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Biomedical subjects

Z Q Yang

Publications and source records attributed to Z Q Yang.

At least 19 recordsLinked to original sources

Cloning, chromosomal localization and expression patterns of porcine Kruppel-like factors 4, -5, -7 and the early growth response factor 2.

Kruppel-like factors (KLF) and the early growth response factor 2 (EGR2) are important zinc finger transcription factors in vertebrates. We have cloned the full length coding sequence (CDS) of porcine KLF5, KLF7 and EGR2, which are 1374, 909 and 1416 bp, respectively. KLF4, KLF5 and EGR2 were then chromosomally mapped to porcine 1q28-29, 11q13-14 and 14q23-25, respectively. Moreover, the tissue expression patterns of KLF4, KLF5, KLF7 and EGR2 imply their probable roles in specific tissues. This is the first report of the basic study of these zinc finger transcription factors in pigs; this information will be helpful for future functional studies.

Animals↗

Transforming function of the LSM1 oncogene in human breast cancers with the 8p11-12 amplicon.

Amplification of the 8p11-12 region occurs in 15-20% of breast cancers, but the driving oncogene at this locus has yet to be definitively identified. We mapped the 8p11-12 amplicon in breast cancer cell lines and primary human breast cancers and identified the candidate oncogene human Sm-like protein (hLsm1, LSM1) based on increases in copy number and expression level relative to human mammary epithelial cells. To examine the oncogenic role of LSM1, we overexpressed this gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44 breast cancer cell line, which has a natural amplification and overexpression of LSM1. Our data confirmed that LSM1 is an oncogene from the 8p11-12 amplicon by showing that hLsm1 overexpression induced growth factor-independent proliferation and soft agar colony formation in MCF10A cells, and hLsm1 inhibition in SUM44 cells dramatically reduced soft agar growth. Little is known about hLsm1 function other than its involvement in mRNA degradation; therefore, we used expression microarray analysis to investigate how hLsm1 affects cell transformation in MCF10A and SUM44 cells. We identified numerous genes altered following hLsm1 overexpression common to SUM44 breast cancer cells that play important roles in cell cycle regulation, cell proliferation and other cancer-promoting processes. Future work will continue to characterize these important changes to achieve a more complete understanding of the mechanism of hLsm1's effect on cancer progression.

Breast Neoplasms↗

Cloning, chromosome mapping and expression characteristics of porcine ANGPTL3 and -4.

Angiopoietin-like protein 3 and -4 (ANGPTL3 and -4) are two members of angiopoietin-like proteins (ANGPTLs), which have the signature structure of the angiopoietin family but cannot bind to the TIE2 receptor. It has been reported that they both affect lipid metabolism by inhibiting the activity of lipoprotein lipase (LPL). Here we report the cDNA cloning, chromosome mapping and expression analysis of ANGPTL3 and -4 in pigs. Sequence analysis shows that ANGPTL3 contains an open reading frame of 1,389 bp, which encodes 462 amino acids, and ANGPTL4 contains a coding region of 1,239 bp, which encodes 412 amino acids. Porcine ANGPTL3 deduced amino acid sequence shares 83% and 73.7% identity with human and mouse, respectively, and ANGPTL4 shares 79.4% and 77.7% amino acid identity with human and mouse, respectively. Porcine ANGPTL3 and -4 were mapped to the 6q31-->q35 and 2q21-->q24 region, respectively, by radiation hybrid mapping. Tissue distribution analysis indicated that porcine ANGPTL3 mRNA was exclusively expressed in liver, and porcine ANGPTL4 was ubiquitously expressed with the highest abundance in white adipose tissue. Furthermore, the mRNA level of ANGPTL3 and -4 in liver and the mRNA level of ANGPTL4 in white adipose tissue were significantly higher in genetically obese pigs than in their lean counterparts. This is the first report of molecular cloning and characterization of ANGPTL3 and -4 in pigs, which will be helpful for a better understanding of the role of ANGPTLs in lipid metabolism.

3' Untranslated Regions↗

Cloning, expression and chromosome localization of porcine adiponectin and adiponectin receptors genes.

