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Objective To explore the expression and function of correlative genes in the happening and developing of human pituitary adenoma-subtypes.Methods The whole genome oligonucleotide microarray (Affymetrix 133 plus 2.0) was used to examine the gene expressions of pituitary adenoma tissue in 8 patients with pituitary adenoma (2 with growth hormone adenomas,2 with prolactinomas,2 with gonadotroph adenomas and 2 with null cell adenomas) and normal pooled pituitary tissue.Differentially expressed genes were analyzed by Hierarchical method and bioinformatics.A candidate gene was selected to verify the microarray analyzed result by real-time quantitative PCR.Results Compared with associated genes with normal control,associated genes with pituitary adenoma mainly involved in the following biological processes analyzed from the view of function: binding,apoptosis-or-tumor correlation,metabolism,signal-transducer-activity,cell cycle,transcription-regulator-activity and transporter-activity.The specificity of expression in several differential genes was connected to the development of pituitary adenoma-subtypes.Conclusion The development of pituitary adenoma is a complex regulation process involving lots of genes,molecules and pathways.However,the molecular mechanism related to the individual pituitary adenoma-subtypes is different.
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<p><b>UNLABELLED</b>To reduce the huge labor-cost in the screening in traditional monoclonal antibody generation, We established a new system for monoclonal antibody generation integrating with protein array. BALB/c mice were immunized by eight recombinant proteins respectively, and the positive hybridoma cells were obtained by cell fusion and ELISA screening. All the eight kinds of positive hybridoma cells were mixed, cloned, screened by protein array, and definite dilution cloned.</p><p><b>RESULTS</b>175 single cell clones were obtained by complex cloning, and 119 of those were positive clones. Then 8 positive cell lines were generated by the following 2 rounds definite dilution cloning. By comparing with the traditional method, we got 8 monoclonal antibodies using the combined protein array screening and multiplex cloning method in 1 cycle, and fewer amounts of antigens were used. As a result, the combined protein array and multiplex cloning method could be used as an economical, rapid and simple tool applying in high throughput monoclonal antibody generation.</p>
Subject(s)
Animals , Female , Humans , Mice , Antibodies, Monoclonal , Allergy and Immunology , Hybridomas , Metabolism , Mice, Inbred BALB C , Protein Array AnalysisABSTRACT
<p><b>BACKGROUND</b>The renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population.</p><p><b>METHODS</b>Fifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.</p><p><b>RESULTS</b>The patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P=0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P=0.030; diastolic BP: P=0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P=0.007).</p><p><b>CONCLUSIONS</b>AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angiotensinogen , Genetics , Cytochrome P-450 CYP11B2 , Genetics , Genotype , Hydrochlorothiazide , Therapeutic Uses , Hypertension , Drug Therapy , Genetics , Oligonucleotide Array Sequence Analysis , Peptidyl-Dipeptidase A , Genetics , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of thiazide-sensitive Na+ -Cl* cotransporter (TSC) gene 1784C/T and 2736G/A polymorphisms with the risk of essential hypertension (EH) in a Han nationality population.</p><p><b>METHODS</b>A community-based, case-control study including 190 EH patients and 94 sex- and age-matched controls was conducted. Genotypes of TSC gene 1784C/T and 2736G/A polymorphisms were analyzed by gene chip technology.</p><p><b>RESULTS</b>The genotype (1784C/T CC, CT, TT:87, 88, 15 vs 36, 52, 6û2736G/A GG, AG, AA:167, 22, 1 vs 83, 10, 1) and alleles frequency (1784C/T C, T:68.9%, 31.1% vs 66.0%, 34.0%; 2736G/A G,A:93.7%, 6.3% vs 93.6%, 6.4%) distribution of 1784C/T and 2736G/A showed no significant difference between the EH group and the control group (P >0.05). Moreover, no significant difference was observed in the frequencies distribution of four haplotypes (P > 0.05); Logistic regression analysis of haplotypes showed that the risk of EH had no significant difference in the population with different haplotypes (P > 0.05).</p><p><b>CONCLUSION</b>The 1784C/T and 2736G/A polymorphisms of TSC gene may not play an important role in the etiology of EH in a Han nationality population. The studies in the future are warranted to validate our findings.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Hypertension , Epidemiology , Genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Receptors, Drug , Genetics , Risk , Sodium Chloride Symporters , GeneticsABSTRACT
Objective To investigate the association of angiotensinogen(AGT)gene A-6G、T174M and G-217A polymorphisms with the risk of essential hypertension(EH)in the elderly of Han nationality.Methods Genotypes of AGT gene A-6G,T174M and G-217A polymorphisms in 177 aged EH patients and 86 sex and age-matched controls were analyzed with gene chip technology.Results The A-6G and T174M polymorphisms of AGT gene were significantly associated with EH.The numbers of the three genotypes of A-6G were 113,58 and 6 in the patient group and 70,15 and 1 in the control group(P= 0.014)and those of T174M were 94,77 and 6,60,25 and 1(P=0.031),respectively.G-217A polymorphism was not related to EH.Individuals carrying A-6G AA and T174M CC genotypes showed 57% and 56% lower risk of EH(OR=0.43;95%CI=0.23-0.82 and OR=0.44;95%CI=0.25-0.79, respectively).Conclusions The A-6G AA and the T174M CC genotype may be related with decreased risk of EH and G-217A polymorphism may have little role in the etiology of EH in Han nationality.