Background
Epigastric pain, vomiting, and other gastrointestinal problems are among the most important symptoms of malaria infection as they suggest the possibility that the condition is serious. Pathophysiologies such as gastric mucosal changes and delayed gastric emptying have been reported in serious cases of malaria infection. However, it is unclear whether or not pathophysiological involvement of the upper gastrointestinal tract occurs in
Plasmodium berghei
ANKA (PbA)-infected mice.
Methods
PbA-infective
Anopheles
mosquitoes were used to infect mice via the natural route of infection. Fifteen PbA-C57BL/6 mice were used as a cerebral malaria model and the same numbers of PbA-BALB/c mice were used as a cerebral malaria-resistant model, and then we investigated the pathophysiological involvement of the stomach and small intestine.
Results
On day 8 post infection, six PbA-C57BL/6 mice showed cerebral malaria and nine others had uncomplicated infection. All the PbA-C57BL/6 mice on that same day showed severe weight loss with multiple, red gastric patches and changes to the course of the small intestine with villus goblet cell enlargement. In addition, cerebral malaria cases showed gastric gas retention with submucosal edema and small intestinal shortening. In PbA-BALB/c mice, overextension of the stomach and gas retention were evident from week 2 after PbA infection, as well as changes to the course of the small intestine and mesenteric thinning with fragility.
Conclusions
We described the upper gastrointestinal pathophysiology representing new findings directly linked to malarial severity and subsequent death in PbA-infected mice as a mouse model of malaria infection.
Melanoma has been a prototype for cancer immunology research, and the mechanisms of anti-tumor T-cell responses have been extensively investigated in patients treated with various immunotherapies. Individual differences in cancer-immune status are defined mainly by cancer cell characteristics such as DNA mutations generating immunogenic neo-antigens, and oncogene activation causing immunosuppression, but also by patients' genetic backgrounds such as HLA types and genetic polymorphisms of immune related molecules, and environmental and lifestyle factors such as UV rays, smoking, gut microbiota and concomitant medications; these factors have an influence on the efficacy of immunotherapy. Recent comparative studies on responders and non-responders in immune-checkpoint inhibitor therapy using various new technologies including multi-omics analyses on genomic DNA, mRNA, metabolites and microbiota and single cell analyses of various immune cells have led to the advance of human tumor immunology and the development of new immunotherapy. Based on the new findings from these investigations, personalized cancer immunotherapies along with appropriate biomarkers and therapeutic targets are being developed for patients with melanoma. Here, we will discuss one of the essential subjects in tumor immunology: identification of immunogenic tumor antigens and their effective use in various immunotherapies including cancer vaccines and adoptive T-cell therapy.
Ticks can potentially transmit lethal pathogens to humans. At Ashikaga Red Cross Hospital in Tochigi Prefecture, Japan, tick bites became prominent around 2015; however, identi cation of tick species or evaluation of epidemiological risk factors was not performed. In addition, a noninvasive tick removal method was desired from the perspective of patient safety. erefore, we examined tick species, age at bite, sex, bitten body part, and location (address) of 72 patients with tick bites who visited Ashikaga Red Cross Hospital for consultation between 2017 and 2019. We found that 62 of the 72 cases (86%) of bites were of Amblyomma testudinarium, which has not been previously reported in Tochigi Prefecture. Tick bites occurred mainly in the elds or gardens around the residential areas adjacent to low mountains, from March to October, peaking in May and June. Among the 72 cases, 53 (74%) were aged 50 years or above, and 44 (61%) were females. In June 2018, we introduced a tick remover as an alternative to scalpel incision. Subsequently, the tick remover was used for 6 cases in 2018 and for 21 cases in 2019 without any remnant of the tick mouthpiece.
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