Publications by authors named "Atsushi Yamanaka"

79 Publications

Corticosteroids May Have Negative Effects on the Management of Patients with Severe Fever with Thrombocytopenia Syndrome: A Case-Control Study.

Viruses 2021 04 28;13(5). Epub 2021 Apr 28.

Department of Rheumatology, Infectious Diseases, and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever in China, Korea, and Japan. To date, no standardized treatment protocol for SFTS has been established. Corticosteroids (CS) may be administered to patients with SFTS and hemophagocytic syndrome, but its effectiveness and safety are still debatable. We conducted a retrospective case series review at four medical facilities in Miyazaki, Japan. Based on the medical records, clinical data, including the patients background, symptoms, physical findings, laboratory data at initial presentation, treatment, and outcome, were compared between the CS-treated and the non-CS-treated group. A total of 47 patients with confirmed SFTS in each hospital were enrolled in this study; there were 14 fatal cases and 33 nonfatal cases. The case fatality ratio was 29.8%. After adjusting patients' background by propensity score matching, the case fatality ratio was higher ( = 0.04) and complications of secondary infections, including invasive pulmonary aspergillosis, tended to be more frequent ( = 0.07) in the CS-treated group than in the non-CS-treated group. These data suggested that administration of CS to patients with SFTS should be carefully considered.
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http://dx.doi.org/10.3390/v13050785DOI Listing
April 2021

The Periodontium Damage Induces Neuronal Cell Death in the Trigeminal Mesencephalic Nucleus and Neurodegeneration in the Trigeminal Motor Nucleus in C57BL/6J Mice.

Acta Histochem Cytochem 2021 Feb 16;54(1):11-19. Epub 2021 Feb 16.

Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

Proprioception from masticatory apparatus and periodontal ligaments comes through the trigeminal mesencephalic nucleus (Vmes). We evaluated the effects of tooth loss on neurodegeneration of the Vmes and trigeminal motor nucleus (Vmo). Bilateral maxillary molars of 2-month-old C57BL/6J mice were extracted under anesthesia. Neural projections of the Vmes to the periodontium were confirmed by injecting Fluoro-Gold (FG) retrogradely into the extraction sockets, and for the anterograde labeling adeno-associated virus encoding green fluorescent protein (AAV-GFP) was applied. For immunohistochemistry, Piezo2, ATF3, Caspase 3, ChAT and TDP-43 antibodies were used. At 1 month after tooth extraction, the number of Piezo2-immunoreactive (IR) Vmes neurons were decreased significantly. ATF3-IR neurons were detected on day 5 after tooth extraction. Dead cleaved caspase-3-IR neurons were found among Vmes neurons on days 7 and 12. In the Vmo, neuronal cytoplasmic inclusions (NCIs) formation type of TDP-43 increased at 1 and 2 months after extraction. These indicate the existence of neural projections from the Vmes to the periodontium in mice and that tooth loss induces the death of Vmes neurons followed by TDP-43 pathology in the Vmo. Therefore, tooth loss induces Vmes neuronal cell death, causing Vmo neurodegeneration and presumably affecting masticatory function.
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http://dx.doi.org/10.1267/ahc.20-00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947638PMC
February 2021

A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome.

PLoS Negl Trop Dis 2021 Feb 22;15(2):e0009103. Epub 2021 Feb 22.

Department of Hematology, Clinical Immunology and Infectious Disease, Ehime University Graduate School of Medicine, Toon, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7-14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.
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http://dx.doi.org/10.1371/journal.pntd.0009103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899362PMC
February 2021

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Small-Animal Veterinarians and Nurses in the Japanese Prefecture with the Highest Case Load.

Viruses 2021 02 2;13(2). Epub 2021 Feb 2.

Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging tick-borne disease in East Asia, and is maintained in enzootic cycles involving ticks and a range of wild animal hosts. Direct transmission of SFTSV from cats and dogs to humans has been identified in Japan, suggesting that veterinarians and veterinary nurses involved in small-animal practice are at occupational risk of SFTSV infection. To characterize this risk, we performed a sero-epidemiological survey in small-animal-practice workers and healthy blood donors in Miyazaki prefecture, which is the prefecture with the highest per capita number of recorded cases of SFTS in Japan. Three small-animal-practice workers were identified as seropositive by ELISA, but one had a negative neutralization-test result and so was finally determined to be seronegative, giving a seropositive rate of 2.2% (2 of 90), which was significantly higher than that in healthy blood donors (0%, 0 of 1000; < 0.05). The seroprevalence identified here in small-animal-practice workers was slightly higher than that previously reported in other high-risk workers engaged in agriculture and forestry in Japan. Thus, enhancement of small-animal-practice workers' awareness of biosafety at animal hospitals is necessary for control of SFTSV.
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http://dx.doi.org/10.3390/v13020229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912989PMC
February 2021

A potent neutralizing mouse monoclonal antibody specific to dengue virus type 1 Mochizuki strain recognized a novel epitope around the N-67 glycan on the envelope protein: A possible explanation of dengue virus evolution regarding the acquisition of N-67 glycan.

