Search

Your search keyword '"Lachowicz J"' showing total 199 results
Start Over Author "Lachowicz J"
199 results on '"Lachowicz J"'

2. Cytotoxicity, Oxidative Stress, and Autophagy in Human Alveolar Epithelial Cell Line (A549 Cells) Exposed to Standardized Urban Dust

Author

Lukaszewicz, A., Cwiklinska, M., Zarzecki, M., Szoka, P., Lachowicz, J., Holownia, A., COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Pokorski, Mieczyslaw, editor

Published
2019
Full Text
View/download PDF

8. Human breast milk cells are positive for the pioneer transcription factor ISL1.

Author

PIRAS, M., CONI, P., PILUDU, M., CONI, S., LACHOWICZ, J. I., JAREMKO, M., FAA, G., CAU, F., SCANO, A., ORRÙ, G., MURRU, R., and PICHIRI, G.

Abstract

OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic ® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events. [ABSTRACT FROM AUTHOR]

Published
2023

12. Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes (vol 6, mgen000405, 2021)

Author

Rajendra, KC, Leong, KWC, Harkness, NM, Lachowicz, J, Gautam, SS, Cooley, LA, McEwan, B, Petrovski, S, Karupiah, G, O'Toole, RF, Rajendra, KC, Leong, KWC, Harkness, NM, Lachowicz, J, Gautam, SS, Cooley, LA, McEwan, B, Petrovski, S, Karupiah, G, and O'Toole, RF

Published
2021

16. Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

Author

Rajendra, KC, Leong, KWC, Harkness, NM, Lachowicz, J, Gautam, SS, Cooley, LA, McEwan, B, Petrovski, S, Karupiah, G, O'Toole, RF, Rajendra, KC, Leong, KWC, Harkness, NM, Lachowicz, J, Gautam, SS, Cooley, LA, McEwan, B, Petrovski, S, Karupiah, G, and O'Toole, RF

Abstract

Nontypeable Haemophilus influenzae (NTHi) colonizes human upper respiratory airways and plays a key role in the course and pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (COPD). Currently, it is not possible to distinguish COPD isolates of NTHi from other clinical isolates of NTHi using conventional genotyping methods. Here, we analysed the core and accessory genome of 568 NTHi isolates, including 40 newly sequenced isolates, to look for genetic distinctions between NTHi isolates from COPD with respect to other illnesses, including otitis media, meningitis and pneumonia. Phylogenies based on polymorphic sites in the core-genome did not show discrimination between NTHi strains collected from different clinical phenotypes. However, pan-genome-wide association studies identified 79 unique NTHi accessory genes that were significantly associated with COPD. Furthermore, many of the COPD-related NTHi genes have known or predicted roles in virulence, transmembrane transport of metal ions and nutrients, cellular respiration and maintenance of redox homeostasis. This indicates that specific genes may be required by NTHi for its survival or virulence in the COPD lung. These results advance our understanding of the pathogenesis of NTHi infection in COPD lungs.

Published
2020

26. Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one

Author

Lachowicz, J. I., primary, Nurchi, V. M., additional, Crisponi, G., additional, Jaraquemada-Pelaez, M. G., additional, Arca, M., additional, Pintus, A., additional, Santos, M. A., additional, Quintanova, C., additional, Gano, L., additional, Szewczuk, Z., additional, Zoroddu, M. A., additional, Peana, M., additional, Domínguez-Martín, A., additional, and Choquesillo-Lazarte, D., additional

Published
2016
Full Text
View/download PDF

30. Seasonal variations of the digestive tract of the Eurasian beaver Castor fiber.

Author

Bełżecki, G., Miltko, R., Kowalik, B., Demiaszkiewicz, A., Lachowicz, J., Giżejewski, Z., Obidziński, A., and McEwan, N.

Abstract

Forage availability for wild rodents varies with season. In turn, the composition of food can affect morphometric parameters of the digestive tract. This study was performed in Eurasian beavers ( Castor fiber) whose population was close to extinction in most Eurasian countries, but has now increased. Due to the previous low number of studies, information about the effect of forage availability on the digestive tract morphology has previously been lacking. This study was performed using beavers captured from the natural environment during three seasons of different forage availability: winter, summer and autumn. It was found that the diet of the beaver varied during the year; in winter it was dominated by woody material consisting of willow shoots, whereas in summer the diet was primarily herbs, grass and leaves. Season also affected the mass of digested contents of the digestive tract. The digestive content increased in the caecum and colon in winter and autumn, when poor-quality food dominated the beaver's diet. The results indicated that the digestive tract parameters of beavers varied based on the composition of available forage. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

