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101.
Thierbach R Schulz TJ Isken F Voigt A Mietzner B Drewes G von Kleist-Retzow JC Wiesner RJ Magnuson MA Puccio H Pfeiffer AF Steinberg P Ristow M 《Human molecular genetics》2005,14(24):3857-3864
We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals. 相似文献
102.
We present the cloning of 10 N-methyl-D-aspartate (NMDA) receptor subunits from the zebrafish. These subunits fall into five subtypes, each containing two paralogous genes. Thus, we report two NMDAR1 genes (NR1.1 and NR1.2), and eight NMDAR2 genes, designated NR2A.1 and NR2A.2, NR2B.1 and NR2B.2, NR2C.1 and NR2C.2, and NR2D.1 and NR2D.2. The predicted sequences of the NR1 paralogs display 90% identity to the human protein. The NR2 subunits show less identity, differing most at the N- and C-termini. The NR1 genes are both expressed embryonically, although in a nonidentical manner. NR1.1 is found in brain, retina, and spinal cord at 24 hours postfertilization (hpf). NR1.2 is expressed in the brain at 48 hpf but not in the spinal cord. NR2 developmental gene expression varies: both paralogs of the NR2A are expressed at 48 hpf in the retina, only one paralog of the NR2B is expressed at low levels in the heart at 48 hpf. Neither of the NR2C is expressed embryonically. Both paralogs of the NR2D are expressed: 2D.1 is in the forebrain, retina, and spinal cord at 24 hpf, whereas the 2D.2 is only found in the retina. Our findings demonstrate that the zebrafish can serve as a useful model system for investigating the role of NMDA receptors in the development of the nervous system. 相似文献
103.
KI Wheeler GM Schmölzer CJ Morley PG Davis 《Acta paediatrica (Oslo, Norway : 1992)》2011,100(1):67-70
Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency. 相似文献
104.
Battaglia C; Artini PG; Giulini S; Salvatori M; Maxia N; Petraglia F; Volpe A 《Human reproduction (Oxford, England)》1997,12(11):2477-2482
The objective of this study was to evaluate the Doppler flow variations
which occur following the use of different protocols of ovarian stimulation
in an IVF programme, and to investigate the thromboxane production by
cultured endometrial cells and its influence on embryo implantation. A
total of 60 patients underwent three different ovarian stimulation
protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short
GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler
analysis were performed before and during the treatment. On the day that
the Doppler examination took place, luteinizing hormone, follicle
stimulating hormone, plasma oestradiol and thromboxane concentrations were
assayed. On the day of oocyte retrieval, endometrial cells were collected
and cultured, and their thromboxane production evaluated. No significant
differences in hormonal, ultrasonographic or Doppler parameters were
observed between the three groups. Ten out of 56 patients who had a
successful embryo transfer became pregnant. In the group of pregnant women
the pulsatility index values of both uterine and spiral arteries was lower
than in non-pregnant patients, and was associated with significantly lower
thromboxane concentrations from cultured endometrial cells. It is concluded
that thromboxane plays a role in embryo implantation, and that Doppler flow
analysis of uterine and spiral arteries in infertile patients may be
important in the management of ovarian stimulation.
相似文献
105.
Catt SL; Sakkas D; Bizzaro D; Bianchi PG; Maxwell WM; Evans G 《Molecular human reproduction》1997,3(9):821-825
Controlling the sex of offspring by the separation of X and Y
chromosome-bearing spermatozoa using flow cytometry has been reported as a
clinical technique aiding prevention of X-linked diseases. Although this
technique has resulted in several hundred normal births in animals and at
least one human birth, there is still concern over its genetic safety due
to the involvement of two potentially mutagenic agents: UV light and the
fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly
those considered abnormal, may be more likely to suffer DNA damage
following exposure to mutagenic agents, compared with other mammalian
species. The stability of normal fresh and decondensed human spermatozoa
were examined after exposure to a range of levels of UV and H33342
staining, using an assay that detects endogenous nicks in the DNA of
spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed
human spermatozoa was examined following UV laser, H33342 staining and flow
cytometry treatments utilizing the same assay. There was an increase in the
presence of endogenous nicks when spermatozoa were decondensed compared
with fresh spermatozoa. There was no increase in the incidence of nicks in
any group of spermatozoa after UV and fluorochrome exposure compared with
controls without exposure.
相似文献
106.
Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. Many promoters in embryonic stem (ES) cells harbor a distinctive histone modification signature that combines the activating histone H3 Lys 4 trimethylation (H3K4me3) mark and the repressive H3K27me3 mark. These bivalent domains are considered to poise expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals. Recent advances shed light on the establishment and function of bivalent domains; however, their role in development remains controversial, not least because suitable genetic models to probe their function in developing organisms are missing. Here, we explore avenues to and from bivalency and propose that bivalent domains and associated chromatin-modifying complexes safeguard proper and robust differentiation. 相似文献
107.
