Gender difference in alcoholic liver injury]

Gender differences of alcoholic liver injury have been described previously, but mechanisms have only partially characterized. For example, it is known that females develop alcoholic liver injury more rapidly and to a greater extent than males. It now appears that estrogen participates in several aspects of this phenomenon. On the other hand, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cell and alcohol-induced liver injury.     

Effect of providing risk information on undergoing cervical cancer screening: a randomized controlled trial

Background

In Japan, the cervical cancer screening rate is extremely low. Towards improving the cervical cancer screening rate, encouraging eligible people to make an informed choice, which is a decision-making process that relies on beliefs informed by adequate information about the possible benefits and risks of screening, has attracted increased attention in the public health domain. However, there is concern that providing information on possible risks of screening might prevent deter from participating.

Methods

In total, 1,912 women aged 20–39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 3 groups. Group A received a printed reminder with information about the possible benefits of screening, group B received a printed reminder with information about possible benefits and risks, and group C received a printed reminder with simple information only (control group).

Results

Out of 1,912 participants, 169 (8.8%) participated in cervical cancer screening. In the intervention groups, 137 (10.9%) participated in cervical cancer screening, compared to only 32 (4.9%) of the control group (p < 0.001). In addition, logistic regression analysis revealed that there was no significant difference in screening rate between group A and group B (p = 0.372).

Conclusions

Providing information on the possible risks of screening may not prevent people from taking part in cervical cancer screening among a Japanese non-adherent population.     

Regulation of intercellular adhesion molecule-1 gene expression involves multiple mRNA stabilization mechanisms: effects of interferon- gamma and phorbol myristate acetate

Although the intercellular adhesion molecule-1 (ICAM-1) is constitutively expressed at a low level on a subpopulation of hematopoietic cells, on vascular endothelium, on fibroblasts, and on certain epithelial cells, it is dramatically increased at sites of inflammation. Interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA) are known to increase the expression of ICAM-1 on many cell types. Because both human and murine ICAM-1 mRNAs contain putative destabilizing AUUUA sequences in their 3' untranslated regions (UTRs), we examined the role of mRNA stability in the regulation of ICAM-1 gene expression. The treatment of the murine monocytic cell line P388D1, which constitutively expresses ICAM-1 mRNA at a low level, with IFN- gamma or PMA rapidly enhanced the level of ICAM-1 mRNA and dramatically prolonged its half-life. To determine whether the putative destabilizing sequences are responsible for this effect of IFN-gamma and PMA, fibroblast L cells were transfected with either the full- length ICAM-1 cDNA or a truncated form (ICAM-1 delta 3) lacking the putative destabilizing AUUUA sequences. Although ICAM-1 delta 3 mRNA was more stable than the full-length ICAM-1 mRNA, IFN-gamma treatment induced the accumulation of both mRNA species and prolongation of their half-lives. The transplantation of the ICAM-1 delta 3' UTR into a stable ICAM-2 mRNA rendered it unstable, and it was unresponsive to IFN- gamma. Therefore, the treatment with IFN-gamma stabilizes the otherwise labile ICAM-1 mRNA, but the IFN-gamma-responsive sequence may at least in part reside within the protein coding region. PMA also upregulated ICAM-1 gene expression by mRNA stabilization. However, unlike IFN- gamma, PMA treatment only increased the level of the full-length, but not of the truncated, ICAM-1 mRNA. This shows that the PMA-responsive element is located within the 3'UTR. Furthermore, the effect of PMA on ICAM-1 delta 3 mRNA was recovered by ligating multiple AUUUA sequences derived from a heterologous gene fragment. The stability of this chimeric mRNA and the full-length ICAM-1 mRNA was markedly increased by PMA treatment, indicating that the AUUUA multimers in the 3'UTR are important in the PMA-induced upregulation of ICAM-1 mRNA.     

Factors predicting the response to low-dose methotrexate therapy in patients with rheumatoid arthritis: a better response in male patients

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan, MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at a dosage of no more than 8 mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether it is comparable to that in Western countries, where 15–20 mg/week of MTX is used, as well as to elucidate the factors associated with the favorable response to MTX. Around 8 mg/week of MTX was effective in half of the RA patients in the current study, and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For the remaining patients, an increase in the MTX dosage to more than 8 mg/week or the use of biologics such as the anti-tumor necrosis factor (TNF)-α monoclonal antibody may be required.     

Impact of Triggering Events on Outcomes of Acute Heart Failure

Background

The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes.

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Slow receptor acquisition by NK cells regenerated in vivo from transplanted fetal liver or adult bone marrow stem cells

Adult mouse natural killer (NK) cells express two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2, whereas fetal and neonatal NK cells express only CD94/NKG2. After birth, Ly49(+) NK cells slowly increase and CD94/NKG2(+) NK cells decrease. The aim of this study was to determine whether murine NK cells develop differently from transplants of fetal liver and adult marrow stem cells and whether the adult marrow microenvironment is critical for NK receptor maturation. Enriched populations of stem cells were transplanted into adult mice, and the kinetics of NK receptor acquisition was examined. NK cells from osteopetrotic Csf1(op)/Csf1(op) mice, in which hematopoiesis within the marrow is severely limited, were also analyzed.NK cells regenerated from both fetal and adult stem cells initially resembled neonatal NK cells in their slow acquisition of Ly49 over several weeks, although the adult stem cell-derived NK cells matured approximately 10 days sooner. NK cells from adult Csf1(op)/Csf1(op) mice expressed normal levels of Ly49. Maturation of the NK receptor repertoire is a slow process regardless of their stem cell origin or reduced marrow space caused by osteopetrosis.