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1.
Lupus ; 28(11): 1337-1343, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31423896

ABSTRACT

OBJECTIVE: We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey's post hoc test. RESULTS: Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset (p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells (p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups (p = 0.293). CONCLUSION: Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , B-Cell Activating Factor/immunology , Immunosuppressive Agents/pharmacology , Lupus Erythematosus, Systemic/drug therapy , Adult , Animals , B-Lymphocyte Subsets/immunology , Female , Humans , Leukocytes, Mononuclear/immunology , Lupus Erythematosus, Systemic/immunology , Male , Mice , Middle Aged , Precursor Cells, B-Lymphoid/immunology , Species Specificity , Young Adult
2.
Virology ; 530: 1-10, 2019 04.
Article in English | MEDLINE | ID: mdl-30753975

ABSTRACT

Conditions of elevated temperature and CO2 levels [30 °C and 970 parts-per-million (ppm), respectively] reduced the systemic titers of a potato virus Y (PVY) isolate in Nicotiana benthamiana plants, relative to standard conditions (25 °C, ~405 ppm CO2). Under controlled conditions we studied how these growing environments affected the transmission of infection by aphids. Probabilities of transmission of infection by insects that fed on infected donor plants kept at either standard conditions, or at 30 °C and 970 ppm CO2 were both determined and found to positively correlate with titers in donor leaves, independently of the ambient conditions in which recipient plantlets would grow. With these data, viral prevalence was simulated under conditions of elevated temperature and CO2 levels and found that for it to remain comparable to that simulated under standard conditions, insect arrivals to recipient plants in the former scenario would have to increase several-fold in their frequency.


Subject(s)
Aphids/virology , Carbon Dioxide/metabolism , Environmental Exposure , Nicotiana/virology , Plant Diseases/virology , Potyvirus/isolation & purification , Temperature , Animals , Plant Leaves/drug effects , Plant Leaves/radiation effects , Plant Leaves/virology , Nicotiana/drug effects , Nicotiana/parasitology , Nicotiana/radiation effects , Viral Load
3.
J Comp Pathol ; 161: 43-54, 2018 May.
Article in English | MEDLINE | ID: mdl-30173857

ABSTRACT

Infectious bronchitis viruses (IBVs) circulating in Malaysia are classified into two groups as Malaysian QX-like and variant strains. In this study, the pathogenicity of IBS130/2015 (QX-like) and IBS037A/2014 (variant) IBVs in 1-day-old and 30-day-old specific pathogen free (SPF) chickens was characterized. Both strains caused respiratory and kidney infections based on immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (qPCR) and a ciliostasis study; however, the results showed that the QX-like strain was more pathogenic, caused higher mortality and showed higher tissue tropism for the kidney than the variant strain. In contrast, despite causing low or no mortality depending on the age of the infected chickens, the Malaysian variant strain showed high tissue tropism for the respiratory tract compared with the QX-like strain. IHC and qPCR indicated the presence of both IBV strains in the epithelial lining of villi in the jejunum and the caecal tonsil; however, no pathological changes were detected in these organs. Both the Malaysian QX-like and variant IBV strains are able to infect the respiratory tract and kidney of chickens irrespective of age.


Subject(s)
Coronavirus Infections/veterinary , Infectious bronchitis virus/pathogenicity , Poultry Diseases/pathology , Poultry Diseases/virology , Animals , Chickens , Malaysia , Specific Pathogen-Free Organisms
4.
Mol Psychiatry ; 23(4): 843-849, 2018 04.
Article in English | MEDLINE | ID: mdl-28397839

ABSTRACT

Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography 'connectome blueprint' to plan surgical targeting in 11 participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the post-operative probabilistic tractography map to the pre-surgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, 9 of 11 patients (81.8%) were responders, with 6 of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.


