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101.
D.?C.?Melles L.?Schouls P.?Fran?ois S.?Herzig H.?A.?Verbrugh A.?van?Belkum J.?Schrenzel 《European journal of clinical microbiology & infectious diseases》2009,28(1):39-45
This study investigates aspects of the general assumption that, in bacteria, genetic variation in functionally-constrained
genomic regions accumulates at a lower rate than in regions of hypermutability such as DNA repeat loci. We compared whole
genome polymorphism (using high-throughput amplified fragment length polymorphism [ht-AFLP]) as well as short sequence repeat
length variation (using multi-locus variable number of tandem repeat analysis [MLVA]) for 994 Staphylococcus aureus strains isolated from both healthy carriers and invasive infections. MLVA and ht-AFLP minimum spanning trees (MSTs) were
similar in their identification of totally different types of genetic variants. This suggests that, despite the enhanced inherent
variability of repeats, clusters of strains remain traceable. Finally, no specific molecular marker of epidemicity or virulence
was identified in this large strain collection by the MLVA approach. We demonstrate that there is a difference in the rates
of cross-genome mutation versus regional repeat variability in the clonal bacterial pathogen S. aureus. Despite these dynamic differences, a conservation of type assignments as based upon these two inherently different typing
techniques was observed. 相似文献
102.
HT Syyong HHC Yang G Trinh C Cheung KH Kuo C van Breemen 《British journal of pharmacology》2009,156(4):587-600
Background and purpose:
Uridine 5''-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca2+ waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca2+ waves in VSMCs of the rat basilar artery.Experimental approach:
Isometric force and intracellular Ca2+ ([Ca2+]i) were measured in endothelium-denuded rat basilar artery using wire myography and confocal microscopy respectively.Key results:
Uridine 5''-triphosphate (0.1–1000 µmol·L−1) concentration-dependently induced tonic contraction (pEC50 = 4.34 ± 0.13), associated with sustained repetitive oscillations in [Ca2+]i propagating along the length of the VSMCs as asynchronized Ca2+ waves. Inhibition of Ca2+ reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca2+ waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca2+ waves by 40% and tonic contraction by 52%, and the nifedipine-insensitive component was abolished by SKF-96365, an inhibitor of receptor- and store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na+/Ca2+ exchange. Ongoing Ca2+ waves and tonic contraction were also abolished after blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2-aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine-sensitive SR Ca2+ stores prior to UTP stimulation prevented Ca2+ waves.Conclusions and implications:
Uridine 5''-triphosphate-induced Ca2+ waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca2+ release from the SR through inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca2+ waves requires SR Ca2+ reuptake from Ca2+ entry across the plasma membrane via L-type Ca2+ channels, receptor- and store-operated channels, and reverse-mode Na+/Ca2+ exchange. 相似文献103.
Denise A Castronovo Kenneth KH Chui Elena N Naumova 《Environmental health : a global access science source》2009,8(1):61
Background
Epidemiologic studies are often confounded by the human and environmental interactions that are complex and dynamic spatio-temporal processes. Hence, it is difficult to discover nuances in the data and generate pertinent hypotheses. Dynamic mapping, a method to simultaneously visualize temporal and spatial information, was introduced to elucidate such complexities. A conceptual framework for dynamic mapping regarding principles and implementation methods was proposed. 相似文献104.
The present study is the first report on the bioactivity of venom from the Australian theraphosid spider Selenotholus foelschei. Venom from female specimens was used in all experiments. Adult spiders yielded an average of 2.2 mg dried venom per milking with a maximum yield of 7.2 mg. To evaluate the activity of pooled S. foelschei venom in invertebrates, a toxicity test in crickets (Acheta domesticus) was used. The results suggest the presence of several insecticidal toxins with different but synergistic modes of action, leading to a fast onset of paralysis as well as persistent paralysis and lethal effects (starting at 4 h after injection) in crickets. Vertebrate activity of S. foelschei venom was tested by using the isolated chick biventer cervicis nerve-muscle preparation. The venom produced a significant reduction in baseline tension (at a concentration of 10 microg/mL) and twitch height (at 0.2-10 microg/mL). Twitches were not restored after repeated washing. The response of the muscle to exogenous acetylcholine (1 mM) and carbachol (0.02 mM) was not reduced by the venom. These results indicate the presence of a vertebrate-active neurotoxin in S. foelschei that irreversibly blocks muscle twitches by acting either on voltage-activated Na(+)-channels or on other pre-synaptically located receptors. 相似文献
105.
