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Biomedical subjects

G Cai

Publications and source records attributed to G Cai.

At least 19 recordsLinked to original sources
PubMed2006

Linkage analysis of circulating levels of adiponectin in Hispanic children.

INTRODUCTION: Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and proinflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VIVA LA FAMILIA Study by use of a systematic genome scan. METHODS: The present study included extended families with at least one overweight child between 4 and 19 years old. Overweight was defined as body mass index (BMI) 95th percentile. Fasting blood was collected from 466 children from 127 families. Adiponectin was assayed by radioimmunoassay (RIA) technique in fasting serum. A genome-wide scan on circulating levels of adiponectin as a quantitative phenotype was conducted using the variance decomposition approach. RESULTS: The highest logarithm of odds (LOD) score (4.2) was found on chromosome 11q23.2-11q24.2, and a second significant signal (LOD score=3.0) was found on chromosome 8q12.1-8q21.3. In addition, a signal suggestive of linkage (LOD score=2.5) was found between 18q21.3 and 18q22.3. After adjustment for BMI-Z score, the LOD score on chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found on chromosome 3 (LOD score=2.1) and 10 (LOD score=2.5). Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this region for adiponectin levels. Our suggestive linkages on chromosomes 10 and 3 replicate results for adiponectin seen in other populations. The influence of loci on chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in the present study. CONCLUSION: Our genome scan in children has identified a novel QTL and replicated QTLs in chromosomal regions previously shown to be linked with obesity and type 2 diabetes (T2D)-related phenotypes in adults. The genetic contribution of loci to adiponectin levels may vary across different populations and age groups. The strong linkage signal on chromosome 11 is most likely underlain by a gene(s) that may contribute to the high susceptibility of these Hispanic children to obesity and T2D.

Adiponectin↗
PubMed2006

The effect of tibial lengthening on immature articular cartilage of the knee joint.

OBJECTIVE: To investigate the acute response of immature articular cartilage, in the distraction and consolidation phases, to 30% tibial lengthening. DESIGN: Sixteen immature New Zealand white rabbits underwent diaphyseal lengthening of the left tibia by callotasis at a distraction rate of 0.4mm twice daily. A sham control group of 12 rabbits underwent fixation and osteotomy without lengthening. In each group, half of the rabbits were killed at the end of the distraction phase or at an equivalent time period and the rest were killed after an additional 5 weeks (consolidation phase). The tibial condyles and synovial fluid in the knee joint cavity were taken for laboratory examination. Sulfated glycosaminoglycan in synovial fluid was estimated using a colorimetric method. Sections along the mid-coronal plane of the whole of the tibial condyles were examined histologically and by scanning electron microscopy. A grading system was used to make a semiquantitative assessment of the histopathological changes in articular cartilage. RESULTS: Damage to the immature articular cartilage had occurred by the end of the distraction period and the cartilage continued to deteriorate in the consolidation phase of 5 weeks. However, when compared with a similar study in a mature rabbit model, damage to immature cartilage appeared less severe. CONCLUSION: This model of 30% lengthening caused acute cartilage damage which did not recover in the short term. The result may have implications for longer lengthening in children; the effects may be disadvantageous and lead to degenerative diseases later in life.

Animals↗
PubMed2005

Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons.

INTRODUCTION: The hormone resistin was recently discovered in adipose tissue of mice. Functional tests suggest a role for resistin in the regulation of insulin sensitivity. However, human studies have reported controversial results on the metabolic function of this hormone. METHODS: A 1 g omental adipose tissue biopsy was obtained from 404 adult baboons. Resistin mRNA expression was assayed by real-time, quantitative RT-PCR, and univariate and bivariate quantitative genetic analyses were performed, via the variance decomposition approach. A genome scan analysis was conducted using resistin mRNA abundance in omental adipose tissue as a quantitative phenotype. RESULTS: A significant heritability of h2 = 0.23 (P = 0.003) was found for resistin mRNA abundance in omental adipose tissue. A genome scan detected a quantitative trait locus for resistin expression with an LOD score of 3.8, in the region between markers D19S431 and D19S714, corresponding to human chromosome 19 p13. This chromosomal region contains genes related to insulin resistance phenotypes, such as resistin, insulin receptor, angiopoietin-like 4 protein and LDL receptor. CONCLUSIONS: Individual variation in resistin mRNA expression has a significant genetic component, and a gene or genes on chromosome 19 p13 may regulate resistin mRNA levels in baboon omental adipose tissue.

