Mechanisms responsible for resistance of sublines derived from leukemia cell lines to an antitumor agent 9-beta-D-arabinofuranosyl-2-fluoroadenine

An agent 9-beta-D-arabinofuranosyl-2-fluoroadenine (2-F-Ara-A) is a main metabolite of fludarabine, a fluorinated purine analogue with antitumor activity in lymphoproliferative malignancies. In this study, the mechanism responsible for the resistance of cancer cells to fludarabine was examined using the 2-F-Ara-A-resistant sublines JOK-1/F-Ara-A and L1210/F-Ara-A from a human hairy leukemic cell line (JOK-1) and a mouse leukemic cell line (L1210) respectively, which were established by continuous treatment of the parental cell lines with 2-F-AraA. JOK-1/F-Ara-A and L1210/F-Ara-A cells were more than 55 and 29 times more resistant to 2-F-Ara-A than were their parent cell lines, and showed a high cross-resistance to 1-beta-D-arabinofuranosylcytosine but not to doxorubicin or vincristine. These resistant sublines intracellularly accumulated almost the same amount of 2-F-Ara-A as did their parent cell lines. However, the amount of 2-F-Ara-ATP, a cytotoxic metabolite of 2-F-Ara-A, decreased by 2.6% (JOK-1/F-Ara-A C3), 6% (L1210/F-Ara-A C1) and 3.7% (L1210/F-Ara-A C7) relative to the levels in the parent cell lines. Enzymatically, these resistant cells hardly activated deoxycytidine (dCyd) and 2-F-Ara-A. In addition, the abilities to phosphorylate deoxyadenosine and deoxyguanosine were also decreased in the resistant cells in comparison with the parent cells. These findings suggest that the deficiency in activity of dCyd kinase may contribute to the resistance of 2-F-Ara-A.     

Fine specificity of anti-V3 antibodies induced in chimpanzees by HIV candidate vaccines

The fine specificity of the anti-V3 antibody responses induced in chimpanzees immunized by various human immunodeficiency type 1 (HIV-1) candidate vaccines and challenged by heterologous strains of HIV-1 was analyzed by enzyme-linked immunosorbent assay (ELISA) and Pepscan epitope mapping. Two chimpanzees immunized with the recombinant canarypox virus ALVAC-HIV (vCP125) expressing gp160MN and boosted with purified gp160MN/LAI alone, then with both immunogens in combination, were not protected against challenge with HIV-1 SF2. Their sera mainly recognized one epitope of the V3 loop, located in the NH2-terminal half. By contrast, immunization of two other chimpanzees with purified gp160MN/LAI and boosting with a synthetic V3MN peptide elicited a strong anti-V3 antibody response with a broader specificity directed against multiple epitopes all along the V3 loop. These chimpanzees were protected against infection by HIV-1 SF2. However, when these two chimpanzees were challenged later with a HIV-1 clade E strain virus, they became infected. We failed to detect any reactivity with the peptide of the ectodomain of gp41 of sera harvested after immunization with the various immunogens or after challenge with HIV-1 SF2 or HIV-1 90CR402. These results demonstrated that anti-V3 antibodies with a restricted fine specificity were induced in chimpanzees immunized with gp160 purified or expressed by recombinant canarypox confirming our previous results obtained in three different species (human, guinea pig and, macaque). In contrast, a boost with the V3 peptide broadened antibody responses, suggesting that the mode of presentation of the V3 loop to the immune system strongly influences the epitope specificity of the resulting antibody response.     

Evaluating the patient satisfaction questionnaire after inpatient treatment in phoniatrics and pediatric audiology--a contribution to quality control?]

