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J Huang

Publications and source records attributed to J Huang.

At least 73 records · Page 4Linked to original sources
PubMed2003

Overexpression of transcription factor AP-2alpha suppresses mammary gland growth and morphogenesis.

AP-2 transcription factors are key regulators of mouse embryonic development. Aberrant expression of these genes has also been linked to the progression of human breast cancer. Here, we have investigated the role of the AP-2 gene family in the postnatal maturation of the mouse mammary gland. Analysis of AP-2 RNA and protein levels demonstrates that these genes are expressed in the mammary glands of virgin and pregnant mice. Subsequently, AP-2 expression declines during lactation and then is reactivated during involution. The AP-2alpha and AP-2gamma proteins are localized in the ductal epithelium, as well as in the terminal end buds, suggesting that they may influence growth of the ductal network. We have tested this hypothesis by targeting AP-2alpha expression to the mouse mammary gland using the MMTV promoter. Our studies indicate that overexpression of AP-2alpha inhibits mammary gland growth and morphogenesis, and this coincides with a rise in PTHrP expression. Alveolar budding is severely curtailed in transgenic virgin mice, while lobuloalveolar development and functional differentiation are inhibited during pregnancy and lactation, respectively. Our studies strongly support a role for the AP-2 proteins in regulating the proliferation and differentiation of mammary gland epithelial cells in both mouse and human.

Animals↗
PubMed2003

Fate and assessment of persistent organic pollutants in water and sediment from Minjiang River Estuary, Southeast China.

Persistent organochlorine compounds were analyzed in surface water, porewater and surficial sediment samples from Minjiang River Estuary, which is the first large river in Fujian Province, Southeast of China. The total concentrations of 18 organochlorine pesticides were 214.4-1819, 4541-13,699 ng/l, 28.79-52.07 ng/g in surface water, porewater and sediments (dry weight) respectively, and those of 21 polychlorinated biphenyls (PCBs) in the three phases were: 203.9-2473, 3192-10,855 ng/l, 15.14-57.93 ng/g respectively. The results showed that the concentrations of these selected organochlorine pesticides and PCBs in porewater were higher than those in surface water. It may be due to the fact that these organic hydrophobic pollutants tend to stay in the sediments, and then re-suspend from the sedimentary phase to the upper water. We have analyzed the distribution characteristics of individual organochlorine pesticide components and PCBs, and found that alpha-HCH, DDE, Heptachlor, Endosulfan II, Methoxychlor were the most common organochlorine pesticides contaminants. Considering the groups of HCHs (HCHs=alpha-HCH+beta-HCH+gamma-HCH+delta-HCH) and DDTs (DDTs=DDT+DDD+DDE), the predominance of beta-HCH, DDE in all water, porewater and sediment samples was clearly observed. This observation suggested that beta-HCH was resistant to biodegradation and the DDTs had been transformed to its metabolites, DDE and DDD, of which DDE that was more un-degradable. The PCB congeners containing 3-6 chlorines had the great preponderance in the three phase. These results were compared with those present in other estuaries and harbors. A risk assessment was evaluated for the persistent organic pollutants in the Minjiang River Estuary.

China↗
PubMed2003

Angiotensin II subtype 1A (AT1A) receptors in the rat sensory vagal complex: subcellular localization and association with endogenous angiotensin.

Angiotensin II (Ang II) type 1 (AT1) receptors are prevalent in the sensory vagal complex including the nucleus tractus solitarii (NTS) and area postrema, each of which has been implicated in the central cardiovascular effects produced by Ang II. In rodents, these actions prominently involve the AT1A receptor. Thus, we examined the electron microscopic dual immunolabeling of antisera recognizing the AT1A receptor and Ang II to determine interactive sites in the sensory vagal complex of rat brain. In both the area postrema and adjacent dorsomedial NTS, many somatodendritic profiles were dually labeled for the AT1A receptor and Ang II. In these profiles, AT1A receptor-immunoreactivity was often seen in the cytoplasm beneath labeled portions of the plasma membrane and in endosome-like granules as well as Golgi lamellae and outer nuclear membranes. In addition, AT1A receptor labeling was detected on the plasma membrane and in association with cytoplasmic membranes in many small axons and axon terminals. These terminals were morphologically heterogeneous containing multiple types of vesicles and forming either inhibitory- or excitatory-type synapses. In the area postrema, AT1A receptor labeling also was detected in many non-neuronal cells including glia, capillary endothelial cells and perivascular fibroblasts that were less prevalent in the NTS. We conclude that in the rat sensory vagal complex, AT1A receptors are strategically positioned for involvement in modulation of the postsynaptic excitability and intracrine hormone-like effects of Ang II. In addition, these receptors have distributions consistent with diverse roles in regulation of transmitter release, regional blood flow and/or vascular permeability.

