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Biomedical subjects

A M Albrecht

Publications and source records attributed to A M Albrecht.

At least 19 recordsLinked to original sources

Membrane properties of archaeal macrocyclic diether phospholipids.

Several biophysical properties of four synthetic archaeal phospholipids [one polyprenyl macrocyclic lipid A and three polyprenyl double-chain lipids (B, C, D) bearing zero, one or four double bonds in each chain] were studied using differential scanning calorimetry, electron and optical microscopies, stopped-flow/light scattering and solid-state 2H-NMR techniques. These phospholipids gave a variety of self-organized structures in water, in particular vesicles and tubules. These assemblies change in response to simple thermal convection. Some specific membrane properties of these archaeal phospholipids were observed: They are in a liquid-crystalline state over a wide temperature range; the dynamics of their polyprenyl chains is higher than that of n-acyl chains; the water permeability of the membranes is lower than that of n-acyl phospholipid membranes. It was also found that macrocyclization remarkably improves the barrier properties to water and the membrane stability. This may be related to the adaptation of Methanococcus jannaschii to the extreme conditions of the deep-sea hydrothermal vents.

Cryoelectron Microscopy↗

Proanthocyanidins and human health: systemic effects and local effects in the gut.

Proanthocyanidins share common properties with other polyphenols, in particular their reducing capacity and ability to chelate metal ions. However, their polymeric nature clearly makes them different. They have a high affinity for proteins and their absorption through the gut barrier is likely limited to the molecules of low polymerization degree and to the metabolites formed by the colonic microflora, as suggested by in vitro experiments. The nutritional significance of proanthocyanidins is discussed in relation to their physico-chemical properties and bioavailability.

Anthocyanins↗

Is coordination of two-joint leg muscles during load lifting consistent with the strategy of minimum fatigue?

The purpose of this study was to examine if strong correlations reported for a back lift task between activity (EMG) of two-joint rectus femoris (RF), hamstrings (HA), and gastrocnemius (GA) and the difference in the joint moments could be predicted by minimizing an objective function of minimum fatigue. Four subjects lifted barbell weights (9 and 18 kg) using a back lift technique at three speeds normal, slow, and fast. Recorded ground reaction forces and coordinates of the leg joints were used to calculate the resultant joint moments. Surface EMG of five muscles crossing the knee joint were also recorded. Forces of nine muscles were calculated using static optimization and a minimum fatigue criterion. Relationships (i) (RF EMG-HA EMG) vs (knee moment hip moment) and (ii) GA EMG vs. (ankle moment knee moment) were closely related (coefficients of determination were typically 0.9 and higher). Qualitatively similar relationships were predicted by minimizing fatigue. Gastrocnemius and hamstrings had the agonistic action at both joints they cross during load lifting, and their activation and predicted forces increased with increasing flexion knee moments and extension ankle and hip moments. The rectus femoris typically had the antagonistic action at the knee and hip, and its activation and predicted force were low. Patterns of predicted muscle forces were qualitatively similar to the corresponding EMG envelopes (except in phases of low joint moments where accuracy of determining joint moments was presumably poor). It was suggested that muscle coordination in load lifting is consistent with the strategy of minimum muscle fatigue.

Ankle Joint↗

Differential effects of plant sterols on water permeability and on acyl chain ordering of soybean phosphatidylcholine bilayers.

To gain some insight into the structural and functional roles of sterols in higher plant cells, various plant sterols have been incorporated into soybean phosphatidylcholine (PtdCho) bilayers and tested for their ability to regulate water permeability and acyl chain ordering. Sitosterol was the most efficient sterol in reducing the water permeability of these vesicles and stigmasterol appeared to have no significant effect. Vesicles containing 24zeta-methylcholesterol exhibited an intermediate behavior, similar to that of vesicles containing cholesterol. Cycloartenol, the first cyclic biosynthetic precursor of plant sterols, reduced the water permeability in a very effective way. Of two unusual plant sterols, 24-methylpollinastanol and 14alpha,24zeta-dimethylcholest-8-en-3beta-ol, the former was found to be functionally equivalent to sitosterol and the latter was found to be relatively inefficient. 2H NMR experiments have been performed with oriented bilayers consisting of soybean PtdCho with sitosterol, stigmasterol, or 24-methylpollinastanol. The results provided clear evidence that sitosterol and 24zeta-methylpollinastanol exhibit a high efficiency to order PtdCho acyl chains that closely parallels their ability to reduce water permeability. By contrast, stigmasterol shows a low efficiency for both functions. These results show that sitosterol and stigmasterol, two major 24-ethylsterols differing only by the absence or presence of the Delta22 double bond in the side chain, probably play different roles in regulating plant membrane properties; they also may explain why 9beta,19-cyclopropylsterols behave as good surrogates of sitosterol.

Journal Article↗

4-Chloroacetylpyridine adenine dinucleotide. A highly reactive and chromophoric affinity label of glyceraldehyde-3-phosphate dehydrogenase from sturgeon.

