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1.
H Dolk P De Wals Y Gillerot M F Lechat S Ayme M Cornel A Cuschieri E Garne J Goujard K M Laurence 《Teratology》1991,44(5):547-559
In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a population of 380,000 births in CEM were analysed to find if there were differences in the ratio of prevalence rates between UKI and CEM according to site of the defect and association with non-central nervous system (CNS) anomalies. The prevalence rate ratio was high for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida, and low for encephalocele, lower spina bifida, and anencephaly without other neural tube defects. There was a greater female excess for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida than for other defects in both geographic areas. There was a female excess for encephalocele in UKI but a male excess in CEM. Certain sites (anencephaly with accompanying spina bifida, iniencephaly, and encephalocele) were more likely to have accompanying non-CNS anomalies. The prevalence rate ratio of multiply malformed NTD was in general lower than for isolated NTD but showed the same pattern by site. The prevalence rate ratio was high for multiply malformed anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida. The sex ratio was similar between isolated and multiply malformed cases when site of the defect is taken into account. It is concluded that the geographic prevalence pattern and sex ratio differ according to site of NTD but do not differ substantially according to whether NTD is isolated or associated with non-CNS anomalies. 相似文献
2.
Suborganellar Localization and Molecular Characterization of Nonproteolytic Degraded Leukoplast Pyruvate Kinase from Developing Castor Oil Seeds 总被引:1,自引:1,他引:0
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Several genes involved in the ability of Synechococcus sp. PCC 7942 to grow under different CO2 concentrations were mapped in the genomic region of rbcLS (the operon encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase). Insertion of a cartridge encoding kanamycin resistance within open reading frame (ORF) 78, designated ccmJ, located 7 kb upstream of rbcLS, resulted in a kanamycin-resistant, high-CO2-requiring mutant, M3, which does not contain normal carboxysomes. ccmJ shows significant homology to csoS1 encoding a carboxysomal shell polypeptide in Thiobacillus neopolitanus. Analysis of the polypeptide pattern of a carboxysome-enriched fraction indicated several differences between the wild type and the mutant. The amount of the ribulose-1,5-bisphosphate carboxylase/oxygenase subunits was considerably smaller in the carboxysomal fraction of the mutant when compared to the wild type. On the basis of the sequence analyses, ORF286 and ORF466, located downstream of ccmJ, were identified as chlL and chlN, respectively, which are involved in chlorophyll biosynthesis in the dark. 相似文献
3.
George C. Nadăş Marian A. Taulescu Lidia Ciobanu Nicodim I. Fiţ Chirilă Flore Sorin Răpuntean Cosmina M. Bouari Cornel Catoi 《Mycopathologia》2013,175(3-4):221-230
Recent studies suggest that Candida albicans colonization is associated with several gastrointestinal inflammatory disorders and is also responsible for the delay in ulcer healing. No data are reported about the effects of C. albicans on the nonsteroidal anti-inflammatory drugs (NSAIDs)-induced necroinflammatory lesions. On the other hand, beneficial effects of NSAIDs regarding the colonization potential with C. albicans have been reported. Our aim was to investigate whether the association between NSAIDs and C. albicans could potentially induce necroinflammatory lesions in the guinea pigs gastric and enteral mucosa. Three interventional groups of 11 guinea pigs each were investigated after 5 days of receiving indomethacin, C. albicans or the association of both. C. albicans and necroinflammatory lesions were graded based on histological examinations. Statistical analysis used Mann–Whitney nonparametric test. NSAIDs did not significantly decrease C. albicans colonization grades on gastrointestinal mucosa. Administration of indomethacin subsequent to C. albicans determined significantly more severe necroinflammatory lesions compared to group that only received C. albicans. The association of NSAIDs and C. albicans did not cause significantly more severe degenerative or inflammatory lesions compared to the administration of only NSAIDs in this experimental model. Associations between NSAIDs and C. albicans caused significantly more severe necroinflammatory injuries than the lesions produced by C. albicans, without enhancing the mucosal injury or inflammation caused by NSAIDs. 相似文献
4.
