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71.
5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease. 相似文献
72.
GS Prins M Marmer C Woodham W Chang G Kuiper JA Gustafsson L Birch 《Canadian Metallurgical Quarterly》1998,139(3):874-883
Neonatal exposure to estrogens permanently alters rat prostate growth and epithelial differentiation leading to prostatic dysplasia on aging. The effects are lobe-specific, with the greatest response observed in the ventral lobe. Recently, a novel estrogen receptor (ER) complementary DNA was cloned from the rat prostate and termed ER-beta (ER beta) due to its high homology with the classical ER alpha. The protein possesses high affinity for 17beta-estradiol, indicating that ER beta is an alternate molecule for mediating estrogenic effects. Importantly, ER beta messenger RNA (mRNA) was localized to rat prostatic epithelial cells, which contrasts with the stromal localization of ER alpha in the rat prostate. The present study was undertaken to determine the ontogeny of ER beta mRNA expression in the rat prostate lobes and to examine the effects of early estrogen exposure on prostatic ER beta expression. Male rat pups were given 25 microg estradiol or oil on days 1, 3, and 5; were killed on day 1, 3 (oils only), 6, 10, 30, or 90; and prostate lobes were frozen. Longitudinal sections were processed for in situ hybridization using an 35S-labeled antisense mRNA probe corresponding to a 400-bp EcoRI-AccI fragment in the 5' untranslated region of rat ER beta complementary DNA. Image analysis was used to quantitate silver grains. In addition, total RNA was isolated from the ventral prostate (VP) and used for semiquantitative RT-PCR. Results from in situ hybridization revealed that at birth, ER beta was equivalently expressed at low levels in both mesenchymal and epithelial cells in oil-treated rats. From day 1 onwards, expression in all stromal cells slowly and significantly declined, so that in the control adult prostate, stromal ER beta mRNA was slightly above background. In the oil-treated control rats, epithelial ER beta mRNA increased to moderate levels between days 6-10 in the VP and days 10-15 in the dorsal and lateral lobes as cells began differentiation and ducts lumenized. A further significant increase in ER beta message was observed at day 30, which indicates that full epithelial ER beta expression may require the completion of functional differentiation. By day 90, expression levels were maximal and similar between the lobes. RT-PCR substantiated this developmental increase in ER beta between days 1-90. Neonatal exposure to estrogens did not have an immediate effect on prostatic ER beta mRNA levels as determined by in situ hybridization and RT-PCR. However, the marked increase in epithelial cell expression at day 30 observed in the control VP was dampened in the VP of animals exposed neonatally to estrogens. By day 90, the VP of estrogenized rats possessed low ER beta message levels compared with the high expression in oil controls. In contrast, the dorsal and lateral lobes of neonatally estrogenized rats possessed high levels of ER beta mRNA at day 90, equivalent to controls. The present data demonstrate that ER beta mRNA expression in the rat prostate is developmentally regulated, and that neonatal estrogen can affect this expression in the adult VP. Because the effect of neonatal estrogens was not immediate, the data imply that early estrogen exposure may not directly autoregulate ER beta expression, and suggests that the adult effects on ER beta mRNA expression may be indirect. The differences in ER beta mRNA imprinting in the separate lobes may account for or reflect the lobe-specific neonatal estrogen imprints previously observed in the rat prostate. 相似文献
73.
HR Figulla H Mudra N Reifart GS Werner 《Canadian Metallurgical Quarterly》1998,43(3):245-52; discussion 253
Coronary stenting is the primary therapeutic option for many coronary lesions, after the risk of subacute stent thrombosis and bleeding complications has been reduced by antithrombotic regimens and improved stent expansion. It would be desirable to shorten the procedure and the duration of ischemia, and to reduce the risk of ischemic complications during balloon inflation by implanting the stent without previous dilatation of the lesion. This is not possible with the presently available stent delivery systems. This new therapeutic concept was tested with a specially designed balloon catheter, on which slotted-tube stents can be fixed between two conical radiopaque markers. Sixty-one patients eligible for angioplasty underwent direct stent implantation without predilatation. Four procedures were performed for acute myocardial infarction, and two as high-risk PTCA. Single slotted-tube stents (Palmaz-Schatz, NIR, or JOStent) of 14-16-mm length were mounted between the conical radiopaque markers of a special balloon which provided a fixation for the crimped stent. The direct implantation was successful in 80% of all patients, while in 10% the stent could be deployed after predilatation of the lesion. In 10% of lesions a stent could not be implanted with this and any other delivery system. When patients with successful direct stenting were compared with those with indirect (after predilatation) or unsuccessful stent deployment, the presence of angiographically visible calcification was higher in the unsuccessful cases (75% vs. 19%; P < 0.01), and the patients were older (72+/-8 vs. 61+/-12 years; P < 0.01). Radiation exposure time was only 8.7+/-5.1 min as compared with 12.6+/-7.6 min in conventional stent procedures with predilatation (P < 0.05). The number of balloons used per lesion was also lower than with conventional stenting. Stent dislocation was observed in 5%, and no embolization occurred. The new therapeutic approach of direct stenting without predilatation proved to be a safe and successful procedure in this initial series of coronary angioplasties. When calcified coronary lesions are avoided, it provides a way to rationalize stent implantation with shorter radiation exposure times, fewer balloons, and the potential advantage of fewer ischemic complications as no balloon predilatation is required. 相似文献
74.
