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1.  Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression 
Cell Death & Disease  2014;5(11):e1514-.
Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one of the major compounds in coffee beans, has been reported to have anti-carcinogenic activity and tumor cell growth-inhibitory activity, and we examined whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in normal human skin fibroblast. Furthermore, combined treatment with cafestol and ABT-737 markedly reduced tumor growth compared with either drug alone in xenograft models. We found that cafestol inhibited Mcl-1 protein expression, which is important for ABT-737 resistance, through promotion of protein degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT-737. Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression.
PMCID: PMC4260730  PMID: 25375379
2.  Cortical–striatal gene expression in neonatal hippocampal lesion (NVHL)-amplified cocaine sensitization 
Genes, brain, and behavior  2013;12(5):564-575.
Cortical–striatal circuit dysfunction in mental illness may enhance addiction vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual diagnosis causality by producing a schizophrenia syndrome with enhanced responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 probesets were used to examine separate and co-occurring effects of NVHLs and cocaine sensitization (15 mg/kg/day × 5 days) on gene expression within medial prefrontal cortex (MPFC), nucleus accumbens (NAC), and caudate-putamen (CAPU). Two weeks after NVHLs robustly amplified cocaine behavioral sensitization, brains were harvested for genes of interest defined as those altered at P < 0.001 by NVHL or cocaine effects or interactions. Among 135 genes so impacted, NVHLs altered twofold more than cocaine, with half of all changes in the NAC. Although no genes were changed in the same direction by both NVHL and cocaine history, the anatomy and directionality of significant changes suggested synergy on the neural circuit level generative of compounded behavioral phenotypes: NVHL predominantly downregulated expression in MPFC and NAC while NVHL and cocaine history mostly upregulated CAPU expression. From 75 named genes altered by NVHL or cocaine, 27 had expression levels that correlated significantly with degree of behavioral sensitization, including 11 downregulated by NVHL in MPFC/NAC, and 10 upregulated by NVHL or cocaine in CAPU. These findings suggest that structural and functional impoverishment of prefrontal-cortical-accumbens circuits in mental illness is associated with abnormal striatal plasticity compounding with that in addictive disease. Polygenetic interactions impacting neuronal signaling and morphology within these networks likely contribute to addiction vulnerability in mental illness.
PMCID: PMC4170677  PMID: 23682998
Behavioral sensitization; cocaine; dual diagnosis; gene expression; hippocampus; microarray; nucleus accumbens; prefrontal cortex; schizophrenia; striatum
3.  Emergence of Antiviral Resistance During Oral Valganciclovir Treatment of an Infant with Congenital Cytomegalovirus (CMV) Infection 
Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity, including sensorineural hearing loss (SNHL), in newborns. Antiviral therapy with ganciclovir (GCV) and its oral prodrug, valganciclovir (VAL-GCV) are increasingly being administered to infected infants, toward the goal of improving neurodevelopmental and auditory outcomes. In this case report, we describe a symptomatic congenitally infected infant treated with VAL-GCV in whom GCV resistance was suspected, based on a 50-fold increase in viral load after 6 weeks of oral therapy. Analyses of CMV sequences from both blood and urine demonstrated populations of viruses with M460V and L595F mutations in the UL97 phosphotransferase gene. In contrast, analysis of viral DNA retrieved from the newborn dried blood spot demonstrated wild-type UL97 sequences. DNAemia resolved after the discontinuation of VAL-GCV. Long-term VAL-GCV therapy in congenitally infected infants can select for resistant viral variants, and anticipatory virological monitoring may be warranted.
PMCID: PMC3807863  PMID: 23688863
congenital cytomegalovirus infection; antiviral therapy; ganciclovir resistance; UL97 mutation
4.  Bovine Leukemia Virus DNA in Human Breast Tissue 
Emerging Infectious Diseases  2014;20(5):772-782.
Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease.
