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Biomedical subjects

Gang Liu

Publications and source records attributed to Gang Liu.

At least 145 records · Page 8Linked to original sources

[Effect of chronic electrical stimulation of phrenic nerve at different frequencies on mRNA and protein expression of skeletal DHPR(alpha1) and RyRs in the diaphragm muscle of rabbits].

The mRNA and protein expression of skeletal dihydropyridine receptor isoform alpha1 subunit (DHPR(alpha1)) and ryanodine receptor(1-3) (RyR(1-3)) during chronic electrical stimulation (CES) of phrenic nerve have rarely been explored. In the present study, we explored the signal translation mode of calcium release unit in diaphragm muscle of rabbits after CES. Thirty rabbits were used and randomly divided into the normal, 10, 20, 50 and 100 Hz groups. Phrenic nerve was continuously (5 weeks, 2x 2 h/d) stimulated at 10, 20, 50 and 100 Hz respectively (impulse width 0.2 ms, 3~6 waves/time, 45 times/min, 10~20 V). Reverse transcription PCR and immunohistochemical methods were employed. The results showed that mRNA and protein expressions of DHPR(alpha1) and RyR(1) in 10 and 20 Hz groups were more significantly lower than those in the control group (P<0.01), but mRNA and protein expressions of DHPR(alpha1) and RyR(1) were significantly higher in 50 and 100 Hz groups than those in the control group (P<0.01); a lower level of mRNA expression of RyR(2) was found in 10 and 20 Hz groups. It is suggested that the calcium release unit and the signal transduction mode between DHPR and RyRs were altered from conformational changes of linked proteins to Ca(2+)-induced Ca(2+) release (CICR) in the diaphragmatic muscle of rabbits after chronic low-frequency electrical stimulation of phrenic nerve for 5 weeks.

Animals↗

Ligand-dependent scope and divergent mechanistic behavior in nickel-catalyzed reductive couplings of aldehydes and alkynes.

A new procedure for catalytic reductive coupling of aldehydes and alkynes has been developed. The procedure uses Ni(COD)2 with an imidazolium carbene ligand as the catalyst and triethylsilane as the reducing agent. A crossover deuterium-labeling experiment illustrated that variants involving trialkyl phosphines and imidazolium carbene ligands with a nickel catalyst proceed by different mechanisms.

Aldehydes↗

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma.

Twenty-five to thirty percent of patients with node-negative breast cancer are expected to relapse following surgery, therefore great efforts have been made to identify new prognostic markers that could be useful in defining patients for additional therapy. The expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. In the present study we examined the prognostic value of immunoreactive MMP-2/MMP-9 protein in 270 consecutive lymph node negative cases who received radical mastectomy or modified radical mastectomy. Among the patients, 211 cases received adjuvant endocrine therapy and/or adjuvant chemotherapy. Using immunohistochemical assay, we found that 56.7% of the resected tumors were positive for MMP-2 whereas 59.6% of the samples were positive for MMP-9. Chi2 test demonstrated a significant direct association between MMP-2 and MMP-9 (p < 0.001); positive immunostaining of MMP-2 was significantly related to higher tumor grade (p < 0.001) and larger tumor size (p = 0.012); positive immunostaining of MMP-9 was significantly related to higher tumor grade (p = 0.002). In univariate analysis, using Cox-proportional hazard model we found MMP-2, MMP-9 and the co-expression of MMPs (MMP2/MMP9) were significantly associated with patients' relapse free survival (p = 0.016, 0.015 and 0.013 respectively) but not overall survival (p = 0.122, 0.320 and 0.091 respectively). Log-rank test also showed that MMP-2, MMP-9 or the co-expression of MMP2/MMP9 was unfavorable prognostic factor for relapse free survival but not overall survival. In subgroup analysis, we found MMPs were more prognostic for patients with no adjuvant treatment than for patients with adjuvant therapy. In multivariate analysis, using Cox-proportional hazard model we found co-expression of MMPs, larger tumor size and higher tumor grade were unfavorable for relapse free survival (p = 0.038, 0.007 and 0.015 for each). We concluded that MMP-2 and MMP-2 are unfavorable prognostic factors in breast cancer patients. They might be potential predictive factor for adjuvant systemic therapy. The co-expression of MMP-2 and MMP-9 has significantly prognostic value in node-negative patients.

