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1

Han, Yu Du, and Jae Heon Yun. "Performance of Restarted Homotopy Perturbation Method for TV-Based Image Denoising Problem." Mathematical Problems in Engineering 2015 (2015): 1–18. http://dx.doi.org/10.1155/2015/207541.

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We first propose a restarted homotopy perturbation method (RHPM) for solving a nonlinear PDE problem which repeats HPM process by computing only the first few terms instead of computing infinite terms, and then we present an application of RHPM to TV- (Total Variation-) based image denoising problem. The main difficulty in applying RHPM to the nonlinear denoising problem is settled by using binomial series techniques. We also provide finite difference schemes for numerical implementation of RHPM. Lastly, numerical experiments for several test images are carried out to demonstrate the feasibility, efficiency, and reliability of RHPM by comparing the performance of RHPM with that of existing TM and recently proposed RHAM methods.
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2

Shcherba, V. E. "Method for estimating the operating time in the compressor mode of a reciprocating hybrid power machine with regenerative heat exchange." Proceedings of Higher Educational Institutions. Маchine Building, no. 10 (751) (October 2022): 96–102. http://dx.doi.org/10.18698/0536-1044-2022-10-96-102.

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The influence of the average wall temperature on the main consumption and energy characteristics of a reciprocating hybrid power machine (RHPM) with regenerative heat exchange has been studied. A significant effect of a change in the average wall temperature on the supply coefficient and the indicator isothermal efficiency of the RHPM operating in the compressor mode is shown. Based on the results obtained, a method has been developed for determining the operating time of the RHPM in the compressor mode, based on the given average value of the indicator isothermal efficiency in the studied interval of the average temperature of the wall of the surface of the working chamber, or the operating time of the RHPM.
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3

Vázquez-Leal, Héctor. "Rational Homotopy Perturbation Method." Journal of Applied Mathematics 2012 (2012): 1–14. http://dx.doi.org/10.1155/2012/490342.

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The solution methods of nonlinear differential equations are very important because most of the physical phenomena are modelled by using such kind of equations. Therefore, this work presents a rational version of homotopy perturbation method (RHPM) as a novel tool with high potential to find approximate solutions for nonlinear differential equations. We present two case studies; for the first example, a comparison between the proposed method and the HPM method is presented; it will show how the RHPM generates highly accurate approximate solutions requiring less iteration, in comparison to results obtained by the HPM method. For the second example, which is a Van der Pol oscillator problem, we compare RHPM, HPM, and VIM, finding out that RHPM method generates the most accurate approximated solution.
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4

PEIRIS, T. S. G., and R. O. THATTIL. "THE STUDY OF CLIMATE EFFECTS ON THE NUT YIELD OF COCONUT USING PARSIMONIOUS MODELS." Experimental Agriculture 34, no. 2 (April 1998): 189–206. http://dx.doi.org/10.1017/s0014479798002051.

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The coconut yield is harvested in six picks per year at two-monthly intervals. The yield variation between and within years is very complex and this variability has not yet been explained. The analysis of long-term nut yield and monthly climate data: rainfall (RF), pan evaporation (EV), sunshine duration (SS), wind velocity (WV), minimum and maximum air temperatures (TMIN and TMAX), and relative humidity in forenoons and afternoons (RHAM and RHPM), using multivariate methods enabled the use of the variables TMAX, RHPM and EV as significantly important determinants (parsimonious set of variables) to represent the effects of climate on coconut irrespective of picks. Parsimonious models developed using these three variables explain how the development of bunches during the active growth period responded to climate variables without physiological parameters. The models are desirable where interpretation is concerned. The yields of picks one to six were determined by the climate variability during February, June, July, September, December and February respectively. Based on the models the proper timing of the use of some agronomic practices to enhance the productivity was recommended. A common model was also fitted (R2 = 0.81; p < 0.002) to estimate the annual yield 18 months in advance using EV, RHPM and TMAX. The three variables influence the microclimate around the crown of the palm for utilizing solar radiation in dry matter partitioning and thereby nut production. The method used to screen climatic variables so as to develop parsimonious crop–weather models using multivariate and univariate techniques can be used for other tree crops.
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5

Vazquez-Leal, Hector, Hüseyin Koçak, and Inan Ates. "Rational Approximations for Heat Radiation and Troesch’s Equations." International Journal of Computational Methods 13, no. 03 (May 31, 2016): 1650039. http://dx.doi.org/10.1142/s0219876216500390.

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In this paper, a new tool for the solution of nonlinear differential equations is presented. It is named rational homotopy perturbation method (RHPM). It delivers a high precision representation of the nonlinear differential equation using a few linear algebraic terms. In order to assess the benefits of this proposal, three nonlinear problems are solved and compared against other semi-analytic methods or numerical methods. Furthermore, in order to deal with BVP problems, we propose a modification of RHPM method. The obtained results show that RHPM is a powerful tool capable to generate highly accurate rational solutions.
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6

Han, Yu Du, and Jae Heon Yun. "Performance of the Restarted Homotopy Perturbation Method and Split Bregman Method for Multiplicative Noise Removal." Mathematical Problems in Engineering 2018 (December 6, 2018): 1–21. http://dx.doi.org/10.1155/2018/7696798.

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In this paper, we first propose restarted homotopy perturbation methods (RHPM) for multiplicative noise removal of the RLO and AA2 models. The main difficulty in applying the RHPM to the nonlinear denoising problem is settled by using binomial series techniques. We next propose the split Bregman methods for multiplicative noise removal of the RLO and AA2 models. The difficulty in applying the split Bregman method to the nonlinear denoising problem can be handled by transforming ill-conditioned linear systems into well-conditioned linear systems using splitting techniques of singular matrices. Lastly, numerical experiments for several test problems are provided to demonstrate the efficiency and reliability of the RHPM and split Bregman methods.
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7

Nishimoto, Norihiro, Mitsuko Sasai, Yoshihito Shima, Masashi Nakagawa, Tomoshige Matsumoto, Toshikazu Shirai, Tadamitsu Kishimoto, and Kazuyuki Yoshizaki. "Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy." Blood 95, no. 1 (January 1, 2000): 56–61. http://dx.doi.org/10.1182/blood.v95.1.56.

