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31.
A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases delta and epsilon. While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the consequences of p21/PCNA interaction on cell cycle progression have not yet been determined. Here, we show, using a tetracycline-regulated system, that expression of wild-type p21 in p53-deficient DLD1 human colon cancer cells inhibits DNA synthesis and causes G1 and G2 cell cycle arrest. Similar effects are observed in cells expressing p21CDK-, a mutant impaired in the interaction with CDKs, but not in cells expressing p21PCNA-, a mutant deficient for the interaction with PCNA. Analysis of cells treated with a p21-derived PCNA-binding peptide provides additional evidence that the growth inhibitory effects of p21 and p21CDK result from their ability to bind to PCNA. Our results suggest that p21 might inhibit cell cycle progression by two independent mechanisms, inhibition of cyclin/CDK complexes, and inhibition of PCNA function resulting in both G1 and G2 arrest.  相似文献   
32.
We investigated the role of prostaglandin E2 (PGE2) and its interactions with nitric oxide (NO) on cell death and NO-mediated cytotoxicity in the murine macrophage cell line J774. Stimulation of the J774 cells with lipopolysaccharide together with interferon-gamma resulted in a dose-dependent cytotoxicity and production of PGE2 and NO, measured as nitrite. Our results showed a linear correlation between PGE2 release and cytotoxicity. The cyclooxygenase (COX) inhibitor indomethacin completely inhibited PGE2 biosynthesis, without affecting NO production or cell death. This supports previous reports suggesting that overproduction of endogenous PGE2 is mainly the consequence of cell death and does not cause it. In contrast, the NO synthase inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) gave a significant, though incomplete suppression of NO release and cell death. This points to the presence of other cytotoxic factors besides NO. To evaluate the toxic effect solely due to NO, macrophages were exposed to the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Incubation with SNAP also resulted in a concentration-dependent cell injury and PGE2 production. When exogenously added, PGE2 protected against SNAP-mediated cytotoxicity and simultaneously increased PGE2 release into the medium, without inducing COX-2. The cytoprotection and the stimulation of PGE2 release were both reversed by indomethacin. In conclusion, PGE2 biosynthesis may represent a mechanism by which inflammatory macrophages protect themselves against the cytotoxic effects of NO.  相似文献   
33.
The paper presents 30-year experience in treating 158 patients with congenital cystic diseases of the liver and bile ducts. Depending on the pattern of hepatobiliary lesions, the diagnostic value of techniques, such as ultrasound, computerized tomography, scintigraphy of the liver duodenoscopy with THCG was defined. Analyzing the late outcomes provided recommendations for the most optimal surgical management: cystic fenestration and tunneling in hepatic polycystosis, pericystectomy in solitary cysts of the liver, different varieties of bile draining operations in choledochal cysts and Caroli's disease.  相似文献   
34.
上罗拉皮圈是复杂的纺线生产流程中一个很小的细节。然而,由于它们对成纱质量有较大影响,必须对它们进行优先考虑。质量不是一个简单的问题,它包括多个方面(橡胶质量、正确的加工、定期的保养)。因此,皮圈的选择就像保养操作的自动化程度一样影响成本产生。本文将就这个问题进行讨论。  相似文献   
35.
Conclusions  
1.  The design of the steel-reinforced concrete pressure conduit was checked for four calculated cross sections: I-I, II-II, III-III, and IV-IV. The calculated check was made in accordance with Russian standards by analytical and numerical methods. The usual load combination of the operating period was taken as the main variant.
2.  The calculations showed that the strength condition of the conduit is fulfilled; in this case there is a considerable safety factor with respect to the shell and reinforcement, which attests to the degree of reliability and safety.
3.  Calculations of stresses in the steel shell and reinforcement by the FEM were made on the bases of finite-element models of cross sections with consideration of the formation of cracks in them. The calculated stresses do not exceed the strength of the steel shell and reinforcement.
4.  Conduit cross sections under temperature effects were calculated. Annual variations of the temperatures of the air, water, concrete of the dam, etc., were taken as the loads. The calculations showed that thermal stresses in the steel shell and reinforcement increase by not more than 24 MPa.
5.  A check of the design of the steel-reinforced concrete conduit showed complete fulfillment of the strength condition and high reliability of the design. The design of the steel-reinforced concrete conduits is recommended for realization when constructing structure of the Three Gorges hydro development.
Translated from Gidrotekhnicheskoe Stroitel'stvo, No. 4, pp, 40–45, April, 1999.  相似文献   
36.
Even simple and relatively safe provocation procedures like nasal allergen challenges, should aim to allow detection of positivity with the less possible discomfort to the patient. The objective of this work was to evaluate if the use of rhinomanometric measurements during nasal provocation procedures could allow a decrease in the total administered allergen dose, causing less symptoms to the patients but without increasing the number of false-negatives, comparatively to clinical scores or nasal peak-flow measurements. Our results showed that performing rhinomanometric measurements during nasal HDM challenge procedures can lead in many patients to a reduction in the total dose of allergen administered during the challenge, without loss of sensitivity or specificity. This allergen dose reduction translates in less time consumed during the provocation and less patients' discomfort.  相似文献   
37.
We studied whether ambulatory utilization review (UR) alters how many patients internal medicine residents refer to sub-specialists, and whether the effect persists without reinforcement. We compared referral rates of residents from a firm that held UR meetings (intervention firm residents, n = 20) with those of residents from a firm that did not (control firm residents, n = 21). We then compared referral rates of 17 intervention firm residents while they were participating in UR with their rates after not participating for at least 4 weeks. Intervention firm residents submitted 30% fewer referrals than control firm residents (9% vs 13%, p = .05). However, the effect was short-lived; after 4 weeks without UR, intervention firm resident referral rates were similar to control firm referral rates.  相似文献   
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