Inhibition of dopamine receptor D1 signaling promotes human bile duct cancer progression via WNT signaling

Bile duct cancer (BDC) frequently invades the nerve fibers, making complete surgical resection difficult. A single tumor mass contains cells of variable malignancy and cell-differentiation states, with cancer stem cells (CSCs) considered responsible for poor clinical outcomes. This study aimed to investigate the contribution of autosynthesized dopamine to CSC-related properties in BDC. Sphere formation assays using 13 commercially available BDC cell lines demonstrated that blocking dopamine receptor D1 (DRD1) signaling promoted CSC-related anchorage-independent growth. Additionally, we newly established four new BDC patient-derived organoids (PDOs) and found that blocking DRD1 increased resistance to chemotherapy and enabled xenotransplantation in vivo. Single-cell analysis revealed that the BDC PDO cells varied in their cell-differentiation states and responses to dopamine signaling. Further, DRD1 inhibition increased WNT7B expression in cells with bile duct-like phenotype, and it induced proliferation of other cell types expressing Wnt receptors and stem cell-like signatures. Reagents that inhibited Wnt function canceled the effect of DRD1 inhibition and reduced cell proliferation in BDC PDOs. In summary, in BDCs, DRD1 is a crucial protein involved in autonomous CSC proliferation through the regulation of endogenous WNT7B. As such, inhibition of the DRD1 feedback signaling may be a potential treatment strategy for BDC.     

Robotic gastrectomy for gastric cancer: systematic review and future directions

Gastric Cancer - Robotic gastrectomy (RG) using the da Vinci Surgical System for gastric cancer was approved for national medical insurance coverage in Japan in April 2018, and its number has been...     

Suicide attempt using potassium tablets for congenital chloride diarrhea: A case report

BACKGROUND Congenital chloride diarrhea(CCD)is a rare inherited disorder of intestinal electrolyte transport that results in a large wastage of electrolytes and water.Advances in substitution therapy using sodium chloride(NaCl)and potassium chloride(KCl)have dramatically improved survival for patients with CCD.Slowrelease KCl is widely prescribed as a potassium supplement;however,it has also occasionally been used in suicide attempts,as potassium poisoning can generate life-threatening hyperkalemia.CASE SUMMARY A 26-year-old female presented to the emergency department(ED)with selfpoisoning,having taken 30 tablets of slow-release KCl(total:240 mmol potassium)following an auditory hallucination.The patient had been undergoing substitution therapy with NaCl and KCl for CCD and been followed up in the pediatric department.One month prior,she developed insomnia and anxiety and had consulted a psychiatrist.At the ED,although her general condition was good,she appeared agitated.Her serum potassium level was 7.0 mmol/L,indicating hyperkalemia,and electrocardiographic changes showed tenting of the T-waves.She responded to the administration of calcium gluconate,sodium bicarbonate,and insulin with glucose,and the serum potassium level improved.Finally,she was diagnosed with schizophrenia.CONCLUSION In CCD management,physicians should pay careful attention to patients’extraintestinal issues,including psychological disorders that may emerge in adulthood.     

Vasodilator‐stimulated phosphoprotein (VASP) is recruited into dendritic spines via G‐actin‐dependent mechanism and contributes to spine enlargement and stabilization

Actin organization and dynamics are modulated by diverse actin regulators during dendritic spine development. To understand the molecular network that regulates actin organization and spine morphology, it is important to investigate dynamic redistribution of actin regulators during spine development. One of the actin regulators, vasodilator‐stimulated phosphoprotein (VASP), has multiple functions in actin regulation and is known to regulate spine morphology. However, dynamics and temporal regulation of VASP during spine development have not been clarified. In this study, we performed time‐lapse imaging of mouse hippocampal dissociated neurons to analyse the change in localization of VASP during spine development. We found that accumulation of VASP within spines precedes the start of persistent F‐actin increase, which are temporally coupled with spine enlargement. Using domain deletion or mutation constructs of VASP, we revealed that the interaction with G‐actin is important for the preceding accumulation of VASP. Furthermore, we showed that accumulation of VASP contributes to actin enrichment within spines and stabilization of spine morphology by dominant negative experiments. These data suggest that G‐actin‐dependent VASP recruitment has dual functions in spine development, enlargement and stabilization, through the interaction with actin and other cytoskeletal regulators.     