PMCID: PMC4012802  PMID: 24750974
bovine leukemia virus; human; bovine; bovid; breast tissue; viruses; zoonosis; zoonoses; United States; breast cancer; leukemia; lymphoma; cancer; DNA
5.  Multiple myeloma presenting as plasmacytoma of the jaws showing prominent bone formation during chemotherapy 
Dentomaxillofacial Radiology  2013;42(4):20110143.
A 65-year-old female visited our hospital complaining of a swelling on the left cheek area of 2 years' duration. A panoramic radiograph revealed an ill-defined osteolytic radiolucent bony lesion involving the left mandibular angle, ascending ramus, coronoid process and condylar process. Histological examination showed the mandibular lesion to be a plasmacytoma, and a systemic work-up was obtained to rule out multiple myeloma. Contrast-enhanced CT images showed a well-defined and slightly enhanced round mass on the left ramal area, accompanied by the destruction of the left ramus and posterior maxilla. An 18F-fluorodeoxy-glucose positron emission tomography CT (18F-FDG PET/CT) scan revealed a hypermetabolic mass extending from the left mandible to the left maxillary sinus. The patient had M-protein in serum and urine, plasma cells up to 36.5% on bone marrow biopsy and anaemia as a clinical complication. The patient was diagnosed with multiple myeloma and received chemotherapy with thalidomide, cyclophosphamide and dexamethasone. A PET/CT scan taken 6 months later revealed that the hypermetabolic mass had disappeared and there was remarkable bone formation on the left mandible compared with a previous PET/CT scan. A panoramic radiograph taken 8 months later also demonstrated a prominent bone formation of the affected site. To the best of our knowledge, the current case is the first report of multiple myeloma presenting as plasmacytoma of the mandible with an FDG PET/CT scan. The lesion was solitary at diagnosis, and remarkable bone formation was newly observed on the radiographic examination during chemotherapy.
PMCID: PMC3667514  PMID: 23520399
multiple myeloma; plasmacytoma; positron-emission tomography; jaw; bone formation
6.  Drainage Failure Because of Spontaneous Fracture of the Peritoneal Dialysis Catheter 
PMCID: PMC3598116  PMID: 23478378
Peritoneal dialysis catheter; spontaneous catheter fracture; drainage failure
7.  Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin 
Cell Death & Disease  2014;5(3):e1112-.
Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.
PMCID: PMC3973237  PMID: 24625971
dimethoxycurcumin; curcumin; paraptosis; malignant breast cancer cells; proteasomal inhibition
8.  An Attenuated CMV Vaccine with a Deletion in Tegument Protein GP83 (pp65 Homolog) Protects against Placental Infection and Improves Pregnancy Outcome in a Guinea Pig Challenge Model 
Future virology  2013;8(12):1151-1160.
Congenital human cytomegalovirus (HCMV) infection can lead to long-term neurodevelopmental sequelae, including mental retardation and sensorineural hearing loss. Preconception vaccine strategies relevant to prevention of HCMV-mediated injury to the newborn can be studied in the guinea pig cytomegalovirus (GPCMV) model. The objectives of this study were: 1) to assess in guinea pigs the protective efficacy against congenital infection and disease of a recombinant live, attenuated vaccine with a targeted deletion of the GPCMV homolog of the HCMV pUL83 tegument protein, GP83; and, 2) to compare the extent of placental infection in vaccine and control groups, using an in situ hybridization (ISH) assay.
Materials and methods
Outbred Hartley guinea pigs were vaccinated prior to pregnancy with a two-dose series of 5×104 pfu of vAM409, a GP83 deletion virus. Deletion of the GP83 gene resulted in an attenuated virus, and vAM409 vaccinated animals did not demonstrate evidence of DNAemia following vaccination, although ELISA antibody responses were comparable to those observed in natural infection. After mating, pregnant animals were challenged with salivary gland-adapted (SG) GPCMV (1×106 pfu) in the second trimester, and pregnancy outcomes were compared to controls.
