声触诊组织量化技术（VTQ）测量肝硬度与血清AST/ALT比值评价肝硬化患者严重程度及预后分析

摘要 目的：探讨VTQ测量肝硬度与血清AST/ALT比值对肝硬化患者严重程度及预后的评价价值。方法：回顾性选择2018年1月至2022年10月来我院诊治的肝硬化患者80例,根据Child-Pugh分级将80例患者分为Child-Push A级30例、B级25例、C级25级,根据是否存在并发症将80例患者分为并发症组（45例）与非并发症组（35例）,80例患者均用VTQ法检测VTQ值,检测所有患者的血清ALT、AST水平,计算ALT/AST比值。对比不同Child-Push分级患者不同部位的VTQ值,对比不同Child-Push分级患者的AST、ALT水平及AST/ALT比值,对比有无并发症组的不同部位VTQ值,对比有无并发症组患者的AST、ALT水平及AST/ALT比值,分析80例患者不同部位VTQ值与AST、ALT、AST/ALT比值的相关性。结果：C组患者不同肝脏部位的VTQ值明显较A组及B组高,B组患者不同肝脏部位的VTQ值较A组高（P<0.05）。C组的AST水平、AST/ALT值明显较A组、B组高,B组的AST水平、AST/ALT值明显较A组高（P<0.05）,C组的ALT水平较A组、B组高,B组的ALT水平较A组高,但组间对比无统计学意义（P>0.05）。并发症组不同肝脏部位的VTQ值明显较无并发症组高（P<0.05）。并发症组的AST、AST/ALT比值明显较无并发症组高（P<0.05）,并发症组的ALT较无并发症组高,但组间对比无统计学意义（P>0.05）。80例肝硬化患者的AST、AST/ALT比值与不同部位的VTQ值正相关（P<0.05）,ALT水平与不同部位的VTQ值无相关性（P>0.05）。结论：VTQ测量肝硬度与血清AST/ALT比值可用于评价肝硬化严重程度及预后。     

Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity

Background

Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT≥1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue.

Methodology/Principal Findings

We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT≥1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve = 0.62; 95% confidence interval [CI]: 0.57–0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve = 0.56; 95% CI: 0.52–0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF.

Conclusions

Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.     

Performance of an Optimized Paper-Based Test for Rapid Visual Measurement of Alanine Aminotransferase (ALT) in Fingerstick and Venipuncture Samples

BackgroundA paper-based, multiplexed, microfluidic assay has been developed to visually measure alanine aminotransferase (ALT) in a fingerstick sample, generating rapid, semi-quantitative results. Prior studies indicated a need for improved accuracy; the device was subsequently optimized using an FDA-approved automated platform (Abaxis Piccolo Xpress) as a comparator. Here, we evaluated the performance of the optimized paper test for measurement of ALT in fingerstick blood and serum, as compared to Abaxis and Roche/Hitachi platforms. To evaluate feasibility of remote results interpretation, we also compared reading cell phone camera images of completed tests to reading the device in real time.Methods96 ambulatory patients with varied baseline ALT concentration underwent fingerstick testing using the paper device; cell phone images of completed devices were taken and texted to a blinded off-site reader. Venipuncture serum was obtained from 93/96 participants for routine clinical testing (Roche/Hitachi); subsequently, 88/93 serum samples were captured and applied to paper and Abaxis platforms. Paper test and reference standard results were compared by Bland-Altman analysis.FindingsFor serum, there was excellent agreement between paper test and Abaxis results, with negligible bias (+4.5 U/L). Abaxis results were systematically 8.6% lower than Roche/Hitachi results. ALT values in fingerstick samples tested on paper were systematically lower than values in paired serum tested on paper (bias -23.6 U/L) or Abaxis (bias -18.4 U/L); a correction factor was developed for the paper device to match fingerstick blood to serum. Visual reads of cell phone images closely matched reads made in real time (bias +5.5 U/L).ConclusionsThe paper ALT test is highly accurate for serum testing, matching the reference method against which it was optimized better than the reference methods matched each other. A systematic difference exists between ALT values in fingerstick and paired serum samples, and can be addressed by application of a correction factor to fingerstick values. Remote reading of this device is feasible.     

Comparison of Histologic Characteristics of Chinese Chronic Hepatitis B Patients with Persistently Normal or Mildly Elevated ALT

Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer''s classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log₁₀copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.     