Virus Res 2021 Mar 31;294:198278. Epub 2020 Dec 31.

Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.

The analysis of neutralizing epitope of dengue virus (DENV) is important for the development of an effective dengue vaccine. A potent neutralizing mouse monoclonal antibody named 7F4 was previously reported and, here, we further analyzed the detailed epitope of this antibody. 7F4 recognized a novel conformational epitope close to the N-67 glycan on the envelope protein. This antibody was specific to the DENV that lacks N-67 glycan, including the Mochizuki strain. Interestingly, the Mochizuki strain acquired N-67 glycan by 7F4 selective pressure. Considering that most of the currently circulating DENVs possess N-67 glycan, DENVs may have evolved to escape from antibodies targeting 7F4 epitope, suggesting the potency of this neutralizing epitope. In addition, this study demonstrated the existence of the epitopes close to 7F4 epitope and their crucial role in neutralization. In conclusion, the epitopes close to the N-67 glycan are attractive targets for the dengue vaccine antigen. Further analysis of this epitope is warranted.
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http://dx.doi.org/10.1016/j.virusres.2020.198278DOI Listing
March 2021

Tensile, compressive, and fatigue strength of a quasi-isotropic carbon fiber reinforced plastic laminate with a punched hole.

Heliyon 2020 Dec 10;6(12):e05690. Epub 2020 Dec 10.

Department of Mechanical Engineering, College of Industrial Technology, Nihon University, 1-2-1 Izumicho, Narashino, Chiba, 275-8575, Japan.

The mechanical properties of a quasi-isotropic carbon fiber reinforced plastic (CFRP) laminate with a punched hole were investigated. During the punching process, pressure was applied to the laminate through the upper and lower blank holders of a punching machine; the clearance between the punch and blank holders was set to be small to suppress damage in the CFRP laminates. Due to the dragging of plies encountered during punching, the surface of the punched hole was relatively uneven as compared to that of the drilled hole. However, the effect of the uneven surface created during the punching process was not as significant on the tensile and compressive strength of the open hole as compared to the manufacturing damages generated by drilling processes. The stress-number of cycles to failure curves for the open-hole tension-tension fatigue tests also showed comparable results between the punched- and drilled-hole specimens. These results indicate that there were no significant differences in the mechanical properties of CFRP laminates with a punched hole, and thus present the possibility of a highly productive hole-making process using the punching method.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733007PMC
December 2020

Direct Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from Domestic Cat to Veterinary Personnel.

Emerg Infect Dis 2020 12;26(12):2994-2998

Two veterinary personnel in Japan were infected with severe fever with thrombocytopenia syndrome virus (SFTSV) while handling a sick cat. Whole-genome sequences of SFTSV isolated from the personnel and the cat were 100% identical. These results identified a nosocomial outbreak of SFTSV infection in an animal hospital without a tick as a vector.
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http://dx.doi.org/10.3201/eid2612.191513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706950PMC
December 2020

A Novel Sub-Lineage of Chikungunya Virus East/Central/South African Genotype Indian Ocean Lineage Caused Sequential Outbreaks in Bangladesh and Thailand.

Viruses 2020 11 17;12(11). Epub 2020 Nov 17.

Mahidol-Osaka Center for Infectious Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

In recent decades, chikungunya virus (CHIKV) has become geographically widespread. In 2004, the CHIKV East/Central/South African (ECSA) genotype moved from Africa to Indian ocean islands and India followed by a large epidemic in Southeast Asia. In 2013, the CHIKV Asian genotype drove an outbreak in the Americas. Since 2016, CHIKV has re-emerged in the Indian subcontinent and Southeast Asia. In the present study, CHIKVs were obtained from Bangladesh in 2017 and Thailand in 2019, and their nearly full genomes were sequenced. Phylogenetic analysis revealed that the recent CHIKVs were of Indian Ocean Lineage (IOL) of genotype ECSA, similar to the previous outbreak. However, these CHIKVs were all clustered into a new distinct sub-lineage apart from the past IOL CHIKVs, and they lacked an alanine-to-valine substitution at position 226 of the E1 envelope glycoprotein, which enhances CHIKV replication in . Instead, all the re-emerged CHIKVs possessed mutations of lysine-to-glutamic acid at position 211 of E1 and valine-to-alanine at position 264 of E2. Molecular clock analysis suggested that the new sub-lineage CHIKV was introduced to Bangladesh around late 2015 and Thailand in early 2017. These results suggest that re-emerged CHIKVs have acquired different adaptations than the previous CHIKVs.
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http://dx.doi.org/10.3390/v12111319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698486PMC
November 2020

Impact of C-Reactive Protein Levels on Differentiating of Severe Fever With Thrombocytopenia Syndrome From Japanese Spotted Fever.

Open Forum Infect Dis 2020 Nov 7;7(11):ofaa473. Epub 2020 Oct 7.

