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51.
Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators. 相似文献
52.
53.
This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
54.
Fernando Corvillo Laura Gonzlez-Snchez Alberto Lpez-Lera Emilia Arjona Giovanni Ceccarini Ferruccio Santini David Araújo-Vilar Rebecca J Brown Joan Villarroya Francesc Villarroya Santiago Rodríguez de Crdoba Teresa Caballero Pilar Nozal Margarita Lpez-Trascasa 《International journal of molecular sciences》2021,22(12)
55.
In this paper, we propose a content-based method the for semi-automatic organization of photo albums based on the analysis of how different users organize their own pictures. The goal is to help the user in dividing his pictures into groups characterized by a similar semantic content. The method is semi-automatic: the user starts to assign labels to the pictures and unlabeled pictures are tagged with proposed labels. The user can accept the recommendation or made a correction. To formulate the suggestions is exploited the knowledge encoded in how other users have partitioned their images. The method is conceptually articulated in two parts. First, we use a suitable feature representation of the images to model the different classes that the users have collected, second, we look for correspondences between the criteria used by the different users. Boosting is used to integrate the information provided by the analysis of multiple users. A quantitative evaluation of the proposed approach is obtained by simulating the amount of user interaction needed to annotate the albums of a set of members of the flickr® photo-sharing community. 相似文献
56.
The purpose of this study was to characterize the physicochemical properties of calcific deposits that cause the failure of tissue-derived heart valve bioprostheses. This was done in an effort to understand the mechanism of pathologic biomineralization in the cardiovascular system and potentially prevent deterioration of bioprostheses. Calcific deposits taken from 10 failed bioprosthetic valves that had been implanted in patients for 2-13 years were characterized by chemical analysis, x-ray diffraction, FTIR spectroscopy, scanning electron microscopy, polarized light microscopy, and solubility measurements. The combined results identified the biomineral as an apatitic calcium phosphate salt with substantial incorporation of sodium, magnesium and carbonate. The average Ca/PO4 ratio for this "young" pathologic biomineral was approximately 1.3, considerably lower than approximately 1.7 found in mature atherosclerotic plaque biomineral and mature skeletal biomineral, both of which approximate hydroxyapatite in composition. Deproteinated calcific deposits from bioprostheses had thermodynamic solubilities comparable to those of both atherosclerotic plaque, typical pathologic biomineral and hydrolyzed octacalcium phosphate (OCP, Ca4H(PO4)3 x 2.5 H2O), a proposed precursor phase to biomineral apatite. This later finding, together with chemical composition and structural details of the bioprosthetic deposits themselves, supports a mechanism of cardiovascular calcification in which OCP plays a crucial role in the formation of the final apatitic phase. This suggests an approach toward prevention of bioprosthetic tissue calcification through control of the formation of the kinetically favored OCP precursor and/or its transformation into bioapatite. 相似文献
57.
MB Hossain D van der Helm FJ Schmitz EO Pordesimo RA Magarian KL Meyer LB Overacre BW Day 《Canadian Metallurgical Quarterly》1994,37(11):1670-1683
Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity. 相似文献
58.
EH Hopman FJ Voorhorst P Kenemans CJ Meyer TJ Helmerhorst 《Canadian Metallurgical Quarterly》1995,58(2):206-209
The purpose of this work was to study intraobserver and interobserver variation in the interpretation of colposcopic images of cervical intraepithelial neoplasia (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic images presented on slides and to select the biopsy site. Eleven cases were independently interpreted twice with an interval of 2-3 months by all observers. No information about the cytological classification was available. In each case the "majority assessment" was considered as the standard, being "no CIN" in 2 cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was found to be 52.4 and 51.0% in the first and second sessions, respectively, while the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for biopsy, 77.4% of all observers agreed while the same site was selected in 85.3% of cases by the individual colposcopist in the two sessions. Overall, CIN I and II interpretations revealed lower levels of agreement than no CIN or CIN III interpretations. It is concluded that observer variability in interpreting colposcopic images and selecting the site for biopsy is in the same range as observer variation in other subjective diagnostic tests such as cytology and histopathology. This variation should be taken into account in the colposcopical management of patients with abnormal cytology. 相似文献
59.
The myth of Eve: molecular biology and human origins 总被引:1,自引:0,他引:1
FJ Ayala 《Canadian Metallurgical Quarterly》1995,270(5244):1930-1936
It has been proposed that modern humans descended from a single woman, the "mitochondrial Eve" who lived in Africa 100,000 to 200,000 years ago. The human immune system DRB1 genes are extremely polymorphic, with gene lineages that coalesce into an ancestor who lived around 60 million years ago, a time before the divergence of the apes from the Old World monkeys. The theory of gene coalescence suggests that, throughout the last 60 million years, human ancestral populations had an effective size of 100,000 individuals or greater. Molecular evolution data favor the African origin of modern humans, but the weight of the evidence is against a population bottleneck before their emergence. The mitochondrial Eve hypothesis emanates from a confusion between gene genealogies and individual genealogies. 相似文献
60.
The effects of placement of a miniature implantable stimulator on motor unit recruitment were examined in the posterior head of cat biceps femoris. The implantable stimulator (13-mm long x 2-mm diameter) was injected either proximally near the main nerve branch, or distally near the muscle insertion, through a 12-gauge hypodermic needle. Glycogen-depletion methods were used to map the distribution of fibers activated by electrical stimulation. Muscle fibers were found to be depleted at most or all proximodistal levels of the muscle, but the density of depleted fibers varied transversely according to the stimulus strength and proximity of the device to the nerve-entry site. Thus, muscle cross sections often had a "patchy" appearance produced because different proportions of depleted fibers intermingled with undepleted fibers in different parts of the cross section. In other preparations, the force of muscle contraction was measured when stimuli of varying strengths were delivered by the stimulator positioned at the same proximal or distal sites within the muscle. Devices placed close to the nerve-entry site produced the greatest forces. Those placed more distally produced less force. As stimulus current and/or pulse width increased, muscle force increased, often in steps, until a maximum was reached, which was usually limited by the compliance voltage of the device to less than the force produced by whole nerve stimulation. 相似文献