33. EXPERIMENTAL THERAPEUTICS AND PHARMACOLOGY

Author

Aaberg-Jessen, C., primary, Fogh, L., additional, Halle, B., additional, Jensen, V., additional, Brunner, N., additional, Kristensen, B. W., additional, Abe, T., additional, Momii, Y., additional, Watanabe, J., additional, Morisaki, I., additional, Natsume, A., additional, Wakabayashi, T., additional, Fujiki, M., additional, Aldaz, B., additional, Fabius, A. W. M., additional, Silber, J., additional, Harinath, G., additional, Chan, T. A., additional, Huse, J. T., additional, Anai, S., additional, Hide, T., additional, Nakamura, H., additional, Makino, K., additional, Yano, S., additional, Kuratsu, J.-i., additional, Balyasnikova, I. V., additional, Prasol, M. S., additional, Kanoija, D. K., additional, Aboody, K. S., additional, Lesniak, M. S., additional, Barone, T., additional, Burkhart, C., additional, Purmal, A., additional, Gudkov, A., additional, Gurova, K., additional, Plunkett, R., additional, Barton, K., additional, Misuraca, K., additional, Cordero, F., additional, Dobrikova, E., additional, Min, H., additional, Gromeier, M., additional, Kirsch, D., additional, Becher, O., additional, Pont, L. B., additional, Kloezeman, J., additional, van den Bent, M., additional, Kanaar, R., additional, Kremer, A., additional, Swagemakers, S., additional, French, P., additional, Dirven, C., additional, Lamfers, M., additional, Leenstra, S., additional, Balvers, R., additional, Kleijn, A., additional, Lawler, S., additional, Gong, X., additional, Andres, A., additional, Hanson, J., additional, Delashaw, J., additional, Bota, D., additional, Chen, C.-C., additional, Yao, N.-W., additional, Chuang, W.-J., additional, Chang, C., additional, Chen, P.-Y., additional, Huang, C.-Y., additional, Wei, K.-C., additional, Cheng, Y., additional, Dai, Q., additional, Morshed, R., additional, Han, Y., additional, Auffinger, B., additional, Wainwright, D., additional, Zhang, L., additional, Tobias, A., additional, Rincon, E., additional, Thaci, B., additional, Ahmed, A., additional, He, C., additional, Lesniak, M., additional, Choi, Y. A., additional, Pandya, H., additional, Gibo, D. M., additional, Fokt, I., additional, Priebe, W., additional, Debinski, W., additional, Chornenkyy, Y., additional, Agnihotri, S., additional, Buczkowicz, P., additional, Rakopoulos, P., additional, Morrison, A., additional, Barszczyk, M., additional, Hawkins, C., additional, Chung, S., additional, Decollogne, S., additional, Luk, P., additional, Shen, H., additional, Ha, W., additional, Day, B., additional, Stringer, B., additional, Hogg, P., additional, Dilda, P., additional, McDonald, K., additional, Moore, S., additional, Hayden-Gephart, M., additional, Bergen, J., additional, Su, Y., additional, Rayburn, H., additional, Edwards, M., additional, Scott, M., additional, Cochran, J., additional, Das, A., additional, Varma, A. K., additional, Wallace, G. C., additional, Dixon-Mah, Y. N., additional, Vandergrift, W. A., additional, Giglio, P., additional, Ray, S. K., additional, Patel, S. J., additional, Banik, N. L., additional, Dasgupta, T., additional, Olow, A., additional, Yang, X., additional, Mueller, S., additional, Prados, M., additional, James, C. D., additional, Haas-Kogan, D., additional, Dave, N. D., additional, Desai, P. B., additional, Gudelsky, G. A., additional, Chow, L. M. L., additional, LaSance, K., additional, Qi, X., additional, Driscoll, J., additional, Ebsworth, K., additional, Walters, M. J., additional, Ertl, L. S., additional, Wang, Y., additional, Berahovic, R. D., additional, McMahon, J., additional, Powers, J. P., additional, Jaen, J. C., additional, Schall, T. J., additional, Eroglu, Z., additional, Portnow, J., additional, Sacramento, A., additional, Garcia, E., additional, Raubitschek, A., additional, Synold, T., additional, Esaki, S., additional, Rabkin, S., additional, Martuza, R., additional, Wakimoto, H., additional, Ferluga, S., additional, Tome, C. L., additional, Forde, H. E., additional, Netland, I. A., additional, Sleire, L., additional, Skeie, B., additional, Enger, P. O., additional, Goplen, D., additional, Giladi, M., additional, Tichon, A., additional, Schneiderman, R., additional, Porat, Y., additional, Munster, M., additional, Dishon, M., additional, Weinberg, U., additional, Kirson, E., additional, Wasserman, Y., additional, Palti, Y., additional, Gramatzki, D., additional, Staudinger, M., additional, Frei, K., additional, Peipp, M., additional, Weller, M., additional, Grasso, C., additional, Liu, L., additional, Berlow, N., additional, Davis, L., additional, Fouladi, M., additional, Gajjar, A., additional, Huang, E., additional, Hulleman, E., additional, Hutt, M., additional, Keller, C., additional, Li, X.