Publications by authors named "Yoshitaka Goto"

74 Publications

Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette-Guérin.

Tuberculosis (Edinb) 2021 Mar 4;128:102067. Epub 2021 Mar 4.

Japan BCG Laboratory, 3-1-5, Matsuyama, Kiyose-shi, Tokyo, 204-0022, Japan.

Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette-Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early childhood. Therefore, we first devised a system to assess the efficacy of a candidate booster vaccine. Specifically, variant strain BCG-II, a minor component of BCG-Tokyo strain, which elicits weak immunity, was administered to guinea pigs. Vaccine-induced immunity and protection against Mycobacterium tuberculosis (Mtb) infection were evaluated using skin delayed-type hypersensitivity (DTH) and Mtb colony forming unit counts in organs, respectively. Candidate booster vaccine containing the mycobacterial DNA-binding protein 1 (MDP1) as antigen and CpG oligodeoxynucleotide G9.1 as adjuvant increased T-bet expression and IFN-γ production in human peripheral blood mononuclear cells. Intradermal administration of MDP1 or MDP1 and G9.1 to unimmunized guinea pigs produced DTH on MDP1-inoculated skin. Boosting BCG-II-primed guinea pigs with this protocol effectively enhanced DTH against MDP1 and protection against Mtb infection, particularly when combined with G9.1. The candidate vaccine may contribute to efforts to prevent tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tube.2021.102067DOI Listing
March 2021

Suppurative necrotizing bronchopneumonia caused by Nocardia cyriacigeorgica infection in a stranded striped dolphin (Stenella coeruleoalba) in Japan.

J Vet Med Sci 2021 Jan 11;83(1):146-150. Epub 2020 Dec 11.

Laboratory of Veterinary Pathology, Faculty of Agriculture, University of Miyazaki, Nishi 1-1, Gakuen-Kibana, Miyazaki 889-2192, Japan.

On a coastline in Miyazaki Prefecture, Japan, a wild subadult female striped dolphin was found dead. Necropsy revealed poor nutritional status and bilateral pneumonia, which was histologically diagnosed as severe suppurative necrotizing bronchopneumonia. Special staining detected numerous intralesional filamentous, branching bacteria, which was identified as Nocardia cyriacigeorgica by sequencing of 16S ribosomal RNA and gyrB genes. Other main histological findings included lymphoid depletion in the spleen and superficial cervical and pulmonary lymph nodes. Suppurative nocardiosis without a granulomatous reaction is uncommon, and it is assumed its pathogenesis was related to the host's immune status. This paper discusses the variable inflammatory response to nocardiosis and describes the first case of N. cyriacigeorgica infection in a wild striped dolphin in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.20-0234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870406PMC
January 2021

Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients.

Sci Rep 2020 09 21;10(1):15367. Epub 2020 Sep 21.

Department of Radiology, Mie University Hospital, Tsu, Japan.

Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72417-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506012PMC
September 2020

Cardiovascular magnetic resonance feature tracking for characterization of patients with heart failure with preserved ejection fraction: correlation of global longitudinal strain with invasive diastolic functional indices.

J Cardiovasc Magn Reson 2020 06 4;22(1):42. Epub 2020 Jun 4.

Departments of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Background: Left ventricular (LV) diastolic dysfunction is the main cause of heart failure with preserved ejection fraction (HFpEF), and is characterized by LV stiffness and relaxation. Abnormal LV global longitudinal strain (GLS) is frequently observed l in HFpEF, and was shown to be useful in identifying HFpEF patients at high risk for a cardiovascular event. Cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT) enables the reproducible and non-invasive assessment of global strain from cine CMR images. However, the association between GLS and invasively measured parameters of diastolic function has not been investigated. We sought to determine the prevalence and severity of GLS impairment in patients with HFpEF by using CMR-FT, and to evaluate the correlation between GLS measured by CMR-FT and that measured by invasive diastolic functional indices.

Methods: Eighteen patients with HFpEF and 18 age- and sex-matched healthy control subjects were studied. All subjects underwent cine, pre- and post-contrast T1 mapping and late gadolinium-enhancement CMR. In the HFpEF patients, invasive pressure-volume loops were obtained to evaluate LV diastolic properties. GLS was quantified from cine CMR, and extracellular volume fraction (ECV) was quantified from pre- and post-contrast T1 mapping as a known imaging biomarker for predicting LV stiffness.

Results: GLS was significantly impaired in patients with HFpEF (- 14.8 ± 3.3 vs.-19.5 ± 2.8%, p < 0.001). Thirty nine percent (7/18) of HFpEF patients showed impaired GLS with a cut-off of - 13.9%. Statistically significant difference was found in ECV between HFpEF patients and controls (32.2 ± 3.8% vs. 29.9 ± 2.6%, p = 0.044). In HFpEF patients, the time constant of active LV relaxation (Tau) was strongly correlated with GLS (r = 0.817, p < 0.001), global circumferential strain (GCS) (r = 0.539, p = 0.021) and global radial strain (GRS) (r = - 0.552, p = 0.017). Multiple linear regression analysis revealed GLS as the only independent predictor of altered Tau (beta = 0.817, p < 0.001) among age, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, GCS, GRS and GLS.