Quantitative rat liver function test by galactose single point method

The purpose of this study was to investigate the galactose single point (GSP) method, a residual liver function test recently recommended by the US Food and Drug Administration, which can be a useful tool for rat liver function measurement. Rats were treated either with carbon tetrachloride (CCl(4)) alone (1 mL/kg, intraperitoneally [i.p.]) for one day or with isoniazid (INH) alone (150 mg/kg, i.p.) or (in order to ameliorate the effects of INH) with a combination of INH and bis-p-nitrophenyl phosphate (BNPP) (25 mg/kg, i.p.) for 21 days. Hepatotoxicity was assayed by plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and scores of histological activity index-necroinflammation (HAI-NI) of the respective liver specimens. The GSP method in rats was defined by the galactose blood level after 60 min. Significant differences in GSP values were observed between controls and the CCl(4)-treated rats. After 21 days of treatment, no significant changes in AST and ALT values were observed among the control, INH and INH-BNPP groups. There were significant differences in average GSP values for controls (P < 0.001) and INH-BNPP (P < 0.001) compared with INH alone. Highly significant correlations (P < 0.001) were obtained between GSP and scores of HAI-NI for all the groups. GSP was concluded to be a more sensitive biomarker of INH-induced hepatotoxicity than AST or ALT in the rats. The GSP method has been proved to be a simple and useful tool for the quantitative determination of liver function in rats, which can possibly be extended to other animals.     

Carbon Isotope Ratios of Epidermal and Mesophyll Tissues from Leaves of C3 and CAM Plants

The ¹³C values for epidermal and mesophyll tissues of two C₃plants, Commelina communis and Tulipa gesneriana, and a CAMplant, Kalancho daigremontiana, were measured. The values forthe tissues of both C3 plants were similar. In young leavesof Kalancho, the epidermis and the mesophyll showed S13C valueswhich were nearly identical, and similar to those found in C3plants. However, markedly more negative values for epidermalcompared to mesophyll tissue, were obtained in the mature Kalancholeaf. This is consistent with the facts that the epidermis ina CAM leaf is formed when leaves engage in C₃ photosynthesisand that subsequent dark CO₂ fixation in guard cells or mesophyllcells makes only a small contribution to total epidermal carbon. (Received January 27, 1981; Accepted May 14, 1981)     

Some Methods for the Measurements of Tonoplast Resistance of Nitellopsis obtusa

Measurements of tonoplast resistance for unit area, T were carriedout by four methods. The T values obtained by two of these methods,when taking into account a correction for leakage current, were0.024 and 0.010 k cm². The other two methods, which made itpossible to neglect leakage current, gave the T values of 0.036and 0.021 k cm². Thus, the mean value of tonoplast resistancein the investigated cells of Nitellopsis obtusa was 0.023 kcm², while the measurements in which leakage current was nottaken into account gave the value 10.6 k cm². The results obtainedin this study indicate the fact that leakage current significantlyaffects measurements of tonoplast resistance and that the truevalue of that resistance is smaller by two or three orders ofmagnitude than that usually reported.     

Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity

In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L ≤; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11-0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function.     

A correlative study on serum cholylglycine levels in hepatobiliary disease.

The serum cholylglycine (CG), alanine aminotransferase (ALT) and total bilirubin levels were studied in 210 patients with hepatobiliary disease and in 70 healthy subjects. Serum CG concentrations in all the hepatobiliary diseases were found to be significantly higher than those of their controls. Patients with abnormal increases in ALT and bilirubin levels also showed raised CG concentrations; however, some patients with normal ALT and bilirubin levels, still had markedly elevated CG values. Patients with hepatic cirrhosis had high serum CG levels, followed, in descending order, by chronic active hepatitis and chronic persistent hepatitis. In the cholecystitis and cholelithiasis cases, their CG levels were significantly higher than those of the controls but lower than the values in hepatic disease patients; however, more cholecystitis cases had abnormally high serum bilirubin levels than CG. The results also show that serum CG concentrations vary in the different hepatobiliary diseases, and that serial CG measurements are more sensitive than measuring ALT and bilirubin levels in the diagnosis of hepatic diseases. Serum CG can be used as an index for evaluating the activity of chronic hepatitis; it can also be employed as a diagnostic tool in cholecystitis and cholelithiasis.     

Epidemiology of serum aminotransferase activities in the elderly.

