Keratin inclusions alter cytosolic protein localization in hepatocytes

Aim:  Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined.
Methods:  Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18-transfected cells. In this study, we treated green fluorescent protein-tagged wild-type keratin 18-transfected cells with several proteasome inhibitors and performed immunofluorescent analyses.
Results:  Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens-1 and β-catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14-3-3 ζ protein and glucose-6-phosphate dehydrogenase were also relocated to inclusions. Moreover, E-cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion-containing cells.
Conclusion:  These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.     

Markedly improved glycemic control and enhanced insulin sensitivity in a patient with type 2 diabetes complicated by a suprasellar tumor treated with pioglitazone and metformin

A patient with type 2 diabetes and hypothalamic damage due to a suprasellar tumor developed impaired glycemic control and central obesity. The patient showed exaggerated adrenocorticotropic hormone responsiveness as determined by a corticotrophin releasing hormone test and elevated serum leptin concentrations associated with ravenous appetite and insulin resistance mediated in part through disturbances in leptin signaling. Combination treatment with metformin and pioglitazone was markedly effective in improving glycemic control. Additionally, metformin treatment showed marked anorectic effects on the hyperphagia. This case has important implications for the pathogenesis and management of diabetes in patients with hypothalamic-pituitary-adrenal axis deficiencies.     

Clinical and pathological characteristics of surgically resected intrapulmonary lymph nodes: Can they be differentiated from other malignant nodules?

Background

Intrapulmonary lymph nodes (IPLNs) are often recognized as sub-centimeter solid pulmonary nodules (SCPNs). The present study investigated their clinical and pathological characteristics to allow clinicians to distinguish them from malignant nodules.

Gastrospirillum hominis-associated gastritis: The first reported case in Japan

Tightly coiled spiral micro-organisms (Gastrospirillum hominis), distinct fromHelicobacter pylori, were found in the gastric mucosa of a 66-year-old man with a 4-month history of intermittent epigastric pain. The organisms were distributed in the antral mucosa, which showed erosive gastritis; histologically, the affected mucosa presented moderate to severe chronic gastritis with focal neutrophil infiltration. After a 2-week administration of cimetidine, his symptoms resolved and the active inflammation was reduced, both endoscopically and histologically, but the organisms still remained. Biopsy specimens taken 4 weeks after treatment with minocycline and cimetidine showed normal gastric mucosa without the spiral organisms. The above clinical course suggests the possible role ofGastrospirillum hominis in the pathogenesis of gastritis.     

Clinical significance of a papillary adenocarcinoma component in early gastric cancer: a single-center retrospective analysis of 628 surgically resected early gastric cancers

Background

We recently reported that the presence of a papillary adenocarcinoma (pap) component was an independent risk factor for lymphatic involvement in endoscopically resected early gastric cancer (EGC). This study aimed to investigate the potential association between the presence of a pap component in EGC and lymph node metastasis (LNM).

Methods

In order to evaluate the association between LNM and clinicopathological features, including a pap component, we reviewed 628 surgically resected EGCs at our institution between 2009 and 2012. Clinicopathological features included age, gender, tumor location, macroscopic type, tumor size, histological type, depth, ulcerative findings, and lymphatic and venous involvement. In addition, the association between clinicopathological features and lymphatic involvement was also evaluated.

Results

LNM was observed in 52 cases (8.3%). Univariate analyses revealed a significant correlation between a pap component and LNM as well as tumor size, depth, macroscopic type, a poorly differentiated adenocarcinoma component, and lymphatic and venous involvement. The percentage of positive LNM among the EGC cases with a pap component was significantly higher than in those without the component (18.2 vs. 7.3%, P = 0.010). Via multivariate analyses lymphatic involvement was identified as the strongest risk factor for LNM [odds ratio (OR) 14.1] and a pap component was revealed as an independent risk factor for lymphatic involvement (OR 3.1).

Conclusion

Our study revealed that EGC cases with a pap component were at higher risk of lymphatic involvement and showed a higher percentage of positive LNM. More attention should be paid to a pap component in EGC.