Conclusions: CMR-FT is a noninvasive approach that enables identification of the subgroup of HFpEF patients with impaired GLS. CMR LV GLS independently predicts abnormal invasive LV relaxation index Tau measurements in HFpEF patients. These findings suggest that feature-tracking CMR analysis in conjunction with ECV, may enable evaluation of diastolic dysfunction in patients with HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-020-00636-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271439PMC
June 2020

Feasibility of extracellular volume fraction calculation using myocardial CT delayed enhancement with low contrast media administration.

J Cardiovasc Comput Tomogr 2020 Nov - Dec;14(6):524-528. Epub 2020 Feb 15.

Department of Radiology, Mie University Hospital, Tsu, Japan.

Background: Myocardial extracellular volume fraction (ECV) derived from CT delayed enhancement (CTDE) may allow assessment of diffuse myocardial fibrosis. However, the amount of contrast medium required for ECV estimation has not been established. Since ECV estimation by CT is typically performed in combination with coronary CT angiography (CCTA) in clinical settings, we aimed to investigate whether reliable ECV estimation is possible using the contrast dose optimized for CCTA without additional contrast administration.

Methods: Twenty patients with known or suspected coronary artery disease who underwent CTDE with a dual-source scanner using two protocols (Protocols A and B) within 2 years were retrospectively enrolled. In Protocol A, CTDE was obtained with 0.84 ml/kg of iopamidol (370 mgI/ml) injected for CCTA. In Protocol B, stress CT perfusion imaging, which requires 40 ml of contrast medium, was added to Protocol A. ECV values calculated from the two protocols were compared.

Results: Despite the different contrast doses, no significant difference in mean myocardial ECV was seen between Protocols A and B at the patient level (28.7 ± 4.3% vs. 28.7 ± 4.4%, respectively, P = 0.868). Excellent correlations in ECV were seen between the two protocols (r = 0.942, P < 0.001). Bland-Altman analysis showed slight bias (+0.06%), within a 95% limit of agreement of -2.9% and 3.0%. The coefficient of variation was 5.2%.

Conclusion: Reliable ECV estimation can be achieved with the contrast doses optimized for CCTA. Despite the differing contrast administration schemes and doses, ECV values calculated from the two protocols showed excellent agreement, indicating the robustness of ECV estimation by CT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcct.2020.01.013DOI Listing
January 2021

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement.

JACC Cardiovasc Imaging 2020 08 12;13(8):1721-1734. Epub 2020 Feb 12.

Department of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

Objectives: This study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.

Background: The prognostic value of stress dynamic CTP with CTDE is unknown.

Methods: Participants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.

Results: During a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).

Conclusions: Stress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2019.12.017DOI Listing
August 2020

Myocardial Coverage and Radiation Dose in Dynamic Myocardial Perfusion Imaging Using Third-Generation Dual-Source CT.

Korean J Radiol 2020 01;21(1):58-67

Department of Radiology, Mie University Hospital, Mie, Japan.

Objective: Third-generation dual-source computed tomography (3rd-DSCT) allows dynamic myocardial CT perfusion imaging (dynamic CTP) with a 10.5-cm z-axis coverage. Although the increased radiation exposure associated with the 50% wider scan range compared to second-generation DSCT (2nd-DSCT) may be suppressed by using a tube voltage of 70 kV, it remains unclear whether image quality and the ability to quantify myocardial blood flow (MBF) can be maintained under these conditions. This study aimed to compare the image quality, estimated MBF, and radiation dose of dynamic CTP between 2nd-DSCT and 3rd-DSCT and to evaluate whether a 10.5-cm coverage is suitable for dynamic CTP.

Materials And Methods: We retrospectively analyzed 107 patients who underwent dynamic CTP using 2nd-DSCT at 80 kV (n = 54) or 3rd-DSCT at 70 kV (n = 53). Image quality, estimated MBF, radiation dose, and coverage of left ventricular (LV) myocardium were compared.

Results: No significant differences were observed between 3rd-DSCT and 2nd-DSCT in contrast-to-noise ratio (37.4 ± 11.4 vs. 35.5 ± 11.2, = 0.396). Effective radiation dose was lower with 3rd-DSCT (3.97 ± 0.92 mSv with a conversion factor of 0.017 mSv/mGy·cm) compared to 2nd-DSCT (5.49 ± 1.36 mSv, < 0.001). Incomplete coverage was more frequent with 2nd-DSCT than with 3rd-DSCT (1.9% [1/53] vs. 56% [30/54], < 0.001). In propensity score-matched cohorts, MBF was comparable between 3rd-DSCT and 2nd-DSCT in non-ischemic (146.2 ± 26.5 vs. 157.5 ± 34.9 mL/min/100 g, = 0.137) as well as ischemic myocardium (92.7 ± 21.1 vs. 90.9 ± 29.7 mL/min/100 g, = 0.876).