Department of Rheumatology, Infectious Diseases, and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever in China, Korea, and Japan. Japanese spotted fever (JSF), which belongs to spotted fever group rickettsioses, is also endemic to Western Japan. Patients with SFTS and those with JSF display many of the same clinical manifestations. Sudden fever, rash, tick bite, and neurological and gastrointestinal symptoms may be seen in both infections, but the frequency and severity of each disease have not been compared and studied. Because laboratory confirmation of pathogens takes time, it is important to predict diagnosis of SFTS vs JSF based on the features of the clinical characteristics at the initial presentation, particularly in primary care settings.

Methods: We conducted a case series review at 4 medical facilities in Miyazaki, Japan. Based on the medical records, clinical and laboratory characteristics were compared between patients with SFTS and those with JSF.

Results: Eighty-one patients were enrolled in this study, including 41 with SFTS and 40 with JSF. The absence of rash (< .001), leukopenia (< .001), and normal C-reactive protein (CRP) levels (< .001) were the variables distinguishing SFTS from JSF. Normal CRP levels (≤1.0 mg/dL) had a 95% sensitivity (84%-99%) and 97% specificity (87%-100%) for SFTS, with a positive likelihood ratio of 37.1 (5.35-257).

Conclusions: Normal serum CRP levels were shown to differentiate SFTS from JSF with a very high probability.
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http://dx.doi.org/10.1093/ofid/ofaa473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651123PMC
November 2020

Dengue virus susceptibility in novel immortalized myeloid cells.

Heliyon 2020 Nov 3;6(11):e05407. Epub 2020 Nov 3.

Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Human dendritic cells (DCs) are the main target cells of dengue virus (DENV). Because humans injected with even a small volume of DENV from mosquito saliva display a high level of viremia, DCs are expected to be highly susceptible to DENV. In the present study, we assessed the efficiency of DENV infection using the novel immortalized human myeloid cell lines iPS-ML and iPS-DC. To prepare the DC-like myeloid cell line (iPS-DC), iPS-ML cells were cultured in the presence of IL-4 for 72 h. iPS-DC cells were the most susceptible to DENV, followed by iPS-ML, Vero and K562 cells. In contrast, the highest infective yield titer was observed in Vero cells. To investigate further uses of iPS-ML and iPS-DC, these cells were applied to an assay measuring antibody-dependent enhancement (ADE) activity in DENV infection. Serum samples collected from healthy Thai participants and mouse monoclonal antibodies displayed similar ADE activity patterns when examined with iPS-ML, iPS-DC, or K562 cells, the last of which are usually used in conventional ADE assays. Interestingly, iPS-ML cells showed greater susceptibility to ADE activity than iPS-DC and K562 cells. Here, we demonstrated the potential utility of the novel immortalized human myeloid cell lines iPS-ML and iPS-DC in future research on DENV.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644905PMC
November 2020

The effect of eleutherococcus senticosus on metabolism-associated protein expression in 3T3-L1 and C2C12 cells.

Phys Act Nutr 2020 Sep 30;24(3):13-18. Epub 2020 Sep 30.

Bizen Chemical Co., Ltd., Akaiwa, Okayama, Japan.

Purpose: In vivo studies have demonstrated the ergogenic benefits of eleutherococcus senticosus (ES) supplementation. ES has been observed to enhance endurance capacity, improve cardiovascular function, and alter metabolic functions (e.g., increased fat utilization); however, the exact mechanisms involved remain unknown. We aimed to determine whether ES could effectively induce fat loss and improve muscle metabolic profiles through increases in lipolysis- and lipid metabolism-associated protein expression in 3T3-L1 adipocytes and C2C12 skeletal muscle cells, respectively, to uncover the direct effects of ES on adipocytes and skeletal muscle cells.

Methods: Different doses of ES extracts (0.2, 0.5, and 1.0 mg/mL) were added to cells (0.2 ES, 0.5 ES, and 1.0 ES, respectively) for 72 h and compared to the vehicle control (control).

Results: The intracellular triacylglycerol (TG) content significantly decreased (p < 0.05 for 0.2 ES, p < 0.01 for 0.5 ES and 1.0 ES) in 3T3-L1 cells. Adipose triglyceride lipase, which is involved in active lipolysis, was significantly higher in the 1.0 ES group than in the control group (p < 0.01) of 3T3-L1 adipocytes. In C2C12 cells, the mitochondrial protein voltage-dependent anion channel (VDAC) was significantly increased in the 1.0 ES group (p < 0.01). Furthermore, we found that 1.0 ES activated both 5' AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in skeletal muscle cells (p < 0.01).

Conclusion: These findings suggest that ES extracts decreased TG content, presumably by increasing lipase in adipocytes and metabolism-associated protein expression as well as mitochondrial biogenesis in muscle cells. These effects may corroborate previous in vivo findings regarding the ergogenic effects of ES supplementation.
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http://dx.doi.org/10.20463/pan.2020.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669464PMC
September 2020

Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer's Disease in 3×Tg-AD Model Mice.

