Publications by authors named "Yao Lee"

17 Publications

  • Page 1 of 1

Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses.

Viruses 2021 02 24;13(3). Epub 2021 Feb 24.

Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.

Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.
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http://dx.doi.org/10.3390/v13030356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995974PMC
February 2021

Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats.

Viruses 2021 01 22;13(2). Epub 2021 Jan 22.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USA.

Felid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- deletion mutants (gE-TK- and PK-) using bacterial artificial chromosome (BAC) mutagenesis and shown safety and immunogenicity in vitro. Here, we compare the safety and efficacy of a prime boost FeHV-1 gE-TK- and FeHV-1 PK- vaccination regimen with commercial vaccination in cats. Cats in the vaccination groups were vaccinated at 3-week intervals and all cats were challenge infected 3 weeks after the last vaccination. Evaluations included clinical signs, nasal shedding, virus neutralizing antibodies (VN), cytokine mRNA gene expression, post-mortem histology and detection of latency establishment. Vaccination with gE-TK- and PK- mutants was safe and resulted in significantly reduced clinical disease scores, pathological changes, viral nasal shedding, and viral DNA in the trigeminal ganglia (the site of latency) following infection. Both mutants induced VN antibodies and interferons after immunization. In addition, after challenge infection, we observed a reduction of IL-1β expression, and modulation of TNFα, TGFβ and IL10 expression. In conclusion, this study shows the merits of using FeHV-1 deletion mutants for prevention of FeHV-1 infection in cats.
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http://dx.doi.org/10.3390/v13020163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911815PMC
January 2021

Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection.

Pathogens 2021 Jan 7;10(1). Epub 2021 Jan 7.

Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.

Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory disease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell-associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathology results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA sequencing. When comparing transcriptomes of PBMCs during peak viremia to those prior to EHV-1 infection, we found 51 differentially expressed equine genes (48 upregulated and 3 downregulated). After gene ontology analysis, processes such as the interferon defense response, response to chemokines, the complement protein activation cascade, cell adhesion, and coagulation were overrepresented during viremia. Additionally, transcripts for EHV-1, EHV-2, and EHV-5 were identified in pre- and post-EHV-1-infection samples. Looking at micro RNAs (miRNAs), 278 known equine miRNAs and 855 potentially novel equine miRNAs were identified in addition to 57 and 41 potentially novel miRNAs that mapped to the EHV-2 and EHV-5 genomes, respectively. Of those, 1 EHV-5 and 4 equine miRNAs were differentially expressed in PBMCs during viremia. In conclusion, this work expands our current knowledge about the role of PBMCs during EHV-1 viremia and will inform the focus on future experiments to identify host and viral factors that contribute to clinical EHM.
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http://dx.doi.org/10.3390/pathogens10010043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825769PMC
January 2021

Deep cerebral microbleeds are associated with poor cholinesterase inhibitor treatment response in people with Alzheimer disease.

Clin Neurol Neurosurg 2020 08 25;195:105959. Epub 2020 May 25.

Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Objectives: Cholinesterase inhibitors (ChEIs) are the most effective treatment for Alzheimer disease (AD), but the response to treatment varies. Vascular lesions are associated with the pathogenesis of AD, and cerebral microbleeds (CMBs) are an indicator of hemorrhagic vascular pathology, which can be detected through susceptibility-weighted magnetic resonance imaging (SWMRI). This study investigated the association between CMBs and ChEI treatment response in patients with AD.

Patients And Methods: We reviewed the medical records of 112 Taiwanese people with mild to moderate AD and at least 2 years of ChEI treatment between 2009 and 2016. Their baseline CMBs were quantified using the Microbleed Anatomical Rating Scale on SWMRI. Cognitive function of the patients was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student t test and multivariable logistic regression were used to analyze the association between cognitive decline and CMBs.

Results: The mean age of the study population was 76.0 ± 8.0 years. In total, 79 out of 112 patients were women. The presence of deep, but not lobar CMBs at baseline was associated with a significant cognitive decline according to the MMSE and CASI, particularly in long-term memory, attention, orientation, mental manipulation, and verbal fluency. Among deep CMBs, those in the basal ganglia and thalamus were significantly associated with cognitive decline.

Conclusions: Deep CMBs, particularly those in the basal ganglia and thalamus, but not lobar CMBs, are associated with poor response to ChEI treatment in people with AD. This can serve as a biomarker for predicting ChEI treatment response.
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http://dx.doi.org/10.1016/j.clineuro.2020.105959DOI Listing
August 2020

Characterization of feline herpesvirus-1 deletion mutants in tissue explant cultures.

Virus Res 2020 07 19;284:197981. Epub 2020 Apr 19.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USA. Electronic address:

Feline herpesvirus-1 (FHV-1) is the primary cause of viral respiratory and ocular disease in cats. While commercial vaccines can provide clinical protection, they do not protect from infection or prevent latency. Moreover, they are not safe for intranasal administration. Our overall objective is to develop a new mucosal vaccine against FHV-1 disease to address these shortcomings. Feline herpesvirus-1 deletion mutants of glycoprotein C (gC-), gE (gE-), US3-encoded serine/threonine protein kinase (PK-), and both gE and thymidine kinase (gE-TK-) were generated by bacterial artificial chromosome (BAC) mutagenesis. Tracheal tissue explants from eight cats were used to compare the pattern of viral infection and associated tissue damage, as well as virus spread through the basement membrane following inoculation with wild-type virus (WT), and gE-, gE-TK-, PK-, and gC- mutants. Tissues were collected at 24, 48, or 72  hours post-inoculation (hpi) followed by immunohistochemistry (IHC) for FHV-1. Histological changes were graded based on the distribution of virus infected cells and the severity of tissue damage. Inoculations with the WT virus resulted in maximal scores at 72 hpi both at a multiplicity of infection (MOI) of 1 and 0.1. Inoculation with the gE- mutant produced scores similar to scores of explants inoculated with the WT virus at 24 and 48 hpi, but scores were significantly decreased at 72 hpi. Explants inoculated with the gE-TK- mutant showed significantly decreased scores at all time points. Further, the majority of explants inoculated with the PK- mutant resulted in scores of zero at all time points, regardless of MOI. Finally, inoculation with WT resulted in significant stromal invasion below the infected epithelium, while stromal invasion was observed in less than 50 % of the samples following inoculation with gE-, gE-TK-, PK-, or gC- mutants and confined closely to the area surrounding the infected epithelium. In conclusion, the gE-TK- and PK- mutants exhibited significantly reduced virulence, tissue damage and spread to the underlying stroma, suggesting that they may be good vaccine candidates for in vivo testing.
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http://dx.doi.org/10.1016/j.virusres.2020.197981DOI Listing
July 2020

Asymmetric Hydroarylation of Enones via Nickel-Catalyzed 5- Cyclization.

Org Lett 2019 08 24;21(15):5990-5994. Epub 2019 Jul 24.

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology , Peking University Shenzhen Graduate School , Nanshan District , Shenzhen 518055 , China.

A nickel-catalyzed reductive cyclization of enones affords a wide array of indanones in high enantiomeric induction. The reaction is featured with an unprecedented broad scope of substrates. The versatility of the new method is demonstrated in several short stereoselective syntheses of medically valuable ()-tolterodine, parent and deuterated (+)-indatraline, and an antitumor natural product, (+)-multisianthol. In comparison, these compounds cannot be prepared satisfactorily via analogous processes catalyzed by palladium.
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http://dx.doi.org/10.1021/acs.orglett.9b02130DOI Listing
August 2019

Treatment outcomes for one-stage concurrent surgical resection and reconstruction of synchronous esophageal and head and neck squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2019 Oct 22;276(10):2929-2940. Epub 2019 Jul 22.

Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Purpose: It is not uncommon to see the synchronous presentation of esophageal squamous carcinoma (ESCC) and head and neck cancer (HNC), and most patients were treated with staged interventions. This study retrospectively reported the outcomes of patients with synchronous ESCC and HNC treated with one-stage concurrent surgical resection and reconstruction.

Methods: We identified 17 consecutive patients with synchronous ESCC and HNC undergoing primary concurrent surgical resections between 2011 and 2017 at our hospital. All patients had received esophageal screenings prior to treatment.

Results: The HNC patients in this study had the following subsite involvements: oral cavity (n = 5), oropharynx (n = 4), larynx (n = 1), hypopharynx (n = 9), and thyroid gland (n = 1). Eighty percent of the HNC subsites (16/20) were treated in advanced stages, while most ESCCs were treated at early stages. The mean follow-up time was 3.2 ± 1.6 years. Surgery-associated morbidity and mortality were 94.1% and 0%, respectively, and the most common complication was anastomotic leakage. The two-year overall survival, 2-year loco-regional recurrence-free survival, and 2-year distant metastasis-free survival were 86.7%, 85.6%, and 78.7%, respectively. No significant difference was found between overall survival and HNC subsite or anastomotic leakage. Four patients (23.5%) developed secondary primary malignancies (SPMs) within a mean follow-up period of 2.9 years (standard deviation 1.6 years).