Angiotensin II↗
PubMed2003

Multiple schwannomas of the sciatic nerve.

Schwannomas are rare benign tumours of nerve sheath cells of neural crest origin. Often these tumours are solitary and encapsulated. Multiple schwannomas can arise from the peripheral nervous system including cranial nerves, spinal roots, the brachial and lumbar-sacral plexus or major peripheral nerves. We report an extremely rare case of schwannomatosis of the sciatic nerve in a young female and include a comprehensive literature review. Treatment options are discussed.

Adolescent↗
PubMed2003

Patient acceptance of self-sampling for human papillomavirus in rural china.

OBJECTIVE.: To test a new survey instrument and determine the acceptance and potential barriers of cervicovaginal self-sampling for high-risk human papillomavirus in rural Chinese women. MATERIALS AND METHODS.: Data from thirteen survey questions assessed acceptance of the self-sampling procedure. Pain, comprehension, and cultural beliefs were potential barriers evaluated by the survey. RESULTS.: A total of 1,560 women were surveyed. The average and mode number of steps of the self-sampling procedure recalled was 5 (out of 7). Ninety-one percent preferred performing the test at a clinic versus their home. The major barrier encountered was related to the educational level of the women. CONCLUSIONS.: The measure performed well in this population. The self-collection brush was well accepted by these women. Education is the largest hurdle to overcome in implementing a self-sampling screening program.

Journal Article↗
PubMed2003

Lytic viral replication as a contributor to the detection of Epstein-Barr virus in breast cancer.

Epstein-Barr virus (EBV) has an accepted association with the epithelial malignancy nasopharyngeal carcinoma and has also been reported in other more controversial carcinoma settings. Evaluation of EBV association with epithelial carcinomas such as breast cancer would benefit from a better understanding of the outcome of EBV infection of these cells. Cell-free preparations of a green fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell lines, which were then examined for EBV gene expression and viral genome copy number. Reverse transcription-PCR analyses revealed that the cells supported a mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein expression was detected by immunohistochemistry, and DNA PCR analyses estimated an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic EBV expression was also found in breast tissue, where reverse transcription-PCR analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4 of 10 normal tissues from the same patients. Scattered cells immunoreactive for Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1% of the cells contained viral genomes. We suggest that sporadic lytic EBV infection may contribute to PCR-based detection of EBV in traditionally nonvirally associated epithelial malignancies.

Antigens, Viral↗
PubMed2003

Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium.

Members of the Wnt family of signaling molecules are important in cell specification and epithelial-mesenchymal interactions, and targeted gene deletion of Wnt-7a in mice results in complete absence of uterine glands and infertility. To assess potential roles of the Wnt family in human endometrium, an endocrine-responsive tissue, we investigated in the proliferative and secretory phases of the menstrual cycle, endometrial expression of several Wnt ligands (Wnt-2, Wnt-3, Wnt-4, Wnt-5a, Wnt-7a, and Wnt-8b), receptors [Frizzled (Fz)-6 and low-density lipoprotein receptor-related protein (LRP)-6], inhibitors [FrpHE and Dickkopf (Dkk)-1], and downstream effectors (Dishevelled-1, glycogen synthase kinase-3beta, and beta-catenin) by RT-PCR, real-time PCR and in situ hybridization. No significant menstrual cycle dependence of the Wnt ligands (except Wnt-3), receptors, or downstream effectors, was observed. Wnt-3 increased 4.7-fold in proliferative compared with secretory endometrium (P < 0.05). However, both inhibitors showed dramatic changes during the cycle, with 22.2-fold down-regulation (P < 0.05) of FrpHE and 234.3-fold up-regulation (P < 0.001) of Dkk-1 in the secretory, compared with the proliferative phase. In situ hybridization revealed cell-specific expression of different Wnt family genes in human endometrium. Wnt-7a was exclusively expressed in the luminal epithelium, and Fz-6 and beta-catenin were expressed in both epithelium and stroma, without any apparent change during the cycle. Both FrpHE and Dkk-1 expression were restricted to the stroma, during the proliferative and secretory phase, respectively. These unique expression patterns of Wnt family genes in different cell types of endometrium and the differential regulation of the inhibitors during the proliferative and secretory phase of the menstrual cycle strongly suggest functions for a Wnt signaling dialog between epithelial and stromal components in human endometrium. Also, they underscore the likely importance of this family during endometrial development, differentiation and implantation.

