PURPOSE: In bladder, sensory afferent nerve fibers contain the "sensory neuropeptides" substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP), which interact with tachykinin NK-1 and NK-2 receptors and CGRP receptors, respectively. The purpose of this study was to examine the autoradiographic distribution of these three receptor types in the human bladder, to determine whether the anatomic location of the receptors was consistent with their known functional roles. MATERIALS AND METHODS: Specimens of urinary bladder from 9 patients (58-74 years) were obtained at cystectomy. Frozen sections of dome were labeled with [125I]-Bolton-Hunter [Sar9,Met(O2)11]-SP (NK-1 receptors), [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) (NK-2 receptors) and [125I]-rat CGRP-I. Binding sites were visualized using emulsion autoradiography. RESULTS: NK-1 receptors were found over the endothelium of arterial blood vessels within the detrusor muscle and lamina propria, and over small vessels in the subepithelium. NK-2 receptors were seen over the detrusor muscle and very sparsely over blood vessels, whereas CGRP receptors were expressed densely over the smooth muscle layer of arteries and arterioles, and weakly over collecting venules. NK-1 and CGRP receptors were not observed over the detrusor muscle. CONCLUSIONS: Although the afferent nerves contain all three peptides, not all cell types express receptors for each peptide. The general distribution of receptors is in good agreement with the location of nerves, and with the known actions of SP and CGRP as vasodilator agents, and of NKA (but not SP or CGRP) in contracting the detrusor muscle. 相似文献
Acute lung injury (ALI) or its more severe form, the acute respiratory distress syndrome (ARDS), is a common, devastating clinical syndrome that affects both medical and surgical patients. The most common cause of ALI is sepsis. There is now well-documented evidence that pulmonary inflammation contributes to the devel-opment of ALI. Despite significant advances in our un-derstanding of pathophysiology and technologies in the supportive management, mortality from ALI remains excessive. C… 相似文献
PURPOSE: Many cancer lines are methionine dependent and decrease proliferation when methionine supply is limited. Methylenetetrahydrofolate reductase (MTHFR) generates the folate derivative for homocysteine remethylation to methionine. We investigated the effect of antisense-mediated inhibition of MTHFR on survival of human cancer cells. EXPERIMENTAL DESIGN: We examined the in vitro and in vivo anticancer effects of a combination of MTHFR antisense and standard cytotoxic drugs. RESULTS: Specific antisense against MTHFR (EX5) showed significant inhibitory effects on growth of human colon, lung, breast, prostate, and neuroblastoma tumor cells in vitro compared with that of the control oligonucleotide. Cytotoxic drugs (5-fluorouracil, cisplatin, or paclitaxel) potentiated the effect of EX5. In vivo, antisense alone or in combination with cytotoxic drugs inhibited the growth of human colon and lung carcinoma xenografts. In comparison with control oligonucleotide, treatment with EX5 inhibited growth of colon tumors and lung tumors by 60% and 45%, respectively. EX5 with 5-fluorouracil decreased growth of colon tumors by an additional 30% compared with EX5 alone, and EX5 with cisplatin decreased growth of lung tumors by an additional 40% compared with cisplatin alone. Growth inhibition by EX5 was associated with decreased amounts of MTHFR protein and with increased amounts of an apoptosis marker. CONCLUSIONS: Our results confirm that MTHFR inhibition decreases tumor growth and suggest that inhibition of MTHFR by antisense or small molecules may be a novel anticancer approach. 相似文献
??Objective??To detect the level of fecal primary and secondary bile acids in infants with infantile cholestatic hepatopathy??ICH??and analyze its clinical value. Methods??Thirty infants with ICH were enrolled in this study??who were diagnosed with infantile cholestatic hepatopathy. Thirty infants with good health condition were enrolled as the healthy control group. The fecal samples were collected respectively in the preparatory treatment phase and treatment phase from infants with ICH and from the healthy infants. Bile acids were extracted from infants’ feces and were quantitatively analyzed by liquid chromatography-mass spectroscopy. Results??Among the fecal primary bile acids??the level of cholic acid??chenodeoxycholic and glycochenodeoxycholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group??P??0.016??.The level of fecal cholic acid and chenodeoxycholic acid of ICH treatment group was higher than in the ICH preparatory treatment group??P??0.016??. Among the fecal secondary bile acids??the level of lithocholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group??P??0.016????and the level of ursodeoxycholic acid in the ICH preparatory treatment group was lower than that in the ICH treatment group and healthy control group??P??0.016??. Conclusion??In infants with ICH, the changes of fecal primary bile acids and fecal secondary bile acids have their own characteristics at the early stage of treatment, which may be caused by the short-term treatment, the prognosis of the disease itself and the changes of intestinal function, including intestinal bacteria. Clinical attention should be paid to these changes. 相似文献