A multicenter, double-blind, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of camostat mesilate in patients with COVID-19 (CANDLE study).

BACKGROUND: In vitro drug screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). METHODS: This was a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were enrolled, randomized, and allocated to each group using an interactive web response system. Randomization was performed using a minimization method with the factors medical institution, age, and underlying diseases (chronic respiratory disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular diseases, and obesity). The patients, investigators/subinvestigators, study coordinators, and other study personnel were blinded throughout the study. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. RESULTS: One-hundred fifty-five patients were randomized to receive camostat mesilate (n = 78) or placebo (n = 77). The median time to the first test was 11.0 days (95% confidence interval [CI]: 9.0-12.0) in the camostat mesilate group and 11.0 days (95% CI: 10.0-13.0) in the placebo group. Conversion to negative viral status by day 14 was observed in 45 of 74 patients (60.8%) in the camostat mesilate group and 47 of 74 patients (63.5%) in the placebo group. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. CONCLUSIONS: Camostat mesilate did not substantially reduce the time to viral clearance, based on upper airway viral loads, compared with placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04657497. Japan Registry for Clinical Trials, jRCT2031200198.

Randomized, Controlled Study of Opicapone in Japanese Parkinson's Patients with Motor Fluctuations.

OBJECTIVES: This placebo-controlled, randomized study evaluated the efficacy and safety of opicapone 25-mg and 50-mg tablets in Japanese levodopa-treated patients with Parkinson's disease and motor fluctuations. METHODS: Japanese adults (n = 437, age 39-83 years) with Parkinson's disease (United Kingdom Parkinson's Disease Society criteria) received opicapone 25-mg (n = 145), opicapone 50-mg (n = 145), or placebo (n = 147) tablets over the double-blind treatment period (14-15 weeks). The primary efficacy assessment was change in OFF-time; secondary efficacy assessments included OFF/ON-time responders (≥1 hour change from baseline), total ON-time, ON-time with and without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale. RESULTS: The least squares mean (standard error) change in OFF-time from baseline to the last visit was -0.42 (0.21) hour for the placebo group, -1.16 (0.22) hour for the opicapone 25 mg group, and -1.04 (0.21) hour for the opicapone 50 mg group. The percentage of ON-time responders, changes in total ON-time/ON-time without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale II (at OFF) all showed statistically significant improvements versus placebo for both opicapone tablet doses (P < 0.05). Unified Parkinson's Disease Rating Scale III (at ON) was improved versus placebo in patients who received opicapone 50 mg (P < 0.05). Adverse events were more common in patients treated with opicapone 25 mg (60.0%) or opicapone 50 mg (54.5%) versus placebo (48.3%). The most commonly reported adverse event was dyskinesia (placebo, 2.7%; opicapone 25 mg, 9.0%; opicapone 50 mg, 12.4%). CONCLUSIONS: In Japanese patients, both opicapone 25 and 50 mg were significantly more effective than placebo with no dose-dependent difference in efficacy, and both doses were well tolerated. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long-term safety and efficacy of opicapone in Japanese Parkinson's patients with motor fluctuations.

The double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson's Disease) study in Japanese levodopa-treated patients with Parkinson's disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [- 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [- 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [- 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells.

Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome.

Higher Tissue Levels of Thymidylate Synthase Determined by ELISA Are Associated with Poor Prognosis of Patients with Lung Cancer.

Thymidylate synthase (TS) is essential in thymidylate biosynthesis and DNA replication. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in pyrimidine catabolism and is important in catabolism of 5-fluorouracil (5-FU). The significance of TS and DPD expressed in lung cancer remains controversial. Here we analyzed the relationship between TS and DPD expression and clinicopathological features of lung cancer. Enzyme-linked immunosorbent assays (ELISAs) were used to measure TS and DPD levels in paired tumor and non-tumor lung tissues obtained from 168 patients (107 adenocarcinomas, 39 squamous cell carcinomas, and 22 others), who had operations at the Shinshu University Hospital from 2004 to 2007 and were followed up for a median of 57.0 months. TS and DPD expression levels were higher in tumor tissues, and TS expression levels were significantly lower in adenocarcinomas than those in other subtypes. In addition, patients with low TS levels survived longer compared with patents with high TS levels. By contrast, DPD expression levels were not correlated with overall patient survival. Importantly, patients with low TS and DPD levels exhibited significantly prolonged survival than those with high TS and DPD. Among the 168 patients, 59 patients were treated with tegafur-uracil (UFT), a DPD-inhibitory fluoropyrimidine, and the UFT-treated patients with high TS and high DPD levels showed worst prognosis. Our study demonstrates a significant correlation between low TS expression levels and long-term prognosis of patients with lung cancer. Thus, ELISA is a clinically useful method to measure TS and DPD expression in lung cancer tissues.

