Left ventricular cardiac hemangioma in a patient with chronic heart failure

Cardiac hemangiomas are rare benign tumors. Here, we report the case of a man in his 30s who had a cardiac hemangioma with no symptoms. He was being treated with β-blockers for chronic heart failure with hypertensive heart disease at Osaka Minato Central Hospital. Routine echocardiography revealed a mobile spherical mass in the left ventricle that had not been detected on echocardiography performed 4 months previously. Subsequently, the tumor was excised to prevent potential embolic events and was pathologically diagnosed as a cardiac hemangioma. This case demonstrates the relatively rapid progress of a cardiac hemangioma regardless of β-blocker administration, which is occasionally used for the treatment of hemangiomas. The efficacy of β-blockers in treating cardiac hemangiomas may vary according to the type of β-blocker. Echocardiography is useful in screening and follow-up of cardiac hemangiomas; however, additional imaging modalities are needed for differential diagnosis.     

SVEP1 plays a crucial role in epidermal differentiation

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.     

Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease

Erythropoietin (Epo) gene expression is under the control of hypoxia-inducible factor 1 (HIF-1), and is negatively regulated by GATA. Interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), which increase the binding activity of GATA and inhibit Epo promoter activity, are increased in patients with anemia of chronic disease (ACD). We previously demonstrated the ability of K-7174 (a GATA-specific inhibitor), when injected intraperitoneally, to improve Epo production that had been inhibited by IL-1beta or TNF-alpha treatment. In the present study, we examined the ability of both K-11706, which inhibits GATA and enhances HIF-1 binding activity, and K-13144, which has no effect on GATA or HIF-1 binding activity, to improve Epo production following inhibition by IL-1beta or TNF-alpha in Hep3B cells in vitro and in an in vivo mouse assay. Oral administration of K-11706 reversed the decreases in hemoglobin and serum Epo concentrations, reticulocyte counts, and numbers of erythroid colony-forming units (CFU-Es) induced by IL-1beta or TNF-alpha. These results raise the possibility of using orally administered K-11706 for treating patients with ACD.     

Specific cellular immune responses to pancreatic antigen in chronic pancreatitis and Sjögren's syndrome

The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögren's syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index >2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%;P<0.05), 6 of 7 patients with Sjögren's syndrome-associated chronic pancreatitis (86%;P<0.0005), and 6 of 11 patients with Sjögren's syndrome (55%;P<0.01), compared to normal controls whose stimulation index was 0.94±0.28 (mean ± SD;n=14; range, 0.56–1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%;n=12), stone-related chronic pancreatitis (0%;n=7), primary biliary cirrhosis-associated chronic pancreatitis (33%;n=3), primary biliary cirrhosis (0%;n=4), systemic lupus erythematosus (17%;n=6), and autoimmune thyroiditis (0%;n=6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4⁺ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögren's syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.     

Relationship between surrounding tissue morphology and directional collective migration of the posterior lateral line primordium in zebrafish

Collective cell migration, in which cells assemble and move together, is an essential process in embryonic development, wound healing and cancer metastasis. Chemokine signaling guides cell assemblies to their destinations. In zebrafish posterior lateral line primordium (PLLP), a model system for collective cell migration, it has been proposed that the chemokine ligand Cxcl12a secreted from muscle pioneer cells (MPs) and muscle fast fibers (MFFs), which are distributed along with the horizontal midline, binds to the receptor Cxcr4b in PLLP and that Cxcl12a–Cxcr4b signaling guides the anterior‐to‐posterior migration of PLLP along the horizontal midline. However, how the surrounding tissues affect PLLP migration remains to be elucidated. Here, we investigated the relationship between the PLLP and the surrounding tissues and found that a furrow between the dorsal and ventral myotomes is generated by Sonic hedgehog (Shh) signaling‐dependent MP and MFF differentiation and that the PLLP migrates in this furrow. When transient inhibition of Shh signaling impaired both the furrow formation and differentiation of cxcl12a‐expressing MPs/MFFs, directional PLLP migration was severely perturbed. Furthermore, when differentiated MPs and MFFs were ablated by femtosecond laser irradiations, the furrow remained and PLLP migration was relatively unaffected. These results suggest that the furrow formation between the dorsal and ventral myotomes is associated with the migratory behavior of PLLP.     

Epidemiological evidence that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated mean corpuscular volume in alcohol drinkers

BACKGROUND: Elevated mean corpuscular volume (MCV) is a traditional biological marker for alcohol abuse and alcoholism, but the underlying mechanism is unclear. Three recent epidemiologic studies consistently showed that MCV was elevated by alcohol drinking more markedly among individuals with genetically inactive aldehyde dehydrogenase-2 (ALDH2) (encoded by ALDH2*2 mutant allele) than those with active ALDH2 (encoded by ALDH2*1/2*1 genotype), suggesting that the elevated MCV was etiologically linked to acetaldehyde exposure. The purpose of the present study was to clarify further this relationship by examining the status of folate and vitamin B12. METHODS: The study participants were 159 men who were aged 40 to 69 years and randomly selected from a Japanese rural population. The genetic polymorphism of ALDH2 was determined by PCR-restriction fragment length polymorphism method; data on alcohol drinking and other lifestyles were collected using a structured questionnaire; serum concentrations of folate and vitamin B12 were measured using the protein competitive reaction method, and blood cell counts were measured by routine methods. A multiple linear regression model was used to analyze the data. RESULTS:: The relationship between alcohol drinking and serum folate concentration was significantly different between ALDH2 genotypes, indicating that the reduction of serum folate by alcohol drinking was more marked in men with ALDH2*1/2*2 than those with ALDH2*1/2*1. The relationship between alcohol drinking and elevated MCV was significantly stronger in men with ALDH2*1/2*2 than those with ALDH2*1/2*1 even after adjustment for serum folate and vitamin B12 concentrations. CONCLUSIONS: These findings indicate that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated MCV by alcohol drinking.