Adiponectin is a cytokine secreted specifically by adipocytes that has been proposed to enhance insulin sensitivity and prevent atherosclerosis. Adiponectin receptors (adipoR1 and adipoR2) are recently found in mice which act as receptors for globular and full-length adiponectin to mediate the fatty-acid oxidation and glucose uptake in muscle and liver. The primary goal of this study was to examine chromosome localization of porcine adiponectin and adiponectin receptors and the gene expression pattern in various tissues of pigs of the three genes. Radiation hybrid mapping demonstrated that porcine adiponectin, adipoR1 and adipoR2 were located to chromosome13q36-41, 10p11 and 5q25, in the regions that were syntenic to the homologs of human genes, respectively. Semi-quantitative RT-PCR showed that porcine adiponectin mRNA was specifically expressed in adipose tissue and porcine adipoR1 and adipoR2 mRNA were ubiquitously expressed in many tissues except brain. Comparison to adipoR2 mRNA which was highly expressed in liver, heart, kidney, adipose tissues and lung, adipoR1 mRNA was expressed at relatively high levels in porcine muscle, leukocytes and epididymis. Our data provide basic molecular information useful for the further investigation on the function of the three genes.

Adiponectin↗

Cloning and characterization of porcine resistin gene.

Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance.

Amino Acid Sequence↗

Dental fluorosis in primary teeth: a study in rural schoolchildren in Shaanxi Province, China.

OBJECTIVE: The aim of this study was to assess the prevalence and severity of fluorosis in the primary dentition of 7-8-year-old Chinese schoolchildren in areas with fluoride concentrations in the drinking water ranging from 0.35 to 7.6 mg L-). SUBJECTS AND METHODS: Four hundred and seventy-two children from 13 different schools were divided into four groups according to the fluoride concentration of the drinking water: (A) <or=1.0 mg L-1; (B) 1.1-2.0 mg L-1; (C) 2.1-3.8 mg L-1; and (D) 7.6 mg L-1. Clinical examinations were made under field conditions, and dental fluorosis on the buccal surfaces of all teeth was recorded using the Thylstrup-Fejerskov Index (TFI). RESULTS: The prevalence of dental fluorosis in primary teeth varied from 6.2% to 96.6% according to the fluoride concentration of the drinking water. The differences of median of TFI scores between all groups were statistically significant (P<0.001) except for groups B and C. No statistically significant difference in the severity of dental fluorosis was observed between genders. The second primary molars were most severely affected by dental fluorosis. Disregarding group A, TFI scores between 3 and 4 were most frequently recorded. Dental fluorosis was symmetrically distributed in both jaws. CONCLUSION: Dental fluorosis is prevalent in the primary teeth of children living in areas supplied with drinking water with fluoride concentrations higher than 1.0 mg L-1. The primary teeth may act as biomarkers of fluoride exposure. The examination of primary teeth may give an early warning of this condition, and thus, provide a basis for intervention to prevent dental fluorosis in the permanent teeth.

Age Distribution↗

Variability of G1 gene of hantaviruses occurring in the Hubei Province, P.R. China from 1985 to 2000.

We studied variability of G1 gene of hantaviruses occurring in the Hubei province, P.R. China. Serum samples were collected from 229 patients with hemorrhagic fever with renal syndromes (HFRS) during 1985--1989 and 1996--2000 and were tested by RT-PCR for the presence of Hantaan and Seoul viruses (HTNVs, SEOVs) and by restriction fragment length polymorphism (RFLP) analysis for the respective pattern. Out of 229 sera 166 (72.5%) were hantavirus-positive by RT-PCR, including 124 from 1985--1989 and 42 from 1996--2000, with HTNVs in majority (80.1%) and SEOVs in minority (19.9%). By RFLP analysis, four types of RFLP pattern were recognized. In the 133 HTNV isolates the A pattern was most predominant (62.5%), while the remaining patterns B, C, and D were present in minority. This kind of the RFLP pattern distribution was observed regardless the year of virus isolation. In contrast, only one type of RFLP pattern was obtained from 33 SEOVs, but this was different from that of R22 virus. Our results indicate that temporal factor, represented by years 1985--2000 seems to be too short to affect markedly the genetic makeup of the hantaviruses investigated.

Adolescent↗

Effect of cordycepin on Hantaan virus 76-118 infection of primary human embryonic pulmonary fibroblasts--characterization of apoptotic effects.

The cDNA microarray technique was used to study gene epression in human embryonic pulmonary fibroblasts (HEPF) infected with Hantaan virus (HTNV) under the influence of cordycepin (Cor), an inhibitor of post-transcriptional pre-mRNA polyadenylation. Four apoptotic genes, the insulin-like growth factor binding protein 1, NFkB inhibitor alpha, caspase-3 and NFkB1 were up-regulated in both infected and uninfected Cor-treated cells and two cell cycle-associated genes, CDC-like kinase and beta-induced transforming growth factor were up-regulated in Cor-untreated cells but down-regulated in Cor-treated cells. Cell morphology examination, quantitative RT-PCR, and immunofluorescence (IF) test suggested that following the Cor treatment the HTNV infection took place, but late viral gene expression was slightly reduced. Three parameters, namely caspase-3 activity, annexin V binding, and cell cycle were used to detect apoptosis. The results suggested that the induction of apoptosis in HEPF by HTNV started at 6 hrs post infection (p.i.). Following the Cor treatment, however, the caspase-3 activity began to increase at 24 hrs p.i. Thus it is suggested that inhibition of de novo late viral protein synthesis by Cor changes the apoptosis pathway and cell cycle by delaying caspase-3 gene expression and by up/down-regulating of expression of other apoptotic and cell cycle-associated genes. This implicates that HTNV can induce apoptosis in HEPF even without de novo viral protein synthesis and with a reduced and slowed viral maturation.

