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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 379 records · Page 21Linked to original sources

Adhesion molecules in antibacterial defenses: effects of bacterial extracts.

Adhesion of polymorphonuclear leukocytes (PMN) to vascular endothelium is one of the first events in their response against local bacterial infection. Different adhesion molecules sequentially mediate PMN adherence to endothelium and extravasation into inflamed tissues. We show that bacterial extracts OM-85 BV and OM-89 increase the expression of adhesion molecules at the surface of PMN and we suggest that this upregulation could be linked to the beneficial effect of bacterial extracts in the prevention of respiratory tract infections.

Humans↗

Accuracy of respiratory inductive plethysmography during wakefulness and sleep in patients with obstructive sleep apnea.

To assess the accuracy of the respiratory inductive plethysmograph (RIP) during sleep in obese patients with obstructive sleep apnea (OSA), we monitored 13 patients with OSA during wakefulness and nocturnal sleep with simultaneous measurements of tidal volume from RIP and integrated airflow. Patients wore a tightly fitting face mask with pneumotachograph during wakefulness and sleep. Calibrations were performed during wakefulness prior to sleep and compared with subsequent wakeful calibrations at the end of the study. Patients maintained the same posture during sleep (supine, 11; lateral, two) as during calibrations. There were no significant differences in calibrations before sleep and after awakening. The mean error in 13 patients undergoing RIP measurements of tidal volume during wakefulness was -0.7 +/- 3.4 percent while that during sleep was 2.1 +/- 14.9 percent (p < 0.001). The standard deviation (SD) of the differences between individual breaths measured by RIP and integrated airflow was 9.8 +/- 5.5 percent during wakefulness and 25.5 +/- 18.6 percent during sleep (p < 0.001). During both wakefulness and sleep, errors in RIP tidal volume were not significantly correlated with body mass index. In 12 patients with at least 10 percent time in each of stages 1 and 2 sleep, SD was greater in stage 2 sleep compared with wakefulness and stage 1 (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non-REM sleep (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non REM sleep (p < 0.001). This was associated with paradoxic motion of the rib cage in two patients during REM. We conclude that, despite increased errors in individual breath measurements during sleep, more marked during stages 2 and REM sleep, RIP is clinically useful to measure ventilation quantitatively in obese patients with sleep apnea. The criterion of a decrease of 50 percent in tidal volume assessed by RIP is appropriate to define hypopneas in such patients.

Adult↗

Distance perception in the spiny mouse Acomys cahirinus: vertical jumping.

Acomys cahirinus, a precocial muroid, that has shown precise jumping in the natural habitat, did not jump from 25 cm in a laboratory situation. To investigate this further, A. cahirinus were observed jumping from platforms at two different heights, onto different sized checkered substrates and from a visual cliff. Adult animals discriminated between platforms that were 6.4 cm and 25.4 cm above the substrate and between small and large checkered patterns on the floor. Most adult animals and neonates jumped down on the shallow side of the visual cliff. Animals developed individual patterns of jumping over a series of trials, with some jumping often, some rarely, and others jumping only from the low platform. Good distance perception was indicated when they did not jump from heights, and by their making appropriate postural adjustment when they did jump from heights and landed without mishap. Different spacing of trials indicated that height was a more effective stimulus for animals which had all four conditions on the same day, while floor pattern was more effective for animals with each of the four conditions on a separate day.

Adult↗

[Anti-neutrophil cytoplasmic antibodies (ANCA): major progress in the diagnosis of vasculitis].

ANCA antibodies represent a family of autoantibodies directed against neutrophil enzymes. Immunofluorescence patterns allow to distinguish c-ANCAs from p-ANCAs. The detection of ANCAs is often a key element for the diagnosis of Wegener's granulomatosis, microperiarteritis, Churg-Strauss syndrome and idiopathic rapidly progressive glomerulonephritis. Although the pathogenic role of ANCAs is not firmly established, their detection often allows an early therapeutic decision in necrotizing vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗

Differential effects of pentoxifylline on the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells.

Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha) by monocytic cells. In this study, we found that PTX differentially regulates the production of TNF-alpha and interleukin-6 (IL-6). Indeed, PTX at high concentrations triggers the production of IL-6 but not of TNF-alpha by peripheral blood mononuclear cells (PBMC). Further experiments indicated that monocytes are responsible for this PTX-induced IL-6 production. When PBMC were stimulated with LPS, PTX was found to inhibit the secretion of TNF-alpha as well as the accumulation of TNF-alpha messenger RNA (mRNA). In contrast, no inhibitory effect was observed on the induction of IL-6. Similar results were obtained when PBMC were stimulated with OKT3 monoclonal antibody (mAb). In addition, the in vivo administration of PTX in transplant patients receiving the first dose of OKT3 allowed to decrease the systemic release of TNF-alpha but not of IL-6. Since monocytes represent a major source of TNF-alpha and IL-6 in these settings, additional experiments were performed in vitro on purified T cells stimulated with the CLB-T3/3, an anti-CD3 mAb which does not require the presence of accessory cells to activate T cells. In this system, PTX was found to inhibit the secretion of both TNF-alpha and IL-6 by T cells. We suggest that cAMP could be involved in these differential effects of PTX on production of TNF-alpha and of IL-6.

