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排序方式: 共有254条查询结果,搜索用时 15 毫秒
1.
Elizabeth A. Grimm William L. Crump III April Durett Jeane P. Hester Sandhya Lagoo-Deenadalayan Laurie B. Owen-Schaub 《Cancer immunology, immunotherapy : CII》1988,27(1):53-58
Summary Employing serum-free media, human peripheral blood mononuclear cells, and purified recombinant interleukin-2 (IL-2), conditions were observed in which the development of IL-2-driven cytotoxic activity was suppressed. The cytotoxic activity of such IL-2-generated lymphokine activated killing (LAK) was tested against natural killer-resistant cultured tumor cells (Daudi, Raji, and a glioma). LAK generation was inhibited by addition of some normal sera, normal platelets, or some tumor cells. Because recent reports have indicated that transforming growth factor-beta (TGF-beta)-like factors are often secreted by tumors and the acidic alpha granules of platelets and can be present in sera, we tested the effect of purified human TGF-beta on the activation of LAK. Our results indicated that TGF-beta is very suppressive for LAK induction, and can completely prevent both the IL-2-driven proliferation and cytotoxicity at concentrations as low as 5 ng/ml. Titrations of IL-2 and of TGF-beta indicated that the suppression is dose-dependent and can be avoided by employing higher levels of IL-2. It was also found that the suppressive effect of TGF-beta can be overcome by washing suppressed cell populations and further culture in low levels of IL-2. Collectively, these data indicate that TGF-beta can be a potent inhibitor of LAK generation under standard activation conditions, but that this effect is regulated by the relative level of IL-2 and may be overcome and/or reversed in vitro. 相似文献
2.
The effects of mispair and nonpair correction in hybrid DNA on base ratios (G + C content) and total amounts of DNA 总被引:1,自引:0,他引:1
Base ratios and total DNA amounts can vary substantially between and within
higher taxa and genera, and even within species. Gene conversion is one of
several mechanisms that could cause such changes. For base substitutions,
disparity in conversion direction is accompanied by an equivalent disparity
in base ratio at the heterozygous site. Disparity in the direction of gene
conversion at meiosis is common and can be extreme. For transitions (which
give purine [R]/pyrimidine [Y] mispairs) and for transversions giving
unlike R/R and Y/Y mispairs in hybrid DNA, this disparity could give slow
but systematic changes in G + C percentage. For transversions giving like
R/R and Y/Y mispairs, it could change AT/TA and CG/GC ratios. From the
extent of correction direction disparity, one can deduce properties of
repair enzymes, such as the ability (1) to excise preferentially the purine
from one mispair and the pyrimidine from the other for two different R/Y
mispairs from a single heterozygous site and (2) to excise one base
preferentially from unlike R/R or Y/Y mispairs. Frame-shifts usually show
strong disparity in conversion direction, with preferential cutting of the
nonlooped or the looped-out strand of the nonpair in heterozygous h-DNA.
The opposite directions of disparity for frame-shifts and their intragenic
suppressors as Ascobolus suggest that repair enzymes have a strong,
systematic bias as to which strand is cut. The conversion spectra of
mutations induced with different mutagens suggest that the nonlooped strand
is preferentially cut, so that base additions generally convert to mutant
and deletions generally convert to wild-type forms. Especially in
nonfunctional or noncoding DNA, this could cause a general increase in DNA
amounts. Conversion disparity, selection, mutation, and other processes
interact, affecting rates of change in base ratios and total DNA.
相似文献
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B J Crump J E Cubbon M F Drummond R A Hawkes M D Marchment 《BMJ (Clinical research ed.)》1991,302(6792):1582-1584
OBJECTIVE--To estimate the financial effect of random yearly variations in need for services on fundholding practices with various list sizes. DESIGN--A simulation model was derived using historical data on general practitioner referrals for the 113 surgical procedures covered by the general practitioner fund, combined with data on the hospital prices for those procedures. PATIENTS--Resident population of Central Birmingham Health Authority. MAIN OUTCOME MEASURES--Expected expenditure on the relevant surgical procedures for the whole district and for practices with list sizes of 9000, 12,000, 15,000, 18,000, 21,000, or 24,000 for each of 100 simulated years. RESULTS--By using average hospital prices for the West Midlands region the mean (SD) annual expenditure for the 179,400 residents was 4,832,471 pounds (87,149 pounds); the random variation between the 5th and 95th most expensive years was 5.7% of the mean cost. For a practice with a list size of 9000 the values were 244,891 pounds (18,349 pounds), with a variation of 27.5%. With a list size of 24,000 the values were 652,762 pounds (32,512 pounds), with a variation of 15.3%. CONCLUSIONS--Random variations in need for inpatient services will have a significant financial impact on the practice fund. The problem will be particularly great for smaller practices. Additional measures are required to ensure that the scheme is not undermined and that the potential benefits are secured. 相似文献
5.
Data obtained from 423 individuals were analyzed for mode of inheritance of extra triradii on palmar interdigital area II and IV separately, and in combination. It indicates that a single dominant allele A for extra triradius in the area II, and an allele D in the area IV, may be responsible for the presence of the patterns in the respective area, with 75 to 80 per cent penetrance. There are numbers of individuals in which extra triradii are present in both interdigital areas II and IV. The mode of inheritance has been estimated from the data obtained and was found to have co-dominant alleles A and D for the presence in their respective areas. Further analysis revealed the existence of three alleles. A and D for presence, and 0 for absence. The alleles A and D are co-dominant, if combined in the genotype AD, but either allele is dominant in heterozygous combination with 0. 相似文献
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Uche V. Amazigo Stephen G. A. Leak Honorat G. M. Zoure Chukwu Okoronkwo Maimouna Diop Ly Sunday Isiyaku Andy Crump Joseph C. Okeibunor Boakye Boatin 《PLoS neglected tropical diseases》2021,15(3)
The neglected tropical diseases (NTDs) affect hundreds of millions of people, predominantly in rural, often difficult-to-access areas, poorly served by national health services. Here, we review the contributions of 4.8 million community-directed distributors (CDDs) of medicines over 2 decades in 146,000 communities in 27 sub-Saharan African countries to control or eliminate onchocerciasis and lymphatic filariasis (LF). We examine their role in the control of other NTDs, malaria, HIV/AIDS interventions, immunisation campaigns, and support to overstretched health service personnel. We are of the opinion that CDDs as community selected, trained, and experienced “foot soldiers,” some of whom were involved in the Ebola outbreak responses at the community level in Liberia, if retrained, can assist community leaders and support health workers (HWs) in the ongoing Coronavirus Disease 2019 (COVID-19) crisis. The review highlights the improved treatment coverage where there are women CDDs, the benefits and lessons from the work of CDDs, their long-term engagement, and the challenges they face in healthcare delivery. It underscores the value of utilising the CDD model for strong community engagement and recommends the model, with some review, to hasten the achievement of the NTD 2030 goal and assist the health system cope with evolving epidemics and other challenges. We propose that, based on the unprecedented progress made in the control of NTDs directly linked to community engagement and contributions of CDDs “foot soldiers,” they deserve regional and global recognition. We also suggest that the World Health Organization (WHO) and other international stakeholders promote policy and guidance for countries to adapt this model for the elimination of NTDs and to strengthen national health services. This will enhance the accomplishment of some Sustainable Development Goals (SDGs) by 2030 in sub-Saharan Africa. 相似文献
10.
Holly M. Biggs Julian T. Hertz O. Michael Munishi Renee L. Galloway Florian Marks Wilbrod Saganda Venance P. Maro John A. Crump 《PLoS neglected tropical diseases》2013,7(12)