Adipose Tissue↗
PubMed2005

A family study in Oman: large, consanguineous, polygamous Omani Arab pedigrees.

OBJECTIVE: To establish a suitable human model for the study of the genetics of complex diseases. METHODS: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. RESULTS: Outstanding statistical power to detect susceptibility loci was obtained. CONCLUSIONS: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.

Consanguinity↗
PubMed2004

Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype.

To determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5' end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAP(China 1)), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; P=0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAP(China 2)) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; P=0.003, rr 2.2) and was also significant using parental controls only (P=0.0047, rr 2.1). A four-marker haplotype at the 3' end of the NRG1 gene, HAP(China 3), was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (P=0.000042, rr=2.0) but was not significant in the case-control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese.

Asian People↗
PubMed2001

A combined in vitro/in vivo selection for polymerases with novel promoter specificities.

BACKGROUND: The DNA-dependent RNA polymerase from T7 bacteriophage (T7 RNAP) has been extensively characterized, and like other phage RNA polymerases it is highly specific for its promoter. A combined in vitro/in vivo selection method has been developed for the evolution of T7 RNA polymerases with altered promoter specificities. Large (10(3)-10(6)) polymerase libraries were made and cloned downstream of variant promoters. Those polymerase variants that can recognize variant promoters self-amplify both themselves and their attendant mRNAs in vivo. Following RT / PCR amplification in vitro, the most numerous polymerase genes are preferentially cloned and carried into subsequent rounds of selection. RESULTS AND CONCLUSIONS: A T7 RNA polymerase library that was randomized at three positions was cloned adjacent to a T3-like promoter sequence, and a 'specialist' T7 RNA polymerase was identified. A library that was randomized at a different set of positions was cloned adjacent to a promoter library in which four positions had been randomized, and 'generalist' polymerases that could utilize a variety of T7 promoters were identified, including at least one polymerase with an apparently novel promoter specificity. This method may have applications for evolving other polymerase variants with novel phenotypes, such as the ability to incorporate modified nucleotides.

Amino Acid Substitution↗
PubMed2001

Affected sibling pair linkage analysis of qualitative and quantitative traits for schizophrenia on chromosome 22 in a Chinese population.

We performed nonparametric linkage analysis on 136 families with two or more siblings with schizophrenia from Sichuan, southwestern China. In addition to categorical diagnosis, we used quantitative trait information from the Positive and Negative Symptom Scale and the modified Overt Aggression Scale. Categorical analysis using the diagnosis of schizophrenia and a maximum likelihood identity-by-descent method produced scores of close to 0 throughout the whole region tested. Multipoint analysis allowed exclusion of most markers with a relative risk of > 2, but did not exclude the possibility of a relative risk of < 1.5 for four of the markers. Our results provide no significant evidence for a locus for schizophrenia on chromosome 22. Quantitative linkage analysis using the PANSS-G scale score produced a maximum LOD score of approximately 1.2 with the marker D22S310, using either the Haseman-Elston method or maximum likelihood variance estimation with or without dominance. PANSS-N produced a maximum LOD score of 1.2 at the D22S283 locus. LOD score of about 1 are easily produced by chance. Thus, we conclude that under quantitative trait we also find no evidence of linkage between schizophrenia and markers on chromosome 22 in our Chinese sibling pair sample.

Adolescent↗
PubMed2001

Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens.