Conclusion: The radiation increase inherent to the widened z-axis coverage in 3rd-DSCT can be balanced by using a tube voltage of 70 kV without compromising image quality or MBF quantification. In dynamic CTP, a z-axis coverage of 10.5 cm is sufficient to achieve complete coverage of the LV myocardium in most patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2019.0323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960309PMC
January 2020

Extended-spectrum β-lactamase-producing isolated from healthy Thoroughbred racehorses in Japan.

J Equine Sci 2019 Sep 2;30(3):47-53. Epub 2019 Oct 2.

Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.

Extended-spectrum β-lactamase-producing (ESBLEC) have become a major health concern in both human and veterinary medicine. These bacteria could become a critical problem in equine medicine due to the limited number of antimicrobial drugs available. However, there are no previous reports of ESBLEC isolated from horses in Japan. The objectives of this study were to investigate the occurrence of ESBLEC isolated from feces in healthy Thoroughbred racehorses in Japan. Feces samples were collected from 147 healthy Thoroughbred racehorses by equine veterinarians at the Japan Racing Association (103 from Miho Training Center and 44 from Ritto Training Center) between March 2017 and April 2018. Samples were screened for ESBLECs using MacConkey agar supplemented with 1 µg/ml cefotaxime. Detection of ESBL genes was performed by PCR and confirmed by DNA sequencing. Horizontal transmission was demonstrated by conjugation assay. In this study, 24 ESBLECs were isolated from twelve horse feces samples (8.2%). All ESBLECs harbored bla, and both bla and bla were detected in nine isolates (37.5%). ESBLECs showed resistance to all β-lactam antibiotics (100%) tested, followed by trimethoprim (66.7%), streptomycin (62.5%), tetracycline (25.0%), and oxytetracycline (25.0%). Horizontal transmission was successfully demonstrated by conjugation assay in eight of 13 isolates, and bla was detected by PCR in all transconjugants. This study showed that racehorses in Japan are potential reservoirs of ESBLECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1294/jes.30.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773619PMC
September 2019

Co-infection of epithelial cells established from the upper and lower bovine respiratory tract with bovine respiratory syncytial virus and bacteria.

Vet Microbiol 2019 Aug 12;235:80-85. Epub 2019 Jun 12.

Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan; Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan. Electronic address:

Bovine respiratory disease complex is a major disease affecting the global cattle industry. Multiple infections by viruses and bacteria increase disease severity. Previously, we reported that bovine respiratory syncytial virus (BRSV) infection increases adherence of Pasteurella multocida to human respiratory and bovine kidney epithelial cells. To examine the interaction between the virus and bacteria in bovine respiratory cells, we generated respiratory epithelial cell lines from bovine trachea (bTEC), bronchus (bBEC), and lung (bLEC). Although all established cell lines were infected by BRSV and P. multocida susceptibility differed according to site of origin. The cells derived from the lower respiratory tract (bBEC and bLEC) were significantly more susceptible to BRSV than those derived from the upper respiratory tract (bTEC). Pre-infection of bBEC and bLEC with BRSV increased adherence of P. multocida; this was not the case for bTEC. These results indicate that BRSV may reproduce better in the lower respiratory tract and encourage adherence of bacteria. Thus, we identify one possible mechanism underlying severe pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetmic.2019.06.010DOI Listing
August 2019

Genotyping of swine Mycobacterium avium subsp. hominissuis isolates from Kyushu, Japan.

J Vet Med Sci 2019 Aug 3;81(8):1074-1079. Epub 2019 Jun 3.

Laboratory of Veterinary Microbiology, Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai Nishi, Miyazaki, Miyazaki 889-2192, Japan.

The incidence of diseases caused by nontuberculous mycobacteria (NTM) is increasing annually worldwide, including Japan. Mycobacterium avium subsp. hoiminissuis (MAH) is one of the most common NTM species responsible for chronic lung diseases in animals and humans. In the current study, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was employed to characterize the genetic diversity of swine MAH isolates from Kyushu, Japan. In total, 309 isolates were obtained from the lymph nodes of 107 pigs not displaying any clinical signs of disease, of which 307 were identified as MAH, comprising 173 strains. Based on eight established MIRU-VNTR loci, the MAH strains represented 50 genotypes constituting three lineages, and 29 had not been described in the Mac French National Institute for Agricultural Research Nouzilly MIRU-VNTR (Mac-INMV) database. MAH was the dominant M. avium complex (MAC) in pigs from Kyushu, and there was high genetic diversity among genotype profiles of MAH from Kyushu. We identified three predominant genotype profiles in the tested area sharing high relatedness with genotype profiles of strains isolated in European countries. MAH was the most common NTM in pigs from Kyushu and exhibited high diversity, with new strain-derived genotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715914PMC
August 2019

Comparison of the different imaging time points in delayed phase cardiac CT for myocardial scar assessment and extracellular volume fraction estimation in patients with old myocardial infarction.

Int J Cardiovasc Imaging 2019 May 18;35(5):917-926. Epub 2018 Dec 18.

Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Delayed enhancement cardiac CT is a potential tool for myocardial viability assessment and is essential for extracellular volume fraction (ECV) estimation with CT. The objective of this study is to determine the optimal delay time for acquisition of delayed CT scans. Thirty-five patients with enhancement pattern typical of previous myocardial infarction on delayed CT and 17 control subjects comprised the study population. Delayed scans were acquired at 3, 5 and 7 min after contrast material injection. Image quality and estimated ECV were compared among the three time points. Delayed CT at 5 min showed the highest signal-to-noise ratio of 15.2 ± 1.0 [p < 0.0001; vs. 3 min (13.6 ± 1.0), p = 0.0015; vs. 7 min (14.9 ± 1.0)]. Contrast-to-noise ratio of infarcted and remote myocardium was highest at 7 min (6.4 ± 2.5), but was not significantly different from 5 min (6.1 ± 2.2, p = 0.08). The ECV values were constant over the three time points, although, in segments containing infarcted myocardium, trend of lower values was noted at 3 min compared to 5 and 7 min. ECV values at 5 min was 27.1% ± 2.1% in control subjects, 27.2% ± 3.0% in remote segments of patients with infarction, and 39.6% ± 5.3% in segments containing infarcted myocardium. Myocardial scars are equally best visualized with delay time of 5 and 7 min post contrast administration. No significant difference was observed in ECV of healthy myocardium or focal scars among delay time of 3, 5, and 7 min. Delay time of 5 min after contrast injection may be recommended for CT delayed enhancement imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-018-1513-zDOI Listing
May 2019

Full genome analysis of bovine papillomavirus type 1 derived from a calf with severe cutaneous multiple papillomatosis.

J Vet Med Sci 2018 Nov 12;80(11):1691-1695. Epub 2018 Sep 12.

Division of Infection Control and Disease Prevention, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan.

Severe papillomatosis occasionally causes astasia leading to euthanizing cattle. There are currently a limited number of reports on virologic approach in severe bovine papillomatosis. Here we report a full genome characterization of bovine papillomavirus type 1 (BPV-1) from the case of severe papillomatosis. A calf developed numerous papillomas on the skin and some nodules in the upper gastrointestinal tract at seven months old. The skin lesion was diagnosed as the epithelial papilloma with BPV antigen expression, while the gastrointestinal lesions were diagnosed as the fibropapilloma without BPV antigen. Full genome analysis revealed that BPV-1s detected in all the lesions were exactly the same. Compared with the reference BPV-1 sequence, there was a single nucleotide insertion in the upstream regulatory region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.18-0289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261810PMC
November 2018

Real-time decision-making during emergency disease outbreaks.

PLoS Comput Biol 2018 07 24;14(7):e1006202. Epub 2018 Jul 24.

Department of Life Sciences, University of Warwick, Coventry, United Kingdom.

In the event of a new infectious disease outbreak, mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic. In the early stages of such outbreaks, substantial parameter uncertainty may limit the ability of models to provide accurate predictions, and policymakers do not have the luxury of waiting for data to alleviate this state of uncertainty. For policymakers, however, it is the selection of the optimal control intervention in the face of uncertainty, rather than accuracy of model predictions, that is the measure of success that counts. We simulate the process of real-time decision-making by fitting an epidemic model to observed, spatially-explicit, infection data at weekly intervals throughout two historical outbreaks of foot-and-mouth disease, UK in 2001 and Miyazaki, Japan in 2010, and compare forward simulations of the impact of switching to an alternative control intervention at the time point in question. These are compared to policy recommendations generated in hindsight using data from the entire outbreak, thereby comparing the best we could have done at the time with the best we could have done in retrospect. Our results show that the control policy that would have been chosen using all the data is also identified from an early stage in an outbreak using only the available data, despite high variability in projections of epidemic size. Critically, we find that it is an improved understanding of the locations of infected farms, rather than improved estimates of transmission parameters, that drives improved prediction of the relative performance of control interventions. However, the ability to estimate undetected infectious premises is a function of uncertainty in the transmission parameters. Here, we demonstrate the need for both real-time model fitting and generating projections to evaluate alternative control interventions throughout an outbreak. Our results highlight the use of using models at outbreak onset to inform policy and the importance of state-dependent interventions that adapt in response to additional information throughout an outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1006202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075790PMC
July 2018

Incremental Prognostic Value of Myocardial Blood Flow Quantified With Stress Dynamic Computed Tomography Perfusion Imaging.

JACC Cardiovasc Imaging 2019 07 18;12(7 Pt 2):1379-1387. Epub 2018 Jul 18.

Department of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

Objectives: This study aimed to evaluate whether myocardial blood flow (MBF) quantified with dynamic computed tomography perfusion imaging (CTP) has an incremental prognostic value over coronary CT angiography (CTA) for major adverse cardiac events (MACEs) in patients with suspected coronary artery disease (CAD).

Background: The incremental prognostic value of CTP over CTA is unclear. The quantification of MBF with dynamic CTP may potentially enhance risk stratification.

