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5. Lactose drives Enterococcus expansion to promote graft-versus-host disease

Author

Stein-Thoeringer, C. K., primary, Nichols, K. B., additional, Lazrak, A., additional, Docampo, M. D., additional, Slingerland, A. E., additional, Slingerland, J. B., additional, Clurman, A. G., additional, Armijo, G., additional, Gomes, A. L. C., additional, Shono, Y., additional, Staffas, A., additional, Burgos da Silva, M., additional, Devlin, S. M., additional, Markey, K. A., additional, Bajic, D., additional, Pinedo, R., additional, Tsakmaklis, A., additional, Littmann, E. R., additional, Pastore, A., additional, Taur, Y., additional, Monette, S., additional, Arcila, M. E., additional, Pickard, A. J., additional, Maloy, M., additional, Wright, R. J., additional, Amoretti, L. A., additional, Fontana, E., additional, Pham, D., additional, Jamal, M. A., additional, Weber, D., additional, Sung, A. D., additional, Hashimoto, D., additional, Scheid, C., additional, Xavier, J. B., additional, Messina, J. A., additional, Romero, K., additional, Lew, M., additional, Bush, A., additional, Bohannon, L., additional, Hayasaka, K., additional, Hasegawa, Y., additional, Vehreschild, M. J. G. T., additional, Cross, J. R., additional, Ponce, D. M., additional, Perales, M. A., additional, Giralt, S. A., additional, Jenq, R. R., additional, Teshima, T., additional, Holler, E., additional, Chao, N. J., additional, Pamer, E. G., additional, Peled, J. U., additional, and van den Brink, M. R. M., additional

Published
2019
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9. Lactose drives Enterococcus expansion to promote graft-versus-host disease

Author

Stein-Thoeringer, C. K., Nichols, K. B., Lazrak, A., Docampo, M. D., Slingerland, A. E., Slingerland, J. B., Clurman, A. G., Armijo, G., Gomes, A. L. C., Shono, Y., Staffas, A., da Silva, M. Burgos, Devlin, S. M., Markey, K. A., Bajic, D., Pinedo, R., Tsakmaklis, A., Littmann, E. R., Pastore, A., Taur, Y., Monette, S., Arcila, M. E., Pickard, A. J., Maloy, M., Wright, R. J., Amoretti, L. A., Fontana, E., Pham, D., Jamal, M. A., Weber, D., Sung, A. D., Hashimoto, D., Scheid, C., Xavier, J. B., Messina, J. A., Romero, K., Lew, M., Bush, A., Bohannon, L., Hayasaka, K., Hasegawa, Y., Vehreschild, M. J. G. T., Cross, J. R., Ponce, D. M., Perales, M. A., Giralt, S. A., Jenq, R. R., Teshima, T., Holler, E., Chao, N. J., Pamer, E. G., Peled, J. U., van den Brink, M. R. M., Stein-Thoeringer, C. K., Nichols, K. B., Lazrak, A., Docampo, M. D., Slingerland, A. E., Slingerland, J. B., Clurman, A. G., Armijo, G., Gomes, A. L. C., Shono, Y., Staffas, A., da Silva, M. Burgos, Devlin, S. M., Markey, K. A., Bajic, D., Pinedo, R., Tsakmaklis, A., Littmann, E. R., Pastore, A., Taur, Y., Monette, S., Arcila, M. E., Pickard, A. J., Maloy, M., Wright, R. J., Amoretti, L. A., Fontana, E., Pham, D., Jamal, M. A., Weber, D., Sung, A. D., Hashimoto, D., Scheid, C., Xavier, J. B., Messina, J. A., Romero, K., Lew, M., Bush, A., Bohannon, L., Hayasaka, K., Hasegawa, Y., Vehreschild, M. J. G. T., Cross, J. R., Ponce, D. M., Perales, M. A., Giralt, S. A., Jenq, R. R., Teshima, T., Holler, E., Chao, N. J., Pamer, E. G., Peled, J. U., and van den Brink, M. R. M.

Abstract

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Published
2019

14. Forecasting in vivo oral absorption and food effect of micronized and nanosized aprepitant formulations in humans

Author

Shono, Y. Jantratid, E. Kesisoglou, F. Reppas, C. Dressman, J.B.

Abstract

This study coupled results from biorelevant dissolution tests with in silico simulation technology to forecast in vivo oral absorption of micronized and nanosized aprepitant formulations in the pre- and post-prandial states. In vitro dissolution tests of the nanosized aprepitant formulation and micronized drug were performed in biorelevant and compendial media. An in silico physiologically based pharmacokinetic (PBPK) model was developed based on STELLA® software using dissolution kinetics, standard gastrointestinal (GI) parameters and post-absorptive disposition parameters. GI parameters (gastric emptying rate and GI fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the in vivo oral PK data. Predictions of in vivo performance in each prandial state were evaluated using the AUC and Cmax generated from the simulated PK profiles. To predict oral absorption from the extremely fast dissolving nanosized aprepitant formulation, several variations on a previously published model were evaluated. Although models that assumed that the formulation behaved as an oral solution or that adjusted the dissolution kinetics according to the different numbers of particles per gram between micronized and nanosized aprepitant generated profiles similar to the observed in vivo data in the fed state, simulated profiles for the fasted state showed much faster absorption than that observed in the in vivo data. This appeared to result from the assumption of no absorption restrictions in those models. To better predict in vivo performance in both fasted and fed states, a model that adds permeability restrictions to absorption was applied. This model not only simulated the in vivo profiles for aprepitant well in both prandial states, but also predicted the dependency of the pharmacokinetics on the dose and the particle size of aprepitant. In conclusion, a model based on STELLA® software combined with dissolution results in biorelevant media successfully forecasts the in vivo performance of both nanosized and micronized formulations of aprepitant in the fed and fasted states. Although dissolution is the primary limitation to the rate of absorption for micronized aprepitant, some permeability restrictions are revealed for the nanosized formulation. The results also indicate that biorelevant dissolution media have strong advantages over compendial media in forecasting the in vivo behavior of aprepitant. © 2010 Elsevier B.V.

