Association between KIR genes and dust mite sensitization in a Brazilian population

Background

Killer cell immunoglobulin-like receptors (KIRs), found on the surface of natural killer (NK) cells, play a key role in controlling the innate response. Such response depends on a series of cellular interactions between these receptors and HLA activating/inhibiting ligands. Atopic diseases have been associated with genes that regulate cytokine production and HLA genes, which may either protect or predispose to hypersensitivity.

Perspectives on mobile robots as tools for child development and pediatric rehabilitation

Mobile robots (i.e., robots capable of translational movements) can be designed to become interesting tools for child development studies and pediatric rehabilitation. In this article, the authors present two of their projects that involve mobile robots interacting with children: One is a spherical robot deployed in a variety of contexts, and the other is mobile robots used as pedagogical tools for children with pervasive developmental disorders. Locomotion capability appears to be key in creating meaningful and sustained interactions with children: Intentional and purposeful motion is an implicit appealing factor in obtaining children's attention and engaging them in interaction and learning. Both of these projects started with robotic objectives but are revealed to be rich sources of interdisciplinary collaborations in the field of assistive technology. This article presents perspectives on how mobile robots can be designed to address the requirements of child-robot interactions and studies. The authors also argue that mobile robot technology can be a useful tool in rehabilitation engineering, reaching its full potential through strong collaborations between roboticists and pediatric specialists.     

Application of an individual-based model with real data for transportation mode and location to pandemic influenza

Currently, an individual-based model is a basic tool for creating a plan to prepare for the outbreak of pandemic influenza. However, even if we can construct the model as finely as possible, it cannot mimic the real world precisely. Therefore, we should use real data for transportation modes and locations, and simulate the diffusion of an infectious disease into that real data. In the present study, we obtained data on the transportation modes and locations of 0.88 million persons a day in the Tokyo metropolitan area. First, we defined the location of all individuals in the data set every 6 min. Second, we determined how many people they came in contact with in their household, in each area, and on the train, and then we assumed that a certain percentage of those contacted would become infected and transmit the disease. Data for natural history and other parameters were taken from previous research. The average number of contacts in each area was 51 748 (95% confidence intervals [CI],46 846–56 650]), at home it was 246 (95% CI, 232–260), and on the train it was 91 (95% CI, 81–101). The number of newly infected people was estimated to be 3032 on day 7 and 126 951 on day 10. The geographic diffusion on day 7, the day when the earliest response would have started, expanded to the whole of the Tokyo metropolitan area. We were able to realize the speed and geographic spread of infection with the highest reality. Therefore, we can use this model for making preparedness plans.     

Peroxisome proliferator-activated receptor α mediates di-(2-ethylhexyl) phthalate transgenerational repression of ovarian Esr1 expression in female mice

Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalate ester that binds peroxisome proliferator-activated receptor α (PPARα) to induce proliferation of peroxisomes and regulate the expression of specific target genes. The question of whether the effect of DEHP on female reproductive processes is mediated via PPARα-dependent signaling is controversial. In this study, we investigated the effect of exposure to DEHP on ovarian expression of estrogen receptor α (Esr1) and aromatase (Cyp19a1) in three generations of Sv/129 wild-type (WT, +/+) and PPARα (−/−) knockout mice. Compared with untreated controls, ovarian expression of Esr1 decreased in response to DEHP treatment in the F0 (0.56-fold, P = 0.19), F1 (0.45-fold, P = 0.023), and F2 (0.35-fold, P = 0.014) generations of WT mice, but not PPARα-null mice. Our data indicate that transgenerational repression by DEHP of ovarian Esr1 gene expression is mediated by PPARα-dependent pathways. Further studies are required to elucidate the mechanisms underlying crosstalk between PPARα and Esr1 signaling in reproductive processes.     

Relationship of maternal malnutrition caused by Di(2-ethylhexyl) phthalate exposure with lifestyle disease in offspring

The hypothesis that offspring growing up malnourished during their fetal period have a high risk of lifestyle diseases in later life has been attracting great attention. Although animal experiments and epidemiological studies have been reported, most of them focused on the deficiency of maternal malnutritional elements or starvation. We found that di(2-ethylhexyl) phthalate (DEHP) decreased maternal plasma triglyceride levels, which is a significant source of nutrients for fetuses, in mice. Therefore, we analyzed how offspring exposed to malnutritional status during their fetal period develop potential adverse effects in later life. Male and female wild-type (mPPARα), Pparα-null, and hPPARα mice were treated with diets containing 0 or 0.05% DEHP. After 4 weeks, males and females in the same genotype and dose group were mated. After continued exposure until weaning, each group was divided into two groups, and one of them was dissected. The remaining was further divided into two subgroups; one was fed normal feed (control-diet group), while the other was fed a high-fat diet (HFD group). After 8-week feeding, all the mice were dissected. In the control-diet group, DEHP exposure at the fetal and pup stages increased food consumption in mPPARα and hPPARα mice, but not in Ppara-null mice. In contrast, DEHP exposure decreased plasma leptin levels in mPPARα and hPPARα mice at the weaning stage. In the HFD group, DEHP exposure at the fetal and pup stages influenced neither food consumption nor leptin levels. These findings suggest that maternal malnutrition may be caused by not only nutritional deficiency but also exposure to some chemicals such as DEHP, and the latter case may also influence feeding behavior in offspring. These effects may be related to hepatic PPARα and diminished by HFD feeding. Further study is warranted as to whether such feeding behavior influences the risk of lifestyle diseases such as obesity.     

Differential effects of aging, drinking and exercise on serum cholesterol levels dependent on the PPARA-V227A polymorphism

Peroxisome proliferator-activated receptor alpha (PPARA alpha) plays a pivotal role in lipid metabolism. Our previous study reported that PPARA-V227A was a major polymorphism in Japanese, which was associated with markedly lower serum total cholesterol (TC) levels, which were significantly affected by alcohol drinking compared to subjects with the wild-type (PPARA-WT) allele. However, serum lipids are also associated with aging and exercise frequency. The objective of the present study was to evaluate the relationship between PPARA-V227A and these factors. Genetic analysis of the polymorphism was performed in 1058 Japanese men and 281 women, and the relationship with aging, drinking and exercise on serum lipids was analyzed in 989 men and 245 women after exclusion criteria had been applied. In men, drinking increased high-density lipoprotein cholesterol (HDL-C) levels in both PPARA-WT and A227 carriers, but to a significantly higher degree in the latter. In women, TC and low-density lipoprotein cholesterol (LDL-C) levels in the A227 carriers drinking at least once a week were significantly higher than in PPARA-WT carriers. TC and LDL-C levels in males with PPARA-WT increased with aging regardless of drinking habit, while LDL-C levels in the A227 drinking carriers were significantly lower in 45-yr-old or older subjects than in 35- to 45-yr-olds. In addition, no effect of exercising was observed in the A227 carriers, while increase in the HDL-C of the PPARA-WT carriers was exercise frequency dependent. These results suggest that the influence of drinking, aging or exercise on TC, LDL-C and HDL-C levels in the A227 carriers may be different from those in the PPARA-WT subjects.     

3-Methyl-4-nitrophenol metabolism by uridine diphosphate glucuronosyltransferase and sulfotransferase in liver microsomes of mice, rats, and Japanese quail (Coturnix japonica)