BACKGROUND: Our study used data collected in Chung-Hsing Village in May 1998 to explore the distribution of serum aminotransferase activities and the relationship between aminotransferase and its related factors in the elderly. METHODS: All individuals aged 65 and over were recruited as study subjects. A total of 1093 persons, out of 1774 registered residents, were contacted by face-to-face interview. The response rate was 61.6 percent. However, only 586 subjects had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. In order to study the significant related factors of abnormal aminotransferase activities, the t-test, ANOVA, chi-square analysis, and multivariate logistic regression were used. RESULTS: There were 66 percent men and 34 percent women. The mean age was 73.1 +/- 5.3 years. The mean values of aspartate aminotransferase (AST) were 29.3 +/- 14.5 u/l in men and 27.8 +/- 10.7 u/l in women (p > .05). The mean values of alanine aminotransferase (ALT) were 30.9 +/- 25.2 u/l in men and 26.3 +/- 12.6 u/l in women (p < .01). The abnormality rates of AST (> or = 40 u/l) were 10.5 percent in men and 12.2 percent in women (p > .05). The abnormality rates of ALT (> or = 40 u/l) were 16.7 percent in men and 12.6 percent in women (p > .05). After controlling for the other covariates, the multivariate logistic regression analysis showed that the significant related factor of abnormal AST was retirement status (odds ratio 4.4; 95 percent confidence interval = 1.5-13.3; p < .01). The significant related factors of abnormal ALT were obesity (odds ratio = 2.2; 95 percent confidence interval = 1.1-4.2; p < .05) and hypertriglyceridemia (odds ratio = 2.7; 95 percent confidence interval = 1.5-4.9; p < .01). CONCLUSIONS: We raise the hypothesis that evidence of liver disease with abnormal ALT may co-vary with other indicators of chronic diseases. A large-scale investigation will be suggested in the future to demonstrate the causal-effect issue between abnormal ALT and obesity or hypertriglyceridemia.     

Tissue polypeptide antigen (TPA) modifications in hepatic cirrhosis, aggressive chronic hepatitis, persistent chronic hepatitis, and in minimal pathology

A total of 104 patients with various liver diseases were studied. Hepatic biopsy was performed and the AST, ALT and TPA in serum were measured. Higher levels of TPA, AST and ALT were found in CAH and LC, lower in CPH and MHP. High serum TPA values, usually suggesting the possibility of neoplasm, should be considered with attention. A follow-up with periodic TPA assays (in addition to AST and ALT) is suggested in patients with acute hepatitis, in order to predict further possible complications such as CAH and LC.     

Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence

Background & Aims

There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding.

Methods

A total of 975 school children (aged 7–18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls.

Results

In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor.

Conclusions

In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.     

Expression, purification, and initial characterization of human alanine aminotransferase (ALT) isoenzyme 1 and 2 in High-five insect cells

Alanine aminotransferase (ALT) is a key enzyme for gluconeogenesis as well as a widely used serum marker for liver injury. We have identified two ALT isoenzymes, ALT1 and ALT2, which are encoded by separate genes. In this study, we described the expression, purification and initial characterization of human ALT1 and ALT2 proteins in High-five insect cells. Human ALT1 and ALT2 were expressed as His-tagged fusion proteins by recombinant baculovirus in insect cells and purified into homogeneity in one step by using immobilized Ni²⁺-affinity chromatography. Tag-free ALT1 and ALT2 were obtained by cleavage of enterokinase digestion and used for initial characterization of the enzymes. The specific ALT activity of purified fusion or His-tag-removed ALT1 was about 15-fold higher than that of ALT2 and their enzymatic activities decreased quickly at 37 °C and −20 °C, but were well preserved at −80 °C. Nevertheless, the ALT1 and ALT2 activities remained stable in a buffer containing 25% glycerol. The pH profile was similar between hALT1 and hALT2 in that both enzymes remained fully active between pH 6.5 and 8.0. The purified ALT recombinant proteins can not only be used as a reference protein standard for the ALT assay in clinical chemistry, but also will be useful for understanding the biochemical and biological significance of the isoenzymes and for developing ALT isoform-specific assays for clinical or preclinical diagnostic use.     

Lack of sexual dimorphism in alcohol-induced liver damage (ALD) in rats treated chronically with ethanol-containing low carbohydrate diets: The role of ethanol metabolism and endotoxin

Evidence has been presented suggesting that females are significantly more susceptible to alcohol-induced liver damage (ALD) than males. In the current study, we examined sexual dimorphism in hepatic pathology, metabolism and cytokine profiles using two different rat models of ALD. Male and female Sprague-Dawley or Wistar rats were fed ethanol-containing low-carbohydrate liquid diets using oral or intragastric methods for 42 or 60 days. In both models, ethanol treatment produced similar significant liver hyperplasia accompanied by increases in plasma ALT, steatosis, inflammation and necrosis (p < 0.05). Greater pathology scores were observed in the intragastrically infused rats. Males did not differ significantly from females in serum ALT values or pathology despite greater elevations in TNFalpha and IL-1beta mRNAs in ethanol-treated female rat livers (p < 0.05). Furthermore, there was no sexual dimorphism in blood ethanol concentrations or CYP2E1-induction even though sexually dimorphic alterations in other hepatic cytochrome P450 enzymes were observed. These data do not support previous observations that female rats have a greater susceptibility to ethanol-induced hepatotoxicity than males.     

