Coronary vessel anomalies affect up to 1% of the population. These blood vessels constantly supply the myocardium with oxygen and nutrients. The proepicardium (PE) is a source of progenitor cells for the epicardium and coronary vessels. It is a transitory cluster of epithelial‐like mesothelial cells that lies dorsal to the primitive heart tube. During cardiovascular development, epithelial cells of the PE migrate toward the heart tube and adhere to the myocardium to form the epicardium. Epicardial cells proliferate, undergo apoptosis and epithelial‐mesenchymal transition (EMT) to become epicardial‐derived cells (EPDCs). EPDCs delaminate and invade the myocardium to form a subset of coronary vascular cells. Conditional deletion of the Tbx5 transcription factor in the PE impairs epicardium and coronary vessel formation during mouse heart development and reduces cardiac expression of adherens junction‐associated protein 1 (AJAP1). AJAP1 is a cell adhesion molecule that regulates epithelial cell behavior in cancer cells by influencing migration, adhesion and epithelial‐mesenchymal transition (EMT). We observed AJAP1 expression in the PE, epicardium and coronary vessels of mouse embryos. However, its role in cardiovascular development is unknown. Study Objective Our goal was to determine how AJAP elicits changes in epithelial cell behaviors integral to cardiovascular development. Previous investigators indicated that AJAP1 repression in hepatocellular cancer cells increased β‐catenin nuclear translocation. This led to increased metastasis and tumor growth via β‐catenin‐induced transcriptional activation. We hypothesize that AJAP1 interacts with the β‐catenin‐E‐cadherin complex in normal epithelial cells to influence gene expression and regulate cell behaviors that are necessary for epicardium and coronary vessel formation. Methods We used primary human mammary epithelial cells (HMEpiCs) to examine in vitro contributions of AJAP1 to epithelial cell behaviors that are necessary for epicardium and coronary vessel formation. Small interfering RNAs (siRNA) silenced endogenous AJAP1 mRNA and reduced protein expression. We analyzed siRNA‐transfected HMEpiCs for associations between cell migration and cell expression and localization of β‐catenin‐E‐cadherin complexes. Also, we examined these cells for changes in gene expression that contribute to epicardium and coronary vessel formation. Results siRNA‐mediated silencing of AJAP1 led to a >85% decrease in AJAP1 mRNA expression in HMEpiCs. Epithelial cell migration was altered in AJAP1‐silenced HMEpiCs compared to control cells. β‐catenin expression was observed in AJAP1‐silenced cells. Also, we noted changes in gene expression that account for these observable differences. Conclusion Our data indicates that AJAP1 contributes to epithelial cell functions by altering cell migration. This behavior is potentially mediated through interactions with the β‐catenin‐E‐cadherin complex. These findings will enable us to understand the developmental role of AJAP1 during formation of the e...
Ganser syndrome (GS) is a rare neurological disorder characterized by answer approximation, clouded consciousness, somatic conversion symptoms, and visual or auditory hallucinations. The objective of this case report is to elucidate the presentation of a patient with GS and to highlight the interplay of psychological and organic determinants in this condition. We present a 66-year-old man with a history of concussion and short-term memory loss who presented with selective, remote, and recent memory loss following the death of his wife, visual hallucinations, approximation of answers regarding his current state, and limited insight into his condition. We found the patient oriented only to place and person, with impaired shortterm memory and no language abnormalities. Montreal cognitive assessment (MOCA) exam showed mild-to-moderate cognitive impairment. The patient's presentation can be explained by both psychological and organic causes. Negative results from imaging and testing showed that the patient's recent emotional stressor, the death of his wife, may be contributing to the current state. However, the patient also has a history of hospitalization for traumatic brain injury (TBI) and a recent history of progressive memory loss. Therefore, the combination of psychological and organic factors likely played supplementary roles in the patient's current presentation. This case supports the literature that GS is a psychogenic disorder. However, an organic cause from the long-term sequelae of TBI needs further exploration.
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