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201.
van Lint A Ayers M Brooks AG Coles RM Heath WR Carbone FR 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(1):392-397
HSV infects skin or mucosal epithelium as well as entering the sensory nerves and ganglia. We have used TCR-transgenic T cells specific for the immunodominant class I-restricted determinant from HSV glycoprotein B (gB) combined with a flank zosteriform model of infection to examine the ability of CD8+ T cells to deal with infection. During the course of zosteriform disease, virus rapidly spreads from the primary inoculation site in the skin to sensory dorsal root ganglia and subsequently reappears in the distal flank. Virus begins to be cleared from all sites about 5 days after infection when gB-specific CD8+ T cells first appear within infected tissues. Although activated gB-specific effectors can partially limit virus egress from the skin, they do so only at the earliest times after infection and are ineffective at halting the progression of zosteriform disease once virus has left the inoculation site. In contrast, these same T cells can completely clear ongoing lytic replication if transferred into infected immunocompromised RAG-1-/- mice. Therefore, we propose that the role of CD8+ T cells during the normal course of disease is to clear replicating virus after infection is well established rather than limit the initial spread of HSV from the primary site of inoculation. 相似文献
202.
Heath L Martin DP Warburton L Perrin M Horsfield W Kingsley C Rybicki EP Williamson AL 《Journal of virology》2004,78(17):9277-9284
Psittacine beak and feather disease (PBFD), caused by Beak and feather disease virus (BFDV), is the most significant infectious disease in psittacines. PBFD is thought to have originated in Australia but is now found worldwide; in Africa, it threatens the survival of the indigenous endangered Cape parrot and the vulnerable black-cheeked lovebird. We investigated the genetic diversity of putative BFDVs from southern Africa. Feathers and heparinized blood samples were collected from 27 birds representing 9 psittacine species, all showing clinical signs of PBFD. DNA extracted from these samples was used for PCR amplification of the putative BFDV coat protein (CP) gene. The nucleotide sequences of the CP genes of 19 unique BFDV isolates were determined and compared with the 24 previously described sequences of BFDV isolates from Australasia and America. Phylogenetic analysis revealed eight BFDV lineages, with the southern African isolates representing at least three distinctly unique genotypes; 10 complete genome sequences were determined, representing at least one of every distinct lineage. The nucleotide diversity of the southern African isolates was calculated to be 6.4% and is comparable to that found in Australia and New Zealand. BFDVs in southern Africa have, however, diverged substantially from viruses found in other parts of the world, as the average distance between the southern African isolates and BFDV isolates from Australia ranged from 8.3 to 10.8%. In addition to point mutations, recombination was found to contribute substantially to the level of genetic variation among BFDVs, with evidence of recombination in all but one of the genomes analyzed. 相似文献
203.
Opioids have been shown to relieve thermal hyperalgesia associated with neuropathic pain. We used a novel technique to produce liposome-encapsulated hydromorphone (LEH), which we then tested in a chronic constriction injury (CCI) thermal hyperalgesia model of neuropathic pain. Rats were divided into sham-operated and CCI groups. Treatments consisted of LEH or standard hydromorphone, administered at surgery or 3 d after surgery, when thermal hyperalgesia had developed in the CCI rats. We measured thermal withdrawal latencies on days 0, 3, and 5. CCI rats given liposome-encapsulated vehicle or standard hydromorphone at surgery developed full thermal hyperalgesia. CCI rats given LEH at surgery exhibited no significant change compared with baseline values in thermal withdrawal latency, indicating that this preparation prevented hyperalgesia after a single injection. CCI rats given LEH on day 3 (that is, after they had developed hyperalgesia) showed reversal of hyperalgesia that persisted to day 5, whereas CCI rats given standard hydromorphone on day 3 showed only brief (approximately 90 min) reversal of hyperalgesia. Preemptive injection of LEH prevented hyperalgesia in this model for as long as 5 d. In addition, hyperalgesia was alleviated for at least 2 d after injection of a single dose of LEH. These results suggest that liposome-encapsulation of hydromorphone offers a convenient and effective means to provide relief from neuropathic pain in this rodent model. 相似文献
204.