Pingxi Xu Young-Moo Choo Julien Pelletier Fernando R. Sujimoto David T. Hughes Fen Zhu Elizabeth Atungulu Anthony J. Cornel Charles W. Luetje Walter S. Leal 《Journal of insect physiology》2013
The Southern house mosquito Culex quinquefasciatus has the largest repertoire of odorant receptors (ORs) of all mosquitoes and dipteran species whose genomes have been sequenced to date. Previously, we have identified and de-orphanized two ORs expressed in female antennae, CquiOR2 and CquiOR10, which are sensitive to oviposition attractants. In view of a new nomenclature for the Culex genome (VectorBase) we renamed these ORs as CquiOR21 (formerly CquiOR10) and CquiOR121 (CquiOR2). In addition, we selected ORs from six different phylogenetic groups for deorphanization. We cloned four of them by using cDNA from female antennae as a template. Attempts to clone CquiOR87 and CquiOR110 were unsuccessful either because they are pseudogenes or are not expressed in adult female antennae, the main olfactory tissue. By contrast, CquiOR1, CquiOR44, CquiOR73, and CquiOR161 were highly expressed in female antennae. To de-orphanize these ORs, we employed the Xenopus oocyte recording system. CquiORx–CquiOrco-expressed oocytes were challenged with a panel of 90 compounds, including known oviposition attractants, human and vertebrate host odorants, plant kairomones, and naturally occurring repellents. While CquiOR161 did not respond to any test compound in two different laboratories, CquiOR1 showed the features of a generic OR, with strong responses to 1-octen-3-ol and other ligands. CquiOR44 and CquiOR73 showed preference to plant-derived terpenoids and phenolic compounds, respectively. While fenchone was the best ligand for the former, 3,5-dimethylphenol elicited the strongest responses in the latter. The newly de-orphanized ORs may be involved in reception of plant kairomones and/or natural repellents. 相似文献
5.
Umans VA Cornel JH Velthoven SS Kloeg P Bartels P Bronzwaer J 《International journal of cardiovascular interventions》1999,2(4):223-230
BACKGROUND: Although balloon angioplasty has assumed an important role in the management of refractory unstable angina (UA), that is, UA that does not respond to conventional therapy, it is limited by complications related to thrombosis and acute coronary occlusion. The complication rate is higher in patients with UA than in those whose condition is stable. Preprocedural use of abciximab, a monoclonal platelet glycoprotein IIb/IIIa receptor blocker, has been used effectively in patients with UA, but its acceptance may be limited by safety concerns and economic constraints. The current trial investigated a protocol for abciximab pretreatment in patients with UA awaiting transfer from referring hospitals to a site of intervention (the 'drip and ship' protocol). AIMS: This observational study was conducted to evaluate whether a prophylactic, preprocedural regimen of abciximab can be safely and effectively administered to UA patients in referring hospitals while awaiting coronary angioplasty at the interventional clinic. METHODS: From April 1996 to December 1998, 168 consecutive patients with refractory UA (Braunwald class II or III) received abciximab prospectively at the referring clinic before undergoing PTCA or stent implantation at the interventional clinic. The following cost-conscious protocol was used: a 0.25 mg/kg bolus of abciximab followed by 10 micro g/min intravenously for 16 hours, in addition to intravenous nitrates, heparin and aspirin therapy. Patients were then transferred to a facility with PTCA capability via high-speed ambulance transport. No specific alterations of routine-transfer protocol were needed. Platelet aggregation studies were conducted during abciximab infusion. All interventions were performed while abciximab was given. Procedural and clinical success and long-term outcomes also were assessed. RESULTS: The primary angiographic success rate (patients with post-PTCA diameter stenosis < 50%) was 98%, and the in-hospital clinical success rate (angiographic success without major complications) was 98%. No major bleeding complications occurred during the abciximab pretreatment period. Platelet aggregation findings in the study patients showed a stable inhibition of >80% at the time of angioplasty. At 30-day follow-up, all patients were alive and 91% were free of major adverse events. Outcomes of balloon angioplasty and stenting were equally favorable, indicating no device-specific effect. Event-free survival at six months was 89% with a target vessel revascularization rate of 10%. CONCLUSION: Abciximab was administered safely and effectively to angioplasty patients with refractory UA awaiting transfer from a noninterventional setting to the site of angioplasty. These results extend the current knowledge base that has been established in randomized trials performed in interventional centers. The study protocol potentially could make abciximab therapy more feasible economically, and therefore more widely available to patients who are most likely to benefit from prophylactic administration. 相似文献
6.
The scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products. 相似文献
7.
Background
A large body of data derived from animal, epidemiological and clinical studies indicate that n-3 polyunsaturated fatty acids have a favourable effect on the prognosis of patients with cardiovascular disease in general, and on reducing sudden death in particular. Depressed heart rate variability (HRV), an indicator of impairment of the autonomic nervous system, has been shown to be a powerful predictor of subsequent mortality in patients surviving an acute myocardial infarction. A multitude of studies have demonstrated this strong association, suggesting that the imbalance in the sympathic/parasympathetic system may facilitate emergence of ventricular arrhythmias. Heart rate variability parameters will be assessed in the present study, with the primary objective of evaluating the possible superiority of Omacor (a highly refined, concentrated omega-3 fatty acid) versus placebo in improving HRV from baseline to endpoint in patients with recent uncomplicated myocardial infarction. Both groups will receive optimal conventional treatment. The study will also explore and quantify improvement in time domain HRV indices and will assess the safety of administering Omacor to optimally treated post-infarction patients (conventional treatment).Methods
This multi-centre study will evaluate the effect of Omacor 1 g, o.d. on time-domain HRV parameters in comparison to placebo o.d. in patients with recent uncomplicated transmural myocardial infarction. Patients will be screened during the first few days after the acute event as appropriate for the patient's condition, and after obtaining informed consent. Based on inclusion/exclusion criteria, a first 24-hour Holter recording will be performed. Two to five days later, screened patients still eligible for the study will undergo a second 24-hour Holter recording. After the second Holter recording, all patients will be randomly allocated to treatment with Omacor 1 g, o.d. or placebo o.d. One hundred patients will be followed in double-blind fashion for a six-month period after randomization. Visits, including 24-hour Holter recording and assessment of adverse events, will take place at one-month intervals ± five days after randomization, i.e., six times in all. 相似文献8.
Teratogen-induced activation of ERK, JNK, and p38 MAP kinases in early postimplantation murine embryos 总被引:1,自引:0,他引:1
BACKGROUND: Although many teratogens are known to activate apoptotic pathways culminating in abnormal development, little is known about how the embryo transduces a teratogenic exposure into specific responses. Signal reception and transduction are regulated by a number of signal transduction pathways, including the extracellular signal-regulated protein kinases (ERKs), c-Jun N-terminal kinases (JNKs) and the stress-activated protein kinase, p38. METHODS: To analyze the effects of teratogens on MAP kinases, we used whole embryo culture, Western blot analyses, and antibodies recognizing inactive or active MAP kinases, or both. RESULTS: We show that heat shock (HS) induces a rapid, strong, but transient activation of ERK, JNK, and p38 with maximal activation occurring within 30 min of the heat shock. By contrast, cyclophosphamide (CP) and staurosporine (ST) failed to activate ERK or JNK during the time period studied (7. 5 hr). ST and CP did induce a low but reproducible activation of p38 beginning at around 3 hr and 5 hr, respectively, after the initiation of exposure. Previous work has shown that heat shock induces elevated cell death in the embryo, primarily in the developing neuroepithelium, but not in the embryonic heart. Thus, we also compared the activation of these three MAP kinase pathways in heads, hearts, and trunks isolated from day 9 embryos exposed to 43 degrees C for 15 min. The results show that ERK, JNK, and p38 are activated in heads, hearts, and trunks. CONCLUSIONS: Our results show that day 9 embryos do activate MAP kinase signaling pathways in response to teratogenic exposures; however, activation of a particular pathway does not appear to be required for teratogen-induced apoptosis. 相似文献
9.
Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:15,自引:9,他引:6
The neutral theory of molecular evolution predicts that the ratio of
polymorphisms to fixed differences should be fairly uniform across a region
of DNA sequence. Significant heterogeneity in this ratio can indicate the
effects of balancing selection, selective sweeps, mildly deleterious
mutations, or background selection. Comparing an observed heterogeneity
statistic with simulations of the heterogeneity resulting from random
phylogenetic and sampling variation provides a test of the statistical
significance of the observed pattern. When simulated data sets containing
heterogeneity in the polymorphism-to-divergence ratio are examined,
different statistics are most powerful for detecting different patterns of
heterogeneity. The number of runs is most powerful for detecting patterns
containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic
is most powerful for detecting patterns in which one end of the gene has
high polymorphism and the other end has low polymorphism; and a newly
developed statistic, the mean sliding G statistic, is most powerful for
detecting patterns containing one or two peaks of polymorphism with reduced
polymorphism on either side. Nine out of 27 genes from the Drosophila
melanogaster subgroup exhibit heterogeneity that is significant under at
least one of these three tests, with five of the nine remaining significant
after a correction for multiple comparisons, suggesting that detectable
evidence for the effects of some kind of selection is fairly common.
相似文献
10.