Ribosomal DNA ITS2 sequences differentiate six species in the Anopheles crucians complex (Diptera: Culicidae)

Anopheles crucians Wiedemann (sensu lato) was investigated for the presence of cryptic species using rDNA ITS2 sequences. This complex of species presently contains the named species An. crucians, An. bradleyi King, and An. georgianus King. Adult female mosquitoes were collected at 28 sites in Alabama, Florida, Georgia, North Carolina, Mississippi, and Louisiana, resulting in 245 progeny broods. Species were identified using preliminary morphological characters, and the internal transcribed spacer two (ITS2) was amplified from all broods. The result was five distinct sizes of amplification product, and based on morphological characters, one of the size classes was suspected to consist of two species. All six putative species were then sequenced: five directly, and the sixth, because of extreme intragenomic (each individual with many variants) size variability, cloned. The ITS2 sequences were markedly distinct for all six species. Species designations and ITS2 sequence lengths (base pairs in parentheses) were A (461), B (1,000+), C (204), D (293), E (195), and An. bradleyi (208). Species B showed both large intraspecific and intragenomic sequence variability and is distinguished by having the longest ITS2 found so far in an Anopheles. Based on these data, we found that all species could be identified with polymerase chain reaction (PCR) using a mixture of four primers in a single reaction. Members of this complex were often found in sympatry, with the adults of five species collected at a single site in central Florida.     

Intragenomic heterogeneity of rDNA internal transcribed spacer 2 in Anopheles messeae (Diptera: Culicidae)

Because Anopheles messeae Falleroni (Diptera: Culicidae) is one of the main vectors of malaria in Russia, studying its genetic markers is important for reliable identification of this species. This species is distributed nearly throughout the Palearctic region, and it exhibits high genetic variability. We investigated polymorphism of the rDNA internal transcribed spacer (ITS) 2 of An. messeae in various regions of Russia, and we found intragenomic heterogeneity of ITS2 copies verified by chromatograms, polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis, and cloning PCR products. In total, we found nine different ITS2 variants. ITS2 variants that were considered specific to An. messeae and Anopheles daciae Linton, Nicolescu & Harbach were simultaneously present in one individual. These findings improve methods of species identification of An. messeae, and they do not support the species status of An. daciae.     

Intragenomic and intraspecific heterogeneity of the 16S rRNA gene in seven bacterial species from the respiratory tract of cystic fibrosis patients assessed by PCR-Temporal Temperature Gel Electrophoresis

16S rRNA gene-based cultivation-independent methods are increasingly used to study the diversity of microbiota during health and disease. One bias of these methods is the variability of 16S rRNA gene that may exist among strains of a same species (intraspecific heterogeneity) or between rrs copies in a genome (intragenomic heterogeneity). We evaluated the level of intraspecific and intragenomic 16S rDNA variability in seven species frequently encountered in respiratory tract samples in cystic fibrosis (CF). A total of 179 strains were subjected to V3 region 16S rDNA PCR-TTGE. Using this easy-to-perform and rapid method, different levels of V3 region rrs heterogeneity were demonstrated. No intraspecific and intragenomic rrs heterogeneity was demonstrated for Moraxella catarrhalis (n=16), Pseudomonas aeruginosa (n=31) and Streptococcus pneumoniae (n=14) showing a single PCR-TTGE band characteristic of the species. Low level of intraspecific heterogeneity was observed for Staphylococcus aureus (n=30), Stenotrophomonas maltophilia (n=29) and Achromobacter xylosoxidans (n=28), and 17%, 38% and 96% of these strains showed intragenomic heterogeneity (two to four different rrs copies), respectively. Haemophilus influenzae (n=31) displayed the higher level of intraspecific variability with 23 different PCR-TTGE patterns and 61% of the strains showed intragenomic rrs heterogeneity (two to four different rrs copies). Although only one hypervariable region of the 16S rRNA gene was explored, intraspecific and intragenomic rrs heterogeneity was frequently observed in this study and should be taken into consideration for a better interpretation of 16S rRNA gene-based diversity profiles in denaturing gels and to avoid any overestimation of the respiratory microbiota diversity in CF.     

The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage

Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)(n) repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)(n) microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in Hardy-Weinberg equilibrium. The HO-1 (GT)(n) microsatellite repeat numbers ranged from 13 to 37, with (GT)(23) and (GT)(30) being the most common alleles in both groups. We compared alleles consisting of < or =27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.32-0.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.86-1.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)(n) microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)(n) microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.     

Association analysis between mood disorder and monoamine oxidase gene

To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000.     

The Hyrcanus group of Anopheles (Anopheles) in China (Diptera: Culicidae): species discrimination and phylogenetic relationships inferred by ribosomal DNA internal transcribed spacer 2 sequences

The Hyrcanus group comprises many closely related species with wide distributions in the Oriental and Palaearctic regions. The sequences of the second internal transcribed spacer (ITS2) of ribosomal DNA were determined for 12 species in China--An. crawfordi, An. hyrcanus, An. junlianensis, An. kunmingensis, An. kweiyangensis, An. lesteri, An. liangshanensis, An. peditaeniatus, An. pullus, An. sinensis, and two unknown species within the group. The length of the ITS2 ranged from 436 bp in An. hyrcanus to 469 bp in An. crawfordi, with GC contents of 44.9-46.8%. Intraspecific variation was found in three species (An. junlianensis, An. liangshanensis, and An. pullus) at the level of 0.0-0.4%, whereas interspecific differences ranged from 1.6% between An. liangshanensis and An. kunmingensis to 50.8% between An. peditaeniatus and sp. 1. The ITS2 comparisons revealed two unknown species, verified the valid species status for An. kunmingensis, and found An. pullus in China. We agree that An. anthropophagus is a junior synonym of An. lesteri. The validation of An. junlianensis awaits recognition of the molecular identity of the entity identified as An. yatsushiroensis. The ITS2 divergences were used for inferring phylogenetic relationships among 12 species in China. The estimation revealed close relationships among An. liangshanesis, An. kunmingensis, An. kweiyangensis, An. lesteri, and An. sinensis. Our study emphasizes the need for the molecular identity of the species members in integrated studies in systematics, bionomics, and population genetics for the Hyrcanus group.     

(GT)N dinucleotide repeat polymorphism of haem oxygenase-1 promotor region is not associated with inflammatory bowel disease risk or disease course

Haem oxygenase-1 (HO-1) up-regulation was suggested to reduce mucosal tissue damage in inflammatory bowel disease (IBD) and an up-regulation of HO-1 expression in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated. A HO-1 gene promoter microsatellite (GT)(n) dinucleotide repeat polymorphism was associated with regulation of HO-1 in response to inflammatory stimuli. We therefore hypothesized that IBD patients might segregate into phenotypes with high or low HO-1 inducibility. Ethylenediamine tetraacetic acid blood samples were obtained from 179 CD patients, 110 UC patients and 56 control patients without inflammation. Genomic DNA was purified and the 5'-flanking region of the HO-1 gene containing the (GT)(n) dinucleotide repeat was amplified. Polymerase chain reaction (PCR) products were purified and the length of the PCR fragments was analysed. The number of (GT)(n) repeats in the population studied ranged from 13 to 42. The distribution of the allele frequencies was comparable in patients and controls for both the short and the long alleles. The frequencies of short-, middle- and long-sized alleles were not changed among the groups studied. No correlation was found between IBD and microsatellite instability detected in five individals. Our data indicate that (GT)(n) dinucleotide repeats of the HO-1 promotor region have no significance for the pathophysiology and disease course of IBD.     

Linkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes.

Attention-deficit hyperactivity disorder (ADHD) is a prevalent behavioral disorder in children and the etiology of this disorder is not clear. Molecular genetic and pharmacological studies suggest the involvement of dopaminergic and noradrenergic neurotransmitter systems in ADHD, e.g., several reports have found association between ADHD and the dopamine receptor gene DRD-4, the dopamine transporter gene DAT1, and the catecholamine clearance enzyme catechol-O-methyltransferase. Monoamine oxidase (MAO) A and B genes encode enzymes that participate in the metabolism of neurotransmitters of the dopaminergic and noradrenergic systems. MAO inhibitors have been shown to be effective in the treatment of ADHD. Our previous studies showed an association between ADHD and the DXS7 locus, which is located in close vicinity to the MAO genes on chromosome X. These findings suggest that there might be linkage between ADHD and MAO genes. To test this hypothesis, we used the transmission/disequilibrium test (TDT) to test for linkage between a VNTR polymorphism at the MAOA(CA)(n) or MAOB(GT)(n) locus and DSM-III-R-diagnosed ADHD in 82 nuclear families of the Chinese population. The TDT analysis revealed linkage between ADHD and the MAOA(CA)(n) locus (chi-square = 15.25, df = 7, P < 0.05), but not the MAOB(GT)(n) locus (chi-square = 11.18, df = 7, P > 0.05). The data showed that ADHD was in linkage with the MAOA gene and suggested that MAOA might be a susceptibility factor for ADHD.     

Usefulness of examination of the cholesterol versus triglyceride ratio for lipoprotein fractions in a patient with marked hyper-triglyceridemia

A patient consulted the emergency room with acute pancreatitis, hypertriglyceridemia, and diabetes mellitus, and was later admitted to the hospital. Serum levels of total cholesterol(TC) and total triglyceride (TTG), and the cholesterol(Chol) versus triglyceride(TG) ratio(Chol/TG) for lipoprotein fractions were examined periodically during the course of treatment using Chol/Trig Combo, which identifies Chol and TG by differential staining. On admission, the patient's TTG, pancreatic amylase and glucose levels were 4020 mg/dl, 2012 IU/l, and 242 mg/dl, respectively. Clinofibrate administration resulted in a decrease in Chol and TG values for all fractions. However, the Chol/TG ratios were unchanged(HDL of 0.2 to 0.4, VLDL of approximately 0.13, and LDL of 0.1 to 0.2: Reference values from 103 healthy students were as follows: HDL 5.8 +/- 2.0, VLDL 0.39 +/- 0.1, and LDL 4.9 +/- 1.3[Mean +/- SD].). During clinofibrate treatment, TC and TG values gradually increased. Clinofibrate was discontinued and fenofibrate administration was initiated. This was followed by a dramatic improvement in TC, TTG and Chol/TG values for both HDL and LDL. The monitoring of lipoprotein fraction values proved useful for determining the treatment regimen for this patient with hypertriglyceridemia.     

Analysis of a GT microsatellite in the promoter of the foxp3/scurfin gene in autoimmune diseases

The aim of this study was to assess the possible association of the functional (GT)(n) microsatellite polymorphism in the FOXP3 gene with predisposition to several autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease, and celiac disease. We analyzed a case-control cohort composed of 231 SLE patients, 293 RA patients, 528 inflammatory bowel disease (354 Crohn's disease patients and 260 UC patients) patients, 103 celiac disease patients, and 274 healthy controls ethnically matched. Genotyping of (GT)(n) microsatellite was performed by polymerase chain reaction (PCR)-based method combined with fluorescent technology. We found no evidence for association of this polymorphism between controls and these autoimmune disease patients. Additionally, no differences in the genotype and allele distribution were found when patients were stratified according to clinical manifestation. The (GT)(n) microsatellite of the FOXP3 gene may not play a relevant role in the susceptibility to SLE, RA, inflammatory bowel disease, and celiac disease in our population.     

Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia

The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.     

Dinucleotide repeat polymorphism in intron II of human Toll-like receptor 2 gene and susceptibility to rheumatoid arthritis

Human Toll-like receptors (TLRs) participate in innate immune response and signal the activation of adaptive immunity. The presence of a functional intronic polymorphism consisting of guanine-thymine repeats in TLR2 gene was recently reported. Here, we investigated a dinucleotide repeat polymorphism in intron II of TLR2 in Korean patients with rheumatoid arthritis (RA). The numbers of guanine-thymine [(GT)(n)] repeats in intron II of the TLR 2 gene were counted in 183 patients with RA and in 148 healthy controls, using the gene scanning technique. We classified alleles into two subclasses for further analysis, 12-16 GT repeats (S allele) and 17-28 repeats (L allele). By subgroup analysis, we also examined whether the S allele is associated with the presence of shared epitope (SE), rheumatoid factor (RF), joint erosion and extra-articular complications. S-allele frequency was significantly increased in patients with RA than in healthy controls [30.3% vs. 23.0%, P = 0.03, or 1.46, 95% confidence interval (CI) 1.03-2.07], and genotypes containing S alleles were more frequent in patients with RA than in healthy controls (54.4% vs. 46.5%. P = 0.04, or 1.57, 95% CI 1.01-2.42). A skewed S-allele distribution was not found to be related to the presence of SE. Subgroup analysis showed no genotypic or allele frequency differences between patients with/without RF, joint erosion, or extra-articular complications. Genotype containing shorter GT repeats in intron II of the TLR2 gene may confer susceptibility to RA in Koreans.     

