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Biomedical subjects

M Adrian

Publications and source records attributed to M Adrian.

At least 55 records · Page 3Linked to original sources

Direct visualization of supercoiled DNA molecules in solution.

The shape of supercoiled DNA molecules in solution is directly visualized by cryo-electron microscopy of vitrified samples. We observe that: (i) supercoiled DNA molecules in solution adopt an interwound rather than a toroidal form, (ii) the diameter of the interwound superhelix changes from about 12 nm to 4 nm upon addition of magnesium salt to the solution and (iii) the partition of the linking deficit between twist and writhe can be quantitatively determined for individual molecules.

DNA, Superhelical↗

Evaporation during preparation of unsupported thin vitrified aqueous layers for cryo-electron microscopy.

Evaporation of water cannot be fully avoided when an unsupported thin vitrified film of an aqueous suspension is prepared for cryo-electron microscopy. This results in increasing concentration of solute which could affect the observed material. We have quantitatively studied this effect by measuring the contrast of polystyrene spheres in a metrizamide solution. The drying effect is generally negligible when specimens are prepared on a hydrophilic perforated support but it is frequently important when hydrophobic films are used instead. A flow of humid air, double blotting with minimal exposure of the thin liquid film to the atmosphere, or an automatic plunger optimizing the blotting conditions are simple methods for reducing drying effects. With this third device acting on a hydrophilic supporting film, the increase of solute concentration is limited to less than 20%.

Cold Temperature↗

Influence of carnitine acyltransferase inhibitors on the performance and metabolism of rat cardiac muscle.

The effects of carnitine palmitoyl transferase I inhibitors were studied in isolated perfused rat heart and in in vivo studies with normal and diabetic rats. In isolated perfused rat hearts of acutely diabetic and Zucker rats, clomoxir (sodium 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate) inhibited the oxidation rate of endogenous fatty acids and increased the oxidation rate of glucose. Etomoxir, an analogue of clomoxir, was used in the in vivo studies with normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 6 days by intraperitoneal injection. This carnitine palmitoyl transferase inhibitor significantly ameliorated the decreased heart performance in diabetic rats. The concentrations of glucose, glycerol, triacylglycerol, cholesterol, and phospholipids in serum were lower compared with untreated diabetic animals. On the other hand, the lipid and the carnitine content of heart and liver increased in the etomoxir-treated rats. Carnitine palmitoyl transferase inhibitors have clear antidiabetic effects, but before using as an oral antidiabetic drug, the long-term changes of the lipid and carnitine metabolism should be evaluated.

Acyltransferases↗

Benzodiazepine use and abuse in Canada.

Benzodiazepines are frequently prescribed, yet the extent of their use in Canada has not been described. Such data would be valuable in assessing patient exposure to benzodiazepines and would provide a context to estimate the risk-benefit ratio of these drugs. Analysis of benzodiazepine sales in 1978-87 in Canada, expressed as the defined daily dose (DDD) per 1000 inhabitants per day, showed that the use of these drugs was stable during the first half of the decade, at 33 DDD/1000 inhabitants per day, then steadily increased from 1983 to 1987, reaching 48 DDD/1000 inhabitants per day in 1987. The total use of slowly eliminated benzodiazepines declined, whereas the overall use of rapidly eliminated benzodiazepines increased linearly. In 1978-83 Canada had the second-lowest total benzodiazepine use among several Western countries. The patterns of use and abuse of rapidly eliminated benzodiazepines in 1978-84 showed a close correlation. Our findings indicate that data on drug use can be monitored and linked to clinical data, providing a mechanism for monitoring the relation between use and related illness.

Benzodiazepines↗

Effects of foot orthoses on center-of-pressure patterns in women.

The purpose of this study was to determine the effects of foot orthoses on the pattern of center of pressure in women with forefoot deformities during walking. Nine subjects with a forefoot varus and nine subjects with a forefoot valgus walked across a force platform three times for each of the following five treatment conditions: 1) barefoot, 2) shoes only, 3) rigid orthoses with shoes, 4) semi-rigid orthoses with shoes, and 5) soft orthoses with shoes. Force data were analyzed to determine the area under the center-of-pressure curve. A significant omnibus F ratio was obtained for treatments (p less than .001) and the deformity X treatments interaction (p less than .05) using a two-factor, mixed analysis of variance for repeated measures. Tukey's post hoc comparisons for the Varus Group resulted in significant differences (p less than .05) between the following treatment conditions: 1) barefoot and shoes only, 2) barefoot and rigid orthoses with shoes, 3) barefoot and semi-rigid orthoses with shoes, and 4) barefoot and soft orthoses with shoes. Tukey's post hoc comparisons for the Valgus Group resulted in significant differences (p less than .05) between the following treatment conditions: 1) barefoot and rigid orthoses with shoes, 2) barefoot and semi-rigid orthoses with shoes, and 3) barefoot and soft orthoses with shoes. The shoes-only treatment condition, in comparison with the barefoot condition, significantly reduced the center-of-pressure area for the Varus Group only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of heel lifts on ground reaction force patterns in subjects with structural leg-length discrepancies.