Subject(s)
Deep Brain Stimulation/methods , Depressive Disorder, Treatment-Resistant/therapy , Prefrontal Cortex/physiology , Adult , Connectome/methods , Depression/therapy , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/physiopathology , Diffusion Tensor Imaging , Female , Gyrus Cinguli/physiology , Humans , Male , Middle Aged , Nerve Net , Pilot Projects , Prefrontal Cortex/metabolism , Prefrontal Cortex/surgery , Prospective Studies , Retrospective Studies , White Matter/physiology
5.
Poult Sci ; 96(12): 4193-4199, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29053823

ABSTRACT

Maternally derived antibodies (MDAs) are important for protection against very virulent infectious bursal disease virus (vvIBDV). In this study, 5-day-old commercial broilers with non-uniform MDA titers (with a coefficient of variation of 50%) were challenged with vvIBDV and given free contact with each other during a 2-week period. The chicks were assigned to four MDA-titer subgroups, GI-1 (very low MDA), GI-2 (low MDA), GI-3 (medium MDA), and GI-4 (high MDA). Transient symptoms of infection were observed in 35.7% of challenged birds. Body weight gain was significantly lower in GI-2, GI-3, and GI-4 birds than in an unchallenged control group. Seroconversion was observed in GI-1 birds and some GI-2 birds. The frequency of virus shedding via the cloaca in vvIBDV-challenged birds increased from 7.1% of GI birds at 5 days post inoculation (dpi) to 35.7% at 14 dpi. The timing of virus shedding was progressively later from GI-1 to GI-4. At 14 dpi, significant atrophy of the bursa of Fabricius (BF) was observed in GI birds compared with GII controls; atrophy was most severe in GI-1 birds and least severe in GI-4 birds. BF lesion scores decreased from GI-1 to GI-4. The proportion of birds with IBDV antigen in the BF at 14 dpi was higher in GI-2 and GI-3 than in GI-1 and GI-4, whereas the viral load in positive birds increased from GI-1 to GI-4. Our results indicate that high levels of MDAs would protect chicks from initial vvIBDV infection but that progressive decay of these MDAs would result in delayed infection by virus shedding in initially infected birds with low MDA titers, resulting in continuous circulation of the virus in a flock with non-uniform MDA titers.


Subject(s)
Birnaviridae Infections/veterinary , Chickens , Infectious bursal disease virus/physiology , Poultry Diseases/immunology , Animals , Birnaviridae Infections/immunology , Birnaviridae Infections/virology , Immunity, Maternally-Acquired , Poultry Diseases/virology , Random Allocation , Virus Shedding
6.
Iran J Vet Res ; 18(1): 13-17, 2017.
Article in English | MEDLINE | ID: mdl-28588628

ABSTRACT

Bovine viral diarrhea virus (BVDV) is an economically important pathogen of the livestock industry worldwide. BVDV is classified into cytopathic (cp) and noncytopathic (ncp), depending on its effects on cultured cells. BVDV is known to alter the host's immune response. Of this, major histocompatibility complex (MHC) class II molecules play a central role in the development and function of the immune system, and are comprised of two types, DR and DQ, in cattle. In this study, we investigated the expression of MHC class II on monocytes infected with ncp BVDV1 or ncp BVDV2. Using flow cytometry (P<0.01), mRNA level quantification (quantitative real time RT-PCR, P<0.01), and western blot (P<0.001), we found that the expressions of MHC class IIDQ was significantly decreased in ncp BVDV2-infected monocytes compared with that in ncp BVDV1-infected cells. Furthermore, interferon gamma (IFN) production was markedly decreased in ncp BVDV2-infected monocytes (P<0.001) compared to those with ncp BVDV1 infection. These findings suggest that ncp BVDV2 causes reduced expressions of MHC class II DQ and a decreased production of IFN, resulting in evasion of immune recognition and suppression of the antiviral defense mechanism of the innate immune response. Consequently, the results demonstrate that ncp BVDV1 and ncp BVDV2 interact differently with the host innate immune response. Thus, our data provide insight into the mechanism by which, unlike ncp BVDV1, ncp BVDV2 impairs antigen presentation, fails to control the viral infection, and causes more severe disease.

7.
Trop Biomed ; 34(2): 263-269, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-33593006

ABSTRACT

Theileria infections are encountered worldwide, occasionally resulting in serious economic losses for the livestock industry. This study is an epidemiological survey of Theileria infections in Korean indigenous cattle populations in the Republic of Korea (ROK). Blood samples were collected from 100 cattle in April (n=50) (prior to pastureland grazing), and again four months later, in August (n=50) (half of the cattle put out for grazing and the other half kept in housing). All samples were tested for the presence of Theileria infection based on PCR amplification of the small subunit of ribosomal RNA gene. Twenty-two samples across the whole study were verified as positive for Theileria infection by PCR methods. In August, Theileria infection was markedly increased in grazing cattle (16/25 animals, 64%) compared with indoor cattle (4/25 animals, 16%); affected animals exhibited no clinical signs of infection. The red blood cell, hematocrit, and hemoglobin values were significantly lower in Theileriapositive cattle than in Theileria-negative cattle. Phylogenetic analysis demonstrated that the isolates from this study belonged to the T. buffeli species, and were significantly related to Types A, B, C, and E, and were distinct from T. buffeli Type D, which is known to be more pathogenic. These findings indicate that T. buffeli identified in Korean indigenous cattle have a low-to-mild pathogenicity. These results suggest that the T. buffeli infection is relatively higher in the ROK, and the infection rate may increase following grazing. Taken together, T. buffeli infection may not only be seasonally correlated, but also may be affected by management practices such as pastureland grazing.

8.
Tropical Biomedicine ; : 263-269, 2017.
Article in English | WPRIM (Western Pacific) | ID: wpr-630981

ABSTRACT

Theileria infections are encountered worldwide, occasionally resulting in serious economic losses for the livestock industry. This study is an epidemiological survey of Theileria infections in Korean indigenous cattle populations in the Republic of Korea (ROK). Blood samples were collected from 100 cattle in April (n=50) (prior to pastureland grazing), and again four months later, in August (n=50) (half of the cattle put out for grazing and the other half kept in housing). All samples were tested for the presence of Theileria infection based on PCR amplification of the small subunit of ribosomal RNA gene. Twenty-two samples across the whole study were verified as positive for Theileria infection by PCR methods. In August, Theileria infection was markedly increased in grazing cattle (16/25 animals, 64%) compared with indoor cattle (4/25 animals, 16%); affected animals exhibited no clinical signs of infection. The red blood cell, hematocrit, and hemoglobin values were significantly lower in Theileria- positive cattle than in Theileria-negative cattle. Phylogenetic analysis demonstrated that the isolates from this study belonged to the T. buffeli species, and were significantly related to Types A, B, C, and E, and were distinct from T. buffeli Type D, which is known to be more pathogenic. These findings indicate that T. buffeli identified in Korean indigenous cattle have a low-to-mild pathogenicity. These results suggest that the T. buffeli infection is relatively higher in the ROK, and the infection rate may increase following grazing. Taken together, T. buffeli infection may not only be seasonally correlated, but also may be affected by management practices such as pastureland grazing.

9.
Poult Sci ; 95(4): 790-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26769266

ABSTRACT

Newcastle disease virus (NDV) strain NDRL0901 was developed as a live vaccine candidate for control of Newcastle disease. NDV isolate KR/duck/13/07 (DK1307) of duck origin was used as the selected vaccine strain. DK1307 was passaged 6 times in chickens. Then a single clone from the chicken-adapted virus (DK1307C) was finally selected, and the vaccine strain was named NDRL0901. DK1307C and the clone NDRL0901 viruses showed enhanced immunogenicity compared to the DK1307 virus. Principal component analysis based on fusion and hemagglutinin-neuraminidase genes revealed the codon usage pattern in the dataset is distinct separating duck viral sequences and avian sequences, and passage of the duck origin virus into the chicken host causes deviation in the codon usage pattern. The NDRL0901 virus was avirulent and did not acquire viral virulence even after 7 back passages in chickens. When day-old chicks were vaccinated with the NDRL0901 virus via spray, eye drops, and drinking water, the vaccinated birds showed no clinical signs and had significant protection efficacy (>80%) against very virulent NDV (Kr005 strain) infection regardless of the administration route employed. The results indicate that the NDRL0901 strain is safe in chickens and can offer protective immunity.