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Abstract Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)
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8

Nishimoto, Norihiro, Mitsuko Sasai, Yoshihito Shima, Masashi Nakagawa, Tomoshige Matsumoto, Toshikazu Shirai, Tadamitsu Kishimoto, and Kazuyuki Yoshizaki. "Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy." Blood 95, no. 1 (January 1, 2000): 56–61. http://dx.doi.org/10.1182/blood.v95.1.56.001k13_56_61.

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Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)
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9

&NA;. "rhPM-1 beneficial in Castleman's disease." Inpharma Weekly &NA;, no. 1226 (February 2000): 9. http://dx.doi.org/10.2165/00128413-200012260-00019.

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10

Albalawi, Kholoud Saad, Badr Saad Alkahtani, Ashish Kumar, and Pranay Goswami. "Numerical Solution of Time-Fractional Emden–Fowler-Type Equations Using the Rational Homotopy Perturbation Method." Symmetry 15, no. 2 (January 17, 2023): 258. http://dx.doi.org/10.3390/sym15020258.

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The integral-order derivative is not suitable where infinite variances are expected, and the fractional derivative manages to consider effects with more precision; therefore, we considered time-fractional Emden–Fowler-type equations and solved them using the rational homotopy perturbation method (RHPM). The RHPM method is based on two power series in rational form. The existence and uniqueness of the equation are proved using the Banach fixed-point theorem. Furthermore, we approximate the term h(z) with a polynomial of a suitable degree and then solve the system using the proposed method and obtain an approximate symmetric solution. Two numerical examples are investigated using this proposed approach. The effectiveness of the proposed approach is checked by representing the graphs of exact and approximate solutions. The table of absolute error is also presented to understand the method’s accuracy.
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11

El Sharnouby, M. M., and M. H. El Naggar. "Field investigation of lateral monotonic and cyclic performance of reinforced helical pulldown micropiles." Canadian Geotechnical Journal 55, no. 10 (October 2018): 1405–20. http://dx.doi.org/10.1139/cgj-2017-0330.

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Different forms of grouted helical piles are increasingly used to support new and existing foundations. In particular, different methods are used to enhance the lateral and cyclic performance of helical piles for applications in seismic regions. This paper presents a field study on the lateral monotonic and cyclic behaviour of steel fibre–reinforced helical pulldown micropiles (RHPM) and fibre-reinforced polymer – steel fibre–reinforced helical pulldown micropiles (FRP–RHPM). The study shows that the grout shaft and (or) the fibre-reinforced polymer (FRP) sleeve significantly improve the helical pile lateral performance. In addition, the piles showed a significant ductility (no observed failure up to 75 mm displacement or 50% of pile diameter). Two-way cyclic loading resulted in overall degradation in pile response relative to its static performance. Degradation is found to stem from the formation of gaps between the pile and soil, rather than soil stiffness degradation. Formation of gaps leads to the piles having a “preferential direction” with one side providing higher resistance (i.e., stiffness) than the other side. Design charts of various pile configurations are presented.
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12

Awan, Farah Jabeen, Asif Mehmood, Syed Tauseef Mohyud-Din, and Saleh M. Hassan. "On Modified Algorithm for Fourth-Grade Fluid." Mathematical Problems in Engineering 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/350403.

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This paper shows the analysis of the thin film flow of fourth-grade fluid on the outer side of a vertical cylinder. Solution of the governing nonlinear equation is obtained by Rational Homotopy Perturbation Method (RHPM); comparison with exact solution reflects the reliability of the method. Analysis shows that this method is reliable for even high nonlinearity. Graphs and tables strengthen the idea.
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13

Vazquez-Leal, H., K. Boubaker, L. Hernandez-Martinez, and J. Huerta-Chua. "Approximation for Transient of Nonlinear Circuits Using RHPM and BPES Methods." Journal of Electrical and Computer Engineering 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/973813.

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The microelectronics area constantly demands better and improved circuit simulation tools. Therefore, in this paper, rational homotopy perturbation method and Boubaker Polynomials Expansion Scheme are applied to a differential equation from a nonlinear circuit. Comparing the results obtained by both techniques revealed that they are effective and convenient.
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14

Xiao, Yanmei, Lefu Lan, Chuntao Yin, Xin Deng, Douglas Baker, Jian-Min Zhou, and Xiaoyan Tang. "Two-Component Sensor RhpS Promotes Induction of Pseudomonas syringae Type III Secretion System by Repressing Negative Regulator RhpR." Molecular Plant-Microbe Interactions® 20, no. 3 (March 2007): 223–34. http://dx.doi.org/10.1094/mpmi-20-3-0223.

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The Pseudomonas syringae type III secretion system (T3SS) is induced during interaction with the plant or culture in minimal medium (MM). How the bacterium senses these environments to activate the T3SS is poorly understood. Here, we report the identification of a novel two-component system (TCS), RhpRS, that regulates the induction of P. syringae T3SS genes. The rhpR and rhpS genes are organized in an operon with rhpR encoding a putative TCS response regulator and rhpS encoding a putative biphasic sensor kinase. Transposon insertion in rhpS severely reduced the induction of P. syringae T3SS genes in the plant as well as in MM and significantly compromised the pathogenicity on host plants and hypersensitive response-inducing activity on nonhost plants. However, deletion of the rhpRS locus allowed the induction of T3SS genes to the same level as in the wild-type strain and the recovery of pathogenicity upon infiltration into plants. Overexpression of RhpR in the ΔrhpRS deletion strain abolished the induction of T3SS genes. However, overexpression of RhpR in the wild-type strain or overexpression of RhpR(D70A), a mutant of the predicted phosphorylation site of RhpR, in the ΔrhpRS deletion strain only slightly reduced the induction of T3SS genes. Based on these results, we propose that the phosphorylated RhpR represses the induction of T3SS genes and that RhpS reverses phosphorylation of RhpR under the T3SS-inducing conditions. Epistasis analysis indicated that rhpS and rhpR act upstream of hrpR to regulate T3SS genes.
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15

Deng, Xin, Lefu Lan, Yanmei Xiao, Megan Kennelly, Jian-Min Zhou, and Xiaoyan Tang. "Pseudomonas syringae Two-Component Response Regulator RhpR Regulates Promoters Carrying an Inverted Repeat Element." Molecular Plant-Microbe Interactions® 23, no. 7 (July 2010): 927–39. http://dx.doi.org/10.1094/mpmi-23-7-0927.