J Alzheimers Dis 2020 ;76(4):1443-1459

Laboratory of Neurodegenerative Diseases, chool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.

Background: The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs.

Objective: We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-β (Aβ) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function.

Methods: The molars of 3×Tg-AD mice were extracted, and the mice were reared for one week to 4 months. Immunohistochemical analysis, and spatial learning/memory assessment using the Barnes maze were carried out.

Results: In 4-month-old 3×Tg-AD mice, aggregated cytotoxic Aβ42 was found in granules in Vmes neurons. Neuronal death in the Vmes occurred after tooth extraction, resulting in the release of cytotoxic Aβ42 and an increase in CD86 immunoreactive microglia. Released Aβ42 damaged the LC, in turn inducing a significant reduction in hippocampal neurons in the CA1 and CA3 regions receiving projections from the LC. Based on spatial learning/memory assessment, after the tooth extraction in the 4-month-old 3×Tg-AD mice, increased latency was observed in 5-month-old 3×Tg-AD mice 1 month after tooth extraction, which is similar increase of latency observed in control 8-month-old 3×Tg-AD mice. Measures of cognitive deficits suggested an earlier shift to dementia-like behavior after tooth extraction.

Conclusion: These findings suggest that tooth extraction in the predementia stage can trigger the spread of neurodegeneration from the Vmes, LC, and hippocampus and accelerate the onset of dementia.
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http://dx.doi.org/10.3233/JAD-200257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505011PMC
January 2020

Clinical Evaluation of Endoscopic Bronchial Occlusion with an Endobronchial Watanabe Spigot for the Management of Intractable Pneumothorax, Pyothorax with Bronchial Fistula, and Postoperative Air Leakage.

Intern Med 2020 Aug 30;59(15):1835-1839. Epub 2020 Apr 30.

Department of Surgery, Miyazaki Prefectural Miyazaki Hospital, Japan.

Objective The present study aimed to evaluate the clinical effectiveness of endoscopic bronchial occlusion (EBO) with endobronchial Watanabe spigots (EWSs) for the management of prolonged pulmonary air leaks, such as intractable pneumothorax, pyothorax with bronchial fistula, and postoperative air leakage. Methods This was a retrospective study. Between April 2005 and March 2018, we recruited 21 patients with intractable pneumothorax (10 cases), pyothorax with bronchial fistula (7 cases), and postsurgical pulmonary fistula (4 cases) in whom appropriate drainage for 2 weeks had been unsuccessful and who were unsuitable for surgery. An EWS was inserted using a flexible bronchoscope via an endotracheal or a tracheostomy tube. Results The mean number of sessions with EWS procedures was 1.94, and the mean number of inserted EWS per patient was 6.5. In addition to EWS procedures, pleural washing and pleural adhesion therapy were performed in all cases with pyothorax, whereas pleural adhesion therapy was performed in three patients with pneumothorax. The successful treatment rate was 85.7%. Reduction of air leakage was observed in 19/21 patients. The mean duration of reduction of air leaks was 4.1 days (median, 1; range, 0-24 days) following EWS procedures. The mean duration from tube insertion to chest tube removal was 43.4 days (median, 29; range, 16-105 days). Complications included spigot migration and infection (aspergillosis); no complications caused significant mortality. Conclusion Performing EBO using an EWS appears to be a reasonable option for the management of intractable pneumothorax, pyothorax with pulmonary fistula, and postoperative air leakage.
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http://dx.doi.org/10.2169/internalmedicine.3900-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474981PMC
August 2020

Severe tracheal stenosis after first administration of pembrolizumab rescued by Dumon Y-stent in a lung cancer patient.

Respir Med Case Rep 2019 12;28:100923. Epub 2019 Aug 12.

Department of Anatomic Pathology, Miyazaki Prefectural Miyazaki, Hospital, 5-30 Kitatakamatsu-cho, Miyazaki-shi, Miyazaki, 880-8510, Japan.

A 70-year-old woman diagnosed with advanced, non-resectable programmed cell death ligand 1-positive-non-small-cell lung carcinoma was treated with pembrolizumab as first-line therapy. Soon after therapy initiation, she presented with severe dyspnea, and chest computed tomography revealed a soft tissue mass in the lower trachea of the right main bronchus. During bronchoscopy, she became severely hypoxic, and we performed endoscopic tumor ablation and Dumon Y-stent placement. We considered this severe deterioration caused by pseudoprogression, and suggest that it is necessary to perform bronchoscopy and to prepare for the bronchial intervention when treating patients with immune checkpoint inhibitors.
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http://dx.doi.org/10.1016/j.rmcr.2019.100923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704354PMC
August 2019

Intraperitoneal injection with dengue virus type 1-infected K562 cells results in complete fatality among immunocompetent mice.

Antiviral Res 2019 10 13;170:104560. Epub 2019 Jul 13.

BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400, Thailand; BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.