Conclusion: Although one-stage concurrent surgical resection and reconstruction of synchronous ESCC and HNC were highly invasive and complicated, survival was promising. Isolated distant metastasis remained the most common failure pattern. Vigilant follow-up strategy is mandatory to detect secondary primary malignancies (SPMs), especially within the first 3 years following initial treatment.
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http://dx.doi.org/10.1007/s00405-019-05564-9DOI Listing
October 2019

Viral replication and innate immunity of feline herpesvirus-1 virulence-associated genes in feline respiratory epithelial cells.

Virus Res 2019 04 20;264:56-67. Epub 2019 Feb 20.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USA. Electronic address:

Feline herpesvirus-1 (FHV-1) infection occurs worldwide and is a leading cause of respiratory and ocular diseases in cats. Current vaccines reduce the severity of symptoms but do not prevent infection and, therefore, do not provide defense against an establishment of latency and reactivation. We hypothesize that immunomodulation of FHV-1 is the cause of lack in protection and that deletion of virulence/immune modulatory genes of FHV-1 will enhance safety and immunogenicity. Our objective was to use feline respiratory epithelial cell (FREC) cultures to define in vitro growth characteristics and immunomodulation resulting from infection of FRECs with the virulent FHV-1 strain C27 (WT) and glycoprotein C-deletion (gC-), glycoprotein E-deletion (gE-), serine/threonine protein kinase-deletion (PK-), as well as gE and thymidine kinase-double-deletion (gE-TK-) mutants generated by bacterial artificial chromosome mutagenesis. Differentiated FRECs were mock inoculated or inoculated with WT, gC-, gE-, PK-, or gE-TK- mutants. Virus titration and real-time quantitative PCR assays were performed on samples collected at 1 hpi followed by 24 h intervals between 24 and 96 hpi to determine growth kinetics. Real-time PCR was used to quantitate IFNα, TNFα, IL-1β, IL-10, and TGFβ-specific mRNA levels. Immunoassays were performed to measure the protein levels of subsets of cytokines/chemokines secreted by FRECs. Inoculation of FRECs with gE-TK- resulted in significantly lower end-point titers than inoculation with WT or gE-. Both PK- and gC- inoculated FRECs also produced significantly lower end-point titers at 96 hpi than WT. Overall, intracellular virus titers were higher than those of extracellular virus. PCR results for viral DNA paralleled the virus titration results. Further, in contrast to WT inoculation, an increase in IFNα and IL-10 mRNA expression was not observed following inoculation with gE-TK- and PK-, but inoculation with gE-TK- and PK- did result in increased TGFβ expression in FRECs compared to responses following infection with WT. Moreover, gE-TK- and PK- blocked the inhibition of IL-8 and neutrophil chemoattractant (KC), which was observed following inoculation with WT. In summary, the results obtained in FRECs may be used to predict the safety and immunogenicity characteristics of these mutants in vivo. Our study highlights the value of the FREC system for studying replication kinetics/immune modulation factors of FHV-1 and screening prospective vaccine candidates before their use in experimental cats.
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http://dx.doi.org/10.1016/j.virusres.2019.02.013DOI Listing
April 2019

Suboptimal Baseline Serum Vitamin B12 Is Associated With Cognitive Decline in People With Alzheimer's Disease Undergoing Cholinesterase Inhibitor Treatment.

Front Neurol 2018 9;9:325. Epub 2018 May 9.

Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

Objectives: Cholinesterase inhibitors (ChEIs) are the mainstream treatment for delaying cognitive decline in Alzheimer's disease (AD). Low vitamin B12 is associated with cognitive dysfunction, and its supplementation has been applied as the treatment for certain types of reversible dementia. The present study hypothesized that baseline serum vitamin B12 is associated with the deterioration of cognitive function in people with AD undergoing ChEI treatment.

Materials And Methods: Between 2009 and 2016, medical records from 165 Taiwanese with mild to moderate AD who underwent ChEI treatment for at least 2 years were reviewed. Their baseline serum vitamin B12 levels were measured before treatment initiation. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student's test and multivariable logistic regression were used to analyze the association between cognitive decline and vitamin B12 level. Statistical analyses were performed using SPSS 19.0.

