Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Non-invasive diagnosis of cutaneous leishmaniasis by the direct boil loop-mediated isothermal amplification method and MinION™ nanopore sequencing

Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION? sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings.     

Higher susceptibility to osmolality of the medaka (Oryzias latipes) mutants in orthologue genes of mammalian skin transglutaminases

Transglutaminase (TG) is an essential enzyme to catalyze cross-linking reactions of epidermal proteins. Recently, we biochemically characterized human skin TG orthologues for medaka (Oryzias latipes), a model fish. By genome editing, gene-modified fishes for the two orthologues were obtained, both of which lack the ordinal enzymes. These fish appeared to exhibit higher susceptibility to osmolality at the period of larvae.     

Dizziness in peri- and postmenopausal women is associated with anxiety: a cross-sectional study

Background

Although dizziness is one of the most common symptoms of menopause, the underlying mechanism is not precisely known. Therefore, this study aimed to investigate the prevalence of, and the factors associated with, dizziness in peri- and postmenopausal women.

Methods

We conducted a cross-sectional study in which we analyzed the first-visit records of 471 Japanese women aged 40 to 65?years who enrolled in a health and nutrition education program at a menopause clinic. The prevalence of dizziness was estimated according to the participants’ responses to the Menopausal Health-Related Quality of Life Questionnaire. The background characteristics of age, menopause status, body composition, cardiovascular parameters, basal metabolism, and physical fitness; other menopausal symptoms, including vasomotor, insomnia, depression, and anxiety symptoms; and lifestyle characteristics were assessed for their associations with dizziness.

Results

The percentage of women who suffered from dizziness once a week or more frequently was 35.7%. Compared to the women without dizziness, those with the symptom were younger; had a higher body weight, body mass index, body fat percentage, muscle mass, and waist-to-hip ratio; had higher systolic pressure; were slower in reaction time; had higher physical and psychological symptom scores of menopause; exercised less regularly; and consumed less alcohol. A multivariate logistic regression analysis revealed that the anxiety symptom, which was evaluated by the Hospital Anxiety and Depression Scale, was the sole factor that was independently associated with dizziness (adjusted odds ratio 1.14; 95% confidence interval 1.08–1.20).

Conclusions

Dizziness is highly prevalent in Japanese peri- and postmenopausal women and it is associated with anxiety. The treatment of anxiety in this population might improve the symptom.

     

The yeast mitochondrial permeability transition is regulated by reactive oxygen species,endogenous Ca2+ and Cpr3, mediating cell death

We investigated the properties of the permeability transition pore (PTP) in Saccharomyces cerevisiae in agar-embedded mitochondria (AEM) and agar-embedded cells (AEC) and its role in yeast death. In AEM, ethanol-induced pore opening, as indicated by the release of calcein and mitochondrial membrane depolarization, can be inhibited by CsA, by Cpr3 deficiency, and by the antioxidant glutathione. Notably, the pore opening is inhibited, when mitochondria are preloaded by EGTA or Fluo3 to chelate matrix Ca²⁺, or are pretreated with 4-Br A23187 to extract matrix Ca²⁺, prior to agar-embedding, or when pore opening is induced in the presence of EGTA; opened pores are re-closed by sequential treatment with CsA, 4-Br A23187 plus EGTA and NADH, indicating endogenous matrix Ca²⁺ involvement. CsA also inhibits the pore opening with low conductance triggered by exogenous Ca²⁺ transport with ETH129. In AEC, the treatment of tert-butylhydroperoxide, a pro-oxidant that triggers transient pore opening in high conductance in AEM, induces yeast death, which is also dependent on CsA and Cpr3. Furthermore, AEMs from mutants lacking three ADP/ATP carrier (AAC) isoforms and with defective ATP synthase dimerization exhibit high and low conductance pore openings with CsA sensitivity, respectively. Collectively, these data show that the yeast PTP is regulated by Cpr3, endogenous matrix Ca²⁺, and reactive oxygen species, and that it is involved in yeast death; furthermore, ATP synthase dimers play a key role in CsA-sensitive pore formation, while AACs are dispensable.     

Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice

Mulberry is commonly used to feed silkworms. Here we examined whether a dietary intake of mulberry leaf (ML) could affect atherogenesis in vivo and in vitro. Apolipoprotein E-deficient mice were fed either normal chow (control group) or a diet containing 1% ML powder (ML group) from 6 weeks of age. The mice were sacrificed after 12 weeks. The susceptibility of plasma lipoprotein to oxidation was assessed using diene formation. A significant increase in the lag time of lipoprotein oxidation was detected in the ML group compared with the control group. Furthermore, the ML group showed a 40% reduction in atherosclerotic lesion size in the aortae compared with the control. We also examined the direct anti-oxidative activity of ML in vitro. Aqueous extract of ML had a strong scavenging effect on 1,1-diphenyl-2-picrylhydrazyl and inhibited lipoprotein oxidation. These results confirm that ML contains anti-oxidative substances that might help prevent atherosclerosis.     

Production and characterization of transgenic mice harboring mutant human UMOD gene

Familial juvenile hyperuricemic nephropathy is caused by mutations in the UMOD gene encoding uromodulin. A transgenic mouse model was developed by introducing a human mutant UMOD (C148W) cDNA under control of the mouse umod promoter. Uromodulin accumulation was observed in the thick ascending limb cells in the kidney of transgenic mice. However, the urinary excretion of uromodulin in transgenic mice did not decrease and LC-MS/MS analysis indicated it was of mouse origin. Moreover, the creatinine clearance was not different between wildtype and transgenic animals. Consequently, the onset of the disease was not observed in transgenic mice until 24 weeks of age.