Biomedical subjects

Hoang Nguyen

Publications and source records attributed to Hoang Nguyen.

9 recordsLinked to original sources

PubMed2006

Tcf3 governs stem cell features and represses cell fate determination in skin.

Many stem cells (SCs) respond to Wnt signaling, but whether beta-catenin's DNA binding partners, the Tcfs, play a role in SCs in the absence of Wnts, is unknown. In adult skin, quiescent multipotent progenitors express Tcf3 and commit to a hair cell fate in response to Wnt signaling. We find that embryonic skin progenitors also express Tcf3. Using an inducible system in mice, we show that upon Tcf3 reactivation, committed epidermal cells induce genes associated with an undifferentiated, Wnt-inhibited state and Tcf3 promotes a transcriptional program shared by embryonic and postnatal SCs. Further, Tcf3-repressed genes include transcriptional regulators of the epidermal, sebaceous gland and hair follicle differentiation programs, and correspondingly, all three terminal differentiation pathways are suppressed when Tcf3 is induced postnatally. These data suggest that in the absence of Wnt signals, Tcf3 may function in skin SCs to maintain an undifferentiated state and, through Wnt signaling, directs these cells along the hair lineage.

Animals↗

PubMed2006

The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2.

MEF is an ETS-related transcription factor with strong transcriptional activating activity that affects hematopoietic stem cell behavior and is required for normal NK cell and NK T-cell development. The MEF (also known as ELF4) gene is repressed by several leukemia-associated fusion transcription factor proteins (PML-retinoic acid receptor alpha and AML1-ETO), but it is also activated by retroviral insertion in several cancer models. We have previously shown that cyclin A-dependent phosphorylation of MEF largely restricts its activity to the G(1) phase of the cell cycle; we now show that MEF is a short-lived protein whose expression level also peaks during late G(1) phase. Mutagenesis studies show that the rapid turnover of MEF in S phase is dependent on the specific phosphorylation of threonine 643 and serine 648 at the C terminus of MEF by cdk2 and on the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex SCF(Skp2), which targets MEF for ubiquitination and proteolysis. Overexpression of MEF drives cells through the G(1)/S transition, thereby promoting cell proliferation. The tight regulation of MEF levels during the cell cycle contributes to its effects on regulating cell cycle entry and cell proliferation.

Amino Acid Sequence↗

PubMed2004

Molecular epidemiology of hepatitis C virus in a social network of injection drug users.

BACKGROUND: We aimed to measure the overlap between the social networks of injection drug users (IDUs) and the patterns of related hepatitis C virus (HCV) infections among IDUs. METHODS: A cohort of 199 IDUs (138 of whom were HCV RNA positive) was recruited from a local drug scene in Melbourne, Australia, and was studied using social network analysis and molecular phylogenetic analysis of 2 regions of the HCV genome. RESULTS: Eighteen clusters of related infections involving 51 IDUs (37.0% of HCV RNA-positive IDUs) were detected; these clusters could be separated into 66 discrete pairs. Twelve (18.2%) of the 66 IDU pairs with related infections reported having previously injected drugs together; conversely, only 12 (3.8%) of the 313 pairs of HCV RNA-positive IDUs who were injection partners had strong molecular evidence of related infections. The social and genetic distances that separated IDUs with identical genotypes were weakly associated. Significant clusters of phylogenetically related sequences identified from core region analysis persisted in the analysis of the nonstructural 5a protein region. Genotyping and sequence analysis revealed 2 mixed-genotype infections. CONCLUSIONS: Static social network methods are likely to gather information about a minority of patterns of HCV transmission, because of the difficulty of determining historical infection pathways in an established social network of IDUs. Nevertheless, molecular epidemiological methods identified clusters of IDUs with related viruses and provided information about mixed-genotype infection status.

Australia↗

PubMed2004

Radial optic neurotomy in the porcine eye without retinal vein occlusion.

