Primary drug resistance and transmission analysis of HIV-1 in acute and recent drug-naïve seroconverters in Singapore

Objectives

The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.

Methods

Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.

Results

Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.

Conclusions

In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.

     

Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review)

Ovarian cancer remains the leading cause of death from gynecologic malignancy in Western countries. This cancer results from a succession of genetic alterations involving oncogenes and tumor suppressor genes which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, HER-2/neu, c-myc and K-ras, and of the tumor suppressor gene p53, have frequently been observed in sporadic ovarian cancer. In the context of high risk families, the most frequently involved genes are BRCA1 and BRCA2. We review the function of these different proteins, the incidence of mutations in their genes in carcinogenesis and as potential prognostic factors in sporadic and hereditary ovarian cancer.     

Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene

Marked variation in phenotypic expression among BRCA1 and BRCA2 mutation carriers may be partly explained by modifier genes that influence mutation penetrance. Variation in CAG/CAA repeat lengths coding for stretches of glutamines in the C-terminus of the AIB1 protein (amplified in breast cancer 1, a steroid receptor coactivator) has been proposed to modify the breast cancer risk in women carrying germline BRCA1 mutations. We genotyped the AIB1 repeat length polymorphism from the genomic DNA of a group of 851 BRCA1 and 324 BRCA2 female germline mutation carriers to estimate an association with breast cancer risk modification. Hazard ratios (HR) were calculated using a Cox proportional hazards model. For BRCA1 and BRCA2 mutation carriers, analyzed separately and together, we found that women who carried alleles with 28 or more polyglutamine repeats had no increased risk of breast cancer compared to those who carried alleles with fewer repeats (HR for BRCA1/2 carriers = 0.88, 95% CI [confidence interval] = 0.75-1.04). Analyzing average repeat lengths as a continuous variable showed no excess risk of breast cancer (BC) in BRCA1 or BRCA2 mutation carriers (HR for average repeat length in BRCA1/2 carriers = 1.01, 95% CI = 0.92-1.11). These results strongly suggest that contrary to previous studies, there is no significant effect of AIB1 genetic variation on BC risk in BRCA1 mutation carriers and provide an indication that there is also no strong risk modification in BRCA2 carriers.     

异舒吉与美乐心联合治疗冠心病心绞痛44例

1临床资料我院2001-04/2002-06住院冠心病心绞痛患者86例,分为治疗组44例(≥60岁26例),男23例,女21例,年龄38～70岁;对照组42例(≥60岁25例),男21例,女21例,年龄40～70岁.     

GSTM1, smoking and lung cancer: a case-control study

BACKGROUND: We conducted a case-control study to examine the risk of lung cancer in relation to GSTM1 polymorphism and cigarette smoking (primarily of black tobacco) in a French population. METHODS: The 611 subjects were 301 incident lung cancer cases and 310 hospital controls. We were able to constitute a DNA bank for 547 subjects (89.5%) and gather detailed information on smoking history for all of them. Results presented here concern 247 cases and 254 controls. RESULTS: Taking non- or light smokers as the reference category, we estimated odds ratios (OR) of 4.2 (95% CI: 2.6-6.7) and 5.2 (95% CI: 3.3-8.3) for the medium and heavy smokers respectively. On the other hand we estimated that the crude OR associating GSTM1 with lung cancer was 1.3 (95% CI: 0.9-1.8). Furthermore our data do not depart significantly from a multiplicative model of the combined effects of smoking and GSTM1 deficiency. CONCLUSIONS: We conclude that smoking and the GSTM1 gene are each a risk factor for lung cancer, and that their combined effect does not differ significantly from that of a multiplicative model.     

Loss of heterozygosity at the ATM locus in colorectal carcinoma

Patients homozygous for mutation of the ATM gene exhibit constitutional genetic instability and have a high risk of cancer. A-T heterozygotes also have an increased tendency to develop adenocarcinomas. Colorectal cancer (CRC) is the second most common cancer in western populations, and tumors of the right colon are typically highly genetically unstable. The DNA mismatch repair genes mutated in most familial and some sporadic CRCs account for one route by which cells acquire additional oncogenic mutations during the progression of malignancy. Mismatch repair defects, however, do not seem to account for the majority of CRCs. Because of its role in maintaining genomic stability, and the high risk of cancer to homozygotes, ATM is a candidate gene for inactivation in the evolution of chromosomal instability in tumor cells. We have examined 114 CRC patients for loss of heterozygosity (LOH) using six microsatellite markers tightly linked to the ATM locus. Our data suggest that LOH of this region is not associated with cancer of the proximal colon. In the distal colon, LOH was found in 23-31% of cases, which is moderately elevated above the non-specific LOH reported in tumors of this tissue. No correlations were found with regard to clinicopathological variables aside from tumor location.     

环磷酰胺对大鼠早期胚胎发育里程的影响

目的：为探索烷化剂对哺乳动物早期胚胎发育里程的影响及其可能的机制。方法：孕大鼠第３ 天ｉｐ 环磷酰胺（Ｃｙｃ １０ 、２０ 、４０ｍｇ／ｋｇ） ,孕第４ 天评价胚胎的胚胎化作用,胚胎发育时相,及蜕变胚胎率;同时显微外科分离胚胎内细胞团及滋养层细胞,评价两群细胞受损情况。结果：在Ｃｙｃ １０ｍｇ／ｋｇ 时,胚胎的胚泡化作用,胚胎发育时相均未受明显影响;４０ｍｇ／ｋｇ 时,蜕变胚胎率明显提高。胚泡化率及胚胎细胞数呈剂量依赖性减少,其中内细胞团细胞减少尤甚。结论：Ｃｙｃ 在未引起早期胚胎蜕变率显著增加时,可影响细胞周期,但不影响发育里程;高剂量时,显著影响发育里程并伴蜕变率显著增加     

高效液相色谱法测定斑纹芦荟中芦荟苷含量

目的：采用高效液相色谱法测定斑纹芦蔡中芦荟苷含量。方法：芦荟叶汁浓缩物用甲醇超声提取总蒽醌,经薄层色谱分离后,用高效液相色谱法测定,结果：方法回收率为９６．１７％,ＲＳＤ为１．００％（ｎ＝５）。结论：该法准确,且简便可靠,重现性好,为开发利用芦荟资源提供依据。