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Serotonin (5-HT) is a mediator (through 5-HT1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED50 0.3 μM). This effect was not antagonized by the 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT1 agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT4 agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT1/5-HT2 antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT4 antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT2 receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT2 receptor failed to reveal the presence of 5-HT2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc. 相似文献
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Vasileios Mourmouras Gabriele Cevenini Elena Cosci Maria C. Epistolato Maurizio Biagioli Letizia Barbagli Pietro Luzi Susanna Mannucci and Clelia Miracco 《Journal of cutaneous pathology》2009,36(6):637-646
Background: Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.
Methods: We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results: Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion: An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma. 相似文献
Methods: We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results: Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion: An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma. 相似文献
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Esparza-Gordillo Jorge; Goicoechea de Jorge Elena; Buil Alfonso; Berges Luis Carreras; Lopez-Trascasa Margarita; Sanchez-Corral Pilar; Rodriguez de Cordoba Santiago 《Human molecular genetics》2005,14(8):1107
Some MCP SNP and aHUS-associated MCP mutation 相似文献
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Abstract – Aim: To evaluate the pulp and periodontal healing of laterally luxated permanent teeth. Material and methods: Patients presenting with lateral luxation of permanent teeth during 2001–2002 were enrolled in this clinical study. Laterally luxated teeth were repositioned and splinted with a TTS/composite resin splint for 4 weeks. Immediate (prophylactic) root‐canal treatment was performed in severely luxated teeth with radiographically closed apices. All patients received tetracycline for 10 days. Re‐examinations were performed after 1, 2, 3, 6, 12 and 48 months. Results: All 47 laterally luxated permanent teeth that could be followed over the entire study period survived. In 10 teeth (21.3%), a prophylactic root‐canal treatment was performed within 2 weeks following injury. The remaining 37 teeth showed the following characteristics at the 4‐year re‐examination: 19 teeth (51.4%) had pulp survival (no clinical or radiographic signs or symptoms), nine teeth (24.3%) presented with pulp canal calcification, and pulp necrosis was seen in another nine teeth (24.3%), within the first year after trauma. None of the teeth with a radiographically open apex at the time of lateral luxation showed complications. External root resorption was only seen in one tooth. Conclusions: Laterally luxated permanent teeth with incomplete root formation have a good prognosis, with all teeth surviving in this study. The most frequent complication was pulp necrosis that was only seen in teeth with closed apices. 相似文献
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José Abal Arca Isaura Parente Lamelas Raquel Almazán Ortega José Blanco Pérez María Elena Toubes Navarro Pedro Marcos Velázquez 《Archivos de bronconeumologia》2009,45(10):502-507
Background and objectiveTo analyse frequency, characteristics and patient survival with lung cancer (LC) and Common Obstructive Pulmonary Disease (COPD), comparing them with patients that do not have COPD.Material and methodsA retrospective study, of patients diagnosed by means of cytohistology. Survival was estimated by the Kaplan-Meier method. Statistical analysis was carried out using SPSS 15.0.ResultsA total of 996 patients were diagnosed, 39.8% with COPD. Mean age70±9.19 years. GOLD stages: I 18.2%, II 53.6%, III 24%, IV 4.2%. The histological types: squamous cell carcinoma 48.2%, adenocarcinoma 22%, and small cell carcinoma 22.5%. Survival was longer in the COPD group.ConclusionsLC and COPD are combined in 39.8%. Squamous cell type is more frequent and survival was longer in the COPD group. 相似文献
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A Parra F Gabi?o A Ramírez H Valencia I Coria A Espinosa de los Monteros 《Contraception》1991,44(5):541-547
The study was undertaken to analyze the basal and metoclopramide-stimulated serum PRL levels in healthy parous women users (group 1, n = 12) and non-users (group 2, n = 12) of a TCu-380 IUD. All women had regular menses and were studied between days 18 to 22 of their cycle; none had lactated nor regularly ingested any type of medication during the last six months. After a 10-12 hour overnight fast, peripheral venous blood samples were obtained through an indwelling catheter at -30, -15 and 0 minutes and at 60, 90 and 120 minutes after oral metoclopramide (10 mg). There were no significant differences in serum PRL between both groups, in basal levels nor throughout the test, whether analyzing the mean values at each sampling time, the sum of PRL levels from 60-120 minutes, or the peak levels. No correlation was observed between PRL levels and any of the clinical or obstetric characteristics of the women in both groups. Serum progesterone was greater than or equal to 4.0 ng/ml in all women. Thus, the use of alpha TCu-380 IUD did not induce any significant changes in basal nor in stimulated serum PRL levels. 相似文献