Subject(s)
Chickens , Ducks , Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Poultry Diseases/prevention & control , Vaccines, Attenuated/immunology , Animals , Newcastle Disease/immunology , Newcastle Disease/virology , Poultry Diseases/immunology , Poultry Diseases/virology , Viral Vaccines/immunology
10.
Dis Esophagus ; 29(7): 752-759, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26471351

ABSTRACT

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.


Subject(s)
Carcinoma, Squamous Cell/pathology , Early Detection of Cancer/methods , Esophageal Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Neoplasms, Multiple Primary/diagnosis , Population Surveillance/methods , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/pathology , Esophagoscopy/methods , Female , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/pathology , Iodides , Male , Middle Aged , Multivariate Analysis , Narrow Band Imaging , Neoplasms, Multiple Primary/epidemiology , Neoplasms, Multiple Primary/pathology , Odds Ratio , Prevalence , Prognosis , Prospective Studies , Pyriform Sinus/pathology , Risk Factors , Squamous Cell Carcinoma of Head and Neck , Survival Rate , Young Adult
11.
Transbound Emerg Dis ; 63(1): 56-67, 2016 Feb.
Article in English | MEDLINE | ID: mdl-24661833

ABSTRACT

To determine the prevalence of Bartonella species and identify which species of Bartonella naturally infects the striped field mouse (Apodemus agrarius) in the Republic of Korea (ROK), spleens from 200 mice were assayed by nested polymerase chain reaction (nPCR) targeting the RNA polymerase subunit beta (rpoB) gene and the 16S-23S internal transcribed spacer (ITS) region for members of the genus Bartonella. Utilizing PCR techniques, the prevalence of Bartonella spp. ranged from 31.5% (63/200) to 62.0% (124/200) for the rpoB and ITS gene fragments, respectively. The most prevalent species, Bartonella grahamii, was assigned to 17 genotypes and closely related to the zoonotic pathogens, B. taylorii, B. tribocorum, B. phoceensis and B. henselae, which also were detected. Two Bartonella isolates (KRBG28 and KRBG32) were recovered from blood of A. agrarius captured in Gyeonggi Province, ROK. Comparison of the 16S rRNA, hemin-binding protein E (hbpE), glutamate dehydrogenase 1 (gdh1), invasion-associated protein B (ialB), cell division protein (ftsZ), citrate synthase (gltA), 60 kDa heat shock protein (groEL), rpoB gene fragments and the ITS region sequences from the isolates with GenBank was confirmed as B. grahamii. Phylogenetic analysis based on the alignment of concatenated sequences (4933 bp) of KRBG28 and KRBG32 clustered with B. grahamii, forming an independent clade between Asian and American/European B. grahamii genogroups.


Subject(s)
Bartonella Infections/microbiology , Bartonella/isolation & purification , Mice/microbiology , Animals , Bartonella/classification , Bartonella/genetics , DNA Primers/genetics , Genotype , Phylogeny , Polymerase Chain Reaction/methods , RNA, Ribosomal, 16S/genetics , Republic of Korea , Sequence Analysis, DNA , Spleen/microbiology
12.
Transplant Proc ; 47(2): 451-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25769589