OBJECTIVE: To demonstrate the histopathologic changes in the porcine eye without retinal vein occlusion after radial optic neurotomy (RON). METHODS: A RON was performed in 14 normal eyes of 12 Yorkshire Cross pigs. One radial stab incision at the edge of the nasal optic nerve head was made using a 20-gauge microvitreoretinal blade (Visitec) while the intraocular pressure was elevated. Surgery was concluded when hemostasis was achieved. Weekly ophthalmoscopic examinations were performed. Group 1 eyes (4 eyes of 2 pigs) were enucleated at the end of surgery. Group 2 eyes (4 eyes of 4 pigs) were enucleated 1 week postoperatively, and group 3 eyes (4 eyes of 4 pigs) were enucleated 3 weeks postoperatively. In group 4 (2 eyes of 2 pigs), animals underwent vitrectomy and RON, and eyes were enucleated 3 weeks postoperatively. RESULTS: Ophthalmoscopic examination demonstrated engorged blood vessels at the RON site up to 3 weeks after surgery with minimal or no hemorrhage. Histological examination of the optic nerve demonstrated foci of hemorrhage, interstitial edema, reactive gliosis, and rare inflammatory cells. At 3 weeks, there was complete axonal nerve fiber loss distal to the neurotomy site. CONCLUSIONS: After RON, marked gliosis and complete axonal nerve fiber loss occur at the neurotomy site. Although bleeding was rare intraoperatively in this porcine model, hemorrhage and interstitial edema were present within the optic nerve at the neurotomy site histologically. Clinical Relevance Radial optic neurotomy remains a controversial method of treatment for central retinal vein occlusion. To our knowledge, this is the first study in the literature describing the histopathologic findings after RON.

Animals↗

PubMed2004

Effects of indocyanine green on the retina and retinal pigment epithelium in a porcine model of retinal hole.

PURPOSE: This study was designed to emulate human macular hole surgery and to test the effects of indocyanine green (ICG) on the retina and retinal pigment epithelium (RPE). METHODS: Yorkshire Cross pigs (n = 23) underwent vitrectomy, separation of the posterior cortical vitreous, and creation of a single retinal hole. In three study groups (n = 6, each group), air-fluid exchange was performed, following which balanced salt solution (BSS), 1.0% ICG, or 0.5% ICG was applied over the retinal hole. In one additional group (n = 5), 0.5% ICG was injected into the fluid-filled eye. At 4 weeks, the eyes were examined clinically, and fundus photographs were obtained before enucleation and light microscopic examination. RESULTS: Clinical evaluations documented a statistically significant difference between study groups (P = 0.036). There was a higher rate of moderate or severe RPE atrophy among animals where 1% or 0.5% ICG was applied in air-filled eyes (83% and 67%, respectively) compared with BSS controls (17%) and fluid-filled eyes receiving 0.5% ICG (40%). Histologic evaluation demonstrated a statistically significant difference between groups (P = 0.044), with extensive outer retinal degeneration observed in air-filled eyes receiving 1% or 0.5% ICG (66% and 60%, respectively) compared with BSS controls or fluid-filled eyes receiving 0.5% ICG (none of the eyes in either group). None of the study groups had any changes in the inner retina except at the retinal hole site. CONCLUSIONS: Retina exposed to ICG concentrations used in human vitreoretinal surgery had greater RPE atrophy and outer retinal degeneration than control eyes undergoing the same surgery without ICG. Eyes filled with infusion fluid during ICG injection had less damage to the RPE and outer retina than did air-filled eyes receiving ICG.

Air↗

PubMed2004

Noncatalytic requirement for cyclin A-cdk2 in p27 turnover.

