Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

Electron transfer by domain movement in cytochrome bc1

The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.     

Clinical presentation and prognostic factors in sodium monofluoroacetate intoxication

From 1970 to 1992 a total of 63 patients underwent operation for ampullary tumor: 40 pancreatoduodenectomies (PDs), 3 total PDs, 8 ampullectomies, and 12 bypass or exploratory laparotomies. The resectability rate was 68%. There were 9 benign tumors, 1 anaplastic tumor, and 53 adenocarcinomas. According to Martin's classification, there were 7 stage I, 11 stage II, 14 stage III, and 21 stage IV tumors. All patients with stage I, II, and III tumors underwent resection. Patients with stage IV tumors had either resection (n = 11) or bypass (n = 10). The mean duration of hospital stay was 20.6 days. Operative mortality was 12.7% for the whole series and 7.5% after PD (2.5% for the last 10 years). Overall survival was 40% at 5 years (85% for stage I, 65% for stage II, 44% for stage III, and 8% for stage IV). Survival was better for stages I, II, and III after PD than after ampullectomy. For stage IV patients survival was 70% after PD versus 20% after bypass at 1 year and 25% versus 0% after 2 years. In our opinion, PD should be proposed even for benign lesions because two of our patients had to undergo repeat operation (PD) 4 and 22 years later, respectively, for stage IV disease. PD is our choice for all tumors of the ampulla.     

Hippocampal atrophy in normal aging. An association with recent memory impairment

OBJECTIVE: To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN: One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING: This study was conducted at a research clinic for the investigation of age-associated neuropsychological and neuroradiologic changes. PARTICIPANTS: Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES: Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS: Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION: We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia.     

Premature separation of centromere and aneuploidy: an indicator of high risk in unaffected individuals from familial breast cancer families?

OBJECTIVES: Injury is the leading cause of death in the male working population of Brazil. An important fraction of these deaths are work related. Very few cohort studies of steel workers, and none from developing countries, have reported on mortality from injuries. This paper analyses mortality from work and non-work related injuries among Brazilian steel workers. METHODS: Deaths during employment from 1 January 1977 to 30 November 1992 were analysed in a cohort of 21,816 male steel workers. Mortality rates specific for age and calendar year among the workers were compared with those of the male population of the state where the plant is located. Work related injuries were analysed by comparing the mortality rates for different subgroups of the cohort. RESULTS: The number of deaths (391) was less than half that expected based on death rates of the general population. Over 60% (242) of deaths were due to injuries. Mortality from most causes was substantially below that in the general population, but that from unintentional injury, was 50% above that of the general population. Standardised mortality ratios (SMRs) were highest for the youngest and the oldest employees and for labourers and clerical workers. Mortality from motor vehicle injury was twice that expected from population rates (SMR = 209, 95% confidence interval (95% CI) 176-244). There was a 67% fall in the age adjusted mortality from occupational injuries in the study period. CONCLUSION: The healthy worker effect in this cohort was greater than that commonly found in studies of occupational groups in developed countries, probably because of a greater socioeconomic gap between employed and unemployed populations in Brazil, and unequal distribution of health care resources. Mortality was especially high for motor vehicle injuries. The fall in mortality from occupational injuries during the study period was probably due to improvement in safety standards, increased automation, and better medical care. There is a need to investigate risk factors for unintentional injuries among steel workers, especially those due to motor vehicle injuries. Prevention of occupational and nonoccupational injuries should be a main priority in Brazil.     

大型离心复合球墨铸铁轧辊的生产

简述了我公司为舞阳铜厂试制４２００ｍｍ厚板轧机离心复合球墨铸铁轧辊的性能要求、内外层双重金属铸造工艺参数的选择及整个铸造生产工艺过程。     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

High-transconductance n-type Si/SiGe modulation-doped field-effecttransistors

The authors report on the fabrication and the resultant device characteristics of the first 0.25-μm gate-length field-effect transistor based on n-type modulation-doped Si/SiGe. Prepared using ultrahigh vacuum/chemical vapor deposition (UHV/CVD), the mobility and electron sheet charge density in the strained Si channel are 1500 (9500) cm²/V-s and 2.5×10¹² (1.5×10¹² ) cm^-2 at 300 K (77 K). At 77 K, the devices have a current and transconductance of 325 mA/mm and 600 mS/mm, respectively. These values far exceed those found in Si MESFETs and are comparable to the best results achieved in GaAs/AlGaAs modulation-doped transistors     

Hg_（1－x）Cd_xTe的扫描光致发光研究

用傅里叶变换红外扫描光致发光方法研究了Ｈｇ１－ｘＣｄｘＴｅ体单晶样品，该方法可直接得到ＨｇＣｄＴｅ晶片组分的二维平面分布，并可得到辐射复合在复合机制中所占比重的平面分布，以及晶体中非平衡载流子寿命的分布