Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2.

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin-like enzymes. PAR-2 is highly expressed by small intestinal enterocytes where it is activated by luminal trypsin. The location, mechanism of activation, and biological functions of PAR-2 in the colon, however, are unknown. We localized PAR-2 to the muscularis externa of the rat colon by immunofluorescence. Myocytes in primary culture also expressed PAR-2, assessed by immunofluorescence and RT-PCR. Trypsin, SLIGRL-NH2 (corresponding to the PAR-2 tethered ligand), mast cell tryptase, and a filtrate of degranulated mast cells stimulated a prompt increase in [Ca2+]i in myocytes. The response to tryptase and the mast cell filtrate was inhibited by the tryptase inhibitor BABIM, and abolished by desensitization of PAR-2 with trypsin. PAR-2 activation inhibited the amplitude of rhythmic contractions of strips of rat colon. This response was unaffected by indomethacin, l-NG-nitroarginine methyl ester, a bradykinin B2 receptor antagonist and tetrodotoxin. Thus, PAR-2 is highly expressed by colonic myocytes where it may be cleaved and activated by mast cell tryptase. This may contribute to motility disturbances of the colon during conditions associated with mast cell degranulation.     

Pregnancy-associated changes in renal toxicity of cadmium-metallothionein: possible role of intracellular metallothionein

Nulliparous female, 10-day and 20-day pregnant rats were injected intraperitoneally with saline or labelled cadmium-metallothionein (109Cd-MTh) at a single dose of 25 or 250 micrograms Cd as cadmium-metallothionein (Cd-MTh)/kg and sacrificed at 24 h. The renal toxicity was manifested by increased 24-h urinary excretion of beta 2-microglobulin (beta 2-m) and the increased number of damaged convoluted proximal tubules at 24 h. The renal excretion of 109Cd and 109Cd content in the maternal liver and kidney and in the foeto-placental unit were determined. The binding of 109Cd to kidney proteins and the level of intracellular metallothionein (MTh) in livers and kidneys were also determined. It was found that the nephrotoxicity of injected Cd-MTh did not differ in nulliparous and 10-day pregnant rats. This result was consistent with the absence of difference in the renal uptake of 109Cd, its binding to kidney proteins and in the content of endogenous MTh in the kidneys between nulliparous and 10-day pregnant rats. In contrast, 20-day pregnant rats exhibited much more nephrotoxicity than nulliparous rats. The most prominent finding in relation to the extreme sensitivity of 20-day pregnant rats was a lower basal level of intracellular MTh in the kidneys and the accumulation of 109Cd in the high molecular weight proteins in the soluble fraction. It is suggested that the decrease of intracellular MTh in the kidneys of 20-day pregnant rats is the reason for the low protection against the renal toxicity of injected Cd-MTh.     

Lung reflexes in anaesthetized rabbits with elastase-induced emphysema

The effects of elastase-induced emphysema on vagal pulmonary reflexes were studied in seven rabbits, given 600 IU of porcine pancreatic elastase intratracheally (E group), and eight untreated rabbits (U group) under pentobarbital anaesthesia. The presence of emphysema was confirmed by histological and pathological criteria and by documented changes in lung mechanics seven months after treatment. The strength of the Hering-Breuer inflation reflex (HBIR), indicative of pulmonary stretch receptor excitability, was unchanged in the U group, but was significantly increased in the E group at inflation volumes greater than the tidal volume (VT) range, as she slope of the curve relating HBIR to inflation volume was significantly steeper (0.40 vs 0.22 ml-1; p less than 0.05). The early ventilatory response (first 3 breaths) to right atrial injections of phenyldiguanide (20 and 30 micrograms X kg-1 i.v.) was used as an indication of the excitability of lung receptors with non-myelinated vagal afferents. This response, characterized by a significant decrease in expiratory duration (TE) without effect on VT or inspiratory time (TI), was not significantly different between the E and U groups. The overall pattern of breathing in the E group showed a significant decrease in VT associated with an increase in TI.     

Substance P recognition by a subset of human T lymphocytes.

The interaction of substance P with human blood T-lymphocytes, which stimulates T-lymphocyte proliferation, was quantified by both flow cytometric and direct binding assays. Fluorescence-detection flow cytometry recorded the binding of dichlorotriazinylamino-fluorescein-labeled substance P to 21 +/- 10% (mean +/- SD, n = 6) and 35 +/- 8% (n = 2) of human blood T-lymphocytes before and after stimulation with 10 micrograms/ml of phytohemagglutinin, respectively. The suppressor-cytotoxic (leu 2a) and helper-inducer (leu 3a) subsets identified by phycoerythrin-labeled monoclonal antibodies contained substance P-reactive T-lymphocytes at respective mean frequencies of 10 and 18%. [3H]substance P bound rapidly and reversibly to a mean of 7035 +/- 2850 sites/T-lymphocyte, which exhibited a dissociation constant (KD) of 1.85 +/- 0.70 X 10(-7) M (mean +/- SD, n = 5). [D-Pro2,D-Phe7,D-Trp9]substance P inhibited the binding of dichlorotriazinylamino-fluorescein-labeled substance P and [3H]substance P to T-lymphocytes at concentrations that suppressed the proliferative response to substance P. Substance P, eledoisin, and substance K (alpha-neurokinin), which all share with substance P the carboxy-terminal substituent -Gly-Leu-Met-NH2, were more potent than substance P in inhibiting the binding of [3H]substance P to T-lymphocytes, suggesting the importance of this sequence in the interaction. Purified human blood B-lymphocytes, monocytes, polymorphonuclear leukocytes, and platelets, and cultured Hut 78 cutaneous lymphoma T-cells, Jurkat cells, Molt-4 lymphoblasts, and HL-60 and U-937 monocyte-like cells all showed only minimal specific binding of [3H]substance P. The recognition of substance P by T-lymphocytes provides one mechanism for selective modulation of immunity by sensory nerves.     

Kyste dermoïde du IV ventricule chez un sujet présentant depuis 20 ans des troubles mentaux. Etude anatomo-pathologique

Résumé Un kyste dermoïde du IV ventricule est décrit, découvert chez un homme de 48 ans brusquement décédé au cours de troubles respiratoires alors qu'il présentait depuis 20 ans des troubles mentaux et neurologiques. La tumeur, rompue dans le IV ventricule contient dans sa paroid des poils et annexes glandulaires (glandes «apocrines»). Il existe une réaction cellulaire macrophagique dans la leptoméninge du tronc cérébral. Les auteurs passent en revue la littérature et insistent sur différents points: ces tumeurs sont très rares dans le système nerveux central — mais elles sont très souvent localisées sur la ligne médiane du tronc cérébral — la difficulté de différencier le type dermoïde et le type épidermoide dans la littérature et quelquefois sur les différentes coupes d'une même tumeur.

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Summary Dermoid tumor is reported in a man 48 years old with mental and nervous signs since 20 years. He died suddenly with repiratory signs. The tumor ruptured contains hairs and apocrin glands and is situated in the IVth ventricle. There is a lipophagic reaction in the arachnoid surrounding brain stem. The authors after a review of the literature, insist on different points: These tumors are very rare in the Central Nervous System, but they are very often localised in the mediane line of brain stem; difficulty to differentiate dermoid type and epidermoid type in many papers and sometimes in the different slides of the same case.

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Avec 9 Figures dans le Texte

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L'étude clinique a fait l'objet d'une présentation parMM. H. Collomb, H. Payan, M. Berard-Badier etJ. Laurent à la Société Médico-Psychologique de Lyon, le 21 décembre 1958.