Results: Overall, 122 participants were women. Their median age was 76 years (ranging from 54 to 91). For people with optimal baseline vitamin B12 (above the median level of 436 ng/L), the rates of MMSE and CASI decline were 0.78 ± 1.28 and 2.84 ± 4.21 per year, respectively, which were significantly slower than those with suboptimal vitamin B12 (1.42 ± 1.67 and 4.94 ± 5.88 per year;  = 0.007 and 0.009, respectively). After adjustment for age, sex, education level, hypertension, diabetes, history of stroke, and baseline cognitive function, the baseline serum vitamin B12 level was negatively associated with MMSE and CASI decline.

Conclusion: Suboptimal baseline serum vitamin B12 level is associated with cognitive decline in people with AD undergoing ChEI treatment.
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http://dx.doi.org/10.3389/fneur.2018.00325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954104PMC
May 2018

Characterization of respiratory dendritic cells from equine lung tissues.

BMC Vet Res 2017 Nov 6;13(1):313. Epub 2017 Nov 6.

Department of Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Rd, A13, East Lansing, MI, 48824, USA.

Background: Dendritic cells (DCs) are professional antigen-presenting cells that have multiple subpopulations with different phenotypes and immune functions. Previous research demonstrated that DCs have strong potential for anti-viral defense in the host. However, viruses including alphaherpesvirinae have developed strategies to interfere with the function or maturation of DCs, causing immune dysfunction and avoidance of pathogen elimination. The goal of the present study was to isolate and characterize equine lung-derived DCs (L-DCs) for use in studies of respiratory viruses and compare their features with equine blood-derived DCs (B-DCs), which are currently used for these types of studies.

Results: We found that L-DCs were morphologically similar to B-DCs. Overall, B-DCs demonstrated higher expression of CD86 and CD172α than L-DCs, but both cell types expressed high levels of MHC class II and CD44, as well as moderate amounts of CD163, CD204, and Bla36. In contrast, the endocytic activity of L-DCs was elevated compared to that of B-DCs. Finally, mononuclear cells isolated from lung (L-MCs), which are used as precursors for L-DCs, expressed more antigen-presenting cell-associated markers such as MHC class II and CD172α compared to their counterparts from blood.

Conclusions: Our results indicate that L-DCs may be in an earlier differentiation stage compared to B-DCs. Concurrent with this observation, L-MCs possessed significantly more antigen-uptake capacity compared to their counterparts from blood. It is likely that L-DCs play an important role in antigen uptake and processing of respiratory pathogens and are major contributors to respiratory tract immunity and may be ideal tools for future in vitro or ex vivo studies.
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http://dx.doi.org/10.1186/s12917-017-1240-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674750PMC
November 2017

Fashion misadventure: small bowel perforation caused by magnetic tongue studs usage.

ANZ J Surg 2018 Apr 17;88(4):E355-E356. Epub 2015 Nov 17.

Department of General Surgery, Khoo Teck Puat Hospital, Singapore.

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http://dx.doi.org/10.1111/ans.13367DOI Listing
April 2018

The pathogenic role of torque teno sus virus 1 and 2 and their correlations with various viral pathogens and host immunocytes in wasting pigs.

Vet Microbiol 2015 Nov 29;180(3-4):186-95. Epub 2015 Aug 29.

Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC. Electronic address:

The pathogenic role of torque teno sus virus (TTSuV) in swine is controversial among different studies. The present study intended to evaluate the potential pathogenicity of TTSuV based on its correlations with the histopathological changes, various common concurrently infected viral pathogens including porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV), as well as changes in the distribution and population of host immunocytes such as B lymphocytes, T lymphocytes, and macrophages by using the superficial inguinal lymph nodes (siLNs) of wasting pigs. A tissue microarray consisting of 270 available siLNs collected from 262 clinically wasting and 8 healthy pigs, respectively, were used for the detection of TTSuV1, TTSuV2, PCV2, PRRSV, and PPV by either in situ hybridization (ISH) or immunohistochemical (IHC) staining, and for the detection of various subsets of immunocytes by IHC staining with monoclonal antibodies to CD3, CD79a, and lysozyme. The slides were then subject to digital scanning followed by a semi-quantitative positive pixel evaluation for further statistical analysis. Although a high prevalence of TTSuV1 and/or TTSuV2 infection was noted in both wasting and healthy pigs, the wasting pigs had a significantly higher intensity in both TTSuV1 and TTSuV2 ISH-positive signals than healthy ones did. In the wasting pigs, a significant positive correlation in the tissue viral load was noted between TTSuV1 and TTSuV2 and between TTSuV2 and PCV2, but not between TTSuV1 and PCV2. Conversely, a significant negative correlation in the tissue viral load was revealed between TTSuV2, but not TTSuV1, and PRRSV. The tissue viral load of TTSuV1 was significantly correlated with B cell hyperplasia, while the tissue viral load of TTSuV2 was significantly correlated with increased macrophage population. The ISH positivity of TTSuV2 was significantly correlated with lymphoid depletion and granulomatous inflammation, which are the characteristic histopathological findings in postweaning multisystemic wasting syndrome-affected pigs. These findings suggest that both TTSuV species may have the potential involving the development of porcine circovirus-associated lymphoid lesions via alternating the host immune system.
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http://dx.doi.org/10.1016/j.vetmic.2015.08.027DOI Listing
November 2015