The analogue of NAD+, 4-chloroacetylpyridine-adenine dinucleotide (clac4PdAD+), inactivated the glyceraldehyde-3-phosphate dehydrogenase from sturgeon at a high rate. An affinity labeling was shown to occur with clac4PdAD+. The mononucleotide 4-chloroacetylpyridine 1-beta-D-ribose 5'-phosphate (clac4PdMN+) reacted with the enzyme in a second-order reaction whose rate was much smaller than that calculated for clac4PdAD+ taken as a second-order rate reagent. The rate of the reaction of clac4PdAD+ with the enzyme was determined by stopped flow, using as a probe the long-wavelength absorption maximum (430 nm) formed concomitantly with inactivation of the enzyme. Computer-assisted graphic simulation showed that the clac4PdAD+ analogue could bind to the active site of the enzyme from Bacillus stearothermophilus in a similar manner to that of NAD+, and that the reactive carbon and the reactive thiolate of Cys-149 were within bonding distance. The absorption at 430 nm was linearly proportional to the substoichiometric concentration of clac4PdAD+/mole subunit. Thiol titration suggested the modification of one thiol residue per subunit. The modified thiol was identified by degradation as Cys-149. In contrast to the absorption band generated during the reaction of the 3-chloroacetylpyridine-adenine dinucleotide (clac3PdAD+) with the same enzyme [Eur. J. Biochem. (1982) 127, 519-524; 129, 437-446], enzyme inactivated with clac4PdAD+ and clac4PdMN+ exhibited an absorption maximum at long wavelength which was still present after denaturation. The chromophore is proposed to be the enol form of the alpha-thioether ketone produced by alkylation of the thiolate of Cys-149 by the chloroacetyl group.

Affinity Labels↗

Comparison of the effects of inserted C40- and C50-terminally dihydroxylated carotenoids on the mechanical properties of various phospholipid vesicles.

We have measured the extent of incorporation of zeaxanthin (C40) and decaprenozeaxanthin (C50) in unilamellar vesicles of dimyristoylphosphatidylcholine (n-C14) and dipalmitoylphosphatidylcholine (n-C16). The incorporation is larger when the molecular length of the carotenoid corresponds to the thickness of the phospholipid bilayer. Stereochemically pure 2,3-di-O-phytanyl-sn-glycero-1-phosphocholine was prepared by modification of the polar heads of the phospholipids of Halobacterium halobium. Vesicles of this branched-chain ether phospholipid incorporate poorly the carotenoids, whereas egg lecithin vesicles incorporate them better. Osmotic swelling and water permeability of vesicles, with or without carotenoids, were measured in a stopped-flow, light-scattering system. The reinforcing effect (lower permeability and higher rigidity) of carotenoids at 1.5 mol% incorporation into diphytanylphosphatidylcholine vesicles is comparable to that of 5 mol% cholesterol; however, carotenoids have no measurable effect on the egg lecithin vesicles. These results imply that the reinforcement of the membrane depends on a subtle adjustment of the phospholipid-carotenoid system.

1,2-Dipalmitoylphosphatidylcholine↗

Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin.

An enzyme that catalyzes the hydrolysis of folic acid and the antifolate methotrexate nearly 20 times more rapidly than the hydrolysis of 5-methyltetrahydrofolate was extraced from a gram-negative bacterium tentatively identified as a Flavobacterium sp. The enzyme was purified 500-fold and found to have a molecular weight of about 53,000. Apparently a metallo-enzyme, it is inhibited by citrate and ethylenediaminetetraacetic acid (EDTA). Ca2+, Co2+, Mg2+, and Zn2+ reverse inhibition by EDTA, whereas Ca2+ and Zn2+ are weak activators in the absence of EDTA. The enzymatic reaction releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid. Substituents on N5 of the pteridine ring decrease the velocity of hydrolysis. Some non-specificity for the terminal amino acid is expressed. The strikingly different rates of hydrolysis of methotrexate and 5-methyltetrahydrofolate have stimulated interest in this enzyme for its potential clinical value in improving the therapeutic index of methotrexate.

Carboxypeptidases↗

Biopterin content of human neuroblastoma cells in culture.

The biopterin (Crithidia activity) content of several cell lines of human neuroblastoma was quantified. Adrenergic cell lines contained markedly higher levels than those found in cholinergic neuroblastoma cells, fibroblast-like cells and glioblastoma cells in culture.

Biopterins↗

Regulatory control of tetrahydrofolate coenzymes in folate auxotrophs.

The interrelated enzymic reactions of folate metabolism are presented and key tetrahydrofolate-producing reactions are emphasized. As observed with the methotrexate (MTX)-resistant mutant strain Streptococcus faecium var. durans/Ak, the regulatory roles of serine and purines in controlling their own synthesis by the repression of enzymes required for co-factor synthesis are reviewed. Positive induction of the dihydrofolate reductase activity of this mutant by folate and the antagonism of the folate effect by purines and thymine are discussed. A protective agent of the reductase-active protein, MTX is viewed also as a "positive" inducer of dihydrofolate reductase. Preliminary studies with L1210 leukemia-bearing mice and the murine leukemia ERLD in vitro suggest that citrovorum factor (CF) also triggers a positive induction of the reductase of the small intestine and of ERLD cells without apparently influencing the reductase level of L1210 in vivo. The possibility that control mechanisms, by which MTX and CF indirectly regulate enzyme synthesis in drug-stressed, CF-rescued cells, contribute to the success of high-dose MTX-CF rescue therapy is introduced.

Animals↗

Radiation-induced murine leukemia ERLD in cell culture.

The lymphoblastic leukemia ERLD, induced by radiation in a C57BL/6 mouse, was established in culture. Three cell lines, ERLD/Y3, ERLD/T ERLD/Two, have been in culture for nearly three years. Their isolation and growth depended upon the presence of 2-mercaptoethanol, glutamine, and asparagine in the medium. The cell lines, except ERLD/T, possess the TL antigen, a characteristic of ERLD and of other murine leukemia cells in vivo and of normal thymus cells of certain mouse strains, but not of C57BL/6. A distinctive submetacentric marker chromosome is also common to ERLD and the derived cell lines. The successful establishment of ERLD in culture provides a malignant thymocyte-related cell system for studies in nutrition and immunobiology.

Animals↗