Detection of hepatitis B virus polymerase variations resistant to lamivudine therapy

Objective To investigate variations in hepatitis B virus (HBV) polymerase gene in chronic HBV infected patients resistant to lamivudine therapy. Methods Specimens were obtained from nine patients with chronic HBV infection, who were resistant to lamivudine therapy. Partial segments of the HBV DNA polymerase gene we re amplified by polymerase chain reaction (PCR). Nucleotide sequence was performed using an applied 373 automated sequencer. Titre of HBV DNA was measured by branched DNA assay (Chiron). Results Of nine patients with HBV DNA positive after 64 weeks of treatment, five (56%) had variations in the highly conserved YMDD motif in domain C of the HBV polymerase, three of those were substitutions of isoleucine for methionine(M), and two were substitutions of valine(V) for methionine. Additionally, in two patients with variations characterized by substitutions of V for M, one had a simultaneous amino acid change from the first aspartic acid to glycine and this pattern of variation was not reported in other literatures. With respect to viremia, in two subjects with low titre of HBV DNA (<100 MEq/ml), no variation was found in the YMDD motif, whereas in seven patients with high titre of HBV DBA (>300 MEq/ml), five (71%) had variations in the YMDD motif. Conclusions Lamivudine is a potent anti-viral agent for treatment of chronic HBV infection. Resistance to lamivudine is likely caused by the variations in the YMDD motif of the HBV polymerase gene.     

糖尿病家系及群体胰岛素受体基因变异的对照研究

目的　进一步了解 2型糖尿病胰岛素抵抗的发生机理。方法　运用聚合酶链反应及单链构型多态性 (PCR- SS-CP)技术 ,分析 4个 2型糖尿病家系、5 2例 2型糖尿病患者及 5 4例正常对照者的胰岛素受体基因第 17及 2 0外显子的变异。结果　 17外显子 10 0 8位甘氨基 (Gly)的 GGC→ GGT多态性频率在 2型糖尿病家系及群体分别为 18%和 2 9.4% ,而正常对照组为 9.3% (χ2 =12 .7133,P<0 .0 0 0 5 )。与正常对照组比较 ,2型糖尿病家系、群体的相对危险性分别为 RR=1.944 ,RR=3.738。家系连锁分析显示 L OD最大值为 0 .46 5 736 (θ=0 .0 0 0 0 )。 2 0外显子 Gly的 116 9位 GGT→ GGC多态性频率在 2型糖尿病家系、群体及正常对照组分别为 10 .0 %、15 .4%和 3.7% (χ2 =3.2 36 ,P>0 .0 5 ) ,该位点在 2型糖尿病家系、群体的相对危险性分别为 RR=2 .70 0 ,RR=3.92 7。家系连锁分析显示 L OD最大值为 1.80 334 (θ=0 .0 0 0 0 )。结论　 Gly1 0 0 8和 Gly1 1 6 9位点多态性可能是 2型糖尿病的遗传标志。     

灭活前后HIV-1包膜基因变异的研究

目的 深入了解ＨＩＶ在灭活因素作用下包膜基因变异。方法 对ＨＩＶ－１Ｂ３亚型毒株在Ｓ／Ｄ法及低ｐＨ法灭活作用前后的样品,套式ＰＣＲ扩增其民膜基因Ｃ２￣Ｃ３区５６４ｂｐ的核酸自段,进行核苷酸序列测定和分析。结果 两种方法活前后,包膜基因变异均不显著,核苷酸同源性均为９８％。结论 Ｓ／Ｄ法及低ｐＨ法灭活作用前后ＨＩＶ包膜基因变异不显著。体外传代ＨＩＶ包膜基因趋于稳定。     

Variable activation of lovastatin by hydrolytic enzymes in human plasma and liver

