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101.
Surface roughness mediates its effects on osteoblasts via protein kinase A and phospholipase A2 总被引:1,自引:0,他引:1
Barbara D. Boyan Victor L. Sylvia Yuhong Liu Ruben Sagun David L. Cochran Christoph H. Lohmann David D. Dean Zvi Schwartz 《Biomaterials》1999,20(23-24)
Earlier studies have shown that implant surface roughness influences osteoblast proliferation, differentiation, matrix synthesis and local factor production. Moreover, the responsiveness of osteoblasts to systemic hormones, such as 1,25-(OH)2D3, at the implant surface is also influenced by surface roughness and this effect is mediated by changes in prostaglandins. At present, it is not known which signaling pathways are involved in mediating cell response to surface roughness and how 1,25-(OH)2D3 treatment alters the activation of these pathways. This paper reviews a series of studies that have addressed this question. MG63 osteoblast-like cells were cultured on commercially pure titanium (cpTi) surfaces of two different roughnesses (Ra 0.54 and 4.92 μm) in the presence of control media or media containing 1,25-(OH)2D3 or 1,25-(OH)2D3 plus H8 (a protein kinase A inhibitor) or quinacrine (a phospholipase A2 inhibitor). At harvest, the effect of these treatments on cell number and alkaline phosphatase specific activity was measured. Compared to cultures grown on the smooth surface, cell number was reduced on the rough surface. 1,25-(OH)2D3 inhibited cell number on both surfaces and inhibition of protein kinase A in the presence of 1,25-(OH)2D3 restored cell number to that seen in the control cultures. Inhibition of phospholipase A2 in the presence of 1,25-(OH)2D3 caused a further reduction in cell number on the smooth surface, and partially reversed the inhibitory effects of 1,25-(OH)2D3 on the rough surface. Alkaline phosphatase specific activity was increased in cultures grown on the rough surface compared with those grown on the smooth surface; 1,25-(OH)2D3 treatment increased enzyme specific activity on both surfaces. Cultures treated with H8 and 1,25-(OH)2D3 displayed enzyme specific activity that approximated that seen in control cultures. Inhibition of phospholipase A2 also inhibited the 1,25-(OH)2D3-dependent effect on the smooth surface, but on the rough surface there was an inhibition of the 1,25-(OH)2D3 effect as well as a partial inhibition of the surface roughness-dependent effect. The results indicate that surface roughness and 1,25-(OH)2D3 mediate their effects through phospholipase A2, which catalyzes one of the rate-limiting steps in prostaglandin E2 production. Further downstream, prostaglandin E2 activates protein kinase A. 相似文献
102.
Alexander D. Orsi Paul K. Canavan Askhan Vaziri Ruben Goebel Onaly A. Kapasi Hamid Nayeb-Hashemi 《The Knee》2017,24(3):525-535
Background
Intercondylar notch impingement is detrimental to the anterior cruciate ligament (ACL). Notchplasty is a preventative remodeling procedure performed on the intercondylar notch during ACL reconstruction (ACLR). This study investigates how ACL graft geometry and both tibial and femoral insertion site location may affect ACL-intercondylar notch interactions post ACLR. A range of ACL graft sizes are reported during ACLR, from six millimeters to 11 mm in diameter. Variability of three millimeters in ACL insertion site location is reported during ACLR. This study aims to determine the post-operative effects of minor variations in graft size and insertion location on intercondylar notch impingement.Methods
Several 3D finite element knee joint models were constructed using three ACL graft sizes and polar arrays of tibial and femoral insertion locations. Each model was subjected to flexion, tibial external rotation, and valgus motion. Impingement force and contact area between the ACL and intercondylar notch compared well with experimental cadaver data from literature.Results
A three millimeter anterior–lateral tibial insertion site shift of the maximum size ACL increased impingement force by 242.9%. A three millimeter anterior–proximal femoral insertion site shift of the maximum size ACL increased impingement by 346.2%. Simulated notchplasty of five millimeters eliminated all impingement for the simulation with the greatest impingement. For the kinematics applied, small differences in graft size and insertion site location led to large increases in impingement force and contact area.Conclusions
Minor surgical variations may increase ACL impingement. The results indicate that notchplasty reduces impingement during ACLR. Notchplasty may help to improve ACLR success rates. 相似文献103.
