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排序方式: 共有808条查询结果,搜索用时 15 毫秒
721.
Jacques-André St-Pierre Yvan Dumont Dominique Nouel Herbert Herzog Edith Hamel Rémi Quirion 《British journal of pharmacology》1998,123(2):183-194
- Neuropeptide Y (NPY) and NPY receptors are most abundant in the hippocampal formation where they modulate cognitive functions. Expression of NPY receptors in rat cultured primary hippocampal cells was investigated in the present study by use of combined molecular, pharmacological and immunohistochemical approaches, including the cloning of the rat Y2 receptor described here for the first time.
- More than 70% of the hippocampal neurones were endowed with [125I]-[Leu31,Pro34]PYY Y1-like receptor silver grain accumulations and Y1 receptor immunostaining. These radio- and immuno-labelling signals were distributed over cell bodies and processes of bipolar, stellate and pyramidal-like neuronal cells, as confirmed by neurone-specific enolase and MAP-2 staining.
- Competition binding profiles revealed that specific [125I]-[Leu31,Pro34]PYY binding was competitively displaced according to a ligand selectivity pattern prototypical of the Y1 receptor sub-type with [Leu31,Pro34]substituted NPY/PYY analogues>>C-terminal fragments=pancreatic polypeptides, with the non-peptide antagonist BIBP3226 being most potent. This profile excludes the possible labelling by [125I]-[Leu31,Pro34]PYY of the newly cloned Y4, Y5 and Y6 receptors.
- The expression of the genuine Y1 receptor was confirmed by RT–PCR in hippocampal cultures. In contrast, negligible levels of Y2-like/[125I]-PYY3–36 binding were detected in these cultures in spite of the presence of its mRNA, as characterized by RT–PCR. The expression of both the Y1 and the Y2 receptor mRNAs was also noted in normal embryonic hippocampal tissues showing that signals expressed in cultured neurones were also present in utero.
- Taken together, these results suggest that the Y1 receptor subtype may be of critical importance in the normal functioning of the rat hippocampus, especially during brain development and maturation.
722.
Glatt H; Davis W; Meinl W; Hermersdorfer H; Venitt S; Phillips DH 《Carcinogenesis》1998,19(10):1709-1713
Tamoxifen increases the risk of human endometrial cancer and is a potent
carcinogen in rat liver, in which it produces DNA adducts and cytogenetic
damage. Nevertheless its prophylactic use against breast cancer in healthy
women is under investigation in several large trials. To investigate
whether rat hepatocarcinogenicity predicts human hepatocarcinogenicity we
used genetically engineered bacterial and mammalian target cells to
investigate how alpha-hydroxy-tamoxifen, a major phase I metabolite of
tamoxifen, is further metabolised by rat and human phase II enzymes,
sulfotransferases, to mutagenic and DNA- adduct-forming species. We
expressed rat hydroxysteroid sulfotransferase a, a liver-specific enzyme,
and corresponding human sulfotransferase in bacteria (Salmonella
typhimurium) and in a mammalian cell line (Chinese hamster V79 cells) and
tested alpha- hydroxytamoxifen for DNA adduct formation and mutagenicity in
these systems, using unmodified cells as controls. In cells that expressed
rat hydroxysteroid sulfotransferase, alpha-hydroxytamoxifen was mutagenic
and formed the same pattern of DNA adducts as that found in the liver of
tamoxifen-treated rats. Alpha-hydroxytamoxifen was not activated, or was at
least 20 times less active in cells expressing human hydroxysteroid
sulfotransferase. All the other six known human xenobiotic-metabolising
sulfotransferases were also expressed in S. typhimurium. None activated
alpha-hydroxytamoxifen to a mutagen. These results suggest that the risk of
DNA adduct formation, and cancer, in the human liver is low and explain why
tamoxifen is a powerful carcinogen to the rat liver, and why standard
short-term tests fail to detect its mutagenicity.
相似文献
723.
Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI and GSTM1 genotypes in lung patients 总被引:4,自引:5,他引:4
Relationships between smoking status and levels of bulky DNA adducts were
investigated in bronchial tissue of lung patients in relation to their
GSTM1 and CYP1A1 MspI genotypes. A total of 150 Hungarian patients
undergoing pulmonary surgery were included in the study, 124 with lung
malignancies and 26 with non-malignant lung conditions. There were
significant relationships between smoking status and bulky DNA adduct
levels, as determined by 32P-post-labelling analysis, in macroscopically
normal bronchial tissues. There was a highly significant difference in the
adduct levels of a combined group consisting of current smokers and
short-term ex-smokers (< or = 1 year abstinence) compared with life-time
non-smokers and long-term ex- smokers (> 1 year abstinence) (P =
0.0001). The apparent half-life was estimated to be 1.7 years for bulky DNA
adducts in the bronchial tissue from ex-smokers. There were no
statistically significant correlations between (i) daily cigarette dose and
DNA adduct levels in current smokers, (ii) DNA adduct level and
histological type of lung cancer, or (iii) GSTM1 and CYP1A1 MspI genotypes
and DNA adduct levels after adjustment for either smoking status or
malignancy. By multiple logistic regression analysis, smoking and GSTM1
null genotype were found to be risk factors for squamous cell carcinoma.
However, bulky DNA adduct levels in bronchial tissue did not appear to be a
statistically-significant risk factor for the major histological types of
lung cancer.
相似文献
724.
Metaphyseal growth arrest lines are seen in children who experience significant physical stress such as infection or malnutrition over a sufficient period of time. These lines have not been reported previously in children with psychosocial short stature (PSS). Two boys and a girl with PSS with metaphyseal growth arrest lines on skeletal radiographs at the time of maximal stress in their homes are described. All three had reversible growth hormone insufficiency during admission, which is pathognomic for PSS. Multiple growth arrest lines in the distal end of the radius or vertebrae should alert clinicians to an alternative diagnosis in a child with growth hormone insufficiency. This may provide a clue to the diagnosis of occult PSS. 相似文献
725.
Exposure to sinusoidal (power-frequency) magnetic fields during prenatal development is implicated in adulthood behavioral impairments. However, the effects of prenatal exposure to weak-intensity, nonsinusoidal complex magnetic fields (CMFs), an increasingly common feature of the modern environment, have not been rigorously examined. In the present study, male and female Wistar-strain rats were exposed continually during prenatal development to one of three extremely low-frequency CMFs or a sham condition. As adults, rats were trained in an acquisition/reversal radial maze task. All rats exposed to the prenatal CMFs increased their commission of reference memory errors, but differences in working memory and motivation to complete the maze task were specific to the type of prenatal CMF. These results provide the first evidence that prenatal exposures to specific shapes of CMFs impair complex learning behaviors into adulthood. 相似文献
726.
727.
Radiographic damage in rheumatoid arthritis correlates with functional disability but not direct medical costs. 总被引:4,自引:0,他引:4
A E Clarke Y St-Pierre L Joseph J Penrod J T Sibley M Haga H K Genant 《The Journal of rheumatology》2001,28(11):2416-2424
OBJECTIVE: Few longitudinal data exist on the relationship between radiographic damage and self-reported functional disability and direct medical costs in rheumatoid arthritis (RA). We assessed these relationships. METHODS: One hundred thirty patients with RA (at time of the first available radiograph, mean age 56.6 yrs, 16.9% male, mean disease duration 16.8 yrs) were followed for up to 13.4 years. Semiannually, they reported on functional disability (0 = no difficulty, 3 = unable to do), global severity (0 = very well, 100 = very poor), pain (0 = no pain, 3 = severe pain), and health services utilization through completion of the Stanford Health Assessment Questionnaire (HAQ). Concurrent hand radiographs were scored for erosions and joint space narrowing using the Genant method and a single score summing both erosions and joint space narrowing for both hands was calculated (0 = no damage, 200 = maximum damage). The univariate association of functional disability, global severity, pain, or direct medical costs with concurrent radiographic damage was assessed through Spearman correlations and hierarchical regression models. The hierarchical models permit exploitation of the between-patient and within-patient variation present in our longitudinal data. RESULTS: At the time of the first available radiograph, mean (SD) levels of functional disability, global severity, and pain were 1.3 (0.7), 39.4 (21.0), and 1.1 (0.7), respectively. At entry into the study, the average radiograph score was 49.7 and upon leaving the study it was 66.9. Patients were followed an average of 6.7 years, with radiograph scores increasing at an average rate of 2.5 units/yr. The Spearman correlation [95% confidence interval (CI)] between average per-patient radiograph score and average per-patient HAQ disability index, average per-patient global severity, average per-patient pain score, and average per-patient direct medical costs was, respectively, 0.42 (0.26, 0.55), 0.23 (0.06, 0.39), 0.20 (0.03, 0.36), and 0.06 (-0.11, 0.23). The mean slope (95% CI) for disability on radiograph score was 0.0186 (0.0132, 0.0226), for severity on radiographs 0.1889 (0.1295, 0.2498), and for pain on radiographs 0.0057 (0.0027, 0.0084). As an example, over 10 years, a 25 unit (i.e., 50%) increase in radiograph scores would, on average, be associated with a 0.46 unit (i.e., 35%) increase in disability, a 4.72 unit (12%) increase in global severity score, and a 0.14 unit (13%) increase in pain, all expressed on the HAQ scales. There was little association between radiograph score and direct medical costs. CONCLUSION: A clinically meaningful association exists between radiographic damage and self-reported functional disability, suggesting that interventions that slow radiographic progression may improve the patient's health status. Such a relationship was not observed between radiographic damage and direct medical costs. 相似文献
728.