Baker and confectioner apprentices have been included in a prospective follow-up study in the region of East Thuringia, to evaluate risk factors for the development of hand dermatitis. Starting in August 1996, the apprentices have been interviewed and examined in a standardized way right at the beginning (n=91) of their vocational training, 6 (n=79) and 12 months (n=63) later. To gain objective data, TEWL score was also assessed at 3 standardized sites on the hands. In their case histories, 3.3% (n=3) of the apprentices reported hand dermatitis. The 1st assessment after 2 to 4 weeks vocational training revealed hand eczema in 17.5% (n=16) of the individuals. At the follow-up after 6 months of training 29.1% (n=23), and after 12 month of training 27.0% (n=17), of the apprentices had hand dermatitis of mild to moderate severity. Within 6 months, the TEWL score rose significantly (p<0.001) from 11.9 g m(-2) h(-1) (-/+5.4) to 16.8 g m(-2) h(-1) (-/+9.5). After 12 months, the TEWL score was 14.9 g m(-2) h(-1) (-/+4.6). For the atopic skin diathesis (>10 points of Diepgen's atopy score), there was a significant tendency to be a predictive factor for the development of occupational hand dermatitis. TEWL score failed to correlate with the development of skin damage in our study. The same was true for respiratory atopy and metal sensitization.     

微弱辐射测量仪的研制

本文介绍一种高灵敏，宽动态范围的辐射测量仪的研制情况，着重对线路的噪声性能进行了分析，并据此完成了元件的选择。文中还给出了仪器达到的指标。     

双面肖特基势垒型GaAs粒子探测器的电特性研究

研究了有源面积为９ｍｍ２的双面肖特基势垒ＧａＡｓ粒子探测器的电特性。器件工艺简单，结构新颖，反向耐压高于３００Ｖ，反向漏电流密度低（９１ｎＡ／ｍｍ２），该器件能经受能量为１．５ＭｅＶ、剂量为１０００ｋＧｙ的电子照射，电特性正常，是一种抗辐照的粒子探测器。     

Mechanical properties of Al2O3 particle-Y-TZP matrix composite and its toughening mechanism

Dense Al₂O₃ particle-Y-TZP matrix (Al₂O₃<40 vol%) composite was prepared by pressureless sintering at 1550°C. Composites with 10–30 vol% Al₂O₃ particles showed enhanced fracture toughness, bending strength and Vicker's hardness as compared to single-phase Y-TZP. The highest strength (1150 MPa) and highest toughness (12.4 MPa m^1/2) were obtained for the composite containing 10 vol% Al₂O₃. It was found that, in addition to the contribution by the crack-deflection effect, the enhanced phase transformation from tetragonal to monoclinic during fracture was the main toughening mechanism in operation in the composites.     

新型后坐加速度开关阵列传感器

分析了国外后坐加速度传感器发展动向。介绍了新型后坐加速度开关阵列传感器的结构、原理、参数选择和性能设计。给出了原理性静态、动态试验结果，以证明新方案的可行性。最后指出了这种新型结构的传感器所具有的特点。     

Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche

Girls with a history of premature pubarche, i.e. appearance of pubic hair before 8 years of age, show hyperinsulinism in response to an oral glucose tolerance test. As hyperinsulinaemia has a major role in dyslipaemia, and is considered an independent risk factor for cardiovascular disease, we assessed the patterns of plasma insulin concentration after a standard oral glucose tolerance test as well as fasting serum lipid, lipoprotein, and sex hormone-binding globulin concentrations in girls (n = 81) with premature pubarche compared with girls (n = 55) matched with them for stage and bone age to ascertain their metabolic states to identify those potentially at risk for the development of premature cardiovascular disease. Mean serum insulin concentrations were higher in patients at all pubertal stages, and associated with elevated serum triglyceride, very low density cholesterol and very low density triglyceride concentrations (p value range 0.04 to < 0.0001) but reduced sex hormone-binding globulin. Premature pubarche patients also displayed higher low density to high density lipoprotein cholesterol ratios compared with control subjects (p = 0.004 to 0.008). In conclusion, hyperinsulinaemia, decreased sex hormone-binding globulin concentrations and an unfavourable lipid pattern are common features in premature pubarche girls supporting the contention that atherogenic abnormalities composing the metabolic syndrome could start in childhood. To determine the clinical sequelae of such clustering of metabolic deviations, girls who were identified need to be followed up for the potential development of premature cardiovascular disease.