Gastric undifferentiated carcinoma with diffuse c-kit overexpression and focal neuroendocrine differentiation

A case of gastric undifferentiated carcinoma with diffuse c-kit overexpression and focal neuroendocrine differentiation is described. A 76-year-old man presented appetite loss for 1 month. Gastric endoscopy showed an exophytic huge nodular mass with central ulceration at the gastric prepylorus. Distal gastrectomy was performed with lymph node dissection. Histology indicated anaplastic medium- to large-sized round tumor cells in discohesive sheets. Adenocarcinomatous areas forming tubular glands or with intracytoplasmic mucin on PAS and Alcian-blue staining were not found in any sections. Immunohistochemistry showed that the tumor cells were diffusely positive for cytokeratin, vimentin, c-kit and focally positive for chromogranin A and synaptophysin.     

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson’s disease

Clinical Autonomic Research - Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and...     

Notch-Hes1 signaling activation in Caroli disease and polycystic liver disease

The Notch signaling pathway plays a key role in the morphogenesis of the biliary tree, but its involvement in cystic biliary diseases, such as Caroli disease (CD) and polycystic liver disease (PLD), has yet to be determined. Immunostaining was performed using liver sections of CD and PLD, and the results were compared with those of congenital hepatic fibrosis (CHF) and von Meyenburg complex (VMC). The expression of Notch receptor 1 (Notch1) was increased in the nuclei of biliary epithelial cells in all cases of CD and PLD, whereas it remained at a low level in CHF and VMC. In addition, Notch2 and Notch3 were preferably expressed in the nuclei of biliary epithelial cells of PLD. Accordingly, the Notch effector Hes1 was highly expressed in biliary epithelial cells of CD and PLD, and the cell proliferative activity was significantly higher in CD and PLD. The expression of the Notch ligand Delta-like 1 was significantly increased in biliary epithelial cells of CD and PLD, which may be causally associated with the nuclear overexpression of Notch1 and Hes1. These results indicate that aberrant activation of the Notch-Hes1 signaling pathway may be responsible for the progression of biliary cystogenesis in CD and PLD.     

Chronic Oral Administration of Magnesium-L-Threonate Prevents Oxaliplatin-Induced Memory and Emotional Deficits by Normalization of TNF-α/NF-κB Signaling in Rats

Antineoplastic drugs such as oxaliplatin (OXA) often induce memory and emotional deficits. At present, the mechanisms underlying these side-effects are not fully understood, and no effective treatment is available. Here, we show that the short-term memory deficits and anxiety-like and depression-like behaviors induced by intraperitoneal injections of OXA (4 mg/kg per day for 5 consecutive days) were accompanied by synaptic dysfunction and downregulation of the NR2B subunit of N-methyl-D-aspartate receptors in the hippocampus, which is critically involved in memory and emotion. The OXA-induced behavioral and synaptic changes were prevented by chronic oral administration of magnesium-L-threonate (L-TAMS, 604 mg/kg per day, from 2 days before until the end of experiments). We found that OXA injections significantly reduced the free Mg²⁺ in serum and cerebrospinal fluid (from ~ 0.8 mmol/L to ~ 0.6 mmol/L). The Mg²⁺ deficiency (0.6 mmol/L) upregulated tumor necrosis factor (TNF-α) and phospho-p65 (p-p65), an active form of nuclear factor-kappaB (NF-κB), and downregulated the NR2B subunit in cultured hippocampal slices. Oral L-TAMS prevented the OXA-induced upregulation of TNF-α and p-p65, as well as microglial activation in the hippocampus and the medial prefrontal cortex. Finally, similar to oral L-TAMS, intracerebroventricular injection of PDTC, an NF-κB inhibitor, also prevented the OXA-induced memory/emotional deficits and the changes in TNF-α, p-p65, and microglia. Taken together, the activation of TNF–α/NF–κB signaling resulting from reduced brain Mg²⁺ is responsible for the memory/emotional deficits induced by OXA. Chronic oral L-TAMS may be a novel approach to treating chemotherapy-induced memory/emotional deficits.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00563-x) contains supplementary material, which is available to authorized users.     

Bacterial concentration and composition in liquid baby formula and a baby drink consumed with an artificial nipple

ObjectivesTo clarify the characteristics and growth of bacteria that may infiltrate liquid baby formula during feeding and after storage for more than 3 h, the transfer of oral bacteria through artificial nipples, and bacterial survival in liquid baby formula and a baby drink were examined immediately after drinking and after storage at 4 °C for 12 h and 24 h.MethodsThirteen human subjects (aged 19–24 years) were asked to drink approximately 50 mL of liquid baby formula and a baby drink, via the artificial nipple of a baby bottle. Samples of the remaining liquid after storage at 4 °C for 12 h and 24 h were inoculated onto blood agar plates and incubated anaerobically at 37 °C for 7 days. Genomic DNA was extracted from individual colonies, and the bacterial species were identified by 16S rRNA gene sequencing.ResultsThe mean concentrations of bacteria in the liquid baby formula were (2.6 ± 2.8) × 10⁴ and (4.1 ± 6.6) × 10⁴ colony-forming unit/mL after storage at 4 °C for 12 h and 24 h, respectively. Streptococcus (43.2%), Veillonella (9.3%), and Schaalia (8.2%) species were recovered from the remaining liquid baby formula after storage at 4 °C for 12 h. In contrast, no bacteria were detected in the remaining baby drink after storage at 37 °C for 24 h.ConclusionsThe levels of bacteria immediately after drinking and after storage at 4 °C for 12 h or 24 h were similar, suggesting that remaining liquid baby formula may be preserved safely in a refrigerator for more than 3 h.