Antineoplastic Agents, Hormonal↗

Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans.

BACKGROUND: The role of eNOS gene polymorphisms on plasma nitrite or nitrate (NOx) level, endothelial function, and blood pressure (BP) remains unclear. METHODS: We estimated the relationship of eNOS polymorphisms (the T(-786)C in the 5'-flanking promoter region, T(-786)C; 27-bp repeat in intron 4, eNOS4; and Glu298Asp in exon 7, G894T) with plasma NOx level, brachial endothelial function assessed by ultrasound measure of brachial artery flow-mediated dilation (FMD), and BP in 60 healthy African Americans, 30 men and 30 women aged 18 to 73 years. RESULTS: Among them, 73.1%, 23.9%, and 3.0% carried TT, TC, and CC of T(-786)C, respectively, 14.5%, 27.5%, 53.6%, and 1.4% carried aa, ab, bb, and bc of eNOS4 polymorphism, respectively, and 70.4%, 23.9%, and 5.6% carried GG, GT, and TT of G894T, respectively. G894T and eNOS4 were observed in linkage disequilibrium. Mean values of age, plasma NOx, FMD, systolic and diastolic BPs were not significantly different (P >.05) by eNOS polymorphisms. Plasma NO(x) level was found to be associated with systolic BP (r = 0.51, P =.03), and diastolic BP (r = 0.41, P =.08), but not with FMD, in individuals with "a" allele of eNOS4 polymorphism after adjustment for age, body mass index, serum glucose, and smoking status. CONCLUSIONS: We reveal a positive association between plasma NOx level and BP in normotensive African Americans who carry the "a" allele of eNOS4. Because the frequency of the rare allele "a" is significantly higher in African Americans than in other ethnic groups, this finding may provide a clue to understanding the genetic susceptibility to hypertension in African Americans.

Adolescent↗

Effects of amino acids and its metabolites on prolidase activity against various iminodipeptides in erythrocytes from normal human and a patient with prolidase deficiency.

BACKGROUND: The characteristics of prolidase in erythrocytes from controls and patient with prolidase deficiency were investigated. METHODS: The erythrocytes were isolated from the heparinized blood of normal human and a patient with prolidase deficiency. Effects of various amino acids and their metabolites on prolidase activity against iminodipeptides in presence of 1 mmol/l MnCl(2) were investigated. RESULTS: Prolidase activity against glycylproline in erythrocytes from normal human was strongly enhanced by glycine, L-alanine, L-serine with MnCl(2), but the activity was strongly inhibited by L-valine, and L-leucine. However, the stereoisomers, D-leucine and D-valine enhanced the activity. The prolidase activity against methionylproline in erythrocytes from the patient with prolidase deficiency was also enhanced by glycine, L-alanine and L-serine. The activity was inhibited by l-leucine, but D-leucine and L-valine enhanced the activity against various iminodipeptides. CONCLUSION: Prolidase activity against glycylproline in normal human erythrocytes and against methionylproline from the prolidase-deficient patient was enhanced strongly by glycine, alanine and serine with MnCl(2). However, this activity was inhibited by L-leucine, but was enhanced by D-leucine.

Amino Acids↗

Contig assembly and microsynteny analysis using a bacterial artificial chromosome library for Epichloë festucae, a mutualistic fungal endophyte of grasses.

We constructed and characterized a bacterial artificial chromosome (BAC) library for Epichloë festucae, a genetically tractable fungal plant mutualist. The 6144 clone library with an average insert size of 87kb represents at least 18-fold coverage of the 29 Mb genome. We used the library to assemble a 110kb contig spanning the putative ornithine decarboxylase (odc) ortholog and subsequently expanded it to 228kb with a single walking step in each direction. Furthermore, we evaluated conservation of microsynteny between E. festucae and some model filamentous fungi by comparing sequence available from a 43kb region at the end of one BAC to publicly available fungal genome sequences. Orthologs to the 13 contiguous open reading frames (ORFs) identified in E. festucae are syntenic in Neurospora crassa and Magnaporthe grisea occurring in small sets of two, three or four colinear ORFs. This library is a valuable resource for research into traits important for the development and maintenance of a plant-fungus mutualistic symbiosis.

Chromosomes, Artificial, Bacterial↗

Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study.

