Publications by authors named "Vivian Yu"

26 Publications

  • Page 1 of 1

Distinct transcriptomic response to Newcastle disease virus infection during heat stress in chicken tracheal epithelial tissue.

Sci Rep 2021 Apr 2;11(1):7450. Epub 2021 Apr 2.

Feed the Future Innovation Lab for Genomics to Improve Poultry, University of California, Davis, CA, 95616, USA.

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.
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http://dx.doi.org/10.1038/s41598-021-86795-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018950PMC
April 2021

Functional responses between PMP3 small membrane proteins and membrane potential.

Environ Microbiol 2020 08 20;22(8):3066-3080. Epub 2020 May 20.

Division of Life Science, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China.

The Plasma Membrane Proteolipid 3 (PMP3, UPF0057 family in Uniprot) family consists of abundant small hydrophobic polypeptides with two predicted transmembrane helices. Plant homologues were upregulated in response to drought/salt-stresses and yeast deletion mutants exhibited conditional growth defects. We report here abundant expression of Group I PMP3 homologues (PMP3(i)hs) during normal vegetative growth in both prokaryotic and eukaryotic cells, at a level comparable to housekeeping genes, implicating the regular cellular functions. Expression of eukaryotic PMP3(i)hs was dramatically upregulated in response to membrane potential (Vm) variability (Vm ), whereas PMP3(i)hs deletion-knockdown led to Vm changes with conditional growth defects. Bacterial PMP3(i)h yqaE deletion led to a shift of salt sensitivity; Vm alternations with exogenous K addition downregulated prokaryotic PMP3(i)hs, suggesting [K ]-Vm axis being a significant feedback element in prokaryotic ionic homeostasis. Remarkably, the eukaryotic homologues functionally suppressed the conditional growth defects in bacterial deletion mutant, demonstrating the conserved cross-kingdom membrane functions by PMP3(i)hs. These data demonstrated a direct reciprocal relationship between PMP3(i)hs expression and Vm differentials in both prokaryotic and eukaryotic cells. Cumulative with PMP3(i)hs ubiquitous abundance, their lipid-binding selectivity and membrane protein colocalization, we propose [PMP3(i)hs]-Vm axis as a key element in membrane homeostasis.
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http://dx.doi.org/10.1111/1462-2920.15027DOI Listing
August 2020

Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention.

Fam Cancer 2020 04 24;19(2):143-151. Epub 2020 Feb 24.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Box 356460, Seattle, WA, 98195-6460, USA.

Salpingectomy with interval oophorectomy has gained traction as an ovarian cancer prevention strategy, but is not currently recommended for high risk women. Nevertheless, some choose this approach. We aimed to understand risk perception and plans for oophorectomy in BRCA1 and BRCA2 (BRCA) mutation carriers choosing salpingectomy for ovarian cancer prevention. This was a longitudinal survey study of BRCA mutation carriers who underwent bilateral salpingectomy to reduce ovarian cancer risk. An initial written questionnaire and telephone interview was followed by annual phone interviews. 22 women with BRCA mutations were enrolled. Median follow-up was three years. The median age at salpingectomy was 39.5 years (range 27-49). Perceived lifetime ovarian cancer risk decreased by half after salpingectomy (median risk reduction 25%, range 0-40%). At final follow-up, five (22.7%) had undergone oophorectomy and five women (22.7%) were not planning to undergo completion oophorectomy. BRCA mutation carriers who had salpingectomy after the recommended age of prophylactic surgery (vs. before the recommended age) were less likely to plan for future oophorectomy (28.6% vs. 66.7%, p = 0.037). All women were satisfied with their decision to undergo salpingectomy with eighteen (81.8%) expressing decreased cancer-related worry. There were no diagnoses of ovarian cancer during our study period. In conclusion, most BRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy in BRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven.
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http://dx.doi.org/10.1007/s10689-020-00166-5DOI Listing
April 2020

Integrated Proteomic and Transcriptomic Analysis of Differential Expression of Chicken Lung Tissue in Response to NDV Infection during Heat Stress.

Genes (Basel) 2018 Nov 27;9(12). Epub 2018 Nov 27.

