NFκB attenuates IL-5 production and upregulates T-box transcription factors in Th2-like T cells.

IL-5 plays important roles in eosinophil differentiation, expansion, and recruitment. The regulation of IL-5 seems critical for the treatment of eosinophil-mediated allergic reactions. However, the precise mechanisms for IL-5 regulation remain unknown. In this study, we investigated how IL-5 production is regulated. The transduction of GATA-3 into a murine T cell hybridoma resulted in acquiring the ability to produce IL-5 in response to an antigenic stimulus like Th2 cells. This production was dependent on the cAMP-PKA pathway, but not on p38 activation. Transduction of NIK largely impaired IL-5 production. RelA and RelB similarly impaired IL-5 production. RelA decreased not only IL-5 protein amount but mRNA. RelA also inhibited Il5-luciferase reporter activity. The transduction of GATA-3 decreased the expression of Tbx21 and Eomes, but the additional transduction of RelA abrogated the decreased expression of GATA-3-induced Tbx21 and Eomes. Furthermore, the transduction of T-bet or Eomes into the GATA-3-transduced T cell hybridoma impaired IL-5 production. These results suggested that strong enhancement of the NFκB pathway downregulates IL-5 production and upregulates T-box protein expression to shift an immune response from Th2 to inflammatory Th1.

Assessing injury severity in bicyclists involved in traffic accidents to more effectively prevent fatal bicycle injuries in Japan.

The objective of this study was to clarify the relationship between injury severity in bicyclists involved in traffic accidents and patient outcome or type of vehicle involved in order to propose effective measures to prevent fatal bicycle injuries. Hospital records were reviewed for all patients from 2007 to 2010 who had been involved in a traffic accident while riding a bicycle and were subsequently transferred to the Shock Trauma Center of Dokkyo Medical University Koshigaya Hospital. Patient outcomes and type of vehicle that caused the injury were examined. The mechanism of injury, Abbreviated Injury Scale (AIS) score, and Injury Severity Score (ISS) of the patient were determined. A total of 115 patients' records were reviewed. The mean patient age was 47.1 ± 27.4 years. The average ISS was 23.9, with an average maximum AIS (MAIS) score of 3.7. The ISS, MAIS score, head AIS score, and chest AIS score were well correlated with patient outcome. The head AIS score was significantly higher in patients who had died (mean of 4.4); however, the ISS, MAIS score, and head AIS score did not differ significantly according to the type of vehicle involved in the accident. The mean head AIS scores were as high as 2.4 or more for accidents involving any type of vehicle. This study provides useful information for forensic pathologists who suspect head injuries in bicyclists involved in traffic accidents. To effectively reduce bicyclist fatalities from traffic accidents, helmet use should be required for all bicyclists.

Analysis of child-vehicle collision injuries by vehicle type.

PURPOSE: This study aimed to determine the severity of injuries to each body region of child pedestrians struck by different types of vehicles. METHODS: We collected in-depth data from the Institute for Traffic Accident Research and Data Analysis on pedestrians younger than 13 years with any bodily injuries from collisions with vehicles between 1993 and 2004. RESULTS: Sixty-eight patients with a mean age of 6.9 ± 2.4 years were included in the study. In collisions, vehicles caused higher Abbreviated Injury Scale (AIS) scores than those from impact with the road. Injury Severity Score and AIS values were higher with one-box or sports utility vehicles compared with those in sedan vehicles, but the differences were not statistically significant. The mean AIS score of head injuries was significantly higher with one-box or sports utility vehicles than that with sedans (1.6 ± 2.1 vs 0.5 ± 1.1, P < .05). The mean AIS score of the lower extremities was significantly higher with sedans than that with one-box or sports utility vehicles (1.2 ± 1.0 vs 0.5 ± 0.9, P < .05). CONCLUSIONS: The type and severity of injuries in child-car collisions vary by type of vehicle and pedestrian kinematics.

Severity of child pedestrian injuries due to bonnet-type-vehicle collision.

BACKGROUND: The aim of this study was to clarify the pattern of child pedestrian injury, injury severity, and its relation to collision velocity in bonnet-type-vehicle collision. METHODS: In-depth data were retrospectively collected from the Institute for Traffic Accident Research and Data Analysis on pedestrians younger than 13 years old with any bodily injuries from collisions with bonnet-type vehicles between 1993 and 2004. RESULTS: Forty-seven patients from 43 collisions with a mean age of 6.9 ± 2.5 years were included in the study. Injury severity was not significantly different between patients who were hit by the front of the vehicle and those who were hit by the side of the vehicle. In front collisions, impact with the vehicle was associated with significantly higher Abbreviated Injury Scale (AIS) scores than those for impact with the road, especially for the lower extremities (mean: 1.2 vs 0.2, P < 0.001). Injury severity of the lower extremities and collision velocity were examined. The estimated collision velocity of the vehicle was not significantly different between patients with lower extremity AIS scores of 0 or 1 and those of 2 or 3. CONCLUSIONS: Some pediatric pedestrians suffer from collisions with bonnet-type vehicles without lower extremity fractures owing to the characteristics of child pedestrians. Providing injury prevention programs for children in communities and schools, developing active safety devices in the vehicle, and modifying the vehicle body to a pediatric pedestrian-friendly structure may increase pedestrian protection.

A novel application of infrared imaging for the diagnosis of death by fire.

This paper demonstrates a novel and simple technique for the diagnosis of death by fire using a digital infrared (IR) camera system. At autopsy, the inhalation of soot by a fire victim is a definite indicator proving a vital reaction during the fire. However, there can be difficulties in confirming the presence of soot because of the relative lack of soot or the similarity in color between soot and surrounding tissues. To evaluate the effectiveness of IR imaging at autopsy, we acquired internal images of the respiratory and gastrointestinal system by both an ordinary color and IR cameras. Using our method, the inhaled soot is visible as black particles or deposits, while the blood is transparent and the surrounding tissue is whitened. This technique enables the detection of normally undiscriminating soot in an ordinary color image. This is the first report suggesting the usefulness of IR imaging in forensic autopsy for the diagnosis of death by fire.

CD2-mediated regulation of peripheral CD4(+) CD25(+) regulatory T-cell apoptosis accompanied by down-regulation of Bim.

Extensive studies on CD4(+)  CD25(+) regulatory T (Treg) cells suggest that they are important in regulating immune responses. However, mechanisms of peripheral Treg cell homeostasis are unknown. We found that stromal cells isolated from secondary lymphoid organs such as spleen and lymph nodes could support the survival of Treg cells. This was dependent on CD2 engagement and a direct interaction between Treg cells and stromal cells. In the presence of stromal cells, Bim, a pro-apoptotic factor, was partially decreased in Treg cells. This effect could be inhibited by anti-CD2 blocking antibodies, indicating that stimulation through CD2 on Treg cells regulates Bim expression, which may be relevant to Treg cell apoptosis. Therefore, Treg cell interactions with stromal cells through CD2 may be essential for Treg cell survival. Surprisingly, the expression of CD2 ligands on stromal cells was not detected. Hence, it is not clear how CD2 on Treg cells contributes to a direct interaction with the stromal cells and participates in survival support for Treg cells. Taken together, CD2 stimuli were mandatory for Treg cell survival with reduced Bim expression, but CD2 may not function as a direct receptor for molecules on stromal cells.

Simultaneous identification of the enantiomers and diastereomers of N,O-di-trifluoroacetylated ephedrine and norephedrine in blood plasma using chiral capillary gas chromatography-mass spectrometry with selected ion monitoring.

A method for identifying the enantiomers of N,O-di-trifluoroacetylated ephedrine (EP) and norephedrine (NE) and the enantiomers of pseudoephedrine (PEP) and pseudonorephedrine (PNE) in plasma was developed using chiral capillary gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM). N,O-Di-trifluoroacethyl (TFA) derivatization was accomplished in a dried hydrochloride extract of plasma (minimum quantity of 0.2 mL). An SIM GC-MS method with a ß-cyclodextrin chiral capillary column allowed the successful and simultaneous detection of each TFA-derivatized stereoisomer of EP, NE, PEP, PNE, and an internal standard (IS; S-(+)-ethylamphetamine). Each TFA-drivatized stereoisomer was identified using four mass fragment ions (m/z 140, 154, 168, and 230). The TFA-derivatized stereoisomers of EP, NE, PEP, PNE, and IS were separated completely and were detected with sufficient sensitivity. The assay allowed the stereoisomers to be determined in a linear range of 12.5-1250 ng/mL for the EP stereoisomers and a linear range of 5-1250 ng/mL for the PEP, NE, and PNE stereoisomers. The detection limits were 7.5 ng/mL for the EP stereoisomers and 2.5 ng/mL for the PEP, NE, and PNE stereoisomers. The intra- and interday precisions were less than 5.9% and 8.2%, respectively. This chiral capillary SIM GC-MS method was sufficiently effective in the analysis of plasma from users of over-the-counter cold medicines and was also fully applicable to the plasma analysis of guinea pigs following their treatment with racemic EP.