Dengue is one of the most important mosquito-borne viral diseases. Over half of the world's population is living in dengue endemic countries, where 100 million cases are estimated to occur annually. Although one dengue vaccine is currently available commercially, unfortunately its safety and efficacy has not been demonstrated for seronegative populations. Therefore, other vaccine candidates as well as antivirals are urgently required to control dengue diseases. To contribute to the development of preventative measures, in the present study we established an immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain. Following intraperitoneal injection with K562 cells infected with Mochizuki strain, all mice injected with ≥1 × 10 cells were killed within 7-11 days. Mice injected with ≥1 × 10 cells showed viremia (~10-10 FFU/ml) within 24 h of injection. Since a higher infective titer was detected in the mouse brain, this suggested that viruses were transmitted from the blood circulation into the brain. In further experiments, mice immunized with two types of DNA vaccines were challenged with virus. In contrast to the non-immunized control mice, all vaccinated mice survived after challenge. This immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain may be a useful tool to evaluate vaccines and preventive medicines against dengue virus.
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http://dx.doi.org/10.1016/j.antiviral.2019.104560DOI Listing
October 2019

Key Amino Acid Substitution for Infection-Enhancing Activity-Free Designer Dengue Vaccines.

iScience 2019 Mar 18;13:125-137. Epub 2019 Feb 18.

BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand; BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

Dengue is a globally important disease caused by four serotypes of dengue virus. Dengue vaccine development has been hampered by antigenic cross-reactivity among serotypes, which potentially causes antibody-dependent enhancement of infection and disease severity. Here we found that a single amino acid substitution in the envelope protein at position 87 from aspartic acid to asparagine or at position 107 from leucine to phenylalanine is critical for suppressing the induction of infection-enhancing antibody in a mouse model. The site and type of amino acid substitution were determined via neutralization escape using an enhancing-activity-only monoclonal antibody that was engineered to reveal neutralizing activity. Mutated dengue type 1 DNA vaccines containing either or both amino acid substitutions induced neutralizing antibodies devoid of enhancing activity against all serotypes. The effect of substitution was further demonstrated using other serotypes and a tetravalent formulation. This finding may contribute to the development of infection-enhancing-activity-free dengue vaccines.
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http://dx.doi.org/10.1016/j.isci.2019.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402262PMC
March 2019

Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand.

PLoS One 2018 12;13(11):e0207220. Epub 2018 Nov 12.

Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand.

Dengue is a mosquito-borne disease that has spread to over 100 countries. Dengue fever is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. DENV comprises 4 serotypes (DENV-1 to DENV-4), and each serotype is divided into distinct genotypes. Thailand is an endemic area where all 4 serotypes of DENV co-circulate. To understand the current genotype distribution of DENVs in Thailand, we enrolled 100 cases of fever with dengue-like symptoms at the Bamrasnaradura Infectious Diseases Institute during 2016-2017. Among them, 37 cases were shown to be dengue-positive by real-time PCR. We were able to isolate DENVs from 21 cases, including 1 DENV-1, 8 DENV-2, 4 DENV-3, and 8 DENV-4. To investigate the divergence of the viruses, RNA was extracted from isolated DENVs and viral near-whole genome sequences were determined. Phylogenetic analysis of the obtained viral sequences revealed that DENV-2 genotype Cosmopolitan was co-circulating with DENV-2 genotype Asian-I, the previously predominating genotype in Thailand. Furthermore, DENV-3 genotype III was found instead of DENV-3 genotype II. The DENV-2 Cosmopolitan and DENV-3 genotype III found in Thailand were closely related to the respective strains found in nearby countries. These results indicated that DENVs in Thailand have increased in genotypic diversity, and suggested that the DENV genotypic shift observed in other Asian countries also might be taking place in Thailand.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207220PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231660PMC
April 2019

High-throughput neutralization assay for multiple flaviviruses based on single-round infectious particles using dengue virus type 1 reporter replicon.

Sci Rep 2018 11 9;8(1):16624. Epub 2018 Nov 9.

Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.

Diseases caused by the genus Flavivirus, including dengue virus (DENV) and Zika virus (ZIKV), have a serious impact on public health worldwide. Due to serological cross-reactivity among flaviviruses, current enzyme-linked immunosorbent assay (ELISA) for IgM/G cannot reliably distinguish between infection by different flaviviruses. In this study, we developed a reporter-based neutralization assay using single-round infectious particles (SRIPs) derived from representative flaviviruses. SRIPs were generated by transfection of human embryonic kidney 293 T cells with a plasmid encoding premembrane and envelope (prME) proteins from DENV1-4, ZIKV, Japanese encephalitis virus, West Nile virus, yellow fever virus, Usutu virus, and tick-borne encephalitis virus, along with a plasmid carrying DENV1 replicon containing the luciferase gene and plasmid for expression of DENV1 capsid. Luciferase activity of SRIPs-infected cells was well correlated with number of infected cells, and each reporter SRIP was specifically neutralized by sera from mice immunized with each flavivirus antigen. Our high-throughput reporter SRIP-based neutralization assay for multiple flaviviruses is a faster, safer, and less laborious diagnostic method than the conventional plaque reduction neutralization test to screen the cause of primary flavivirus infection. The assay may also contribute to the evaluation of vaccine efficacy and assist in routine surveillance and outbreak response to flaviviruses.
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http://dx.doi.org/10.1038/s41598-018-34865-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226426PMC
November 2018

Human monoclonal antibodies against West Nile virus from Japanese encephalitis-vaccinated volunteers.

Antiviral Res 2018 06 14;154:58-65. Epub 2018 Apr 14.

Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan. Electronic address:

West Nile virus (WNV) is a positive-sense single-stranded RNA flavivirus belonging to the Japanese encephalitis virus (JEV) serocomplex of the Flaviviridae family and causes mosquito-borne infections. Although most human infection cases are asymptomatic, approximately one in 150 infected individuals develops meningoencephalitis, with a mortality rate of 4-14%. While the development of human neutralizing antibody therapeutics against WNV is strongly anticipated, WNV is difficult to study in conventional laboratories due to its high safety level requirement. In this study, we established fully human WNV-neutralizing monoclonal antibodies from the peripheral blood mononuclear cells of inactivated-JEV-vaccinated individuals, and these antibodies exhibited WNV neutralization both in vitro and in vivo. Our results demonstrate a new antibody cross-reactivity strategy to develop immunological therapeutic reagents for WNV and other JEV serotype viruses.
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http://dx.doi.org/10.1016/j.antiviral.2018.04.011DOI Listing
June 2018

Neuropeptides and ATP signaling in the trigeminal ganglion.

Jpn Dent Sci Rev 2017 Nov 15;53(4):117-124. Epub 2017 Mar 15.

Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

Peripheral nociceptive stimuli from orofacial structures are largely transmitted by the trigeminal nerve. According to the peripheral noxious stimuli, neurons in the trigeminal ganglion (TG) produce neuropeptides such as substance P, and calcitonin-gene-related peptide, etc. Beside the production of neuropeptides, there exists unique non-synaptic interaction system between maxillary and mandibular neurons in the TG. Neurons in the TG are surrounded by satellite glial cells (SGCs), which initially receive the signal from TG neurons. These activated SGCs secrete a transmitter to activate adjacent SGCs or TG neurons, thereby amplifying the signal, for example, from mandibular neurons to maxillary neurons in the TG. Similar to the dorsal root ganglion, in the TG, microglia/macrophage-like cells (MLCs) are activated by uptake of a transmitter from TG neurons or SGCs. This communication between neurons, SGCs, and MLCs results in responses such as ectopic pain, hyperesthesia, or allodynia. The focus of this review is the cooperative interaction of the maxillary and mandibular nerves in the TG by neuropeptides, and adenosine 3'-phosphate (ATP) signaling from neurons to SGCs and MLCs. Stimulated neurons either secrete ATP by means of vesicular nucleotide transporters, or secrete neuropeptides from the neuronal cell body to mediate signal transmission.
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http://dx.doi.org/10.1016/j.jdsr.2017.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703691PMC
November 2017

Dorsal and ventral parts of thalamic nucleus submedius project to different areas of rat orbitofrontal cortex: A single neuron-tracing study using virus vectors.

J Comp Neurol 2017 Dec 12;525(18):3821-3839. Epub 2017 Sep 12.

Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

The rodent orbitofrontal cortex is involved in a variety of cognitive and behavioral functions that require thalamic input to be successfully expressed. Although the thalamic nucleus submedius (Sm) is a major source of afferents to the orbitofrontal cortex, thalamocortical projection from the Sm has not been fully elucidated. In the present study, we first divided the rat Sm into dorsal and ventral parts according to the distribution of vesicular glutamate transporter 2-immunoreactive varicosities, which were somatosensory afferents from the brain stem. Subsequently we investigated dendritic and axonal arborizations of individual dorsal and ventral Sm neurons by visualizing the processes with Sindbis virus vectors expressing membrane-targeted fluorescent proteins. The number of dendritic processes of ventral Sm neurons was greater than that of dorsal Sm neurons. In the cerebral cortex, all the reconstructed Sm neurons sent axons primarily to layers 2-5. Interestingly, dorsal Sm neurons formed a single axon arbor exclusively within the ventrolateral orbital area, whereas ventral Sm neurons made two axon arbors in the lateral orbital and ventral orbital areas simultaneously. The spread of each axon arbor was 500-1000 µm in diameter in the direction tangential to the cortical surface. These results indicate that the dorsal and ventral Sm comprise two distinct thalamocortical pathways. The dorsal Sm pathway relay somatosensory information to the ventrolateral orbital area and may be involved in emotional and aversive aspects of nociceptive information processing, whereas the ventral Sm pathway seems to co-activate distant orbitofrontal cortical areas, and may link their functions under certain circumstances.
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http://dx.doi.org/10.1002/cne.24306DOI Listing
December 2017

Dorsal and Ventral Parts of Thalamic Nucleus Submedius Project to Different Areas of Rat Orbitofrontal Cortex: A Single Neuron-Tracing Study Using Virus Vectors.