High expression of eosinophil chemoattractant ecalectin/galectin-9 in drug-induced liver injury.

BACKGROUND: Ecalectin/galectin-9 (ECL/GL9) is an eosinophil chemoattractant isolated from T lymphocytes. Drug-induced liver injury (DILI), often caused by an allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In this study, we intended to determine whether DILI can induce augmentation of ECL/GL9 expression. Further, we investigated whether this augmentation is associated with tissue eosinophilia. METHODS: We examined the expression of ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A rabbit anti-ECL/GL9 antibody was produced by immunizing rabbits with synthetic peptide corresponding to a molecular epitope of ECL/GL9. Thereafter, immunohistochemical staining with the use of this antibody was performed on 16 DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis, liver cirrhosis, and normal liver tissues as controls. RESULTS: In all cases of DILI specimens, but not in control liver specimens, a clear positive staining for ECL/GL9 was observed. Such positive staining was noted on Kupffer cells, fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the intensity of immunolabeling did not correlate with the extent of eosinophile leukocyte infiltration. CONCLUSION: High expression of ECL/GL9 is suggested to be a specific finding of DILI. However, tissue eosinophilia in DILI cannot be explained by the augmentation of ECL/GL9 expression.     

Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease

Point mutations in the mitochondrial (mt) tRNA(Leu(UUR)) gene are responsible for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a subgroup of mitochondrial encephalomyopathic diseases. We previously showed that mt tRNA(Leu(UUR)) with an A3243G or T3271C mutation derived from patients with MELAS are deficient in a normal taurine-containing modification (taum5U; 5-taurinomethyluridine) at the anticodon wobble position. To examine decoding disorder of the mutant tRNA due to the wobble modification deficiency independent of the pathogenic point mutation itself, we used a molecular surgery technique to construct an mt tRNA(Leu(UUR)) molecule lacking the taurine modification but without the pathogenic mutation. This "operated" mt tRNA(Leu(UUR)) without the taurine modification showed severely reduced UUG translation but no decrease in UUA translation. We thus concluded that the UUG codon-specific translational defect of the mutant mt tRNAs(Leu(UUR)) is the primary cause of MELAS at the molecular level. This result could explain the complex I deficiency observed clinically in MELAS.     

Immunohistochemical study of the distribution of endogenous biotin and biotin-binding enzymes in ductal structures of salivary gland tumours

To clarify the pathologic value of endogenous biotin in the salivary gland, we examined in a series of neoplasms of the salivary gland by immunohistochemical staining the distribution of endogenous biotin and of biotin-binding enzymes, namely, acetyl CoA carboxylase (AC), which is a cytosolic enzyme, and pyruvate carboxylase (PC), which is a mitochondrial enzyme. In pleomorphic adenoma, we found biotin and PC in ductal epithelial elements, while AC was found mainly in myoepithelial elements. Carcinoma ex pleomorphic adenoma, adenocarcinoma and mucoepidermoid carcinoma were frequently immunopositive for biotin, PC and AC, while adenoid cystic carcinoma was rarely immunopositive for biotin, PC or AC. These results indicate that endogenous biotin might be associated with the mitochondrial enzyme, which is present at high levels in ductal cells of the salivary gland. However, the neoplastic cells in adenoid cystic carcinoma seemed to have an unusual expression of biotin and related enzymes.     

Acute septic arthritis of the temporomandibular joint derived from otitis media: a report and review of the English and Japanese literature

Septic arthritis of the temporomandibular joint (SATMJ) is an extremely rare disease with characteristic features of preauricular pain, swelling, redness, and malocclusion. The present report describes a case of SATMJ derived from otitis media, which resulted in a good outcome. We also reviewed the English and Japanese literature with special interest in etiology. It is generally agreed that contiguous or distant infection and trauma are common etiological factors of SATMJ. So far, these etiological factors are mainly discussed based on hypotheses rather than sufficient evidence. Therefore, in many past cases, accurate causes were not identified. To our knowledge, our case is the third report of SATMJ following otitis media. In addition, this is the first case in which the pathogenic bacterium responsible for the otitis media was the definite cause of the SATMJ. Cases of SATMJ are sometimes misdiagnosed with otitis media, and SATMJ derived from otitis media is extremely rare. Dentists and otolaryngologists should collaborate for the management of this disease as needed.     

OK-432 pleurodesis for the treatment of pneumothorax in patients with interstitial pneumonia

Background

Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin.