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Biomedical subjects

P Leblanc

Publications and source records attributed to P Leblanc.

At least 91 records · Page 5Linked to original sources

Localization of membrane proteins by the use of a photoreactive fatty acid incorporated in vivo into vesicular stomatitis virus.

Vesicular stomatitis virus grown in the presence of omega-[9-3H]diazirinophenoxy nonanoate resulted in the biosynthetic incorporation of this photoreactive fatty acid into viral phospholipids as well as into the membrane anchoring domain of the viral G glycoprotein. Photolysis of the isolated virus at 360 nm resulted in extensive labeling of the G protein but none of the other proteins by the viral phospholipids. In addition, a new product was obtained and was identified as a G-G dimer by its molecular weight and its reaction with anti-G antibody. These results demonstrate the use of photoreactive fatty acid to identify integral membrane proteins and to make photoaffinity probes of fatty acylated membrane proteins.

Animals↗

Influence of chronic obstructive lung disease on the disposition of an acidic drug (sulfamethazine).

The influence of chronic respiratory failure (CRF) on the pharmacokinetics of an acidic drug has been studied in 11 patients and in eight normal volunteers who received 10 mg/kg of oral sulfamethazine. Blood and urine samples were collected for 24 and 48 hours, respectively. No differences were observed in the rate of sulfamethazine absorption, but bioavailability was decreased when compared with control subjects. Sulfamethazine volume of distribution (Vd) was larger in patients than in control subjects. These differences in Vd may be secondary to an increase in sulfamethazine unbound fraction. No differences were observed in sulfamethazine elimination. It is concluded that in patients with CRF sulfamethazine bioavailability decreases, and Vd increases secondary to a decrease in binding. Despite the fact that plasma concentrations of the test drug will be decreased, the administration of higher doses may not be advisable.

Absorption↗

Biphasic pattern of follicle stimulating and luteinizing hormone responses to gonadotropin-releasing hormone in vitro.

Increasing concentrations of LHRH or its active analog des-gly10 (D-ala6) LHRH induced a bimodal pattern of FSH and LH release from incubated male rat pituitaries. A low amplitude response (40% increase of LH over baseline levels) was observed for concentrations of LHRH and the agonist in the range of 10(-12) and 10(-13) M respectively. After a plateau of gonadotropin stimulation, a further high amplitude response (180-240% increase over baseline levels) occurred between 3.10(-10) and 10(-8) for LHRH and 3.10(-11) and 3.10(-9) M for des-gly10 (D-ala6) LHRH. Corresponding half maximal effective concentrations (ED50) were 2 and 0.3 nM respectively. Stimulation of FSH release closely paralleled that of LH. The low amplitude, high apparent affinity response was only obtained when the peptides were diluted in low concentrations of acidic tissue extracts. A preliminary study indicated that this method of dilution minimized peptide loss by adsorption. In addition, the low amplitude, high affinity response was never observed on pituitaries sampled from castrates. These experiments suggest the presence of two distinct populations of LHRH recognition sites on pituitary gonadotrophs. Under our experimental conditions, the appearance of the higher affinity response was dependent upon prior exposure to sex steroids. This could be due to a direct action of the steroid on the expression of a high affinity LHRH receptor.

Animals↗

Synthesis and biosynthetic utilization of radioactive photoreactive fatty acids.

A synthesis of a homologous series of highly radioactive photoreactive fatty acids has been developed. Oxidative cleavage of the cis double bonds of unsaturated fatty acids by NaIO4/OsO4 produced the omega-oxo fatty acids; subsequent reduction by [3H]NaBH4 afforded a series of highly radioactive [omega-3H]hydroxy fatty acids to which a variety of photoreactive probes can be readily attached. In this study, the m-diazirinophenoxy group was coupled to the omega-hydroxy groups of the fatty acids, yielding the omega-(m-diazirinophenoxy) derivatives of nonanoic, undecanoic, tridecanoic, and pentadecanoic acid. These photoreactive derivatives were incorporated by L-cells into their major phospholipids; in addition, a number of proteins were shown to be acylated by these fatty acids. The photoreactive group was shown to remain intact as indicated by the cross-linking of the resulting photoreactive phospholipids to other phospholipids as well as to a number of L-cell proteins upon photolysis. This procedure thus identifies integral membrane proteins and directly produces photoaffinity derivatives of those proteins normally acylated by fatty acids.

Animals↗

[Working out a system for the parameters of intra-uterine pressure wave forms. A comparative study of spontaneous labour and induced labor (author's transl)].

