Search PubMed⌕ Search

Biomedical subjects

M Laberge

Publications and source records attributed to M Laberge.

30 records · Page 2Linked to original sources

Spectral splitting in the alpha (Q0,0) absorption band of ferrous cytochrome c and other heme proteins.

The alpha or Q0,0 absorption band of horse iron(II) cytochrome c splits and shifts to the blue as temperature decreases over the temperature range of 290-10 K. At room temperature, its maximum is at 18 150 cm-1 and the spectral width is 273 cm-1, whereas at 10 K, the two bands of the Q0,0 transition occur at 18 364 and 18 253 cm-1 and the width of the lowest-energy band is 96 cm-1. Temperature dependent splitting also occurs for zinc cytochrome c, a derivative in which Fe has been replaced by Zn; at 10 K, the peaks in the Q0,0 band region occur at 17 106 and 16 996 cm-1. The peak positions are independent of the cryosolvent (aqueous ethylene glycol or glycerol mixtures). The splitting of the Q0,0 band seen in the protein (approximately 110 cm-1 for iron and zinc cytochrome c) is comparable to the crystal field splitting observed for metalloporphyrins in mixed crystals. In contrast, the Q0,0 band of zinc coproporphyrin III in a glassy solvent (dimethylformamide/ethylene glycol) or in poly(vinyl chloride) shows a blue shift with temperature decrease but no evidence of Q0,0 splitting. Available spectral data show that the Q0,0 band is composed of two nearly degenerate electronic transitions and the split is due to the asymmetry in the heme pocket of the protein that arises from the surrounding polypeptide chain. This asymmetry results in the stabilization of one form of the excited state over the other, according to a Jahn-Teller mechanism.

Animals↗

Stark effect experiments in cytochrome c-type proteins: structural hierarchies.

We performed hole-burning Stark effect experiments on cytochrome c in which the iron of the herne was either removed or replaced by Zn. According to the experiments, the free-base compound has an effective inversion center, even in the protein. The Zn compound, on the other hand, shows quite peculiar features: in the low-frequency range of the inhomogeneous band, it definitely has a dipole moment, as indicated by a splitting of the hole in the external field. However, in the maximum of the inhomogeneous band, a severe charge redistribution occurs, as the experiments show. In addition to the Stark experiments, we performed calculations of the electrostatic fields at the pyrrole rings and at the metal site of the heme group. We interpret our findings with a model based on structural hierarchies: the protein can exist in a few subconformations, which can be distinguished through the structure of the heme pocket. The different pocket structures support different structures of the chromophore, which, in turn, can be distinguished through their behavior in an external field. These distinct structures, in turn, correspond to a rather broad distribution of protein structures, which leave, however, the pocket structure largely unchanged. These structures show up in inhomogeneous broadening.

Animals↗

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients.

We report the clinical, electrophysiologic, ophthalmologic, and neuropsychologic features of six patients with hyperammonemia-hyperornithinemia-homocitrullinuria syndrome, an inborn error of ornithine metabolism. Pyramidal signs, decreased vibration sense, bucco-facio-lingual dyspraxia, and learning difficulties or subnormal intelligence were found in the majority. Anomalies of peripheral nerve conduction velocity and of evoked potentials were common, and one patient had markedly abnormal white matter images on cranial magnetic resonance imaging. One patient had retinal depigmentation and chorioretinal thinning. The clinical severity varied greatly among patients; in general, the three younger patients had less neurologic and intellectual impairment than did the three older patients. Only two of our patients have had episodes of symptomatic hyperammonemia. We conclude that hyperammonemia-hyperornithinemia-homocitrullinuria syndrome can be associated with widespread manifestations in the central and peripheral nervous systems. Although the control of hyperammonemia is an essential element in the treatment of these patients, the relationship of hyperammonemia to the chronic neuropsychologic problems of these patients is unclear.

Adolescent↗

Scientific basis for bilateral animal models in orthopaedics.

