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21.
Th1 memory: implications for vaccine development 总被引:3,自引:0,他引:3
Summary: T‐helper 1 (Th1) cells play a critical role, via interferon‐γ (IFN‐γ) production, in mediating intracellular killing against a variety of infectious pathogens. Thus, understanding the regulation of Th1 responses could provide better insight into vaccine design for infections requiring Th1 immunity. The cellular and molecular mechanisms that control the induction of Th1 effector cells have been well characterized. More recently, there has been substantial progress in furthering our understanding of the factors that regulate the development of Th1 memory cells. It is clear that Th1 responses are functionally heterogeneous, as defined by their ability to produce IFN‐γ. Furthermore, this heterogeneity has profound implications for the capacity of distinct lineages of Th1 cells to develop into memory cells. This review emphasizes the mechanisms controlling the differentiation of naïve CD4+ T cells into effector and then memory cells in a progressive manner. It highlights the importance of IFN‐γ as a positive regulator for inducing Th1 responses but a negative regulator for sustaining Th1 effector cells. In conclusion, we discuss how this current understanding of Th1 differentiation will inform vaccine design and better define immune correlates of protection. 相似文献
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Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8-
Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic
lesion that is widely regarded as a reliable index of oxidative DNA damage.
The purpose of this study was to examine the effects of X- radiation on
levels of 8-OHdG in the context of an experimental model for breast cancer
in which chronic radiation exposure has been shown to be carcinogenic in
Sprague-Dawley rats. A secondary objective of this study was to determine
if the use of phenol during DNA isolation affected the concentration of
8-OHdG subsequently measured. Our results indicate that a profoundly
carcinogenic dose of radiation induced a small but significant increase in
8-OHdG concentration in mammary gland DNA, and that the use of a
phenol-based versus a salt-based method of DNA isolation had no significant
impact on the levels of 8-OHdG detected in either control or irradiated
tissue.
相似文献
24.
van Kranen HJ; van Iersel PW; Rijnkels JM; Beems DB; Alink GM; van Kreijl CF 《Carcinogenesis》1998,19(9):1597-1601
The variation in colorectal cancer (CRC) incidence worldwide strongly
suggests a role for dietary influences. Based on epidemiological data,
protective effects of vegetables and fruit intake on CRC are widely
claimed, while other data indicate a possible increased CRC risk from
(higher) dietary fat intake. Therefore, we have investigated single and
interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in
the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this
study, four different diets (A-D) were compared, which were either low in
fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In
addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced
by a freeze-dried VFM. The diets were balanced so that they only differed
among each other in fat/carbohydrate content and the presence of specific
plant-constituents. Because the initiation of intestinal tumors in ApcMin
mice occurs relatively early in life, exposure to the diets was started in
utero. Without the addition of VFM, mice maintained at a high-fat diet did
not develop significantly higher numbers of small or large intestinal
adenomas than mice maintained at a low-fat diet. VFM added to a low-fat
diet significantly lowered multiplicity of small intestinal polyps (from
16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male
ApcMin mice only. Strikingly, addition of VFM to female mice maintained on
a low-fat diet and to both sexes maintained on a high-fat diet
significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
polyps/mouse). In conclusion, our results indicate that neither a lower fat
intake nor consumption of VFM included in a high-fat diet decreases the
development of polyps in mice genetically predisposed to intestinal tumor
development.
相似文献
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MUHAMMAD N RAZA MUHAMMAD HADID CHARLES E KEEN CORALIE BINGHAM ANDREW HJ SALMON 《Nephrology (Carlton, Vic.)》2012,17(8):748-753
Background: The use and timing of steroids in the management of acute tubulointerstitial nephritis (ATIN) remains debatable. Aims: To determine the incidence and aetiology of ATIN in our unit, and to examine trends in the use of steroids and their impact on renal outcomes. Methods: Patients with a histological diagnosis of ATIN over a 9‐year period were identified and divided into steroid‐treated (StG) and steroid‐naïve groups (SnG). Mean change in estimated glomerular filtration rate (eGFR) was determined. Results: Forty‐nine patients had ATIN as their main diagnosis, 67% of cases were drug‐induced, and proton pump inhibitors (PPI) were the second commonest implicated drug category. Majority (75%) of patients received steroids, and eGFR improved to a significantly greater degree in these steroid‐treated patients (3.4‐fold improvement vs 2.0‐fold in SnG; P < 0.05, unpaired t‐test). Despite comparable eGFR at presentation (StG: 11.7; SnG: 15.4), steroid‐treated patients were less likely to receive dialysis, although not significantly so (OR 0.27; 95% CI 0.06–1.15, P = 0.066, chi‐squared test). However, there was no significant relation between the degree of eGFR improvement and delay in starting steroids (Pearson r = ?0.25, P > 0.45), and no difference in eGFR at the time of last follow‐up (StG: 33 ± 3; SnG: 32 ± 7; P > 0.9, unpaired t‐test). Conclusion: StG patients had a greater degree of improvement in renal function, but with no correlation between degree of improvement in eGFR and delay in starting steroids, and similar eGFR values at final follow‐up. PPI were the second commonest drug category among drug‐induced cases. 相似文献
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