Genomics to Improve Poultry Innovation Lab, University of California, Davis, CA 95616, USA.

Newcastle disease virus (NDV) is a devastating worldwide poultry pathogen with major implications for global food security. In this study, two highly inbred and genetically distinct chicken lines, Fayoumis and Leghorns, were exposed to a lentogenic strain of NDV, while under the effects of heat stress, in order to understand the genetic mechanisms of resistance during high ambient temperatures. Fayoumis, which are relatively more resistant to pathogens than Leghorns, had larger numbers of differentially expressed genes (DEGs) during the early stages of infection when compared to Leghorns and subsequently down-regulated their immune response at the latter stages to return to homeostasis. Leghorns had very few DEGs across all observed time points, with the majority of DEGs involved with metabolic and glucose-related functions. Proteomic analysis corroborates findings made within Leghorns, while also identifying interesting candidate genes missed by expression profiling. Poor correlation between changes observed in the proteomic and transcriptomic datasets highlights the potential importance of integrative approaches to understand the mechanisms of disease response. Overall, this study provides novel insights into global protein and expression profiles of these two genetic lines, and provides potential genetic targets involved with NDV resistance during heat stress in poultry.
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http://dx.doi.org/10.3390/genes9120579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316021PMC
November 2018

Noncytotoxic-Related Primary Ovarian Insufficiency in Adolescents: Multicenter Case Series and Review.

J Pediatr Adolesc Gynecol 2018 Dec 27;31(6):597-604. Epub 2018 Jun 27.

Medstar Health, Division of Pediatric and Adolescent Gynecology, Departments of OB/GYN and Pediatrics, Washington, DC.

Study Objective: Primary ovarian insufficiency (POI) in adolescents not due to cytotoxic therapy has not been well studied. Causes of POI have been described in adults, but adolescents might represent a unique subset necessitating a targeted approach to diagnosis, workup, and treatment. We sought to better characterize adolescent POI through a descriptive multicenter study.

Design: Case series of patients with POI.

Setting: Six tertiary care institutions.

Participants: Patients presenting from 2007 to 2014 aged 13-21 years diagnosed with noncytotoxic POI, with exclusions for those who received gonadotoxic therapy, with 46XY gonadal dysgenesis, or lack of evidence of hypergonadotropic hypogonadism on chart review.

Interventions: Review and data extraction of records identified according to International Classification of Diseases Ninth or Tenth Revision codes.

Main Outcome Measures: Data were analyzed for signs and symptoms, workup, and treatments. Complete workup was on the basis of American College of Obstetricians and Gynecologists guidelines. Characteristics of patients with POI who presented with delayed puberty/primary amenorrhea vs secondary amenorrhea were compared.

Results: One hundred thirty-five records were identified. Those who had received cytotoxic therapy (n = 52), 46XY gonadal dysgenesis (n = 7), or on review did not have POI (n = 19) were excluded. Of 57 remaining cases, 16 were 45X, 2 had galactosemia, and 4 had X-chromosome abnormalities. Most did not undergo full etiologic evaluation. Girls diagnosed after primary amenorrhea/delayed puberty were less symptomatic and more likely to receive an estrogen patch than those diagnosed after secondary amenorrhea.

Conclusion: Noncytotoxic POI in adolescents is an uncommon condition with, to our knowledge, only 64 cases in 6 institutions over 7 years. These patients might not undergo complete etiological workup. Aside from 45X, the most common etiologies were X-chromosome abnormalities or galactosemia.
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http://dx.doi.org/10.1016/j.jpag.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620114PMC
December 2018

Role for ribosome-associated complex and stress-seventy subfamily B (RAC-Ssb) in integral membrane protein translation.

J Biol Chem 2017 12 2;292(48):19610-19627. Epub 2017 Oct 2.