-N., additional, Meltzer, P., additional, Quezado, M., additional, Quist, M., additional, Raabe, E., additional, Spellman, P., additional, Truffaux, N., additional, van Vurden, D., additional, Wang, N., additional, Warren, K., additional, Pal, R., additional, Grill, J., additional, Monje, M., additional, Green, A. L., additional, Ramkissoon, S., additional, McCauley, D., additional, Jones, K., additional, Perry, J. A., additional, Ramkissoon, L., additional, Maire, C., additional, Shacham, S., additional, Ligon, K. L., additional, Kung, A. L., additional, Zielinska-Chomej, K., additional, Grozman, V., additional, Tu, J., additional, Viktorsson, K., additional, Lewensohn, R., additional, Gupta, S., additional, Mladek, A., additional, Bakken, K., additional, Carlson, B., additional, Boakye-Agyeman, F., additional, Kizilbash, S., additional, Schroeder, M., additional, Reid, J., additional, Sarkaria, J., additional, Hadaczek, P., additional, Ozawa, T., additional, Soroceanu, L., additional, Yoshida, Y., additional, Matlaf, L., additional, Singer, E., additional, Fiallos, E., additional, Cobbs, C. S., additional, Hashizume, R., additional, Tom, M., additional, Ihara, Y., additional, Santos, R., additional, Torre, J. D. L., additional, Lepe, E., additional, Waldman, T., additional, James, D., additional, Huang, X., additional, Yu-Jen, L., additional, Gupta, N., additional, Solomon, D., additional, Zhang, Z., additional, Hayashi, T., additional, Adachi, K., additional, Nagahisa, S., additional, Hasegawa, M., additional, Hirose, Y., additional, Gephart, M. H., additional, Su, Y. S., additional, Hingtgen, S., additional, Kasmieh, R., additional, Nesterenko, I., additional, Figueiredo, J.-L., additional, Dash, R., additional, Sarkar, D., additional, Fisher, P., additional, Shah, K., additional, Horne, E., additional, Diaz, P., additional, Stella, N., additional, Huang, C., additional, Yang, H., additional, Wei, K., additional, Huang, T., additional, Hlavaty, J., additional, Ostertag, D., additional, Espinoza, F. L., additional, Martin, B., additional, Petznek, H., additional, Rodriguez-Aguirre, M., additional, Ibanez, C., additional, Kasahara, N., additional, Gunzburg, W., additional, Gruber, H., additional, Pertschuk, D., additional, Jolly, D., additional, Robbins, J., additional, Hurwitz, B., additional, Yoo, J. Y., additional, Bolyard, C., additional, Yu, J.-G., additional, Wojton, J., additional, Zhang, J., additional, Bailey, Z., additional, Eaves, D., additional, Cripe, T., additional, Old, M., additional, Kaur, B., additional, Serwer, L., additional, Le Moan, N., additional, Ng, S., additional, Butowski, N., additional, Krtolica, A., additional, Cary, S. P. L., additional, Johns, T., additional, Greenall, S., additional, Donoghue, J., additional, Adams, T., additional, Karpel-Massler, G., additional, Westhoff, M.-A., additional, Kast, R. E., additional, Dwucet, A., additional, Wirtz, C. R., additional, Debatin, K.-M., additional, Halatsch, M.-E., additional, Merkur, N., additional, Kievit, F., additional, Stephen, Z., additional, Wang, K., additional, Kolstoe, D., additional, Ellenbogen, R., additional, Zhang, M., additional, Kitange, G., additional, Haefner, E., additional, Knubel, K., additional, Pernu, B. M., additional, Sufit, A., additional, Pierce, A. M., additional, Nelson, S. K., additional, Keating, A. K., additional, Jensen, S. S., additional, Lachowicz, J., additional, Demeule, M., additional, Regina, A., additional, Tripathy, S., additional, Curry, J.-C., additional, Nguyen, T., additional, Castaigne, J.-P., additional, Davis, T., additional, Davis, A., additional, Tanaka, K., additional, Keating, T., additional, Getz, J., additional, Kapp, G. T., additional, Romero, J. M., additional, Lee, S., additional, Ramisetti, S., additional, Slagle-Webb, B., additional, Sharma, A., additional, Connor, J., additional, Lee, W.-S., additional, Kluk, M., additional, Aster, J. C., additional, Ligon, K., additional, Sun, S., additional, Lee, D., additional, Ho, A. S. W., additional, Pu, J. K. S., additional, Zhang, Z.-q., additional, Lee, N. P., additional, Day, P. J. R., additional, Leung, G. K. K., additional, Liu, Z., additional, Liu, X., additional, Madhankumar, A. B., additional, Miller, P., additional, Webb, B., additional, Connor, J. R., additional, Yang, Q. X., additional, Lobo, M., additional, Green, S., additional, Schabel, M., additional, Gillespie, Y., additional, Woltjer, R., additional, Pike, M., additional, Lu, Y.