Chen LM Rivailler P Hossain J Carney P Balish A Perry I Davis CT Garten R Shu B Xu X Klimov A Paulson JC Cox NJ Swenson S Stevens J Vincent A Gramer M Donis RO 《Virology》2011,412(2):401-410
The evolution of classical swine influenza viruses receptor specificity preceding the emergence of the 2009 H1N1 pandemic virus was analyzed in glycan microarrays. Classical swine influenza viruses from the α, β, and γ antigenic clusters isolated between 1945 and 2009 revealed a binding profile very similar to that of 2009 pandemic H1N1 viruses, with selectivity for α2-6-linked sialosides and very limited binding to α2-3 sialosides. Despite considerable genetic divergence, the ‘human-like’ H1N1 viruses circulating in swine retained strong binding preference for α2-6 sialylated glycans. Interspecies transmission of H1N1 influenza viruses from swine to humans or from humans to swine has not driven selection of viruses with distinct novel receptor binding specificities. Classical swine and human seasonal H1N1 influenza viruses have conserved specificity for similar α2-6-sialoside receptors in spite of long term circulation in separate hosts, suggesting that humans and swine impose analogous selection pressures on the evolution of receptor binding function. 相似文献
104.
History of biological metal utilization inferred through phylogenomic analysis of protein structures
Christopher L. Dupont Andrew Butcher Ruben E. Valas Philip E. Bourne Gustavo Caetano-Anollés 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(23):10567-10572
The fundamental chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Using protein structure and comparative genomics, we elucidate several major influences this chemistry has had upon biology. All of life exhibits the same proteome size-dependent scaling for the number of metal-binding proteins within a proteome. This fundamental evolutionary constant shows that the selection of one element occurs at the exclusion of another, with the eschewal of Fe for Zn and Ca being a defining feature of eukaryotic proteomes. Early life lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins that catalyze electron transport and redox transformations. The development of protein structures for metal homeostasis coincided with the emergence of metal-specific structures, which predominantly bound metals abundant in the Archean ocean. Potentially, this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast, structures binding Cu and Zn evolved much later, providing further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic cellular biology, and Zn bioavailability may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics, and key hypotheses can be tested by alternative geochemical methods. 相似文献
105.
106.
Xiangzhu Xiao Leticia Miravalle Jue Yuan John McGeehan Zhiqian Dong Robert Wyza Gregory T. MacLennan Alan M. Golichowski Geoff Kneale Nicholas King Qingzhong Kong Salvatore Spina Ruben Vidal Bernardino Ghetti Karen Roos Pierluigi Gambetti Wen-Quan Zou 《The American journal of pathology》2009,174(5):1602-1608
The vertical transmission of a prion disease from infected mothers to their offspring is believed to be one of the routes for the natural spread of animal prion diseases. Supporting this notion is the observation that prion infectivity occurs in the placenta of infected ewes. Furthermore, the prion protein (PrP), both in its cellular form (PrPC) and its pathological isoform (PrPSc), has been observed at the fetal-maternal interface of scrapie-infected sheep. However, whether these features of prion infectivity also hold true for human prion diseases is currently unknown. To begin to address such an important question, we examined PrP in the uterus as well as gestational tissues, including the placenta and amniotic fluid, in a pregnant woman with sporadic Creutzfeldt-Jakob disease (CJD). Although the proteinase K (PK)-resistant prion protein, PrP27-30, was present in the brain tissues of the mother, the PrP detected in the uterus, placenta, and amniotic fluid was sensitive to PK digestion. Unlike PrPC in the brain and adjacent cerebrospinal fluid, the predominant PrP species in the reproductive and gestational tissues were N-terminally truncated, similar to urine PrP. Our study did not detect abnormal PrP in the reproductive and gestational tissues in this case of CJD. Nevertheless, examination by a highly sensitive bioassay is ongoing to ascertain possible prion infectivity from CJD in the amniotic fluid.The transmissible prion diseases affecting both humans and animals are characterized by the accumulation of an infectious prion protein particle (PrPSc) mainly in the central nervous system (CNS) and occasionally in the peripheral tissues.1,2,3,4 Animal prion diseases such as scrapie in sheep and goats, chronic wasting disease in deer and elks, and bovine spongiform encephalopathy in cattle are believed to spread naturally by oral transmission, close contact between animals, and maternal transmission. Indeed, Western blot analysis and bioassays have demonstrated that PrPSc and prion infectivity are present not only in the CNS, but also in many peripheral tissues including the tonsils, spleen, lymph nodes, nasal mucosa, distal colon, ovaries, uterus, skeletal muscle, placenta, and amniotic fluid of affected animals.2In humans, the transmission of prion diseases has been observed in the acquired form of the disease including kuru, iatrogenic Creutzfeldt-Jakob disease (iCJD), and variant CJD (vCJD).5 Kuru is associated with cannibalistic rituals,6,7 whereas iCJD is caused by prion exposure in the course of medical or surgical procedures, and vCJD has been attributed to the consumption of prion-contaminated meat.8,9 In addition to CNS, PrPSc has also been detected in the tonsils, spleen, lymph node, retina, optic nerve, rectum, adrenal gland, and thymus of vCJD and in the spleen and skeletal muscles of sporadic CJD (sCJD).3,4 However, it remains unknown whether human prion diseases are vertically transmitted in pregnancy. For instance, none of four offspring born to four gravid women with CJD had reportedly developed the disease when they reached the respective ages of 22, 10, 7, and 3 years.10 In addition, no reports are available concerning examination of PrP in the uterus and gestational tissues from prion-affected patients.We examined PrPSc distribution in CNS, uterus, and gestational tissues from a woman affected with prion disease, who had become pregnant and delivered a baby boy during the time she had the disease. Typical PK-resistant PrP core fragments and neuropathological changes, characteristic of sCJD (with PrPSc type 1 carrying a valine/valine polymorphism at codon 129 of PrP gene), were detected in the brain tissues obtained at either biopsy or autopsy. Although PrP was detectable in the uterus, placenta, and amniotic fluid, it was PK-sensitive. Moreover, neither conventional nor enrichment-based Western blot analysis revealed the presence of abnormal PrP species. In contrast to the PrP in the brain and cerebrospinal fluid (CSF), the PrP detected in the uterus and gestational tissues, including placenta and amniotic fluid, was N-terminally truncated, similar to that normally found in the urine. Although the presence of prion infectivity in tissue remains to be determined by highly sensitive bioassay, our current study suggests that abnormal PrP species, including both PK-resistant and PK-sensitive forms, are undetectable in the uterus and gestational tissues in sporadic CJD. 相似文献
107.