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The two-component system RhpRS was identified in Pseudomonas syringae as a regulator of the genes encoding the type III secretion system and type III effector proteins (together called the T3 genes). In the absence of the sensor kinase RhpS, the response regulator RhpR represses the induction of the T3 gene regulatory cascade consisting of hrpRS, hrpL, and the T3 genes in a phosphorylation-dependent manner. The repressor activity of RhpR is inhibited by RhpS, which presumably acts as a phosphatase under the T3 gene inducing conditions. Here, we show that RhpR binds and induces its own promoter in a phosphorylation-dependent manner. Deletion and mutagenesis analyses revealed an inverted repeat (IR) element, GTATC-N6-GATAC, in the rhpR promoter that confers the RhpR-dependent induction. Computational search of the P. syringae genomes for the putative IR elements and Northern blot analysis of the genes with a putative IR element in the promoter region uncovered five genes that were upregulated and two genes that were downregulated in an RhpR-dependent manner. Two genes that were strongly induced by RhpR were assayed for the IR element activity in gene regulation and, in both cases, the IR element mediated the RhpR-dependent gene induction. Chromatin immunoprecipitation assays indicated that RhpR binds the promoters containing a putative IR element but not the hrpR and hrpL promoters that do not have an IR element, suggesting that RhpR indirectly regulates the transcriptional cascade of hrpRS, hrpL, and the T3 genes.
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16

El Sharnouby, M. M., and M. H. El Naggar. "Axial monotonic and cyclic performance of fibre-reinforced polymer (FRP) – steel fibre–reinforced helical pulldown micropiles (FRP-RHPM)." Canadian Geotechnical Journal 49, no. 12 (December 2012): 1378–92. http://dx.doi.org/10.1139/cgj-2012-0009.

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17

Vindas, Marco A., Ida B. Johansen, Sergio Vela-Avitua, Karoline Sletbak Nørstrud, Marion Aalgaard, Bjarne O. Braastad, Erik Höglund, and Øyvind Øverli. "Frustrative reward omission increases aggressive behaviour of inferior fighters." Proceedings of the Royal Society B: Biological Sciences 281, no. 1784 (June 7, 2014): 20140300. http://dx.doi.org/10.1098/rspb.2014.0300.

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Animals use aggressive behaviour to gain access to resources, and individuals adjust their behaviour relative to resource value and own resource holding potential (RHP). Normally, smaller individuals have inferior fighting abilities compared with larger conspecifics. Affective and cognitive processes can alter contest dynamics, but the interaction between such effects and that of differing RHPs has not been adjudged. We investigated effects of omission of expected reward (OER) on competing individuals with contrasting RHPs. Small and large rainbow trout ( Oncorhynchus mykiss ) were conditioned to associate a light with reward. Thereafter, the reward was omitted for half of the fish prior to a contest between individuals possessing a 36–40% difference in RHP. Small control individuals displayed submissive behaviour and virtually no aggression. By contrast, small OER individuals were more aggressive, and two out of 11 became socially dominant. Increased aggression in small OER individuals was accompanied by increased serotonin levels in the dorsomedial pallium (proposed amygdala homologue), but no changes in limbic dopamine neurochemistry were observed in OER-exposed individuals. The behavioural and physiological response to OER in fish indicates that frustration is an evolutionarily conserved affective state. Moreover, our results indicate that aggressive motivation to reward unpredictability affects low RHP individuals strongest.
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18

Viveen, Jetske, Izaak F. Kodde, Andras Heijink, Koen L. M. Koenraadt, Michel P. J. van den Bekerom, and Denise Eygendaal. "Why does radial head arthroplasty fail today? A systematic review of recent literature." EFORT Open Reviews 4, no. 12 (December 2019): 659–67. http://dx.doi.org/10.1302/2058-5241.4.180099.

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Since the introduction of the radial head prosthesis (RHP) in 1941, many designs have been introduced. It is not clear whether prosthesis design parameters are related to early failure. The aim of this systematic review is to report on failure modes and to explore the association between implant design and early failure. A search was conducted to identify studies reporting on failed primary RHP. The results are clustered per type of RHP based on: material, fixation technique, modularity, and polarity. Chi-square tests are used to compare reasons for failure between the groups. Thirty-four articles are included involving 152 failed radial head arthroplasties (RHAs) in 152 patients. Eighteen different types of RHPs have been used. The most frequent reasons for revision surgery after RHA are (aseptic) loosening (30%), elbow stiffness (20%) and/or persisting pain (17%). Failure occurs after an average of 34 months (range, 0–348 months; median, 14 months). Press-fit prostheses fail at a higher ratio because of symptomatic loosening than intentionally loose-fit prostheses and prostheses that are fixed with an expandable stem (p < 0.01). Because of the many different types of RHP used to date and the limited numbers and evidence on early failure of RHA, the current data provide no evidence for a specific RHP design. Cite this article: EFORT Open Rev 2019;4:659-667. DOI: 10.1302/2058-5241.4.180099
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19

Dures, Emma, Susan Bridgewater, Bryan Abbott, Jo Adams, Alice Berry, Lance M. McCracken, Siobhan Creanor, et al. "Brief intervention to reduce fatigue impact in patients with inflammatory arthritis: design and outcomes of a single-arm feasibility study." BMJ Open 12, no. 7 (July 2022): e054627. http://dx.doi.org/10.1136/bmjopen-2021-054627.

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ObjectivesPatients with inflammatory arthritis report that fatigue is challenging to manage. We developed a manualised, one-to-one, cognitive–behavioural intervention, delivered by rheumatology health professionals (RHPs). The Fatigue - Reducing its Effects through individualised support Episodes in Inflammatory Arthritis (FREE-IA) study tested the feasibility of RHP training, intervention delivery and outcome collection ahead of a potential trial of clinical and cost-effectiveness.MethodsIn this single-arm feasibility study, eligible patients were ≥18 years, had a clinician-confirmed diagnosis of an inflammatory arthritis and scored ≥6/10 on the Bristol Rheumatoid Arthritis Fatigue (BRAF) Numerical Rating Scale (NRS) Fatigue Effect. Following training, RHPs delivered two to four sessions to participants. Baseline data were collected before the first session (T0) and outcomes at 6 weeks (T1) and 6 months (T2). The proposed primary outcome was fatigue impact (BRAF NRS Fatigue Effect). Secondary outcomes included fatigue severity and coping, disease impact and disability, and measures of therapeutic mechanism (self-efficacy and confidence to manage health).ResultsEight RHPs at five hospitals delivered 113 sessions to 46 participants. Of a potential 138 primary and secondary outcome responses at T0, T1 and T2, there were 13 (9.4%) and 27 (19.6%) missing primary and secondary outcome responses, respectively. Results indicated improvements in all measures except disability, at either T1 or T2, or both.ConclusionsThis study showed it was feasible to deliver the intervention, including training RHPs, and recruit and follow-up participants with high retention. While there was no control group, observed within-group improvements suggest potential promise of the intervention and support for a definitive trial to test effectiveness.
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20

Singh, Rachna, M. R. Shivaprakash, and Arunaloke Chakrabarti. "Biofilm formation by zygomycetes: quantification, structure and matrix composition." Microbiology 157, no. 9 (September 1, 2011): 2611–18. http://dx.doi.org/10.1099/mic.0.048504-0.