-J., additional, Luchman, H. A., additional, Stechishin, O., additional, Nguyen, S., additional, Cairncross, J. G., additional, Weiss, S., additional, Lun, X., additional, Wells, J. C., additional, Hao, X., additional, Grinshtein, N., additional, Kaplan, D., additional, Luchman, A., additional, Senger, D., additional, Robbins, S., additional, Madhankumar, A., additional, Rizk, E., additional, Payne, R., additional, Park, A., additional, Pang, M., additional, Harbaugh, K., additional, Wilisch-Neumann, A., additional, Pachow, D., additional, Kirches, E., additional, Mawrin, C., additional, McDonell, S., additional, Liang, J., additional, Piao, Y., additional, Nguyen, N., additional, Yung, A., additional, Verhaak, R., additional, Sulman, E., additional, Stephan, C., additional, Lang, F., additional, de Groot, J., additional, Mizobuchi, Y., additional, Okazaki, T., additional, Kageji, T., additional, Kuwayama, K., additional, Kitazato, K. T., additional, Mure, H., additional, Hara, K., additional, Morigaki, R., additional, Matsuzaki, K., additional, Nakajima, K., additional, Nagahiro, S., additional, Kumala, S., additional, Heravi, M., additional, Devic, S., additional, Muanza, T., additional, Knubel, K. H., additional, Neuwelt, A., additional, Wu, Y. J., additional, Donson, A., additional, Vibhakar, R., additional, Venkatamaran, S., additional, Amani, V., additional, Neuwelt, E., additional, Rapkin, L., additional, Foreman, N., additional, Ibrahim, F., additional, New, P., additional, Cui, K., additional, Zhao, H., additional, Chow, D., additional, Stephen, W., additional, Nozue-Okada, K., additional, Nagane, M., additional, McDonald, K. L., additional, Ogawa, D., additional, Chiocca, E., additional, Godlewski, J., additional, Patel, A., additional, Pasupuleti, N., additional, Gorin, F., additional, Valenzuela, A., additional, Leon, L., additional, Carraway, K., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Phillips, A., additional, Boghaert, E., additional, Vaidya, K., additional, Ansell, P., additional, Shalinsky, D., additional, Zhang, Y., additional, Voorbach, M., additional, Mudd, S., additional, Holen, K., additional, Humerickhouse, R., additional, Reilly, E., additional, Parab, S., additional, Diago, O., additional, Ryken, T., additional, Agarwal, S., additional, Al-Keilani, M., additional, Alqudah, M., additional, Sibenaller, Z., additional, Assemolt, M., additional, Sai, K., additional, Li, W.-y., additional, Li, W.-p., additional, Chen, Z.-p., additional, Saito, R., additional, Sonoda, Y., additional, Kanamori, M., additional, Yamashita, Y., additional, Kumabe, T., additional, Tominaga, T., additional, Sarkar, G., additional, Curran, G., additional, Jenkins, R., additional, Scharnweber, R., additional, Kato, Y., additional, Lin, J., additional, Everson, R., additional, Soto, H., additional, Kruse, C., additional, Liau, L., additional, Prins, R., additional, Semenkow, S., additional, Chu, Q., additional, Eberhart, C., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Shai, R., additional, Pismenyuk, T., additional, Moshe, I., additional, Fisher, T., additional, Freedman, S., additional, Simon, A., additional, Amariglio, N., additional, Rechavi, G., additional, Toren, A., additional, Yalon, M., additional, Shimazu, Y., additional, Kurozumi, K., additional, Ichikawa, T., additional, Fujii, K., additional, Onishi, M., additional, Ishida, J., additional, Oka, T., additional, Watanabe, M., additional, Nasu, Y., additional, Kumon, H., additional, Date, I., additional, Sirianni, R. W., additional, McCall, R. L., additional, Spoor, J., additional, van der Kaaij, M., additional, Geurtjens, M., additional, Veiseh, O., additional, Fang, C., additional, Leung, M., additional, Strohbehn, G., additional, Atsina, K.-K., additional, Patel, T., additional, Piepmeier, J., additional, Zhou, J., additional, Saltzman, W. M., additional, Takahashi, M., additional, Valdes, G., additional, Inagaki, A., additional, Kamijima, S., additional, Hiraoka, K., additional, Micewicz, E., additional, McBride, W. H., additional, Iwamoto, K. S., additional, Gruber, H. E., additional, Robbins, J. M., additional, Jolly, D. J., additional, McCully, C., additional, Bacher, J., additional, Thomas, T., additional, Murphy, R., additional, Steffen-Smith, E., additional, McAllister, R., additional, Pastakia, D., additional, Widemann, B., additional, Chen, P., additional, Hua, M., additional, Liu, H., additional, Woolf, E. C., additional, Abdelwahab, M. G., additional, Fenton, K. E., additional, Liu, Q., additional, Turner, G., additional, Preul, M. C., additional, Scheck, A. C., additional, Shen, W., additional, Brown, D., additional, Pedersen, H., additional, Hariono, S., additional, Yao, T.-W., additional, Sidhu, A., additional, Weiss, W. A., additional, Nicolaides, T. P., additional, and Olusanya, T., additional

