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We propose the name Rickettsia japonica sp. nov. (with type strain YH [= ATCC VR-13631) for a serologically specific species of spotted fever group rickettsiae that are pathogenic for humans (J. Infect. Dis. 159:1122-1126, 1989; J. Clin. Microbiol. 28:1177-1180, 1990). The biologic and genomic characteristics of the organism (G+C content, 31.2 +-0.7 mol%) are essentially the same as those of other pathogenic spotted fever group rickettsiae, although the R. japonica isolates cause a persistent infection in Vero cells for many subcultures.In this paper we formally describe Rickettsia japonica (23,25), which has been identified as the causative agent of a human disease. The first isolate, strain YHT (T = type strain), was isolated in 1985 from the blood of a patient with febrile exanthematous illness in Japan by using a tissue culture technique (20). Five strains of the causative agent, including strain YHT, have been isolated from patients that were serodiagnosed as having a spotted fever group (SFG) rickettsiosis (22).Justification for a new species. The justification for establishing a new species for this organism is based on the current standard method for comparing rickettsial taxonomic types by serologic analysis (23). Experiments involving reciprocal cross-reactions of mouse polyclonal antibodies to strains of the new species and other species of SFG rickettsiae produced by the standard method were carried out to calculate the specificity differences. By using this approach we demonstrated that all five strains belong to a single species that is distinct from all of the previously described SFG rickettsiae that are known to be pathogenic for humans (23). In addition, none of the isolates reacted with mouse monoclonal antibodies that are species specific for other pathogenic SFG rickettsiae (23). Furthermore, the results of Western immunoblotting revealed different electrophoretic mobilities and antigenic reactivities for the major immunodominant high-molecular-weight surface polypeptides of the Japanese isolates and standard pathogenic SFG rickettsial strains (23). Species-specific monoclonal antibodies to R. japonica reacted only with strains of R. japonica, supporting the conclusion that R. japonica is a new species of SFG rickettsiae (25).

Background It is unclear whether the chemotherapy response improves after exposure to immunotherapy. Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects that stimulate tumor shrinkage. We conducted a retrospective study to evaluate improvement of the efficacy of ramucirumab plus docetaxel after the failure of nivolumab as a PD‐1 inhibitor. Methods From February 2016 to December 2017, 152 patients with non‐small cell lung cancer (NSCLC) administered nivolumab in our institution were identified. We reviewed the records of 20 NSCLC patients administered ramucirumab plus docetaxel after nivolumab failure. The overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS) were investigated. Pegylated granulocyte colony‐stimulating factor was prophylactically administered to 18 patients (90%) after the administration of ramucirumab plus docetaxel. Results The median age of the patients was 70 (range: 55–77) years. Twelve patients were male and eight were female. The histology was adenocarcinoma in 16 patients, squamous cell carcinoma in three, and other in one. The ORR of ramucirumab plus docetaxel was 60%, and the PFS and OS were 169 and 343 days, respectively. Among the 20 patients, 12 achieved a partial response, giving an ORR of 60.0%. Six patients had stable disease and two had progressive disease. The disease control rate was 90%. Gastrointestinal adverse events were frequently observed in 19 patients. Conclusions Ramucirumab plus docetaxel achieved a higher response rate when administered immediately after nivolumab failure compared to regimens without prior nivolumab administration.

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BackgroundNeuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel α2δ-1 subunit.ResultsMice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the anti-allodynic effects varied according to its dosing time. The protein levels of α2δ-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of α2δ-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when α2δ-1 subunit protein was abundant.ConclusionsThese findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain.