bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Changes in Upper Airway Collapsibility during Slow Induction of Anesthesia with Propofol
Authors: Hillman David R. , Walsh Jennifer H. , Maddison Kathleen J. , Platt Peter R. , Kirkness Jason P. , Noffsinger William J. , Eastwood Peter R. 
Published: June 2009

Background
Upper airway collapsibility is known to increase under anesthesia. This study assessed how this increase in collapsibility evolves during slow Propofol induction and how it relates to anesthesia-induced changes in upper airway muscle activity and conscious state.

Methods
Nine healthy volunteers were studied. Anesthesia was induced with Propofol in a step-wise manner (effect-site concentration steps of 0.5 microg x ml(-1) from 0 to 3 microg x ml(-1) and thereafter to 4 microg x ml(-1) and 6 microg x ml(-1) [target-controlled infusion]). Airway patency was maintained with continuous positive airway pressure. Pharyngeal collapsibility was assessed at each concentration by measuring critical pressure. Intramuscular genioglossus electromyogram and anesthetic depth (bispectral index score) were monitored throughout. Loss of consciousness was defined as failure to respond to loud verbal command.

Results
Loss of consciousness occurred at varying Propofol effect-site concentrations between 1.5 and 4.0 microg x ml(-1). Initially genioglossus electromyographic activity was sustained with increases in Propofol concentration, increasing in some individuals. At or approaching loss of consciousness, it decreased, often abruptly, to minimal values with an accompanying increase in critical pressure. In most subjects, bispectral index score decreased alinearly with increasing Propofol concentration with greatest rate of change coinciding with loss of consciousness.

Conclusions
Slow stepwise induction of Propofol anesthesia is associated with an alinear increase in upper airway collapsibility. Disproportionate decreases in genioglossus electromyogram activity and increases in pharyngeal critical closing pressure were observed proximate to loss of consciousness, suggesting that particular vulnerability exists after transition from conscious to unconscious sedation. Such changes may have parallels with upper airway behavior at sleep onset.
Coapplication of Lidocaine and the Permanently Charged Sodium Channel Blocker QX-314 Produces a Long-lasting Nociceptive Blockade in Rodents
Authors: Binshtok Alexander M. , Gerner Peter , Oh Seog Bae , Puopolo Michelino , Suzuki Suzuko , Roberson David P. , Herbert Teri , Wang Chi-Fei , Kim Donghoon , Chung Gehoon , Mitani Aya A. , Wang Ging Kuo , Bean Bruce P. , Woolf Clifford J. 
Published: June 2009

Background
Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314-mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia.

Methods
Lidocaine (0.5% [17.5 mM], 1% [35 mM], and 2% [70 mM]) alone, QX-314 (0.2% [5.8 mM]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block.

Results
Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block.

Conclusions
Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.
Nefopam and Alfentanil Additively Reduce the Shivering Threshold in Humans whereas Nefopam and Clonidine Do Not
Authors: Alfonsi Pascal , Passard Andrea , Gaude–Joindreau Valérie , Guignard Bruno , Sessler Daniel I. , Chauvin Marcel 
Published: June 2009

Background
Induction of therapeutic hypothermia is often complicated by shivering. Nefopam reduces the shivering threshold with minimal side effects. Consequently, nefopam is an attractive component for induction of therapeutic hypothermia. However, nefopam alone is insufficient; it will thus need to be combined with another drug. Clonidine and alfentanil each reduce the shivering threshold. This study, therefore, tested the hypothesis that nefopam, combined either with clonidine or alfentanil, synergistically reduces the shivering threshold.

Methods
For each combination, ten volunteers were studied on 4 days. Combination 1: (1) control (no drug); (2) nefopam (100 ng/ml); (3) clonidine (2.5 microg/kg); and (4) nefopam plus clonidine (100 ng/ml and 2.5 microg/kg, respectively). Combination 2: (1) control (no drug); (2) nefopam (100 ng/ml); (3) alfentanil (150 ng/ml); and (4) nefopam plus alfentanil (100 ng/ml and 150 ng/ml, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused to decrease core temperature. Mean skin temperature was maintained at 31 degrees C. The core temperature that increased oxygen consumption to more than 25% of baseline identified the shivering threshold.