Association of α-fetoprotein levels with liver stiffness measurement in outpatients with chronic hepatitis B

The association between α-fetoprotein (AFP) levels with the assessment of liver stiffness (LS) in chronic hepatitis B (CHB) patients were explored. A total of 283 outpatients with CHB were enrolled. Patient age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AFP, platelet (PLT), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), albumin (ALB), globulin, and albumin/globulin (A/G) levels were associated with LS values in the univariate model (P<0.05). Significant associations between AFP and PLT levels with LS values were observed when both variables were included in the multivariate analysis models. Receiver operation characteristic (ROC) analysis indicated that the combination of AFP and PLT levels could enhance the predictive performance of liver fibrosis (area under the curve (AUC) = 0.819, P<0.001) and that PLT levels (PLT < 100 × 10⁹/l) combined with high AFP levels (AFP > 8 ng/ml) significantly increased the prediction of liver fibrosis (OR = 11.216). More importantly, LS values associated with higher AFP levels (AFP > 8 ng/ml), independently of higher ALT or AST values, were significantly higher than those of low AFP level groups. In conclusion, in Chinese outpatients with CHB, AFP outperformed ALT and/or AST levels in terms of their association with LS. AFP and PLT levels were independently associated with LS, and their combined assessment could enhance the diagnostic and predictive performance of liver fibrosis among CHB patients.     

Laboratory assessment of chronic hepatitis in Syrian hamsters.

Clinical chemistry studies in the diagnosis of hamster diseases have received little attention. Although normal values exist for serum constituents, the effects of disease on these values are not well documented. Chronic hepatitis is endemic in several Syrian hamster (Mesocricetus auratus) colonies and is reported mainly through routine histologic examination. We investigated whether any differences in serum clinical chemistries were present in animals with hepatobiliary disease versus unaffected hamsters. Only serum alanine aminotransferase (ALT) and bile acids were significantly elevated in hamsters with chronic hepatitis only. In hamsters that had both chronic hepatitis and biliary disease, the serum ALT, alkaline phosphatase, cholesterol, and bile acids were significantly elevated. The results of this study indicated that serum clinical chemistries may be a useful antemortem diagnostic test for chronic hepatobiliary disease in hamsters.     

微量法与试管比色法检测ALT的比较

经实验建立了一种用于检测血浆中丙氨酸氨基转移酶(ALT)含量的微量测定法,并与比色法（传统赖氏法)进行了比较。用两种方法检测定值血清、室内质控及样品并比较标准曲线后,结果无显著性差异,同时微量法重复性较好,结果表明微量法测定ALT酶活力可以替代比色法测定血浆中ALT含量,适合大批量血浆ALT含量的快速检测。     

{delta}15N and {delta}13C Measurements of Antarctic Peninsula Fauna: Trophic Relationships and Assimilation of Benthic Seaweeds

Measurements of ¹³C, ¹⁵N, and C/N for a variety of Antarcticpeninsula fauna and flora were used to quantify the importanceof benthic brown algae to resident organisms and determine foodweb relationships among this diverse littoral fauna. ¹³C valuesranged from–16.8 for benthic algal herbivores (limpets)to –29.8 for the krill, Euphausia superba; the averagepooled value for brown macroalgae, including their attachedfilamentous diatoms, was–20.6. There was no correlationbetween biomass ¹³C or ¹⁵N with C/N content, and consequentlyboth ¹³C and ¹⁵N values were useful in evaluating trophic relationships.¹⁵N values of the fauna ranged from 3.1 to 12.5, with lowestvalues recorded in suspension feeders (e.g., bryozoans) andhighest values in Adelie penguins (12.5) collected in 1989.The comparatively lower ¹⁵N value for a Chinstrap penguin (6.9)collected in 1997 is attributed to the different dietary foodsources consumed by these species as reflected in their respective¹³C values. Significant amounts of benthic macroalgal carbonis incorporated into the tissues of invertebrates and fishesthat occupy up to four trophic levels. For many benthic andepibenthic species, including various crustaceans and molluscs,assimilation of benthic algal carbon through detrital pathwaysranges from 30 to 100%. Consequently, the trophic importanceof benthic brown algae may well extend to many pelagic organismsthat are key prey species for birds, fishes, and marine mammals.These data support the hypothesis that benthic seaweeeds, togetherwith their associated epiphytic diatoms, provide an importantcarbon source that is readily incorporated into Antarctic peninsulafood webs.     