Ubiquitin-dependent proteolysis makes a major contribution to decreasing the levels of p27. Ubiquitin-dependent proteolysis of p27(kip1) is growth and cell cycle regulated in two ways: first, skp2, a component of the E3-ubiquitin ligase, is growth regulated, and second, a kinase must phosphorylate the threonine-187 position on p27 so that it can be recognized by skp2. In vitro, p27 is phosphorylated by cyclin E- and cyclin A-associated cdk2 as well as by cyclin B1-cdk1. Having analyzed the effect of different cyclin-cyclin-dependent kinase complexes on ubiquitination of p27 in a reconstitution assay system, we now report a noncatalytic requirement for cyclin A-cdk2. Multiparameter flow cytometric analysis also indicates that p27 turnover correlates best with the onset of S phase, once the levels of cyclin A become nearly maximal. Finally, increasing the amount of both cyclin E-cdk2 and skp2 was less efficient at promoting p27 ubiquitination than was increasing the amount of cyclin A-cdk2 alone in extracts prepared from cultures of >93%-purified G(1) cells. Together these lines of evidence suggest that cyclin A-cdk2 plays an ancillary noncatalytic role in the ubiquitination of p27 by the SCF(skp2) complex.

CDC2-CDC28 Kinases↗

PubMedDate not supplied

Associative memory in three aplysiids: correlation with heterosynaptic modulation.

Much recent research on mechanisms of learning and memory focuses on the role of heterosynaptic neuromodulatory signaling. Such neuromodulation appears to stabilize Hebbian synaptic changes underlying associative learning, thereby extending memory. Previous comparisons of three related sea-hares (Mollusca, Opisthobranchia) uncovered interspecific variation in neuromodulatory signaling: strong in Aplysia californica, immeasureable in Dolabrifera dolabrifera, and intermediate in Phyllaplysia taylori. The present study addressed whether this interspecific variation in neuromodulation is correlated with memory of associative (classical conditioning) learning. We differentially conditioned the tail-mantle withdrawal reflex of each of the three species: Mild touch to one side of the tail was paired with a noxious electrical stimulus to the neck. Mild touch to the other side served as an internal control. Post-training reflex amplitudes were tested 15-30 min after training and compared with pre-test amplitudes. All three species showed conditioning: training increased the paired reflex more than the unpaired reflex. However, the temporal pattern of conditioning varied between species. Aplysia showed modest conditioning that grew across the post-test period. Dolabrifera showed distinctly short-lived conditioning, present only on the first post-test. The time course of memory in Phyllaplysia was intermediate, although not statistically distinguishable from the other two species. Taken together, these experiments suggest that evolutionary changes in nonassociative heterosynaptic modulation may contribute to evolutionary changes in the stability of the memory of classical conditioning.

Animals↗

PubMedDate not supplied

Ocular coherence tomography findings with retained submacular perfluoron.

Herein a case of retained perfluorocarbon liquid beneath the macula, following surgical repair of a complicated retinal detachment, is reported. The ocular coherence tomography findings were helpful in distinguishing retained perfluorocarbon liquid from residual subretinal fluid, macular cyst or cystoid macular oedema.

Diagnostic Techniques, Ophthalmological↗

PubMedDate not supplied

Perceptions of children's body sizes among mothers living on the Texas-Mexico border (La Frontera).

OBJECTIVES: The objectives of this study were to quantify mothers' perceptions of their children's sizes and explore mothers' views of child growth, diet, activity, and health. Photographs of children from the Berkeley Longitudinal Growth Study (on Centers for Disease Control and Prevention [CDC] Web site) were used to stimulate discussion with mothers about child sizes. DESIGN: A descriptive, cross-sectional study examined mothers' perceptions of their children's size and their beliefs about child size, growth, and health. SAMPLE: The convenience sample included 25 mother-child dyads of 3-year-old children at two Head Start Centers in a county on the Texas-Mexico border. All mothers self-identified as Hispanic. MEASUREMENT: Photographs of children were shown to elicit mothers' perceptions of children's body sizes. The children and mothers were weighed and measured and their body mass indices (BMIs) were computed. The mothers were interviewed about their beliefs on child health, growth, and feeding. RESULTS: No congruence was found between mothers' perceptions of child sizes in the pictures and their children's sizes. CONCLUSIONS: Using CDC photographs does not appear to be a useful way to educate mothers about child body sizes. A child who is happy, active, and can accomplish normal childhood activities is not considered by mothers as overweight, regardless of the child's BMI.

Adult↗