Results
With nefopam and clonidine, the shivering thresholds were significantly lower than on the control day. The shivering threshold decreased significantly less than would be expected on the basis of the individual effects of each drug (P = 0.034). In contrast, the interaction between nefopam and alfentanil on shivering was additive, meaning that the combination reduced the shivering threshold as much as would be expected by the individual effect of each drug.

Conclusions
Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.
Mutation of the Membrane-Associated M1 Protease APM1 Results in Distinct Embryonic and Seedling Developmental Defects inArabidopsis
Authors: Peer Wendy Ann , Hosein Fazeeda N. , Bandyopadhyay Anindita , Makam Srinivas N. , Otegui Marisa S. , Lee Gil-Je , Blakeslee Joshua J. , Cheng Yan , Titapiwatanakun Boosaree , Yakubov Bahktiyor , Bangari Bharat , Murphy Angus S. 
Published: June 2009

AbstractAminopeptidase M1 (APM1), a single copy gene in Arabidopsis thaliana, encodes a metallopeptidase originally identified via its affinity for, and hydrolysis of, the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Mutations in this gene result in haploinsufficiency. Loss-of-function mutants show irregular, uncoordinated cell divisions throughout embryogenesis, affecting the shape and number of cotyledons and the hypophysis, and is seedling lethal at 5 d after germination due to root growth arrest. Quiescent center and cell cycle markers show no signals in apm1-1 knockdown mutants, and the ground tissue specifiers SHORTROOT and SCARECROW are misexpressed or mislocalized. apm1 mutants have multiple, fused cotyledons and hypocotyls with enlarged epidermal cells with cell adhesion defects. apm1 alleles show defects in gravitropism and auxin transport. Gravistimulation decreases APM1 expression in auxin-accumulating root epidermal cells, and auxin treatment increases expression in the stele. On sucrose gradients, APM1 occurs in unique light membrane fractions. APM1 localizes at the margins of Golgi cisternae, plasma membrane, select multivesicular bodies, tonoplast, dense intravacuolar bodies, and maturing metaxylem cells. APM1 associates with brefeldin A–sensitive endomembrane structures and the plasma membrane in cortical and epidermal cells. The auxin-related phenotypes and mislocalization of auxin efflux proteins in apm1 are consistent with biochemical interactions between APM1 and NPA.
A 1-Megadalton Translocation Complex Containing Tic20 and Tic21 Mediates Chloroplast Protein Import at the Inner Envelope Membrane
Authors: Kikuchi Shingo , Oishi Maya , Hirabayashi Yoshino , Lee Dong Wook , Hwang Inhwan , Nakai Masato 
Published: June 2009

AbstractChloroplast protein import is mediated by two hetero-oligomeric protein complexes, the Tic and Toc translocons, which are located in the inner and outer envelope membranes. At the inner membrane, many Tic components have been identified and characterized, but it remains unclear how these Tic proteins are organized to form a protein-conducting channel or whether a stable Tic core complex that binds translocating preproteins exists. Here, we report the identification of a 1-megadalton (MD) translocation complex as an intermediate during protein translocation across the inner membrane in Arabidopsis thaliana and pea (Pisum sativum). This complex can be detected by blue native PAGE using the mild detergent digitonin without any chemical cross-linkers. The preprotein arrested in the 1-MD complex can be chased into its fully translocated form after a subsequent incubation. While Tic20 and Tic21 appear to be involved in the 1-MD complex, Tic110, a well-characterized Tic component, exists as a distinct entity from the complex. Several lines of evidence suggest that the 1-MD complex functions in between the Toc and Tic110-containing complexes, most likely as a protein-conducting channel at the inner envelope.
Phase II study of oral fludarabine in combination with rituximab for relapsed indolent B‐cell non‐Hodgkin lymphoma
Authors: Tobinai Kensei , Ishizawa Ken‐ichi , Ogura Michinori , Itoh Kuniaki , Morishima Yasuo , Ando Kiyoshi , Taniwaki Masafumi , Watanabe Takashi , Yamamoto Joji , Uchida Toshiki , Nakata Masanobu , Terauchi Takashi , Nawano Shigeru , Matsusako Masaki , Hayashi Masaki , Hotta Tomomitsu 
Published: June 2009

Oral fludarabine is more convenient than intravenous fludarabine in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine in combination with rituximab in patients with relapsed indolent B‐cell non‐Hodgkin lymphoma (B‐NHL), we conducted a multicenter phase II study. Patients with relapsed indolent B‐NHL with two or fewer prior regimens and up to 16 doses of rituximab were eligible. Patients received 375 mg/m2 rituximab on day 1, and 40 mg/m2 oral fludarabine once daily on days 1 through 5 every 28 days for up to six cycles. The primary endpoint was the overall response rate. Forty‐one patients were enrolled, including 38 (93%) with follicular lymphoma. Thirty‐four patients (83%) had received rituximab as prior therapy. Twenty‐seven patients (66%) completed the planned six cycles. Dose reduction of oral fludarabine was required in 17 patients (41%). The overall response rate was 76% (31 of 41 patients; 95% confidence interval, 60–88%) with a complete response rate of 68% (28 of 41 patients; 95% confidence interval, 52–82%). Median progression‐free survival for the 41 patients was 19.7 months (95% confidence interval, 12.3–26.5 months). Hematological toxicities, including grade 4 neutropenia (68%), were the most frequent toxicities. Non‐hematological toxicities were mild, except for one patient who died of Pneumocystis jiroveci pneumonia 4 months after the protocol treatment. In conclusion, oral fludarabine in combination with rituximab is a highly effective and convenient therapy for patients with relapsed indolent B‐NHL who have mostly been pretreated with rituximab. (ClinicalTrials.gov number, NCT00311129.) (Cancer Sci 2009; 100: 1951–1956)
c‐Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor‐β signaling in diffuse‐type gastric carcinoma
Authors: Kiyono Kunihiko , Suzuki Hiroshi I. , Morishita Yasuyuki , Komuro Akiyoshi , Iwata Caname , Yashiro Masakazu , Hirakawa Kosei , Kano Mitsunobu R. , Miyazono Kohei 
Published: June 2009

c‐Ski, originally identified as a proto‐oncogene product, is an important negative regulator of transforming growth factor (TGF)‐β family signaling through interaction with Smad2, Smad3, and Smad4. High expression of c‐Ski has been found in some cancers, including gastric cancer. We previously showed that disruption of TGF‐β signaling by dominant‐negative TGF‐β type II receptor in a diffuse‐type gastric carcinoma model accelerated tumor growth through induction of tumor angiogenesis by decreased expression of the anti‐angiogenic factor thrombospondin (TSP)‐1. Here, we examined the function of c‐Ski in human diffuse‐type gastric carcinoma OCUM‐2MLN cells. Overexpression of c‐Ski inhibited TGF‐β signaling in OCUM‐2MLN cells. Interestingly, c‐Ski overexpression resulted in extensive acceleration of the growth of subcutaneous xenografts in BALB/c nu/nu female mice (6 weeks of age). Similar to tumors expressing dominant‐negative TGF‐β type II receptor, histochemical studies revealed less fibrosis and increased angiogenesis in xenografted tumors expressing c‐Ski compared to control tumors. Induction of TSP‐1 mRNA by TGF‐β was attenuated by c‐Ski in vitro, and expression of TSP‐1 mRNA was decreased in tumors expressing c‐Ski in vivo. These findings suggest that c‐Ski overexpression promotes the growth of diffuse‐type gastric carcinoma through induction of angiogenesis. (Cancer Sci 2009; 100: 1809–1816)
Capacity of purified peanut allergens to induce degranulation in a functional in vitro assay: Ara h 2 and Ara h 6 are the most efficient elicitors
Authors: Blanc F. , Adel‐Patient K. , Drumare M.‐F. , Paty E. , Wal J.‐M. , Bernard H. 
Published: June 2009

SummaryBackground
Peanut is a most common and potent food allergen. Many peanut allergens have been characterized using, in particular, IgE‐binding studies.Objectives
We optimized an in vitro functional assay to assess the capacity of peanut allergens to degranulate humanized rat basophilic leukaemia cells, RBL SX‐38 cells, after sensitization by serum IgE from peanut‐allergic patients. We thus compared the activity of the main peanut allergens, i.e. Ara h 1, Ara h 2, Ara h 3 and Ara h 6, purified from roasted peanut.Methods
Sera of 12 peanut‐allergic patients were collected and total and peanut‐specific IgE were measured. They were used to sensitize RBL SX‐38 cells and the degranulation was induced by incubation with ranging concentrations of a whole peanut protein extract or of purified peanut allergens. The mediator release was quantified by the determination of β‐hexosaminidase activity in the supernatant. The intensity of the degranulation was expressed as maximum release and as EC50, corresponding to the dose of allergen that induced 50% of the maximum release.Results
For each serum, only 10 IU/mL of human IgE was necessary to sensitize the cells and obtain an optimal degranulation. With all the allergens, the release was positively correlated with the concentration of allergen‐specific IgE in the serum used to sensitize the cells. The medians of EC50 obtained for Ara h 2 and Ara h 6 were 2.1 and 2.8 pm, respectively, while they were much higher for Ara h 3 and Ara h 1 (65 and 150 pm, respectively).Conclusion
The RBL SX‐38 release assay proved to be sensitive, specific and reproducible. It allowed the comparison of the degranulation potential of different peanut allergens. For all the sera tested, Ara h 2 and Ara h 6 were more potent than Ara h 1 or Ara h 3.
Regulatory T cells and asthma
Authors: Robinson D. S. 
Published: June 2009

AbstractAirway inflammation in asthma is characterized by activation of T helper type‐2 (Th2) T cells, IgE production and eosinophilia. In many cases, this process is related to an inappropriate T cell response to environmental allergens, and other T cell‐dependent pathways may also be involved (such as Th17). Regulatory T cells (Tregs) are T cells that suppress potentially harmful immune responses. Two major subsets of Treg are CD25hi, Foxp3+Tregs and IL‐10‐producing Tregs. There is evidence that the numbers or function of both subsets may be deficient in patients with atopic allergic disease. Recent work has extended these findings into the airway in asthma where Foxp3 expression was reduced and CD25hi Treg‐suppressive function was deficient. In animal models of allergic airways disease, Tregs can suppress established airway inflammation and airway hyperresponsiveness, and protocols to enhance the development, recruitment and function of Tregs have been described. Together with studies of patients and in vitro studies of human T cells, these investigations are defining potential interventions to enhance Treg function in the airway in asthma. Existing therapies including corticosteroids and allergen immunotherapy act on Tregs, in part to increase IL‐10 production, while vitamin D3 and long‐acting β‐agonists enhance IL‐10 Treg function. Other possibilities may be enhancement of Treg function via histamine or prostanoid receptors, or by blocking pro‐inflammatory pathways that prevent suppression by Tregs (activation of Toll‐like receptors, or production of cytokines such as IL‐6 and TNF‐α). As Tregs can also suppress the potentially beneficial immune response important for controlling infections and cancer, a therapeutic intervention should target allergen‐ or site‐specific regulation.
Comparison of the soil hydraulic conductivity predicted from its water retention expressed by the equation of Van Genuchten and different capillary models
Authors: Touma J. 
Published: June 2009

SummaryKnowledge of water retention and conductivity is essential to study water transport in soil. Determination of the conductivity curve is difficult, and it is often predicted by application of a capillary model to the water retention relationship. Three expressions are predicted from the water retention described by the equation of Van Genuchten. Two expressions are obtained in combination with the capillary models of Mualem and Burdine. The third expression is obtained by a combination with the capillary model of Fatt & Dykstra. The three sets of soil properties were applied to clay in order to compute infiltration and infiltration rates according to the series solution of Philip. Comparison with this solution showed that the results of the first two combinations were severely under‐estimated, while those of the third were satisfactory. Similar results were obtained for sand by comparison with experimental data. Because conductivity estimated from the capillary model of Fatt & Dykstra is complicated, it was expressed by a power equation, the exponent of which is obtained by applying the Fatt & Dykstra capillary model to the water retention curve expressed according to Brooks & Corey and having the same asymptotic behaviour as the Van Genuchten equation. Application of this procedure to fifty soils selected from a published database gave satisfactory results. It is concluded that the hydraulic conductivity of a soil can be predicted from its water retention as expressed by the equation of Van Genuchten subject to the condition of the capillary model of Fatt & Dykstra and as expressed by the equation of Brooks & Corey, for which the exponent is obtained according to the same capillary model.
A stochastic‐geometric model of soil variation
Authors: Lark R. M. 
Published: June 2009

SummaryStochastic models of soil variation are used in geostatistical analysis, but in general they bear no relation to our mechanistic understanding of the processes in soil that cause its properties to vary spatially. It is proposed that we require a suitable stochastic model in which space is partitioned into discrete domains as a first step towards random spatial models that incorporate our understanding of processes in soil. Even though the soil is essentially continuous in its spatial variation, there are components of soil variation (e.g. differences between parent materials) which are discontinuous. This paper shows how variogram models can be derived directly from the Poisson Voronoi Tessellation (PVT), a stochastic‐geometric partition of d‐dimensional space. The PVT variogram models, for d= 2 and 3, were fitted to variograms estimated from data over disparate scales, including computerized tomographic images of soil aggregates (pixels of a few tens of micrometres long) and the land systems of Swaziland. In all cases, PVT variogram models fitted better than the conventional geostatistical ones. The good performance of PVT variogram models at these disparate scales encourages further work on tessellation models for soil variation. In principle such models could incorporate information on underlying factors of soil formation such as the spatial distribution of individual plants, the origin and growth of microbial colonies, spatial processes in soil chemistry (such as reaction–diffusion processes) and geometrical information on boundaries between geological strata or contrasting plant communities. PVT models may therefore be one component of a random model of soil variation which reflects our understanding of soil‐forming processes, and so have a stronger scientific basis than the models that are now in standard use.
Estimating the regional mean status and change of soil properties: two distinct objectives for soil survey
Authors: Lark R. M. 
Published: June 2009

SummaryThere is a general requirement for inventories to establish the status of soils with respect to key indicator properties, and for monitoring to detect changes in these indicators. The design of sampling protocols for soil survey must meet these dual requirements. This paper emphasizes that the status and change of an indicator are different variables and so their variability may differ. We therefore may not assume that a sampling scheme that is suitable for inventory is also suitable for monitoring; this poses a practical problem since information on the variability of the change in soil is not in general available at present.In this paper some plausible statistical models of change in the soil are examined, and their implications for sampling to estimate mean change in large regions are considered. Paired sampling, with baseline and resampling at common sites, is generally preferable to sampling at independent sites on the two dates, unless the error from relocation of the sample sites is large by comparison to other sources of variation.A simple process model of soil organic carbon in soils of lowland tropical forest is used to examine the problem of resampling to estimate change. This shows the expected advantages of paired sampling for change, and the very different sampling requirements that may pertain for inventory and monitoring. One implication of these results is that, while sampling schemes for inventory may be designed on the basis of available information (from samples taken at a single time), the precise requirements for monitoring might not be apparent until a reconnaissance resampling is undertaken subsequently.