The bacterium Burkholderia pseudomallei causes a life-threatening disease called melioidosis. In vivo experiments in mice have identified that a rapid IFN-gamma response is essential for host survival. To identify the cellular sources of IFN-gamma, spleen cells from uninfected mice were stimulated with B. pseudomallei in vitro and assayed by ELISA and flow cytometry. Costaining for intracellular IFN-gamma vs cell surface markers demonstrated that NK cells and, more surprisingly, CD8(+) T cells were the dominant sources of IFN-gamma. IFN-gamma(+) NK cells were detectable after 5 h and IFN-gamma(+) CD8(+) T cells within 15 h after addition of bacteria. IFN-gamma production by both cell populations was inhibited by coincubation with neutralizing mAb to IL-12 or IL-18, while a mAb to TNF had much less effect. Three-color flow cytometry showed that IFN-gamma-producing CD8(+) T cells were of the CD44(high) phenotype. The preferential activation of NK cells and CD8(+) T cells, rather than CD4(+) T cells, was also observed in response to Listeria monocytogenes or a combination of IL-12 and IL-18 both in vitro and in vivo. This rapid mechanism of CD8(+) T cell activation may be an important component of innate immunity to intracellular pathogens.

Animals↗
PubMed2001

[Study on distribution of single nucleotide polymorphism in 5'-regulatory region of beta(2)-adrenoceptor gene in hypertensives].

OBJECTIVE: To detect single nucleotide polymorphisms (SNP) existing in 5'-regulatory region of beta(2)-adrenoceptor (beta(2)-AR) gene and to investigate their associations with hypertension. METHODS: beta(2)-AR gene was sequenced by fluorescent labeling automatic sequencing method in unrelated Chinese Han population distributed in Dabie Mountain in Anhui Province. Genotypes of the SNP were typed by PCR-RFLP method. RESULTS: Two SNP of 1.3 kb long were identified at position 1023 and 654 respectively. They were both G-->A substitution. The frequency of genotype of the two SNP complied well with the Hardy-Weinberg equilibrium. The distribution of the SNP genotype AA, GA and GG at position 1023 in the severe hypertension group was significantly different from that in normal group (chi(2) = 9.53, df = 2, P < 0.01), AA frequency is significantly higher in the severe hypertension group than in the normal group (chi(2) = 9.21, df = 1, P < 0.01). CONCLUSION: The SNP at locus 1023 of human beta(2)-AR gene is associated with severe hypertension in Chinese Han population.

Aged↗
PubMed2001

Herbicides and the microtubular apparatus of Nicotiana tabacum pollen tube: immunofluorescence and immunogold labelling studies.

Herbicides are chemical compounds widely used in agriculture. As their intensive application is becoming a cause of environmental pollution, detailed and more sophisticated investigations are needed to understand better their consequences at the biological level. After herbicides are dispersed in the fields, they establish chemical interactions with both target and non-target plants. In both cases, herbicides can interact with the plant reproductive apparatus; consequently they could play a role during the fertilisation process in higher plants. Using an antibody to the alpha-tubulin subunit in immunofluorescence and immunoelectron microscopy techniques, we investigated the distribution of microtubules in Nicotiana tabacum pollen tubes grown under in vitro conditions in the presence of five different herbicides selected among those used frequently in central Italy. Herbicides have a specific effect on the microtubular apparatus of both pollen tube and generative cell. In addition to other tests and assays, these results suggest that the microtubule cytoskeleton of pollen tubes can be used as a bioindicator for studying the toxicity effects induced by herbicides.

Dicamba↗
PubMed2001

Maize endosperm secretes a novel antifungal protein into adjacent maternal tissue.

A series of endosperm transfer layer-specific transcripts has been identified in maize by differential screening of a cDNA library of transcripts at 10 days after pollination. Sequence comparisons revealed among this class of cDNAs a novel, small gene family of highly diverged sequences encoding basal layer antifungal proteins (BAPs). The bap genes mapped to two loci on chromosomes 4 and 10. So far, bap-homologous sequences have been detected only in maize, teosinte and sorghum, and are not present in grasses outside the Andropogoneae tribe. BAP2 is synthesized as a pre-proprotein, and is processed by successive removal of a signal peptide and a 29-residue prodomain. The proprotein can be detected exclusively in microsomal membrane-containing fractions of kernel extracts. Immunolocalization reveals BAP2 to be predominantly located in the placentochalazal cells of the pedicel, adjacent to the basal endosperm transfer layer (BETL) cells, although the BAP2 transcript is found only in the BETL cells. The biological roles of BAP2 propeptide and mature peptide have been investigated by heterologous expression of the proprotein in Escherichia coli, and by tests of its fungistatic activity and that of the fully processed form in vitro. The mature BAP2 peptide exhibits potent broad-range activity against a range of filamentous fungi, including several plant pathogens.