John A. Carver Peter J. Duggan Heath Ecroyd Yanqin Liu Adam G. Meyer C. Elisabet Tranberg 《Bioorganic & medicinal chemistry》2010,18(1):222-228
Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN than literature results for Aβ fibril inhibition, however, with few exceptions, they showed a similar trend in potency. The convenience and reproducibility of the RCM-κ-CN assay make it an economic alternative first screen for Aβ inhibitory activity, especially for use with large compound libraries. 相似文献
205.
Richard J. Perner John R. Koenig Stanley DiDomenico Arthur Gomtsyan Robert G. Schmidt Chih-Hung Lee Margaret C. Hsu Heath A. McDonald Donna M. Gauvin Shailen Joshi Teresa M. Turner Regina M. Reilly Philip R. Kym Michael E. Kort 《Bioorganic & medicinal chemistry》2010,18(13):4821-4829
The synthesis and structure–activity relationships of a series of 5-monosubstituted and 4,5-disubstituted 2-arylaminooxazoles as novel antagonists of the transient receptor potential vanilloid 1 (TRPV1) receptor are described. The 7-hydroxy group of the tetrahydronaphthyl moiety on the 2-amino substituent of the oxazole ring was important for obtaining excellent in vitro potency at the human TRPV1 receptor, while a variety of alkyl and phenyl substituents at the 4- and 5-positions of the oxazole ring were well tolerated and yielded potent TRPV1 antagonists. Despite excellent in vitro potency, the 5-monosubstituted compounds suffered from poor pharmacokinetics. It was found that 4,5-disubstitution on the oxazole ring was critical to the improvement of the overall pharmacokinetic profile of these analogues, which led to the discovery of compound (R)-27, a novel TRPV1 antagonist with good oral activity in preclinical animal models of pain. 相似文献
206.
DiDonato M Krishna SS Schwarzenbacher R McMullan D Jaroszewski L Miller MD Abdubek P Agarwalla S Ambing E Axelrod H Biorac T Chiu HJ Deacon AM Elsliger MA Feuerhelm J Godzik A Grittini C Grzechnik SK Hale J Hampton E Haugen J Hornsby M Klock HE Knuth MW Koesema E Kreusch A Kuhn P Lesley SA Moy K Nigoghossian E Okach L Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2006,63(1):256-260
207.
Mathews II Krishna SS Schwarzenbacher R McMullan D Jaroszewski L Miller MD Abdubek P Agarwalla S Ambing E Axelrod HL Canaves JM Carlton D Chiu HJ Clayton T DiDonato M Duan L Elsliger MA Grzechnik SK Hale J Hampton E Haugen J Jin KK Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Levin I Morse AT Nigoghossian E Okach L Oommachen S Paulsen J Quijano K Reyes R Rife CL Spraggon G Stevens RC van den Bedem H White A Wolf G Xu Q Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2006,65(1):249-254
208.
Han GW Sri Krishna S Schwarzenbacher R McMullan D Ginalski K Elsliger MA Brittain SM Abdubek P Agarwalla S Ambing E Astakhova T Axelrod H Canaves JM Chiu HJ DiDonato M Grzechnik SK Hale J Hampton E Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Kreusch A Kuhn P Miller MD Morse AT Moy K Nigoghossian E Oommachen S Ouyang J Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J Wang X West B White A Wolf G Xu Q Hodgson KO Wooley J Deacon AM Godzik A 《Proteins》2006,64(4):1083-1090
209.
Xu Q Krishna SS McMullan D Schwarzenbacher R Miller MD Abdubek P Agarwalla S Ambing E Astakhova T Axelrod HL Canaves JM Carlton D Chiu HJ Clayton T DiDonato M Duan L Elsliger MA Feuerhelm J Grzechnik SK Hale J Hampton E Han GW Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Kreusch A Kuhn P Morse AT Nigoghossian E Okach L Oommachen S Paulsen J Quijano K Reyes R Rife CL Spraggon G Stevens RC van den Bedem H White A Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2006,65(3):777-782
210.
DiDonato M Krishna SS Schwarzenbacher R McMullan D Agarwalla S Brittain SM Miller MD Abdubek P Ambing E Axelrod HL Canaves JM Chiu HJ Deacon AM Duan L Elsliger MA Godzik A Grzechnik SK Hale J Hampton E Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Kreusch A Kuhn P Lesley SA Levin I Morse AT Nigoghossian E Okach L Oommachen S Paulsen J Quijano K Reyes R Rife CL Spraggon G Stevens RC van den Bedem H White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2006,65(3):771-776