Published
2013
Full Text
View/download PDF

34. Doxorubicin chemotherapy for presumptive cardiac hemangiosarcoma in dogs†.

Author

Mullin, C.M., Arkans, M.A., Sammarco, C.D., Vail, D.M., Britton, B.M., Vickery, K.R., Risbon, R.E., Lachowicz, J., Burgess, K.E., Manley, C.A., and Clifford, C.A.

Subjects
DOXORUBICIN, ANGIOSARCOMA, DOG diseases, CANCER chemotherapy, PROGRESSION-free survival, UNIVARIATE analysis, THERAPEUTICS
Abstract

Sixty-four dogs were treated with single-agent doxorubicin ( DOX) for presumptive cardiac hemangiosarcoma ( cHSA). The objective response rate ( CR + PR) was 41%, and the biologic response rate ( CR + PR + SD), or clinical benefit, was 68%. The median progression-free survival ( PFS) for treated dogs was 66 days. The median survival time ( MST) for this group was 116 days and was significantly improved compared to a MST of 12 days for untreated control dogs ( P = 0.0001). Biologic response was significantly associated with improved PFS ( P < 0.0001) and OS ( P < 0.0001). Univariate analysis identified larger tumour size as a variable negatively associated with PFS. The high rate of clinical benefit and improved MST suggest that DOX has activity in canine cHSA. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