Compared to placebo-immunized controls, vaccination resulted in significantly reduced maternal DNAemia following SG challenge, and there was significantly decreased pup mortality in litters born to vaccinated dams (3/29; 10%), compared to control (35/50; 70%; p<0.001). By in situ hybridization study, recovered placentas in the vAM409 vaccine group demonstrated reduced infection and fewer infectious foci compared to the control group.
In summary, preconception immunization with a GP83 deletion vaccine reduced maternal DNAemia and results in protection against congenital GPCMV-associated pup mortality compared to unvaccinated controls. Vaccination resulted in reduced placental infection, probably related to the reduction in maternal DNAemia. Although the pp65 homolog in GPCMV, GP83, is a known target of protective T cell immune responses, it is nevertheless dispensable for effective vaccination against maternal and fetal CMV disease in this model.
PMCID: PMC3900008  PMID: 24465269
Cytomegalovirus; Guinea pig cytomegalovirus; Cytomegalovirus vaccine; Live; attenuated CMV vaccine; CMV UL83; CMV pp65; GPCMV GP83; Vaccine efficacy; Guinea pig challenge model; cytomegalovirus immune evasion
9.  An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model 
Development of a vaccine against congenital cytomegalovirus (CMV) infection is a public health priority, but CMVs encode immune evasion genes that complicate live virus vaccine design. To resolve this problem, this study employed guanosyl phosphoribosyl transferase (gpt) mutagenesis to generate a recombinant guinea pig CMV (GPCMV) with a knockout of a viral chemokine gene, GPCMV MIP (gp1). MIP deletion virus replicated with wild-type kinetics in cell culture but was attenuated in nonpregnant guinea pigs, demonstrating reduced viremia and reduced inflammation and histopathology (compared to a control virus with an intact GPCMV MIP gene) following footpad inoculation. In spite of attenuation, the vaccine was immunogenic, eliciting antibody responses comparable to those observed in natural infection. To assess its protective potential as a vaccine, either recombinant virus or placebo was used to immunize seronegative female guinea pigs. Dams were challenged in the early 3rd trimester with salivary gland-adapted GPCMV. Immunization protected against DNAemia (1/15 in vaccine group versus 12/13 in the control group, P < 0.01). Mean birth weights were significantly higher in pups born to vaccinated dams compared to controls (98.7 g versus 71.2 g, P < 0.01). Vaccination reduced pup mortality, from 35/50 (70%) in controls to 8/52 (15%) in the immunization group. Congenital GPCMV infection was also reduced, from 35/50 (70%) in controls to 9/52 (17%) in the vaccine group (P < 0.0001). We conclude that deletion of an immune modulation gene can attenuate the pathogenicity of GPCMV while resulting in a viral vaccine that retains immunogenicity and demonstrates efficacy against congenital infection and disease.
PMCID: PMC3755440  PMID: 24000289
10.  Larval and Post-Larval Stages of Pacific Oyster (Crassostrea gigas) Are Resistant to Elevated CO2 
PLoS ONE  2013;8(5):e64147.
The average pH of surface oceans has decreased by 0.1 unit since industrialization and is expected to decrease by another 0.3–0.7 units before the year 2300 due to the absorption of anthropogenic CO2. This human-caused pH change is posing serious threats and challenges to the Pacific oyster (Crassostrea gigas), especially to their larval stages. Our knowledge of the effect of reduced pH on C. gigas larvae presently relies presumptively on four short-term (<4 days) survival and growth studies. Using multiple physiological measurements and life stages, the effects of long-term (40 days) exposure to pH 8.1, 7.7 and 7.4 on larval shell growth, metamorphosis, respiration and filtration rates at the time of metamorphosis, along with the juvenile shell growth and structure of the C. gigas, were examined in this study. The mean survival and growth rates were not affected by pH. The metabolic, feeding and metamorphosis rates of pediveliger larvae were similar, between pH 8.1 and 7.7. The pediveligers at pH 7.4 showed reduced weight-specific metabolic and filtration rates, yet were able to sustain a more rapid post-settlement growth rate. However, no evidence suggested that low pH treatments resulted in alterations to the shell ultrastructures (SEM images) or elemental compositions (i.e., Mg/Ca and Sr/Ca ratios). Thus, larval and post-larval forms of the C. gigas in the Yellow Sea are probably resistant to elevated CO2 and decreased near-future pH scenarios. The pre-adapted ability to resist a wide range of decreased pH may provide C. gigas with the necessary tolerance to withstand rapid pH changes over the coming century.