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Most studies on fungal biofilms have focused on Candida in yeasts and Aspergillus in mycelial fungi. To the authors’ knowledge, biofilm formation by zygomycetes has not been reported previously. In this study, the biofilm-forming capacity of Rhizopus oryzae, Lichtheimia corymbifera, Rhizomucor pusillus and Apophysomyces elegans was evaluated. At appropriate seeding spore densities, Rhp . oryzae (105 c.f.u. ml−1), L. corymbifera (104 c.f.u. ml−1) and Rhm. pusillus (104 c.f.u. ml−1) produced highly intertwined, adherent structures on flat-bottomed polystyrene microtitre plates after 24 h at 37 °C. The adhered fungal hyphae were encased in an extracellular matrix, as confirmed by phase-contrast and confocal microscopy. The thickness of Rhp. oryzae, L. corymbifera and Rhm. pusillus biofilms was 109.67±10.02, 242±23.07 and 197±9.0 µm (mean±sd), respectively. Biochemical characterization of the biofilm matrix indicated the presence of glucosamine, constituting 74.54–82.22 % of its dry weight, N-acetylglucosamine, glucose and proteins. Adherence and biofilm formation were not observed in A. elegans. Although A. elegans spores germinated at all three seeding densities tested (1×107, 1×106 and 1×105 c.f.u. ml−1), no significant difference was observed (P>0.05) between the A 490 of wells inoculated with A. elegans and the cut-off A 490 for biofilm detection. This study highlights the potential for biofilm formation by at least three medically important species of zygomycetes.
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21

Hsueh, Yuan-Shuo, Yan-Jye Shyong, Hsiu-Ching Yu, Shu-Jhen Jheng, Shang-Wen Lin, Hua-Lin Wu, and Jui-Chen Tsai. "Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration." Pharmaceutics 13, no. 9 (September 2, 2021): 1386. http://dx.doi.org/10.3390/pharmaceutics13091386.

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Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.
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22

Grinnell, BW, JD Walls, C. Marks, AL Glasebrook, DT Berg, SB Yan, and NU Bang. "Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties." Blood 76, no. 12 (December 15, 1990): 2546–54. http://dx.doi.org/10.1182/blood.v76.12.2546.2546.

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Abstract Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12–664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12–664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.
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Grinnell, BW, JD Walls, C. Marks, AL Glasebrook, DT Berg, SB Yan, and NU Bang. "Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties." Blood 76, no. 12 (December 15, 1990): 2546–54. http://dx.doi.org/10.1182/blood.v76.12.2546.bloodjournal76122546.

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Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12–664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12–664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.
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24

Smith, P. D., C. L. Lamerson, H. L. Wong, L. M. Wahl, and S. M. Wahl. "Granulocyte-macrophage colony-stimulating factor stimulates human monocyte accessory cell function." Journal of Immunology 144, no. 10 (May 15, 1990): 3829–34. http://dx.doi.org/10.4049/jimmunol.144.10.3829.

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Abstract We investigated the effect of recombinant human granulocyte-macrophage CSF (rhGM-CSF) on the accessory cell function of purified human monocytes. Compared with untreated monocytes, rhGM-CSF-treated monocytes promoted enhanced mitogen- and Ag-stimulated lymphocyte proliferation. This enhancement was significantly inhibited by mAb to rhGM-CSF. In experiments designed to define the mechanism of rhGM-CSF augmentation of accessory cell function, rhGM-CSF was shown to cause a dose-dependent increase in monocyte expression of surface HLA-DR molecules and stimulated secretion of IL-1, both important in monocyte T cell interactions. Further studies demonstrated that levels of HLA-DR and IL-1 mRNA were increased by rhGM-CSF, indicating transcriptional regulation of gene expression for HLA-DR and IL-1. Thus, rhGM-CSF augments accessory cell function by human monocytes, and this augmentation correlates with rhGM-CSF-induced increases in transcription of the HLA-DR and IL-1 genes leading to increased expression of surface HLA-DR and secretion of IL-1.
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25

Dyson, Sue, and Danica Pollard. "Application of the Ridden Horse Pain Ethogram to Horses Competing in British Eventing 90, 100 and Novice One-Day Events and Comparison with Performance." Animals 12, no. 5 (February 25, 2022): 590. http://dx.doi.org/10.3390/ani12050590.

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The Ridden Horse Pain Ethogram (RHpE) was applied to 1010 competition starts at British Eventing (BE) 90, 100 and Novice one-day events and compared with performance. The overall median RHpE score was 4/24 (IQR 2,6; range 0,12). There were moderate positive correlations between RHpE scores and dressage penalties (Spearman’s rho = 0.508, 0.468, 0.491, all p < 0.001 for BE 90, 100 and Novice, respectively). There were weak positive correlations between RHpE scores and final placings (Spearman’s rho = 0.157, p = 0.033, BE90; rho = 0.263, p < 0.001, BE 100; rho = 0.123, p = 0.035, Novice). In showjumping, 1.7% of starters were eliminated or retired, compared with 9.8% of cross-country starters. Horse or rider falls occurred in 2.6% of cross-country starts. Horses placed first, second or third had lower median RHpE scores (2/24, IQR 1,4; range 0,8) than other horses that finished (p < 0.001), those that were eliminated or retired (p < 0.001) or were withdrawn (p < 0.001). The RHpE score was ≥8/24 for 9.3% of starters; horses with a RHpE score ≥8/24 had higher total penalty scores (p < 0.001) than horses with a RHpE score <8/24. The overall low median RHpE score supports the social licence to compete, but 9% of starters had a RHpE score ≥8/24. Investigation and treatment of these horses may improve both welfare and performance.
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26

Yamakawa, Kazuma, Shinjiro Saito, Shigehiko Uchino, Daisuke Kudo, Yusuke Iizuka, Masamitsu Sanui, Kohei Takimoto, Toshihiko Mayumi, Kota Ono, and Mineji Hayakawa. "Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation." Thrombosis and Haemostasis 115, no. 06 (2016): 1157–66. http://dx.doi.org/10.1160/th15-12-0987.

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SummaryRecombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574–0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624–0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.
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Kono, Hiroshi, Naohiro Hosomura, Hidetake Amemiya, Hiromichi Kawaida, Shinji Furuya, Katsutoshi Shoda, Hidenori Akaike, Yoshihiko Kawaguchi, and Daisuke Ichikawa. "Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats." ImmunoHorizons 7, no. 1 (January 1, 2023): 159–67. http://dx.doi.org/10.4049/immunohorizons.2200094.

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Abstract This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(−) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.
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Fitzgerald, TJ, GA Neale, SC Raimondi, and RM Goorha. "Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia." Blood 80, no. 12 (December 15, 1992): 3189–97. http://dx.doi.org/10.1182/blood.v80.12.3189.3189.

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Abstract A frequent site for nonrandom recombination in T-cell acute lymphoblastic leukemia (T-ALL) is chromosome 11 at p13. The molecular characterization of a (7;11)(q35;p13) translocation showed that the translocation breakpoint was 2 kb 5′ to the T-ALLbcr locus resulting in the juxtaposition of the T-cell receptor (TCR) beta gene to the rhom-2 gene locus. Northern blot analysis did not detect expression of the rhom-2 gene in the leukemic blasts of the (7;11) translocation. However, using a sensitive polymerase chain reaction (PCR)-based assay, the (7;11) translocation showed a trace expression of rhom-2 at a level of 0.01% of TCR-beta message. Because rhom-2 is considered a proto- oncogene, the significance of the trace expression of rhom-2 in the (7;11) translocation was investigated by comparing the level of rhom-2 expression in 7 additional T-ALLs, normal thymocytes, and CEM (pre-T) and HPB (mature-T) cell lines using the PCR assay. The CEM cells, normal thymocytes, and one patient, whose blasts had no cytogenetic abnormality of chromosome 11, did not express rhom-2 indicating that rhom-2 is not normally expressed in T cells. The other six T-ALLs fell into three categories: (1) two T-ALLs overexpressed rhom-2 in the presence of a translocation; (2) two T-ALLs had trace expression in the presence of a translocation; and (3) two T-ALLs had trace expression with no observable abnormalities on chromosome 11 at p13. Therefore, the data indicate that not all translocations at the T-ALLbcr locus result in overexpression of rhom-2. To account for the sharp contrast in rhom-2 expression seen in these T-ALLs, a model is proposed with a negative regulatory element in the T-ALLbcr locus that is disrupted in some of the cases leading to overexpression of rhom-2.
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29

Fitzgerald, TJ, GA Neale, SC Raimondi, and RM Goorha. "Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia." Blood 80, no. 12 (December 15, 1992): 3189–97. http://dx.doi.org/10.1182/blood.v80.12.3189.bloodjournal80123189.

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A frequent site for nonrandom recombination in T-cell acute lymphoblastic leukemia (T-ALL) is chromosome 11 at p13. The molecular characterization of a (7;11)(q35;p13) translocation showed that the translocation breakpoint was 2 kb 5′ to the T-ALLbcr locus resulting in the juxtaposition of the T-cell receptor (TCR) beta gene to the rhom-2 gene locus. Northern blot analysis did not detect expression of the rhom-2 gene in the leukemic blasts of the (7;11) translocation. However, using a sensitive polymerase chain reaction (PCR)-based assay, the (7;11) translocation showed a trace expression of rhom-2 at a level of 0.01% of TCR-beta message. Because rhom-2 is considered a proto- oncogene, the significance of the trace expression of rhom-2 in the (7;11) translocation was investigated by comparing the level of rhom-2 expression in 7 additional T-ALLs, normal thymocytes, and CEM (pre-T) and HPB (mature-T) cell lines using the PCR assay. The CEM cells, normal thymocytes, and one patient, whose blasts had no cytogenetic abnormality of chromosome 11, did not express rhom-2 indicating that rhom-2 is not normally expressed in T cells. The other six T-ALLs fell into three categories: (1) two T-ALLs overexpressed rhom-2 in the presence of a translocation; (2) two T-ALLs had trace expression in the presence of a translocation; and (3) two T-ALLs had trace expression with no observable abnormalities on chromosome 11 at p13. Therefore, the data indicate that not all translocations at the T-ALLbcr locus result in overexpression of rhom-2. To account for the sharp contrast in rhom-2 expression seen in these T-ALLs, a model is proposed with a negative regulatory element in the T-ALLbcr locus that is disrupted in some of the cases leading to overexpression of rhom-2.
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30

Kanazawa, Nobuhiro, Masayuki Iyoda, Shohei Tachibana, Kei Matsumoto, Yukihiro Wada, Taihei Suzuki, Ken Iseri, and Takanori Shibata. "Therapeutic Potential of Thrombomodulin in Renal Fibrosis of Nephrotoxic Serum Nephritis in Wistar-Kyoto Rats." Kidney and Blood Pressure Research 45, no. 3 (2020): 391–406. http://dx.doi.org/10.1159/000506286.

