Biological roles of anti-GM1 antibodies in patients with Guillain–Barré syndrome for nerve growth factor signaling

AbstractTo reveal the biological and pathological roles of anti-GM1 antibody in Guillain–Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS

Consulting System of Undergraduate Course Guidance

This paper mainly presents the reasoning method in our consulting system in order to predict how many credits the students can get. It is necessary to use a prior knowledge obtained by the grade data of the students. So we adopt the probabilistic logic model due to Niki in this sense. Numerical results for actual grade data in our university are shown

Differences in Ocular Complications Between Candida albicans and Non-albicans Candida Infection Analyzed by Epidemiology and a Mouse Ocular Candidiasis Model

Objectives:Candida species are a major cause of hospital infections, including ocular candidiasis, but few studies have examined the propensities of specific species to invade the eye or the unique immunological responses induced. This study examined the frequency and characteristics of species-specific Candida eye infections by epidemiology and experiments using a mouse ocular candidiasis model.Methods: We reviewed medical records of candidemia patients from January 2012 to March 2017. We also evaluated ocular fungal burden, inflammatory cytokine and chemokine profiles, and inflammatory cell profiles in mice infected with Candida albicans, Candida glabrata, or Candida parapsilosis.Results: During the study period, 20 ocular candidiasis cases were diagnosed among 99 candidemia patients examined by ophthalmologists. Although C. parapsilosis was the most frequent candidemia pathogen, only C. albicans infection was significantly associated with ocular candidiasis by multivariate analysis. In mice, ocular fungal burden and inflammatory mediators were significantly higher during C. albicans infection, and histopathological analysis revealed invading C. albicans surrounded by inflammatory cells. Ocular neutrophil and inflammatory monocyte numbers were significantly greater during C. albicans infection.Conclusion:Candida albicans is strongly associated with ocular candidiasis due to greater capacity for invasion, induction of inflammatory mediators, and recruitment of neutrophils and inflammatory monocytes

Evaluation of trimethoprim-sulfamethoxazole based combination therapy against Stenotrophomonas maltophilia: in vitro effects and clinical efficacy in cancer patients

Objectives: The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia. Methods: In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed. Results: SXT + LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT + TIM showed synergy in 71, and no interactions in 18. SXT + MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT + fluoroquinolone was not associated with improved prognosis compared with monotherapy. Conclusions: The in vitro data indicated that SXT + TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT + fluoroquinolone combination therapy for S. maltophilia infection

2709. Breakthrough fungal infection after isavuconazole primary prophylaxis in patients with hematologic malignancy and hematopoietic stem cell transplant: Systematic Review

Abstract Background Isavuconazole (ISA) is a relatively newer triazole with a broad spectrum of anti-fungal activity and has been used for both treatment and prophylaxis of invasive fungal infections (IFIs) in patients with hematologic malignancy (HM) and hematopoietic stem cell transplant (HSCT) with a more favorable side-effect profile as compared to other agents. Widespread prophylactic use of mold-active agents has resulted in a decline in the incidence of IFIs, but breakthrough (bIFIs) has been reported previously. Thus, we performed a systematic review of HM and HSCT patients receiving ISA as primary prophylaxis to determine incidence and clinical characteristics of bIFI in this vulnerable population. Methods We conducted a comprehensive literature search with search term of ISA, prophylaxis and either HM and/or HSCT in several search engines (Embase, Scopus Web of Science, MEDLINE and CENTRAL). The database search strategy was developed by an academic health science librarian. We excluded patients who had ISA as treatment or secondary prophylaxis. Results With initial search, 630 unique articles were identified and after reviewing abstracts, we finally conducted a full-text review of 70 articles, of which 27 studies were included (Figure), of which 17 studies included more than or equal to 10 patients on ISA prophylaxis. Overall, ISA was well tolerated during primary prophylaxis. Of note, of the 17 studies, 717 patients received ISA as primary prophylaxis, out of which 58 patients (8.1%) developed bIFI with range of 0%-20% and occurred 13-138 days after initiation (Table). ISA levels were checked in 6 studies with a plasma level between 1.5-6.3 μg/mL. Out of 58 bIFI cases, 33 cases were identified including 6 Mucorales spp., 3 Fusarium spp., 8 Candida spp and 14 Aspergillus spp. Most commonly used regimen for treatment of bIFI was combination of Liposomal amphotericin B with Posaconazole. Overall mortality after bIFI was 0%-66.7%. Conclusion Our systematic review shows a high incidence of bIFI in patients with underlying HM or HSCT receiving ISA prophylaxis. Caution should be used in patients receiving long term prophylaxis with ISA. Further studies are needed to assess for risk factors that predispose to bIFI in patients receiving ISA prophylaxis. Disclosures John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bond