Antigens, CD↗

[Favourable effects of some HLA-DR disparities on kidney graft survival. Proposal for a new recipient selection policy].

In a previous retrospective study conducted from 1980 to 1987 on 275 renal cadaveric transplants, we have shown that HLA-DR disparities between donor and recipient exerted differential effects on graft survival. Thus, the presence of DR4, DR5 and DR7 in the donor, or of DR5 in the recipient was associated with an excellent survival, whereas disparities due to the presence of DR1 and DR2 in the donor, or of DR2, DRw6 and DR7 in the recipient were detrimental for the graft. A prospective study on 158 renal cadaveric transplants performed from 1988 to 1990 yielded results that were similar to those of the retrospective study. Graft survival at 18 months was similar in recipients who had either the same DR antigens as those present in their donor or beneficial DR disparities only (83-90 percent), and significantly higher than in recipients with DR detrimental disparities only (62-65 percent). Graft survival in recipients with either mixed or neutral DR disparities occupied an intermediate position (77-78 percent). In conclusion, grafts with excellent outcome, similar to that observed in DR identical pairs, may be proposed to an ever increasing number of patients awaiting a renal transplant by adopting a selection policy based on the choice of beneficial DR disparities when a DR identical recipient is not available in the pool.

Actuarial Analysis↗

Trusses.

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Aged↗

Endothelium-dependent effects of pentoxifylline in rat aorta.

Experiments were performed with isolated rat aortas to study the vasoactive properties of pentoxifylline, a cyclic AMP phosphodiesterase inhibitor, which is used as a hemorheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1 microM), pentoxifylline (10 nM-10 microM) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3 microM) but which were almost completely abolished after incubation with methylene blue (10 microM) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10 microM) for 30 min, the concentration-response curves for endothelium-dependent relaxations to acetylcholine were shifted to the left and the serotonin-induced contractions were decreased, while the relaxations to forskolin, which are endothelium-independent and cyclic AMP-mediated, were not altered. We conclude that pentoxifylline exerts vasoactive effects that are mediated by endothelium-derived relaxing factor (EDRF), and that pentoxifylline has negligible endothelium-independent vasodilating properties. These properties of inducing or potentiating EDRF-mediated effects might contribute to the efficacy of pentoxifylline in the treatment of vascular disease.

Acetylcholine↗

Dermal absorption of niclosamide in rats and minipigs.

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.

Administration, Cutaneous↗

Endothelial cell seeding.

Endothelial cell seeding is a technique that has developed over the past 15 years in response to the need for a high performance synthetic vascular graft. This review details our present knowledge of seeding and examines the various problems that have hampered its introduction into clinical practice.

Animals↗

Enzymatic degradation of tumor necrosis factor by activated human neutrophils: role of elastase.

Although the role of tumor necrosis factor-alpha (TNF) as mediator of inflammation is now well established, its interactions with polymorphonuclear neutrophils (PMN) are not fully understood. Therefore, we investigated the possible hydrolytic action on TNF of intra-lysosomal enzymes released by activated PMN in the extracellular medium. We first incubated 125I radiolabeled TNF in vitro with activated PMN and by HPLC analysis, we observed a degradation process completely blocked by the previous addition of alpha 1-Antitrypsin (AT) to the incubation medium. By comparing several degradative patterns of TNF obtained with purified leukocyte proteases and supernatant of activated PMN, we identified elastase as the major enzyme involved in this catabolic process of TNF. In a second part, we determined the bioactivity of the cleavage fragments of recombinant human TNF (rhTNF) by a cytotoxicity assay. None of the fragments was found biologically active. Our results suggest that, at inflammatory sites, an enzymatic degradation of TNF may occur in the pericellular area of activated PMN. This new catabolic pathway leading to inactivation of TNF might be regarded as an effective local negative feed-back process limiting the potentially toxic effects of this cytokine.

Cathepsin G↗

TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunity.

Systemic autoimmune diseases can be induced experimentally in rodents by graft-versus-host or host-versus-graft reactions and by chemicals such as HgCl2, gold salts and D-penicillamine. These models share several features, such as productions of anti-nuclear antibodies, immune glomerulonephritis, MHC class II hyperexpression on B cells, hyper-IgE, increased IL-4 activity and impairment of IL-2 production. This profile of cytokines suggests a central role for TH2-type cells in their pathogenesis. Here, Michel Goldman and colleagues review the data supporting this hypothesis and discuss the possible molecular bases for T-cell activation in chemically-induced systemic autoimmunity.

Animals↗