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Background: Recombinant human soluble thrombomodulin (rhTM) was approved in 2008 and has been used for treatment of disseminated intravascular coagulation in Japan. The antifibrotic effects of rhTM in acute exacerbation of idiopathic pulmonary fibrosis are well established, but the therapeutic potential of rhTM in renal fibrosis remains poorly understood. Methods: Nephrotoxic serum nephritis (NTS-N) was induced in 22 female Wistar-Kyoto (WKY) rats on day 0. Rats were administered either rhTM or vehicle intraperitoneally, every day from day 4 to day 55. Rats were sacrificed on day 56 when renal fibrosis was established and renal morphological investigations were performed. In vitro, rat renal fibroblasts (NRK-49F) were pretreated with rhTM or saline, and expression levels of profibrogenic gene induced by thrombin were analyzed by real-time reverse transcription polymerase chain reaction. Results: Compared to WKY-GN-vehicle rats, the body weights of WKY-GN-rhTM rats were significantly greater on day 55. By day 56, rhTM had significantly reduced serum creatinine levels in NTS-N. On the other hand, urinary protein excretion was comparable between the two treatment groups throughout the study. The percentage of Masson trichrome-positive areas in WKY-GN-rhTM rats was significantly lower compared to that in WKY-GN-vehicle rats. Glomerular fibrin deposition was significantly reduced in WKY-GN-rhTM rats. In addition, rhTM significantly reduced the renal cortical mRNA expression levels of TNF-α, Toll-like receptor 4, MYD88, TGF-β, αSMA, collagen I, collagen III, fibronectin, and protease-activated receptor 1 (PAR1), a thrombin receptor. In vitro, thrombin stimulation of NRK-49F cells significantly enhanced the mRNA expression levels of αSMA and PAR1, and these upregulations were significantly reduced by pretreatment with rhTM. Conclusions: Administration of rhTM after establishment of crescentic glomerulonephritis (GN) attenuated the subsequent development of renal fibrosis in NTS-N, possibly in part by inhibiting thrombin-mediated fibrogenesis. Our results suggest that rhTM may offer a therapeutic option for limiting the progression of chronic kidney disease in crescentic GN.
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31

Nemunaitis, J., C. Anasetti, R. Storb, JA Bianco, CD Buckner, N. Onetto, P. Martin, J. Sanders, K. Sullivan, and M. Mori. "Phase II trial of recombinant human granulocyte-macrophage colony- stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors." Blood 79, no. 10 (May 15, 1992): 2572–77. http://dx.doi.org/10.1182/blood.v79.10.2572.2572.

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Abstract The safety and possible efficacy of recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2-hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF-treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM-CSF-treated group had a higher proportion of “good risk” patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus- host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM-CSF is required to confirm these suggestive data.
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32

Nemunaitis, J., C. Anasetti, R. Storb, JA Bianco, CD Buckner, N. Onetto, P. Martin, J. Sanders, K. Sullivan, and M. Mori. "Phase II trial of recombinant human granulocyte-macrophage colony- stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors." Blood 79, no. 10 (May 15, 1992): 2572–77. http://dx.doi.org/10.1182/blood.v79.10.2572.bloodjournal79102572.

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The safety and possible efficacy of recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2-hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF-treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM-CSF-treated group had a higher proportion of “good risk” patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus- host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM-CSF is required to confirm these suggestive data.
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33

Du, Z., Y. Li, H. Xia, A. M. Irani, and L. B. Schwartz. "Recombinant human granulocyte-macrophage colony-stimulating factor (CSF), but not recombinant human granulocyte CSF, down-regulates the recombinant human stem cell factor-dependent differentiation of human fetal liver-derived mast cells." Journal of Immunology 159, no. 2 (July 15, 1997): 838–45. http://dx.doi.org/10.4049/jimmunol.159.2.838.

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Abstract The effects of recombinant human granulocyte CSF (rhG-CSF) and recombinant human granulocyte-macrophage CSF (rhGM-CSF) on the recombinant human stem cell factor (rhSCF)-dependent development of human mast cells from fetal liver progenitors were examined. Mast cells were identified by immunohistochemical staining for tryptase and by flow cytometric analysis of surface Kit expression. Only rhGM-CSF affected mast cell development. When rhGM-CSF (1, 10, or 100 ng/ml) and rhSCF (50 ng/ml) were added to cell cultures from day 0, both the percentage and absolute numbers of mast cells were diminished after 4 wk compared with cultures exposed to rhSCF alone. Half of the maximal response was achieved at a dose of rhGM-CSF between 0.1 and 1 ng/ml. The Kit+ cells developing in the presence of rhGM-CSF and rhSCF exhibited an intensity of surface Kit expression comparable to that of cells exposed to rhSCF alone. Also, if the initial exposure to rhGM-CSF was delayed for 1 to 3 wk, attenuation of mast cell development waned. These findings are consistent with uncommitted progenitor cells being diverted to nonmast cell lineages by rhGM-CSF, while cells committed to a mast cell lineage, albeit immature, appear to be resistant to the lineage directives of rhGM-CSF. Exposure of fetal liver cells to rhGM-CSF for 1 to 3 days before addition of rhSCF further diminishes the number of mast cells that develop compared with the simultaneous addition of these growth factors on day 0. Whether administration of rhGM-CSF to humans before or together with rhSCF diminishes the mast cell hyperplasia that occurs with rhSCF alone remains to be determined.
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34

Monroy, RL, RR Skelly, TJ MacVittie, TA Davis, JJ Sauber, SC Clark, and RE Donahue. "The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow." Blood 70, no. 5 (November 1, 1987): 1696–99. http://dx.doi.org/10.1182/blood.v70.5.1696.1696.

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Abstract The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.
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35

Monroy, RL, RR Skelly, TJ MacVittie, TA Davis, JJ Sauber, SC Clark, and RE Donahue. "The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow." Blood 70, no. 5 (November 1, 1987): 1696–99. http://dx.doi.org/10.1182/blood.v70.5.1696.bloodjournal7051696.

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The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.
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36

Hamm, J., J. H. Schiller, C. Cuffie, M. Oken, R. I. Fisher, F. Shepherd, and G. Kaiser. "Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma." Journal of Clinical Oncology 12, no. 12 (December 1994): 2667–76. http://dx.doi.org/10.1200/jco.1994.12.12.2667.

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PURPOSE This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. PATIENTS AND METHODS A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. RESULTS In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/microliters, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P < or = .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.5% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 micrograms/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P < or = .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paresthesia, diarrhea, myalgia, musculoskeletal pain, Pruritus, and rash (P < or = .10). Fever occurred more frequently in the 10- and 20-micrograms/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-microgram/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. CONCLUSION rhGM-CSF at 5 to 10 micrograms/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies.
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McNeel, Douglas G., Kathy Schiffman, and Mary L. Disis. "Immunization With Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor as a Vaccine Adjuvant Elicits Both a Cellular and Humoral Response to Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor." Blood 93, no. 8 (April 15, 1999): 2653–59. http://dx.doi.org/10.1182/blood.v93.8.2653.