Monitoring for bovine arboviruses in the most southwestern islands in Japan between 1994 and 2014.

BACKGROUND: In Japan, epizootic arboviral infections have severely impacted the livestock industry for a long period. Akabane, Aino, Chuzan, bovine ephemeral fever and Ibaraki viruses have repeatedly caused epizootic abnormal births and febrile illness in the cattle population. In addition, Peaton, Sathuperi, Shamonda and D'Aguilar viruses and epizootic hemorrhagic virus serotype 7 have recently emerged in Japan and are also considered to be involved in abnormal births in cattle. The above-mentioned viruses are hypothesized to circulate in tropical and subtropical Asia year round and to be introduced to temperate East Asia by long-distance aerial dispersal of infected vectors. To watch for arbovirus incursion and assess the possibility of its early warning, monitoring for arboviruses was conducted in the Yaeyama Islands, located at the most southwestern area of Japan, between 1994 and 2014. RESULTS: Blood sampling was conducted once a year, in the autumn, in 40 to 60 healthy cattle from the Yaeyama Islands. Blood samples were tested for arboviruses. A total of 33 arboviruses including Akabane, Peaton, Chuzan, D' Aguilar, Bunyip Creek, Batai and epizootic hemorrhagic viruses were isolated from bovine blood samples. Serological surveillance for the bovine arboviruses associated with cattle diseases in young cattle (ages 6-12 months: had only been alive for one summer) clearly showed their frequent incursion into the Yaeyama Islands. In some cases, the arbovirus incursions could be detected in the Yaeyama Islands prior to their spread to mainland Japan. CONCLUSIONS: We showed that long-term surveillance in the Yaeyama Islands could estimate the activity of bovine arboviruses in neighboring regions and may provide a useful early warning for likely arbovirus infections in Japan. The findings in this study could contribute to the planning of prevention and control for bovine arbovirus infections in Japan and cooperative efforts among neighboring countries in East Asia.

Dose-dependent responses of pigs infected with foot-and-mouth disease virus O/JPN/2010 by the intranasal and intraoral routes.

Foot-and-mouth disease virus (FMDV) infection was successfully initiated in pigs by intraoral inoculation of both 10(6) and 10(3) TCID50 of FMDV O/JPN/2010 isolated from the 2010 epidemic in Japan. By intranasal inoculation, infection was established in pigs with 10(6) TCID50 of the isolate, but not with 10(3) TCID50 of the isolate. In the pigs inoculated with 10(6) TCID50 of the isolate, viruses and viral RNAs were obtained earlier from the pigs inoculated by the intraoral route than from the pigs inoculated by the intranasal route. These results support the theory that primary infection of a pig herd is more likely to occur by ingestion than by inhalation and that the oral cavity is likely to be a major entry route for FMDV in naturally exposed pigs.

Experimental infection of cattle and goats with a foot-and-mouth disease virus isolate from the 2010 epidemic in Japan.

In this study, we carried out experimental infections in cattle and goats using a foot-and-mouth disease virus (FMDV) isolate from the 2010 epidemic in Japan to analyze clinical manifestations, virus-shedding patterns and antibody responses in the animals. We found that the FMDV O/JPN/2010 isolate is virulent in cattle and goats, produces clinical signs, is spread efficiently by direct contact within the same species, and is persistently infectious in cattle. Quantitative analysis of levels of viral RNA in the tissues of cattle and goats infected with the isolate showed that the pharyngeal region is an important major target of the FMDV O/JPN/2010. Time course data of viral loads, excretion and transmission of the FMDV O/JPN/2010 in this study are key in providing quantitative data essential for epidemiological investigation and risk analysis in relation to disease controls.

Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient's postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered.

Potential involvement of N-terminal acetylation in the quantitative regulation of the ε subunit of chloroplast ATP synthase under drought stress.

In plants, modulation of photosynthetic energy conversion in varying environments is often accompanied by adjustment of the abundance of photosynthetic components. In wild watermelon (Citrullus lanatus L.), proteome analysis revealed that the ε subunit of chloroplast ATP synthase occurs as two distinct isoforms with largely-different isoelectric points, although encoded by a single gene. Mass spectrometry (MS) analysis of the ε isoforms indicated that the structural difference between the ε isoforms lies in the presence or absence of an acetyl group at the N-terminus. The protein level of the non-acetylated ε isoform preferentially decreased in drought, whereas the abundance of the acetylated ε isoform was unchanged. Moreover, metalloprotease activity that decomposed the ε subunit was detected in a leaf extract from drought-stressed plants. Furthermore, in vitro assay suggested that the non-acetylated ε subunit was more susceptible to degradation by metalloaminopeptidase. We propose a model in which quantitative regulation of the ε subunit involves N-terminal acetylation and stress-induced proteases.

Surgical outcomes in patients with small cell lung cancer: comparative analysis of computed tomograpy-detected patients with others.

BACKGROUND: It is shown that low-dose computed tomography (CT) screening is useful for a reduction in lung-cancer-specific mortality in heavy smokers. However, the information about effectiveness according to the histological types of lung cancer has not been adequately investigated especially small cell lung cancer (SCLC). The present study was performed to see the clinical benefit of CT screening in patients with SCLC following thoracotomy. METHODS: We retrospectively reviewed the outcome in patients with early stage SCLC who initially underwent thoracotomy. The clinical stages and actuarial survival were estimated according to the three means of detection of SCLC: chest CT, radiographic screen, and symptomatically prompted cases. RESULTS: Sixty-nine patients (men/women, 63/6; mean age, 70 years) with SCLC underwent thoracotomy between 1991 and 2010 including chest CT (n = 13), radiographic screening (n = 39), and symptomatically prompted cases (n = 17). Pathological staging information included stage IA (n = 25), IB (n = 8), IIA (n = 13), IIB (n = 5), IIIA (n = 11), and IIIB (n = 7). Median survival time was 30.0 (95% confidence interval (CI): 22.0 to 57.0) months, with overall survival at 5 years of 34.3% (95% CI, 23.47 to 47.3). Nine patients (69%) with stage I were detected by CT which was significantly higher than those in other detection arms. However, there were no significant differences in the survival between CT and other detection arms. CONCLUSIONS: CT examination may be useful for detection in early stage SCLC potentially suitable for surgery, but the contribution to better clinical outcome in patients with SCLC remains unclear.

Effects of irradiation on cumulative mortality in mice: shifting toward a younger age of death.

Recently, the question of whether cancer risk is only accelerated but not increased by radiation exposure has been raised. To explore this matter, we analyzed whether the cumulative mortality of irradiated mice could be explained by x-axis (age) shifted cumulative mortality of nonirradiated mice. We reanalyzed publicly available data on observed cumulative mortality or prevalence in irradiated female B6C3F1 mice that lived their entire lifespan. The results showed that the irradiated curve was well matched to uniformly shifted nonirradiated curve for the cumulative mortality of all causes of death but not for the cumulative mortality of all solid tumors and prevalence of ovarian tumors as is. After adjusting lifetime mortalities, it was also well matched for all solid and ovarian tumors. The shifted days by irradiation were 71-116 days for all causes of death, 56-135 days for all solid tumors, and 41-140 days for ovarian tumors in the 1.9 Gy-irradiated group. The response was switched between irradiation at 35 and 105 days consistently for all the above indexes, supporting the hypothesis that radiation sensitivity differs between juvenile and adults. The shifted days of all causes of death showed a tendency of linear response to dose. This concept of shifting the age of death can be applied not only for all cause of death but also for mortality of all solid tumors after adjusting the magnitude. These findings contribute to the discussion on the application of the 'shifting age of death' concept to radiation protection.