Detection of torque teno sus virus 1 and 2 in porcine tissues by in situ hybridization using multi-strained pooled probes.

Vet Microbiol 2014 Aug 10;172(3-4):390-9. Epub 2014 Jun 10.

Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Porcine torque teno sus virus (TTSuV) has been suggested as a co-factor for the development of porcine circovirus-associated diseases. However, the pathogenic role of TTSuV is still inconclusive, and the target cell and tissue tropism of this virus are also ambiguous. In the present study, a multi-strained pooled probe-based in situ hybridization was established to detect the nucleic acids of TTSuV1 and TTSuV2 in the tissue. The strategy of using polymerase chain reaction-derived digoxigenin-labeled multi-strained pooled probe, instead of single-strained probe or oligonucleotide, was to overcome the fact of high sequence diversity among TTSuV strains and simultaneous infection with distinct strains of TTSuV in the same animal. The cell tropism and tissue distribution were evaluated by grading system with tissues from major organs. Lymphoid tissues, including superficial inguinal, mesenteric, and hilar lymph nodes, tonsil, intestinal lamina propria of mucosa and Peyer's patches, and sometimes spleen, generally contained higher levels of positive signals and are considered as the target sites for TTSuV. Morphologically, the distribution of TTSuV-positive signals had a strong correlation with the T lymphocyte zone. T lymphocytes are, thus, speculated as the major target cells for TTSuV.
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http://dx.doi.org/10.1016/j.vetmic.2014.06.002DOI Listing
August 2014

The first acupuncture center in the United States: an interview with Dr. Yao Wu Lee, Washington Acupuncture Center. Interview by Arthur Yin Fan.

Authors:
Yao Wu Lee

Zhong Xi Yi Jie He Xue Bao 2012 May;10(5):481-92

McLean Center for Complementary and Alternative Medicine, PLC. Vienna, VA 22182, USA.

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May 2012

Monocyte-derived dendritic cells enhance cell proliferation and porcine circovirus type 2 replication in concanavalin A-stimulated swine peripheral blood lymphocytes in vitro.

Vet Immunol Immunopathol 2012 Jan 21;145(1-2):368-78. Epub 2011 Dec 21.

Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan, ROC.

Dendritic cells (DCs) are professional antigen presenting cells cooperating with other immune cells for the activation of innate and adaptive immune responses. The objective of the present study was to investigate the replication activity of porcine circovirus type 2 (PCV2) in DCs and/or lymphocytes during their cross talk and its possible mechanism. Two models were set, herein. Swine blood monocyte (Mo)-derived DCs (MoDCs) or peripheral blood lymphocytes (PBLs) were inoculated with PCV2 prior to their co-cultivation. Bacterial lipopolysaccharide (LPS) and concanavalin A (Con A) were used to stimulate MoDCs and PBLs, respectively. During 6 days of cultivation, a high PCV2 antigen-containing rate without detectable intranuclear signals and a slight but significant increase in the copy number of PCV2 genome were detected in PCV2-inoculated MoDCs. The presence of LPS alone or PCV2-free PBLs, however, had no effect on the location of PCV2 antigens or copy number of PCV2 genome in PCV2-inoculated MoDCs. On the contrary, active PCV2 replication occurred in Con A-stimulated PCV2-inoculated PBLs. When compared with blood Mos, MoDCs induced significantly higher cell proliferation and intensified PCV2 replication in Con A-stimulated PCV2-inoculated PBLs, for which direct contact between MoDCs and lymphocytes was required. Among the cytokines secreted by Con A-activated PBLs, interleukin (IL)-2, but not IL-4 or interferon-γ, could induce cell proliferation and PCV2 replication in PCV2-inoculated PBLs. The findings suggest that although MoDCs support only limited PCV2 replication in themselves, their accessory cell function is required for cell proliferation and PCV2 replication in PCV2-infected lymphocytes.
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http://dx.doi.org/10.1016/j.vetimm.2011.12.009DOI Listing
January 2012