Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We now attempted to differentiate effects of cysteinyl-leukotrienes and leukotriene B4 on antigen-induced pulmonary reaction by using a selective leukotriene D4/E4 (CysLT1) receptor antagonist and a selective LTB4 (BLT) receptor antagonist in rats. An intratracheal challenge with ovalbumin to Brown-Norway rats actively sensitized with ovalbumin produced two phases of airway responses which were estimated based on airway resistance, the immediate-type airway response within 30 min, and the delayed-type airway response beginning from 4 to 6 h after the challenge. Pretreatment of the rats with a CysLT1 receptor antagonist (pranlukast) failed to reduce the elevation of airway resistance, and pretreatment with a BLT receptor antagonist (ONO-4057; 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-5E-hexenyl]- oxyphenoxy] valeric acid) also produced no decrease. In contrast, combined pretreatment of the rats with pranlukast and ONO-4057 did not reduce the amplitude of the immediate-type airway response, but did allow the elevated airway resistance to return to its baseline level and also significantly inhibited the delayed-type airway response. Histological examination at 6 h after ovalbumin challenge showed infiltration of inflammatory cells with a predominance of neutrophils and scattered eosinophils in the bronchial submucosa. While pretreatment with neither pranlukast nor with ONO-4057 inhibited the infiltration of inflammatory cells in the bronchial submucosa, pretreatment with the two antagonists combined significantly inhibited the infiltration of granulocytes into the bronchial submucosa. On the contrary, intratracheal administration of either leukotriene D4 or leukotriene B4 up to 10 microg resulted in the infiltration of granulocytes into the bronchial submucosa, but no synergism for the infiltration of granulocytes was observed after combined administration. These results suggest that leukotriene B4 appears to play a significant role in the antigen-induced pulmonary reaction in association with cysteinyl-leukotrienes. Accordingly, the combined antagonism at the CysLT1 receptor and BLT receptor may be a useful intervention for the treatment of bronchial asthma.
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PMID:Synergistic effects of pranlukast and leukotriene B4 receptor antagonist on antigen-induced pulmonary reaction. 1032 64

Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6-4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6-2.1; P<0.001). Treatment with a 5-lipoxygenase enzyme inhibitor (SB 210661, 10 mg kg(-1), p.o.) and a specific cysteinyl leukotriene (CysLT1) receptor antagonist, pranlukast (SB 205312, 30 mg kg(-1), p.o.), both attenuated ASM cell DNA synthesis. Treatment with a specific leukotriene B4 (BLT) receptor antagonist (SB 201146, 15 mg kg(-1), p.o.) had no effect. There was also a significant, 2 fold increase in the number of epithelial cells incorporating BrdU per unit length of basement membrane after repeated allergen exposure. This response was not inhibited by treatment with SB 210661, pranlukast or SB 201146. A significant increase in ASM thickness was identified following repeated allergen exposure and this response was attenuated significantly by SB 210661, pranlukast and SB 201146. Rats exposed to chronic allergen exhibited bronchial hyperresponsiveness to acetylcholine and had significant eosinophil recruitment into the lungs. Treatment with SB 210661, pranlukast or SB 201146 significantly attenuated eosinophil recruitment into the lungs, whilst having no significant effect on airway hyperresponsiveness. These data indicate that the cysteinyl leukotrienes are important mediators in allergen-induced ASM cell DNA synthesis in rats, while both LTB4 and cysteinyl leukotrienes contribute to ASM thickening and eosinophil recruitment following repeated allergen exposure.
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PMID:Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats. 1045 61

This study examined the ability of an asymmetrical dot location memory test (Brown Location Test, BLT) and two verbal memory tests (Verbal Selective Reminding Test (VSRT) and California Verbal Learning Test, Second Edition (CVLT-II)) to correctly lateralize left (LTLE) or right (RTLE) mesial temporal lobe epilepsy that was confirmed with video-EEG. Subjects consisted of 16 patients with medically refractory RTLE and 13 patients with medically refractory LTLE who were left hemisphere language dominant. Positive predictive values for lateralizing TLE correctly were 87.5% for the BLT, 72.7% for the VSRT, and 80% for the CVLT-II. Binary logistic regression indicated that the BLT alone correctly classified 76.9% of patients with left temporal lobe epilepsy and 87.5% of patients with right temporal lobe epilepsy. Inclusion of the verbal memory tests improved this to 92.3% of patients with left temporal lobe epilepsy and 100% correct classification of patients with right temporal lobe epilepsy. Though of a limited sample size, this study suggests that the BLT alone provides strong laterality information which improves with the addition of verbal memory tests.
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PMID:Spatial memory for asymmetrical dot locations predicts lateralization among patients with presurgical mesial temporal lobe epilepsy. 2639 92