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51.
We previously reported that intracellular oxidation-reduction (redox)
regulates NK cell functions and that IL-2-activated NK cells undergo
apoptosis upon contact with NK-sensitive target cells. We now report that
apoptosis in activated human NK cells is also regulated by redox. Thiol
deprivation increased apoptosis in NK cells induced by anti-Fas mAb or Fas
ligand-transfected cells, and pretreatment of cells with N- acetyl
cysteine, which increased intracellular glutathione, partially inhibited
the apoptosis and reversed the effect of thiol-deficient medium, suggesting
that Fas-induced apoptosis in NK cells is also redox sensitive. Thiol
deprivation did not alter cell surface Fas expression, but did increase
ceramide generation following Fas engagement. Although exogenous ceramides
induced apoptosis of NK cells, thiol depletion had no effect on this
apoptosis. Thiol deprivation increased CPP32 activation induced by Fas
engagement, but not by ceramides. These findings suggest that, if ceramide
is required for Fas-induced apoptosis, thiol deprivation affects the
Fas-mediated signaling pathway at the generation of ceramide and/or
upstream thereof. Though tyrosine phosphorylation following Fas engagement
was not significantly affected by thiol deprivation, tyrosine
dephosphorylation was delayed, suggesting that tyrosine phosphatases may
also be redox sensitive. The notion that dephosphorylation is important in
the Fas signaling pathway is supported by the finding that tyrosine
phosphatase inhibitors significantly enhanced both CPP32 activity and
apoptosis following Fas ligation. We conclude that events downstream of
tyrosine phosphorylation and upstream of CPP32 activation, including
tyrosine dephosphorylation and possibly ceramide generation, are sensitive
to regulation by redox in human NK cells, requiring a reducing environment
for optimal protection from apoptosis induced by Fas ligation.
相似文献
52.
53.
应用免疫络化S-P法检测88例食管浸润世鳞癌P16蛋白的表达,结果P16蛋白阳性率为55.68%(49/88),其阳性颗粒位于细胞浆内;组织学Ⅰ、Ⅱ、Ⅲ级阳性率分予的85.71%(18/21)、55.13%(16/29)、39.47%(15/38)(P<0.01);淋巴结转移组和无转移组阳世事分别为36.36%(12/33),67.27%(37/55)(P<0.01);3年生存率P16蛋白阳性组和阴性组分别36%和16.67%。结果表明食管鳞癌中P16蛋白的表达可以反映肿瘤的分化程度和转移情况.提示P16蛋白的检测可作为食管鳞癌的重要预后指标之一。 相似文献
54.
Experiments were performed to assess the ability of bencianol (ZY15051) to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the aetiology of migraine and cerebral arterial spasm. Bencianol caused a dose-related (1-100 micrograms ml-1) reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin F2 alpha, and U-46619 (a thromboxane-A2 mimetic). Bencianol was more effective against contractions induced by EC50 compared to maximal concentrations of each agent, and was least effective against the thromboxane-A2 mimetic, U-46619. In addition, contractions induced by thromboxane-A2-like substances generated from guinea-pig lungs were also reversed by bencianol but only at the highest concentration used (100 micrograms ml-1). The relevance of this action of bencianol to migraine and cerebral arterial spasm is discussed. 相似文献
55.
56.
Piwoz EG Iliff PJ Tavengwa N Gavin L Marinda E Lunney K Zunguza C Nathoo KJ Humphrey JH 《The Journal of nutrition》2005,135(4):950-955
International guidance on HIV and infant feeding has evolved over the last decade. In response to these changes, we designed, implemented, and evaluated an education and counseling program for new mothers in Harare, Zimbabwe. The program was implemented within the ZVITAMBO trial, in which 14,110 mother-baby pairs were enrolled within 96 h of delivery and were followed at 6 wk, 3 mo, and 3-mo intervals. Mothers were tested for HIV at delivery but were not required to learn their test results. Infant feeding patterns were determined using data provided up to 3 mo. Formative research was undertaken to guide the design of the program that included group education, individual counseling, videos, and brochures. The program was introduced over a 2-mo period: 11,362, 1311, and 1437 women were enrolled into the trial before, during, and after this period. Exclusive breast-feeding was recommended for mothers of unknown or negative HIV status, and for HIV-positive mothers who chose to breast-feed. A questionnaire assessing HIV knowledge and exposure to the program was administered to 1996 mothers enrolling after the program was initiated. HIV knowledge improved with increasing exposure to the program. Mothers who enrolled when the program was being fully implemented were 70% more likely to learn their HIV status early (<3 mo) and 8.4 times more likely to exclusively breast-feed than mothers who enrolled before the program began. Formative research aided in the design of a culturally sensitive intervention. The intervention increased relevant knowledge and improved feeding practices among women who primarily did not know their HIV status. 相似文献
57.
Sperm nitric oxide and motility: the effects of nitric oxide synthase stimulation and inhibition 总被引:2,自引:1,他引:2
Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes
known as the nitric oxide synthases (NOS). We have recently shown a NOS
similar to constitutive brain NOS (bNOS) and endothelial NOS (ecNOS) to be
present in spermatozoa. The aim of this study is to investigate NO
production by human spermatozoa and the effects of stimulation and
inhibition of NOS. This was carried out using the Iso-NO, an isolated NO
meter and sensor, which provides rapid, accurate and direct measurements of
NO. Semen samples with normozoospermic and asthenozoospermic profiles were
prepared using a direct swim-up technique. Basal concentrations of NO and
stimulated NO production were measured after exposure to the calcium
ionophore (A23187; 0.01-10 microM) a potent activator of constitutive NOS.
NO production in human spermatozoa was significantly increased by the
addition of A23187 30 seconds after stimulation. Furthermore, this response
was greatly diminished by pre-incubating the samples with competitive
inhibitors of L-arginine, the substrate for NOS, before treatment with
calcium ionophore. In the presence of N(G)-nitro-L-arginine methyl ester
(L- NAME), N(G)-nitro-L-arginine (L-NA) or N(G)-methyl-L-arginine (L-NMMA;
all at 10 microM), NO production was inhibited with a rank order of potency
L-NAME > L-NMMA > L-NA which is in accordance with the inhibition of
an endothelial type of constitutive NOS.
相似文献
58.
59.
WT Cade DN Reeds KE Mondy ET Overton J Grassino S Tucker C Bopp E Laciny S Hubert S Lassa‐Claxton KE Yarasheski 《HIV medicine》2010,11(6):379-388
Objective
People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV‐infected adults relative to standard of care treatment in a matched control group.Methods
Sixty HIV‐infected adults with mild–moderate CVD risk were assigned to 20 weeks of supervised yoga practice or standard of care treatment. Baseline and week 20 measures were: 2‐h oral glucose tolerance test with insulin monitoring, body composition, fasting serum lipid/lipoprotein profile, resting blood pressures, CD4 T‐cell count and plasma HIV RNA, and the Medical Outcomes Study Short Form (SF)‐36 health‐related QOL inventory.Results
Resting systolic and diastolic blood pressures improved more (P=0.04) in the yoga group (−5 ± 2 and −3 ± 1 mmHg, respectively) than in the standard of care group (+1 ± 2 and+2 ± 2 mmHg, respectively). However, there was no greater reduction in body weight, fat mass or proatherogenic lipids, or improvements in glucose tolerance or overall QOL after yoga. Immune and virological status was not adversely affected.Conclusion
Among traditional lifestyle modifications, yoga is a low‐cost, simple to administer, nonpharmacological, popular behavioural intervention that can lower blood pressure in pre‐hypertensive HIV‐infected adults with mild–moderate CVD risk factors.60.