HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes

High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions

Magnetic resonance imaging and symptoms in patients with neurosarcoidosis and central diabetes insipidus

Introduction: In the clinical setting, the diagnosis of neurosarcoidosis in patients with central diabetes insipidus (CDI) is typically based both on symptoms (i.e. polydipsia or polyuria) and brain magnetic resonance imaging (MRI) findings (e.g. pituitary abnormality). However, inconsistent changes in the patient’s symptoms and brain MRI findings may occur during the clinical course of the disease. This review was performed to summarise the relationship between symptoms and brain MRI findings in previously reported cases of neurosarcoidosis with CDI. Material and methods: Case studies of patients diagnosed with neurosarcoidosis with CDI were collected via a PubMed search of studies published through 30 June 2018. Results: Thirteen eligible studies were reviewed (20 patients; 12 men, 8 women; mean age 33 years). Polydipsia or polyuria was the first symptom in 13 patients. The mean duration from disease onset to diagnosis was 3.4 months. Brain MRIs showed abnormal findings in the hypothalamus and pituitary for 17 patients. Immunosuppressive drugs were used in 17 patients. For 14 patients, MRI findings improved, while symptoms did not. Conclusion: Patients with both neurosarcoidosis and CDI symptoms often do not improve, despite the fact that brain MRI findings often improve following treatment. More studies involving detailed pathological analyses and longer follow-up periods are necessary

The effect of Humanitude care methodology on improving empathy: a six-year longitudinal study of medical students in Japan.

BACKGROUND: Empathy, which involves understanding another person\u27s experiences and concerns, is an important component for developing physicians\u27 overall competence. This longitudinal study was designed to test the hypothesis that medical students\u27 empathy can be enhanced and sustained by Humanitude Care Methodology, which focuses on perception, emotion and speech. METHODS: This six-year longitudinal observational study examined 115 students who entered Okayama University Medical School in 2013. The study participants were exposed to two empathy-enhancing programs: (1) a communication skills training program (involving medical interviews) and (2) a Humanitude training program aimed at enhancing their empathy. They completed the Jefferson Scale of Empathy (JSE) seven times: when they entered medical school, before participation in the first program (medical interview), immediately after the first program, before the second program (Humanitude exercise), immediately after the second program, and in the 5th and 6th year (last year) of medical school. A total of 79 students (69% of the cohort) completed all seven test administrations of the JSE. RESULTS: The mean JSE scores improved significantly after participation in the medical interview program (p \u3c 0.01) and the Humanitude training program (p = 0.001). However, neither program showed a sustained effect. CONCLUSIONS: The Humanitude training program as well as medical interview training program, had significant short-term positive effects for improving empathy among medical students. Additional reinforcements may be necessary for a long-term sustained effect