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Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion. 总被引:21,自引:7,他引:14
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R J Coffey Jr L J Kost R M Lyons H L Moses N F LaRusso 《The Journal of clinical investigation》1987,80(3):750-757
Transforming growth factor beta (TGF beta), a recently discovered polypeptide, modulates growth of normal and neoplastic cells. Since little is known concerning in vivo disposition of TGF beta, we performed studies to examine the hepatic processing of biologically active 125I-TGF beta in the rat. After intravenous injection, 125I-TGF beta disappeared from the plasma with an initial t1/2 of 2.2 min; partial hepatectomy delayed the plasma disappearance of 125I-TGF beta by 80%. 60 min after intrafemoral injection, 63% of the recovered label was present in liver and/or bile; by 90 min, most of the label removed by the liver (83%) had been slowly excreted into bile. Nearly all the label in bile (96%) was soluble in trichloracetic acid and not immunoprecipitable by specific antiserum. Colchicine and vinblastine inhibited cumulative biliary excretion of label by 28 and 37%, respectively; chloroquine and leupeptin each increased the amount of label in bile that was precipitable by trichloracetic acid and that coeluted with authentic 125I-TGF beta on molecular sieve chromatography. There was efficient first-pass hepatic extraction of 125I-TGF beta (36%) in the isolated perfused rat liver, which was inhibited by unlabeled TGF beta (but not by epidermal growth factor, EGF) and by lectins in a dose-dependent manner; prolonged fasting also decreased clearance (26%). After fractionation of liver by differential or isopycnic centrifugation, radiolabel codistributed with marker enzymes for lysosomes. The results indicate rapid, extensive, inhibitable, and organ-selective extraction of TGF beta by the liver. After extraction, TGF beta undergoes efficient transhepatic transport, extensive intracellular metabolism, and slow but complete biliary excretion of its metabolites. Liver fractionation studies and pharmacologic manipulations suggest that these processes are associated with organelles that include microtubules and lysosomes. The data suggest that the liver is a major target tissue or site of metabolism for biologically active TGF beta. 相似文献
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LEE JS IM HH JUNG Y JUNG IS JANG JY CHUN YK CHO YD KIM JO CHO JY KIM YS SHIM CS & KIM BS 《Neurogastroenterology and motility》2006,18(6):493-494
Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future. 相似文献
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Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. 总被引:13,自引:0,他引:13
P W Cook M R Pittelkow W W Keeble R Graves-Deal R J Coffey G D Shipley 《Cancer research》1992,52(11):3224-3227
Amphiregulin (AR) is a heparin-regulated, epidermal growth factor-like growth factor capable of stimulating the proliferation of non-tumorigenic cells while inhibiting cell proliferation in some human tumor cell lines in vitro. In the present study, we have investigated AR mRNA expression in normal, hyperproliferative, and neoplastic human epithelium. Our results demonstrate that, compared with the adjacent uninvolved epithelium, AR mRNA expression is markedly elevated in epidermal biopsies derived from three human psoriatic lesions as well as in biopsies derived from five human colon carcinomas and three human stomach carcinomas. Moreover, analysis of a colon carcinoma by in situ hybridization revealed that AR mRNA is localized to the epithelium. 相似文献
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K. .SANDVEJ L.K. KRENÁCS S.J. HAMILTON-DUTOIT J.L. RINDUM J.J. PINDBORG G. PALLESEN 《Histopathology》1992,20(5):387-395
Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed. 相似文献
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D A Young M C McKee B Coffey S Cool N Roth R L Yolton 《Journal of the American Optometric Association》1988,59(5):364-371
Snellen letter and Vistech sine wave grating charts were used as refraction targets to determine differences in times required to accomplish subjective refractions, endpoint refractive values, and subject preferences. Thirty hyperopes and 30 myopes, divided into three age groups, were selected as subjects. Two examiners tested each subject using each chart. Both timed their subjective refractions and recorded their findings. After all data were recorded, each subject completed a questionnaire to determine chart preference. There were no clinically significant mean differences between the charts in terms of endpoint refractive data, but, on average, the Snellen chart was faster to use. Chart rating depended on the subject's refractive status with more myopes preferring the Snellen chart and more hyperopes rating the grating chart higher. 相似文献
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Nancy J. Fishwick RN PhD CS 《Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG》1998,27(6):661-670
Nearly 4 million women in the United States were physically hurt by their husbands or boyfriends in 1994. The health and well-being of these women and their children, as well as the women who are overlooked in these statistics, are jeopardized by past and current experiences with abuse within intimate relationships. Strategies for nurses in women's health care settings to screen women for current or past abuse within their intimate personal relationships, guidelines for effective responses to disclosure of abuse, and supportive interventions are described. 相似文献
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