From the Departments of Molecular and Cell Biology and

Targeting of most integral membrane proteins to the endoplasmic reticulum is controlled by the signal recognition particle, which recognizes a hydrophobic signal sequence near the protein N terminus. Proper folding of these proteins is monitored by the unfolded protein response and involves protein degradation pathways to ensure quality control. Here, we identify a new pathway for quality control of major facilitator superfamily transporters that occurs before the first transmembrane helix, the signal sequence recognized by the signal recognition particle, is made by the ribosome. Increased rates of translation elongation of the N-terminal sequence of these integral membrane proteins can divert the nascent protein chains to the ribosome-associated complex and stress-seventy subfamily B chaperones. We also show that quality control of integral membrane proteins by ribosome-associated complex-stress-seventy subfamily B couples translation rate to the unfolded protein response, which has implications for understanding mechanisms underlying human disease and protein production in biotechnology.
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http://dx.doi.org/10.1074/jbc.M117.813857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712606PMC
December 2017

Screening of transporters to improve xylodextrin utilization in the yeast Saccharomyces cerevisiae.

PLoS One 2017 8;12(9):e0184730. Epub 2017 Sep 8.

Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.

The economic production of cellulosic biofuel requires efficient and full utilization of all abundant carbohydrates naturally released from plant biomass by enzyme cocktails. Recently, we reconstituted the Neurospora crassa xylodextrin transport and consumption system in Saccharomyces cerevisiae, enabling growth of yeast on xylodextrins aerobically. However, the consumption rate of xylodextrin requires improvement for industrial applications, including consumption in anaerobic conditions. As a first step in this improvement, we report analysis of orthologues of the N. crassa transporters CDT-1 and CDT-2. Transporter ST16 from Trichoderma virens enables faster aerobic growth of S. cerevisiae on xylodextrins compared to CDT-2. ST16 is a xylodextrin-specific transporter, and the xylobiose transport activity of ST16 is not inhibited by cellobiose. Other transporters identified in the screen also enable growth on xylodextrins including xylotriose. Taken together, these results indicate that multiple transporters might prove useful to improve xylodextrin utilization in S. cerevisiae. Efforts to use directed evolution to improve ST16 from a chromosomally-integrated copy were not successful, due to background growth of yeast on other carbon sources present in the selection medium. Future experiments will require increasing the baseline growth rate of the yeast population on xylodextrins, to ensure that the selective pressure exerted on xylodextrin transport can lead to isolation of improved xylodextrin transporters.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591001PMC
October 2017

High-yield chemical synthesis by reprogramming central metabolism.

Nat Biotechnol 2016 11;34(11):1128-1129

Departments of Chemistry and Molecular &Cell Biology, University of California, Berkeley, USA.

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http://dx.doi.org/10.1038/nbt.3723DOI Listing
November 2016

Cellobionic acid utilization: from Neurospora crassa to Saccharomyces cerevisiae.

Biotechnol Biofuels 2015 16;8:120. Epub 2015 Aug 16.

Department of Molecular and Cell Biology, University of California, Berkeley, CA USA.

Background: Economical production of fuels and chemicals from plant biomass requires the efficient use of sugars derived from the plant cell wall. Neurospora crassa, a model lignocellulosic degrading fungus, is capable of breaking down the complex structure of the plant cell wall. In addition to cellulases and hemicellulases, N. crassa secretes lytic polysaccharide monooxygenases (LPMOs), which cleave cellulose by generating oxidized sugars-particularly aldonic acids. However, the strategies N. crassa employs to utilize these sugars are unknown.

Results: We identified an aldonic acid utilization pathway in N. crassa, comprised of an extracellular hydrolase (NCU08755), cellobionic acid transporter (CBT-1, NCU05853) and cellobionic acid phosphorylase (CAP, NCU09425). Extracellular cellobionic acid could be imported directly by CBT-1 or cleaved to gluconic acid and glucose by a β-glucosidase (NCU08755) outside the cells. Intracellular cellobionic acid was further cleaved to glucose 1-phosphate and gluconic acid by CAP. However, it remains unclear how N. crassa utilizes extracellular gluconic acid. The aldonic acid pathway was successfully implemented in Saccharomyces cerevisiae when N. crassa gluconokinase was co-expressed, resulting in cellobionic acid consumption in both aerobic and anaerobic conditions.

Conclusions: We successfully identified a branched aldonic acid utilization pathway in N. crassa and transferred its essential components into S. cerevisiae, a robust industrial microorganism.
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http://dx.doi.org/10.1186/s13068-015-0303-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537572PMC
August 2015

Expanding xylose metabolism in yeast for plant cell wall conversion to biofuels.