Significant linkage and association between a functional (GT)n polymorphism in promoter of the N-methyl-D-aspartate receptor subunit gene (GRIN2A) and schizophrenia

Dysfunction of the N-methyl-d-aspartate (NMDA) type glutamate receptor has been proposed as a mechanism in the etiology of schizophrenia, based on the observation that non-competitive antagonists of the NMDA receptor, such as phencyclidine, induce schizophrenia-like symptoms. Previous study identified a variable (GT)n polymorphism in the promoter region of the N-methyl-d-aspartate (NMDA) subunit gene (GRIN2A), and showed its association with schizophrenia in a case-control study, together with a correlation between the length of the repeat and severity of chronic outcome. Our present study was aimed at confirming the association of the (GT)n polymorphism of GRIN2A promoter with schizophrenia using 122 Han Chinese sib-pair families. Non-parametric linkage analysis and transmission/disequilibrium test (TDT) were undertaken using the GENEHUNTER, v2.1. In non-parametric linkage analysis, suggestive linkage was found for the (GT)n polymorphism (NPL=2.77, P=0.002902). The TDT was significant for (GT)n polymorphism and that the (GT)23 was preferentially transmitted to schizophrenia-affected children (T/NT: 123:72, chi(2)=13.34, P=0.000260). Our results indicate that the (GT)n polymorphism in the promoter of GRIN2A gene may play a significant role in the etiology of schizophrenia among our samples.     

A chromosome study and localization of 18S rDNA in Khawia saurogobii (Cestoda: Caryophyllidea)

This paper reports results of the first cytogenetic study carried out on a recently described monozoic tapeworm, Khawia saurogobii Xi et al., 2009, from the Chinese lizard gudgeon (Saurogobio dabryi). The karyotype of this species is composed of eight pairs of metacentric and telocentric chromosomes (2n?=?16; $ n = {\text{3m}} + {\text{5t}} $ ), metacentric chromosomes representing the first, sixth, and eight pairs. All chromosomes except the largest pair displayed 4′,6-diamidino-2-phenylidole (DAPI) positive heterochromatin in centromeric regions. In mitotic preparations stained with Giemsa, one of the homologues of a smaller metacentric chromosome pair (No. 7) showed a distinct secondary constriction, whereas the other did not. Fluorescent in situ hybridization (FISH) with 18S ribosomal DNA (rDNA) probe revealed that the chromosomes No. 7 carry each a cluster of ribosomal genes associated with the centromeric heterochromatin and confirmed that this chromosome pair contains a nucleolar organizer region (NOR). The rDNA-FISH also confirmed heteromorphism in the size of NOR (i.e., secondary constriction) observed after Giemsa staining. The present cytogenetic analysis revealed species-specific characters of K. saurogobii and showed that FISH may represent a new valuable cytogenetic tool suitable for comparative taxonomic or phylogenetic studies within the order Caryophyllidea in the future.     

注意缺陷多动障碍儿童的工作记忆损害特征

目的:探讨注意缺陷多动障碍(ADHD)儿童工作记忆功能特征。方法:本研究为横断面研究。根据美国精神疾病诊断和统计手册第4版(DSM-IV),对符合ADHD诊断标准的未经治疗的100名门诊患儿及年龄、性别相匹配的100名正常儿童分别采用韦氏儿童智力测验量表中国修订本(C-WISC)及其中的顺背数字(反映言语存贮、加工)、倒背数字(反映言语存贮、加工、中央执行)、Corsi木块和空间n-Back任务(反映视空间存贮和中央执行)进行言语及空间工作记忆测试。结果:ADHD组儿童在顺背数字最高位数及总得分、倒背数字最高位数及总得分、Corsi木块最多木块数及总得分均低于对照组儿童,空间2-Back任务反应时短于对照组儿童(均P0.05)。结论:ADHD儿童存在工作记忆功能缺陷,此缺陷涉及言语环路、视空间存贮系统及中央执行。     