Sudden illness while driving a vehicle--a retrospective analysis of commercial drivers in Japan.

OBJECTIVE: We performed a retrospective analysis of commercial drivers to clarify the background of incidents of sudden illness while driving. METHODS: The analysis used reports submitted by employers to the Japan Ministry of Land, Infrastructure, Transport, and Tourism regarding commercial drivers who had been ordered to stop driving owing to health problems. RESULTS: Of 211 cases with an average work history of 15.2 years, there were 88 bus drivers, 70 taxi drivers, and 53 truck drivers, 36.0% of who had died as a result of their disease. Among taxi and truck drivers, more than 70% of incidents were due to cardiac, aortic, and cerebrovascular disease. More than 80% of these were unable to avoid traffic accidents caused by sudden illness. However, among bus drivers, cardiac, aortic, and cerebrovascular disease accounted for only 23.5% of incidents, and accidents were avoided in more than half of the cases. The duration between starting work and the incident time was significantly shorter among bus drivers [mean 3.3 hours, standard deviation (SD) 3.1] than taxi (7.7 hours, SD 5.8) and truck (7.2 hours, SD 6.3) drivers (P<0.01). CONCLUSIONS: The difference between the sudden illness rates of taxi and truck drivers and those of bus drivers is due to both reporting bias and differences in the awareness needed to prevent disabling events while driving. As a precaution, physicians should advise commercial drivers to stop driving as soon as they detect slight discomfort. To prevent accidents, more assertive health promotion aimed at professional drivers is needed.

Support for stroke patients in resumption of driving: patient survey and driving simulator trial.

BACKGROUND: Encouragement of stroke patients to resume driving is important to promote their reintegration into the community. Limited rehabilitation has been performed in this regard, owing to lack of specific knowledge on the part of medical staff. To establish an effective support program for stroke patients who wish to resume driving, we propose comprehensive training by medical staff using a driving simulator. METHODS: A survey of stroke patients admitted to the Tokyo Metropolitan Rehabilitation Hospital was first performed. A questionnaire was sent to 525 patients. Of 218 responses, the answers of 118 patients who had been driving before their stroke were analyzed. More than 80% of stroke patients did not obtain enough information about resuming driving during their hospital stay, and 38.1% of patients would have liked to have had driving training with a simulator. From these results, we set out to determine the effect of driving training using a realistic and technically advanced driving simulator. Twenty-four stroke patients and 20 healthy controls were included in the study. RESULTS: Repeat training with the simulator resulted in an increased ability to perform braking and an improvement in driving ability. The majority of stroke patients who had the mental and physical ability to drive a car were likely to be assessed as being able to resume driving as a result of the training program. CONCLUSION: This study indicates that comprehensive support by medical staff and provision of adequate information about resumption of driving and the opportunity for training on a driving simulator are likely to aid resumption of driving by stroke patients, thus enhancing their rehabilitation and social reintegration.

Differential gene expression of multiple chondroitin sulfate modification enzymes among neural stem cells, neurons and astrocytes.

Chondroitin sulfate/dermatan sulfate (CS/DS) polysaccharides have been reported to play a crucial role in the proliferation and maintenance of neural stem cells (NSCs). However, little is known about the structural changes and functional role of CS/DS chains in the differentiation of NSCs. Western blots of NSCs, neurons and astrocytes in culture, with three CS-polysaccharide antibodies of different specificities, revealed marked differences in CS structure among the three cell types. To confirm this finding, we measured gene expression levels of CS sulfotransferases and C5-epimerase in these cell types, as these are responsible for producing the high structural diversity of CS/DS. Expressions of chondroitin 4-O-sulfotransferase, chondroitin 6-O-sulfotransferase, and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase mRNAs were low in cultures of differentiated neural cells, such as neurons and astrocytes, in comparison to NSCs. In contrast, expressions of uronyl 2-O-sulfotransferase and C5-epimerase mRNAs were higher in the differentiated neural cells than NSCs. Thus, we first provide evidence to support the hypothesis that CS/DS undergoes structural changes during NSC differentiation. The structural changes in CS/DS may be implicated in the regulation of NSC differentiation through interactions with growth/neurotrophic factors and cytokines.

Analysis of maxillofacial injuries of vehicle passengers involved in frontal collisions.

