoselectivity for the sn-1 position was observed. Solvents, such as diethyl ether and dichloromethane, strongly inhibited the esterification reaction, but the enzymatic activity could be restored upon removal of such solvents by washing with hexane indicating reversible inhibition.

Esterification

Chlorinated hydrocarbon content of fetal and maternal body tissues and fluids in full term pregnant women: a comparison of Germany versus Tanzania.

Chlorinated hydrocarbons are distributed worldwide and due to their lipophilic properties and chemical stability they accumulate in the foodchain. The concentrations of 19 different chlorinated hydrocarbons (hexachlorohexane (HCH), DDT and various metabolites and nine different polychlorinated phenyl (PCB) congeners were detected in various body tissues and fluids (maternal and fetal serum, adipose tissue, placenta, amniotic fluid) of full term pregnant women from Germany and Tanzania. Great variation of total toxin burden and toxin distribution within the different body compartments was found. This was in part due to local differences of exposure to some of the chlorinated hydrocarbons. Comparing samples from Germany and Tanzania, typical distribution patterns reflected the specific economic situation of the two countries with a high burden of insecticides (DDT and Dieldrin) in the agricultural country and high levels of constituents of industrial products (hexachlorobenzene (HCB) and PCBs) in Germany. Different chlorinated hydrocarbons seem to show different distribution patterns in body tissues, probably due to their chemical structure, the lipid content of the compartment and the overall toxin burden of the individual. A 10 to 100 fold accumulation of chlorinated hydrocarbons was observed in maternal adipose tissue compared with the other compartments. The concentrations of certain toxins in fetal cord serum and placenta were higher than in maternal serum.

Adipose Tissue

Biotransformation of alkylglycerols in plant cell cultures: production of platelet activating factor and other biologically active ether lipids.

Plant cells in culture are capable of incorporating exogenous 1-O-alkyl-sn-glycerols into various neutral and ionic ether lipids. 1-O-Alkyl-2-acyl-sn-glycero-3-phosphocholines, the major class of compounds thus formed, are used for the preparation of platelet activating factor (PAF) in high yields. Similarly, the prochiral 2-O-alkyl-sn-glycerols are transformed to chiral 2-O-alkyl glycerophospholipids from which compounds can be obtained that exhibit antiviral activity in plant and animal cells. Reaction of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholines with phospholipase D in the presence of ethanolamine leads to 1-O-alkyl-2-acyl-sn-glycero-3-phosphoethanolamines, which serve as starting material for the preparation of 1-O-alkyl-2-acyl-sn-glycero-3-phospho-(N-acyl)ethanolamines, compounds known to have antitumor activity.

Biotransformation

Biologically active ether lipids. Biotransformation of rac-1(3)-O-alkylglycerols in cell suspension cultures of rape and semisynthesis of 1-O-alkyl-2-palmitoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamines, potent antitumor agents.

Biotransformation of rac-1(3)-O-hexadecylglycerol by photomixotrophic rape (Brassica napus) cells in suspension culture leads to 1-O-hexadecyl-2-acyl-sn-glycero-3-phosphocholines and small proportions of other ether lipids, e.g. 1-O-hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamines. Reaction of the hexadecylacyl-glycerophosphocholines with ethanolamine in the presence of phospholipase D from Streptomyces chromofuscus yields additional hexadecylacylglycerophosphoethanolamines. Partial hydrolysis of the combined hexadecylacylglycerophosphoethanolamines followed by reacylation of the resulting lyso compound with palmitic anhydride gives 1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phospho-(N-palmitoyl) ethanolamine, a nontoxic ether glycerophospholipid with antitumor activity. The corresponding 1-O-tetradecyl,1-O-octadecyl, and 1-O-[(Z)-9'-octadecnyl] derivatives are prepared similarly.

Antineoplastic Agents

A simple enzymatic method for the preparation of radiolabeled erucoyl-CoA and other long-chain fatty acyl-CoAs and their characterization by mass spectrometry.

A simple two-step method for the biosynthesis of radiolabeled erucoyl-coenzyme A of high specific activity and other long-chain fatty acyl-coenzyme A (acyl-CoA) thioesters is reported. 1-14C-labeled erucic and oleic acids, as well as unlabeled ricinoleic and nervonic acids, were incubated at 35 degrees C with coenzyme A in the presence of ATP, MgCl2, and acyl-CoA synthetase (EC 6.2.1.3) from Pseudomonas spp. to yield the corresponding CoA thioesters. Following incubation, each thioester was purified by rapid passage through a disposable reverse-phase C18 extraction column. The overall yields were greater than 90% and the purities greater than 95%, based on the distribution of radioactivity, and chromatographic and spectral properties. Fast ion bombardment-mass spectrometry was employed to confirm the structures of the various acyl-CoAs.