3-Methyl-4-nitrophenol (PNMC) is a component of diesel exhaust particles and one of the major breakdown products of the insecticide fenitrothion. This chemical has a high potential for reproductive toxicity in Japanese quail (Coturnix japonica) and rats. Because PNMC inhaled by the body is metabolized by uridine diphosphate glucuronosyltransferase (UGT) and sulfotransferase, we investigated these enzyme activities in the hepatic microsomes and cytosols of quail (as a model of wild birds) and compared these activities with those of rats and mice as models of ecological and human risk assessment. The maximum velocity of the UGT for PNMC in quail was 12.7 nmol/min/mg, which was one third and one fourth those of rats and mice, respectively. The Michaelis-Menten constant of UGT for PNMC in quail was 0.29 mM, which was 1.3- and 1.8-fold higher than that in mice and rats, respectively, but not significantly different. In accordance with these results, UGT activities for PNMC were lowest in quail, with those in mice and rats being 4.4- and 2.7-fold higher, respectively. Sulfotransferase activity for PNMC was considerably less than that of UGT in all animals, including quail; no significant differences in the activities were found among mice, rats, and quail. These results suggest that glucuronidation may be involved primarily in PNMC elimination from wild birds as well as mammals and that the UGT activity in quail is less than that in the rodents.     

Research on choices of people with mild symptoms of common cold between consulting physicians and taking OTC (over-the-counter) medicine using a hypothetical question method

PURPOSE: This study was aimed at predicting the demand for medical services of people with mild symptoms of common cold. Three alternatives to cope with this condition were presented in questionnaires, which were: consulting physicians, taking OTC (over-the-counter) medicine, and doing nothing. Our prediction of employees' choices with these alternatives will contribute to cost-containment policies of health insurers. METHOD: We mailed questionnaires to 12,000 selected randomly employees, insured by "A" health insurance company. The questionnaires were designed a hypothetical question method, utilizing several criteria, including number of OTC medicines on hand, and socioeconomic status. A multinomial probit model was used for our estimation and analysis, with alternatives set as dependent variables. RESULTS: There were 3139 respondents, and the response rate was 26.2%. Gender, age, number of family members, and income level did not have any significant effect on the choice of any of the three alternaives. On the other hand, having a family doctor and a number of OTC medicines on hand had significant consequences. In males with a family doctor and without OTC medicine, the probabilities of choose to consult with a physicians, take on OTC medication, or doing nothing, were predicted to be 0.46, 0.32, and 0.22, respectively. People with three or more kinds of OTC medicine are more likely to choose OTC medication than physicians. CONCLUSION: The study suggests that more kinds of OTC medicine on hand of for individual with mild symptoms of common cold, the leaves the demand for medical services. To reduce medical expenses through consulting medical services, it might be effective for health insurers to provide insured employees with incentives to keep more OTC medicines on hand.     

Toxicity of diazinon and its metabolites increases in diabetic rats

The effect of diazinon (DZN) on the activities of cholinesterase (ChE) in plasma and acetylcholinesterase (AChE) in erythrocyte and brain was investigated in normal and streptozotocin-induced diabetic rats. Hepatic drug-metabolizing enzyme activity was also estimated by measuring the systemic clearance of antipyrine, and the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP1A2, which is closely related to the metabolism from DZN to DZN-oxon, a strong inhibitor of both ChE and AChE. No significant differences in the activities of ChE in plasma and AChE in erythrocyte were observed between normal and diabetic rats. Treatment with DZN significantly decreased these activities in diabetic rats more than in normal rats 6 h after injection (6.5 mg/kg). Treatment with DZN significantly decreased the activity of AChE in brain of diabetic rats than normal rats 3 h after injection (65 mg/kg), although no significant difference in the activity was found between normal and diabetic rats. The urinary recovery of diethylphosphate (DEP), a metabolite of DZN-oxon, was significantly increased in diabetic rats, but that of diethylthiophosphate (DETP), a metabolite of DZN, was unchanged. Significant increases in the systemic clearance of antipyrine and protein levels of hepatic CYP1A2, not CYP3A2, were observed in diabetic rats. These results suggest the possibility that a metabolite of DZN, DZN-oxon, causes higher toxicity in diabetic rats due to the enhancement of hepatic CYP1A2-mediated metabolism of DZN.