Biochemical evidence for an ecto alkaline phosphodiesterase I in human airways

Because dinucleotides are signaling molecules that can interact with cell surface receptors and regulate the rate of mucociliary clearance in lungs, we studied their metabolism by using human airway epithelial cells. A membrane-bound enzyme was detected on the mucosal surface of polarized epithelia that metabolized dinucleotides with a broad substrate specificity (diadenosine polyphosphates and diuridine polyphosphates [Up(n)U], n = 2 to 6). The enzymatic reaction yielded nucleoside monophosphates (NMP) and Np(n)(-)(1) (N = A or U), and was inhibited by nucleoside 5'-triphosphates (alpha,betamet adenosine triphosphate [ATP] > ATP >/= uridine triphosphate > guanidine triphosphate > cytidine triphosphate). The apparent Michaelis constant (K(m,app)) and apparent maximal velocity (V(max,app)) for [(3)H]Up(4)U were 22 +/- 4 microM and 0.24 +/- 0.05 nmoles. min(-)(1). cm(-)(2), respectively. Thymidine 5'-monophosphate p-nitrophenyl ester and adenosine diphosphate (ADP)- ribose, substrates of ecto alkaline phosphodiesterase I (PDE I) activities, were also hydrolyzed by the apical surface of airway epithelia. ADP-ribose competed with [(3)H]Up(4)U, with a K(i) of 23 +/- 3 microM. The metabolism of ADP-ribose and Ap(4)A was not affected by inhibitors of cyclic nucleotide phosphodiesterases (3-isobutyl-1-methylxanthine, Ro 20-1724, and 1,3-dipropyl-8-p-sulfophenylxanthine), but similarly inhibited by fluoride and N-ethylmaleimide. These results suggest that a PDE I is responsible for the hydrolysis of extracellular dinucleotides in human airways. The wide substrate specificity of PDE I suggests that it may be involved in several signaling events on the luminal surface of airway epithelia, including purinoceptor activation and cell surface protein ribosylation.     

苯扎贝特改善2型糖尿病合并高甘油三酯血症患者 胰岛素抵抗的临床分析

目的 探讨苯扎贝特对2型糖尿病合并高甘油三酯血症患者降低血脂,同时改善胰岛素敏感性的影响及作用机制。方法选取我院2016年12月~2018年2月收治的符合入选标准2型糖尿病合并高甘油三酯血症患者56例,随机分为A组（n=29）和B组（n=27）。两组均使用苯扎贝特及非诺贝特降脂治疗,其他常规服用药物不变。A组:治疗顺序为苯扎贝特+非诺贝特,疗程各1个月,期间清洗期为1周;B组:治疗顺序为非诺贝特+苯扎贝特,疗程各1个月,期间清洗期为1周。监测两组患者实验前、第一阶段及第二阶段的甘油三酯（TG）、胆固醇、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）,并计算胰岛素敏感指数（IsI）。结果 两组患者实验前、第一阶段和第二阶段的TG和胆固醇水平比较,差异无统计学意义（P＞0.05）。两组实验前和第一阶段的FBG、HbA1c及IsI比较,差异无统计学意义（P＞0.05）;B组第二阶段的FBG高于A组[（6.73±0.28）mmol/L vs （6.52±0.51）mmol/L],HbA1c和IsI均低于A组[（6.54±0.32）% vs （6.76±0.71）%,（-4.19±0.34）vs（-4.13±0.28）],差异有统计学意义（P＜0.05）。结论 苯扎贝特可改善血脂,调节糖代谢,降低2型糖尿病患者血糖,并能改善胰岛β细胞分泌功能,提高机体胰岛素敏感性。     

Fungal metabolite gliotoxin targets flavocytochrome b558 in the activation of the human neutrophil NADPH oxidase

