Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.     

Lifestyles Associated with Prognosis After Eradication of Hepatitis C Virus: A Prospective Cohort Study in Japan

Digestive Diseases and Sciences - Hepatocellular carcinoma develops in some patients with hepatitis C virus (HCV), even after achieving sustained virological response (SVR). We examined factors...     

Prevalence of diabetes mellitus in individuals with airflow obstruction in a Japanese general population: The Yamagata-Takahata Study

Background

Diabetes has been reported as a comorbidity of chronic obstructive pulmonary disease (COPD) in Western countries, but it has not been demonstrated in epidemiological reports in Japan. The purpose of this study was to clarify whether the relationship between airflow obstruction and diabetes can be confirmed in a Japanese general population.

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.     

Brief Report: Optogenetic regulation of embryo implantation in mice using photoactivatable CRISPR-Cas9

Embryo implantation is achieved upon successful interaction between a fertilized egg and receptive endometrium and is mediated by spatiotemporal expression of implantation-associated molecules including leukemia inhibitory factor (LIF). Here we demonstrate, in mice, that LIF knockdown via a photoactivatable CRISPR-Cas9 gene editing system and illumination with a light-emitting diode can spatiotemporally disrupt fertility. This system enables dissection of spatiotemporal molecular mechanisms associated with embryo implantation and provides a therapeutic strategy for temporal control of reproductive functions in vivo.     

Unique maternal deletion of 15q in a patient with some symptoms of Prader-Willi syndrome

BACKGROUND: Human chromosome 15q11-q13 is a critical region for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and most of the genes are under the condition of imprinting mechanism. PWS results from the loss of expression of paternally expressed genes and AS of maternally expressed genes. In this study molecular studies about a patient with congenital anomalies and mental retardation are analyzed. METHODS: Highly polymorphic microsatellite markers were analyzed by PCR. These markers exist within 15q11-q13 and distal to 15q13. RESULTS: Only the maternal D15S986 locus within 15q11-q13 was deleted and other markers were biallelic. CONCLUSIONS: The result of maternal small region deletion in this patient is different from the typical PWS with paternal chromosome deletion and it suggests that nearby the deleted region there exists a gene (genes) which is not imprinted but needs biallelic expression.     

High growing ability of Vibrio vulnificus biotype 1 is essential for production of a toxic metalloprotease causing systemic diseases in humans

Vibrio vulnificus biotype 1, a causative agent of fatal septicemia or wound infection in humans, is known to produce a toxic metalloprotease as an important virulence determinant. V. vulnificus biotype 2 (serovar E), a primary eel pathogen, was found to elaborate an extracellular metalloprotease that was indistinguishable from that of biotype 1. The potential of V. vulnificus biotype 1 for production of the metalloprotease was compared with biotype 2 and other human non-pathogenic Vibrio species (Vibrio anguillarum and Vibrio proteolyticus). When cultivated at 25 degrees C in tryptone-yeast extract broth supplemented with 0.9% NaCl, all bacteria multiplied sufficiently and secreted significant amounts of the metalloprotease. However, at 37 degrees C with 0.9% NaCl, V. anguillarum neither grew nor produced the metalloprotease. In human serum, only V. vulnificus biotype 1 revealed a steady multiplication accompanied with production of the extracellular metalloprotease. This prominent ability of biotype 1 in growth and protease production may contribute to cause serious systemic diseases in humans.     

High Bioavailability of α-Tocopherol Loaded into Poly (DL-Lactic-co-Glycolic Acid) Microspheres in Apolipoprotein B Knockout Mice

PURPOSE: To assess the potential clinical value of alpha-tocopherol-loaded poly (DL-lactic-co-glycolic acid) (PLGA) microspheres, we examined the disposition kinetics of alpha-tocopherol after administration of the microspheres to apolipoprotein B (apo B) knockout mice as a model of abetalipoproteinemia. METHODS: PLGA microspheres containing alpha-tocopherol were prepared by a solvent-evaporation method. The concentration of alpha-tocopherol was measured by gas chromatography-mass spectrometry. RESULTS: The mean value of particle size of alpha-tocopherol-loaded PLGA microspheres was 108 microm. The loading and the trapping efficiency of alpha-tocopherol in PLGA microspheres were 20.8% and 86.6%, respectively. When alpha-tocopherol solution (25 mg/kg) was subcutaneously administered to apob (+/+) and apob (+/-) mice, the plasma concentrations of alpha-tocopherol reached a peak at 6 h and decreased to the endogenous level within 4 days in both types of mice. However, the area under the plasma concentration-time curve (AUC) of apob (+/-) mice was significantly smaller than that in the case of apob (+/+) mice. When alpha-tocopherol-loaded PLGA microspheres (100 mg/kg) were subcutaneously administered, the plasma concentrations of alpha-tocopherol increased slowly and remained about 2-fold higher than the endogenous level at 5 to 10 days after administration in both types of mice, and there was no significant difference between the AUC values. CONCLUSIONS: The PLGA microsphere preparation of alpha-tocopherol is expected to be a very useful drug delivery system in vitamin E supplementation therapy for abetalipoproteinemia.     

Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP

Recently, we reported that combined ingestion of soy isoflavones and curcumin significantly decreased the serum level of prostate-specific antigen based on a randomized placebo-controlled double-blind clinical study. We investigated whether these polyphenols inhibited the proliferation of prostate cancer cells by activating a DNA damage response. The effects of isoflavones and curcumin on the expression and phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2AX variant (H2AX) and checkpoint kinase2 (Chk2) were examined in LNCaP cells. The induction of apoptosis in LNCaP cells was evaluated by poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the effects of a testosterone supplement on modulation of the DNA damage response were examined. Combined treatment of isoflavones and curcumin additively suppressed cellular proliferation and induced phosphorylation of ATM, histone H2AX, Chk2 and p53. Testosterone augmented the activation of the DNA damage response and PARP cleavage induced by curcumin. Our results indicate that activation of the DNA damage response by polyphenols might suppress the malignant transformation of prostate cancer. In addition, testosterone, when combined with curcumin, may have suppressive effects on the progression of prostate cancer.