Ventilator-associated pneumonia (VAP) is a common cause of morbidity, antibiotic use, increased length of stay and, possibly,
increased mortality in ICU patients. Colonization of the oropharyngeal cavity with potentially pathogenic micro-organisms
is instrumental in the pathogenesis of VAP, and selective oropharyngeal decontamination (SOD) with antibiotics (AB-SOD) or
antiseptics, such as chlorhexidine gluconate (CHX-SOD), has been associated with reduced incidences of VAP. In a recent issue
of Critical Care Scannapieco and colleagues investigated differences in oropharyngeal colonization between mechanically ventilated patients
receiving oropharyngeal decontamination with 0.12% CHX-SOD either once or twice daily compared to placebo. CHX-SOD was associated
with a reduction in Staphylococcus aureus colonization, but the study was underpowered to demonstrate a reduction in VAP incidence. We urgently need well-designed
and adequately powered studies to evaluate the potential benefits of CHX-SOD on patient outcome in ICUs. 相似文献
108.
Wolfgang H?rtig Andreas Reichenbach Cornelia Voigt Johannes Boltze Larysa Bulavina Martin U. Schuhmann Johannes Seeger Gerald F. Schusser Christiane Freytag Jens Grosche 《Journal of chemical neuroanatomy》2009,37(2):128-138
The simultaneous detection of glia, vessels and neurons facilitates insights into the complex chemoarchitecture of the central nervous system. Here, we present a simple, robust and versatile approach for the carbocyanine triple fluorescence labelling of neuronal, vascular and glial markers.The usefulness of this procedure is shown for rat brain tissue under physiological conditions, after traumatic brain injury caused by controlled cortical impact injury, and after stroke following middle cerebral artery occlusion. Moreover, the versatility of the method is verified by its application to sections from old triple transgenic mice with age-dependent β-amyloidosis and tau hyperphosphorylation in the hippocampus, modelling neuropathological alterations in Alzheimer‘s disease. To exemplify the usefulness of the approach for analysis of the enteric nervous system, it was applied to whole mounts from the horse intestine.The biotinylated lectin from potato (Solanum tuberosum) is presented as an excellent tool to detect both vessels and microglia. Furthermore, this lectin revealed macrophages after experimental insults, and senile plaques in aged triple transgenic mice. A large portion of astroglia was demonstrated by immunolabelling of glial fibrillary acidic protein. Neurons were detected by monoclonal antibodies directed against neuronal nuclei and, in horse tissues, mouse-anti-HuC/D recognizing a conserved nuclear protein. Confocal laser-scanning microscopy elucidated spatial relationships of the relevant markers and their pathological alterations after experimental insults and in transgenic mice with Alzheimer-like lesions. 相似文献
109.
In this article, the authors discuss different semi-quantitative methods for the analysis of global and regional myocardial function. Analysis of endocardial motion and direct measurements of myocardial velocities are the basic principles. The former is a two-dimensional technique which, however, requires good image quality and which is influenced by motion artefacts. The latter technique has a better signal to noise ratio and offers the opportunity to sufficiently quantify diastole. Strain rate imaging is a new and interesting way to display and evaluate regional myocardial deformation. 相似文献
110.
Risk of papillary thyroid cancer in women in relation to smoking and alcohol consumption 总被引:3,自引:0,他引:3
Rossing MA Cushing KL Voigt LF Wicklund KG Daling JR 《Epidemiology (Cambridge, Mass.)》2000,11(1):49-54
Both smoking and alcohol consumption may influence thyroid function, although the nature of these relations is not well understood. We examined the influence of tobacco and alcohol use on risk of papillary thyroid cancer in a population-based case-control study. Of 558 women with thyroid cancer diagnosed during 1988-1994 identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (N = 410). Controls (N = 574) were identified by random digit dialing, with a response proportion of 73.6%. We used logistic regression to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with cigarette smoking and alcohol consumption. A history of ever having smoked more than 100 cigarettes was associated with a reduced risk of disease (OR = 0.7, 95% CI = 0.5-0.9). This reduction in risk was most evident in current smokers (OR = 0.5, 95% CI = 0.4-0.7). Women who reported that they had ever consumed 12 or more alcohol-containing drinks within a year were also at reduced risk (OR 0.7, 95% CI = 0.5-1.0). Similar to the association noted with smoking, the reduction in risk was primarily present among current alcohol consumers. The associations we observed, if not due to chance, may be related to actions of cigarette smoking and alcohol consumption that reduce thyroid cell proliferation through effects on thyroid stimulating hormone, estrogen, or other mechanisms. 相似文献