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Premature translation termination codons resulting from nonsense or frameshift mutations are common causes of genetic disorders. Complications arising from the synthesis of C-terminally truncated polypeptides can be avoided by 'nonsense-mediated decay' of the mutant mRNAs. Premature termination codons in the beta-globin mRNA cause the common recessive form of beta-thalassemia when the affected mRNA is degraded, but the more severe dominant form when the mRNA escapes nonsense-mediated decay. We demonstrate that cells distinguish a premature termination codon within the beta-globin mRNA from the physiological translation termination codon by a two-step specification mechanism. According to the binary specification model proposed here, the positions of splice junctions are first tagged during splicing in the nucleus, defining a stop codon operationally as a premature termination codon by the presence of a 3' splicing tag. In the second step, cytoplasmic translation is required to validate the 3' splicing tag for decay of the mRNA. This model explains nonsense-mediated decay on the basis of conventional molecular mechanisms and allows us to propose a common principle for nonsense-mediated decay from yeast to man.  相似文献   
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1. To examine whether insulin resistance in vivo is manifest equally in both muscle and adipose tissues, we measured arteriovenous glucose and lactate fluxes across forearm (muscle) and abdominal subcutaneous (adipose) tissue in nine obese, glucose-intolerant subjects and 13 non-obese subjects of similar age and sex. 2. Compared with non-obese subjects, the forearm of the obese subjects was resistant to insulin stimulation of glucose uptake after a mixed meal. In contrast, adipose tissue showed little evidence of insulin stimulation of glucose uptake, and adipose tissue in subjects in both normal and obese groups behaved very similarly (assessed per 100 g of tissue). 3. For lactate flux, adipose tissue behaved very similarly (per 100 g of tissue) in obese and non-obese subjects, and was a consistent lactate exporter. 4. We conclude that insulin resistance of glucose uptake observed in the forearm of obese subjects is not evident in adipose tissue. Adipose tissue glucose uptake in obese, insulin-resistant subjects is similar to that in lean control subjects, although it occurs at elevated circulating insulin and glucose concentrations.  相似文献   
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Immunohistochemistry was applied to AMeX-fixed sections of twelve cases of gastric carcinoma obtained at surgical resection to explore the occurrence and distribution of fibrin deposits in situ. Fibrinogen was distributed in abundance throughout perivascular zones and in the connective tissue of the tumor stroma. Fibrin II (des-fibrinopeptide B-type fibrin) was easily identified in a direct apposition to the surface membranes of viable carcinoma cells, predominantly at the host-tumor interface and in the regions immediately adjacent to the zones of angiogenesis. Further studies are required to identify the triggers of the coagulation reactions as well as fibrinolytic system components in the gastric cancer tissue.  相似文献   
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BACKGROUND: Retinal vessel diameter is an important parameter in blood flow analysis. Despite modern digital image technology, most clinical studies investigate diameters subjectively using projected fundus slides or negatives. In the present study we used a technique to examine vessel diameters by digital image analysis of color fundus slides. We investigated in a retrospective manner diameter changes in twenty diabetic patients before and after panretinal laser coagulation. MATERIAL AND METHODS: Color fundus slides were digitized by a new high resolution scanning device. The resulting images consisted in three channels (red, green, blue). Since vessel contrast was the highest in the green channel, we assessed grey value profiles perpendicular to the vessels in the green channel. Diameters were measured at the half-height of the profile. RESULTS: After panretinal laser coagulation, average venous diameter was decreased, whereas arterial diameter remained unchanged. There was no significant relation between the diameter change and the number of laser burns or the presence of neovascularization. CONCLUSIONS: Splitting digitized images into color planes enables objective measurements of retinal diameters in conventional color slides.  相似文献   
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The case of a 72-yr-old woman with osteoarthritis of the shoulder, is described. A mixture of crystals of hydroxyapatite and calcium pyrophosphate dihydrate was identified in the joint tissues using analytical electron microscopy and infra-red spectroscopy.  相似文献   
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Twelve patients with toxic blood concentrations of paracetamol were treated with either cysteamine or amino-acid solution. None of the patients developed severe liver damage, although transient mild biochemical abnormalities developed in three. None of the patients treated with amino-acid solution had side effects due to therapy, whereas all those treated with cysteamine did. It is recommended that amino-acid solutions be used as a temporary measure in patients suspected of massive paracetamol overdose while awaiting estimation of blood paracetamol concentration.  相似文献   
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