The purpose of this study was to determine the effect of heel lifts on ground reaction force patterns in subjects with structural leg-length discrepancies (LLDs). Eighteen subjects with LLDs ranging from 4.8 to 22.2 mm participated in this study. Subject age range was from 20 to 63 years. A force platform was used to obtain ground reaction force data for four conditions. Data were collected prior to fitting of the heel lift and after a three-week break-in period. Data were analyzed by use of a two-factor within-subject analysis of variance for repeated measures. Before heel-lift fitting, maximum lateral force was greater in the short leg than in the long leg. After heel-lift fitting, maximum vertical force was greater within both legs, and maximum medical force was greater in the long leg than in the short leg. The results suggest that although heel lifts are used to achieve pelvic levelness, the use of heel lifts also resulted in increased ground reaction forces, which may cause increased joint stresses within the lower extremities.

Adult↗

Length and shape variants of the bacteriophage T4 head: mutations in the scaffolding core genes 68 and 22.

The shape and size of the bacteriophage T4 head are dependent on genes that determine the scaffolding core and the shell of the prohead. Mutants of the shell proteins affect mainly the head length. Two recently identified genes (genes 67 and 68) and one already known gene (gene 22), whose products are scaffold constituents, have been investigated. Different types of mutants were shown to strongly influence the proportion of aberrantly shaped particles. By model building, these shape variants could be represented as polyhedral bodies derived from icosahedra, through outgrowths along different polyhedral axes. The normal, prolate particle is obtained by elongation along a fivefold axis. The mutations of the three core genes (genes 67, 68, and 22) affect the width mainly by lateral outgrowths of the prolate particle, although small and large isometric particles are also found. Many of the aberrant particles are multitailed, suggesting a correlation between tail attachment sites and shape.

DNA Mutational Analysis↗

Cryo-electron microscopy of vitrified SV40 minichromosomes: the liquid drop model.

The structure of SV40 minichromosomes has been studied by cryo-electron microscopy of vitrified thin layers of solution. In high-salt buffer (130 mM NaCl), freshly prepared minichromosomes are condensed into globules 30 nm or more in diameter. On the micrograph, they appear to be formed by the close packing of 10 nm granules which give rise to a 10 nm reflection in the optical diffractogram. The globules can adopt many different conformations. At high concentration, they fuse into a homogeneous 'sea' of closely packed 10 nm granules. In low-salt buffer (less than 10 mM NaCl), the globules open, first into 10 nm filaments, and then into nucleosome-strings. The 'liquid drop' model is proposed to explain the condensed structure of the minichromosome in high-salt buffer: nucleosomes stack specifically on top of one another, thus forming the 10 nm filaments. 10 nm filaments in turn, tend to aggregate laterally. Optimizing both these interactions results in the condensation of 10 nm filaments or portions thereof into a structure similar to that of a liquid. Some implications of this model for the structure of cellular chromatin are discussed.

Animals↗

pH-dependent membrane fusion is promoted by various colicins.

The ability of colicin A, a bacteriocin produced by some Enterobacteriaceae, to fuse phospholipid vesicles at acidic pH, was demonstrated by electron microscopy and resonance energy transfer. The fusion depends on protein concentration and on the nature of the phospholipids. Vesicles, prepared from Escherichia coli phospholipids, fused one or more rounds at pH 4.5 upon addition of stoichiometric amounts of colicin A. Fusion was not only induced by pore-forming colicins (E1, K) but also by colicins that contain nuclease activities (E2, E3). By recombinant DNA technology it is shown that the first glycine-rich 70 NH2-terminal amino acids and, most probably, the extreme COOH-terminal end of colicin A are involved in the fusion activity of the protein. The physiological relevance of this property of colicins is discussed.

Colicins↗

Cryo-electron microscopy of vitrified insect flight muscle.

Frozen hydrated sections of vitrified unstained insect flight muscle in the rigor and relaxed states were studied by cryo-electron microscopy. High resolution images with good contrast were obtained. As judged from direct images and from the comparison of optical diffractograms with X-ray diffraction patterns obtained from glycerinated muscle fibres, the vitrified specimen is well preserved. Preparation artifacts encountered in conventional plastic sections are avoided. The preservation of the relaxed structure also seems better than in freeze-etched replicas as the 14.5 nm repeat of crossbridges on thick filaments is easily visible.

Animals↗

Effect of phenformin on the metabolism of glucose, pyruvate and acetate in guinea-pig heart.

In the isolated perfused heart of the guinea-pig, phenformin could be shown to have a characteristic effect on cardiac performance and metabolism. In the working heart, phenformin (1 mmol1/1) decreased dp/dt and increased the end diatolic pressure; this reduced heart performance could not be explained by changes in the content of energy-rich compounds. Furthermore, phenformin increased lactate production in hearts perfused with glucose as substrate and inhibited the utilisation of pyruvate, but not of acetate. The activity of the purified pyruvate dehydrogenase complex was not influenced by phenformin, but the active form of the pyruvate dehydrogenase complex (PDHa) was diminished. This effect may be explained by an inhibition of the pyruvate dehydrogenase phosphatase. An inhibition of pyruvate dehydrogenase and, coincidently, of oxygen consumption might contribute to the development of lactic acidoses and, particularly, might be deleterious for the heart.

Adenine Nucleotides↗

[Spirochetes: coiling direction].

On electron micrographs of spirochetes, the axial fibers are alternatively visible and hidden, i.e. above then under the cytoplasmic cylinder. From this observation the sense of coiling can be inferred. Leptospires are right-handed structures. So are other spirochetes, but it is less conspicuous. The opposite, however, appears on most published photographs and on schematic drawings. The explanation would be that the preparation introduced into the electron microscope was not facing the photographic plate, but turned to the electron beam. Also the picture must not be turned over, neither in the photographic laboratory nor when used as a slide.

Leptospira↗