The tracings of intra-uterine pressure changes that are made during normal labours in primiparous patients, whether the labours were normal or accelerated with oxytocin, were analysed using a semi-automatic time-lag with the help of system of 25 parameters. The classical data of pressures and of time have been made up with a study of the minima and maxima of pressure measurements and the drawing up of new indices to characterise the pressure wave form. A study of the correlations between the different groups of parameters made it possible to make a summary of the information from a smaller number of data which were identical for the two groups of delivery. In particular working out the surfaces dose not seem to give extra information over and above that derived from a simple calculation of the length and intensity of the contractions. A comparative statistical study confirms that in accelerated labour there is a rise in the basal tone, in the maximum pressure and in the frequency of contractions, and shows a minimal scatter of the values obtained which demonstrated that oxytocin has a regulating effect. Using parameters for the shape of contractions, quite independently of the units chosen to measure, has made it possible to design a typical form for the graph for each group of labours.

Female↗

Differences in the kinetics of dopamine uptake in synaptosome preparations of the median eminence relative to other dopaminergically inervated brain regions.

A comparison of the kinetics of dopamine uptake was made in synaptosomal preparations of the median eminence, striatum and olfactory tubercle. Double reciprocal Lineweaver-Burk plots of the initial velocity versus the concentration of dopamine yielded a single straight line in all three areas. The Michaelis constant (Km) in the median eminence (1.8 +/- 0.9 X 10(-6) M) was significantly higher (p < 0.05) than in the striatum (4.2 +/- 0.8 X 10(-8) M) or olfactory tubercle (6.3 +/- 1.9 X 10(-8) M). Uptake in the median eminence appeared to be predominantly into dopaminergic terminals since preincubation with desipramine did not affect the maximum velocity (Vmax) of dopamine uptake. Observed uptake was predominantly due to transport across the neuronal membrane and not into storage granules, since reserpine only caused a small decrease in uptake. The low affinity of dopamine uptake in median eminence synaptosomes is consistent with the neurosecretory nature of these terminals, whereas, in the striatum and olfactory tubercle, high affinity reuptake is consistent with the role of dopamine as a neurotransmitter.

Animals↗

Some actions of purified toxins from Bungarus fasciatus venom on isolated pig-heart mitochondria.

I. In the presence of succinate as an oxidation substrate, neurotoxins alpha, beta and gamma induce the following. Firstly, an increasing stimulation of oxygen uptake, which in potentiated by 25 muM Ca2+, Mg2+ 1.3 mM completely inhibits the effect of toxin alpha but not of toxins beta and gamma. Secondly, a depletion of the Mg2+, Ca2+ and K+ content of the water-soluble and membrane-bound mitochondrial compartments, following complex kinetics, which suggest a multistep interaction mechanism of the toxins with the mitochondria. 25 muM Ca2+ also potentiates the effect of the toxins on these ionic flows. Thirdly, no decrease of turbidity with toxin alpha, and a limited decrease with toxins beta and gamma. 2. In the absence of respiration, the neurotoxins induce a cationic depletion, the kinetics of which are different than with succinate, suggesting an instantaneous maximal effect on the inner membrane. Toxins beta and gamma (but not alpha) induce, under these conditions, a turbidity decrease of large amplitude, which is proportional to the amount of toxin added and tends to reach a maximum. With gamma toxin this turbidity decrease is faster than the rate of water uptake (which never exceeds 18%) indicating that it is due rather to structural modifications than to swelling. The same is observed with beta toxin, provided the mitochondrial protein concentration to be lower than 0.7 mg/ml. For higher concentrations, a continuous decrease of turbidity with a considerable uptake of water probably reflects the onset of phospholipasic activities. 3. It is postulated that structural modifications of the mitochondrial membranes are initiated which lead to the loss of their selective impermeability. The simultaneous loss of respiratory control with succinate may be due to the direct (though Ca2+-potentiated) displacement of the fraction of the membrane-bound Mg2+ ions which controls its energy-transducing properties. 4. In addition, correlations between the effects of the toxins on mitochondria and their neurotoxicity in vivo are discussed.

Animals↗

Functional abnormalities in young asymptomatic smokers with special reference to flow volume curves breathing various gases.

Functional abnormalities have been described in healthy, asymptomatic young smokers. Fifteen subjects between 22 and 30 years of age, who smoked but were completely asymptomatic, were compared with 10 nonsmokers of the same age group using lung volumes, maximal expiratory flow rates, closing volumes, and maximal expiratory flow volume curves breathing air and a helium-oxygen mixture. Lower maximal mid-expiratory flow rates, higher closing volumes, and significant differences in flow volume curves with the helium-oxygen mixture were found in smokers. Special attention was given to the volume expressed as percentage of vital capacity at which the flows with air and the helium-oxygen mixture were equal for each subject ("equal-flow volume"). This volume was found to be significantly higher for smokers than nonsmokers. The authors offer explanations for these differences and suggest that smoking may alter compliance, as reflected by abnormal closing volumes, and resistance of the small airways as determined by differing responses in flow rates after helium-oxygen breathing at low volumes.

Adult↗

[Macrocephalia].

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Head↗