Sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy.

To investigate the sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy a total of 100 hysteromyomectomy patients were randomly divided into the control group and the observation group with 50 in each group. Patients in the control group received the general anesthesia, while those in the observation group received spinal-epidural anesthesia, and intravenous injection of dexmedetomidine. For maintenance of anesthesia, ropivacaine was adopted for both groups. Before anesthesia, at 30 min and 60 min after anesthesia, we measured the heart rate (HR), bispectral index (BIS) and sedative effect. Before anesthesia, HR, BIS and Ramsay scores were compared between two groups, and the results showed that differences had no statistical significance (p>0.05); but at 30 min after anesthesia, HR and BIS of patients in the observation group were significantly lower than those in the control group (p<0.05), and Ramsay score was higher than the control group (p<0.05). No statistical significance was found in differences of the incidence rate of adverse reactions between two groups (p>0.05). Application of dexmedetomidine in spinal-epidural anesthesia gains promising sedative effect and safety in hysteromyomectomy, which is worthy of being promoted in clinical treatment.

Intragenic recombination as a mechanism of genetic diversity in bluetongue virus.

Bluetongue (BT), caused by Bluetongue virus (BTV), is an economically important disease affecting sheep, deer, cattle, and goats. Since 1998, a series of BT outbreaks have spread across much of southern and central Europe. To study why the epidemiology of the virus happens to change, it is important to fully know the mechanisms resulting in its genetic diversity. Gene mutation and segment reassortment have been considered as the key forces driving the evolution of BTV. However, it is still unknown whether intragenic recombination can occur and contribute to the process in the virus. We present here several BTV groups containing mosaic genes to reveal that intragenic recombination can take place between the virus strains and play a potential role in bringing novel BTV lineages.

Genetic polymorphisms of metabolic enzymes CYP1A1, CYP2D6, GSTM1 and GSTT1 and leukemia susceptibility.

The genetic polymorphisms of biotransformation phase I enzymes, cytochrome P450 (CYP1A1 and CYP2D6), and phase II enzymes, glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 204 healthy persons and 348 leukemia patients, who suffered from also acute lymphoblastic leukemia (ALL), acute nonlymphoblastic leukemia (ANLL) chronic myelogenous leukemia (CML), from the Han ethnic group in Changsha City of Hunan Province of China. Our results showed that the frequencies of polymorphisms of CYP1A1, CYP2D6 and GSTT1 among the groups including acute lymphoblastic leukemia, ANLL, chronic myelogenous leukemia and healthy control have no significant differences. The variation of GSTM1-null genotype alone correlated with the development of ANLL. The combined genotypes of GSTM1-null with GSTT1-null, or GSTM1-null with CYP1A1 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant and CYP2D6 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant, CYP2D6 heterozygous mutant and GSTT1-null were found in individuals with high risk of ANLL. All these findings suggest that GSTM1-null genotype alone or in coordination with the relevant genotypes of other metabolic enzymes might be susceptibility factors in the etiology of ANLL.

Genetic polymorphisms of phase II metabolic enzymes and lung cancer susceptibility in a population of Central South China.

A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/-), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/-) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China.

[Study on the relationship between polymorphisms of Cyp1A1, GSTM1, GSTT1 genes and the susceptibility to acute leukemia in the general population of Hunan province].

OBJECTIVE: Based on the distribution of genetic polymorphisms regarding phase I metabolic enzyme cytochrome P450 1A1 (CYP1A1) and phase II metabolic enzymes glutathione S-transferase GSTM1 and GSTT1 genotypes in acute leukemia patients and health controls among general population of Hunan in China, this study was to explore the relationship between these gene polymorphisms and the susceptibility to acute leukemia. METHODS: Using case-control methodology, we studied 204 healthy controls and 232 patients with acute leukemia, of which 112 patients were suffering acute lymphoblastic leukemia (ALL) and 120 with acute non-lymphoblastic leukemia (ANLL). The frequencies of the genotypes were detected by PCR and PCR-RFLP techniques. RESULTS: The variation frequencies of CYP1A1 gene (Msp I polymorphisms, site 3801T-C variation) in ALL and ANLL groups were 74.1% and 70.8% respectively which were higher than 63.3% appeared in the healthy controls. However, the differences between patients (ALL or ANLL) and healthy controls were not statistically significant (P > 0.05 for both). The null genotype of GSTM1 (GSTM1 -/-) in ALL group was 60.7%, which was not significantly different from the controls (55.4%). However, GSTM1 -/- genotype in ANLL group was 68.3%, significantly different from the controls (P < 0.05). The null genotypes among GSTT1 (GSTT1 -/-) in ALL, ANLL and control group were 50.9%, 55.0% and 49.0% but their differences were not statistically significant (P > 0.05). The incidences of GSTM1 -/- and GSTT1 -/- combined genotype in ALL, ANLL and control group were 33.0%, 40.0% and 27.5%, of which the difference between ANLL group and control group was statistically significant (P < 0.05) and CYP1A1 gene heterozygous mutation type or homozygous mutation type combined with GSTM1 -/- and GSTT1 -/- increased the risk of ANLL (OR value 1.890, 95% CI: 1.084-3.295). CONCLUSION: These results indicated that both the variation of CYP1A1 gene or GSTT1 -/- genotype alone might not be associated with the susceptibility of acute leukemia while GSTM1 -/- genotype alone or combined with GSTT1 -/- or the 3801 T-C variation of CYP1A1 gene were correlated with ANLL. These findings suggest that GSTM1 - / - genotype alone or in combination with other defective genotypes might serve as risk factors to the etiology of ANLL.

[Different sensitivity of two chronic myeloid leukemia cell lines to interferon-alpha].

BACKGROUND & OBJECTIVE: The clinical observation has shown that interferon-alpha(IFN-alpha) is one of the most effective therapeutic agents for the malignancies of hemopoietic system and lymphoma. However, IFN-alpha can only induce about 70-80% of the patients with chronic myeloid leukemia (CML) to get hematological remission. The mechanism by which various CML cases respond differently to IFN-alpha is still unclear. METHODS: (1)The effects of IFN-alpha in different concentrations (100, 500, 1,000, 5,000, and 10,000 U/ml) on growth of the two CML cell lines were detected by MTT assay,semisolid colony formation and trypan-blue staining for the cells in liquid culture. (2)The cell apoptosis was examined by flow cytometry(FCM),fluorescence microscopy and gel electrophoresis analysis for DNA fragmentation in 48 hours after IFN-alpha (1,000 U/ml) induction of both KT-1/A3 and K562 cells. (3)The expression levels of bcr/abl chimeric genes were analyzed by relative quantitative RT-PCR at 48 hours after cultivation of both KT-1/A3 and K562 cells with IFN-alpha in 1,000 U/ml. RESULTS: (1)The growth inhibition of KT-1/A3 cells was dose-dependent in IFN-alpha from the concentration of 100 U/ml to 10,000 U/ml. (2)Having been induced with IFN-alpha in 1000 U/ml for 48 hours, the apoptosis rate of KT-1/A3 cells raised from 3.29% to 11.8% and the expression level of bcr/abl chimeric gene in this cell line declined to 66.7% as compared with those of the control. (3)The growth and apoptosis rate as well as bcr/abl gene expression level of K562 cells were not significantly affected by IFN-alpha. CONCLUSION: Different populations of CML cells shows different sensitivity to IFN-alpha.

[Comparison of specific genomic DNA fragment between Microtus fortis calamorum and Microtus fortis fortis].

Microtus fortis(Taxonomy ID: 100897), also named as reed vole, is classified as Microtus, Micotinae, Cricetidae, Rodentia, Mammalia on taxonomy. Microtus fortis mainly distributes in China. Some areas of Russia, North Korea and Mongolia close to Northeast borderland of China also have a small number of Microtus fortis in distribution. Microtus fortis in China has principally 4 subspecies, and most of them live is the drainage area of Yangtse River. Schistosoma japonicum (one of commonly parasites in China) can infect about 40 kinds of mammalian animals, including the human being, but could not infect Microtus foris. It is known as the only animal in Dongting Lake region of China which has the ability of natural resistance to Schistosoma japonicum. The Microtus fortis domesticated in laboratory has the same biological characteristics as the wild one and these characteristics could be inherited to its progeny steadily. We got a specific DNA fragment from genomic library of Microtus fortis. This DNA fragment in genomic DNA of human beings, Kunming mice, Balb/c mice and C57BL/6J mice could not be detected by dot blot hybridization and PCR, apart from genomic DNA of Microtus fortis. In this report, the differences of genomic DNA in 34 Microtus fortis were compared between Microtus fortis calamorum(Dongting Lake region of southern China) and Microtus fortis fortis (Ningxia province of northern China). The residing localion of these two subspecies is far away about 1,200 kilometers from each other. The genomic DNA of Microtus fortis calamorum and Microtus fortis fortis were extracted and amplified by PCR according to the specific genomic DNAs sequence of Microtus fortis reported previously (Accession number in GenBank: AF277394). The amplified DNA fragments were inserted into pGEM-T easy vector and sequenced. The DNA fragment sequencing results from the two subspecies were compared to detect whether there was any difference. 19 alleles were found from Microtus fortis (20 of Microtus fortis calamorum and 14 of Microtus fortis fortis). The results of multiple sequence alignment showed that 25 single nucleotide polymorphism (SNP) sites were existed in the different Microtus fortis individuals, including transition (G-->A,A-->G,T-->C,C-->T), transversion(G-->T,A-->T,T-->A,C-->A), insertion (CA) and deletion (TGTTTT). The difference of genomic DNA from two subspecies were obvious, especially on the sites of 146, 192, 223, 224 and 235. The insertion of CA on the sites of 223 and 224 as well as A-->G transition on the site of 235 was only occurred in Microtus fortis fortis. They are not found in Microtus fortis calamorum so far. They could be divided into two groups according to phylogenetic tree analysis results, one was the genomic DNA of Microtus fortis calamorum and the other one was that of Microtus fortis fortis. However, the homologues reached up to 98% between two subspecies. These results are very important for us to further understand the genetic background, biological characteristics, evolutionary rule and the anti-schistosoma japonicum mechanism of Microtus fortis at the molecular levels. The specific base changes of the DNA fragment between the two subspecies are probably correlative with the animal immigration, survival conditions, and species evolution.