36. LAB-EXPERIMENTAL (PRE-CLINICAL) THERAPEUTICS AND PHARMACOLOGY

Author

Yang, F. H., primary, Zhang, B., additional, Zhou, D. J., additional, Bie, L., additional, Tom, M. W., additional, Drummond, D. C., additional, Nicolaides, T., additional, Mueller, S., additional, Banerjee, A., additional, Park, J. W., additional, Prados, M. D., additional, James, D. C., additional, Gupta, N., additional, Hashizume, R., additional, Strohbehn, G. W., additional, Zhou, J., additional, Fu, M., additional, Patel, T. R., additional, Piepmeier, J. M., additional, Saltzman, W. M., additional, Xie, Q., additional, Johnson, J., additional, Bradley, R., additional, Ascierto, M. L., additional, Kang, L., additional, Koeman, J., additional, Marincola, F. M., additional, Briggs, M., additional, Tanner, K., additional, Vande Woude, G. F., additional, Tanaka, S., additional, Klofas, L. K., additional, Wakimoto, H., additional, Borger, D. R., additional, Iafrate, A. J., additional, Batchelor, T. T., additional, Chi, A. S., additional, Madhankumar, A. B., additional, Slagle-Webb, B., additional, Rizk, E., additional, Harbaugh, K., additional, Connor, J. R., additional, Sarkar, G., additional, Curran, G. L., additional, Jenkins, R. B., additional, Kurozumi, K., additional, Ichikawa, T., additional, Onishi, M., additional, Fujii, K., additional, Ishida, J., additional, Shimazu, Y., additional, Date, I., additional, Ebsworth, K., additional, Walters, M. J., additional, Ertl, L. S., additional, Wang, Y., additional, Berahovich, R. D., additional, Zhang, P., additional, Powers, J. P., additional, Liu, S.-C., additional, Al Omran, R., additional, Sullivan, T. J., additional, Jaen, J. C., additional, Brown, M., additional, Schall, T. J., additional, Yusuke, N., additional, Shimizu, S., additional, Shishido-Hara, Y., additional, Shiokawa, Y., additional, Nagane, M., additional, Wang, J., additional, Sai, K., additional, Chen, F.-R., additional, Chen, Z.-P., additional, Shi, Z., additional, Zhang, J., additional, Zhang, K., additional, Han, L., additional, Chen, L., additional, Qian, X., additional, Zhang, A., additional, Wang, G., additional, Jia, Z., additional, Pu, P., additional, Kang, C., additional, Kong, L.-Y., additional, Doucette, T. A., additional, Ferguson, S. D., additional, Hachem, J., additional, Yang, Y., additional, Wei, J., additional, Priebe, W., additional, Fuller, G. N., additional, Qiao, W., additional, Rao, G., additional, Heimberger, A. B., additional, Chen, P.-Y., additional, Ozawa, T., additional, Drummond, D., additional, Santos, R., additional, Torre, J. D., additional, Ng, C., additional, Lepe, E. L., additional, Butowski, N., additional, Prados, M., additional, Bankiewicz, K., additional, James, C. D., additional, Cheng, Z., additional, Gong, Y., additional, Ma, Y., additional, Muller-Knapp, S., additional, Knapp, S., additional, Antonio Chiocca, E., additional, Kaur, B., additional, Yu, J. S., additional, Judkowski, V., additional, Bunying, A., additional, Ji, J., additional, Li, Z., additional, Bender, J., additional, Pinilla, C., additional, Srinivasan, V., additional, Dombovy-Johnson, M., additional, Carson-Walter, E., additional, Walter, K., additional, Xu, Z., additional, Popp, B., additional, Schlesinger, D., additional, Gray, L., additional, Sheehan, J., additional, Keir, S. T., additional, Friedman, H. S., additional, Bigner, D. D., additional, Kut, C., additional, Tyler, B., additional, McVeigh, E., additional, Li, X., additional, Herzka, D., additional, Grossman, S., additional, Lasky, J. L., additional, Panosyan, E., additional, Meisen, W. H., additional, Hardcastle, J., additional, Wojton, J., additional, Wohleb, E., additional, Alvarez-Breckenridge, C., additional, Nowicki, M., additional, Godbout, J., additional, Lee, S. Y., additional, Sheehan, J. M., additional, Yin, S., additional, Kaluz, S., additional, Devi, S. N., additional, de Noronha, R., additional, Nicolaou, K. C., additional, Van Meir, E. G., additional, Lachowicz, J. E., additional, Demeule, M., additional, Che, C., additional, Tripathy, S., additional, Jarvis, S., additional, Currie, J.-C., additional, Regina, A., additional, Nguyen, T., additional, Castaigne, J.