PMCID: PMC3665819  PMID: 23724027
11.  Synovial chondromatosis in the temporomandibular joint: a case with typical imaging features and pathological findings 
The British Journal of Radiology  2011;84(1007):e215-e218.
Synovial chondromatosis of the temporomandibular joint is a rare benign joint disorder that has been reported in only a few studies. However, we recently encountered a pathologically proven case of this disorder. This case also showed the typical imaging findings on panoramic radiographs and on CT and MR images. Therefore, we report this case and the imaging and pathological findings.
PMCID: PMC3473703  PMID: 22011825
13.  Guinea pig cytomegalovirus GP84 is a functional homolog of the human cytomegalovirus (HCMV) UL84 gene that can complement for the loss of UL84 in a chimeric HCMV 
Virology  2010;410(1):76-87.
The guinea pig cytomegalovirus (GPCMV) co-linear gene and potential functional homolog of HCMV UL84 (GP84) was investigated. The GP84 gene had delayed early transcription kinetics and transient expression studies of GP84 protein (pGP84) demonstrated that it targeted the nucleus and co-localized with the viral DNA polymerase accessory protein as described for HCMV pUL84. Additionally, pGP84 exhibited a transdominant inhibitory effect on viral growth as described for HCMV. The inhibitory domain could be localized to a minimal peptide sequence of 99 aa. Knockout of GP84 generated virus with greatly impaired growth kinetics. Lastly, the GP84 ORF was capable of complementing for the loss of the UL84 coding sequence in a chimeric HCMV. Based on this research and previous studies we conclude that GPCMV is similar to HCMV by encoding single copy co-linear functional homologs of HCMV UL82 (pp71), UL83 (pp65) and UL84 genes.
PMCID: PMC3370892  PMID: 21094510
14.  TRAIL promotes caspase-dependent pro-inflammatory responses via PKCδ activation by vascular smooth muscle cells 
Cell Death & Disease  2011;2(11):e223-.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is best known for its selective cytotoxicity against transformed tumor cells. Most non-transformed primary cells and several cancer cell lines are not only resistant to death receptor-induced apoptosis, but also subject to inflammatory responses in a nuclear factor-κB (NF-κB)-dependent manner. Although the involvement of TRAIL in a variety of vascular disorders has been proposed, the exact molecular mechanisms are unclear. Here, we aimed to delineate the role of TRAIL in inflammatory vascular response. We also sought possible molecular mechanisms to identify potential targets for the prevention and treatment of post-angioplastic restenosis and atherosclerosis. Treatment with TRAIL increased the expression of intercellular adhesion molecule-1 by primary human vascular smooth muscle cells via protein kinase C (PKC)δ and NF-κB activation. Following detailed analysis using various PKCδ mutants, we determined that PKCδ activation was mediated by caspase-dependent proteolysis. The protective role of PKCδ was further confirmed in post-traumatic vascular remodeling in vivo. We propose that the TRAIL/TRAIL receptor system has a critical role in the pathogenesis of inflammatory vascular disorders by transducing pro-inflammatory signals via caspase-mediated PKCδ cleavage and subsequent NF-κB activation.
PMCID: PMC3223690  PMID: 22048166
TRAIL; caspase; signal transduction; inflammation
15.  Implication of Ethanol Wet-bonding in Hybrid Layer Remineralization 
Journal of Dental Research  2010;89(6):575-580.