Methods: A total of 332 patients (67% men; age: 67 ± 10 years) with suspected CAD who underwent CTA and dynamic CTP was analyzed. A MACE was defined as cardiac death, nonfatal myocardial infarction (MI), unstable angina, or hospitalization for congestive heart failure. A summed stress score (SSS) was calculated by adding scores of all myocardial segments according to normalized MBF values. Abnormal perfusion was defined as SSS ≥4. Obstructive CAD was defined as ≥50% stenosis in ≥1 vessel on CTA.

Results: During a median follow-up of 2.5 years, 19 patients had a MACE. Multivariate analysis showed that, when adjusted for obstructive CAD on CTA, abnormal perfusion was significantly associated with hazards for MACEs (hazard ratio [HR]: 5.7; 95% confidence interval [CI]: 1.9 to 16.9; p = 0.002), with a significant improvement in the prognostic value. Abnormal perfusion was an independent predictor even when adjusted for ≥70% stenosis in ≥1 vessel (HR: 5.4; 95% CI: 1.7 to 16.7; p = 0.003) or adjusted for ≥50% stenosis in ≥2 vessels (HR: 6.5; 95% CI: 2.2 to 18.9; p = 0.001). In the setting of obstructive CAD, annualized event rates showed a significant difference between the patients with and without abnormal perfusion for all events (12.2% vs. 1.5%; p = 0.002) and for cardiac death and nonfatal MI (4.2% vs. 0%; p = 0.015).

Conclusions: MBF quantified with dynamic CTP has an incremental prognostic value over CTA. The addition of dynamic CTP to CTA allows improved risk stratification of patients with CTA-detected stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2018.05.021DOI Listing
July 2019

Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells.

Vet Microbiol 2018 Jul 30;220:33-38. Epub 2018 Apr 30.

Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan; Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan. Electronic address:

Primary infection with bovine respiratory syncytial virus (BRSV) predisposes cattle to secondary infection with bacteria that cause bovine respiratory disease complex (BRDC). However, the interaction between BRSV and bacteria is unclear. This in vitro study examined the adherence of Pasteurella multocida (PM) to BRSV-infected cells was assessed in colony forming unit assays, by flow cytometry analysis, and by indirect immunofluorescence analysis (IFA) of epithelial cells (A549, HEp-2, and MDBK). An in vitro model based on infection of BRSV-infected epithelial cells revealed that PM adherence to BRSV-infected cells was 2- to 8-fold higher than uninfected cells. This was confirmed by flow cytometry analysis and IFA. Epithelial cell expression of mRNA encoding cytokines and chemokines increased after exposure to PM, but increased further after co-infection with BRSV and PM. BRSV-mediated adherence of PM to epithelial cells may underlie the serious symptoms of BRDC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetmic.2018.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117154PMC
July 2018

Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy.

JACC Cardiovasc Imaging 2018 01 14;11(1):48-59. Epub 2017 Jun 14.

Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan.

Objectives: The purpose of this study was to examine the histological correlation of native myocardial T1 and extracellular volume fraction (ECV) measurement at 3-T for the assessment of diffuse pathological changes in the myocardial tissue, including myocardial fibrosis and extracellular space in dilated cardiomyopathy (DCM).

Background: Cardiac magnetic resonance T1 techniques allow the quantification of diffuse myocardial fibrosis. However, there are no definitive head-to-head studies of native T1 versus ECV for the detection, quantification, and characterization of pathological changes in the myocardial tissue in DCM by using histological samples for confirmation.

Methods: A total of 36 subjects with DCM (31 men, mean age 56 ± 16 years) underwent pre- and post-contrast T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 3-T. Biopsy samples were used for the quantification of collagen volume fraction using picrosirius red staining and an extracellular space component from hematoxylin and eosin-stained myocardium.

Results: Nonischemic LGE was observed in 14 of 36 patients. Although patients with LGE had significantly greater biopsy-proven collagen volume fraction than those without LGE (21 ± 12% vs. 11 ± 8%; p < 0.01), there was substantial overlap of collagen volume fraction values between patients with and without LGE. Both native T1 value and ECV were similarly and significantly associated with biopsy-proven collagen volume fraction (r = 0.77 and r = 0.66, respectively; p < 0.05). Furthermore, ECV had a strong correlation with the biopsy-proven extracellular space component (r = 0.86), whereas native T1 had only a moderate correlation (r = 0.55). Interobserver and intraobserver reproducibility for native T1 and ECV were 0.89, 0.95, 0.96, and 0.98, respectively.

Conclusions: Native T1 exhibited comparable ability as ECV measurement in the detection and quantification of histological collagen volume fraction, with high reproducibility, and therefore diffuse myocardial fibrosis in DCM may be reliably assessed by native T1 mapping without the administration of gadolinium contrast agent. In addition, cardiac magnetic resonance-derived ECV showed excellent agreement with histological extracellular space.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2017.04.006DOI Listing
January 2018

Diagnostic Accuracy of Endocardial-to-Epicardial Myocardial Blood Flow Ratio for the Detection of Significant Coronary Artery Disease With Dynamic Myocardial Perfusion Dual-Source Computed Tomography.