(1) Bilateral procedures should be used when weight-bearing is an experimental parameter that should be controlled. (2) Bilateral procedures should be used for biocompatibility in osseous tissue and in fact most tissues according to ASTM. (3) Bilateral models in orthopaedics allow a more objective evaluation and characterization of materials and implants, reducing statistical and biological variables by an order of magnitude. Thus, this experimental approach increases the statistical significance of a study with a smaller number of animals.

Animals↗

Porphyrin cytochrome c. pH effects and interaction with cytochrome-c oxidase.

1. Porphyrin cytochrome c, the iron-free derivative of cytochrome c, has been used extensively as a fluorescent analog of cytochrome c. It appears as though its fluorescence intensity but not its relative quantum yield is affected by pH in the physiological range; an apparent pK of about 6.2 is found suggesting a histidine close to the porphyrin. 2. The fluorescence intensity of the porphyrin cytochrome c in the presence of cytochrome c oxidase is independent of pH; this suggests that the oxidase has the capacity to control the pK of whichever group is responsible for the pH sensitivity of the free porphyrin cytochrome c. The most likely candidate for this pH-sensitive group is histidine-18. The N-3 nitrogen of this residue forms one of the axial ligands to the iron in the intact cytochrome c but it is uncoordinated in the iron-free derivative.

Animals↗

Neuromuscular pharmacology of the anterior intestine of Chaetopterus variopedatus, a filter-feeding polychaete.

The motricity of the anterior intestine of Chaetopterus variopedatus was investigated using extracellular electrodes, force displacement transduction and a pharmacological approach. Rhythmic bursts of impulses were associated with peristaltic waves; the latter were not abolished by removal of the ventral nerve cord which caused a drop in tonus. Acetylcholine induced a contracture and an increase in the frequency of peristaltic waves; these effects were potentiated by eserine and reduced by atropine. Similar responses to adrenaline and noradrenaline were antagonized by propranolol and phentolamine in partially different manners. Gamma-aminobutyric acid (GABA) induced large, picrotoxin-sensitive contractures but failed to change the rate of peristalsis. Serotonin (5-HT) produced a short-term increase in the rate of peristalsis as well as a slight contracture, and a long-term inhibition of peristalsis, all actions antagonized by methysergide. The response to GABA was reduced or abolished during the inhibitory phase of the 5-HT effect. A tetrapeptide related to cholecystokinin/gastrin induced contractures and accelerated peristalsis at a concentration as low as 2.5 X 10(-13) M. It is concluded that multiple neurotransmitter pathways may modulate gut motricity by acting on the peristalsis pacemaker as well as on neuromuscular transmission mechanisms.

Animals↗

The gastric antisecretory effects of clofibrate in the rat.

The object of this study was to explore the effect of clofibrate on gastric secretion. The volume and the total acid output of Shay-treated rats (pyloric ligation) was studied after intragastric, intraduodenal, intramuscular and intraperitoneal administration of clofibrate. The experimental model was a factorial (3 X 4) random block design. The treatment factor had 3 levels: water, oil and clofibrate. The route of administration factor had 4 levels: intragastric, intraduodenal, intraperitoneal and intramuscular. The data were analyzed by analysis of variance. Compared to the control group (water and oil) the intraduodenally and intraperitoneally administered clofibrate produced a statistically significant (p less than 0.001) reduction in the volume and total acid output. The intragastric and intramuscular groups did not show a statistically significant reduction on the gastric secretion. It is concluded that clofibrate acts systemically rather than locally to reduce gastric secretion.

Administration, Oral↗

Structured and free-recall measures of worry themes: effect of order of presentation on worry report.

Structured instruments (SI) or free-recall instruments (FRI) can be used to examine worry themes. In the case where both types are use jointly, order of presentation may influence number and content of free-recall worries. Half of a large undergraduate sample (N = 609) received the SI before the FRI and the other half received them in the opposite order. Highly prevalent worries (i.e., common worries reported by more than 25% of the sample) were more numerous when the FRI was used first. However, moderately prevalent and rare worries (reported by 5% to 24% and 0% to 4% of the sample, respectively) were more numerous when the FRI was administered second. Results are discussed in terms of a possible priming effect produced by SI on moderately prevalent and rare free-recall worries.

Adult↗