Animals↗

Stage-specific expression of leukaemia inhibitory factor and its receptor in rabbit pre-implantation embryo and uterine epithelium during early pregnancy.

Leukaemia inhibitory factor (LIF) has been shown to play an important role in the development and implantation of blastocysts in mice. In the current study, the reverse transcription-polymerase chain reaction (RT-PCR) was employed to examine the expression patterns of LIF and its receptor (LIFR) genes in rabbit embryos during pre-implantation development, and the uterine expression of LIF and LIFR was also evaluated by Western blotting. Transcripts for LIFR were detected within morula and blastocyst-stage embryos, while the LIF mRNA was only found in blastocysts (from early to fully expanded blastocoel cavities), indicating that embryo-derived LIF can act in an autocrine manner on the process of blastocyst formation. The expression levels of LIF and LIFR in uterine epithelium were gradually increased during pre-implantation period and reached their highest levels on days 6.5 of pregnancy, just before the time of blastocyst implantation, suggest that paracrine LIF circuit should exist between the endometrium and the early embryos, which may be involved in the embryo-maternal dialogue and important for the blastocyst implantation. The data present here show the stage-specific and dynamic expression patterns of LIF and LIFR, both in embryos and endometrium, during early pregnancy in rabbits, which indicated that LIF might play an important role in the pre-implantation development and subsequent implantation of rabbit embryos.

Animals↗

Effects of mushroom and herb polysaccharides on cellular and humoral immune responses of Eimeria tenella-infected chickens.

We investigated the effects of polysaccharide extracts from 2 mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and an herb, Astragalus membranaceus (AstE), on cellular and humoral immune responses of Eimeria tenella-infected chickens. A total of 150 broiler chicks were assigned to 5 treatment groups: 3 groups were infected with E. tenella and fed with extracts (LenE, TreE, and AstE), and 2 control groups were infected with or without E. tenella. The 3 extracts were given at the level of 1 g/kg of the diet from 8 to 14 d of age. Specific systemic and cecum mucosal antibody production, proliferation of splenocytes, and peripheral T and B lymphocytes were measured during the 3 wk following Eimeria infection. A significantly higher production of specific IgA, IgM (at d 14 and 21 postinfection), and IgG (at d 21 postinfection) were detected in the Eimeria-infected groups fed with the extracts than in the infected group not fed with the extracts. Of the 3 extracts, TreE stimulated a slightly higher production of specific IgM (P = 0.052), and a significantly higher IgG production at 21 d postinfection. The cecal antibody production showed a similar trend to that of serum antibodies. The overall mean levels of cecal-specific IgA and IgG of the groups fed with extracts were significantly higher at 14 and 21 d postinfection compared with the group not fed with extracts. Of the 3 extracts, the AstE-fed group showed the highest IgG production at d 7 postinfection. Both TreE- and LenE-fed groups had significantly higher IgM and IgG levels compared with the AstE group at d 21 postinfection. The extract-fed groups also showed a significantly higher antigen-specific proliferation of splenocytes at 14 and 21 d postinfection compared with the group not fed with the extracts. The overall mean of erythrocyte rosette-forming cells (ERFC %) (at d 14 and 21) and erythrocyte-antibody-complement cells (EAC %) (at d 14) of the groups fed with the extracts was significantly higher compared with the group not fed the extracts. It is concluded from this study that supplementation with mushroom and herb extracts resulted in enhancement of both cellular and humoral immune responses in E. tenella-infected chickens.

Animals↗

Increased expression of resistin and tumour necrosis factor-alpha in pig adipose tissue as well as effect of feeding treatment on resistin and cAMP pathway.

