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321.
322.
Jos A. Andrades Bo Han Jos Becerra Nino Sorgente Frederick L. Hall Marcel E. Nimni 《Experimental cell research》1999,250(2):485
A continuous source of osteoblasts for normal bone maintenance, as well as remodeling and regeneration during fracture repair, is ensured by the mesenchymal osteoprogenitor stem cells of the bone marrow (BM). The differentiation and maturation of osteoprogenitor cells into osteoblasts are thought to be modulated by transforming growth factors-β (TGF-β1 and TGF-β2) and TGF-β-related bone morphogenetic proteins (BMPs). To define the responses of mesenchymal osteoprogenitor stem cells to several growth factors (GFs), we cultured Fischer 344 rat BM cells in a collagen gel medium containing 0.5% fetal bovine serum for prolonged periods of time. Under these conditions, survival of BM mesenchymal stem cells was dependent on the addition of GFs. Recombinant hTGF-β1-F2, a fusion protein engineered to contain an auxiliary collagen binding domain, demonstrated the ability to support survival colony formation and growth of the surviving cells, whereas commercial hTGF-β1 did not. Initially, cells were selected from a whole BM cell population and captured inside a collagen network, on the basis of their survival response to added exogenous GFs. After the 10-day selection period, the surviving cells in the rhTGF-β1-F2 test groups proliferated rapidly in response to serum factors (10% FBS), and maximal DNA synthesis levels were observed. Upon the addition of osteoinductive factors, osteogenic differentiation in vitro was evaluated by the induction of alkaline phosphatase (ALP) expression, the production of osteocalcin (OC), and the formation of mineralized matrix. Concomitant with a down-regulation of cell proliferation, osteoinduction is marked by increased ALP expression and the formation of colonies that are competent for mineralization. During the induction period, when cells organize into nodules and mineralize, the expression of OC was significantly elevated along with the onset of extracellular matrix mineralization. Differentiation of BM mesenchymal stem cells into putative bone cells as shown by increased ALP, OC synthesis, and in vitro mineralization required the presence of specific GFs, as well as dexamethasone (dex) and β-glycerophosphate (β-GP). Although rhTGF-β1-F2-selected cells exhibited the capacity to mineralize, maximal ALP activity and OC synthesis were observed in the presence of rhBMPs. We further report that a novel rhTGF-β1-F2 fusion protein, containing a von Willebrand's factor-derived collagen binding domain combined with a type I collage matrix, is able to capture, amplify, and stimulate the differentiation of a population of cells present in rat BM. When these cells are subsequently implanted in inactivated demineralized bone matrix (iDBM) and/or diffusion chambers into older rats they are able to produce bone and cartilage. The population of progenitor cells captured by rhTGF-β1-F2 is distinct from the committed progenitor cells captured by rhBMPs, which exhibit a considerably more differentiated phenotype. 相似文献
323.
Keerthana Deepti Karunakaran Barry D. Kussman Ke Peng Lino Becerra Robert Labadie Rachel Bernier Delany Berry Stephen Green David Zurakowski Mark E. Alexander David Borsook 《PLoS medicine》2022,19(4)
BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov In a randomized controlled trial, Keerthana Karunakaran, Barry Kussman, and colleagues study whether remifentanil attenuates pain-related brain activity during cardiac ablation surgery. NCT02703090相似文献
324.
Four pigeons were trained to peck a key under different values of a temporally defined independent variable (T) and different probabilities of reinforcement (p). Parameter T is a fixed repeating time cycle and p the probability of reinforcement for the first response of each cycle T. Two dependent variables were used: mean response rate and mean postreinforcement pause. For all values of p a critical value for the independent variable T was found (T=1 sec) in which marked changes took place in response rate and postreinforcement pauses. Behavior typical of random ratio schedules was obtained at T 1 sec and behavior typical of random interval schedules at T 1 sec. 相似文献
325.
J A Andrades J A Santamaría M E Nimni J Becerra 《The International journal of developmental biology》2001,45(4):689-693
The differentiation and maturation of osteoprogenitor cells into osteoblasts are processes which are thought to be modulated by transforming growth factors-beta (TGF-beta) as well as by bone morphogenetic proteins (BMPs). Osteogenic protein-1 (OP-1, also known as BMP-7) is a member of the BMP family, and it is considered to have important regulatory roles in skeletal embryogenesis and bone healing. Rat bone marrow cells were cultured in vitro in a collagen-gel medium containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of 40 ng/ml recombinant human OP-1 (rhOP-1). Under these conditions, survival of the bone marrow cell population was dependent on the presence of rhOP-1. Subsequently, the selected cells were cultured-for 6 days in medium containing 40 ng rhOP-1 and 10% FBS. During the last 2 days, dexamethasone (10(-8) M) and beta-glycerophosphate (2 mM) were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels, colony number and size were determined. Chondro-osteogenic differentiation in vitro was evaluated in terms of the expression of alkaline phosphatase, the production of osteocalcin and the formation of mineralized matrix. After culturing in vitro, cells were placed inside diffusion chambers or inactivated demineralized bone matrix (DBM) cylinders and implanted subdermically into the backs of old rats for 28 days. Biochemical, histological and immunocytochemical analyses provided evidence of cartilage and osteoid tissue inside the diffusion chambers, whereas bone was also observed inside the DBM implants. In conclusion, this experimental procedure is capable of selecting a cell population from bone marrow which, in the presence of rhOP-1, achieves skeletogenic potential under in vitro as well as in vivo environments. 相似文献
326.
327.
Zimmerman PA; Katholi CR; Wooten MC; Lang-Unnasch N; Unnasch TR 《Molecular biology and evolution》1994,11(3):384-392
Polymerase chain reaction (PCR) products were characterized for a repeated
sequence family (designated "O-150") of the human filarial parasite
Onchocerca volvulus. In phylogenetic inferences, the O-150 sequences
clustered into closely related groups, suggesting that concerted evolution
maintains sequence homology in this family. Using a novel mathematical
model based on a nested application of an analysis of variance, we
demonstrated that African rainforest and savannah strain parasite
populations are significantly different. In contrast, parasites collected
in the New World are indistinguishable from African savannah strains of O.
volvulus. This finding supports the hypothesis that onchocerciasis was
recently introduced into the New World, possibly as a result of the slave
trade.
相似文献
328.
Question: What effects do leaf litter and rainfall regime have on seed germination (time and probability) and seedling survival of the endangered tree species Beilschmiedia miersii (Lauraceae)? Location: The species is a native tree from the mediterranean climate region of Chile. Seeds were collected from La Campana National Park (Chile). The study was carried out under controlled conditions at the Laboratory of Ecology, University of Chile, Santiago, Chile. Methods: During April 2001,200 seeds were assigned to four experimental treatments: high precipitation, with and without litter and low precipitation, with and without litter. Each treatment had 50 individual seeds, each seed in an individual pot. For statistical purposes, we considered each seed as one replicate. High and low values of artificial rainfall corresponded to mean dry and wet years, respectively, for the period 1958–1993 in the central zone of Chile. Results: Seeds germinated earlier, and in higher proportion, in the presence of leaf litter, but only under low rainfall. Seedling survival was insensitive to both litter and precipitation. Conclusions: We conclude that the presence of litter in native populations facilitates seed germination and recruitment of B. miersii, particularly during dry years. We suggest that the reduction of leaf litter due to extraction for gardens and horticultural activities might preclude regeneration of this endangered species. 相似文献
329.
Vega MD Peña AI Gullón J Prieto C Barrio M Becerra JJ Herradón PG Quintela LA 《Animal reproduction science》2008,103(3-4):385-391
The possibility of modifying the sex ratio of rabbit litters was examined in two experiments involving artificial insemination (AI) with fresh semen. Three time periods of AI, relative to ovulation, were used in Experiment 1: (a) control, GnRH was administered immediately after AI with ovulation estimated to occur 10-12h after AI; (b) early AI, GnRH was given 6h after AI so that ovulation was delayed until 16-18 h after AI; (c) late AI, GnRH was administered 6h before AI, which was performed 4-6h before ovulation. There were 13 does per treatment, and each doe was used in the same treatment for three AIs at 42-day intervals. The second experiment involved two treatments in which the does were inseminated as for the control in Experiment 1 and AI was performed using semen prepared in the normal manner (Treatment 1) or after centrifugation through 11 discontinuous Percoll gradients (Treatment 2). There were 20 does per treatment, and each doe was used in the same treatment for three AIs at 42-day intervals. The proportion of female kits produced in Experiment 1 was: control 41.7+/-19.1%, early AI 49.8+/-17.8%, and late AI 41.4+/-16.4%. These proportions did not differ significantly between treatments or from the expected 50:50 sex ratio. Fertility was reduced by the early (60.0%) and late (73.7%) AI treatments relative to control AI (80.0%), and the difference between early and control AI almost achieved statistical significance (P<0.07). In Experiment 2, the proportion of female kits was not affected by treatment (control, 51.1%; Percoll, 54.8%), and there was a similar level of fertility for both treatments (control, 76.0%; Percoll, 74.1%). Prolificacy and perinatal mortality were not affected by treatment in either experiment. It was concluded that neither the timing of insemination nor Percoll centrifugation of semen affected the sex ratio at birth of rabbit litters. 相似文献
330.
Said M Becerra R Palomeque J Rinaldi G Kaetzel MA Diaz-Sylvester PL Copello JA Dedman JR Mundiña-Weilenmann C Vittone L Mattiazzi A 《American journal of physiology. Heart and circulatory physiology》2008,295(4):H1669-H1683
Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 muM of the CaMKII inhibitor KN-93, 1 muM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca(2+) uptake, and 30 nM ryanodine or 45 muM dantrolene, to inhibit SR Ca(2+) release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr(17) site of phospholamban (PT-PLN) and SR Ca(2+) load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca(2+) leak, when compared with that of control or with acidosis at the same SR Ca(2+) content. Ca(2+) leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca(2+) load, which appears to be mainly due to the increase in PT-PLN. 相似文献