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排序方式: 共有101条查询结果,搜索用时 31 毫秒
1.
OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia. 相似文献
2.
C. M. Windle I. F. G. Hampton P. Hardcastle M. J. Tipton 《European journal of applied physiology and occupational physiology》1994,68(3):194-199
Two experiments were undertaken to investigate the effects of warming the body upon the responses during a subsequent cold water immersion (CWI). In both experiments the subjects, wearing swimming costumes, undertook two 45-min CWIs in water at 15° C. In experiment 1, 12 subjects exercised on a cycle ergometer until their rectal temperatures (T
re) rose by an average of 0.73°C. They were then immediately immersed in the cold water. Before their other CWI they rested seated on a cycle ergometer (control condition). In experiment 2, 16 different subjects were immersed in a hot bath (40° C) until their T
re rose by an average of 0.9° C; they were then immediately immersed in the cold water. Before their other CWI they were immersed in thermoneutral water (35° C; control condition). Heart rate in both experiments and respiratory frequency in experiment 1 were significantly (P < 0.05) higher during the first 30 s of CWI following active warming. In experiment 1, the rate of fall of T
re during the final 15 min of CWI was significantly (P < 0.01) faster when CWI followed active warming (2.46° C · h–1) compared with the control condition (1.68°C · h–1). However, this rate was observed when absolute T
re was still above that seen in the control CWIs. It is possible, therefore, that if longer CWIs had been undertaken, the two temperature curves may have converged and thereafter fallen at similar rates; this was the case with the aural temperature (T
au) seen in experiment 1 and the T
au and T
re in experiment 2. It is concluded that pre-warming is neither beneficial nor detrimental to survival prospects during a subsequent CWI. 相似文献
3.
Valerie Gray Hardcastle 《Biology & philosophy》1993,8(2):173-192
I examine the branch of evolutionary epistemology which tries to account for the character of cognitive mechanisms in animals and humans by extending the biological theory of evolution to the neurophysiological substrates of cognition. Like Plotkin, I construe this branch as a struggling science, and attempt to characterize the sort of theory one might expect to find this truly interdisciplinary endeavor, an endeavor which encompasses not only evolutionary biology, cognitive psychology, and developmental neuroscience, but also and especially, the computational modeling of artificial life programming; I suggest that extending Schaffner's notion of interlevel theories to include both horizontal and vertical levels of abstraction best fits the theories currently being developed in cognitive science. Finally, I support this claim with examples drawn from computational modeling data using the genetic algorithm. 相似文献
4.
Sex cell contact in Chlamydomonas is due to complementary sex-specific glycoproteins (mating-type substances, MTSs). Their interaction causes an instantaneous but labile flagella agglutination between sexually different gametes. The dynamic nature of this contact permits partner exchange between agglutinated gametes and accounts for the transitoriness of the contact, flagella adhesion being terminated upon ensuing pairing. This paper describes molecular events that underlie the adhesion potential of differentiated (+) gametes. In the contact-establishing interaction with its receptors on the (?) flagella, the agglutinin of differentiated (+) gametes is inactivated. Compensating for this inactivation, the adhesion potential of gametes in agglutination is sustained by continuous replenishment of the inactivated MTS by newly synthesized units. If this glycoprotein neosynthesis is blocked by tunicamycin (TUM), the adhesiveness of differentiated (+) gametes ceases. It is postulated that this complex interaction with incapacitation and neosynthesis forms the basis of the dynamic nature of the flagella contact and eventually accounts for its termination at pairing. 相似文献
5.
The periodic banding pattern of stained collagen fibrils observed in the electron microscopic can be correlated with the charge distribution deduced from the amino acid sequence. Earlier work used alpha 1 chain sequence data only. The present study incorporates alpha 2 as well as alpha 1 sequence data, so that the complete distribution of charged residues is used. Correlation is improved if it is supposed that the extrahelical terminal regions are contracted. The optimal value of the periodicity, D, (previously 232.3 +/- 0.5 residues using alpha 1 data only), is now 234.2 +/- 0.5 residues, assuming uniform spacing of residues in the helical body of the molecule. This value agrees better with values obtained by others from analyses of interactions between molecules, using sequence data alone. Using the improved value of D, the relative axial locations of the charged residues in the fibril are displayed. In this way, the charged residues contributing to each band in the fibril staining pattern can be identified. 相似文献
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8.
Davies TG Bentley J Arris CE Boyle FT Curtin NJ Endicott JA Gibson AE Golding BT Griffin RJ Hardcastle IR Jewsbury P Johnson LN Mesguiche V Newell DR Noble ME Tucker JA Wang L Whitfield HJ 《Nature structural biology》2002,9(10):745-749
Aberrant control of cyclin-dependent kinases (CDKs) is a central feature of the molecular pathology of cancer. Iterative structure-based design was used to optimize the ATP- competitive inhibition of CDK1 and CDK2 by O(6)-cyclohexylmethylguanines, resulting in O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine. The new inhibitor is 1,000-fold more potent than the parent compound (K(i) values for CDK1 = 9 nM and CDK2 = 6 nM versus 5,000 nM and 12,000 nM, respectively, for O(6)-cyclohexylmethylguanine). The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. Cellular studies with O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino) purine demonstrated inhibition of MCF-7 cell growth and target protein phosphorylation, consistent with CDK1 and CDK2 inhibition. The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions. 相似文献
9.
Sara L. Payne Sonsoles Rodriguez-Aristegui Julia Bardos Céline Cano Bernard T. Golding Ian R. Hardcastle Marcus Peacock Nahida Parveen Roger J. Griffin 《Bioorganic & medicinal chemistry letters》2010,20(12):3649-3653
Replacement of the core heterocycle of a defined series of chromen-4-one DNA-PK inhibitors by the isomeric chromen-2-one (coumarin) and isochromen-1-one (isocoumarin) scaffolds was investigated. Structure–activity relationships for DNA-PK inhibition were broadly consistent, albeit with a reduction of potency compared with the parent chromenone. 相似文献
10.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献