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Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important cytokine for the generation and propagation of antigen-presenting cells and for priming a cellular immune response. We report here that use of recombinant human GM-CSF (rhGM-CSF), administered as an adjuvant in a peptide-based vaccine trial given monthly by intradermal injection, led to the development of a T-cell and antibody response to rhGM-CSF. An antibody response occurred in the majority of patients (72%). This antibody response was not found to be neutralizing. In addition, by 48-hour delayed type hypersensitivity (DTH) skin testing, 17% of patients were shown to have a cellular immune response to the adjuvant rhGM-CSF alone. Thymidine incorporation assays also showed a peripheral blood T-cell response to rhGM-CSF in at least 17% of the patients. The generation of rhGM-CSF–specific T-cell immune responses, elicited in this fashion, is an important observation because rhGM-CSF is being used as a vaccine adjuvant in various vaccine strategies. rhGM-CSF–specific immune responses may be incorrectly interpreted as antigen-specific immunity, particularly when local DTH responses to vaccination are the primary means of immunologic evaluation. We found no evidence of hematologic or infectious complications as a result of the development of rhGM-CSF–specific immune responses.
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38

McNeel, Douglas G., Kathy Schiffman, and Mary L. Disis. "Immunization With Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor as a Vaccine Adjuvant Elicits Both a Cellular and Humoral Response to Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor." Blood 93, no. 8 (April 15, 1999): 2653–59. http://dx.doi.org/10.1182/blood.v93.8.2653.408k07_2653_2659.

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important cytokine for the generation and propagation of antigen-presenting cells and for priming a cellular immune response. We report here that use of recombinant human GM-CSF (rhGM-CSF), administered as an adjuvant in a peptide-based vaccine trial given monthly by intradermal injection, led to the development of a T-cell and antibody response to rhGM-CSF. An antibody response occurred in the majority of patients (72%). This antibody response was not found to be neutralizing. In addition, by 48-hour delayed type hypersensitivity (DTH) skin testing, 17% of patients were shown to have a cellular immune response to the adjuvant rhGM-CSF alone. Thymidine incorporation assays also showed a peripheral blood T-cell response to rhGM-CSF in at least 17% of the patients. The generation of rhGM-CSF–specific T-cell immune responses, elicited in this fashion, is an important observation because rhGM-CSF is being used as a vaccine adjuvant in various vaccine strategies. rhGM-CSF–specific immune responses may be incorrectly interpreted as antigen-specific immunity, particularly when local DTH responses to vaccination are the primary means of immunologic evaluation. We found no evidence of hematologic or infectious complications as a result of the development of rhGM-CSF–specific immune responses.
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39

Shimizu, Koji. "A -adic monodromy theorem for de Rham local systems." Compositio Mathematica 158, no. 12 (December 2022): 2157–205. http://dx.doi.org/10.1112/s0010437x2200776x.

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We study horizontal semistable and horizontal de Rham representations of the absolute Galois group of a certain smooth affinoid over a $p$ -adic field. In particular, we prove that a horizontal de Rham representation becomes horizontal semistable after a finite extension of the base field. As an application, we show that every de Rham local system on a smooth rigid analytic variety becomes horizontal semistable étale locally around every classical point. We also discuss potentially crystalline loci of de Rham local systems and cohomologically potentially good reduction loci of smooth proper morphisms.
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40

Tsuda, T., D. Wong, J. Dolovich, J. Bienenstock, J. Marshall, and JA Denburg. "Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation." Blood 77, no. 5 (March 1, 1991): 971–79. http://dx.doi.org/10.1182/blood.v77.5.971.971.

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Abstract We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.
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41

Tsuda, T., D. Wong, J. Dolovich, J. Bienenstock, J. Marshall, and JA Denburg. "Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation." Blood 77, no. 5 (March 1, 1991): 971–79. http://dx.doi.org/10.1182/blood.v77.5.971.bloodjournal775971.

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We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.
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42

Si, Fuchun. "Effects of removing heat and phlegm prescription on the proliferation and autoantigens expression of esophageal carcinoma cell." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e16510-e16510. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16510.

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e16510 Background: o explore the effects of removing heat and phlegm prescription (RHPP) on the proliferation and autoantigens expression of esophageal carcinoma(EC) cell, so as to provide basis for the molecular pathogenesis and clinical medication of EC. Methods: RHPP was developed by us for treating EC, EC autoantigens CK13, CK16, CaD, ACTG2 were identified in our previous studies. The effects of RHPP and and its ethanol extraction on the proliferation, cell cycle and autoantigen protein expression of Eca109 cell, EC9706 cell and TE-1 cell were investigated by MTT assay, flow cytometry and western blot analysis. Results: RHPP and its removing heat (RH) and removing phlegm (RP) separated prescriptions all have inhibitory effects on the proliferation of EC9706, EC109 and TE-1 cells in dose-dependent and time-dependent manner, changed morphology of four esophageal carcinoma cells, which appeared as round with rough edges, karyopyknosis, and karyorrhexis. Ic50 values of RHPP for Ec9706, Eca109 and TE1 cell were 33.31 ug·ml−1, 20.70 ug·ml−1, 21.93 ug·ml−1 respectively, while Ic50 values of RHPP’s ethanol extraction for Ec9706, Eca109, TE1 were 0.653 ug·ml−1, 0.082 ug·ml−1, 0.172 ug·ml−1 respectively. RHPP and RP induced G2/M phase arrest in EC109 and TE-1 cells, while RH induced G0/G1 phase arrest in EC109 and TE-1 cells; RHPP and RP induced G0/G1 phase arrest in EC9706 cells, while RH induced S phase arrest in EC9706 cells. RHPP and its two separated prescription could downregulate CK16, CaD, ACTG2 expression and upregulate CK13 expression. Conclusions: Autoantigens CK13, CK16, CaD and ACTG2 were expressed in EC cell, RHPP could regulate these four autoantigens expression. This study provides new basis for the EC mlecular mechanism and development of anti-esophageal carcinoma drugs in traditional Chinese medicine.
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43

Taguchi, K., A. Shibuya, Y. Inazawa, and T. Abe. "Suppressive effect of granulocyte-macrophage colony-stimulating factor on the generation of natural killer cells in vitro." Blood 79, no. 12 (June 15, 1992): 3227–32. http://dx.doi.org/10.1182/blood.v79.12.3227.3227.