ABSTRACT

BACKGROUND: Adequate nutritional support for patients undergoing major surgery significantly affects postoperative recovery. Data on enteral feeding after liver transplantation (LT) are scarce. The aim of this work was to determine the efficacy and complications of feeding tubes inserted with the use of fluoroscopic assistance, endoscopic assistance, or transperitoneal jejunostomy in patients who underwent LT. METHODS: From January 2008 to August 2013, 2,058 LTs were performed at Asan Medical Center, Seoul, Korea. Enteral feeding tubes were inserted in 155 patients (7.5%) after LT: with the use of fluoroscopic placement in 81 (52%), endoscopic placement in 49 (32%), and transperitoneal jejunostomy in 25 (16%). We retrospectively analyzed the efficacy and complications of enteral feeding tubes. RESULTS: The median age was 55 years (interquartile range [IQR] 49-60). Enteral feeding indications were a high risk of gastric aspiration (n = 90), gastric stasis (n = 27), pneumonia (n = 23), gastrointestinal bleeding (n = 12), and bowel rest (n = 3). Median enteral feeding durations were 14.5 days (IQR 8.0-30.7) for fluoroscopic placement, 20.0 days (IQR 8.0-40.0) for endoscopic placement, and 37.5 days (IQR 18.2-86.2) for transperitoneal jejunostomy. Times to establishment of oral feeding were 13.0 days (IQR 6.2-25.7) for fluoroscopic placement, 24.0 days (IQR 10.5-43.5) for endoscopic placement, and 37.0 days (IQR 17.0-64.2) for transperitoneal jejunostomy. After tube insertion, tube dislocation and blockage occurred in 34 patients (22%) and 16 patients (25%), respectively. CONCLUSIONS: Enteral feeding tube insertion in patients who can not maintain a nasogastric tube or start oral intake for a long time is important for nutritional support after LT. Proper feeding method selection according to patient condition can help patients by improving nutritional support after major operations such as LT.


Subject(s)
Enteral Nutrition/methods , Intubation, Gastrointestinal/methods , Liver Transplantation , Postoperative Care/methods , Adult , Aged , Endoscopy, Gastrointestinal , Enteral Nutrition/adverse effects , Female , Fluoroscopy , Humans , Intubation, Gastrointestinal/adverse effects , Jejunostomy , Male , Middle Aged , Outcome Assessment, Health Care , Radiography, Interventional , Retrospective Studies
13.
Oncogene ; 34(46): 5749-59, 2015 Nov 12.
Article in English | MEDLINE | ID: mdl-25746003

ABSTRACT

The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines.


Subject(s)
Autocrine Communication , Glioblastoma/metabolism , Glioblastoma/pathology , Neoplastic Stem Cells/pathology , Protein Kinase C-delta/metabolism , Animals , Cell Line, Tumor , Humans , Mice , Neoplastic Stem Cells/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Serine/metabolism , Signal Transduction
14.
Br J Cancer ; 112(3): 608-12, 2015 Feb 03.
Article in English | MEDLINE | ID: mdl-25490528

ABSTRACT

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.


Subject(s)
Early Detection of Cancer/methods , Endoscopy, Gastrointestinal , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening/methods , Middle Aged , Neoplasm Staging , Program Evaluation , Republic of Korea
15.
Cell Death Dis ; 5: e1514, 2014 Nov 06.
Article in English | MEDLINE | ID: mdl-25375379

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis Regulatory Proteins/agonists , Carcinoma, Renal Cell/drug therapy , Diterpenes/pharmacology , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/drug therapy , Membrane Proteins/agonists , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , Proto-Oncogene Proteins/agonists , Animals , Apoptosis , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Bcl-2-Like Protein 11 , Biphenyl Compounds/pharmacology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Drug Synergism , Drug Therapy, Combination , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Nude , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Nitrophenols/pharmacology , Piperazines/pharmacology , Primary Cell Culture , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Sulfonamides/pharmacology , Xenograft Model Antitumor Assays
16.
Nat Commun ; 5: 3808, 2014 May 08.
Article in English | MEDLINE | ID: mdl-24806520