AIM: Resistin, a novel hormone, is expressed in mouse, rat and human adipose tissue. Its resistance to insulin is controversial. We hypothesized that resistin has the similar roles like those of tumour necrosis factor-alpha (TNF-alpha), a putative mediator of insulin resistance, and they are in common involved in regulating lipid metabolism in vivo. METHODS: We demonstrated TNF-alpha and resistin expression in different growth-stage adipose tissue of genetically lean and obese pigs using semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting analysis. Moreover, we analysed the variations of resistin and some parameters associated with lipolysis pathway after body-weight reduction in feeding-restricted obese pigs. In addition, we localized resistin expression in the cell types from pig adipose tissue. RESULTS: Overall, the expression of TNF-alpha and resistin in obese pigs was statistically higher than their lean counterparts, although this difference in resistin mRNA expression tailed off with age. In individual pigs, their levels increased progressively with age and degree of obesity. After feeding restriction, resistin expression was gradually decreased. Simultaneously, feeding restriction also resulted in a significant decrease of serum triglyceride and plasma cAMP, free fatty acids and insulin as well as fat adenyl cyclase and cAMP. In addition, in isolated pig adipocytes, our data showed that resistin was localized not only to adipocytes but also to other unidentified stromal vascular cells. CONCLUSIONS: TNF-alpha and resistin are increased in obesity. Weight loss results in the decrease of resistin and lipolysis-associated parameters, suggesting the possible association between resistin and lipolysis pathway. Cell localization of resistin expression implies the possibility of other biological actions of resistin.

Adipose Tissue↗

Serological characterization of a hantavirus from Hubei, China.

Hantavirus HV114, isolated from urine of a patient during epidemic of hemorrhagic fever with renal syndrome (HFRS) in China, was subjected to a detailed serological characterization using enzyme-linked immunosorbent assay (ELISA), neutralization test and indirect immunofluorescence antibody assay (IFA). It has been found that HV114 is antigenically similar to the hantavirus A9 strain isolated in China and to the Hantaan 76-118 virus (HTNV 76-118), but different from the hantaviruses isolated from Apodemus agrarius in the region endemic for HFRS.

Animals↗

Cancer-prone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: report of five infants.

Five infants (two girls and three boys) from four families all had severe pre- and postnatal growth retardation, profound developmental delay, microcephaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four infants developed Wilms tumors, and one showed cystic lesions in bilateral kidneys. All five infants showed variegated mosaic aneuploidy in cultured lymphocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.2% lymphocytes showed total premature chromatid separation (PCS). Their parents had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three infants and their parents, whose chromosomes were prepared at outside laboratories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were similar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger than usual at 2-16 months. The tumors were bilateral in four infants and unilateral in three infants, and cystic changes were present in six infants. Two infants developed botryoid rhabdomyosarcoma. The carriers of the syndrome are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: Am J Hum Genet 69:483-486]), was discussed in connection with tumor development and progression.

Abnormalities, Multiple↗

Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas.

Amplification of chromosomal DNA is thought to be one of the mechanisms that activate cancer-related genes in tumors. In a recent study, we identified high copy-number amplification at 11q21-q23 in cell lines derived from esophageal squamous cell carcinomas (ESCs) using comparative genomic hybridization. Because 11q21-q23 amplification has been reported in tumors of various other types as well, gene(s) associated with tumor progression may lie within this chromosomal region. To identify the most likely target(s) for amplification at 11q21-q23, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed ESC cell lines for expression levels of 11 known genes and one uncharacterized transcript present within the 1.8-Mb commonly amplified region. Only cIAP1, a member of the IAP (antiapoptotic) gene family, was consistently overexpressed in cell lines that showed amplification. Additionally, the cIAP1 protein was overexpressed in the primary tumors from which those cell lines had been established. The ESC cell lines with cIAP1 amplification were resistant to apoptosis induced by chemotherapeutic reagents. An increase in cIAP1 copy number was also detected in 4 of 42 (9.5%) primary ESC tumors that were not related to the cell lines examined. Because inhibition of apoptosis seems to be an important feature of carcinogenesis, cIAP1 is likely to be a target for 11q21-23 amplification and may be involved in the progression of ESC, as well as other malignancies.

Apoptosis↗

SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus.

Amplification of the 3q26 region appears to occur frequently among esophageal squamous cell carcinomas (ESCs). We examined ESC cell lines for amplification and expression levels of four genes in this region: SNO and EVI1, which encode proteins antagonizing transforming growth factor-beta signaling, and two other putative target genes, TERC and PIK3CA. Amplification of SNO was accompanied by significant increases in its expression level, suggesting that this gene is activated in an amplification-dependent manner. SNO was also amplified in 5 of 44 primary ESCs (11.4%). However, expression levels of EVI1, TERC, and PIK3CA did not correlate with their copy-numbers, even though EVI1 and TERC showed the same amplification pattern as SNO. Taken together, the data suggest that of the four candidates, SNO is the most probable target in the 3q26 amplicon for involvement in the progression of ESC.

Carcinoma, Squamous Cell↗