Lustrous White Erosions Surrounded by an Erythematous Mucosa: A Novel Endoscopic Finding of Gastric Lesions in Patients with Wilson Disease

Wilson disease is an inherited copper metabolism disorder. We herein report a novel endoscopic finding in three men with Wilson disease. These patients underwent upper endoscopy due to gastrointestinal symptoms or during follow-up. In each case, endoscopy revealed lustrous white erosions surrounded by an erythematous mucosa in the greater curvature of the gastric body. A biopsy of the lesions showed orcein-positive tissue, indicating copper deposition, in the interstitial stroma and fundic glands of the mucosa. All patients had been receiving treatment with zinc acetate. These endoscopic findings might have been related to the cytotoxicity of the accumulated copper and zinc acetate.     

Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease?

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.     

Histology of the tricuspid valve annulus and right atrioventricular muscle distance

Open in a separate window OBJECTIVESHistologically, the mitral valve annulus comprises a collection of collagen fibres. However, the existence of collagen fibres in the tricuspid valve annulus has not been elucidated. Our goal was to clarify the histology of the tricuspid annulus.METHODSFifty human hearts without heart disease that were autopsied at Osaka City University Hospital between January 2009 and December 2017 were examined. The tricuspid valve was sectioned at 12 sites around the annulus, and the atrioventricular junction distance was measured.RESULTSNone of the tricuspid valve annulus samples had a continuous aggregation of collagen fibres that could be called an annulus. The interventricular space between the right atria and ventricles was composed of adipose tissue only on the anterosuperior and inferior sides, and no adipose tissue was found on the septal side. Comparing the atrioventricular muscle distance of the anterosuperior and inferior sides, the distance at the inferior side was statistically significantly larger than that of the anterosuperior side in 47 cases (P < 0.0001).CONCLUSIONSThere was no continuous circumferential aggregation of collagen fibres in the right atrioventricular junction. The distance between the right atrial and ventricular myocardium was greater at the inferior side than that at the anterosuperior side, which might lead to more inferior annular dilation versus anterosuperior dilation. These anatomical features will be fundamental for future discussions of the suturing method used in prosthetic ring annuloplasty for tricuspid regurgitation.     

Lectin‐like oxidized low‐density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan‐induced arthritis

Objective

The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low‐density lipoprotein (ox‐LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin‐like ox‐LDL receptor 1 (LOX‐1), in arthritic joints using a rat zymosan‐induced arthritis (ZIA) model.

Methods

LOX‐1 expression and ox‐LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti–LOX‐1 and anti–ox‐LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX‐1 on arthritis, ZIA rats were treated with anti–LOX‐1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured.

Results

Immunohistochemical study of ZIA demonstrated LOX‐1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX‐1 was also expressed weakly on both joint cartilage and synovium. Ox‐LDL, a ligand of LOX‐1, was also detected in articular chondrocytes. Administration of anti–LOX‐1 antibody, which blocks LOX‐1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats.

Conclusion

LOX‐1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.

     

Alterations of ATG4A and LC3B in neurons derived from Alzheimer's disease patients

We investigated the alterations in autophagy-related molecules in neurons differentiated from induced pluripotent stem cells obtained from patients with Alzheimer's disease (AD). Consistent with our previous microarray data, ATG4A protein was upregulated in the neurons derived from a familial AD patient with an APP-E693Δ mutation who showed accumulation of intracellular amyloid β peptide (Aβ). This upregulation was reversed by inhibiting Aβ production, suggesting that the intracellular Aβ may be responsible for the upregulation of ATG4A. The LC3B-II/LC3B-I ratio, an index of autophagosome formation, was lower in the neurons derived from the AD patient with APP-E693Δ as well as the neurons derived from other familial and sporadic AD patients. These findings indicate that dysregulation of autophagy-related molecules may accelerate the pathogenesis of AD.