J Comp Neurol 2017 Aug 22. Epub 2017 Aug 22.

Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.

The rodent orbitofrontal cortex is involved in a variety of cognitive and behavioral functions that require thalamic input to be successfully expressed. Although the thalamic nucleus submedius (Sm) is a major source of afferents to the orbitofrontal cortex, thalamocortical projection from the Sm has not been fully elucidated. In the present study, we first divided the rat Sm into dorsal and ventral parts according to the distribution of vesicular glutamate transporter 2-immunoreactive varicosities, which were somatosensory afferents from the brain stem. Subsequently we investigated dendritic and axonal arborizations of individual dorsal and ventral Sm neurons by visualizing the processes with Sindbis virus vectors expressing membrane-targeted fluorescent proteins. The number of dendritic processes of ventral Sm neurons was greater than that of dorsal Sm neurons. In the cerebral cortex, all the reconstructed Sm neurons sent axons primarily to layers 2-5. Interestingly, dorsal Sm neurons formed a single axon arbor exclusively within the ventrolateral orbital area, whereas ventral Sm neurons made two axon arbors in the lateral orbital and ventral orbital areas simultaneously. The spread of each axon arbor was 500-1000 µm in diameter in the direction tangential to the cortical surface. These results indicate that the dorsal and ventral Sm comprise two distinct thalamocortical pathways. The dorsal Sm pathway relay somatosensory information to the ventrolateral orbital area and may be involved in emotional and aversive aspects of nociceptive information processing, whereas the ventral Sm pathway seems to co-activate distant orbitofrontal cortical areas, and may link their functions under certain circumstances. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/cne.12646DOI Listing
August 2017

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata).

J Med Primatol 2017 06 3;46(3):93-100. Epub 2017 Apr 3.

Primate Research Institute, Kyoto University, Aichi, Japan.

Background: A 23-year-old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos.

Methods: The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia.

Results: The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin.

Conclusion: To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.
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http://dx.doi.org/10.1111/jmp.12261DOI Listing
June 2017

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

Jpn J Infect Dis 2017 Sep 28;70(5):579-581. Epub 2017 Mar 28.

BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University.

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.
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http://dx.doi.org/10.7883/yoken.JJID.2016.379DOI Listing
September 2017

Utility of Japanese encephalitis virus subgenomic replicon-based single-round infectious particles as antigens in neutralization tests for Zika virus and three other flaviviruses.

J Virol Methods 2017 05 20;243:164-171. Epub 2017 Feb 20.

BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University,420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand(3); BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.

The introduction of a foreign virus into an area may cause an outbreak, as with the Zika virus (ZIKV) outbreak in the Americas. Preparedness for handling a viral outbreak involves the development of tests for the serodiagnosis of foreign virus infections. We previously established a gene-based technology to generate some flaviviral antigens useful for functional antibody assays. The technology utilizes a Japanese encephalitis virus subgenomic replicon to generate single-round infectious particles (SRIPs) that possess designed surface antigens. In the present study, we successfully expanded the capacity of SRIPs to four human-pathogenic mosquito-borne flaviviruses that could potentially be introduced from endemic to non-endemic countries: ZIKV, Sepik virus, Wesselsbron virus, and Usutu virus. Flavivirus-crossreactive monoclonal antibodies dose-dependently neutralized these SRIPs. ZIKV-SRIPs also produced antibody-dose-dependent neutralization curves equivalent to those shown by authentic ZIKV particles using sera from a Zika fever patient. The faithful expression of designed surface antigens on SRIPs will allow their use in neutralization tests to diagnose foreign flaviviral infections.
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http://dx.doi.org/10.1016/j.jviromet.2017.02.011DOI Listing
May 2017

[A Case of Multiple Venous Thromboses Associated with Acute Cytomegalovirus Infection].

Kansenshogaku Zasshi 2017 Jan;91(1):20-4

A previously healthy 44-year-old male presented with fever, abdominal pain, liver dysfunction and lymphadenopathy. He was diagnosed as having acute cytomegalovirus (CMV) infection with elevated CMV-IgG and IgM, and observed with supportive therapy. He was admitted to our hospital with prolonged fever lasting for a month. Enhanced CT revealed multiple thromboses in the right pulmonary artery and superior mesenteric vein. Follow-up CT after one week revealed new-onset thromboses in the left pulmonary artery and common iliac vein. Screening tests for thrombophilia were negative. His symptoms were improved with anticoagulant therapy with intravenous heparin, followed by oral warfarin. He was discharged on admission day 28 with good condition. Follow-up CT after 6 months revealed complete resolution of the thromboses. Anticoagulant therapy was stopped after 9 months, and he has been well without recurrence. Though vascular thrombosis is a rare complication, we must be alert to the signs and symptoms of thrombosis in patients with acute CMV infection.
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January 2017

Neutralizing and enhancing antibody responses to five genotypes of dengue virus type 1 (DENV-1) in DENV-1 patients.