Lovastatin, widely used to lower cholesterol, is a pro-drug that requires metabolic activation through hydrolysis by carboxyesterases. There appear to be at least three distinct esterases in humans capable of catalysing this reaction, one in plasma and two in the liver.The rate of lovastatin hydroxy acid formation was measured as 15.8 pmol · ml^–1 · min^–1 in plasma, 2.13 pmol · mg^–1 protein · min^–1 in hepatic microsomes and 0.92 pmol · mg^–1 protein · min^–1 in cytosol. The data suggest that on average the three esterases together are capable of activating about 220 nmol (90 g) lovastatin per minute per person, to which the esterases of plasma, liver microsomes and liver cytosol contribute approximately 18, 15 and 67%, respectively.All three esterases showed evidence of inter-individual variability. In one of 17 livers, both cytosolic and microsomal esterase activity was completely missing, while two other liver specimens lacked one esterase.Such variability must be expected to influence the therapeutic efficacy of the drug, and they might be related to its occasional toxicity.     

Data sources, bed supply and performance in hospital systems: An Anglo-Czechoslovak comparison

Background: There were a number of similarities, except fortheir effectiveness, in the health care systems of Czechoslovakiaand England and Wales between the Second World War and the late1980s. In a comparison of Czechoslovakia with England and Wales,the objectives of this study were to examine data sources andto report time trends and regional distributions in hospitalbed supply, hospital doctor supply and hospital utilisation.Methods: For the specialties of general medicine and generalsurgery in both countries from 1960 to 1986, data were collatedon bed supply, hospital doctor supply, discharge rates and lengthof stay. Issues concerning the comparability of the data wereaddressed, for example those of the definitions of specialty,length of stay and casemix. Results: In the period 1960 to 1986,in the specialties of general medicine and general surgery,there was a relative excess in the supply of hospital doctorsand beds in Czechoslovakia compared with England and Wales.Hospital performance in terms of discharge rates, dischargesper bed and length of stay remained relatively static in Czechoslovakiaduring this period compared to marked increases in dischargerates and reduced length of stay in England and Wales. Bothcountries recorded reductions in the regional variation of bedand doctor supply and hospital utilisation. Conclusions: Internationalstudies of hospital utilisation need to be interpreted carefullyin the light of definitions of hospital stay, casemix, the useof day cases and the availability of other services. Subjectto these caveats, discharge rates were high and duration ofstay long In Czechoslovakia compared with England and Wales;however, both countries achieved important improvements in regionalequity.     

谷子种子经高空气球搭载后的遗传变异研究

目的 选育出高产、蛋白质和用脂肪含量高的谷子品（系）种。方法 利用高空气球搭载谷子的干种子,在高空飘游８ｈ后回收种植,对其植物学特性及进行分析研究。结果 种子发芽率比对照低５．２％,发芽热比对照高２１．１％。ＳＰ１代植株高度比对照低６．８ｃｍ,旗叶面积比对照高２５％,穗重比对照高１５．９％;ＳＰ３代大穗型株系性状相对稳定,其中ＳＰ３－２的种子蛋白质和脂肪含量均高于对照经高空气球搭载后的ＳＰＥ－３５     

Statistical concepts and biomedical research

An understanding of statistical concepts is important for biomedical researchers. Statistics and probability are the scientific basis for dealing with sources of variation inherent in most biologic processes. This paper provides an introduction to the statistical framework that is fundamental to scientific methods of inquiry. Topics covered include the role of statistics, hierarchy of evidence, reliability and bias, sample size and power, random samples and random allocation, hypothesis testing, estimation, statistical inference, and publication bias. Future papers will focus on specific statistical techniques commonly used in biomedical research.     

Lithium effects on time estimation and mood in manic-melancholic patients. A study of diurnal variations

Behavioural measurements of time experience and phenomenological self-ratings of mood-variations (Beecher's Mood Scale) have been carried out at night and on the following morning in a group of lithium-treated patients, in a group of psychiatric patients not given lithium, and in an untreated group of healthy subjects. In all the groups investigated the internal "clock" was slower in the morning than in the night. The results indicated that the internal "clock" in lithium-treated patients was slower than in the two other groups, but only at night. Mood variations from night ot morning were observed in all three groups. The group of lithium-treated patients had fewer complaints as to self-report of mood-variations compared with the other groups.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.