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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
981.
982.
Zalacain M Biswas S Ingraham KA Ambrad J Bryant A Chalker AF Iordanescu S Fan J Fan F Lunsford RD O'Dwyer K Palmer LM So C Sylvester D Volker C Warren P McDevitt D Brown JR Holmes DJ Burnham MK 《Journal of molecular microbiology and biotechnology》2003,6(2):109-126
Attempted allelic replacement of 144 Streptococcus pneumoniae open reading frames of previously uncharacterized function led to the identification of 36 genes essential for growth under laboratory conditions. Of these, 14 genes (obg, spoIIIJ2, trmU, yacA, yacM, ydiC, ydiE, yjbN, yneS, yphC, ysxC, ytaG, yloI and yxeH4) were also essential in Staphylococcus aureus and Haemophilus influenzae or Escherichia coli, 2 genes (yrrK and ydiB) were only essential in H. influenzae as well as S. pneumoniae and 8 genes were necessary for growth of S.pneumoniae and S. aureus and did not have a homolog in H. influenzae(murD2, ykqC, ylqF, yqeH, ytgP, yybQ) or were not essential in that organism (yqeL, yhcT). The proteins encoded by these genes could represent good targets for novel antibiotics covering different therapeutic profiles. The putative functions of some of these essential proteins, inferred by bioinformatic analysis, are presented. Four mutants, with deletions of loci not essential for in vitro growth, were found to be severely attenuated in a murine respiratory tract infection model, suggesting that not all targets for antibacterial therapeutics are revealed by simple in vitro essentiality testing. The results of our experiments together with those collated from previously reported studies including Bacillus subtilis, E. coli and Mycoplasma sp. demonstrate that gene conservation amongst bacteria does not necessarily indicate that essentiality in one organism can be extrapolated to others. Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results. 相似文献
983.
984.
The genetic basis of mammalian neurulation 总被引:2,自引:0,他引:2
More than 80 mutant mouse genes disrupt neurulation and allow an in-depth analysis of the underlying developmental mechanisms. Although many of the genetic mutants have been studied in only rudimentary detail, several molecular pathways can already be identified as crucial for normal neurulation. These include the planar cell-polarity pathway, which is required for the initiation of neural tube closure, and the sonic hedgehog signalling pathway that regulates neural plate bending. Mutant mice also offer an opportunity to unravel the mechanisms by which folic acid prevents neural tube defects, and to develop new therapies for folate-resistant defects. 相似文献
985.
986.
Much of the efficiency of the immune system is attributed to the high degree of spatial and temporal organization in the secondary lymphoid organs. Signalling through the lymphotoxin (LT) pathway is a crucial element in the maintenance of this organized microenvironment. The effect of altering lymphoid microenvironments on immune responses remains relatively unexplored. Inhibitors of the LT and LIGHT pathways have been shown to reduce disease in a wide range of autoimmune models. This approach has provided a tool to probe the effect of manipulation of the microenvironment on both normal and pathological immune responses. 相似文献
987.
Newkirk MM Goldbach-Mansky R Lee J Hoxworth J McCoy A Yarboro C Klippel J El-Gabalawy HS 《Arthritis research & therapy》2003,5(2):R82-R90
Advanced glycation end-product (AGE)-damaged IgG occurs as a result of hyperglycemia and/or oxidative stress. Autoantibodies
to IgG-AGE were previously demonstrated in patients with severe, longstanding rheumatoid arthritis (RA). We investigated whether
IgG-AGE and anti-IgG-AGE antibodies were present early in the course of RA and other inflammatory arthropathies. We prospectively
followed a cohort of 238 patients with inflammatory arthritis of duration less than 1 year. Patients were evaluated clinically
and serologically, and radiographs were obtained at initial and 1-year visits. Sera were assayed for IgG-AGE and anti-IgG-AGE
antibodies by enzyme-linked immunosorbent assay (ELISA). Rheumatoid factor (RF) was determined by nephelometry and ELISA.
Of all patients, 29% had RF-positive RA, 15% had RF-negative RA, 18% had spondyloarthropathy, and 38% had undifferentiated
arthritis. IgG-AGE was present in 19% of patients, and was similar in amount and frequency in all groups. Patients with elevated
IgG-AGE levels had significantly higher levels of the inflammatory markers C-reactive protein and erythrocyte sedimentation
rate, but there was no correlation with blood glucose levels. Overall, 27% of the patients had IgM anti-IgG-AGE antibodies.
These antibodies were highly significantly associated with RFs (P < 0.0001) and with swollen joint count (P < 0.01). In early onset arthritis, IgG damaged by AGE was detected in all patient groups. The ability to make IgM anti-IgG-AGE
antibodies, however, was restricted to a subset of RF-positive RA patients with more active disease. The persistence of the
anti-IgG-AGE response was more specific to RA, and was transient in the patients with spondyloarthropathy and with undifferentiated
arthritis who were initially found to be positive for anti-IgG-AGE antibodies. 相似文献
988.
Mitty JA Macalino G Taylor L Harwell JI Flanigan TP 《MedGenMed : Medscape general medicine》2003,5(1):30
Many HIV-infected individuals have not reaped the benefits of combination antiretroviral therapy due to inability either to adhere to medications or to access care. It is now recognized that innovative approaches are needed to increase access and adherence to highly active antiretroviral therapy (HAART), especially among these hard-to-reach populations. Due to the success of directly observed therapy (DOT) for the treatment of Mycobacterium tuberculosis (TB), our group and others have questioned whether DOT can be adapted to deliver HAART to hard-to-reach communities. In this review, we discuss the results of pilot programs that have utilized DOT in multiple different settings and use case studies to explore the diverse issues that can arise when implementing these programs. As we continue to gain more experience with observed therapy, we will be able to better identify the key components for a successful intervention. 相似文献
989.
We bring you the highlights of the second Joint Cold Spring Harbor Laboratory and Wellcome Trust 'Genome Informatics' Conference, organized by Ewan Birney, Suzanna Lewis and Lincoln Stein. There were sessions on in silico data discovery, comparative genomics, annotation pipelines, functional genomics and integrative biology. The conference included a keynote address by Sydney Brenner, who was awarded the 2002 Nobel Prize in Physiology or Medicine (jointly with John Sulston and H. Robert Horvitz) a month later. 相似文献
990.