Elife 2015 Feb 3;4. Epub 2015 Feb 3.

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

Sustainable biofuel production from renewable biomass will require the efficient and complete use of all abundant sugars in the plant cell wall. Using the cellulolytic fungus Neurospora crassa as a model, we identified a xylodextrin transport and consumption pathway required for its growth on hemicellulose. Reconstitution of this xylodextrin utilization pathway in Saccharomyces cerevisiae revealed that fungal xylose reductases act as xylodextrin reductases, producing xylosyl-xylitol oligomers as metabolic intermediates. These xylosyl-xylitol intermediates are generated by diverse fungi and bacteria, indicating that xylodextrin reduction is widespread in nature. Xylodextrins and xylosyl-xylitol oligomers are then hydrolyzed by two hydrolases to generate intracellular xylose and xylitol. Xylodextrin consumption using a xylodextrin transporter, xylodextrin reductases and tandem intracellular hydrolases in cofermentations with sucrose and glucose greatly expands the capacity of yeast to use plant cell wall-derived sugars and has the potential to increase the efficiency of both first-generation and next-generation biofuel production.
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http://dx.doi.org/10.7554/eLife.05896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338637PMC
February 2015

Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

PLoS One 2014 20;9(10):e110145. Epub 2014 Oct 20.

School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0110145PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203766PMC
July 2015

Tetrandrine inhibits hepatocellular carcinoma cell growth through the caspase pathway and G2/M phase.

Oncol Rep 2013 Jun 20;29(6):2205-10. Epub 2013 Mar 20.

School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.

Activation of p53-independent pathways plays an important role in phytochemical-induced apoptosis and is considered to be a crucial factor in the invasion and metastasis of cancer. Previous studies have shown that combined effects of Stephania tetrandra with medicinal herbs exhibit beneficial effects in cancer patients. Tetrandrine, an active component of Stephania tetrandra has been reported to have anticancer properties in cancer cells. However, the mechanism(s) of action of tetrandrine in liver cancer have yet to be fully elucidated. In this study, we investigated the effects of tetrandrine in hepatocellular carcinoma (HCC) cells. The results showed that tetrandrine inhibited HCC cell proliferation by suppression of cell cycle progression at the G2/M phase. Changes in the expression levels of Bax, Bcl, p53, survivin, PCNA, PARP and p21 were observed. In addition, tetrandrine increased caspase-3 expression and induced DNA fragmentation in Huh-7 cells. The results suggest that the anti-cancer effect of tetrandrine in Huh-7 cells may be mediated by p53-independent pathways.
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http://dx.doi.org/10.3892/or.2013.2352DOI Listing
June 2013

Balloon catheter dilatation of Eustachian tube: a preliminary study.

Otol Neurotol 2012 Dec;33(9):1549-52

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, St Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.

Objective: Eustachian tube dysfunction is a common problem and transnasal endoscopic balloon dilation of the Eustachian tube (ET) is a new surgical technique. The goal of this study is to review the evolution of this novel technique and study the preliminary outcomes.

Subjects And Methods: Balloon catheter dilation of the 100 Eustachian tubes in 70 adults was performed at a tertiary medical center from January 2009 to January 2011. A 5-mm sinus balloon catheter was endoscopically placed transnasally into the proximal ET to dilate the cartilaginous ET. Cases were reviewed with respect to indications, outcomes, and complications.

Results: Of the 100 ETs, ear fullness and pressure were improved in 71% of patients studied for 26.3 weeks (± 3.6). Of 8 patients followed for a minimum of 34 months, 87% reported persistent improvement. One complication is reported.

Conclusion: Endoscopic transnasal ET balloon dilation is a novel approach to treating ET dysfunction. Benefits can be durable up to 3 years. This technique holds much promise and merits further investigation.
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http://dx.doi.org/10.1097/MAO.0b013e31826a50c3DOI Listing
December 2012

Active phytochemicals from Chinese herbs as therapeutic agents for the heart.