Amino Acid Sequence↗
PubMed2001

Selected contribution: effects of ischemia-reperfusion on vascular contractility and alpha(1)-adrenergic-receptor signaling in the rat tail artery.

To determine the effects of ischemia-reperfusion (I/R) on alpha(1)-adrenergic-receptor (alpha(1)-AR) functions, alpha(1)-AR-mediated contraction, inositol phosphate (IP) accumulation, and alpha(1)-AR-G protein coupling were examined in the tail arteries of anesthetized rats after 60 min of ischemia and 60 min of reperfusion. The contractile response to norepinephrine (NE) was significantly increased after I/R, whereas the contractile response to KCl remained unchanged. This was accompanied by a 69% increase in NE-stimulated IP accumulation. Furthermore, receptor-stimulated coupling of alpha(1a)-AR to G alpha(q/11) proteins was increased, whereas the coupling of alpha(1b)-AR or alpha(1d)-AR to their G proteins was not altered by I/R. These changes in vascular alpha(1)-AR function occurred without concurrent alteration in expression levels of membrane alpha(1)-AR subtypes or in the associated G proteins. These data demonstrate that I/R increases alpha(1a)-AR-G(q/11) protein coupling and alpha(1)-AR-stimulated IP accumulation in the tail artery. The alterations in alpha(1)-AR signaling are associated with and may underlie the enhanced contractile response of the tail artery to adrenergic stimulation after I/R.

Adenylyl Cyclases↗
PubMed2001

[Single nucleotide polymorphism in beta2-adrenoceptor gene and the distribution in Chinese Han ethnic group].

OBJECTIVE: The study was conducted to investigate single nucleotide polymorphism(SNP) in beta2-adrenoceptor(beta2-AR) gene and the distribution of these identified SNPs in Chinese Han ethnic group. METHODS: beta2-AR gene was sequenced to detect SNPs by fluorescent labeling automatic sequencing method in 80 unrelated samples from territory of Dabie Mountain in Anhui province. RESULTS: A total of 8 SNPs were identified in length of 3.8 kb, including 5 SNPs in code region, 3 SNPs in regulatory region. Although the variations, -468C to G, -367T to C, -47C to T,-20T to C, +79C to G, +100G to A, +491C to T, +1098T to C have been identified in other ethnic groups, they have not been found in our study. The allele distribution of SNPs is in good unity with the Hardy-Weinberg equilibrium. CONCLUSION: The distribution of SNPs in beta2-AR gene is not equable and the SNPs in different ethnic groups differ greatly. The allele distribution of SNPs conforms well to the Hardy-Weinberg equilibrium.

Alleles↗
PubMed2001

[Linkage disequilibrium analysis of chromosome 22 and schizophrenia in a Chinese population].

OBJECTIVE: To explore the molecular genetic relations of chromosome 22 and schizophrenia and locate the susceptibility gene of schizophrenia. METHODS: Six dinucleotide tandem repeat loci on chromosome 22 were chosen to analyze 126 affected sib-pair nuclear families of schizophrenia in Chinese population by fluorescent labeled auto-mated genotyping and transmission/ disequilibrium test(TDT). RESULTS: The TDT-chi square value of IL2Rbeta was 25.30(P=0.01), which suggests there is linkage disequilibrium between IL2R beta and schizophrenia. The P vaules of the other five loci (D22S944, D22S264, D22S303, D22S278 and CYP2D6) were greater than 0.05. CONCLUSION: A susceptive gene of schizophrenia may be located in IL2Rbeta locus or adjacent region.

Chromosomes, Human, Pair 22↗
PubMed2001

[Association of single nucleotide polymorphisms in code region of beta2-adrenoceptor gene with hypertension in Chinese population].

