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Biomedical subjects

A Muller

Publications and source records attributed to A Muller.

At least 127 records · Page 7Linked to original sources

LPS-stimulated bovine aortic endothelial cells produce IL-1 and IL-6 like activities.

Vascular endothelium is known to closely interact with leukocytes and immunocompetent cells. We report here that cultured bovine aortic endothelial cells (BAEC) synthesize both interleukin 1 (IL-1) and interleukin 6 (IL-6) like activities in response to bacterial lipopolysaccharide stimulation. Our results agree with previous data obtained from human venous endothelia and support the concept that IL-1 and IL-6 synthesis are properties common to endothelial cells from different vascular beds. The IL-1 activity was measured by murine thymocyte proliferation assay and by an indirect bioassay using NOB1 cells, which evidenced higher IL-1 amounts than the former. This discrepancy appeared to be partly due to the simultaneous production of one or more inhibitor(s) of the thymocyte proliferation by BAEC. The IL-6 assay was performed with the murine hybridoma cell line B9. In other respects, the cyclooxygenase inhibitor indomethacin enhanced the IL-1 like production, but was ineffective on IL-6 like production. The present study provides additional evidence that endothelial cells from large arteries may also participate in inflammatory and immunological processes.

Animals↗

PAF-induced conjunctivitis in the rabbit is mediated by peptido-leukotrienes.

Platelet activating factor (PAF) released by many cell types is involved in several steps of inflammatory reactions in various organs including the eye. It has been reported that some effects of PAF could be mediated by arachidonic acid metabolites generated after PAF-receptor interaction. In the study we investigated the protective effect of CBS-113A, a dual inhibitor of 5-lipoxygenase/cyclooxygenase in PAF-induced conjunctivitis in the rabbit. Moreover, the characterization of the icosanoid potentially mediating the PAF activity has been performed by using specific pharmacological agents. Subconjunctival injection of PAF (10-1000 ng) provoked Evans' blue extravasation measured in tissues within 30 min. Simultaneous injection of a PAF antagonist (BN 50730) inhibited the dye leakage, showing specific PAF receptor-mediated vascular reaction. CBS-113A applied in eye drops also inhibited Evans' blue extravasation. By contrast, indometacin administered either topically or by subconjunctival injection was not effective in reducing the effect of PAF. These results suggesting the involvement of a 5-lipoxygenase metabolite were confirmed by the effectiveness of local injection of SKF 104353, a specific leukotriene D4 antagonist. The present study shows that PAF-induced plasma leakage in conjunctivitis is mediated by peptido-leukotrienes.

Animals↗

[Intravenous sympatholysis in arterial occlusive diseases and acrosyndromes].

Regional intravenous injection of ismelin is a very common pain treatment in sympathetic reflex dystrophies. In view of the mode of action of ismelin, it would be interesting to use that technique in the symptomatic treatment of chronic obstructive arteriopathies and of Raynaud's phenomenon. Surprisingly, few papers deal with that subject, probably because of fear of aggravating ischemia. However, short-term results are satisfactory in terms of pain relief. Long-term follow-up is unfortunately never mentioned.

Arterial Occlusive Diseases↗

Comparative biological activities of the four synthetic (5,6)-dihete isomers.

(5,6)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids [5,6)-DiHETEs) were synthesized and separated into four pure diastereoisomers. They were tested for comparative binding affinities to leukotriene receptors (LTC4, LTD4, LTB4) in guinea pig lung membranes. Only (5S,6R)-DiHETE was recognized by the LTD4 receptor, the other receptors interacted with neither of the four isomers. (5S,6R)-DiHETE also contracted ileum in vitro and this effect was inhibited by the LTD4 receptor antagonists ICI 198,615 and SKF104,353. These data suggest that the bioproduct (5S,6R)-DiHETE generated by enzymatic conversion of LTA4 could have some LTD4-like activity when produced in large concentrations.

Animals↗

Business recession, alcohol consumption, drinking and driving laws: impact on Oklahoma motor vehicle fatalities and fatal crashes.

In 1982, Oklahoma enacted a series of drinking and driving laws. In the ensuing years, motor vehicle fatalities and fatal crashes were reduced by one-third. Factors contributing to this reduction were examined using interrupted time series analysis of monthly rates of motor vehicle deaths and fatal crashes for the period January 1980 to December 1986. Decreasing per capita alcohol consumption and increased unemployment apparently account for most of the fatality and fatal crash reduction in Oklahoma. The enactment of two traffic safety laws--one specifying the illegal blood alcohol concentration level (BAC law) and the other facilitating license withdrawal from suspected drunk drivers (administrative per se law)--together reduced Oklahoma traffic deaths and fatal crashes by about 9 percent. The effectiveness of the laws appeared to be greatest in the first two years following their enactment.

Accidents, Traffic↗

Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers.

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

ABO Blood-Group System↗

2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride as a dual inhibitor of cyclooxygenase/lipoxygenase and a free radical scavenger. 1st communication: in vitro studies.