ABSTRACT

The integration of nanophotonics and atomic physics has been a long-sought goal that would open new frontiers for optical physics, including novel quantum transport and many-body phenomena with photon-mediated atomic interactions. Reaching this goal requires surmounting diverse challenges in nanofabrication and atomic manipulation. Here we report the development of a novel integrated optical circuit with a photonic crystal capable of both localizing and interfacing atoms with guided photons. Optical bands of a photonic crystal waveguide are aligned with selected atomic transitions. From reflection spectra measured with average atom number N=1.1+/-0.4, we infer that atoms are localized within the waveguide by optical dipole forces. The fraction of single-atom radiative decay into the waveguide is Γ1D/Γ'≃(0.32±0.08), where Γ1D is the rate of emission into the guided mode and Γ' is the decay rate into all other channels. Γ1D/Γ' is unprecedented in all current atom-photon interfaces.

17.
Cell Death Dis ; 5: e1112, 2014 Mar 13.
Article in English | MEDLINE | ID: mdl-24625971

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Curcumin/analogs & derivatives , Proteasome Endopeptidase Complex/drug effects , Proteasome Inhibitors/pharmacology , Transcription Factor CHOP/metabolism , Animals , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Curcumin/pharmacology , Dose-Response Relationship, Drug , Female , Humans , MCF-7 Cells , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Proteasome Endopeptidase Complex/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Interference , Time Factors , Transcription Factor CHOP/genetics , Transfection , Tumor Burden/drug effects , Up-Regulation , Xenograft Model Antitumor Assays
18.
Plant Dis ; 98(1): 162, 2014 Jan.
Article in English | MEDLINE | ID: mdl-30708612

ABSTRACT

In order to investigate the virus infection rate of commercial freesia cultivars in early February 2013, 19 freesia cultivars showing necrotic purple speckles or streaks on leaves, purple streaks parallel to the midrib, and necrotic speckles on leaves were collected from three different regions (Suwon and Icheon in Gyeonggi Province and Jeonju in North Jeonla Province) and used for virus detection. Nucleic acid extracts were analyzed for detection of major freesia-infecting viruses including Freesia sneak virus (FreSV) by reverse transcription (RT)-PCR with specific primer pairs. The FreSV CP gene was amplified using primer pair FreSV-F (5'-TTAGATAGTGAATCCATAAGCTGC-3') and FreSV-R (5'-ATGTCTGGAAAATACTCCGTCCAA-3'). The approximately 1.3-kb fragment of the FreSV amplified product was cloned and sequenced (GenBank Accession No. KC771891 to 98). The nucleotide sequences of CP gene of FreSV korean isolates showed 99.2 to 99.8% similarity to other FreSV isolates DQ885455, FJ807730, and GU071089, which are registered in GenBank. FreSV was detected from 71.7% of 138 plants tested while the infection rate of Freesia mosaic virus (FreMV) was 34.8%. Neither Bean yellow mosaic virus (BYMV) nor Tobacco rattle virus (TRV) were detected from any plants tested in this study. In certain cultivars, such as 'Bluebau' (II) and 'Pretty women,' most plants planted in the field showed purple streak symptoms on the leaves. In conclusion, FreSV was detected from some symptomatic freesia cultivars showing purple streak or speckles on leaves with or without necrotic spots and necrotic speckles on leaves. FreSV is currently widespread in Korea and some freesia plants were mixed infected with FreMV. FreSV has been occurring in the Netherlands for over 40 years (2). It is a plant virus in the family Ophioviridae and Ophiovirus genus. Once it occurs in freesia plantation fields, eradication is almost impossible because FreSV is transmitted by zoospores of Olpidium brassicae, which is a soilborne root-infecting fungus (3). Resting spores of O. brassicae can remain dormant in the soil and can be infective for 20 years (1). To produce virus-free freesia plants, growers should consider whether or not their fields are contaminated with O. brassicae carrying FreSV. To our knowledge, this is the first report of FreSV in freesia plants in Korea. References: (1) R. N. Campbell. Can. J. Bot. 63:2288, 1985. (2) Y. Koot et al. Tijdschrift over Plantenziekten 60:157, 1954. (3) H. J. M. van Dorst. Neth. J. Plant Pathol. 81:45, 1975.