利用基因芯片分析拉米夫定治疗过程中HBV DNA的基因变异

依据乙型肝炎病毒(Hepatitis B virus;HBV)聚合酶基因序列研制HBV基因芯片,此芯片可分析HBV的7个基因型、4种血清型和HBV聚合酶基因rtV173、rtL180、rtM204和rtV207位点的突变。利用此芯片对A、B两组共计45例拉米夫定治疗12个月的患者进行服药前和服药后3、6、9、12个月的动态检测,其中C基因型39例,且血清型均为adr;B基因型6例,其血清型均为adw。在完成全程检测的38例患者中,17例ALT升高的A组出现1例拉米夫定耐药变异株,而21例ALT正常的B组出现4例变异株,且所有变异株均为rtM204 V／rtL180M,其中2例野生株和变异株共存。rtM204V变异最早在服药6个月时出现,随后出现rtL180M变异。10份PCR产物测序分析表明,芯片检测结果与测序结果基本一致,仅在rtL173位点出现1例差异。进一步分析HBV DNA变异与HBV DNA含量、ALT水平和HBeAg血清转换率的相关性,初步结果表明变异株的出现与治疗过程中的DNA反弹呈正相关,而与起始HBVDNA水平、ALT值无关联。HBV基因芯片可初步用于HBV DNA检测,可能是临床追踪评价抗病毒治疗效果的较好方法之一。     

Evaluation of the 15N Natural Abundance Method and Xylem Sap Analysis for Assessing N2 Fixation of Understorey Legumes in Jarrah (Eucalyptus marginata Donn ex Sm.) Forest in S.W. Australia

Hansen, A. P. and Pate, J. S. 1987. Evaluation of the ¹⁵N naturalabundance method and xylem sap analysis for assessing N₂ fixationof understorey legumes in jarrah (Eucalyptus marginata Donnex Sm.) forest in S.W. Australia.—J. exp. Bot 38: 1446–1458. Nodulated seedlings of Acacia pulchella, A. alata and A. extensawere grown in glasshouse sand culture under a range of levels(0–16 mol m³) of nitrate, supplied as ¹⁵NO₃, or as unenrichedlaboratory grade nitrate (¹⁵N value 5·5%_o). Nitrate at8·0 mol m ³ or above was highly inhibitory to growthof all species. Using ¹⁵N dilution analysis of the ¹⁵N enrichedcultures to measure symbiotic dependency, it was shown that¹⁵N values of the parallel unenriched cultures increased innear linear fashion from close to zero in fully symbiotic plantsto values close to that of the supplied NO₃ in plants experiencingnitrate levels (4·0 mol m³ or above) inhibiting N₂ fixationby over 90%. Xylem sap analyses (0·4 mol m³ NO₃ treatments)showed asparagine as the major nitrogenous solute, relativelylittle spill-over of free nitrate, and no evidence of majorshifts in balance of amino compounds with increasing dependenceon nitrate. This essentially invalidated use of the techniqueas a field assay for N₂ fixation by the species. ¹⁵N values for total N of soil sampled at 64 widely distributedsites in jarrah forest ranged from – 2·15 to +5·4(mean +2·1). Comparable values for soil mineral N (NH⁺₄and NO₃) were +0·3 to + 14·2 (mean +5·1).¹⁵N values of the total plant N of the legumes and of non-N₂-fixingreference species were also highly variable between sites, withlittle evidence of reference plant N accurately reflecting the¹⁵N abundance of soil nitrogen, or of visibly well nodulatedlegume components showing consistently lower ¹⁵N values thantheir companion reference plants. At one site it was possibleto compare ¹⁵N values of first season seedling legumes withpreviously published estimates of their progressive N₂ fixationusing C₂H₂ reduction assays. It was concluded that heterogeneity in ¹⁵N discrimination ofsoil within the ecosystem precluded effective use of the ¹⁵Nnatural abundance technique for assessing legume N₂ fixation. Key words: Acacia spp., ¹⁵N natural abundance,, xylem sap analysis,, nitrogen fixation.