-P., additional, Zielinska-Chomej, K., additional, Mohanty, C., additional, Viktorsson, K., additional, Lewensohn, R., additional, Driscoll, J. J., additional, Alsidawi, S., additional, Warnick, R. E., additional, Rixe, O., additional, deCarvalho, A. C., additional, Irtenkauf, S., additional, Hasselbach, L., additional, Xin, H., additional, Mikkelsen, T., additional, Sherman, J. H., additional, Siu, A., additional, Volotskova, O., additional, Keidar, M., additional, Gibo, D. M., additional, Dickinson, P., additional, Robertson, J., additional, Rossmeisl, J., additional, Debinski, W., additional, Nair, S., additional, Schmittling, R., additional, Boczkowski, D., additional, Archer, G., additional, Sampson, J. H., additional, Mitchell, D. A., additional, Miller, I. S., additional, Didier, S., additional, Murray, D. W., additional, Issaivanan, M., additional, Coniglio, S. J., additional, Segall, J. E., additional, Al-Abed, Y., additional, Symons, M., additional, Fotovati, A., additional, Hu, K., additional, Triscott, J., additional, Bacha, J., additional, Brown, D. M., additional, Dunn, S. E., additional, Daniels, D. J., additional, Peterson, T. E., additional, Dietz, A. B., additional, Knutson, G. J., additional, Parney, I. F., additional, Diaz, R. J., additional, Golbourn, B., additional, Picard, D., additional, Smith, C., additional, Huang, A., additional, Rutka, J., additional, Saito, N., additional, Fu, J., additional, Yao, J., additional, Wang, S., additional, Koul, D., additional, Yung, W. K. A., additional, Yuan, Y., additional, Sulman, E. P., additional, Colman, H., additional, Lang, F. F., additional, Slat, E. A., additional, Herzog, E. D., additional, Rubin, J. B., additional, Carminucci, A. S., additional, Amendolara, B., additional, Leung, R., additional, Lei, L., additional, Canoll, P., additional, Bruce, J. N., additional, Wojton, J. A., additional, Chu, Z., additional, Kwon, C.-H., additional, Chow, L. M., additional, Palascak, M., additional, Franco, R., additional, Bourdeau, T., additional, Thornton, S., additional, Qi, X., additional, Kitange, G. J., additional, Mladek, A. C., additional, Su, D., additional, Carlson, B. L., additional, Schroeder, M. A., additional, Pokorny, J. L., additional, Bakken, K. K., additional, Gupta, S. K., additional, Decker, P. A., additional, Wu, W., additional, Sarkaria, J. N., additional, Oddou, M. P., additional, Mollard, A., additional, Call, L. T., additional, Vakayalapati, H., additional, Warner, S. L., additional, Sharma, S., additional, Bearss, D. J., additional, Chen, T. C., additional, Cho, H., additional, Wang, W., additional, Hofman, F. M., additional, Flores, C. T., additional, Snyder, D., additional, Sanchez-Perez, L., additional, Pham, C., additional, Friedman, H., additional, Woolf, E., additional, Abdelwahab, M. G., additional, Turner, G., additional, Preul, M. C., additional, Lynch, A., additional, Rho, J. M., additional, Scheck, A. C., additional, Salphati, L., additional, Heffron, T. P., additional, Alicke, B., additional, Barck, K., additional, Carano, R. A., additional, Cheong, J., additional, Greve, J., additional, Lee, L. B., additional, Nishimura, M., additional, Pang, J., additional, Plise, E. G., additional, Reslan, H. B., additional, Zhang, X., additional, GOuld, S. G., additional, Olivero, A. G., additional, Phillips, H. S., additional, Zadeh, G., additional, Jalali, S., additional, Voce, D., additional, Wei, Z., additional, Shijun, K., additional, Nikolai, K., additional, Josh, W., additional, Clayton, C., additional, Bakhtiar, Y., additional, Alkins, R., additional, Burgess, A., additional, Ganguly, M., additional, Wels, W., additional, Hynynen, K., additional, Li, Y. M., additional, Jun, H., additional, Daniel, V., additional, Walter, H. A., additional, Nakashima, H., additional, Nguyen, T. T., additional, Shalkh, I., additional, Goins, W. F., additional, Chiocca, E. A., additional, Pyko, I. V., additional, Nakada, M., additional, Furuyama, N., additional, Lei, T., additional, Hayashi, Y., additional, Kawakami, K., additional, Minamoto, T., additional, Fedulau, A. S., additional, and Hamada, J.-i., additional