Adult↗
PubMed2002

TNF-related apoptosis-inducing ligand death pathway-mediated human beta-cell destruction.

AIMS/HYPOTHESIS: The aim of this study is to investigate whether apoptosis in human beta cells can be related to the induction of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. METHODS: We examined the expression of TRAIL and TRAIL receptors in two human pancreatic beta-cell lines and in human primary islet cells using RT-PCR assays and flow cytometric analyses and tested TRAIL-mediated beta-cell destruction in (51)Cr release cytotoxicity assays, Annexin-V and APO-DIREC assays. RESULTS: Most of the human beta cells express TRAIL receptors-R1, -R2, -R3, -R4 and/or TRAIL. TRAIL induced much stronger cytotoxicity and apoptosis to beta-cell lines CM and HP62 than did FasL, TNF-alpha, LTalpha1beta2, LTalpha2beta1, LIGHT, and IFN-gamma. The cytotoxicity and apoptosis induced by TRAIL to beta-cell lines CM were inhibited competitively by soluble TRAIL receptors, R1, R2, R3 or R4. Treatment of these beta cells with antibodies against TRAIL receptors was able to block the cytotoxicity of TRAIL to these cells. Beta-cell antigen-specific CTL (CD4(+) and CD8(+)) clones express TRAIL, suggesting that these cells are potential sources of TRAIL-inducing beta-cell destruction. Normal primary islet cells from most donors are resistant to the cytotoxicity mediated by TRAIL. However, treatment with an inhibitor of protein synthesis (cycloheximide) or with an enzyme (PI-PLC) that can remove TRAIL-R3 from the islet-cell membrane was able to increase the susceptibility of TRAIL-resistant primary islet cells to the TRAIL death pathway. CONCLUSION/INTERPRETATION: The TRAIL death pathway is present and can function in human islet beta cells, but unidentified inhibitors of the TRAIL death pathway are present in normal islet cells.

Apoptosis↗
PubMed2002

Time spent in hospital in the last six months of life in patients who died of cancer in Ontario.

PURPOSE: To describe hospital bed utilization in the final 6 months of life in patients dying of cancer in Ontario, Canada. PATIENTS AND METHODS: Hospital separation records were linked to a population-based cancer registry to identify factors associated with hospitalization in the 203,713 patients who died of cancer in Ontario between 1986 and 1998. RESULTS: Between 1986 and 1998, 5.3% of all acute care beds in Ontario were devoted to the care of cancer patients in the last 6 months of life. The mean time spent in hospital in the last 6 months of life decreased from 34.3 days in 1986 to 22.7 days in 1998. Hospitalization rates increased exponentially during the last month of life. Patients younger than 50 years of age, women, and residents of poorer communities spent significantly longer in hospital than others. Hospitalization rates differed very little among the common solid tumors, but patients with CNS malignancies, the lymphomas, and the leukemias spent significantly longer in hospital than the other groups. There was significant interregional variations in hospitalization that were not explained by differences in case mix. There was a statistically significant inverse correlation between the rate of use of palliative radiotherapy and the hospital bed use in the county in which the patient resided. CONCLUSION: The total time spent in hospital in the last 6 months of life has decreased over the last decade, but acute care hospitals continue to play a large role in the care of patients who are dying of cancer.

Adult↗
PubMed2002

Functional characterization of CP-465,022, a selective, noncompetitive AMPA receptor antagonist.

The hypothesis that aberrant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity contributes to epileptogenesis and neurodegeneration has prompted the search for AMPA receptor antagonists as potential therapeutics to treat these conditions. We describe the functional characterization of a novel quinazolin-4-one AMPA receptor antagonist, 3-(2-chloro-phenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one (CP-465,022). This compound inhibits AMPA receptor-mediated currents in rat cortical neurons with an IC(50) of 25 nM. Inhibition is noncompetitive with agonist concentration and is not use- or voltage-dependent. CP-465,022 is selective for AMPA over kainate and N-methyl-D-aspartate receptors. However, the compound is found to be equipotent for AMPA receptors composed of different AMPA receptor subunit combinations. This is indicated by the finding that CP-465,022 is equivalently potent for inhibition of AMPA receptor-mediated responses in different types of neurons that express different AMPA receptor subunits. Thus, CP-465,022 provides a new tool to investigate the role of AMPA receptors in physiological and pathophysiological processes.

