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991.
Introduction
Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model.Measurements and Methods
Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group): SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP) and sham-operated group. We used a N2 pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP), urine output, oxygenation parameters(e.g., SvO2, PO2, PaCO2), peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine) were recorded. Histological examination of liver, intestine, pancreas, and lung was performed.Main Results
Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in SvO2. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP.Conclusions
Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH/ACS-induced exacerbation and to optimize the treatment strategies for counteracting the development of organ dysfunction. 相似文献992.
Ke F Voss A Kerr JB O'Reilly LA Tai L Echeverry N Bouillet P Strasser A Kaufmann T 《Cell death and differentiation》2012,19(6):915-925
BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in Eμ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues. 相似文献
993.
Guang-Lei Liu Ke Wang Ming-Xia Hua Muhammad Aslam Buzdar Zhen-Ming Chi 《Process Biochemistry》2012,47(5):822-827
The psychrotolerant yeast Mrakia frigida 2E00797 isolated from sea sediments in Antarctica was found to be able to produce killer toxin against Metschnikowia bicuspidata, Candida tropicalis and Candida albicans. In the present study, the killer toxin was purified and characterized. The molecular weight of the purified killer toxin was estimated to be 55.6 kDa and the purified killer toxin shared 35.1% sequence homology with a protein kinase. The purified killer toxin's optimal temperature and pH for killing activity were 16 °C and 4.5, respectively, and it was stable in the temperature range from 10 to 25 °C at pH 4.5. The toxin's highest killing activity was observed in the presence of 3.0 g/100 ml NaCl. The purified killer toxin was able to actively kill whole cells of M. bicuspidata but could not kill the protoplast of the sensitive yeast. Of the eight yeast species tested in this study, the killer toxin was able to kill C. tropicalis and C. albicans in addition to M. bicuspidata. 相似文献
994.
Opticin, a small leucine rich repeat protein (SLRP) contributes to vitreoretinal adhesion. This study was conducted to investigate the effects of hypoxia and vascular endothelial growth factor (VEGF) on matrix metalloproteinase (MMP) mediated opticin production in retinal pigment epithelium (RPE) cells. Primary cultured human RPE cells were treated with hypoxia (low oxygen and cobalt chloride) or VEGF (0-100 ng/mL). The mRNA levels of opticin and the protein levels of intra and extracellular opticin in RPE cells were examined by RT-PCR and Western blot assay, respectively. Furthermore, the MMP activity was analyzed by zymography, and EDTA was used as an MMP inhibitor. Analysis of the effect of MMP-2 on opticin was performed by recombinant human (rh) MMP-2 stimulation in RPE cultures and by human vitreous sample digestion with activated rhMMP-2. Our results showed that opticin was expressed by primary cultured human RPE cells. Hypoxia and VEGF stimulation did not alter opticin mRNA and protein expression in RPE cells, but markedly decreased the protein levels of extracellular opticin following increased latent MMP-2 activity. The VEGF- and hypoxia induced opticin degradation in the culture medium was blocked by EDTA. Together, opticin levels in the culture medium were also reduced after rhMMP-2 treatment. In addition, opticin in human vitreous samples could be cleaved by rhMMP-2. These results reveal that VEGF and hypoxia could decrease opticin protein levels in the human RPE secretome, and that opticin may be an enzymatic substrate for MMP-2. 相似文献
995.
996.
Wei Ke Priyaranjan Pattanaik Christopher R. Bethel Anjaneyulu Sheri John D. Buynak Robert A. Bonomo Focco van den Akker 《PloS one》2012,7(11)
Bacterial β-lactamase enzymes are in large part responsible for the decreased ability of β-lactam antibiotics to combat infections. The inability to overcome β-lactamase mediated resistance spurred the development of inhibitors with penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, “suicide-type” inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of β-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine β-lactamases. 相似文献
997.
Jie Tian Jie Ma Ke Ma Bin Ma Xinyi Tang Samuel Essien Baidoo Jia Tong Jun Yan Liwei Lu Huaxi Xu Shengjun Wang 《PloS one》2012,7(10)
Background
β-Glucans have been shown to function as a potent immunomodulator to stimulate innate and adaptive immune responses, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Glucocorticoid-induced TNF receptor ligand (GITRL), a member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells, generates a positive co-stimulatory signal implicated in a wide range of T cell functions, which is important for the development of immune responses.Methodology/Principal Findings
In this study, we found that whole β-glucan particles (WGPs) could activate dendritic cells (DCs) via dectin-1 receptor, and increase the expression of GITRL on DCs in vitro and in vivo. Furthermore, we demonstrated that the increased GITRL on DCs could impair the regulartory T cell (Treg)-mediated suppression and enhance effector T cell proliferation in a GITR/GITRL dependent way. In tumor models, DCs with high levels of GITRL were of great potential to prime cytotoxic T lymphocyte (CTL) responses and down-regulate the suppressive activity of Treg cells, thereby leading to the delayed tumor progression.Conclusions/Significance
These findings suggest that particulate β-glucans can be used as an immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate suppressive immune activity via GITR/GITRL interaction, leading to a more efficient defense mechanism against tumor development. 相似文献998.
A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells. 相似文献
999.
Aunchalee Thanwisai Sarunporn Tandhavanant Natnaree Saiprom Nick R. Waterfield Phan Ke Long Helge B. Bode Sharon J. Peacock Narisara Chantratita 《PloS one》2012,7(9)
Xenorhabdus and Photorhabdus spp. are bacterial symbionts of entomopathogenic nematodes (EPNs). In this study, we isolated and characterized Xenorhabdus and Photorhabdus spp. from across Thailand together with their associated nematode symbionts, and characterized their phylogenetic diversity. EPNs were isolated from soil samples using a Galleria-baiting technique. Bacteria from EPNs were cultured and genotyped based on recA sequence. The nematodes were identified based on sequences of 28S rDNA and internal transcribed spacer regions. A total of 795 soil samples were collected from 159 sites in 13 provinces across Thailand. A total of 126 EPNs isolated from samples taken from 10 provinces were positive for Xenorhabdus (n = 69) or Photorhabdus spp. (n = 57). Phylogenetic analysis separated the 69 Xenorhabdus isolates into 4 groups. Groups 1, 2 and 3 consisting of 52, 13 and 1 isolates related to X. stockiae, and group 4 consisting of 3 isolates related to X. miraniensis. The EPN host for isolates related to X. stockiae was S. websteri, and for X. miraniensis was S. khoisanae. The Photorhabdus species were identified as P. luminescens (n = 56) and P. asymbiotica (n = 1). Phylogenenic analysis divided P. luminescens into five groups. Groups 1 and 2 consisted of 45 and 8 isolates defined as subspecies hainanensis and akhurstii, respectively. One isolate was related to hainanensis and akhurstii, two isolates were related to laumondii, and one isolate was the pathogenic species P. asymbiotica subsp. australis. H. indica was the major EPN host for Photorhabdus. This study reveals the genetic diversity of Xenorhabdus and Photorhabdus spp. and describes new associations between EPNs and their bacterial symbionts in Thailand. 相似文献
1000.
Z Qiaoli H Jianfeng W De W Zijun Z Xinguang Z Haojie D Fan L Zhiquan W Shiwen H Zhenyu Z Yonghui K Changwen Y Dakang L Wenjia L Deqiong C Pinghua 《PloS one》2012,7(8):e42830