Circ J 2017 Sep 25;81(10):1477-1483. Epub 2017 Apr 25.

Department of Radiology, Mie University Hospital.

Background: Previous dynamic stress computed tomography perfusion (CTP) studies used absolute myocardial blood flow (MBF in mL/100 g/min) as a threshold to discriminate flow-limiting coronary artery disease (CAD), but absolute MBF can be vary because of multiple factors. The aim of this study was to compare the diagnostic performance of absolute MBF and the transmural perfusion ratio (TPR) for the detection of flow-limiting CAD, and to clarify the influence of CT delayed enhancement (CTDE) on the diagnostic performance of CTP.Methods and Results:We retrospectively enrolled 51 patients who underwent dual-source CTP and invasive coronary angiography (ICA). TPR was defined as the endocardial MBF of a specific segment divided by the mean of the epicardial MBF of all segments. Flow-limiting CAD was defined as luminal diameter stenosis >90% on ICA or a lesion with fractional flow reserve ≤0.8. Segmental presence and absence of myocardial scar was determined by CTDE. The area under the receiver-operating characteristics curve (AUC) of TPR was significantly greater than that of MBF for the detection of flow-limiting CAD (0.833 vs. 0.711, P=0.0273). Myocardial DE was present in 27 of the 51 patients and in 34 of 143 territories. When only territories containing DE were considered, the AUC of TPR decreased to 0.733.

Conclusions: TPR calculated from absolute MBF demonstrated higher diagnostic performance for the discrimination of flow-limiting CAD when compared with absolute MBF itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-16-1319DOI Listing
September 2017

Comparison of Displacement Encoding With Stimulated Echoes to Magnetic Resonance Feature Tracking for the Assessment of Myocardial Strain in Patients With Acute Myocardial Infarction.

Am J Cardiol 2017 05 28;119(10):1542-1547. Epub 2017 Feb 28.

Department of Radiology, Mie University Hospital, Tsu, Mie, Japan.

The aim of this study was to compare myocardial strain by cardiovascular magnetic resonance feature tracking (CMR-FT) to those derived from displacement encoding with stimulated echoes (DENSE) in patients with acute myocardial infarction (AMI). Twenty patients (65 pa13 years) with AMI underwent cine, DENSE, black-blood T2-weighted and late gadolinium enhancement CMR at 1.5 T. Global and segmental strain was determined by CMR-FT analysis and DENSE on matched 3 short-axis planes. Global circumferential strain by CMR-FT showed a good agreement with that by DENSE (r = 0.85, p <0.001; bias 0.02, limits of agreement -0.03 to 0.06). For segmental circumferential strain, r coefficient between CMR-FT and DENSE was 0.61 (p <0.001) with bias of 0.02, limits of agreement of -0.07 to 0.11. Regional circumferential strain determined by CMR-FT in infarct segments (-0.08 ± 0.05) was significantly altered compared with that in remote normal segments (-0.15 ± 0.05, p <0.001). CMR-FT measurement of regional and global circumferential strain showed good agreement with DENSE in patients with AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2017.02.029DOI Listing
May 2017

Use of Direct LAMP Screening of Broiler Fecal Samples for and in the Positive Flock Identification Strategy.

Front Microbiol 2016 30;7:1582. Epub 2016 Sep 30.

Department of Veterinary Sciences, Faculty of Agriculture, University of MiyazakiMiyazaki, Japan; Center for Animal Disease Control, University of MiyazakiMiyazaki, Japan.

Rapid identification of -positive flocks before slaughter, following freezing and heat treatment for the -positive carcasses at the slaughterhouses is an effective control strategy against foodborne campylobacteriosis. We evaluated a loop-mediated isothermal amplification (LAMP) assay for the direct screening of naturally contaminated chicken cloacal swabs for / to compare this assay with conventional quantitative culture methods. In a comparison study of 165 broilers, the LAMP assay showed 82.8% (48/58 by conventional culture) sensitivity, 100% (107/107) specificity, 100% (48/48) positive predictive value (PPV), and 91.5% (107/117) negative predictive value (NPV). In a comparison of 55 flocks, LAMP showed 90.5% (19/21) sensitivity, 100% (34/34) specificity, 100% (19/19) PPV, and 94.4% (34/36) NPV. In the cumulative total of 28 farm-level comparisons, LAMP showed 100% (12/12) sensitivity, 100% (16/16) specificity, 100% (12/12) PPV, and 100% (16/16) NPV. The LAMP assay required less than 90 min from the arrival of the fecal samples to final results in the laboratory. This suggests that the LAMP assay will facilitate the identification of /-positive broiler flocks at the farm level or in slaughterhouses before slaughtering, which would make it an effective tool in preventing the spread of contamination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2016.01582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043150PMC
September 2016

[Diagnosis of Cardiomyopathy Using Cardiovascular Magnetic Resonance Imaging].