OBJECTIVE: To detect single nucleotide polymorphisms(SNPs) existing in code region of beta(2)-adrenoceptor(2-AR) gene and to investigate association of the identified SNPs with essential hypertension in Chinese Han population. METHODS: Beta(2)-AR gene was sequenced with fluorescent labelling automatic sequencing method in unrelated Chinese Han population from Dabie Mountain in Anhui Province. Genotype of the SNPs were typed with PCR-RFLP method. RESULTS: Two SNPs were identified in length of 774bp, at position + 1053 with G-->C substitution and + 1239 with A-->G substitution respectively. The frequency of genotype of the two SNPs complied well with the Hardy-Weinberg equilibrium in normal group. Distribution of genotype AA, GA, GG of the SNPs at locus + 1239 in hypertension group was significantly different from that in normal group (chi(2) = 6.70, df = 2, P < 0.05). No significant difference was observed in distribution of genotypes of the SNPs at locus + 1053 between the two groups. CONCLUSION: These results indicate that the SNPs at locus + 1239 of beta(2)-AR gene is associated with EH. The SNPs at position + 1053 was not linked to hypertension.

Aged↗
PubMed2000

Identification of a role for NF-kappa B2 in the regulation of apoptosis and in maintenance of T cell-mediated immunity to Toxoplasma gondii.

The NF-kappaB family of transcription factors are involved in the regulation of innate and adaptive immune functions associated with resistance to infection. To assess the role of NF-kappaB(2) in the regulation of cell-mediated immunity, mice deficient in the NF-kappaB(2) gene (NF-kappaB(2)(-/-)) were challenged with the intracellular parasite Toxoplasma gondii. Resistance to this opportunistic pathogen is dependent on the production of IL-12, which is required for the development of innate NK cell and adaptive T cell responses dominated by the production of IFN-gamma necessary to control replication of this parasite. Although wild-type controls were resistant to T. gondii, NF-kappaB(2)(-/-) mice developed severe toxoplasmic encephalitis and succumbed to disease between 3 and 10 wk following infection. However, NF-kappaB(2) was not required for the ability of macrophages to produce IL-12 or to inhibit parasite replication and during the acute stage of infection, NF-kappaB(2)(-/-) mice had no defect in their ability to produce IL-12 or IFN-gamma and infection-induced NK cell responses appeared normal. In contrast, during the chronic phase of the infection, susceptibility of NF-kappaB(2)(-/-) mice to toxoplasmic encephalitis was associated with a reduced capacity of their splenocytes to produce IFN-gamma associated with a loss of CD4(+) and CD8(+) T cells. This loss of T cells correlated with increased levels of apoptosis and with elevated expression of the pro-apoptotic molecule Fas by T cells from infected NF-kappaB(2)(-/-) mice. Together, these results suggest a role for NF-kappaB(2) in the regulation of lymphocyte apoptosis and a unique role for this transcription factor in maintenance of T cell responses required for long-term resistance to T. gondii.

Animals↗
PubMed2000

Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondii.

The capacity of IL-12 to stimulate T and NK cell production of IFN-gamma is required for resistance to Toxoplasma gondii. To identify the transcription factors involved in this mechanism of resistance, mice deficient in STAT4, a protein involved in IL-12 signaling, were infected with T. gondii and their immune responses were analyzed. STAT4-/- mice were unable to control parasite replication and died during the acute phase of infection, whereas wild-type mice controlled parasite replication and survived this challenge. The susceptibility of STAT4-/- mice to toxoplasmosis correlated with a defect in their ability to produce IFN-gamma in response to infection, whereas administration of IFN-gamma to these mice inhibited parasite replication and delayed time to death. Interestingly, analysis of infected STAT4-/- mice revealed that these mice did produce low levels of IFN-gamma during infection, and the ability of splenocytes from infected or uninfected STAT4-/- mice to produce IFN-gamma was enhanced by the addition of IL-2 plus IL-18. Moreover, administration of IL-2 plus IL-18 to STAT4-/- mice resulted in elevated serum levels of IFN-gamma associated with a decreased parasite burden and delayed time to death. In vivo depletion studies demonstrated that the ability of IL-2 plus IL-18 to mediate STAT4-independent resistance to T. gondii is dependent on NK cell production of IFN-gamma. Together, these studies identify STAT4 as an important transcription factor required for development of the innate NK and adaptive T cell responses necessary for resistance to T. gondii. However, other signaling pathways can be used to bypass STAT4-dependent production of IFN-gamma and enhance innate resistance to T. gondii.

Adjuvants, Immunologic↗