Cardiovasc Hematol Agents Med Chem 2012 Sep;10(3):251-5

School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Naturally occurring plant alkaloids, in particular those identified from herbal medicines, are finding therapeutic use. Heart diseases can be well managed with specific formulations of herbal medicines. The combined action of multiple constituents of herbal medicines works with therapeutic benefits in humans. The established formulations of Traditional Chinese medicines show efficacy in treatment of diseases. However, individual herbal principles seldom show pharmacological activity. Nevertheless, some of the active alkaloids and terpenoids from medicinal herbs have been identified. The pharmacological activities of these herbal compounds have been studied. These active constituents of herbal medicine are also used in nutrient supplements, but the modes of action of the active component remain sketchy. The present review describes the recent development of those active principles from herbal medicines as cardiovascular agents. The study will provide insights into herbal medicines for drug development for the treatment of cardiovascular disease.
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http://dx.doi.org/10.2174/187152512802651033DOI Listing
September 2012

Recombinant expression of His-tagged saposin B and pH-dependent binding to the lipid coenzyme Q10.

Anal Biochem 2011 Dec 28;419(2):145-52. Epub 2011 Aug 28.

Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.

The use of coenzyme Q10 (CoQ10) has been increasing rapidly during recent years due to its postulated beneficial properties in human health, providing energy and antioxidant protection. There are no known negative side effects of CoQ10 even at very high levels. Recently, native saposin B (sapB) has been shown to bind CoQ10 and subsequently be excreted. It is thought that this interaction between sapB and CoQ10 could be a mechanism to avoid any possible CoQ10 toxicity. The interaction between sapB and CoQ10 is poorly understood. Here we present an increased fermentative yield of recombinant sapB and demonstrate that recombinant sapB will bind CoQ10 in a pH-dependent manner similar to sapB binding with other lipids. SapB was coated onto an IMAC (immobilized metal affinity chromatography) resin and successfully bound CoQ10 at pH 5.0 with release of the CoQ10 at pH 9.0.
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http://dx.doi.org/10.1016/j.ab.2011.08.042DOI Listing
December 2011

Effect of sialodacryoadenitis virus infection on axonal regeneration.

Microsurgery 2011 Sep 22;31(6):458-64. Epub 2011 Aug 22.

Department of Otolaryngology - Head and Neck Surgery, St. Elizabeth's Medical Center, Brighton, MA, USA.

The effect of sialodacryoadenitis virus (SDAV) infection on axonal regeneration and functional recovery was investigated in male Lewis rats. Animals underwent unilateral tibial nerve transection, immediate repair, and treatment with either FK506 (treated) or control vehicle (untreated). Serial walking track analyses were performed to assess functional recovery. Nerves were harvested for morphometric analysis on postoperative day 18 after an SDAV outbreak occurred that affected the 12 experimental animals. Histomorphometry and walking track data were compared against 36 historical controls. Rats infected with SDAV demonstrated severely impaired axonal regeneration and diminished functional recovery. Total fiber counts, nerve density, and percent neural tissue were all significantly reduced in infected animals (P < 0.05). Active SDAV infection severely impaired nerve regeneration and negated the positive effect of FK506 on nerve regeneration in rats. Immunosuppressive risks must be weighed carefully against the potential neuroregenerative benefits in the treatment of peripheral nerve injuries.
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http://dx.doi.org/10.1002/micr.20914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088328PMC
September 2011

A feasibility study to evaluate a novel drug delivery technique through nasal/sinus mucosa using a biodegradable polymer in a guinea pig model.

Otolaryngol Head Neck Surg 2011 Jun 4;144(6):978-81. Epub 2011 Mar 4.

St Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.

Objective: Targeted topical pharmaceuticals have fewer side effects than systemic therapy and present an interesting option to treat chronic sinus disease. A simple, dependable, resorbable drug delivery mechanism has been elusive. The goal of this study is to examine the feasibility of a novel bioresorbable synthetic polymer for drug delivery in nose and sinuses.

Study Design: Feasibility study.

Setting: Animal study.