PURPOSE: To investigate the risk factors associated with visual field (VF) progression in the Advanced Glaucoma Intervention Study (AGIS) with pointwise linear regression (PLR) analysis of serial VFs. DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: Five hundred nine eyes of 401 patients from the AGIS with a baseline VF score of or=7 VF examinations, and >or=3 years of follow-up were selected. MAIN OUTCOME MEASURE: Visual field progression. METHODS: This is a cohort study of patients enrolled in a prospective randomized clinical trial (AGIS). Worsening of a test location on PLR analysis was defined as a change of threshold sensitivity of >or=1.00 decibels a year, with P<or=0.01. Visual field progression was defined as worsening of at least 2 test locations within a Glaucoma Hemifield Test cluster with PLR analysis. Multivariate logistic regression was used to determine risk factors associated with VF worsening. Intraocular pressure (IOP) fluctuation was defined as standard deviation of the IOP at all visits after the initial surgery. RESULTS: The mean (+/- standard deviation) follow-up time and baseline AGIS score were 7.4 (+/-1.7) years and 7.7 (+/-4.4), respectively. Visual field progression was detected with PLR analysis in 151 eyes (30%). Older age at the initial intervention (P = 0.0012; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.50), larger IOP fluctuation (P = 0.0013; OR, 1.31; 95% CI, 1.12-1.54), increasing number of glaucoma interventions (P = 0.01; OR, 1.74; 95% CI, 1.14-2.64), and longer follow-up (P = 0.02; OR, 1.19; 95% CI, 1.03-1.38) were associated with increased odds of VF progression. When regression analyses were repeated in eyes with and without a history of cataract extraction, IOP fluctuation was the only variable to be consistently associated with VF progression. CONCLUSION: Both increasing age and greater IOP fluctuation increase the odds of VF progression by 30% (for each 5-year increment in age and 1-mmHg increase in IOP fluctuation). The higher risk conferred by IOP fluctuation was consistently observed in eyes with and without a history of cataract extraction.

Adult↗

Solution-phase reductive cyclization of 2-quinoxalinol analogs: systematic study of parallel synthesis.

1,5-Difluoro-2,4-dinitrobenzene starting material was treated via primary and/or secondary substitution with a variety of amino acids or amines and the aromatic m-dinitro groups were then reductively cyclized provide the 2-quinoxalinol analogs. The conditions for 1,5-dialkylamino-2,4-dinitrobenzene reduction have been systematically studied and optimized in solution. Three effective methods are described for the high-throughout generation of 2-quinoxalinol analogs.

Biochemistry↗

Acyclonucleoside iron chelators of 1-(2-hydroxyethoxy)methyl-2-alkyl-3-hydroxy-4-pyridinones: potential oral iron chelation therapeutics.

The method of synthesizing acyclonucleoside iron chelators is both convenient and cost effective compared to that of synthesizing ribonucleoside iron chelators. The X-ray crystal structural analysis shows that the 2-hydroxyethoxymethyl group does not affect the geometry of the iron chelating sites. Therefore, the iron binding and removal properties of the acyclonucleoside iron chelators should remain similar to the ribonucleoside iron chelators, which is confirmed by the titration and competition reaction of the acyclonucleoside chelators with iron and ferritin, respectively. The acyclonucleoside iron chelators are more lipophilic with measured n-octanol and Tris buffer distribution coefficients than ribonucleoside iron chelators.

Chelation Therapy↗

Molecular cloning of TSARG6 gene related to apoptosis in human spermatogenic cells.

Beginning from a mouse EST (GenBank accession No. BE644537) which was significantly up-regulated in cryptorchidism and represented a novel gene, we cloned a new gene (GenBank accession No. AY138810) which is related to apoptosis in human spermatogenic cells by means of GeneScan program and PCR technology. The gene whose full cDNA length is 1875 bp containing 8 exons and 7 introns is located in human chromosome 11q13.3. Its protein containing 316 amino acid residues is a new member of HSP40 protein family because the sequence contains the highly conserved J domain which is present in all DnaJ-like proteins and is considered to have a critical role in DnaJ-DnaK protein-protein interactions. TSARG6 protein displays a 45% identity in a 348-amino acid overlap with DJB5_HUMAN protein. The result of RT-PCR and Northern blot analysis showed that TSARG6 is specifically expressed in adult testis and the transcript is 1.8 kb. Based upon all these observations, it is considered that we cloned a new gene which probably inhibited human testis spermatogenesis apoptosis.

Amino Acid Sequence↗

Identification of a novel gene SRG4 expressed at specific stages of mouse spermatogenesis.

Spermatogenesis is a complex process. Two spermatocytes expression sequence tags (ESTs) BG101130 and BG100990 were found. Their putative amino acid sequences have high homology with rat Spag4 (sperm antigen 4). By electrical hybridization, a novel cDNA encoding polypeptide of 348 amino acid residues was identified from a mouse testis cDNA library. The new gene was designated as SRG4 (Spermatogenesis related gene 4) (GenBank accession No. AY307077). Results of Northern blot and RTPCR revealed that SRG4 expressed specifically in mouse testis. Changes of SRG4 expression in mouse different development stages were observed by RT-PCR. The SRG4 mRNA was hardly detected in 2 weeks postpartum, and expressed abundantly from 3 weeks later, reaching top lever at 4-5 weeks, while slightly down in aging mouse testis. Results of in situ hybridization showed that SRG4 gene expressed abundantly in spermatocytes, round spermatids. This indicated SRG4 gene may play an important role in mouse meiotic divisions of spermatocytes.

Amino Acid Sequence↗

DeltaNp73beta is active in transactivation and growth suppression.

p73, a p53 family protein, shares significant sequence homolog and functional similarity with p53. However, unlike p53, p73 has at least seven alternatively spliced isoforms with different carboxyl termini (p73alpha-eta). Moreover, the p73 gene can be transcribed from a cryptic promoter located in intron 3, producing seven more proteins (DeltaNp73alpha-eta). DeltaNp73, which does not contain the N-terminal activation domain in p73, has been thought to be transcriptionally inactive and dominant negative over p53 or p73. To systemically analyze the activity of the DeltaN variant, we generated stable cell lines, which inducibly express DeltaNp73alpha, DeltaNp73beta, and various DeltaNp73beta mutants by using the tetracycline-inducible expression system. Surprisingly, we found that DeltaNp73beta is indeed active in inducing cell cycle arrest and apoptosis. Importantly, we found that, when DeltaNp73beta is expressed at a physiologically relevant level, it is capable of suppressing cell growth. We then demonstrated that these DeltaNp73beta activities are not cell type specific. We showed that the 13 unique residues at the N terminus are required for DeltaNp73beta to suppress cell growth. We also found that, among the 13 residues, residues 6 to 10 are critical to DeltaNp73beta function. Furthermore, we found that DeltaNp73beta is capable of inducing some p53 target genes, albeit to a lesser extent than does p73beta. Finally, we found that the 13 unique residues, together with the N-terminal PXXP motifs, constitute a novel activation domain. Like DeltaNp73beta, DeltaNp73gamma is active in transactivation. However, unlike DeltaNp73beta, DeltaNp73alpha is inactive in suppressing cell growth. Our data, together with others' previous findings, suggest that DeltaNp73beta may have distinct functions under certain cellular circumstances.

Alternative Splicing↗

Characteristics of prolinase against various iminodipeptides in erythrocyte lysates from a normal human and a patient with prolidase deficiency.

The effect of various amino acids and MnCl2 on prolinase activity in erythrocyte lysates from a healthy individual and a patient with prolidase deficiency was investigated. A concentration of 0.1 mM MnCl2 increased prolinase activity in normal erythrocytes against pro-gly, pro-glu, pro-leu, pro-ser and pro-phe, but inhibited that against pro-ala, pro-val, pro-met and pro-asp. However, prolinase activity against these iminodipeptides was enhanced by pre-incubation with glycine, independent of MnCl2. The same studies on erythrocytes from a prolidase-deficient patient showed almost the same results as the normal control, except that prolinase activity against pro-gly and pro-ser was slightly inhibited by adding 0.1 mM MnCl2. Some amino acids, glutamic acid and glutamine, slightly enhanced prolinase activity against pro-gly in erythrocytes from both the normal control and the prolidase-deficient patient, but N-acetyl-L-glutamic acid, gamma-aminobutyric acid (GABA) and beta-alanine showed no effect. Branched amino acids, L-valine, L-leucine and L-isoleucine strongly inhibited the prolinase activity against pro-gly. However, conversely, their isomers, D-valine, D-leucine and D-isoleucine, enhanced it. The kinetics of prolinase activity in the erythrocytes from both the normal individual and the prolidasedeficient patient were also studied. Their Km values were changed by adding glycine or 0.1 mM MnCl2, but Vmax values were almost the same.