Published
2012
Full Text
View/download PDF

42. Asparaginase and MOPP Treatment of Dogs with Lymphoma.

Author

Brodsky, E. M., Maudlin, G. N., Lachowicz, J. L., and Post, G. S.

Subjects
ASPARAGINASE, LYMPHOMAS, DOXORUBICIN, VINCRISTINE, PREDNISONE, DRUG therapy, HYPERCALCEMIA, T cells
Abstract

Background: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success. Objectives: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated withl-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP). Animals: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. Methods: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement. Results: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications. Conclusions and clinical importance: l-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

44. Dopamine D<INF>1</INF>/D<INF>5</INF> Receptor Antagonists with Improved Pharmacokinetics:  Design, Synthesis, and Biological Evaluation of Phenol Bioisosteric Analogues of Benzazepine D<INF>1</INF>/D<INF>5</INF> Antagonists

Author

Wu, W.-L., Burnett, D. A., Spring, R., Greenlee, W. J., Smith, M., Favreau, L., Fawzi, A., Zhang, H., and Lachowicz, J. E.

Abstract

Benzazepines 1 and 2 (SCH 23390 and SCH 39166, respectively) are two classical benzazepine D1/D5 antagonists, with Ki values 1.4 and 1.2 nM, respectively. Compound 2 has been in human clinical trials for a variety of diseases, including schizophrenia, cocaine addition, and obesity. Both 1 and 2 displayed low plasma levels and poor oral bioavailability, due to rapid first-pass metabolism of the phenol moieties. Several heterocyclic systems containing an N−H hydrogen bond donor were synthesized and evaluated as phenol isosteres. The preference orientation of the hydrogen bond was established by comparison of analogues containing different NH vectors. Replacement of the phenol group of 2 with an indole ring generated the first potent D1/D5 antagonist 11b. Further optimization led to the synthesis of very potent benzimidazolones 19, 20 and benzothiazolone analogues 28, 29. These compounds have excellent selectivity over D2−D4 receptors, α2a receptor, and the 5-HT transporter. Compared to 2, these heterocyclic phenol isosteres showed much better pharmacokinetic profiles as demonstrated by rat plasma levels. In sharp contrast, similar phenolic replacements in 1 decreased the binding affinity dramatically, presumably due to a conformational change of the pendant phenyl group. However, one indazole compound 33 was identified as a potent D1/D5 ligand in this series.

Published
2005

45. Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist

Author

Tagat, J. R., McCombie, S. W., Nazareno, D., Labroli, M. A., Xiao, Y., Steensma, R. W., Strizki, J. M., Baroudy, B. M., Cox, K., Lachowicz, J., Varty, G., and Watkins, R.

Abstract

The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in clinical trials.

Published
2004

46. Improving the Oral Efficacy of CNS Drug Candidates:  Discovery of Highly Orally Efficacious Piperidinyl Piperidine M<INF>2</INF> Muscarinic Receptor Antagonists

Author

Wang, Y., Chackalamannil, S., Hu, Z., Greenlee, W. J., Clader, J., Boyle, C. D., Kaminski, J. J., Billard, W., Binch, H. B., III, Crosby, G., Ruperto, V., Duffy, R. A., Cohen-Williams, M., Coffin, V. L., Cox, K. A., Grotz, D. E., and Lachowicz, J. E.

Abstract

In search of a backup M2 muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models. The improvement of oral efficacy was achieved by modulating both the molecular weight and lipophilicity of the lead compounds.

Published
2002
Full Text
View/download PDF

50. The D2S and D2L dopamine receptor isoforms are differentially regulated in Chinese hamster ovary cells.

Author

Zhang, L J, Lachowicz, J E, and Sibley, D R

Abstract

To investigate and compare the regulatory properties of the two isoforms of the D2 dopamine receptor, we have stably expressed their cDNAs in Chinese hamster ovary (CHO) cells. Cell lines were selected that express similar levels of [3H]methylspiperone-binding activity. Both isoforms mediate a dose-dependent and pharmacologically specific inhibition of adenylyl cyclase activity in both intact cell and membrane preparations. Pretreatment of both D2L and D2S receptor-expressing cells with 100 microM dopamine produces a approximately 5-fold shift (to lower affinity) in the EC50 for dopamine inhibition of cAMP accumulation, with a 25-30% decrease in the maximum response. Dopamine treatment also results in a approximately 25% decrease in the maximum receptor binding activity of the D2S receptor-expressing cells. In contrast, the D2L receptors are up-regulated by about 2-fold in response to dopamine exposure. This difference in response between the D2S and D2L receptors is not cell line specific, inasmuch as other CHO clones expressing these isoforms show identical responses. The dopamine-induced up-regulation of D2L receptor binding is time dependent, reaching maximal levels after 10 hr (t1/2 = 2 hr). Upon removal of dopamine, the receptor binding activity returns to control levels within 20 hr. The adenylyl cyclase desensitization response is also time dependent but exhibits a slower time course (t1/2 = 5 hr) than the receptor up-regulation. Both regulatory responses are induced in a dose-dependent fashion by dopamine, albeit with different potencies (up-regulation EC50 = 100 nM, desensitization EC50 = 2 microM). These regulatory effects are pharmacologically specific, being mimicked by D2-selective agonists but not agonists of other receptor subtypes. The dopamine-induced receptor up-regulation is blocked by prior treatment of the cells with pertussis toxin and is not mimicked by cAMP analogs. Conversely, elevation of intracellular cAMP levels results in down-regulation of the D2L receptor activity. To test whether protein synthesis is required for the D2L receptor up-regulation, cycloheximide was used to block mRNA translation. This was found to completely inhibit the up-regulation of D2L binding activity; however, there was no effect on the desensitization of the adenylyl cyclase response. RNA dot-blot analyses indicate that dopamine treatment is associated with a sustained 2-fold increase in the steady state levels of D2L mRNA, whereas D2S mRNA is transiently increased by only 50%.(ABSTRACT TRUNCATED AT 400 WORDS)

Published
1994

Catalog

Books, media, physical & digital resources
See catalog results