Animals↗
PubMed2002

Birth prevalence of Down syndrome in Singapore from 1993 to 1998.

OBJECTIVE: To examine the livebirth prevalence rate of Down Syndrome in Singapore from 1993 to 1998. DESIGN: Index cases for the National Birth Defects Register were obtained from all neonatal nurseries in Singapore, all hospital discharge summaries, cytogenetic and pathology reports from all pathology laboratories in Singapore and from the compulsory reporting of all termination of pregnancy cases and stillbirths delivered. SETTING: Information for the Register was obtained from case notes retrieved from the medical record offices, antenatal clinics, cytogenetic laboratories, pathology departments and the Registry of Births and Deaths. SUBJECTS: All foetuses with Trisomy 21 diagnosed prenatally together with livebirths and stillbirths with Down Syndrome diagnosed at or after birth were identified from the Registry database. MAIN OUTCOME MEASURES: Prevalence of Down Syndrome RESULTS: From 1993 to 1998, there were 295 Down Syndrome livebirths, four stillbirths and 197 Down Syndrome foetuses aborted. There has been an increasing number of Down Syndrome foetuses diagnosed antenatally ending in termination and this is accompanied by a falling trend in the Down Syndrome livebirth rate in the same years from 1.17 to 0.89 per 1000 total live births. This is despite an expected increase in Down Syndrome livebirth rate obtained by modelling maternal Down Syndrome age-related risks on the maternal age distribution over the years. CONCLUSIONS: The livebirth prevalence of Down Syndrome in Singapore has fallen over the years from 1.17/1000 livebirths in 1993 to 0.89/1000 livebirths in 1998 due to antenatal diagnosis and selective termination.

Abortion, Induced↗
PubMed2001

A score-statistic approach for the mapping of quantitative-trait loci with sibships of arbitrary size.

The Haseman-Elston method is widely used for the mapping of quantitative-trait loci. However, this method does not use all the information in the data, because it only considers the sib-pair trait-value difference. In addition, the Haseman-Elston method was developed for independent sib pairs; its generalization to nonindependent sib pairs is not straightforward. Here we introduce a score test statistic derived from a normal likelihood based on multiplex sibship data, conditional on identical-by-descent sharing statuses. This score test is asymptotically equivalent to the corresponding likelihood-ratio test, but it is much easier to implement. Because the proposed test uses all of the trait values, it makes more efficient use of the data than does the Haseman-Elston method. The proposed test is naturally applicable to sibships of arbitrary size. The finite-sample properties of the proposed score statistic are evaluated via simulations.

Chromosome Mapping↗
PubMed2001

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗
PubMed2001

Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays.

The eubacterial species Streptomyces coelicolor proceeds through a complex growth cycle in which morphological differentiation/development is associated with a transition from primary to secondary metabolism and the production of antibiotics. We used DNA microarrays and mutational analysis to investigate the expression of individual genes and multigene antibiotic biosynthetic pathways during these events. We identified expression patterns in biosynthetic, regulatory, and ribosomal protein genes that were associated highly specifically with particular stages of development. A knowledge-based algorithm that correlates temporal changes in expression with chromosomal position identified groups of contiguous genes expressed at discrete stages of morphological development, inferred the boundaries of known antibiotic synthesis gene loci, and revealed novel physical clusters of coordinately regulated genes. Microarray analysis of RNA from cells mutated in genes regulating synthesis of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) identified proximate and distant sites that contain putative ABC transporter and two-component system genes expressed coordinately with genes of specific biosynthetic pathways and indicated the existence of two functionally and physically discrete regulons in the Red pathway.

Anthraquinones↗
PubMed2001

Cutting edge: histone acetylation and recombination at the TCR gamma locus follows IL-7 induction.

IL-7 signaling is required for V(D)J recombination at the TCRgamma locus. We have recently reported that IL-7 controls chromatin accessibility for RAG-mediated cleavage. Inhibition of histone deacetylase substituted for the IL-7 signal, indicating a role for histone acetylation in altering chromatin accessibility. We found a greatly reduced histone 3 and histone 4 acetylation level in IL-7Ralpha(-/-) thymocytes in comparison with RAG(-/-) thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7Ralpha(-/-) and IL-7(-/-)RAG(-/-) thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCRgamma constant region in cultured thymocytes from IL-7(-/-)RAG(-/-) mice. This induction correlated with increased histone acetylation at the J-promoter and C-enhancer regulatory elements at the TCRgamma locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCRgamma locus.

Acetylation↗