Nihon Naika Gakkai Zasshi 2016 Oct;105(10):2041-7

View Article and Find Full Text PDF

Download full-text PDF

Source
October 2016

An improved loop-mediated isothermal amplification assay for the detection of Mycoplasma bovis.

J Vet Med Sci 2016 Sep 24;78(8):1343-6. Epub 2016 Apr 24.

Department of Veterinary Medical Science, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki 889-2192, Japan.

We improved a loop-mediated isothermal amplification (LAMP) assay permitting sensitive and rapid Mycoplasma bovis detection. A total of 55 bacterial strains were examined in this study, including 33 M. bovis strains, 14 non-M. bovis mycoplasmas and eight non-mycoplasma bacterial strains. M. bovis was successfully detected by the LAMP assay within 60 min without cross-reaction to any other bacteria. Furthermore, a total of 135 nasal swab samples were tested directly using our LAMP assays, the previously reported LAMP assay, conventional PCR assay without pre-culture and comparing standard culture methods. The improved LAMP assay showed sensitivity and specificity of 97.2% and 90.9%, respectively (with a kappa coefficient of 0.8231), and the sensitivity of our revised LAMP assay was increased compared to existing methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053939PMC
http://dx.doi.org/10.1292/jvms.15-0459DOI Listing
September 2016

Underestimation of myocardial blood flow by dynamic perfusion CT: Explanations by two-compartment model analysis and limited temporal sampling of dynamic CT.

J Cardiovasc Comput Tomogr 2016 May-Jun;10(3):207-14. Epub 2016 Jan 13.

Department of Radiology, Mie University Hospital, Tsu, Mie, Japan. Electronic address:

Purpose: Previous studies using dynamic perfusion CT and volume perfusion CT (VPCT) software consistently underestimated the stress myocardial blood flow (MBF) in normal myocardium to be 1.1-1.4 ml/min/g, whilst the O 15-water PET studies demonstrated the normal stress MBF of 3-5 ml/min/g. We hypothesized that the MBF determined by VPCT (MBF-VPCT) is actually presenting the blood-to-myocardium transfer constant, K1. In this study, we determined K1 using Patlak plot (K1-Patlak) and compared the results with MBF-VPCT.

Material And Methods: 17 patients (66 ± 9 years, 7 males) with suspected coronary artery disease (CAD) underwent stress dynamic perfusion CT, followed by rest coronary CT angiography (CTA). Arterial input and myocardial output curves were analyzed with Patlak plot to quantify myocardial K1. Significant CAD was defined as >50% stenosis on CTA. A simulation study was also performed to investigate the influence of limited temporal sampling in dynamic CT acquisition on K1 using the undersampling data generated from MRI.

Results: There were 3 patients with normal CTA, 7 patients with non-significant CAD, and 7 patients with significant CAD. K1-patlak was 0.98 ± 0.35 (range 0.22-1.67) ml/min/g, whereas MBF-VPCT was 0.83 ± 0.23 (range 0.34-1.40) ml/min/g. There was a linear relationship between them: (MBF-VPCT) = 0.58 x (K1-patlak) + 0.27 (r(2) = 0.65, p < 0.001). The simulation study done on MRI data demonstrated that Patlak plot substantially underestimated true K1 by 41% when true K1 was 2.0 ml/min/g with the temporal sampling of 2RR for arterial input and 4RR for myocardial output functions.

Conclusions: The results of our study are generating hypothesis that MBF-VPCT is likely to be calculating K1-patlak equivalent, not MBF. In addition, these values may be substantially underestimated because of limited temporal sampling rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcct.2016.01.008DOI Listing
April 2017

Disagreement between parents on assessment of child temperament traits.

Pediatr Int 2015 Dec 10;57(6):1090-6. Epub 2015 Nov 10.

Kumamoto Paediatric Association, Kumamoto, Japan.

Background: Accuracy of temperament assessment is a prerequisite in research studies. To identify the extent to which parental assessment of child temperament is biased by their personal attributes, we proposed a new structural equation model, in which biases of parental attributes in their assessment of child temperament can be separated from the true (i.e. non-biased) associations between the two.

Methods: We examined 234 father-mother pairs using questionnaires including Emotionality, Activity, Sociability, and Impulsivity; Social Desirability Scale; Hospital Anxiety and Depression Scale; Temperament and Character Inventory; and State-Trait Anger Expression Inventory.

Results: Paternal Depression and Persistence, maternal Trait Anger, and parental Novelty Seeking showed significant bias in assessment of Emotionality. Maternal Self-transcendence showed significant bias in assessment of child Impulsivity.

Conclusion: Researchers should be cautious about biases in parental assessment of children's Emotionality and Impulsivity, but other temperament traits may be free from such biases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.12728DOI Listing
December 2015

Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats.

Basic Clin Pharmacol Toxicol 2015 Jun 17;116(6):524-8. Epub 2014 Dec 17.

The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), Kumamoto, Japan; Graduate School of Medicine, Osaka University, Osaka, Japan.