Acyl Coenzyme A

Random number generation by normal, alcoholic and schizophrenic subjects.

Controls (N = 45), schizophrenics (N = 20) and alcoholics (N = 23) were asked to choose at random a number between 1 and 10, 100 times. The correlation matrices of five different randomization indices were used to study within group variation; these matrices were similar for the normal and alcoholic groups, but very different for the schizophrenic group. The differences between the three groups were studied by canonical analysis and, in terms of the canonical variables, the mean performance of the normal group is clearly discriminated from that of the alcoholic and schizophrenic subjects.

Adult

Studies on intestinal absorption, distribution and metabolism of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro[4-14C]stigmast-5-ene in mice.

A method for the analysis of 3 beta-chloro steroids by high-performance liquid chromatography is described. These compounds are known to occur in commercial protein hydrolysates. The gastro-intestinal absorption, distribution and metabolism of chlorinated steroids were studied after their intragastric application to mice. At 2 hr after stomach intubation of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro-[4-14C]stigmast-5-ene, large proportions of radioactivity had passed through the small intestine and were found to be concentrated in the contents of the caecum and colon. Very small amounts of 3 beta-chlorocholest-5-ene were absorbed by the intestinal mucosa and distributed to organs and tissues outside the alimentary canal, whereas intestinal permeability of 3 beta-chlorostigmast-5-ene was negligible. After administration of labelled 3 beta-chlorocholest-5-ene, the highest value of radioactivity, 120 Bq/g tissue, outside the intestinal tract was detected in liver. Altogether, less than 0.5% of the total radioactivity applied to the animals was found to be transported through the intestinal wall and less than 0.5% of the total radioactivity was detected in various metabolites. In general, 3 beta-chlorostigmast-5-ene was transported in smaller proportions and metabolized to a lesser extent than the corresponding cholesterol derivative. Moreover, metabolites of the two radioactive substrates formed by enzymatic attack of enteric micro-organisms were not detected in the contents of the caecum and colon. It appears that 3 beta-chlorinated steroids are fairly stable products that are metabolized poorly both by the cells of the intestinal mucosa and by enteric micro-organisms of mice.

Animals

Facilitating patient participation: the doctor-patient encounter.

Our purpose in undertaking this review has been to extract from the literature behavioral prescriptions for physicians and strategies for prevention. We have demonstrated that the physician who wishes to be a successful counselor needs to ensure that the patient knows what to do, work toward patient commitment to behavior change, negotiate and tailor the specifics of the treatment, and be a warm, attentive interviewer who provides support to patients by attending to emotional responses as they arise. We have suggested ways that the encounter can be embedded in a functioning primary care organization where other members of the team are involved, and where follow-up mobilization of social support and the systematic application of behavioral techniques can achieve permanent behavior change.

Communication

Metabolism of ether glycolipids with potentially antineoplastic activity by Ehrlich ascites tumor cells.

Ehrlich ascites tumor cells were incubated in vitro with rac-1-O-[1'-14C]octadecyl-2-O-methylglycero-3-beta-D-glucopyranosi de for 24 h. The potentially antineoplastic ether glycolipid was rapidly metabolized by the cells to radioactive 1-O-octadecyl-2-O-methylglycerol (70 pmol/10(6) cells per h) and further acylated to 1-O-octadecyl-2-O-methyl-3-acylglycerols. Incubation of Ehrlich ascites cells with synthetic rac-1-O-[1'-14C]octadecyl-2-O-methyl-3-palmitoylglycerol showed that this metabolite is reconverted by deacylation to 14C-labeled 1-O-octadecyl-2-O-methylglycerol. The latter compound or a metabolite derived therefrom may be the 'toxic principle' of both the ether glyceroglycolipids and ether glycerophospholipids having a 1-O-alkyl-2-O-methylglyceryl moiety, as suggested by Unger et al. (J. Natl. Cancer Inst. 78 (1987) 219-222).

Animals

Metabolism of sitosteryl beta-D-glucoside and its nutritional effects in rats.