Shear stress-mediated F1/FO ATP synthase-dependent CO2 gas excretion from human pulmonary arteriolar endothelial cells.

We studied the physiological role of flow through pulmonary arterioles in CO(2) gas exchange. We established human pulmonary arteriolar endothelial cells (HPAoEC). The cells demonstrated marked immunocytochemical staining of PECAM-1, VEGF R2, ACE-1, and CA type IV on their cell surface. Ten seconds shear stress stimulation caused the co-release of H(+) and ATP via the activation of F(1)/F(O) ATP synthase on the HPAoEC. F(1)/F(O) ATP synthase was immunocytochemically observed on the cell surface of non-permeabilized HPAoEC. In the shear stress-loaded HPAoEC culture media supernatant, ATPase activity increased in a time-dependent manner. The HPAoEC were strongly stained for NTPDase 1, which partially co-localized with purinergic P2Y1. The purinergic P2Y1 receptor agonist UTP (10(-6) M) significantly potentiated the shear stress-induced increase in ATPase activity in the culture medium supernatant. Ten seconds shear stress stimulation also produced stress strength-dependent CO(2) gas excretion from the HPAoEC, which was significantly reduced by the inhibition of F(1)/F(O) ATP synthase or CA IV on the endothelial cell (EC) surface. In conclusion, we have proposed a new concept of CO(2) exchange in the human lung, flow-mediated F(1)/F(O) ATP synthase-dependent H(+) secretion, resulting in the facilitation of a dehydration reaction involving HCO3(-) in plasma and the excretion of CO(2) gas from arteriolar ECs.

Southeast Asian foot-and-mouth disease viruses in Eastern Asia.

Foot-and-mouth disease (FMD) outbreaks recently affected 2 countries (Japan and South Korea) in eastern Asia that were free of FMD without vaccination. Analysis of viral protein 1 nucleotide sequences indicated that FMD serotype A and O viruses that caused these outbreaks originated in mainland Southeast Asia to which these viruses are endemic.

Small peripheral lung carcinomas with five-year post-surgical follow-up: assessment by semi-automated volumetric measurement of tumour size, CT value and growth rate on TSCT.

OBJECTIVES: To retrospectively assess the utility of semi-automated measurements by stratification of CT values of tumour size, CT value and doubling time (DT) using thin-section computed tomography (CT) images. The post-surgical outcomes of favourable and problematic tumours (more advanced p stage than IA, post-surgical recurrence or mortality from lung cancer) were compared using the measured values. The computed DTs were compared with manually measured values. METHODS: The study subjects comprised 85 patients (aged 33-80 years, 48 women, 37 men), followed-up for more than 5 years postoperatively, with 89 lung lesions, including 17 atypical adenomatous hyperplasias and 72 lung cancers. DTs were determined in 45 lesions. RESULTS: For problematic lesions, whole tumour diameter and density were >18 mm and >-400 HU, respectively. The respective values for the tumour core (with CT values of -350 to 150 HU) were >15 mm and >-70 HU. Analysis of tumour core DTs showed interval tumour progression even if little progress was seen by standard tumour volume DT (TVDT). CONCLUSION: Software-based volumetric measurements by stratification of CT values provide valuable information on tumour core and help estimate tumour aggressiveness and interval tumour progression better than standard manually measured 2D-VDTs.

The significance of thermomechanical processing on the cellular response of biomedical Co-Cr-Mo alloys.

Strengthening of biomedical Co-Cr-Mo alloys has been explored via thermomechanical processing for enhancing the durability of their biomedical applications. However, the effects of cold and hot deformation on the cellular activity continue to be unclear. In this study, we prepared Co-Cr-Mo alloy rods via cold swaging and hot-caliber rolling and studied the relationship between the microstructure and cellular response of pre-osteoblasts. The cold-swaged rod experienced strain-induced martensitic transformation, which increased the volume fraction of the hexagonal close-packed (hcp) ε-martensite to ∼60 vol.% with an increase in area reduction (r) to 30%. The 111γ fiber texture of the face-centered cubic (fcc) γ-matrix followed the Shoji-Nishiyama orientation relationship with ε-martensite. Cell culture results revealed beneficial effects of cold swaging on the cell response, in terms of adhesion, proliferation and morphology of cells, although increasing r did not significantly affect cellular metabolism levels. The addition of small content of Zr (0.04 wt.%) led to enhanced focal adhesion of cells, which became more significant at higher r. The microstructural evolution during hot-caliber rolling, namely, grain refinement without any phase transformation and strong texture development, did not appreciably affect the cellular activity. These findings are envisaged to facilitate alloy design and microstructural optimization for favorable tuning the osseointegration of biomedical Co-Cr-Mo alloys.

