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Biomedical subjects

H Deng

Publications and source records attributed to H Deng.

At least 19 recordsLinked to original sources

Regulation of KSHV lytic gene expression.

The life cycle of KSHV, latency versus lytic replication, is mainly determined at the transcriptional regulation level. A viral immediate-early gene product, replication and transcription activator (RTA), has been identified as the molecular switch for initiation of the lytic gene expression program from latency. Here we review progress on two key questions: how RTA gene expression is controlled by viral proteins and cellular signals and how RTA regulates the expression of downstream viral genes. We summarize the interactions of RTA with cellular and other viral proteins. We also discuss critical issues that must be addressed in the near future.

Gene Expression Regulation, Viral↗

Protective roles of quinone reductase and tamoxifen against estrogen-induced mammary tumorigenesis.

We previously reported that antiestrogen-liganded estrogen receptor beta (ERbeta) transcriptionally activates the major detoxifying enzyme quinone reductase (QR) (NAD(P)H:quinone oxidoreductase). Further studies on the functional role of ERbeta-mediated upregulation of antioxidative enzymes indicated protective effects against estrogen-induced oxidative DNA damage (ODD). We now report on in vivo and in vitro studies that show that ERbeta-mediated upregulation of QR are involved in the protection against estrogen-induced mammary tumorigenesis. Using the August Copenhagen Irish (ACI) model of estrogen-induced carcinogenesis, we observed that increased ODD and decreased QR expression occur early in the process of estrogen-induced mammary tumorigenesis. Prevention of ACI mammary gland tumorigenesis by tamoxifen was accompanied by decreased ODD and increased QR levels. These correlative findings were supported by our findings that downregulation of QR levels led to increased levels of estrogen quinone metabolites and enhanced transformation potential of 17beta-estradiol treated MCF10A non-tumorigenic breast epithelial cells. Concurrent expression of ERbeta and treatment with 4-hydroxytamoxifen decreased tumorigenic potential of these MCF10A cells. We conclude that upregulation of QR, through induction by tamoxifen, can inhibit estrogen-induced ODD and mammary cell tumorigenesis, representing a possible novel mechanism of tamoxifen prevention against breast cancer.

8-Hydroxy-2'-Deoxyguanosine↗

Multiphoton route to ZnO nanowire lasers.

With intense femtosecond laser excitation, multiphoton absorption-induced stimulated emission and laser emission in ZnO bulk crystal and nanowires have been demonstrated at room temperature. UV-stimulated emission peaks appeared in both bulk crystal and nanowires when the excitation exceeded certain thresholds, and a sharp lasing peak with a linewidth of ~0.5 nm was observed from ZnO nanowires. The emission properties were attributed to the band-edge emission of the recombination of carriers excited by two- and three-photon absorption processes in the wide-bandgap semiconductor.

Journal Article↗

The role of XPB in cell apoptosis and viability and its relationship with p53, p21(waf1/cip1) and c-myc in hepatoma cells.

BACKGROUND: Accumulation of DNA damage has been implicated in hepatocarcinogenesis. XPB plays a pivotal part in repairing damaged DNA. However, up to now, the biological effect of XPB on hepatoma cells remains elusive. MATERIALS AND METHODS: Here, we investigated the role of XPB in the apoptosis and the viability of hepatoma cells by using the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labelling and cell viability assay; we also investigated their relationship with p53, p21(waf1/cip1) and c-myc by using the RT-PCR and Western blot. RESULTS: Compared with the control cells HepG2/pcDNA3.1 or HepG2, XPB-transfected HepG2 cells (HepG2/pcDNA3.1-XPB) displayed lower viability, weaker activity and higher apoptosis index. At the same time, an increased expression of p21(waf1/cip1) mRNA, protein and p53 protein in addition to a decreased expression of c-myc mRNA and protein were detected in HepG2/pcDNA3.1-XPB cells. CONCLUSIONS: Our results indicated that XPB could inhibit the proliferation of hepatoma cells and had a positive effect on the expression of p53 and p21(waf1/cip1) but a negative effect on c-myc.

Apoptosis↗

Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia.

We investigated the role and mechanisms of inflammatory responses within the dorsal root ganglion (DRG) in the development of chemogenic pathological pain. DRG inflammation was induced by a single deposit of the immune activator zymosan in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small hole drilled through the transverse process. After a single zymosan injection, rats developed bilateral mechanical hyperalgesia and allodynia which began by day 1 after surgery, peaked at days 3-7, and lasted up to 28 days. The number of macrophages in ipsilateral and contralateral DRGs increased significantly, lasting over 14 days. Robust glial activation was observed in inflamed ganglia. Cytokine profile analysis using a multiplexing protein array system showed that, in normal DRG, all but interleukin (IL)-5, IL-10 and granulocyte-macrophage colony stimulating factor (GM-CSF) were detectable with concentrations of up to 180 pg/mg protein. Local inflammatory irritation selectively increased IL-1beta, IL-6, IL-18, monocyte chemoattractant protein-1 (MCP-1), and growth-related oncogene (GRO/KC) up to 17-fold, and decreased IL-2 and IL-12 (p70) up to threefold. Inflaming the DRG also remarkably increased the incidence of spontaneous activity of A- and C-fibers recorded in the dorsal root. Many of the spontaneously active A-fibers exhibited a short-bursting discharge pattern. Changes in cytokines and spontaneous activity correlated with the time course of pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local inflammation induced extensive sprouting of sympathetic fibers, extending from vascular processes within the inflamed DRG. These results demonstrate the feasibility of inducing chronic localized inflammatory responses in the DRG in the absence of traumatic nerve damage, and highlight the possible contribution of several inflammatory cytokines/chemokines to the generation of spontaneous activity and development and persistence of chemogenic pathologic pain.

