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Anthony Wong

Publications and source records attributed to Anthony Wong.

11 recordsLinked to original sources
PubMed2006

Mohs math--where the error hides.

BACKGROUND: Mohs surgical technique allows a full view of surgical margins and has a reported cure rate approaching 100%. METHOD: A survey amongst Mohs surgeons was performed to assess operator technique. In addition, an animated clay model was constructed to identify and quantify tissue movement seen during the processing of Mohs surgical specimens. RESULTS: There is variability in technique used in Mohs surgery in regards to the thickness of layers, and the number of blocks layers are cut into. A mathematical model is described which assesses the clinical impact of this variability. CONCLUSION: Our mathematical model identifies key aspects of technique that may contribute to error. To keep the inherent error rate at a minimum, we advocate minimal division and minimal physical thickness of Mohs specimens.

Clinical Competence↗
PubMed2004

Human bronchial epithelial cells express and secrete MMP-12.

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, which may be responsible for enlargement of alveoli in chronic obstructive pulmonary disease (COPD) and remodeling of pulmonary tissue associated with chronic asthma. Here, we provide novel evidence that MMP-12 is expressed and secreted by normal human bronchial epithelial cell cultures (NHBECs) and reveal the regulation of MMP-12 gene expression by tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), and interferon gamma (IFN-gamma). Reverse transcription-polymerase chain reaction analyses demonstrated MMP-12 mRNA presence in unstimulated differentiated NHBEC cultures. Cultures stimulated independently with EGF or IFN-gamma failed to alter MMP-12 mRNA abundance, while TNF-alpha, TNF-alpha+EGF, or TNF-alpha+IFN-gamma elicited relatively early (6 h) peak increases in MMP-12 mRNA levels. Western blot analyses specifically indicated the presence of MMP-12 in differentiated NHBEC-conditioned media. These findings indicate that the bronchial epithelium may be an important source of elastolytic activity in COPD and tissue remodeling in chronic asthma.

Air↗
PubMed2004

The c-Jun NH2-terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis.

The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases is activated in response to a wide array of cellular stresses and proinflammatory cytokines. Roles for JNK in the developing nervous system and T-cell-mediated immunity have been established by detailed studies of mice with compound mutations in the Jnk genes. However, little is known concerning the roles of JNK in other mammalian tissues. Mice lacking both of the ubiquitously expressed isoforms (JNK1 and -2) die during midgestation with neural tube closure defects and brain abnormalities. Here we show that JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, and lungs. In addition, JNK-deficient mice exhibit an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF. We further demonstrate that adult mice lacking either JNK1 or -2 display striking differences in epidermal proliferation and differentiation, indicative of distinct roles for these kinases in the skin. We conclude that JNK is necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis.

Animals↗
PubMed2004

Determination of bromazepam in human plasma by high-performance liquid chromatography with electrospray ionization tandem mass spectrometric detection: application to a bioequivalence study.

A simple method using a one-step liquid-liquid extraction (LLE) followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of bromazepam in human plasma, using lorazepam as internal standard. The acquisition was performed in the multiple reaction monitoring mode, monitoring the transitions: m/z 316 > 182 for bromazepam and m/z 321 > 275 for lorazepam. The method was linear over the studied range (1-100 ng ml(-1)), with r(2) > 0.98, and the run time was 2.5 min. The intra- and inter-assay precisions were 2.7-14.6 and 4.1-17.3%, respectively and the intra- and inter-assay accuracies were 87-111 and 75.8-109.5%, respectively. The mean recovery was 73.7%, ranging from 64.5 to 79.7%. The limit of quantification was 1 ng ml(-1). At this concentration the mean intra- and inter-assay precisions were 14.6 and 7.1%, respectively, and the mean intra- and inter-assay accuracies were 102.5 and 104%, respectively. Bromazepam stability was evaluated and the results showed that the drug is stable in standard solution and in plasma samples under typical storage and processing conditions. The method was applied to a bioequivalence study in which 27 healthy adult volunteers (14 men) received single oral doses (6 mg) of reference and test bromazepam formulations, in an open, two-period, randomized, crossover protocol. The 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) (peak plasma concentration), AUC(0-96) and AUC(0-inf) (area under the plasma concentration versus time curve from time zero to 96 h and to infinity, respectively) were within the range 80-125%, which supports the conclusion that the test formulation is bioequivalent to the reference formulation regarding the rate and extent of bromazepam absorption.

Anti-Anxiety Agents↗
PubMed2004

Nutritional status and gastrointestinal structure and function in children with ichthyosis and growth failure.

UNLABELLED: Growth failure occurs in several of the ichthyoses, a heterogeneous group of inherited disorders characterized by thickened or scaly skin. This suggests that there may be common pathogenic mechanisms causing failure to thrive. Previous studies have proposed that a hypermetabolic state induced by epidermal inflammation and hyperproliferation or enteropathy leading to malabsorption and nutritional deficiencies might account for the growth failure in icthyosis. OBJECTIVE: The purpose of this study was to examine the extent of enteropathy and nutritional deficiency in children with severe ichthyosis and growth failure. METHODS: Ten children with different types of ichthyoses and growth failure were studied. RESULTS: Evaluation of gastrointestinal structure and function revealed few abnormalities other than mild fat malabsorption in two patients. Total caloric intake exceeded established requirements for age, height, and weight in all patients. Deficiencies of fat-soluble vitamins were identified in a few subjects. Mild elevations in total calcium and magnesium blood level, elevated hematocrit levels, and constipation were observed in many patients. CONCLUSIONS: Nutritional deficiencies and gastrointestinal abnormalities are uncommon in children with ichthyosis and failure to thrive. Chronic hypovolemia caused by impaired epidermal permeability barrier may be common in this population.

Calcium↗
PubMed2004

An intronic enhancer regulates splicing of the twintron of Drosophila melanogaster prospero pre-mRNA by two different spliceosomes.

We have examined the alternative splicing of the Drosophila melanogaster prospero twintron, which contains splice sites for both the U2- and U12-type spliceosome and generates two forms of mRNA, pros-L (U2-type product) and pros-S (U12-type product). We find that twintron splicing is developmentally regulated: pros-L is abundant in early embryogenesis while pros-S displays the opposite pattern. We have established a Kc cell in vitro splicing system that accurately splices a minimal pros substrate containing the twintron and have examined the sequence requirements for pros twintron splicing. Systematic deletion and mutation analysis of intron sequences established that twintron splicing requires a 46-nucleotide purine-rich element located 32 nucleotides downstream of the U2-type 5' splice site. While this element regulates both splicing pathways, its alteration showed the severest effects on the U2-type splicing pathway. Addition of an RNA competitor containing the wild-type purine-rich element to the Kc extract abolished U2-type splicing and slightly repressed U12-type splicing, suggesting that a trans-acting factor(s) binds the enhancer element to stimulate twintron splicing. Thus, we have identified an intron region critical for prospero twintron splicing as a first step towards elucidating the molecular mechanism of splicing regulation involving competition between the two kinds of spliceosomes.

Animals↗
PubMed2003

JNK initiates a cytokine cascade that causes Pax2 expression and closure of the optic fissure.

The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases is stimulated in response to a wide array of cellular stresses and proinflammatory cytokines. Mice lacking individual members of the Jnk family (Jnk1, Jnk2, and Jnk3) are viable and survive without overt structural abnormalities. Here we show that mice with a compound deficiency in Jnk expression can survive to birth, but fail to close the optic fissure (retinal coloboma). We demonstrate that JNK initiates a cytokine cascade of bone morphogenetic protein-4 (BMP4) and sonic hedgehog (Shh) that induces the expression of the paired-like homeobox transcription factor Pax2 and closure of the optic fissure. Interestingly, the role of JNK to regulate BMP4 expression during optic fissure closure is conserved in Drosophila during dorsal closure, a related morphogenetic process that requires JNK-regulated expression of the BMP4 ortholog Decapentaplegic (Dpp).

Animals↗
PubMed2003

Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response.

Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)alpha2 is a critical down-regulatory factor of IL-13-mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Ralpha2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Ralpha2-deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Ralpha2-deficient mice were treated with a soluble IL-13Ralpha2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Ralpha2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response.

Animals↗
PubMed2003

A gene expression profile for endochondral bone formation: oligonucleotide microarrays establish novel connections between known genes and BMP-2-induced bone formation in mouse quadriceps.

Endochondral bone formation has been fairly well characterized from a morphological perspective and yet this process remains largely undefined at molecular and biochemical levels. In vitro and in vivo studies have shown that human bone morphogenetic protein-2 (hBMP-2) is an important developmental growth and differentiation factor, capable of inducing ectopic bone formation in vivo. This study evaluated several aspects of the osteogenic effect of hBMP-2 protein injected into quadriceps of female C57B1/6J SCID mice. Mice were euthanized 1, 2, 3, 4, 7, and 14 days postinjection and muscles were collected for several methods of analysis. Hematoxylin and eosin-stained sections of muscles injected with formulation buffer showed no evidence of osteogenesis. In contrast, sections of muscles injected with hBMP-2 showed evidence of endochondral bone formation that progressed to mineralized bone by day 14. In addition, radiographs of mice injected with hBMP-2 showed that much of the quadriceps muscle had undergone mineralization by day 14. Labeled mRNA solutions were prepared and hybridized to oligonucleotide arrays designed to monitor approximately 1300 murine, full-length genes. Changes in gene expression associated with hBMP-2 were determined from time-matched comparisons between buffer and hBMP-2 samples. A gene expression profile was created for 215 genes that showed greater than 4-fold changes at one or more of the indicated time points. One hundred twenty-two of these genes have previously been associated with bone or cartilage metabolism and showed significant increases in expression, e.g., aggrecan (Agc1), runt related transcription factor 2 (Runx2), bone Gla protein 1 (Bglap1), and procollagens type II (Col2a1) and X (Col10a1). In addition, there were 93 genes that have not been explicitly associated with bone or cartilage metabolism. Two of these genes, cytokine receptor-like factor-1 (Crlf1) and matrix metalloproteinase 23 (Mmp23), showed peak changes in gene expression of 15- and 40-fold on days 4 and 7, respectively. In situ hybridizations of muscle sections showed that Mmp23 and Crlf1 mRNAs were expressed in chondrocytes and osteoblasts, suggesting a role for both proteins in some aspect of cartilage or bone formation. In conclusion, oligonucleotide arrays enabled a broader view of endochondral bone formation than has been reported to date. An increased understanding of the roles played by these gene products will improve our understanding of skeletogenesis, fracture repair, and pathological conditions such as osteoporosis.

Animals↗
PubMed2002

Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses.

The chemokine stromal cell-derived factor 1 (SDF-1) is essential for perinatal viability, B lymphopoiesis, and bone marrow myelopoiesis, and is a potent monocyte and T-lymphocyte chemoattractant. Interactions of SDF-1 with its receptor CXCR4 have been implicated in CD34(+) cell migration and homing. Here it is shown that human SDF-1beta (hSDF-1beta) alone secreted by hSDF-1beta-transduced tumor cells promotes efficacious antitumor responses. The murine C1498 leukemia and B16F1 melanoma models have been studied. For expression of hSDF-1beta by tumor cells (SDF-tumor cells), packaging cell lines secreting retroviruses encoding hSDF-1beta have been used. The results demonstrate that 50% (B16F1) and 90% (C1498) of naive mice injected with SDF-tumor cells reject their tumors. Prophylactic vaccination of naive mice with irradiated SDF-tumor cells leads to systemic immunity, and therapeutic vaccination leads to cure of established tumors. Mice that previously rejected live SDF-tumor cells are immune to the rejected tumor but susceptible to another tumor and have in vitro tumor-specific cytotoxic T lymphocyte (CTL) activity. SDF-tumor cells are not rejected by immunodeficient scid mice. Immunohistochemistry shows significant infiltration of SDF-1 tumors by T cells, and in vivo T-cell depletion studies indicate that CD4(+) T cells are required for SDF-mediated tumor rejection. In conclusion, the present data suggest that SDF-1/CXCR4 interactions have the potential to regulate efficacious antitumor immune responses; exploitation of these interactions may lead to novel therapeutic interventions.

Animals↗