Fungal gliotoxin (GT) is a potent inhibitor of the O(2)(-)-generating NADPH oxidase of neutrophils. We reported that GT-treated neutrophils fail to phosphorylate p47(phox), a step essential for the enzyme activation, because GT prevents the colocalization of protein kinase C betaII with p47(phox) on the membrane. However, it remains unanswered whether GT directly affects any of NADPH oxidase components. Here, we examine the effect of GT on the NADPH oxidase components in the cell-free activation assay. The O(2)(-)-generating ability of membranes obtained from GT-treated neutrophils is 40.0 and 30.6% lower, respectively, than the untreated counterparts when assayed with two distinct electron acceptors, suggesting that flavocytochrome b(558) is affected in cells by GT. In contrast, the corresponding cytosol remains competent for activation. Next, GT addition in vitro to the assay consisting of flavocytochrome b(558) and cytosolic components (native cytosol or recombinant p67(phox), p47(phox), and Rac2) causes a striking inhibition (50% inhibitory concentration = 3.3 microM) when done prior to the stimulation with myristic acid. NADPH consumption is also prevented by GT, but the in vitro assembly of p67(phox), p47(phox), and Rac2 with flavocytochrome b(558) is normal. Posterior addition of GT to the activated enzyme is ineffective. The separate treatment of membranes with GT also causes a marked loss of flavocytochrome b(558)'s ability to reconstitute O(2)(-) generation, supporting the conclusion at the cellular level. The flavocytochrome b(558) heme spectrum of the GT-treated membranes stays, however, unchanged, showing that hemes remain intact. These results suggest that GT directly harms site(s) crucial for electron transport in flavocytochrome b(558), which is accessible only before oxidase activation.     

Role of arachidonyl triglycerides within lipid bodies in eicosanoid formation by human polymorphonuclear cells.

Increasing evidence suggests that the subcellular and glycerolipid localization of esterified arachidonic acid (AA) is a key factor in regulating its availability to lipases. The goal of the current study was to determine the potential of AA stored in triglycerides (TG) to serve as a substrate for lipases and 5-lipoxygenase during neutrophil (polymorphonuclear leukocytes, PMN) activation. PMN containing high concentrations of AA in TG were generated by culturing PMN in vitro with high concentrations of exogenous AA (eAA) for 12 h. Cellular AA increased 2- and 4-fold in PMNs incubated with 5 and 20 microM AA, respectively, and this increase was almost exclusively observed in neutral lipids (NL). Further analysis revealed that 88% of the AA in the NL fraction was associated with TG. Subsequent experiments were designed to determine whether this AA in TG could be mobilized and metabolized to eicosanoids during cell activation. TG pools of AA were increased as previously described and then PMN were stimulated with ionophore, A23187. In contrast to the 43-fold increase in TG AA after eAA loading (20 microM), free AA increased by only 1.9-fold after cell stimulation. Similarly, leukotriene (LT)B(4) production increased only 2-fold after loading TG with large quantities of AA. The magnitude of increase in free AA released and in LTB(4) formation was similar to the magnitude of increase in AA mass in phospholipase (PL), suggesting that PL, and not TG, served as the source of released AA and subsequent product generation. To confirm that AA in TG did not serve as a source for eicosanoid production, cellular pools of AA were differentially labeled with [(14)C]AA and [(3)H]AA, and the [(3)H]AA-to-[(14)C]AA ratio of LTB(4) and 20-hydroxyl LTB(4) produced during cell stimulation was measured. The [(3)H]AA/[(14)C]AA ratios of LTs were markedly different from the ratios in TG, thus providing further evidence that AA pools in TG are not a major source of AA for LT generation.     

注意缺陷多动障碍儿童的工作记忆存储特征

目的:探讨注意缺陷多动障碍(ADHD)儿童工作记忆存储能力特征。方法:对26名符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的ADHD儿童和39名年龄及性别与之匹配的正常儿童,进行中国修订-韦氏儿童智力量表(C-WISC)、背数测验变式、方块图敲击试验变式和Kaufman儿童能力评估成套测验的寻找位置和手动作分测验测试,测查言语工作记忆和视空间工作记忆存储能力。结果:ADHD组在10 s后背数测验[(5.5±1.3)vs.(6.8±1.5)]、倒背数字[(3.3±1.1)vs.(4.1±1.0)]、方块图敲击试验[(4.4±1.1)vs.(5.1±0.8)]、10 s后敲击试验[(3.4±1.3)vs.(4.1±1.1)]、手动作测试[(8.5±3.3)vs.(10.4±3.1)]得分均低于正常组(均P0.05),两组在顺序背数测试[(6.6±1.0)vs.(7.1±1.0)]和寻找位置测试[(10.3±2.8)vs.(11.5±2.8)]得分差异无统计学意义(均P0.05)。多重线性回归分析表明,10 s后背数测试(β=0.31)、方块图敲击测试(β=0.29)、10秒后敲击试验(β=0.24)的得分高低与是否患ADHD相关(P0.05)。结论:ADHD儿童可能存在语音环信息保持能力损害和空间序列性信息存储能力缺陷。