Clinical and neonatal screening methods using a tandem mass spectrometer are clearly a model for modern laboratory testing in the new Millennium. By the year 2000, more than 1 million blood and plasma samples will have been tested in laboratories throughout the world for a battery of metabolic disorders using a tandem mass spectrometer as the primary analytical device. A tandem mass spectrometer is considered the "ultimate" analytical detector in a variety of biochemical and clinical methods because of its very high accuracy, selectivity, precision, versatility and robust nature. The ability to achieve very high and reproducible sample throughput (∼600 samples/ instrument/24 h) has made this technology cost-effective for newborn screening. In order to reliably measure markers of inborn errors of metabolism while maintaining low costs and high efficiency, accuracy and quality, much attention needs to be placed on monitoring and maintenance of all components of the entire testing system. These components include specimen collection and sample preparation methods, analysis by LC tandem mass spectrometry, conversion of raw mass spectra (data) into clinically meaningful results (concentration), expert interpretation of these results so that the clinician can be provided with information to facilitate a diagnose, and follow-up and education so that the maximum benefits of newborn screening translate into prevention of disease symptoms or more effective treatments. Addressing each part of the whole system will produce a quality screening program that will detect a battery of disorders using tandem mass spectrometry with a disease frequency of nearly 1 in 4000 infants. 相似文献
729.
Gelatinase B (MMP-9), but not its inhibitor (TIMP-1), dictates the growth rate of experimental thymic lymphoma. 总被引:3,自引:0,他引:3
F Aoudjit S Masure G Opdenakker E F Potworowski Y St-Pierre 《International journal of cancer. Journal international du cancer》1999,82(5):743-747
Dysregulation of metalloproteinase production at tumor sites contributes to the modification of local stromal tissue necessary for tumor development. Gelatinase B (matrix metalloproteinase-9, MMP-9) is one of the key enzymes that have been associated with the progression of several tumors. Paradoxically, MMP-9 expression by tumor cells, most notably by lymphoma cells, is concomitant with the expression of its physiological inhibitor, TIMP-1. Not only are both genes often co-expressed in the most aggressive forms of lymphomas but also both are up-regulated upon contact with stromal cells. Since TIMP-1 is known to regulate growth in several cell types and some aggressive lymphoma cells express TIMP-1 constitutively without MMP-9, it is unclear whether the over-expression of MMP-9 is counterbalanced by TIMP-1 and whether TIMP-1 expression alone could favor the development of lymphoma. To gain further insight into the respective roles of MMP-9 and TIMP-1 in lymphoma, we generated lymphoma cell lines expressing constitutively high levels of MMP-9 or TIMP-1 and compared these cells for the ability to form thymic lymphoma in vivo. Moreover, we generated lymphoma cell lines expressing constitutively high levels of both MMP-9 and TIMP-1 to reproduce the net physiological balance resulting from the expression of both genes simultaneously and to determine which gene overrides the other. Our results show that mice injected with lymphoma cells expressing MMP-9 constitutively developed thymic lymphoma more rapidly than those injected with control lymphoma cells. Over-expression of TIMP-1 alone did not significantly influence tumor progression of lymphoma nor did it delay the capacity of MMP-9 to accelerate the development of thymic lymphoma. 相似文献
730.
The peach latent mosaic viroid (PLMVd) is a small, circular RNA species that has been shown to induce RNA silencing in plants. With the goal of better understanding the biological mechanism underlying this process, the siRNAs found in PLMVd infected peach leaves were isolated and sequenced. Analysis of the resulting data prompted several conclusions, including: i. PLMVd strands of both polarities are substrates for the Dicer-like enzymes found in peach leaves; ii. the more highly structured regions of PLMVd trigger the activity of the Dicer-like enzymes; and, iii. the circular PLMVd conformers appear to be favored for transport into the cytoplasm. 相似文献