During mineralization, unbound water within the collagen matrix is replaced by apatite. This study tested the null hypothesis that there is no difference in the status of in vitro biomimetic remineralization of hybrid layers, regardless of their moisture contents. Acid-etched dentin was bonded with One-Step with ethanol-wet-bonding, water-wet-bonding, and water-overwet-bonding protocols. Composite-dentin slabs were subjected to remineralization for 1-4 months in a medium containing dual biomimetic analogs, with set Portland cement as the calcium source and characterized by transmission electron microscopy. Remineralization was either non-existent or restricted to the intrafibrillar mode in ethanol-wet-bonded specimens. Extensive intrafibrillar and interfibrillar remineralization was observed in water-wet-bonded specimens. Water-overwet specimens demonstrated partial remineralization of hybrid layers and precipitation of mineralized plates within water channels. The use of ethanol-wet-bonding substantiates that biomimetic remineralization is a progressive dehydration process that replaces residual water in hybrid layers with apatite crystallites.
PMCID: PMC2873130  PMID: 20200419
biomimetics; dentin bonding; ethanol; hybrid layer; intrafibrillar; interfibrillar; remineralization; water
16.  Intravaginal cytomegalovirus (CMV) challenge elicits maternal viremia and results in congenital transmission in a guinea pig model 
Virology Journal  2011;8:89.
The objective of this study was to compare intravaginal (ivg) and subcutaneous (sc) administration of the guinea pig cytomegalovirus (GPCMV) in pregnant and non-pregnant guinea pigs. These studies tested the hypotheses that ivg infection would elicit immune responses, produce maternal viremia, and lead to vertical transmission, with an efficiency similar to the traditionally employed sc route.
Four groups of age- and size-matched guinea pigs were studied. Two groups were pregnant, and two groups were not pregnant. Animals received 5x105 plaque-forming units (PFU) of a GPCMV reconstituted from an infectious bacterial artificial chromosome (BAC) construct containing the full-length GPCMV genome. Seroconversion was compared by IgG ELISA, and viremia (DNAemia) was monitored by PCR. In both pregnant and non-pregnant animals, sc inoculation resulted in significantly higher serum ELISA titers than ivg inoculation at 8 and 12 weeks post-infection. Patterns of viremia (DNAemia) were similar in animals inoculated by either sc or ivg route. However, in pregnant guinea pigs, animals inoculated by both routes experienced an earlier onset of DNAemia than did non-pregnant animals. Neither the percentage of dead pups nor the percentage of GPCMV positive placentas differed by inoculation route.
In the guinea pig model of congenital CMV infection, the ivg route is as efficient at causing congenital infection as the conventional but non-physiologic sc route. This finding could facilitate future experimental evaluation of vaccines and antiviral interventions in this highly relevant animal model.
PMCID: PMC3062623  PMID: 21371319
17.  Accelerated Photobleaching of a Cyanine Dye in the Presence of a Ternary Target DNA, PNA Probe, Dye Catalytic Complex: A Molecular Diagnostic 
Analytical chemistry  2009;81(6):2043-2052.
In many settings, molecular testing is needed but unavailable due to complexity and cost. Simple, rapid, and specific DNA detection technologies would provide important alternatives to existing detection methods. Here we report a novel, rapid nucleic acid detection method based on the accelerated photobleaching of the light-sensitive cyanine dye, 3,3′-diethylthiacarbocyanine iodide (DiSC2(3) I−), in the presence of a target genomic DNA and a complementary peptide nucleic acid (PNA) probe. On the basis of the UV–vis, circular dichroism, and fluorescence spectra of DiSC2(3) with PNA–DNA oligomer duplexes and on characterization of a product of photolysis of DiSC2(3) I−, a possible reaction mechanism is proposed. We propose that (1) a novel complex forms between dye, PNA, and DNA, (2) this complex functions as a photosensitizer producing 1O2, and (3) the 1O2 produced promotes photobleaching of dye molecules in the mixture. Similar cyanine dyes (DiSC3(3), DiSC4(3), DiSC5(3), and DiSCpy(3)) interact with preformed PNA–DNA oligomer duplexes but do not demonstrate an equivalent accelerated photobleaching effect in the presence of PNA and target genomic DNA. The feasibility of developing molecular diagnostic assays based on the accelerated photobleaching (the smartDNA assay) that results from the novel complex formed between DiSC2(3) and PNA–DNA is under way.
