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Biomedical subjects

G Brunet

Publications and source records attributed to G Brunet.

36 records · Page 2Linked to original sources

Antidepressant effect of 5-methoxypsoralen: a preliminary report.

5-Methoxypsoralen (5 MOP) administered daily (40 mg at 9 p.m.) was compared with placebo in the treatment of severe depression. The clinical response was evaluated using the Hamilton Depression Rating Scale after 1 week of treatment. Our preliminary data indicate that patients receiving 5 MOP improved significantly after 1 week, whereas patients treated with placebo did not. The stimulating effect of 5 MOP on the melatonin secretion may be involved in this clinical effect.

5-Methoxypsoralen↗

Immunoelectron microscopical distribution of poly(ADP-ribose)polymerase in the mammalian cell nucleus.

The ultrastructural distribution of poly(ADP-ribose)polymerase has been studied using a specific antibody and immunocytochemistry with immunogold markers. In situ localization in synchronized Chinese hamster ovary cells reveals the antibody associated with mitotic chromosomes, and later with condensed chromatin and perichromatin regions in G1 phase. During S and G2, the label occurs mostly on perichromatin regions where perichromatin fibrils are also observed. In the nucleolus, the label appears especially on the dense fibrillar component and to a minor extent on the granular component. Immunolabeled spread active chromatin preparations from exponentially growing cultured mouse P815 cells indicate preferential association of the antibody with nascent nonribosomal RNP fibrils compared to inactive chromatin. The results, suggesting a relationship between the poly(ADP-ribose)polymerase occurrence and RNA (or RNP) formation, are discussed in view of the present knowledge about possible relations between poly(ADP-ribosylation) and synthesis of RNA and DNA.

Animals↗

Antigen-induced leukotriene release from rat lung in vitro.

Chopped lung from inbred hyperreactive rats was challenged with antigen following active or passive sensitization and supernatants were assayed for the presence of leukotrienes (LTs) by radioimmunoassay. Dose-related increases in the release of LTC4- and LTB4-immunoreactive material were obtained with significantly more material being released following passive sensitization. Chromatographic analysis indicated the presence of LTB4, LTC4 and LTE4. When LT release in inbred rats was compared to Sprague-Dawley or Fischer rats, the amounts released were as follows: Inbred greater than Sprague-Dawley greater than Fischer. It was concluded that the release of LTs in the three strains correlated with the degree of non-specific bronchial hyperreactivity.

Animals↗

Leukotriene B4, polymorphonuclear leukocytes and inflammatory exudates in the rat.

Leukocyte numbers and Leukotriene B4- (LTB4-) and LTC4-immunoreactivity were measured in inflammatory exudates obtained from sponges impregnated with several irritants implanted subcutaneously in the rat. Sponges containing 1% uric acid, carrageenan or zymosan were implanted for 5h and compared to saline sponges. Increases in leukocyte numbers and LTB4-immunoreactivity were found in the presence of irritants, the highest concentrations being observed in the presence of zymosan. The presence of LTB4 was confirmed by liquid chromatographic (HPLC) analysis. A time course study was carried out with zymosan-impregnated sponges and the maximal rate of leukocyte infiltration was found to coincide with the maximal levels of LTB4-immunoreactivity. The LTC4-immunoreactivity was low and following analysis by HPLC was concluded to be unrelated to leukotrienes. The levels of LTB4-immunoreactivity, but not the numbers of leukocytes, were elevated compared to corresponding controls in sponges containing 0.01% ionophore A23187 (untreated rats) or in sponges containing zymosan (rats pretreated with indomethacin; 3 and 10 mg/kg p.o.). Impregnation of sponges with 3 X 10(-6)M LTB4 but not 3 X 10(-5) and 3 X 10(-7)M LTB4 induced a significant leukocyte migration. It was concluded that LTB4 can induce leukocyte migration into sponge exudates in the rat but that measurements of LTB4 in such exudates can not be correlated with the degree of leukocyte infiltration.

Animals↗

Respiratory responses to leukotrienes and biogenic amines in normal and hyperreactive rats.

The effects of leukotriene D4, serotonin, and methacholine were studied on respiratory smooth muscle in vitro and respiratory responses in vivo in three strains of rats. These were an inbred strain of hyperresponsive rats, Sprague Dawley rats, and Fischer rats. Trachea from inbred rats responded in vitro to serotonin and methacholine but not to leukotrienes or histamine. Parenchyma from inbred rats responded to serotonin, methacholine, and leukotrienes. In vivo respiratory responses in inbred rats were observed after aerosol administration of histamine and serotonin, methacholine, and leukotriene D4. When these in vitro and in vivo experiments were repeated in Sprague Dawley and Fischer rats, a clear correlation was observed between the responses of strains of rats to aerosolized antigen and responses to spasmogenic mediators. It is concluded that inbred rats have a nonspecific bronchial hyperreactivity that contributes to their sensitivity to aerosolized antigen and that they may be a useful model for human asthmatic conditions.

Animals↗

Biological activity of leukotriene sulfones on respiratory tissues.