Dynamic changes in the leaf proteome of a C3 xerophyte, Citrullus lanatus (wild watermelon), in response to water deficit.

Wild watermelon (Citrullus lanatus) is a xerophyte native to the Kalahari Desert, Africa. To better understand the molecular mechanisms of drought resistance in this plant, we examined changes in the proteome in response to water deficit. Wild watermelon leaves showed decreased transpiration and a concomitant increase in leaf temperature under water deficit conditions. Comparison of the proteome of stressed plants with that of unstressed plants by two-dimensional gel electrophoresis revealed that the intensity of 40 spots increased in response to the stress, and the intensity of 11 spots decreased. We positively identified 23 stress-induced and 6 stress-repressed proteins by mass spectrometry and database analyses. Interestingly, 15 out of the 23 up-regulated proteins (65% of annotated up-regulated proteins) were heat shock proteins (HSPs). Especially, 10 out of the 15 up-regulated HSPs belonged to the small heat shock protein (sHSP) family. Other stress-induced proteins included those related to antioxidative defense and carbohydrate metabolism. Fifteen distinct cDNA sequences encoding the sHSP were characterized from wild watermelon. Quantitative real-time PCR analysis of the representative sHSP genes revealed strong transcriptional up-regulation in the leaves under water deficit. Moreover, immunoblot analysis confirmed that protein abundance of sHSPs was massively increased under water deficit. Overall, these observations suggest that the defense response of wild watermelon may involve orchestrated regulation of a diverse array of functional proteins related to cellular defense and metabolism, of which HSPs may play a pivotal role on the protection of the plant under water deficit in the presence of strong light.

Responses of the photosynthetic electron transport system to excess light energy caused by water deficit in wild watermelon.

In plants, drought stress coupled with high levels of illumination causes not only dehydration of tissues, but also oxidative damage resulting from excess absorbed light energy. In this study, we analyzed the regulation of electron transport under drought/high-light stress conditions in wild watermelon, a xerophyte that shows strong resistance to this type of stress. Under drought/high-light conditions that completely suppressed CO(2) fixation, the linear electron flow was diminished between photosystem (PS) II and PS I, there was no photoinhibitory damage to PS II and PS I and no decrease in the abundance of the two PSs. Proteome analyses revealed changes in the abundance of protein spots representing the Rieske-type iron-sulfur protein (ISP) and I and K subunits of NAD(P)H dehydrogenase in response to drought stress. Two-dimensional electrophoresis and immunoblot analyses revealed new ISP protein spots with more acidic isoelectric points in plants under drought stress. Our findings suggest that the modified ISPs depress the linear electron transport activity under stress conditions to protect PS I from photoinhibition. The qualitative changes in photosynthetic proteins may switch the photosynthetic electron transport from normal photosynthesis mode to stress-tolerance mode.

Characterization of the complete genomic sequence of the rinderpest virus Fusan strain cattle type, which is the most classical isolate in Asia and comparison with its lapinized strain.

In this study, we characterized the rinderpest virus (RPV) Fusan strain cattle type (B), which is the most classical isolate in Asia, by complete genomic sequence analysis and compared it with its lapinized Nakamura III (L) strain. The transversion rates of the M, F, and H genes were higher than those of other genes. In contrast, the deduced amino acid (aa) substitution rates of the P, C, and V genes were higher than those of other genes, although their transversion rates were not higher. The characteristic nucleotide (nt) or aa residues of the cattle-virulent B and Kabete 'O' strains were observed in the P/C/V, M, and L genes. According to these results, we speculate that nt/aa substitution in the P/C/V genes is one of the key determinants for the difference in the pathogenicity to cattle of the B and L strains.