Amino Acids↗

Inhibition of protein tyrosine phosphatase 1B as a potential treatment of diabetes and obesity.

Diabetes is a prevalent disease which effects over 150 million people worldwide and there is a great medical need for new therapeutic agents to treat it. Inhibition of protein tyrosine phosphatase 1B (PTP1B) has emerged as a highly validated, attractive target for treatment of not only diabetes but also obesity. Discovery of small-molecule inhibitors has been pursued extensively in both academia and industry and a number of very potent and selective inhibitors have been identified. With X-ray crystallography, the binding interactions of several classes of inhibitors have been elucidated. This has resulted in significant progress in understanding important interactions between inhibitors and specific residues of PTP1B, which could help the design of future inhibitors. However, since the active site of PTP1B that most of these inhibitors bind to is highly hydrophilic, it remains a challenge to identify inhibitors with both excellent in vitro potency and drug-like physiochemical properties which would lead to good in vivo activities.

Animals↗

[Uteroglobin G38A polymorphism is associated with the progression of IgA nephropathy in Chinese patients].

OBJECTIVE: Uteroglobin is a multifunctional protein. Both uteroglobin gene knockout and antisense transgenic mouse models developed the pathological and clinical features of IgA nephropathy. Uteroglobin G38A polymorphism has been reported to be associated with the progression of IgA nephropathy in some Caucasian and Asian populations, but there are no documents on Chinese population. The present report was to investigate the associations of uteroglobin G38A polymorphism with the development and progression of IgA nephropathy in Chinese patients. METHODS: Three hundred patients with biopsy proven IgA nephropathy were identified from Renal Disease database. Ninety-three patients had been followed-up for 2-6 years. 145 healthy donors served as normal controls. Genomic DNAs were extracted from peripheral blood leucocytes. The uteroglobin G38A polymorphism was determined by PCR-RFLP. Uteroglobin G38A genotype and allele frequency were compared between patients with IgA nephropathy and normal controls. In addition, associations of G38A polymorphism with blood pressure, hematuria, proteinuria, pathological lesions and prognosis of renal function were analyzed in patients with IgA nephropathy. RESULTS: Distribution of uteroglobin G38A polymorphism in patients with IgA nephropathy (38AA: 13.2%; 38AG: 57.6%; 38GG: 30.2%) and normal controls (38AA: 18.2%; 38AG: 60%; 38GG: 21.8%; P > 0.05) showed no difference. But patients with the 38AA genotype showed a higher odds ratio for progression of renal function (OR = 2.37, 95% CI = 1.12-5.01) as compared to patients with the 38AG/GG genotype. CONCLUSION: Uteroglobin G38A polymorphism had no association with the development of IgA nephropathy, but the homogeneous 38AA genotype maybe one of the genetic markers for disease progression in Chinese IgA nephropathy.

Adult↗

[The isolation of acinetobacter strain from burn wound and the analysis of its antibiotic resistance].

OBJECTIVE: To investigate the distribution and drug resistance of acinetobacter isolated from burn wounds. METHODS: The acinetobacter strains were isolated and identified by routine methods. Based on the recommendation of NCCLS, AmpC enzyme was determined by cefoxiti three-dimensional test, ESBLs by disk diffusion method and bacterial susceptibility by Kirby-Bauer agar diffusion method. RESULTS: Among the 69 strains of acinetobacter clinically isolated from burn wounds, 52 were baumannii (75.6%). The acinetobacter strains were identified to be highly resistant to 17 kinds of antibiotics. The drug resistance rate of beta-lactamase-producing strains (68.25%) was higher than that of non-beta-lactamase-producing strains (20.33%). The strains isolated in our burn ward exhibited multiple drug resistance which was mainly due to the production of many kinds of beta-lactamases. Among the 38 strains of beta-lactamase-producing acinetobacter, those producing AmpC beta-lactamase (AmpC BLA) accounted for 42.1%. CONCLUSION: Acinetobacter strain was one of the pathogens in burn wound infection, and its isolation and identification of its drug resistance could be beneficial to the doctors to make right choice of antibiotics.

Acinetobacter↗