Action Potentials↗

Identification of potential CSF biomarkers in ALS.

BACKGROUND: The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis. OBJECTIVE: To determine if there is a specific protein profile in the CSF that distinguishes patients with ALS from those with purely motor peripheral neuropathy (PN) and healthy control subjects. METHODS: CSF obtained from patients with ALS, disease controls (patients with other neurologic disorders), and normal controls were analyzed using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomics technique. Biomarker sensitivity and specificity was calculated with receiver operating characteristic curve methodology. ALS biomarkers were purified and sequence identified by mass spectrometry-directed peptide sequencing. RESULTS: In initial proteomic discovery studies, three protein species (4.8-, 6.7-, and 13.4-kDa) that were significantly lower in concentration in the CSF from patients with ALS (n = 36) than in normal controls (n = 21) were identified. A combination of three protein species (the "three-protein" model) correctly identified patients with ALS with 95% accuracy, 91% sensitivity, and 97% specificity from the controls. Independent validation studies using separate cohorts of ALS (n = 13), healthy control (n = 25), and PN (n = 7) subjects confirmed the ability of the three CSF protein species to separate patients with ALS from other diseases. Protein sequence analysis identified the 13.4-kDa protein species as cystatin C and the 4.8-kDa protein species as a peptic fragment of the neurosecretory protein VGF. CONCLUSION: Additional application of a "three-protein" biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS.

Adult↗

BubR1 is involved in regulation of DNA damage responses.

Defective mitotic spindles or an impaired spindle-kinetochore interaction activates the spindle checkpoint. We have previously shown that BubR1 haplo-insufficiency results in enhanced genomic instability and tumorigenesis in mice. Here we report that BubR1 deficiency also leads to a compromised response to DNA damage. Following treatment with doxorubicin, BubR1(+/-) murine fibroblast cells (MEF) were defective in undergoing G(2)/M arrest. Thus, whereas in the presence of DNA damage BubR1(+/+) MEF cells remained arrested in mitosis, BubR1(+/-) MEFs rapidly exited from mitosis and divided. The impaired mitotic arrest of BubR1(+/-) MEFs was associated with low levels of phospho-histone H2AX, p53, and p21 after DNA damage caused by treatment with both doxorubicin and ultraviolet light (UV). The impaired expression of p53 and p21 was also confirmed in human cell lines with BubR1 knockdown via RNA interference. Affinity pull-down coupled with mass spectrometry identified Poly(ADP-ribose) polymerase 1 (PARP-1) as one of the proteins interacting with BubR1. Reciprocal co-immunoprecipitation analysis confirmed the physical interaction between BubR1 and PARP-1. Our further study revealed that the ability of retaining intact PARP-1 or its cleavage product p89 was compromised in BubR1(+/-) MEFs upon treatment with doxorubicin or UV. Given that PARP-1 mediates DNA damage responses and regulates the activity of p53, our studies suggest that there exists a cross-talk between the spindle checkpoint and the DNA damage checkpoint and that BubR1 may play an important role in mediating the cross-talk.

Animals↗

Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome.

OBJECTIVE: To determine whether variants in the Slit and Trk-like 1 gene (SLITRK1) are present in American Caucasian population of patients with Tourette syndrome (TS). METHODS: We sequenced the 3'-untranslated region for var321 and the whole coding region in the SLITRK1 gene in 82 Caucasian patients with TS from North America. RESULTS: None of the 82 samples from patients with TS showed the non-coding sequence variant (var321). Only one patient with familial TS was heterozygous for a novel 708C > T (Ile236Ile) nucleotide variant. CONCLUSIONS: The var321 and mutation(s) in the coding region of the SLITRK1 gene probably are a rare cause of TS in a Caucasian population; therefore, genetic heterogeneity of TS should be considered. Tests designed to detect variant(s) in the SLITRK1 gene probably will not have a diagnostic utility in clinical practice.

3' Untranslated Regions↗

[Comparison of IgA/VCA, IgA/EA, IgG/EA in immunoenzyme methods and ZEBRA ELISA in early diagnosis of nasopharyngeal carcinoma.].

BACKGROUND: To develop an ELISA method using Herpesvirus hominis type 4 (EBV) IgG/Zebra as capture antigen for large population screening. METHODS: The ELISA method used purified ZEBRA antigen to detect the IgG/ZEBRA antibody from serum in nasopharyngeal carcinoma (NPC) and normal healthy subjects. RESULTS: Of 288 NPC sera, 262 were detected positive, the sensitivity was 91%, while 5 of 96 normal sera were detected positive, the specificity was 94.8% and the results of NPC group and healthy group displayed significant difference (P less than 0.001). IgA/VCA, IgA/EA, IgG/EA in immunoenzyme methods and ZEBRA ELISA were compared during the NPC screening in two cities: Huizhou, Guangdong and Guiping, Guangxi, 5463 and 2017 samples respectively were tested and 5 earlier NPC patients were found. CONCLUSION: The results indicate that this method has high specificity and sensitivity, and can be used for large population screening to assist early phase NPC diagnosis.

Animals↗

Lead and zinc accumulation and tolerance in populations of six wetland plants.

Wetland plants such as Typha latifolia and Phragmites australis have been indicated to show a lack of evolution of metal tolerance in metal-contaminated populations. The aim of the present study is to verify whether other common wetland plants such as Alternanthera philoxeroides and Beckmannia syzigachne, also possess the same characteristics. Lead and zinc tolerances in populations of six species collected from contaminated and clean sites were examined by hydroponics. In general, the contaminated populations did not show higher metal tolerance and accumulation than the controls. Similar growth responses and tolerance indices in the same metal treatment solution between contaminated and control populations suggest that metal tolerance in wetland plants are generally not further evolved by contaminated environment. The reasons may be related to the special root anatomy in wetland plants, the alleviated metal toxicity by the reduced rooting conditions and the relatively high innate metal tolerance in some species.

Biodegradation, Environmental↗

G309D and W437OPA PINK1 mutations in Caucasian Parkinson's disease patients.

OBJECTIVE: To determine whether the G309D and W437OPA mutations in PINK1 gene are present in American Caucasian population of patients with Parkinson's disease (PD). METHODS: We searched for the G309D and W437OPA mutation by sequencing the regions of interest in the PINK1 gene in 237 unrelated Caucasian patients. RESULTS: None of the 237 samples showed the G309D or W437OPA mutations. CONCLUSIONS: The G309D and W437OPA mutations in PINK1 gene probably do not represent common causes of familial or sporadic PD in a Caucasian population.

Adult↗

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Journal Article↗

Accumulation of lead, zinc, copper and cadmium by 12 wetland plant species thriving in metal-contaminated sites in China.

The concentrations of lead, zinc, copper and cadmium accumulated by 12 emergent-rooted wetland plant species including different populations of Leersia hexandra, Juncus effusus and Equisetum ramosisti were investigated in field conditions of China. The results showed that metal accumulation by wetland plants differed among species, populations and tissues. Populations grown in substrata with elevated metals contained significantly higher metals in plants. Metals accumulated by wetland plants were mostly distributed in root tissues, suggesting that an exclusion strategy for metal tolerance widely exists in them. That some species/populations could accumulate relatively high metal concentrations (far above the toxic concentration to plants) in their shoots indicates that internal detoxification metal tolerance mechanism(s) are also included. The factors affecting metal accumulation by wetland plants include metal concentrations, pH, and nutrient status in substrata. Mostly concentrations of Pb and Cu in both aboveground and underground tissues of the plants were significantly positively related to their total and/or DTPA-extractable fractions in substrata while negatively to soil N and P, respectively. The potential use of these wetland plants in phytoremediation is also discussed.

Cadmium↗

Confirmation and refinement of a genetic locus for disseminated superficial actinic porokeratosis (DSAP1) at 12q23.2-24.1.

BACKGROUND: Our previous study has identified two loci for disseminated superficial actinic porokeratosis (DSAP), but the genes responsible are still unknown. OBJECTIVES: To narrow down the candidate regions and to assess candidate genes. METHODS: A genome-wide scan and linkage analysis were carried out in a newly collected five-generation Chinese family with DSAP. In addition, six candidate genes were screened for possible DSAP-associated mutations. RESULTS: DSAP in this family was associated with chromosome 12q. Fine mapping and haplotype construction refined the DSAP1 locus to a 4.4-cM interval. No disease-associated mutation was detected in CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 or KIAA0789 genes. CONCLUSIONS: The DSAP1 locus was localized to a 4.4-cM interval at chromosome 12q23.2-24.1. CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 and KIAA0789 genes were not associated with DSAP1.

Adolescent↗

ALFRED: the ALelle FREquency Database. Update.

Elaboration of ALFRED (http://alfred.med.yale.edu) is being continued in two directions. One of which is developing tools for efficiently annotating the entries and checking the integrity of the data already in the database while the other is to increase the quantity and accessibility of data. Information contained in ALFRED such as, polymorphic sites, number of populations and frequency tables (one sample typed for one site) has significantly increased.

Alleles↗

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Journal Article↗