2-(2-Hydroxy-4-methylphenyl)aminothiazole hydrochloride (CBS-113 A) inhibits cyclooxygenase in platelets and 5-lipoxygenase in leukocytes at micromolar concentrations. On the other hand the drug is a potent scavenger of oxygen-derived free radicals. Moreover and possibly consequently, CBS-113 A inhibits the oxygen burst of stimulated leukocytes and the release of an interleukin 1-like compound from vascular endothelial cells in culture. These properties could lead to another activity of therapeutic interest in comparison with anti-inflammatory drugs already available.

Animals↗

2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride as a dual inhibitor of cyclooxygenase/lipoxygenase and a free radical scavenger. 2nd communication: anti-inflammatory activity.

The paper describes the topical anti-inflammatory activity of 2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride (CBS-113 A), a dual inhibitor of cyclooxygenase/lipoxygenase and a potent free radical scavenger. When applied in eye drops (0.01 to 0.1% according to the model used), the drug inhibited inflammation in experimental conjunctivitis and uveitis induced by various procedures (e.g. paracentesis, endotoxin, S-antigen, albumin, Fe2+). The compound also inhibited leukocyte infiltration and histamine release when administered locally in pleural cavity with carrageenan. CBS-113 A could decrease plasma leakage induced by arachidonic acid or platelet activating factor in skin and airway, respectively. However, it was devoid of any activity when administered by systemic route. The compound appears as a potentially useful anti-inflammatory drug, in particular in ophthalmology and as an alternative to glucocorticoids, since it does not present the side effects of these steroids (e.g. worsening of herpetic keratitis).

Animals↗

[Application of information technology in orthodontics. 2. Application of a proportional databank system for the realization of a computer assisted patient record system].

The presently existing microcomputer technology makes the realization of a computer assisted patient record system possible in the practice of orthodontics. Advantages and disadvantages of the application of the software used were examined and statements concerning practical pertinence were formulated.

Computer Systems↗

Characterization of specific leukotriene C4 binding sites on cultured human keratinocytes.

Peptidoleukotriene C4 (LTC4) and leukotriene B4 (LTB4) are both suspected of being inflammatory mediators and epidermal mitogenic agents in cutaneous psoriatic lesions. In the present study an LTC4 specific binding site was characterized in membranes from cultured human keratinocytes (Kd, 8.7 nmol/l; Bmax, 1.2 pmol/mg protein). In contrast LTB4 did not show any high affinity binding which could account for its biological effects. These data suggest that LTC4, unlike LTB4, acts on epidermal cells through a receptor-mediated mechanism.

Binding Sites↗

Differential effects of leukotrienes B4 and C4 on bovine aortic endothelial cell proliferation in vitro.

The effect of leukotrienes derivated from arachidonic acid was studied on vascular endothelium proliferation. The peptido-leukotriene LTC4 (0.1 nM - 0.1 microM) promoted a dose-dependent growth of bovine aortic endothelial cells in culture with a maximal effect at 10 nM. This proliferative activity could be receptor-mediated since LTC4 specifically bound to endothelial cell membranes with a Kd value of 50 nM. The leukotriene B4 did not induce any significant proliferation in the same range of concentrations. This result was consistent with the lack of LTB4 specific binding sites. This data suggests that LTC4 could be one of the factors implicated in angiogenesis during inflammatory processes.

Animals↗

Specific binding of leukotriene C4 to endothelial cell membranes.

Vascular endothelium is a target for leukotriene C4 (LTC4) as demonstrated by previous in vivo and culture experiments. Binding assays were carried out at 0 degrees C on membrane fraction obtained from bovine aortic endothelial cells in culture. Specific binding sites (Kd = 49.9 +/- 6.3 nmol X 1(-1), N = 1.2 X 10(6) sites per cell) for LTC4 were demonstrated in this preparation. Competition studies showed that LTB4, LTD4 and LTE4 did not displace LTC4 from its binding sites. FPL 55712, a sulfidopeptide antagonist, was seen to be a weak competitor and reduced glutathione exhibited a significant affinity for the binding site. The possible receptor role of this site is discussed.

Animals↗

[Anti LAV/HTLV III antibodies in blood donors: preliminary results of pool screening of 5 samples].

Serological performances obtained with five reagents for anti-LAV/HTLVIII antibody screening were compared in individual test and in pool. A panel of 55 selected samples and 2,079 pools prepared from 10,395 unselected samples of blood donors was studied. A first dilution is achieved by pooling, then a second dilution allows to obtain the exact working dilution recommended for the test. The sensitivity in pool method is always similar to the sensitivity in individual test, no false negative was observed. The specificity, evaluated on unselected samples, is slightly inferior to that observed in individual test: false-positive rate is in generally less than 3% compared to 2% average rate routinely observed with individual test. These results allow to propose this method, which save about 75% of the reagent cost, for blood donor screening in all laboratories and especially in developing countries.

Antibodies, Viral↗