Developmental Changes in Serotonergic Modulation of GABAergic Synaptic Transmission and Postsynaptic GABA<Subscript>A</Subscript> Receptor Composition in the Cerebellar Nuclei

Outputs from the cerebellar nuclei (CN) are important for generating and controlling movement. The activity of CN neurons is controlled not only by excitatory inputs from mossy and climbing fibers and by γ-aminobutyric acid (GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex but is also modulated by inputs from other brain regions, including serotonergic fibers that originate in the dorsal raphe nuclei. We examined the modulatory effects of serotonin (5-HT) on GABAergic synapses during development, using rat cerebellar slices. As previously reported, 5-HT presynaptically decreased the amplitudes of stimulation-evoked inhibitory postsynaptic currents (IPSCs) in CN neurons, with this effect being stronger in slices from younger animals (postnatal days [P] 11–13) than in slices from older animals (P19–21). GABA release probabilities accordingly exhibited significant decreases from P11–13 to P19–21. Although there was a strong correlation between the GABA release probability and the magnitude of 5-HT-induced inhibition, manipulating the release probability by changing extracellular Ca²⁺ concentrations failed to control the extent of 5-HT-induced inhibition. We also found that the IPSCs exhibited slower kinetics at P11–13 than at P19–21. Pharmacological and molecular biological tests revealed that IPSC kinetics were largely determined by the prevalence of α₁ subunits within GABA_A receptors. In summary, pre- and postsynaptic developmental changes in serotonergic modulation and GABAergic synaptic transmission occur during the second to third postnatal weeks and may significantly contribute to the formation of normal adult cerebellar function.     

Apparent diffusion coefficient histogram analysis for prediction of prognosis in glioblastoma

Background

To investigate the potential to predict prognosis of glioblastoma (GBM) patients by analysis of the broader and lower values in the lower distribution of apparent diffusion coefficient (ADC_L) (B&L-ADC_L) values in the ADC histogram.

Effective use of the Japan Narrow Band Imaging Expert Team classification based on diagnostic performance and confidence level

Five years have passed since the Japan Narrow Band Imaging Expert Team (JNET) classification was proposed in 2014. However, the diagnostic performance of this classification has not yet been established. We conducted a retrospective study and a systematic search of Medical Literature Analysis and Retrieval System On-Line. There were three retrospective single center studies about the diagnostic performance of this classification. In order to clarify this issue, we reviewed our study and three previous studies. This review revealed the diagnostic performance in regards to three important differentiations. (1) Neoplasia from non-neoplasia; (2) malignant neoplasia from benign neoplasia; and (3) deep submucosal invasive cancer (D-SMC) from other neoplasia. The sensitivity in differentiating neoplasia from non-neoplasia was 98.1%-99.8%. The specificity in differentiating malignant neoplasia from benign neoplasia was 84.7%-98.2% and the specificity in the differentiation D-SMC from other neoplasia was 99.8%-100.0%. This classification would enable endoscopists to identify almost all neoplasia, to appropriately determine whether to perform en bloc resection or not, and to avoid unnecessary surgery. This article is the first review about the diagnostic performance of the JNET classification. Previous reports about the diagnostic performance have all been retrospective single center studies. A large-scale prospective multicenter evaluation study is awaited for the validation.     

MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma

Xp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early‐stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC‐TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)‐204‐5p levels in urinary exosomes of 40‐week‐old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA‐204‐5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR‐204‐5p‐containing exosomes. Notably, we also observed increased miR‐204‐5p levels in urinary exosomes in 20‐week‐old renal PRCC‐TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40‐week‐old Tg mice, suggesting that miR‐204‐5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR‐204‐5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC‐TFE3 fusion gene. These findings suggest that miR‐204‐5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.     

Quantitative diagnosis of chronic pancreatitis using EUS elastography

Journal of Gastroenterology - It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to...