J Gen Virol 2017 02 24;98(2):166-172. Epub 2017 Feb 24.

BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

Dengue virus (DENV) has four distinct serotypes, DENV-1-4, with four to six genotypes in each serotype. The World Health Organization recommends tetravalent formulations including one genotype of each serotype as safe and effective dengue vaccines. Here, we investigated the impact of genotype on the neutralizing antibody responses to DENV-1 in humans. Convalescent sera collected from patients with primary infection of DENV-1 were examined for neutralizing antibody against single-round infectious particles of the five DENV-1 genotypes (GI-GV). In both GI- and GIV-infected patients, their neutralizing antibody titres against the five genotypes were similar, differing ≤4-fold from the homogenotypic responses. The enhancing activities against the five genotypes were also similar in these sera. Thus, the genotype strains of DENV-1 showed no significant antigenic differences in these patients, suggesting that GI- or GIV-derived vaccine antigens should induce equivalent levels of neutralizing antibodies against all DENV-1 genotypes.
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http://dx.doi.org/10.1099/jgv.0.000669DOI Listing
February 2017

Complement-independent dengue virus type 1 infection-enhancing antibody reduces complement-dependent and -independent neutralizing antibody activity.

Vaccine 2016 12 17;34(51):6449-6457. Epub 2016 Nov 17.

BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. Electronic address:

Dengue fever and dengue hemorrhagic fever are globally important mosquito-transmitted viral diseases. However, the only licensed vaccine is not highly protective. Viremia is related to disease severity in infected humans, and it is thought to be reduced by neutralizing antibodies but increased by infection-enhancing antibodies. We established an assay system to measure the balance between neutralizing and enhancing antibodies and found that most dengue-immune individuals in endemic areas carry complement-independent enhancing antibodies (CiEAb). Studying CiEAb is important for dengue vaccine development because the enhancing activity of CiEAb does not decrease in the presence of complement, which can reduce the enhancing activity of other antibodies in vitro. Here, we investigated the effects of CiEAb on the activity of neutralizing antibodies (mainly, complement-dependent neutralizing antibodies; CdNAb) using cocktails of mouse monoclonal antibodies (MAbs) against dengue virus type 1 (DENV-1). These cocktails included MAbs with enhancing activity only (represented by D1-V-3H12 [3H12]) or neutralizing activity only (represented by D1-IV-7F4 [7F4]). Because 3H12, an IgG1 subclass antibody, is complement-independent and cross-reacted with all dengue serotypes, it is a suitable model of CiEAb. An approximately equal amount of 3H12 abolished the neutralizing activity of 7F4. The complement-dependent neutralizing activities of the IgG2a and IgG2b variants of 7F4 were also completely inhibited by ⩾3-fold concentrations of the IgG1 variant. The complement-dependent antibody activities of other anti-DENV-1 MAbs and those of MAbs directed against other serotypes were inhibited 50% by 3H12 at various mixing ratios, ranging from one-hundredth to 10-fold. The complement-dependent neutralizing activities of dengue-immune mouse ascites fluids were also effectively inhibited by 3H12. This suggests that concomitantly induced CiEAb exerts an unwanted effect on the protective capacity of a vaccine. Thus, the effective inhibition of the neutralizing activity of CdNAb by CiEAb has implications for dengue pathogenesis and vaccine development.
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http://dx.doi.org/10.1016/j.vaccine.2016.11.021DOI Listing
December 2016

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

J Comp Neurol 2017 01 14;525(1):166-185. Epub 2016 Jul 14.

Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/cne.24054DOI Listing
January 2017

[Streptococcal Toxic Shock-like Syndrome due to Streptococcus suis Serotype 2 in a Japanese Pig Farmer].

Kansenshogaku Zasshi 2015 Nov;89(6):741-4

Streptococcus suis is a major swine pathogen. It has recently been recognized as an emerging zoonosis that causes mainly meningitis and sepsis in human. In particular, toxic shock-like syndrome (TSLS) caused by this pathogen has a high mortality rate. However, misidentification of S. suis by conventional biochemical and commercial identification tests is not rare. The patient was a 71-year-old man who worked as a pig farmer who was admitted for fever, oliguria and subcutaneous hemorrhage. He was diagnosed as having septic shock and blood culture was positive for Gram-positive cocci, mainly diplococcus. This pathogen was identified with S. suis with using MALDI-TOF MS analysis, though a commercial Gram-Positive bacteria identification kit revealed viridans streptococci. His clinical features met the diagnostic criteria of TSLS, and ceftriaxone and clindamycin were administered. On admission day 28, he was discharged in good condition.
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http://dx.doi.org/10.11150/kansenshogakuzasshi.89.741DOI Listing
November 2015