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Abstract We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte- CSF (rhG-CSF) on the generation of natural killer (NK) cells in vitro. NK cells were cultured from selected human bone marrow cells obtained after the elimination of mature T and NK cells. rhGM-CSF significantly suppressed the generation of CD56+ cells and NK activity (P less than .01) in a dose-dependent manner. The generation of large granular lymphocytes (LGL) was also suppressed in the presence of rhGM-CSF (P less than .01). In contrast, rhG-CSF had no effect on LGL (P greater than .05). Both rhGM-CSF and rhG-CSF had no influence on the CD56+ cell count in the peripheral blood. These results suggest that rhGM-CSF suppresses the in vitro generation of NK cells.
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44

Taguchi, K., A. Shibuya, Y. Inazawa, and T. Abe. "Suppressive effect of granulocyte-macrophage colony-stimulating factor on the generation of natural killer cells in vitro." Blood 79, no. 12 (June 15, 1992): 3227–32. http://dx.doi.org/10.1182/blood.v79.12.3227.bloodjournal79123227.

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We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte- CSF (rhG-CSF) on the generation of natural killer (NK) cells in vitro. NK cells were cultured from selected human bone marrow cells obtained after the elimination of mature T and NK cells. rhGM-CSF significantly suppressed the generation of CD56+ cells and NK activity (P less than .01) in a dose-dependent manner. The generation of large granular lymphocytes (LGL) was also suppressed in the presence of rhGM-CSF (P less than .01). In contrast, rhG-CSF had no effect on LGL (P greater than .05). Both rhGM-CSF and rhG-CSF had no influence on the CD56+ cell count in the peripheral blood. These results suggest that rhGM-CSF suppresses the in vitro generation of NK cells.
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45

Zhou, Tianhong, Chunyan Yin, Yingchao Zhang, Heng Shi, Jingru Wang, Linbo Sun, Xiaolong Shao, Ruxia Gao, Wei Wang, and Xin Deng. "Lon Protease Is Involved in RhpRS-Mediated Regulation of Type III Secretion in Pseudomonas syringae." Molecular Plant-Microbe Interactions® 29, no. 10 (October 2016): 807–14. http://dx.doi.org/10.1094/mpmi-06-16-0114-r.

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Pseudomonas syringae depends on the type III secretion system (T3SS) to directly translocate effectors into host cells. Previously, we reported a nonpathogenic rhpS mutant, suggesting that the two-component transduction system rhpRS is an important regulator of T3SS in P. syringae. rhpRS regulates itself and a variety of downstream genes under an inverted repeat element promoter in a phosphorylation-dependent manner. Here, we identify lon as a suppressor of the rhpS mutant through transposon screening. A lon/rhpS double mutant restored the phenotypes of the rhpS mutant. The expression level of lon was higher in rhpS and other T3SS-deficient mutants than the wild-type strain, suggesting a negative feedback mechanism between lon and T3SS genes. lon was also induced by a novel T3SS inhibitor, acetate, which substantially compromises the activation of T3SS genes in minimal medium and bacterial growth in host plants.
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46

Shimina, G. G., A. V. Bateneva, E. S. Tsyplenkova, S. G. Gamaley, T. I. Esina, E. A. Volosnikova, and E. D. Danilenko. "HEMOSTIMULATING PROPERTIES OF THE CONJUGATES OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR WITH ALENDRONIC ACID." Pharmacy & Pharmacology 10, no. 5 (December 15, 2022): 472–82. http://dx.doi.org/10.19163/2307-9266-2022-10-5-472-482.

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The aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in the bone tissue and bone marrow of mice.Materials and methods. The conjugates obtained by a solid-phase synthesis using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide or periodate oxidation, were used. A hemostimulating activity was evaluated in a model of a cytostatic myelosuppression induced by the administration of cyclophosphamide to CBA/Calac mice. RhGM-CSF preparations were injected subcutaneously for 4-5 days at the dose of 90 µg/kg. After the injections cycle had been completed, the total leukocyte and segmented neutrophil counts were carried out in the blood samples, and the total karyocyte count was carried out in the bone marrow samples.The tissue distribution of rhGM-CSF preparations was assessed in outbred CD-1 mice after a single intravenous administration at the effective dose. The content of rhGM-CSF in blood, femoral tissue and bone marrow was determined by enzyme immunoassay.Results. RhGM-CSF conjugates with ALN have been shown to retain the ability of the original protein to increase the number of leukocytes, segmented blood neutrophils, and bone marrow karyocytes under the action of conjugates. The stimulation of the neutrophil production used to be observed at earlier times than in the case of rhGM-CSF. The increase in the total number of bone marrow cells after the introduction of all three conjugates was more pronounced compared to the original protein (by 34%). The increased hemostimulatory effect of the AEG conjugate was accompanied by a more intense accumulation of rhGM-CSF in the bone tissue and bone marrow of mice. The rhGM-CSF introduced into the conjugate was detected in the bone tissue for 24 h and it circulated in the bloodstream for a longer time compared to the original protein.Conclusion. The data obtained make it possible to conclude that further work on the development of effective hemostimulating drugs based on rhGM-CSF conjugates with ALN, is promising.
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47

O'Day, SJ, SN Rabinowe, D. Neuberg, AS Freedman, RJ Soiffer, NA Spector, MJ Robertson, K. Anderson, M. Whelan, and K. Pesek. "A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission." Blood 83, no. 9 (May 1, 1994): 2707–14. http://dx.doi.org/10.1182/blood.v83.9.2707.2707.

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Abstract Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.
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48

O'Day, SJ, SN Rabinowe, D. Neuberg, AS Freedman, RJ Soiffer, NA Spector, MJ Robertson, K. Anderson, M. Whelan, and K. Pesek. "A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission." Blood 83, no. 9 (May 1, 1994): 2707–14. http://dx.doi.org/10.1182/blood.v83.9.2707.bloodjournal8392707.

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Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.
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49

Illusie, Luc. "Rham � coefficients." Duke Mathematical Journal 60, no. 1 (February 1990): 139–85. http://dx.doi.org/10.1215/s0012-7094-90-06005-3.

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50

Nemunaitis, J., CD Buckner, FR Appelbaum, CS Higano, M. Mori, J. Bianco, C. Epstein, J. Lipani, J. Hansen, and R. Storb. "Phase I/II trial of recombinant human granulocyte-macrophage colony- stimulating factor following allogeneic bone marrow transplantation." Blood 77, no. 9 (May 1, 1991): 2065–71. http://dx.doi.org/10.1182/blood.v77.9.2065.2065.

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Abstract Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical “good risk” patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.
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