PMCID: PMC2827246  PMID: 19231844
18.  Expression of the Human Cytomegalovirus UL97 Gene in a Chimeric Guinea Pig Cytomegalovirus (GPCMV) Results in Viable Virus with Increased Susceptibility to Ganciclovir and Maribavir 
Antiviral research  2008;78(3):250-259.
In lieu of a licensed vaccine, antivirals are being considered as an intervention to prevent congenital human cytomegalovirus (HCMV) infection. Ideally, antiviral therapies should undergo pre-clinical evaluation in an animal model prior to human use. Guinea pig cytomegalovirus (GPCMV) is the only small animal model for congenital CMV. However, GPCMV is not susceptible to the most commonly used HCMV antiviral, ganciclovir (GCV), rendering in vivo study of this agent problematic in the guinea pig model. Human cytomegalovirus (HCMV) susceptibility to GCV is linked to the UL97 gene. We hypothesized that GPCMV susceptibility to GCV could be improved by inserting the HCMV (Towne) UL97 gene into the GPCMV genome in place of the homolog, GP97. A chimeric GPCMV (GPCMV::UL97) expressed UL97 protein, and replicated efficiently in cell culture, with kinetics similar to wild-type GPCMV. In contrast, deletion of GP97 resulted in a virus (GPCMVdGP97) that grew poorly in culture. GPCMV::UL97 had substantially improved susceptibility to the inhibitory effects of GCV in comparison to wild-type GPCMV. Additionally, GPCMV::UL97 exhibited improved susceptibility to another antiviral undergoing clinical trials, maribavir (MBV; benzimidazole riboside 1263W94), which also acts through UL97.
PMCID: PMC2787096  PMID: 18325607
Guinea pig cytomegalovirus; ganciclovir; maribavir; congenital CMV infection; antiviral therapy; bacterial artificial chromosome
19.  Acceptability of A/H1N1 vaccination during pandemic phase of influenza A/H1N1 in Hong Kong: population based cross sectional survey 
Objective To investigate the intention of the Hong Kong general population to take up vaccination against influenza A/H1N1.
Setting Cross sectional population based anonymous survey.
Participants Random sample of 301 adults interviewed by telephone (response rate 80%).
Main outcome measure Intention to take up vaccination against influenza A/H1N1 under five hypothetical scenarios: vaccination is free; vaccination per dosage costs less than $HK100 (£8; €9; $13), $HK101-200, or more than $HK200; and no data are available on the efficacy and safety of the vaccine.
Results 45% (n=135) of the participants reported that they would be highly likely take up vaccination if it was free. When vaccination incurred a cost, however, the prevalence of uptake decreased: 36% (n=108) would take up vaccination if it cost less than $HK100, 24% (n=72) if it cost $HK101-200, and 15% (n=45) if it cost more than $HK200; and in absence of proved efficacy and safety decreased to 5% (n=14). Moreover, 32% (n=95) considered universal A/H1N1 vaccination unnecessary. Overall, 39% (n=117) of participants believed that A/H1N1 vaccination would prevent the virus being contracted; 63% (n=189) erroneously believed that efficacy of the vaccine had been confirmed by clinical trials, and 16% (n=49) believed that it is necessary for everyone in Hong Kong to take up vaccination against influenza A/H1N1.
Conclusions The uptake of vaccination against influenza A/H1N1 by the general population of Hong Kong is unlikely to be high and would be sensitive to personal cost. Evidence about safety and efficacy is critical in determining the prevalence of uptake of vaccination.