The biological activity of synthetic leukotriene C4, D4 and E4 sulfone has been determined in respiratory smooth muscle in vitro and in vivo. The sulfones of LTC4, LTD4 and LTE4 were potent contractile agonists on indomethacin-treated guinea pig tracheal chains with respective pD2-values of 8.2, 8.0 and 7.9. Contractions were submaximal (75-85% of the cholinergic maximum), slow in onset, prolonged in duration, slowly reversed by washing (compared to acetylcholine or histamine) and were partially reversed by 2 muM FPL-55712. The sulfones of LTC4, LTD4 and LTE4 also contracted indomethacin-treated guinea pig parenchyma (respective pD2's of 7.9 8.2 and 7.8) and rat parenchyma (respective pD2's of 7.1, 7.2 and 7.2) but were inactive on rat trachea (0.01-2.0 muM). When administered intravenously to anaesthetized guinea pigs, the sulfones of LTD4, LTE4 and to a lesser degree LTC4 (respective ED50's - 0.5; 2.0 and 4.6 microgram/kg) elicited dose-dependent increases in inflation pressure which were antagonized by FPL-55712 and indomethacin. Leukotriene C4, D4 and E4 sulfones display a qualitatively similar profile of biological activity to that of their corresponding sulfides.

Animals↗

Differing mechanisms for leukotriene d4-induced bronchoconstriction in guinea pigs following intravenous and aerosol administration.

Leukotriene D4 (LTD4) when administered intravenously or by aerosol to guinea pigs produced changes in pulmonary mechanics including a decrease in dynamic compliance and an increase in pulmonary resistance. The effects of intravenous LTD4 (0.5 microgram kg-1) were short lived and abolished by pretreatment of the animal with either cyclooxygenase inhibitors, a thromboxane synthetase inhibitor (OKY 1555) or an SRS-A antagonist (FPL 55712). These findings suggest that bronchoconstriction produced by the intravenous infusion of LTD4 at 0.5 microgram kg-1 is due to the release of thromboxane A2. However, in animals treated with indomethacin, LTD4 at higher doses (greater than 0.8 microgram kg-1) still elicited a bronchoconstriction which could be blocked by FPL 55712. Nebulization of 0.1 - 1.0 microgram of LTD4 into the lung produced prolonged changes in pulmonary mechanics which were inhibited by FPL 55712 and were potentiated by indomethacin. LTD4, therefore, when administered by aerosol produced effects on the lung which were not mediated by cyclooxygenase products. Responses to nebulized rather than intravenous LTD4 in the guinea pig may more closely resemble those seen in human tissues.

Aerosols↗

The activity of synthetic leukotriene C-1 on guinea pig trachea and ileum.

The effects of synthetic leukotriene C-1 (LTC-1) on isolated guinea pig trachea and ileum have been determined and compared to histamine. LTC-1 produced a slow contraction of the trachea and the ileum with pD2 values of 8.7 +/- 0.1 (n = 14) and 8.5 +/- 0.1 (n = 13), respectively. In comparison, the pD2 values for histamine were 5.6 +/- 0.1 (n = 6) and 6.2 +/- 0.1 (n = 6), indicating LTC-1 was 2-3 orders of magnitude more potent. LTC-1 was antagonised by FPL 55712 with pA2 values of 6.9 +/- 0.1 (n = 5) and 6.4 +/- 0.1 (n = 7) on the trachea and ileum, respectively. Incubation with lipoxidase produced a time and enzyme dependent loss of biological activity and a concurrent shift in U.V. absorption spectrum.

Animals↗

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Child Welfare↗

An abnormal concentration of cases of Rendu-Osler disease in the Valserine valley of the French Jura: a genealogical and demographic study.

An important concentration of patients with Rendu-Osler disease occurs in the Valserine valley of the French Jura. A study of marriages shows that, in spite of its somewhat remote location, the valley cannot be considered an isolate, but that, on the contrary, exogamy is widely practised. Only 17.8% of the genes of inhabitants during the present century can be traced to the original population, but persons affected with the disease belong to a subgroup of the population which has lived in the villages for more than 10 generations. All the patients in 85 sibships are related. The smallest number of originator couples who lived at the beginning of the eighteenth century amounts to 16, the unique originator may therefore have lived approximately four generations earlier. However, as other patients who lived at the periphery of the Valserine valley do not appear to be related to any patients living in the valley, and because there has been considerable immigration into the valley, a number of hypotheses to explain the distribution of the disease in the region remain possible.

Consanguinity↗

Intermittent treatment with streptokinase in arterial disease of the limbs.

Sixty-two patients with arterial disease of the lower limbs were treated with streptokinase by intermittent administration. All patients had experienced recent aggravation of their arterial disease, and 22 had thrombolysis confirmed by arteriography. In 20 cases clinical study showed repermeation--in 8 cases during the first perfusion and in 8 cases during the third perfusion. During the first perfusion the fall in fibrinogen was significantly greater in the 8 patients with thrombolysis. Further, the third perfusion corresponded to a new phase of fibrinogenolysis. These results support the possibility of the relationship between plasminemia and thrombolysis, and emphasize the limits of the classic theory of Sherry, Fletcher, and Alkjaersig. Permitting phases of repeated but limited plasminemia, the interruption method used here is a compromise between the risk of hemorrhage and the efficacy of treatment at low dosage.

Angiography↗

[Populations and heredity: at an intersection].

A population can be defined using different criteria, for example criteria of a geographical or medical nature. Researchers, or even patients and journalists, have complementary or contradictory views of this notion. Heredity is not only a biological fact; it is also a social fact. A systematic study of the genealogical corpus of a group of patients makes it possible to evaluate the soundness of the phenotypic criterion used to define a subpopulation that shares a common pathological heredity.

Genetics↗