PURPOSE: To clarify the incidence and mechanisms of maxillofacial injuries sustained by motor vehicle passengers, in-depth data from the Institute for Traffic Accident Research and Data Analysis, Japan, were retrospectively analyzed. MATERIALS AND METHODS: From the Institute for Traffic Accident Research and Data Analysis in-depth data for 1993 through 2005, data were collected for 226 individuals with maxillofacial injuries who were adult passengers involved in frontal motor vehicle collisions. The accident information, a subject's medical data, and anatomic Injury Severity Scores were examined. RESULTS: The median Injury Severity Score was 2, and the mean equivalent barrier speed of the vehicles was 35.2 ± 13.0 km/hour. The most common maxillofacial injuries were lacerations (46.7%), followed by abrasions (41.9%), fractures (14.0%), and dental injuries (5.7%). Maxillofacial fractures occurred more often in unrestrained drivers without airbag deployment (18.4%) and less often in restrained drivers with airbag deployment (4.3%). The incidences of fractures caused by impacts with areas other than the steering wheel were markedly decreased using any safety device (35.5% to 0%). CONCLUSION: Combined use of seat belts and airbags by occupants decreases fractures compared with completely unrestrained occupants. Furthermore, wearing a seat belt prevents the free flight of drivers within a vehicle and contact with the interior of a vehicle (other than the steering wheel). Although the anatomic Injury Severity Score of maxillofacial injuries was relatively low, because these injuries are also associated with socioeconomic costs, the correct use of safety devices and further development of more effective injury prevention systems are needed.

Effects of seat belts worn by pregnant drivers during low-impact collisions.

OBJECTIVE: The aim of this study was to understand the injury mechanisms of pregnant drivers and associated fetal outcomes. STUDY DESIGN: Frontal and rear impact tests using a dummy representing the anthropometry of a pregnant woman were conducted. RESULTS: In frontal impact tests without a seat belt, abdominal pressure peaked at the point where the dummy contacted the steering wheel. Rear impact tests without a seat belt showed that the dummy moved forward because of rebound and contacted the steering wheel, which was avoided when a seat belt was worn. CONCLUSION: Wearing a seat belt reduces abdominal pressure or prevents contact with the steering wheel during collisions.

Experimental analysis of the relationship between simulated low-velocity rear-end collisions and fetal outcomes of pregnant rats.

Our study aimed to define the risk for a human fetus of rear-end vehicle collisions. We therefore performed drop tests using pregnant SLC Wistar rats. Pressure applied to the rat uterus and rectum at various stages of acceleration was measured. After being dropped, rats were observed throughout pregnancy. At birth, the numbers, weight and the occurrence of physical anomalies among pups were followed-up for 28 days. Uterine pressure increased exponentially from 2.1 +/- 0.3 kPa at 19-fold gravity (G) to 13.9 +/- 0.8 kPa at 92-fold G. These values are much lower than the mechanical failure level of human fetal membrane tissue or of those at risk of adverse fetal outcomes. Neither the average number of offspring per pregnant rat nor the average body weight of newborn pups differed significantly between control pregnant rats and those which had been exposed to acceleration of 46-fold or 92-fold G. Other variables such as maternal mental distress, motion effects of amniotic fluid or seatbelt-induced uterine injuries might contribute to fetal loss.

Sudden death while driving a four-wheeled vehicle: an autopsy analysis.

We retrospectively analysed forensic autopsies to resolve various issues associated with sudden natural death while driving. We collected information about the medical history, drug treatment, anthropometry and body mass index (BMI) of 34 individuals who suddenly died of natural causes while driving four-wheeled vehicles. The reasons for driving, details of the vehicle, type of collision, perspective of vehicle behaviour and types of avoidance manoeuvres were also examined. The injury severity score (ISS), the Abbreviated Injury Scale (AIS) and the degree of cardiomegaly of the driver were determined from autopsy findings. The dominant cause of death was ischemic heart disease, which closely agreed with previous findings. However, forensic signs indicated that only 20.6% of deceased drivers had attempted avoidance manoeuvres such as braking or steering before the fatal accident, which contradicts previous findings.

Analysis of seating position and anthropometric parameters of pregnant Japanese drivers.