PMCID: PMC2768779  PMID: 19861377
20.  Cerebellar hypermetabolism in paraneoplastic cerebellar degeneration 
A 51 year old man with paraneoplastic cerebellar degeneration from gastric adenocarcinoma showed cerebellar hypermetabolism and increased perfusion on brain FDG‐PET scan and SPECT during the acute stage of his illness. The patient underwent subtotal gastrectomy. The intensity of the hypermetabolism had decreased markedly on follow‐up FDG‐PET 3 months later following two cycles of chemotherapy. We suggest that the cerebellar hypermetabolism may have been due to an acute inflammatory process associated with an immunological reaction.
PMCID: PMC2077501  PMID: 16543536
cerebellar hypermetabolism; FDG PET; paraneoplastic cerebellar degeneration
21.  Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome 
Virology Journal  2008;5:139.
In this report we describe the genomic sequence of guinea pig cytomegalovirus (GPCMV) assembled from a tissue culture-derived bacterial artificial chromosome clone, plasmid clones of viral restriction fragments, and direct PCR sequencing of viral DNA. The GPCMV genome is 232,678 bp, excluding the terminal repeats, and has a GC content of 55%. A total of 105 open reading frames (ORFs) of > 100 amino acids with sequence and/or positional homology to other CMV ORFs were annotated. Positional and sequence homologs of human cytomegalovirus open reading frames UL23 through UL122 were identified. Homology with other cytomegaloviruses was most prominent in the central ~60% of the genome, with divergence of sequence and lack of conserved homologs at the respective genomic termini. Of interest, the GPCMV genome was found in many cases to bear stronger phylogenetic similarity to primate CMVs than to rodent CMVs. The sequence of GPCMV should facilitate vaccine and pathogenesis studies in this model of congenital CMV infection.
PMCID: PMC2614972  PMID: 19014498
22.  Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study 
British Journal of Cancer  2007;97(5):700-704.
We investigated the risk of gastric cancer by subsite in relation to cigarette smoking and alcohol in a large population-based cohort of 669 570 Korean men in an insurance plan followed for an average 6.5 years, yielding 3452 new cases of gastric cancer, of which 127 were cardia and upper-third gastric cancer, 2409 were distal gastric cancer and 1007 were unclassified. A moderate association was found between smoking, cardia and upper-third (adjusted relative risk (aRR) 2.2; 95% confidence interval (CI) 1.4–3.5) and distal cancers (aRR=1.4; 95% CI=1.3–1.6). We also found a positive association between alcohol consumption and distal (aRR=1.3; 95% CI=1.2–1.5) and total (aRR=1.2; 95% CI=1.1–1.4) gastric cancer. Combined exposure to high levels of tobacco and alcohol increased the risk estimates further; cardia and upper-third gastric cancers were more strongly related to smoking status than distal gastric cancer.
PMCID: PMC2360367  PMID: 17637680
cigarette smoking; alcohol intake; gastric cancer; subsite
23.  Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease 
Clinical Endocrinology  2008;68(4):555-560.
Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.
One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography.
Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002).
Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.
PMCID: PMC2344088  PMID: 17941908
24.  China: tobacco museum's "smoky" health information 
Tobacco Control  2005;14(1):4-5.
PMCID: PMC1747975  PMID: 15735289
25.  Fecal Viral Concentration and Diarrhea in Norovirus Gastroenteritis 
Emerging Infectious Diseases  2007;13(9):1399-1401.
Fecal viral concentrations of 40 patients infected with norovirus genogroup GII.4 correlated with diarrhea duration and frequency of vomiting. Higher viral concentration and older age were independently associated with prolonged diarrhea (>4 days). These findings provide information on the pathogenesis and transmission of norovirus infections.
PMCID: PMC2857278  PMID: 18252121
Norovirus; viral concentration; diarrhea; gastroenteritis; Hong Kong; dispatch

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