[4-14C]Sitosteryl beta-D-glucoside, intragastrically administered to rats, was not absorbed by the intestinal mucosa. At three hr after the application, radioactivity was concentrated almost exclusively in the digesta of stomach, small intestine as well as cecum and colon, whereas only low proportions of radioactively labeled compounds were found in the various tissues of the gastrointestinal tract. Minor proportions of labeled metabolites of [4-14C]sitosteryl beta-D-glucoside, such as sitosterol and sitosteryl esters, were formed in the small intestine in vivo and in slices of small intestine in vitro. In the tissues of cecum and colon as well as the digesta derived from them, high proportions of labeled coprositostanol, i.e. 24 alpha-ethyl-5 beta-cholestan-3 beta-ol, that obviously had been formed by bacterial degradation of the substrate were detected. The feeding of sitosteryl beta-D-glucoside (0.5 g/kg body weight X day) over a period of four weeks did not alter significantly body weights or organ weights of rats. Analyses of steryl lipids of the various organs and tissues confirmed the findings obtained with the radioactive substrate: neither sitosteryl beta-D-glucoside nor sitosterol or sitosteryl esters derived therefrom had been transported in appreciable amounts to organs and tissues outside the alimentary canal during the feeding period. Minor proportions of unmetabolized sitosteryl beta-D-glucoside were detected in the tissues of stomach and intestine, whereas large proportions of the substrate were found in feces of rats that had received the sitosteryl beta-D-glucoside-containing diet; coprositostanol was found in feces of these animals in high proportions as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biologically active lipids. Semi-synthesis of 3H-labeled ether glycerophospholipids and ether glyceroglycolipids from ratfish liver oil.

1-O-Alkyl-2,3-diacyl-sn-glycerols, the major constituents of ratfish (Chimaera monstrosa) liver oil, serve as starting material for the preparation of 1-O-alkyl-sn-glycero-3-phosphocholines, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines, 1-O-alkyl-2-O-methyl-sn-glycero-3-phosphocholines, and 1-O-alkyl-2-O-methyl-sn-glycero-3-beta-D-glucopyranosides. Catalytic tritiation of the unsaturated alkyl moieties in these biologically active ether lipids affords the corresponding 3H-labeled substances.

Animals

Biosynthesis and biotransformation of ether lipids.

Some naturally occurring as well as synthetic ether lipids are biologically active. In certain cases, the effects of these substances are enhanced, in others, they are inhibited by compounds that were isolated from natural sources or prepared by chemical synthesis. The biotransformation of natural or "unnatural" ether lipids in microorganisms, plant or animal tissue also can lead to substances that elicit biological effects. The production of such compounds through various biotechnological techniques is a field wide open for future exploration. In addition to animal cell cultures, plant cell cultures may become useful tools in biomedical studies concerned with ether lipids.

Animals

Ether glycerolipids: novel substrates for studying specificity of enzymes involved in glycerolipid biosynthesis in higher plants.

Ether glycerolipids, predominantly alkylacylglycerols and alkylacylglycerophosphocholines, are synthesized in photomixotrophic rape (Brassica napus) suspension cells from various exogenous monoalkylglycerols. The stereospecific distribution of acyl moieties was studied in these ether glycerolipids with regard to chain-length and degree of unsaturation of alkyl moieties and compared with the distribution of acyl moieties in the corresponding endogenous acyl glycerolipids. The results show the following: (1) Alkylacylglycerophosphocholines replaced up to one-half of the corresponding physiological membrane lipids, i.e. diacylglycerophosphocholines, without changing the total amount of cholineglycerophospholipids as compared to untreated cells. (2) The composition of acyl moieties in total lipids of rape cells was practically unaltered by fatty acids derived via oxidative cleavage from the various alkyl moieties of either glycerolipids. (3) In 1-O-alkyl-2-acylglycerols derived from exogenous alkylglycerols and in endogenous 1,2-diacylglycerols compositions of acyl moieties were found to be different indicating that different pathways were operative in the biosynthesis of these two neutral glycerolipids. (4) Enzymes involved in synthesizing molecular species of 1-O-alkyl-2-acylglycerophosphocholines or 2-O-alkyl-1-acylglycerophosphocholines as well as 1,2-diacylglycerophosphocholines showed similar specificities with regard to chain-length and degree of unsaturation of both alkyl and corresponding acyl moieties. Thus, ether glycerolipids formed by plant cells from exogenous alkylglycerols are suitable metabolites for studying the specificity of enzymes involved in the biosynthesis of glyerolipids.

Chemical Phenomena