OBJECTIVE: An anthropometric study was performed to understand the quantitative characteristics of the seating posture of Japanese pregnant drivers. METHODS: Twenty pregnant women with a mean gestation of 31.4 +/- 1.9 weeks and 20 age-matched, non-pregnant women provided written informed consent to participate in this study. A mid-sized, sedan-type passenger vehicle was used for measurement. The subjects, wearing light clothing, sat in the driver's seat of the vehicle and fastened the seatbelt after adjusting the seat to their usual driving posture. Longitudinal displacement of the slide adjuster and the reclining angle of the seat back were measured, relative to the reference position. Seating posture was investigated by measuring the coordinates of the anthropometric datum points of the drivers (head, shoulder, hip joint, knee joint, and the clearance between the steering wheel and the upper torso). RESULTS: The mean horizontal clearance between the lower rim of the steering wheel and the abdomen of the pregnant women was 146 +/- 56 mm, significantly smaller than that of the non-pregnant women (251 +/- 51 mm), due to the protrusion of the abdomen. There was no significant difference in seat adjustment position between the two groups. The height of the pregnant women and the horizontal distance from the lower rim of the steering wheel to the abdomen showed a moderate linear correlation in the pregnant group (R2 = 0.56). CONCLUSIONS: Compared to previous studies, the differences of longitudinal distance were found between American and Japanese subjects without significant differences of body heights, due to the difference of body weights and abdominal circumferences. This is the first report to analyze the seating position and anthropometric parameters of pregnant drivers in an Asian population.

Analysis of cervical injuries in persons with head injuries.

To determine which clinical factors are useful for predicting concomitant injuries of the cervical spine and cervical spinal cord in persons with head injuries, we examined the nature and mechanisms of cervical injuries. For 109 forensic autopsies of persons with head injuries, the cause of injury, mechanism of cervical injury, survival time, and anatomic injury severity (1990 revision of the abbreviated injury scale [AIS] and injury severity score) were determined. Traffic accidents were the most common cause of injuries (41.3%), followed by slips and falls (24.8%), assaults (17.4%), and falls from height (9.2%). The mean maximum AIS scores and the AIS scores of the head or neck were similar in the 4 groups. Cervical spine injuries and epidural or subdural hemorrhages of the cervical spinal cord were more common in persons dying in traffic accidents and falls from height than in persons dying in slips and falls or assaults. Cervical injuries were significantly more common in persons sustaining frontal impacts than lateral or rear impacts. The most common cervical hyperextension injuries were atlanto-occipital and atlantoaxial dislocation and injuries of the 5th intervertebral disc. Our results suggest that persons with injuries of the head due to high-energy frontal impacts should be carefully examined for concomitant cervical injuries. These findings should be helpful for decreasing preventable deaths from undiagnosed cervical injuries in head-injured persons.

Inhibitory effects of neurotransmitters and steroids on human CYP2A6.

Human CYP2A6 catalyzes the metabolism of nicotine, cotinine, and coumarin as well as some pharmaceutical drugs. CYP2A6 is highly expressed in liver and, also, in brain and steroid-related tissues. In this study, we investigated the inhibitory effects of neurotransmitters and steroid hormones on CYP2A6 activity. We found that coumarin 7-hydroxylation and cotinine 3'-hydroxylation by recombinant CYP2A6 expressed in baculovirus-infected insect cells were competitively inhibited by tryptamine (both K(i) = 0.2 microM), serotonin (K(i) = 252 microM and 167 microM), dopamine (K(i) = 49 microM and 22 microM), and histamine (K(i) = 428 microM and 359 microM). Cotinine formation from nicotine was inhibited by tryptamine (K(i) = 0.7 microM, competitive), serotonin (K(i) = 272 microM, noncompetitive), dopamine, noradrenaline, and adrenaline (K(i) = 11 microM, 54 microM, and 81 microM, uncompetitive). Estrogens (K(i) = 0.6-3.8 microM), androgens (K(i) = 60-149 microM), and corticosterone (K(i) = 36 microM) also inhibited cotinine formation, but coumarin 7-hydroxylation and cotinine 3'-hydroxylation did not. Nicotine-Delta(5'(1'))-iminium ion formation from nicotine was not affected by these steroid hormones, indicating that the inhibition of cotinine formation was due to the inhibitory effects on aldehyde oxidase. The nicotine-Delta(5'(1'))-iminium ion formation was competitively inhibited by tryptamine (K(i) = 0.3 microM), serotonin (K(i) = 316 microM), dopamine (K(i) = 66 microM), and histamine (K(i) = 209 microM). Thus, we found that some neurotransmitters inhibit CYP2A6 activity, being related with inter- and intraindividual differences in CYP2A6-dependent metabolism. The inhibitory effects of steroid hormones on aldehyde oxidase may also contribute to interindividual differences in nicotine metabolism.