19.
Poult Sci ; 92(8): 2034-43, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23873550

ABSTRACT

A competitive enzyme-linked immunosorbent assay (C-ELISA) using a baculovirus-expressed recombinant nucleocapsid protein antigen (rNDV-N) and an rNDV-N-specific monoclonal antibody (5B3) was developed for the detection of Newcastle disease virus (NDV) antibodies, and its diagnostic performance was evaluated. The specificity and sensitivity of the C-ELISA was found to be 98.4 and 98.9%, respectively, for chickens, and 98.2 and 97.9% for ducks. However, the C-ELISA showed weak cross-reaction with hyperimmune antisera to some other avian paramyxovirus serotypes. In all experimentally vaccinated chickens, seroconversion rates at 7 d postinoculation were 100 and 40% when measured by C-ELISA and hemagglutination inhibition (HI), respectively. In field trials, the C-ELISA showed positive results in 98.9% of HI-positive sera and 40.8% of HI-negative sera from NDV-vaccinated chickens (n = 705). In domestic ducks (n = 158) from NDV-positive duck farms (n = 8), the positive rates according to C-ELISA were significantly higher than those according to the HI test. At the same time, 98.1% of ducks (n = 209) from NDV-negative duck farms (n = 11) were also negative by C-ELISA. Our results indicate that C-ELISA could be a useful alternative to HI testing for detecting NDV antibodies in different avian species such as chickens and ducks.


Subject(s)
Antibodies, Viral/blood , Enzyme-Linked Immunosorbent Assay/veterinary , Newcastle Disease/blood , Newcastle disease virus/immunology , Animals , Chickens , Ducks , Enzyme-Linked Immunosorbent Assay/methods , Gene Expression Regulation, Viral/physiology , Newcastle Disease/diagnosis , Nucleocapsid Proteins/genetics , Nucleocapsid Proteins/metabolism , Sensitivity and Specificity
20.
Poult Sci ; 92(7): 1783-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23776265

ABSTRACT

Egg drop syndrome virus (EDSV) is an important pathogen of poultry that decreases egg production in chickens and causes respiratory disease in goslings. In 2011, we obtained serum samples from 139 domestic Pekin ducks, 416 one-day-old Pekin ducklings, and 75 wild ducks (67 mallards and 8 pintails) to survey their exposure to EDSV. A total of 123 of 139 sera (88.5%) from Pekin ducks, 396 of the ducklings (95.2%), and 16 of 67 mallards (23.9%) were positive. Field cases of EDSV in wild and domestic ducks were investigated. Six cases from domestic Pekin ducks were identified by PCR detection and were used for virus isolation and molecular analysis. Phylogenetic analyses of the partial hexon and full fiber genes showed that the D11-JW-012 and D11-JW-017 strains among 6 isolates belonged to different clusters compared with other known strains including the 127 strain. We assessed cell growth efficiency by hemagglutination (HA) titers and cytopathic effects in duck embryo liver cells and chicken embryo liver (CEL) cells to investigate host adaptation. The D11-JW-017 strain propagated more in chicken embryo liver than the D11-JW-012 strain and the field isolate from chickens. Our results demonstrate the high prevalence of EDSV in wild and domestic ducks in South Korea and provide information on EDSV from ducks that showed variable adaptability in chickens.


Subject(s)
Adenoviridae Infections/veterinary , Atadenovirus , Ducks , Poultry Diseases/virology , Adenoviridae Infections/epidemiology , Adenoviridae Infections/virology , Animals , Animals, Wild , Atadenovirus/genetics , Phylogeny , Poultry Diseases/epidemiology , Republic of Korea/epidemiology
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