Through the GMG (modified law of health system) the section sign 116b "out-patients department" was newly introduced into the SGB V (5(th) social welfare legislation) in 2004. Thus, the health insurance companies had the possibility to come to an agreement with hospitals concerning rare illnesses such as haemophilia. On this basis a care agreement was agreed upon in 2005 between the University Hospital Eppendorf (Hamburg) and three big health insurance companies. The result leads to positive changes for all concerned: The patients were offered an optimal care through the link to the CCC and this with an adequate compensation for the coagulation section for out-patients. As the therapy programme became more clarified, the communication between the parties involved became more constructive. With the law to strengthen competition (WSG) for the insurance companies, a change of section sign 116b of the SGB V (5(th) social welfare legislation) came into force in 2007. Thus the legal basis for the a. m. agreement was withdrawn. It is now the task of the a. m. parties to find a way to secure the advantages obtained through this agreement, to the benefit of the patients, the coagulation sections for out-patients and the cost bearers. 相似文献
106.
Herzig MC Liang H Johnson AE Woynarowska B Woynarowski JM 《Breast cancer research and treatment》2002,71(2):133-143
Caspase-3 deficiency can limit the efficiency of pro-apoptotic anticancer treatments. Irofulven (hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863) is an antitumor drug, currently in a Phase III and multiple Phase II trials, which can differentiate between tumor and normal cells in apoptosis induction. This study investigated whether apoptosis induced by irofulven requires caspase-3. Irofulven action was compared in breast cancer cells differing in caspase-3 status: deficient MCF-7 cells and proficient MDA-MB-231 cells and in normal human mammary epithelial cells, HMEC. Irofulven induces significant, concentration and time-dependent apoptotic DNA fragmentation in breast cancer cell lines, regardless of caspase-3 status. After 12, 24 and 48h incubation at 1M irofulven ( 3×GI50), fragmented DNA comprised 3.7, 14.1 and 34.6% and 8.4, 12.6 and 20.3% of total DNA in MCF-7 and MDA-MB-231 cells, respectively. Cell viability (trypan blue exclusion) remained largely unaffected during the first 24h but decreased markedly after 48h, indicating secondary necrosis. Net losses in cell numbers were apparent at 48h. Normal HMEC cells were refractory to 1M drug with only 3–9% fragmented DNA after 12–48h, although apoptosis was observed at drug levels >3M. The broad-spectrum caspase inhibitor Z-VAD-fmk inhibited irofulven-induced apoptosis of all cell lines at 20M with nearly complete abrogation of apoptosis at 100M. Irofulven treatment resulted in marginal caspase-3 processing in MDA-MB-231 and HMEC cells. These results indicate that whereas the caspase cascade mediates irofulven- induced apoptosis, caspase-3 is dispensable (supported by NIH CA70091 and CA78706). 相似文献
107.
108.
M. Vlasova A. K. Purhonen M. R. Jarvelin E. Rodilla J. Pascual K. H. Herzig 《Acta physiologica (Oxford, England)》2010,200(2):107-127
It has been well documented that obesity is a major risk factor for the development of the hypertensive state. The correlation between body mass index and blood pressure level is well established. Nevertheless, the exact mechanisms which contribute to obesity-related hypertension remain poorly understood. In the last years, we have realized that the white adipose tissue is not just an inert organ for nutrient storage and isolation but rather depending on the body mass index the biggest endocrinological organ. Thus, the possible contribution of adipokines to the blood pressure elevation becomes an attractive hypothesis to explain the hypertensive state that often occurs in obesity. In this review, we consider direct and indirect effects of main adipokines on structural and functional changes in the cardiovascular system. 相似文献
109.
110.