GS Mela V Savarino A Malesci F Di Mario P Sossai S Vigneri A Zambotti 《Canadian Metallurgical Quarterly》1994,39(7):1416-1424
Continuous 24-hr intragastric pH-metry was prospectively performed in 801 subjects with different clinical conditions using two pH electrodes placed closely adjacent. The aim was to assess the in situ repeatability of the test and to verify whether the removal of artifacts, interference, and noise usually superimposed onto the fundamental signal recorded by the measuring apparatus improves the clinical usefulness of experimental data. The following debugging/filtering procedure was used: first, pH recordings of each channel were amended separately from artifacts, then they underwent 7 min windowed median interference debugging, and finally Wiener noise filtering was applied. Afterwards, the 24-hr mean pH profile was obtained in each subject by averaging the pH tracings of the two channels every minute (1440 data points/24 hr). The efficiency of this procedure was assessed at each step by evaluating the difference among groups using the O'Brien test, a distribution-free nonparametric method well-suited for evaluating differences among groups allocated onto a two-way layout. The differences among groups calculated from raw pH data of the single channels can be very misleading, in that it is possible to find that they are significant on one channel and not significant on the other channel. Conversely, the significance of the differences among groups increases progressively at each step of the above debugging/filtering procedure applied to raw pH profiles of each channel. Seven minutes was shown to be the most suitable time lag for windowed median removal of interference.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
75.
LS Chernin MK Winson JM Thompson S Haran BW Bycroft I Chet P Williams GS Stewart 《Canadian Metallurgical Quarterly》1998,180(17):4435-4441
Quorum sensing control mediated by N-acyl homoserine lactone (AHL) signaling molecules has been established as a key feature of the regulation of exoenzyme production in many gram-negative bacteria. In Chromobacterium violaceum ATCC 31532 a number of phenotypic characteristics, including production of the purple pigment violacein, hydrogen cyanide, antibiotics, and exoproteases are known to be regulated by the endogenous AHL N-hexanoyl-L-homoserine lactone (HHL). In this study we show that C. violaceum produces a set of chitinolytic enzymes whose production is regulated by HHL. The chitinolytic activity was induced in strains grown in the presence of chitin as the sole carbon source and quantitated in the secreted proteins by using p-nitrophenol analogs of disaccharide, trisaccharide, and tetrasaccharide oligomers of N-acetylglucosamine. By using 4-methylumbelliferyl analogs of the same oligomers of N-acetylglucosamine as substrates for proteins separated and renatured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least six enzymes were detected: a chitobiase with high specificity to a dimeric substrate of 87 kDa, two N-acetylglucosaminidases with apparent molecular masses of 162 and 133 kDa, two endochitinases of 108 and 67 kDa, and a chitobiosidase of 56 kDa. In addition, two unidentified bands of >205 kDa were found where a tetrameric chitin derivative was used as a substrate. A pleiotropic mini-Tn5 mutant of C. violaceum (CV026) that is defective in HHL production and other quorum-sensing-regulated factors was also found to be completely deficient in chitinolytic activity. Growth of this mutant on minimal medium with chitin supplemented with culture supernatant from the C. violaceum wild-type strain or 10 microM synthetic HHL restored chitinase production to the level shown by the parental strain. These results constitute the most complete evidence so far for regulation of chitinolytic activity by AHL signaling in a gram-negative bacterium. 相似文献
76.
GS Ogg X Jin S Bonhoeffer PR Dunbar MA Nowak S Monard JP Segal Y Cao SL Rowland-Jones V Cerundolo A Hurley M Markowitz DD Ho DF Nixon AJ McMichael 《Canadian Metallurgical Quarterly》1998,279(5359):2103-2106
Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control of human immunodeficiency virus-type 1 (HIV-1) infection, it has not been possible to demonstrate a direct relation between CTL activity and plasma RNA viral load. Human leukocyte antigen-peptide tetrameric complexes offer a specific means to directly quantitate circulating CTLs ex vivo. With the use of the tetrameric complexes, a significant inverse correlation was observed between HIV-specific CTL frequency and plasma RNA viral load. In contrast, no significant association was detected between the clearance rate of productively infected cells and frequency of HIV-specific CTLs. These data are consistent with a significant role for HIV-specific CTLs in the control of HIV infection and suggest a considerable cytopathic effect of the virus in vivo. 相似文献
77.
Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma 总被引:1,自引:0,他引:1
78.
79.
80.
The aim of the present investigation was to determine spin lock (SL) relaxation parameters for the normal brain tissues and thus, to provide basis for optimizing the imaging contrast at 0.1 T. 68 healthy volunteers were included. On-resonance spin lock relaxation time (T1rho) and off-resonance spin lock relaxation parameters (T1rho(off), Me/Mo), MT parameters (T1sat, Ms/Mo), and T1, T2 were determined for the cortical gray matter, and for the frontal and parietal white matters. The T1rho for the frontal and parietal white matters ranged from 110 to 133 ms and from 122 to 155 ms with locking field strengths from 50 microT to 250 microT, respectively. Accordingly, the values for the gray matter ranged from 127 to 155 ms. With a locking field strength of 50 microT, T1rho(off) for the frontal and parietal white matters were from 114 to 217 ms and from 126 to 219 ms, and for the gray matter from 136 to 267 ms with the angle between the effective magnetic field (B(eff)) and the z-axis (theta) ranging from 60 degrees to 15 degrees, respectively. The T1rho of the white and gray matters increased significantly with increasing locking field amplitude (p < 0.001). The T1rho(off) decreased significantly with increasing theta (p < 0.001). T1rho and T1rho(off) with theta > or = 30 degrees were statistically significantly shorter in the frontal than in the parietal white matters (p < 0.05). The duration, amplitude and theta of the locking pulse provide additional parameters to optimize contrast in brain SL imaging. 相似文献