Published
2010

15. The benefits and costs of prior exposure: a large-scale study of interference effects in stimulus identification

Author

Maura Pilotti, Chodorow, M., and Shono, Y.

Subjects
Association Learning, Reactive Inhibition, Experimental and Cognitive Psychology, Awareness, Verbal Learning, Choice Behavior, Semantics, Memory, Short-Term, Proactive Inhibition, Arts and Humanities (miscellaneous), Developmental and Educational Psychology, Humans, Attention, Cues
Abstract

The effects of proactive and retroactive interference arising from incidental learning were examined in reference to identity priming. The main aim was to determine whether these effects would be modulated by phenomenological awareness. In an incidental surface task, subjects processed 2 lists of orthographically similar or dissimilar words. At test, they were asked to select or generate words that completed test cues and then indicate whether they recognized the words as studied. The test cues were either studied or nonstudied words. Interference was conceptualized as response competition arising from the orthographically similar words subjects encountered at study. Studying orthographically similar words had negative effects on identity priming. When the test required word generation, these interference effects appeared to be modulated by subjects’ awareness of the test cues as studied words. These results add a new perspective to the account of interference as response competition according to which the richness of test cues plays a significant role in shaping the effects of interference.

Published
2009

16. Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling

Author

Shono, Y. Jantratid, E. Janssen, N. Kesisoglou, F. Mao, Y. Vertzoni, M. Reppas, C. Dressman, J.B.

Abstract

Since the rate-determining step to the intestinal absorption of poorly soluble drugs is the dissolution in the gastrointestinal (GI) tract, postprandial changes in GI physiology, in addition to any specific interactions between drug and food, are expected to affect the pharmacokinetics and bioavailability of such drugs. In this study, in vitro dissolution testing using biorelevant media coupled with in silico physiologically based pharmacokinetic (PBPK) modeling was applied to the prediction of food effects on the absorption of a poorly soluble drug, celecoxib, from 200 mg capsules. A PBPK model was developed based on STELLA® software using dissolution kinetics, solubility, standard GI parameters and post-absorptive disposition parameters. Solubility, dissolution profiles and initial dissolution rate from celecoxib 200 mg capsules were measured in biorelevant and compendial media. Standard GI parameters (gastric emptying rate and fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the oral PK data, since intravenous data are not available for celecoxib. Predictions of food effects and average plasma profiles were evaluated using the AUC and Cmax and the difference factor (f1). An approximately 7-fold difference in the maximum percentage dissolved was observed in in vitro dissolution tests designed to represent the fed and fasted states. By contrast, the food effect estimated by simulating the plasma profiles with the PBPK model predicted only a slight delay in the peak plasma level (∼1 h), and modest increases in the Cmax and AUC of ∼1.9-fold and 1.3-fold in the fed state, respectively. The PBPK approach, combining in silico simulation coupled with biorelevant dissolution test results, thus corresponds much better to the food effect observed for celecoxib in vivo. Additionally, point estimates of AUC and Cmax as well as f1 calculations demonstrated clear advantages of using results in biorelevant rather than compendial media in the PBPK model. © 2009 Elsevier B.V. All rights reserved.

Published
2009

19. Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD

Author

Sugita, J, primary, Matsushita, T, additional, Kashiwazaki, H, additional, Kosugi, M, additional, Takahashi, S, additional, Wakasa, K, additional, Shiratori, S, additional, Ibata, M, additional, Shono, Y, additional, Shigematsu, A, additional, Obara, M, additional, Fujimoto, K, additional, Endo, T, additional, Nishio, M, additional, Kondo, T, additional, Hashino, S, additional, Tanaka, J, additional, Asaka, M, additional, and Imamura, M, additional

Published
2011
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23. Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma

Author

TOUBAI, T., primary, HIRATE, D., additional, SHONO, Y., additional, OTA, S., additional, IBATA, M., additional, MASHIKO, S., additional, SUGITA, J., additional, SHIGEMATSU, A., additional, MIURA, Y., additional, KATO, N., additional, UMEHARA, S., additional, KAHATA, K., additional, TSUTSUMI, Y., additional, IWAO, N., additional, TOYOSHIMA, N., additional, TANAKA, J., additional, ASAKA, M., additional, and IMAMURA, M., additional

Published
2007
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24. A41 Analysis of environmental factors affecting efficacy of metofluthrin-impregnated latticework plastic strips against Aedes aegypti (L.) in My Tho city, Tien Giang, Vietnam(General presentation,Abstract,The 58th Annual Meeting of the Japan Society of Medical Entomology and Zoology)

Author

Kawada, H, primary, Iwasaki, T, additional, Loan, Luu Le, additional, Tien, Tran Khanh, additional, Mai, Nguyen Thi Nhu, additional, Shono, Y, additional, Katayama, Y, additional, and Takagi, M, additional

Published
2006
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