Expression of monocyte chemoattractant protein-1 in idiopathic dilated cardiomyopathy

Immunological factors have been involved in the pathogenesis of dilated cardiomyopathy (DCM). The cytotoxic action of macrophages is one of the main factors causing cardiac myocyte damage. Monocyte chemoattractant protein-1 (MCP-1) is a major signal for the accumulation of monocytes/macrophages. We examined whether MCP-1 was expressed in the myocardium of DCM patients and whether the expression level was correlated with the degree of impairment of cardiac function. The expression of MCP-1 in the myocardium was determined by immunohistochemistry in endomyocardial biopsy samples from 13 patients. The expression of MCP-1 was found in all myocardial samples from DCM patients but not in those from control subjects. Positive staining for MCP-1 was distinct in cardiac myocytes, interstitium and infiltrating cells. Semi-quantitative analysis revealed that the expression of MCP-1 was inversely correlated with left ventricular ejection fraction. In conclusion, the expression level of MCP-1 in the myocardium was correlated with the degree of impairment of cardiac function in patients with DCM.</p

Peripartum Serial Echocardiographic Findings in a Patient with Life-threatening Peripartum Cardiomyopathy

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM

PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.

In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies

Transthyretin derived amyloid deposits in the atrium and the aortic valve: insights from multimodality evaluations and mid-term follow up

Abstract Background Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures

Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation against Japanese cedar pollen allergy.

The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation

The body weight and mortality rate.

<p>(A) The average body weights of vehicle (squares with straight line) and PE859 treatment group (triangles with dot line) was indicated by mean ± SEM. There was no significant difference between treatment groups (p = 0.71; two-way RM ANOVA). (B) The mortality rate of vehicle (straight line) and PE859 treatment group (dot line) were indicated by survival curve. The rates of dead mice during this study were 8.2% (4/49) for the vehicle group and 2.0% (1/49) for the PE859 treatment group, and there was also no significant difference between the two groups (p = 0.18; log-rank test).</p

The CD spectra of the aggregated tau.

<p>25 μM 3RMBD in the absence of PE859 (square) and presence of 10 μM PE859 (triangle) were incubated at 37°C for 24 h.</p