Subjects And Methods: Polyurethane sponges soaked in either triamcinolone or gentamicin were placed in the ethmoid cavities of 14 guinea pigs via an external approach; 2 additional animals served as controls. Serum levels of each drug were assayed at intervals up to 21 days. Histopathological examination of the relevant sinonasal anatomy of each animal was performed after 21 days.

Results: Serum levels of each drug were detectable between days 1 and 21. There were no significant differences in the histopathological examination of nasal mucosa in guinea pigs in which either drug was applied compared with control animals in which the bioabsorbable material was soaked in saline. The polyurethane sponge did not cause any foreign body reaction, granuloma, or polypoidal change to the sinus mucosa. Two animals developed a subclinical infection at the surgical site.

Conclusion: The targeted use of topical pharmaceuticals via a synthetic bioresorbable nasal sponge dressing in this guinea pig model demonstrated minimal systemic absorption and minimal histopathological changes. This technology is currently under investigation in human clinical trials.
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http://dx.doi.org/10.1177/0194599811398783DOI Listing
June 2011

Interstitial delivery of vascular endothelial growth factor to skin flaps.

Arch Facial Plast Surg 2010 Sep-Oct;12(5):326-31

Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, MN 55415, USA.

Objectives: To demonstrate the feasibility of using microporous catheters to deliver a growth factor in a skin flap model, and to determine whether removal of excess fluid by ultrafiltration catheters reduces edema.

Methods: In a controlled study at a research laboratory associated with major teaching hospital, vascular endothelial growth factor was delivered to porcine skin flaps by direct infusion using hollow fiber catheters. Treated flaps received either infusion alone or infusion and ultrafiltration via hollow fibers inserted into the distal portion of the flap. Controls had neither type of catheter placed. The main outcome measure was flap survival and edema.

Results: Treated anterior flaps were found to have increased survival (mean [SD] increase, 49.9% [9.4%]) compared with control flaps (44.1% [4.5%]) for group (P = .005) and side (P = .01) but not by interaction (P = .14). Water content was significant by analysis of variance for group, position, and interaction (all P < .001, df = 31) for treated (55.3% [9.7%]) and control (61.9% [8.2%]) groups.

Conclusions: This study demonstrated feasibility of using hollow fiber technology to deliver a growth factor to skin flaps. Further study may yield clinical applications for human patients undergoing reconstructive procedures.
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http://dx.doi.org/10.1001/archfacial.2010.72DOI Listing
January 2011

A preliminary theoretical model of hydrodynamics in the inner ear.

Ear Nose Throat J 2010 Apr;89(4):164-8

Department of Otolaryngology-Head and Neck Surgery, Lahey Clinic, Burlington, MA, USA.

Head movement should create a transient pressure imbalance across the membranous inner ear. We used basic concepts of fluid dynamics to develop a theoretical model of the inner ear. According to this model, two contiguous fluidic systems-the perilymphatic system and the endolymphatic system-are in hydrostatic equilibrium across a compliant membrane. Our model demonstrates that changes in resistance or compliance in one system results in a transient distortion of the membranous inner ear until equilibrium between the two systems is restored. The concept of hydrodynamic pressure changes in the inner ear has received little attention, but it may represent a new approach to understanding the inner ear and treating inner ear diseases.
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April 2010

SET8 plays a role in controlling G1/S transition by blocking lysine acetylation in histone through binding to H4 N-terminal tail.

Cell Cycle 2008 May 3;7(10):1423-32. Epub 2008 Mar 3.

Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

We report evidence suggesting that methyltransferase SET8 plays a novel role in regulating cell cycle by suppressing DNA replication through histone binding. First, the distribution of SET8 is strongly cell cycle-dependent. SET8 was concentrated in the nucleus during G(1) and G(2) phases, and was excluded from the nucleus during S phase. Second, at G(1)/S transition, SET8 was degraded through ubiquitination via SCF/Skp2. Third, it was evident that the SET8 binds to the H4 N-terminal tail (H4NT) and blocks the acetylation of lysine residues K5, K8 and K12 of histone H4 during G(1). Such a blockage can hinder DNA replication. Fourth, SET8 binds to hypoacetylated but not hyperacetylated H4NT. Finally, overexpressing the histone-binding domain of SET8 appeared to suppress DNA replication and arrest the cell cycle before the G(1)/S transition. Taken together, these findings suggest that SET8 can be a negative regulator of DNA replication and the destruction of SET8 is required for the onset of S phase.
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http://dx.doi.org/10.4161/cc.7.10.5867DOI Listing
May 2008

Cervical Cancer Screening for the Reluctant - HPV Testing of Air-Dried Vaginal Discharge.