Amorsolo L. Suguitan Jr. Michael P. Marino Purvi D. Desai Ruben O. Donis 《Virology》2009,395(2):280-288
A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice. 相似文献
108.
The widespread availability of high resolution ultrasound equipment and almost universal routine anatomy scanning in all pregnant women in the developed world has lead to increased detection of abnormalities in the fetal thorax. Already in the 1980s, large pleural effusions and significant macrocystic lesions in the fetus were easily detected on ultrasound. However, smaller lung tumours were often missed. Nowadays, fetal medicine centres receive many referrals for evaluation of fetal lung lesions, of which the most common are congenital cystic adenomatoid malformation and bronchopulmonary sequestration. Almost invariably, both the parents and the referring physicians experience anxiety after detection of large lung masses in the fetus. However, the vast majority of the currently detected fetal lung lesions have an excellent prognosis without the need for prenatal intervention. In the small group of fetuses in which the prognosis is poor, almost exclusively those with concomitant fetal hydrops and cardiac failure, several options for fetal therapy exist, often with a more than 50% survival rate. Indications, techniques, complications and outcomes of these interventions will be described in this review. 相似文献
109.
Lucovnik M Kuon RJ Chambliss LR Maner WL Shi SQ Shi L Balducci J Garfield RE 《Acta obstetricia et gynecologica Scandinavica》2011,90(10):1057-1069
Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given the role of progesterone in maintaining pregnancy, as well as support from basic and clinical research. Progesterone and 17α-hydroxyprogesterone acetate slow the process of cervical ripening, and this is the rationale for prophylactic long-term progestin supplementation mostly studied so far. However, progesterone (but not 17α-hydroxyprogesterone acetate) also inhibits myometrial activity even after the cervix has already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle and route of administration, is the key to finding the optimal progestin treatment for prevention of preterm birth. 相似文献
110.
Ibon Jaunarena Ruben Ruiz Mikel Gorostidi Paloma Cobas Marisa Avila David Del Valle Juan Cespedes Arantza Lekuona 《Journal of minimally invasive gynecology》2019,26(5):954-959
Study ObjectiveTo assess the efficacy of Tissucol Duo (Baxter AG, Vienna, Austria) fibrin sealant in decreasing the incidence of lymphocele (LC) after pelvic laparoscopic lymph node dissection using harmonic shears.DesignRandomized controlled trial (Canadian Task Force classification level I).SettingTertiary referral and educational center.PatientsSeventy-four patients randomized to the use of sealant per hemipelvis.InterventionFibrin sealant.Measurements and Main ResultsAfter bilateral pelvic lymphadenectomy a fibrin sealant was used in 1 hemipelvis but not the other, applied in 41 patients (55.4%) to the left and 33 patients (44.6%) to the right hemipelvis. The primary outcome was the incidence of LC after surgery in symptomatic and asymptomatic patients. Imaging (ultrasound, computed tomography, and magnetic resonance) was performed to detect LC at 3, 6, and 12 months after surgery. Overall, 26 patients (35.1%) developed LC, and 4 were symptomatic (5.4%). Allowing patients to serve as their own treatment group and control, the hemipelvis treated with Tissucol Duo corresponding to the treatment group and that not treated to the control group, LCs were found in 17 (23%) and 14 (19%) cases, respectively, but the difference was not significant. The mean initial LC maximum diameter was 27.1 mm (standard deviaiotn, 35.2), and LCs tended to decrease in size during the first year to a mean of 8.7 mm.ConclusionApplication of Tissucol Duo fibrin sealant after laparoscopic pelvic lymphadenectomy using ultrasonic shears does not decrease the occurrence of symptomatic or asymptomatic LC. 相似文献