Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes ; Diet ; Environment, Controlled ; Firmicutes ; Gastrointestinal Microbiome ; Haplorhini ; Macaca fascicularis ; Methods ; Microbiota ; Obesity ; Prevotella ; Primates ; Spirochaetales

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.
Adenocarcinoma* ; Carcinoma, Endometrioid ; Chemoradiotherapy ; Chemoradiotherapy, Adjuvant ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Risk Factors

No abstract available.
Bone Marrow*

OBJECTIVES: This study aimed to examine the point prevalence of anxiety, depression and the associated risk factors in hospitalized patients with cancer. METHODS: A total of 114 patients with cancer who admitted to the Cancer Center in St. Mary's Hospital were enrolled for a day. The patients were asked to complete Hospital Anxiety and Depression Scale(HADS). Sociodemographic and cancer related clinical variables were also evaluated. RESULTS: The point prevalence of anxiety and depression was 10.5% and 34.2%, respectively, as assessed with HADS. Logistic regression models revealed that distant metastasis was significantly associated with anxiety in patients with cancer and previous chemotherapy and Low socioeconomic status were significantly associated with depression. CONCLUSIONS: Our results indicate that more than one third of patients with cancer suffer from either anxiety or depression. In addition, previous chemotherapy as well as low socioeconomic status and distant metastasis were associated risk factors of anxiety and depression, respectively. These findings suggest the need for screening and systematized psychosocial intervention for psychological distress in hospitalized patients with cancer.
Anxiety* ; Depression* ; Drug Therapy ; Hospitals, General* ; Humans ; Inpatients* ; Logistic Models ; Mass Screening ; Neoplasm Metastasis ; Prevalence* ; Risk Factors ; Social Class

OBJECTIVES: This study was done in Korean elderly people in order to examine the relationship of white matter hyperintensity with clinical neuropsychological function and depression symptom severity. METHODS: A total of 148 subjects diagnosed first major depressive episode after age of 60 years were included. Brain magnetic resonance imaging scan was rated with the modified Fazekas White Matter Rating Scale by researcher blinded to clinical information. Cognitive function was evaluated with a comprehensive neurological battery and depression severity was assessed by Hamilton Depression Scale. Subjects were divided into vascular depression group and non vascular group according to the degree of white matter hyperintensity. Independent t-test was used to compare clinical difference between two groups and correlation analysis was used to identify whether white matter hyperintensity severity is correlated with neuropsychological function and depressive symptom. RESULTS: Vascular depression group was significantly poorer performance in verbal fluency, Boston naming test, Mini-Mental State Examination, trail making test B and stroop test (p<0.05). Furthermore, trail making test B and stroop test performance was correlated with white matter hyperintensity severity. However, Hamilton Depression Scale score was not significantly different between two groups. CONCLUSION: Several findings from our study suggest that white matter hyperintensity is associated with neuropsychological performance, especially executive function. Moreover, executive dysfunction might contribute to poor treatment outcome of vascular depression group.
Aged ; Boston ; Brain ; Depression ; Executive Function ; Humans ; Magnetic Resonance Imaging ; Stroop Test ; Trail Making Test ; Treatment Outcome

Eosinophils are derived from hematopoietic stem cells. Peripheral blood eosinophilia is defined as an absolute eosinophil count of > or =0.5x10(9)/L. Eosinophilia is classified into primary or clonal eosinophilia, secondary eosinophilia, and idiopathic categories including idiopathic hypereosinophilic syndrome. Both hematopoietic and solid neoplasms may be associated with peripheral blood eosinophilia, but multiple myeloma is rarely associated with eosinophilia. We now report the case of a 31-year-old man with multiple myeloma associated with marked eosinophilia who developed multiple organ dysfunction with infiltration of eosinophils. He recovered after treatment with chemotherapy followed by autologous stem cell transplantation.
Adult ; Eosinophilia ; Eosinophils ; Hematopoietic Stem Cells ; Humans ; Hypereosinophilic Syndrome ; Multiple Myeloma ; Stem Cell Transplantation ; Stem Cells ; Transplantation, Autologous

Eosinophils are derived from hematopoietic stem cells. Peripheral blood eosinophilia is defined as an absolute eosinophil count of > or =0.5x10(9)/L. Eosinophilia is classified into primary or clonal eosinophilia, secondary eosinophilia, and idiopathic categories including idiopathic hypereosinophilic syndrome. Both hematopoietic and solid neoplasms may be associated with peripheral blood eosinophilia, but multiple myeloma is rarely associated with eosinophilia. We now report the case of a 31-year-old man with multiple myeloma associated with marked eosinophilia who developed multiple organ dysfunction with infiltration of eosinophils. He recovered after treatment with chemotherapy followed by autologous stem cell transplantation.
Adult ; Eosinophilia ; Eosinophils ; Hematopoietic Stem Cells ; Humans ; Hypereosinophilic Syndrome ; Multiple Myeloma ; Stem Cell Transplantation ; Stem Cells ; Transplantation, Autologous

Gastrointestinal lipomas are benign adipose tumors that are usually submucosal, and most commonly found in the colon. However, they have also been discovered in the small bowel, stomach and very rarely in the esophagus. Although most of gastrointestinal lipomas are asymptomatic and are found incidentally at time of endoscopy, surgery or autopsy, large lipomas can cause acute abdominal pain, bowel habit changes, gastrointestinal bleeding, intussusception or bowel obstruction. Lipomas can be diagnosed by colonoscopy, abdominal CT, barium series and endoscopic ultrasonography (EUS). Large lipomas need to be treated using various techniques. However, the best treatment modality for large lipomas has not yet been established. A surgical resection of lipomas should be considered for a giant lipoma >2 cm in diameter due to the risk of perforation or hemorrhage. Currently, endoscopic snare polypectomy or endo-loop ligation is used to treat symptomatic lipomas, which may reduce the risk of complications associated with endoscopic treatment. We report a case of giant colonic lipoma that was diagnosed successfully with EUS and treated safely using an endoscopic unroofing technique, endoloop ligation and snare polypectomy in phases.
Abdominal Pain ; Autopsy ; Barium ; Colon ; Colonoscopy ; Endoscopy ; Endosonography ; Esophagus ; Hemorrhage ; Intussusception ; Ligation ; Lipoma ; SNARE Proteins ; Stomach