Int J Biomed Sci 2006 Dec;2(4):422-7

Departments of Pathology, Princess Margaret Hospital, Hong Kong SAR, P. R. China;

Despite the availability of the PAP test, cervical cancer continues to cause considerable morbidity and mortality. Many women default cervical cytology for a variety of reasons. This demands the development of alternative screening strategies, such as HPV testing on self-procured cervical-vaginal specimens in order to capture this group of women. We investigated the self-procured air-dried vaginal discharge for HPV testing. We recruited 82 patients with HPV-associated cervical lesions and 36 patients with normal cervical pathology. Participants were briefed and informed consents obtained. Each was then given a kit containing written instructions, a slim napkin, an empty zip-lock plastic bag for soiled napkin specimen, and a return envelope. After wearing the napkin for the day, the patient removes it, dries it, and returns the specimen by mail. Specimens were batched and a 0.5 cm area of each stained napkin was tested for HPV by PCR. Specimens from all 26 patients with high-grade (CIN 2 or above) HPV-induced cervical lesions and 4 of 36 normal subjects tested positive for HPV, giving a sensitivity and specificity of 100% and 88.9%, respectively. We propose offering to women who refuse cervical cytology the alternative screening strategy of testing of self-procured air-dried vaginal discharge for HPV. This method of cervical cancer screening is also suitable for people living in remote regions of the world.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614645PMC
December 2006

Delayed nerve repair is associated with diminished neuroenhancement by FK506.

Laryngoscope 2004 Mar;114(3):570-6

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

Objectives/hypothesis: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days.

Study Design: In vivo laboratory study.

Methods: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively.

Results: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05).

Conclusion: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.
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http://dx.doi.org/10.1097/00005537-200403000-00034DOI Listing
March 2004

Controlled release of nerve growth factor enhances sciatic nerve regeneration.

Exp Neurol 2003 Nov;184(1):295-303

Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.
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http://dx.doi.org/10.1016/s0014-4886(03)00258-9DOI Listing
November 2003

Measuring dynamics of caspase-8 activation in a single living HeLa cell during TNFalpha-induced apoptosis.

Biochem Biophys Res Commun 2003 May;304(2):217-22

Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

In this study, we reported the first measurement of the dynamics of activation of caspase-8 in a single living cell. This measurement was conducted using a specially developed molecular sensor based on the FRET (fluorescence resonance energy transfer) technique. This sensor was constructed by fusing a CFP (cyan fluorescent protein) and a YFP (yellow fluorescent protein) with a linker containing a tandem caspase-8-specific cleavage site. The change of the FRET ratio upon cleavage was larger than 4-fold. Using this sensor, we found that during TNFalpha-induced apoptosis, the activation of caspase-8 was a slower process than that of caspase-3, and it was initiated much earlier than the caspase-3 activation. Inhibition of caspase-9 delayed the full activation of caspase-3 but did not affect the dynamics of caspase-8. Results of these single-cell measurements suggested that caspase-3 was activated by caspase-8 through two parallel pathways during TNFalpha-induced apoptosis in HeLa cells.
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http://dx.doi.org/10.1016/s0006-291x(03)00559-xDOI Listing
May 2003

Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening.

Diagn Cytopathol 2003 Mar;28(3):140-1

Department of Pathology, Princess Margaret Hospital, Hong Kong, China.

Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients.
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http://dx.doi.org/10.1002/dc.10255DOI Listing
March 2003

Massive feto-maternal hemorrhage: an early presentation of women with gestational choriocarcinoma.

Acta Obstet Gynecol Scand 2002 Jun;81(6):573-6

Department of Obstetrics and Gynecology, Princess Margaret Hospital, Hong Kong.

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http://dx.doi.org/10.1034/j.1600-0412.2002.810620.xDOI Listing
June 2002