The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after-effects of toxin diffusion after high-dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2NTX) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether A2NTX has the potential to resolve these issues, we compared the safety of A2NTX, a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1 progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP-TD50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer than A1 progenitor toxin and A1NTX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcpt.12351DOI Listing
June 2015

Comparative analysis of LTR and structural genes in an equine infectious anemia virus strain isolated from a feral horse in Japan.

Arch Virol 2014 Dec 23;159(12):3413-20. Epub 2014 Aug 23.

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

Although equine infectious anemia virus (EIAV) poses a major threat to the equine industry worldwide, the molecular epidemiology of this virus is poorly understood. Recently, an EIAV strain (EIAVMiyazaki2011-A) representing a new monophyletic group was discovered in feral horses in southern Japan. In the present study, the EIAVMiyazaki2011-A proviral genome is compared with evolutionarily divergent EIAV isolates to investigate conservation of functional elements or motifs within the long terminal repeats (LTRs) and structural genes. This analysis represents a significant step forward in increasing understanding of the molecular conservation and variation between geographically distinct strains of this equine lentivirus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-014-2206-0DOI Listing
December 2014

Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

Toxicon 2014 Nov 7;90:97-105. Epub 2014 Aug 7.

The Chemo-Sero- Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.

The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2014.07.013DOI Listing
November 2014

Bovine papillomavirus type 10 with a deletion associated with a lingual papilloma in a cow.

Vet J 2014 Feb 27;199(2):303-5. Epub 2013 Nov 27.

Division of Infection Control and Disease Prevention, Department of Veterinary Medical Science, University of Tokyo, Tokyo 113-8657, Japan. Electronic address:

Different types of papillomavirus usually cause papillomas in specific tissues. Previously, bovine papillomavirus (BPV) type 10 has been associated specifically with cutaneous papillomas in cattle. In this study, BPV-10 was detected in a papilloma on the tongue of a cow. Whole genome analysis demonstrated that the sequence of this BPV-10 strain had a 129 base pair deletion in the E1 open reading frame, which was confirmed by Southern blot analysis, PCR and reverse transcriptase-PCR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2013.11.016DOI Listing
February 2014

Comparison of the immunogenicity of botulinum toxin type A and the efficacy of A1 and A2 neurotoxins in animals with A1 toxin antibodies.

Toxicon 2014 Jan 20;77:114-20. Epub 2013 Nov 20.

The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kita-ku, Kumamoto-shi, Kumamoto 860-8568, Japan.

One issue with botulinum toxin type A products is a reduced therapeutic response in patients that have been injected with frequent dosing over a prolonged period. A possible cause of this is hemagglutinin, found in progenitor toxins, displaying adjuvant activity, enhancing antibody production against the toxin. We investigated whether there is any difference in immunogenicity between the LL toxin-derived subtype A1 (A1LL) and the neurotoxin-derived subtypes A1 and A2 (A1NTX and A2NTX, respectively), and investigated whether A2NTX is effective in animals which produce antibodies against A1LL. Neutralizing antibodies were detected in the A1LL-administered group; however, they were not detected in swine and rabbits administered multiple doses of A2NTX. These results indicate that A2NTX has a lower immunogenicity than A1LL. In rats with neutralizing antibodies, produced by the administration of A1LL, that were administered either A1NTX or A2NTX, A2NTX showed more potent inhibitory neuromuscular transmission than A1NTX. In human sera immunized with the botulinum toxoid vaccine (containing LL, L, and M toxoid derived subtype A1) reacted with either A1NTX or A2NTX, A2NTX showed more potent inhibitory neuromuscular transmission than A1NTX. This suggests that A2NTX has a greater therapeutic value in humans who have neutralizing antibodies against the A1 toxin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2013.11.006DOI Listing
January 2014

Botulinum neurotoxin A2 reduces incidence of seizures in mouse models of temporal lobe epilepsy.

Toxicon 2013 Nov 15;74:109-15. Epub 2013 Aug 15.

Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto 603-8555, Japan. Electronic address:

Temporal lobe epilepsy often shows pharmacoresistance, and well-known anti-convulsants sometimes are not effective for blocking chronic seizures. Botulinum neurotoxins are metalloproteases that act on presynaptic proteins and inhibit neurotransmitter release in both the peripheral and central nerve systems. That is why neurotoxins may elicit an effect for the restraint of the seizures. Meanwhile, it has been suggested that a property and the stability of neurotoxin activities differ among the types A-G, in which type A neurotoxin (ANTX) is, especially, the most stable and can continue having activity for a long term. The present study therefore investigated the effects of hippocampal injections of A2NTX on seizures derived in TLE model mice, received repeated kindling stimulations in the amygdala. The injections induced complete disappearance of grand mal seizures in half of the population of amygdala kindled mice for 4 days. The injections also induced reduction of the evoked seizure level significantly for at least 18 days after injections. Taken together, these results suggest that A2NTX prevents from epileptic seizures, proposing that A2NTX is available as a new antiepileptic reagent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2013.07.027DOI Listing
November 2013