The Effects of Estrogen and Antiestrogen on Chromatin in Human Breast Cancer Cell Line, MCF-7. II.

The effects of estrogen and antiestrogen on chromatin in a human breast cancer cell line, MCF-7, were studied in cells grown in media containing 10-8 M estradiol or 10-6 M tamoxifen for 1, 3 and 8 days. The effect on incorporation of thymidine into DNA was determined. Maximal incorporation occurred on day 1 after administration of estradiol, but was depressed to a low level within 3-8 days. A small increase in incorporation was observed on 1-3 days after administration of tamoxifen, but this was also depressed to a low level within 8 days. The uptake of [32P]orthophosphate into an individual protein band was observed using sodium dodecyl sulfate-polyacrylamide gels in chromatin from the cells on day 1 after administration of estradiol and tamoxifen. The difference in the action mechanisms of estradiol and tamoxifen may be explained in part by the uptake of phosphate into individual protein. The results of the present experiments may be due to influence of either estradiol and tamoxifen on the cell cycle as well

Relationship between Pressure Ulcers in Elderly People and Physiological Indices of the Skin

This study examined the relationship between skin physiological indices and pressure ulcers in elderly people. The subjects were 55 bedridden elderly Japanese patients with a median age of 85 years. The following parame-ters were measured using non-invasive devices: skin surface temperature, moisture content in the stratum corneum, moisture content in the dermis, transepidermal water loss as an index of skin barrier function, skin erythema and skin elasticity. The sacral and 2 heel areas were observed as sites predisposed to pressure ulcers. Within one month after measuring the skin physiological indices, we confirmed pressure ulcers of National Pressure Ulcer Advisory Panel classification Stage II or worse based on medical records. Among the 55 patients, 4 (7.3%) prospectively developed a total of 5 pressure ulcers within 16 days. Only the skin erythema score was significantly higher with than without pressure ulcers (p < 0.001). We performed a binary logistic regression analysis and confirmed a significant relationship between pressure-ulcer development and the level of erythema (odds ratio = 1.026; 95% confidence interval: 1.011-1.042). Skin erythema increased before the development of pressure ulcers. Taken together, our results show that the high skin erythema score can be a predictive indicator of pressure ulcers

MDM2 is a novel E3 ligase for HIV-1 Vif

The human immunodeficiency virus type 1 (HIV-1) Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G). Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3) complex with Cullin5-ElonginB/C. Although Vif itself is also ubiquitinated and degraded rapidly in infected cells, precise roles and mechanisms of Vif ubiquitination are largely unknown. Here we report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif. We also show the mechanisms by which MDM2 only targets Vif, but not A3G that binds to Vif. MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif precludes A3G from binding to Vif. Furthermore, we demonstrate that MDM2 negatively regulates HIV-1 replication in non-permissive target cells through Vif degradation. These data suggest that MDM2 is a regulator of HIV-1 replication and might be a novel therapeutic target for anti-HIV-1 drug

Exome Sequencing Reveals a Homozygous SYT14 Mutation in Adult-Onset, Autosomal-Recessive Spinocerebellar Ataxia with Psychomotor Retardation

Autosomal-recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous disorders associated with diverse neurological and nonneurological features that occur before the age of 20. Currently, mutations in more than 20 genes have been identified, but approximately half of the ARCA patients remain genetically unresolved. In this report, we describe a Japanese family in which two siblings have slow progression of a type of ARCA with psychomotor retardation. Using whole-exome sequencing combined with homozygosity mapping, we identified a homozygous missense mutation in SYT14, encoding synaptotagmin XIV (SYT14). Expression analysis of the mRNA of SYT14 by a TaqMan assay confirmed that SYT14 mRNA was highly expressed in human fetal and adult brain tissue as well as in the mouse brain (especially in the cerebellum). In an in vitro overexpression system, the mutant SYT14 showed intracellular localization different from that of the wild-type. An immunohistochemical analysis clearly showed that SYT14 is specifically localized to Purkinje cells of the cerebellum in humans and mice. Synaptotagmins are associated with exocytosis of secretory vesicles (including synaptic vesicles), indicating that the alteration of the membrane-trafficking machinery by the SYT14 mutation may represent a distinct pathomechanism associated with human neurodegenerative disorders

Sex differences in patients with acute decompensated heart failure in Japan: observation from the KCHF registry

Aims: The association between sex and long‐term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1‐year outcomes between the sexes in a large‐scale database representing the current real‐world clinical practice in Japan. Methods and results: Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1‐year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76–88) years vs. 77 (68–84) years, P < 0.0001]. Hypertensive and valvular heart diseases were more prevalent in women than in men (28.0% vs. 22.5%, P = 0.0001; and 26.9% vs. 14.0%, P < 0.0001, respectively), whereas ischaemic aetiology was less prevalent in women than in men (20.0% vs. 32.5%, P < 0.0001). Women less often had reduced left ventricular ejection fraction (<40%) than men (27.5% vs. 45.1%, P < 0.0001). The cumulative incidence of all‐cause death or hospitalization for heart failure was not significantly different between women and men (33.6% vs. 34.3%, P = 0.71), although women were substantially older than men. After multivariable adjustment, the risk of all‐cause death or hospitalization for heart failure was significantly lower among women (adjusted hazard ratio: 0.84, 95% confidence interval: 0.74–0.96, P = 0.01). Conclusions: Women with heart failure were older and more often presented with preserved EF with a non‐ischaemic aetiology and were associated with a reduced adjusted risk of 1‐year mortality compared with men in the Japanese population