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.

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.

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 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.

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.

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.

Changes in blood viscosity with the recombinant tissue plasminogen activator alteplase.

We measured whole blood viscosity to investigate the time course of the fibrinolytic activity of the recombinant tissue plasminogen activator alteplase. Changes in blood viscosity over time were determined using an oscillation-type viscometer at a shear rate of 400 to 500 per second. Blood viscosity initially increased with alteplase as in untreated blood, but then decreased, reflecting the fibrinolytic activity of generated plasmin. Blood viscosity subsequently stabilized at a level below the initial value owing to the dissolution of both fibrin and fibrinogen by alteplase. To our knowledge, the present study is the first to examine the time course of changes in BV during fibrin formation and degradation. The results indicated that the fibrinolyic agent alteplase might provide the additional benefit of increasing blood flow by lowering blood viscosity.

Isoflavones inhibit nicotine C-oxidation catalyzed by human CYP2A6.

The inhibitory effects of isoflavones (daidzein, genistein, and glycitein) on human cytochrome P450 (CYP) 2A6 activities were investigated. Daidzein, genistein, and glycitein uncompetitively inhibited nicotine C-oxidation catalyzed by recombinant CYP2A6 expressed in baculovirus-infected insect cells with Ki values of 1.3 +/- 0.3 microM, 0.7 +/- 0.2 microM, and 5.2 +/- 0.8 microM, respectively, but not coumarin 7-hydroxylation. Effects of the intake of soy isoflavones on in vivo nicotine metabolism were investigated with 7 healthy Japanese homozygotes of CYP2A6*1. The cotinine/nicotine ratio of the plasma concentrations 2 hours after chewing 1 piece of nicotine gum under the basal condition (after abstaining from soy foods for 1 week) was 8.8 +/- 2.6 (4.4-11.4). The ratio was significantly (P < .05) reduced to 6.7 +/- 1.6 (4.0-8.2) after consumption of a soy isoflavone supplement (60 mg of total isoflavones/d) for 5 days. The authors found that isoflavone contained in soy products significantly decreased nicotine metabolism.

Traffic injuries of the pregnant women and fetal or neonatal outcomes.

OBJECTIVE: To investigate the relationship between pregnancy outcome and injury severity of pregnant woman in traffic accidents. METHOD: We reviewed insurance reports of traffic accidents and collected data on injuries of pregnant women and outcomes of their pregnancies. RESULT: A total of 135 pregnant women, with a mean injury severity score of 1.8+/-4.0, were involved in traffic accidents from 1994 through 2003. Injury severity score, abdominal abbreviated injury scale score were significantly higher in women whose neonates died than in women with healthy newborns. However, neither the likelihood of having been subjected to direct external forces during the accident nor injury severity differed between women with spontaneous abortions and woman with healthy newborns. CONCLUSION: Predicting abortion on the basis of maternal injury severity is difficult. Because unknown variables may contribute to fetal loss, further studies of traffic injuries are needed.

Fungi can be a useful forensic tool.

We present a practical case in which the fungi have contributed to the estimation of postmortem interval of the cadaver. A 71-year-old man wearing a shirt and pants was found dead at the bottom of an open well about 6m below the ground in his garden. Externally the face was dotted with colonies of white fungi, which was devoid of dipteran larvae and other insects. The fungi were identified as Penicillium sp. and Aspergillus terrous. These fungi, widely inhabit in the life circumstances, can generally colonize 3-7 days after attaching on the subjects. The appearance of the body surface, the state of decomposition of various organs, police information describing that the man had last been seen 12 days before discovery and the fungal evidence indicated that the man had been dead for about 10 days. We suggest that fungi can provide an useful means of estimating the minimum interval since death when forensic entomology is not applicable. Although, no data about growth rates of the fungi on human cadavers have been available, further researches should be needed to clarify the successive colonization of fungi on human cadavers.

Analysis of fungi detected in human cadavers.

We examined and identified fungi flora found growing on two human cadavers. The main isolate colonized on the surfaces of the skin and bones was morphologically identified as Eurotium repens. The genus Eurotium usually inhabits soil and exhibits osmophilic properties. Because the cadavers contained abundant organic materials, Eurotium species formed ascomata and conidia. To our knowledge, this is the first study to describe in detail the species of fungus obtained from human cadavers. Because the detection of some species of fungus found in human cadavers may reveal the local habits of them, more forensic cases is needed to develop fungi into the forensic tool.

Accidental choking in a patient with Treacher Collins syndrome.

A 3-year-old boy with Treacher Collins syndrome had undergone tracheostomy and placement of a secured cannula at the age of 4 months. When he was 3 years old, he manually extracted the secured cannula by himself and choked to death. Autopsy revealed upper airway obstruction with posterior deviation and mucosal hyperplasia of the radix linguae, mandibular hyperplasia, and occlusion of the artifical airway owing to intratracheal granuloma due to the long-standing tracheotomy. For safe, long-term use of a tracheostomy to maintain the airway, children with craniofacial abnormalities should be carefully supervised by their families to prevent accidental decannulation.

Accidental strangulation of a mentally retarded patient by a clothing collar: a case report.

A 40-year-old mentally retarded woman died of accidental strangulation in a nursing home. She was found in a kneeling position with her hands on her knees and the collar of her clothing compressing the front and sides of the neck. Before the accident, a nurse had dressed the patient in one-piece overall-style pyjamas put on back to front so that she could not remove the garment herself. The post-mortem findings and reconstruction of the scene of death suggested that the patient had been strangled by the collar of her backward-facing clothing while in a kneeling position. Because patients with psychiatric illnesses may have a limited ability to recognize or communicate symptoms of physical danger, they must be closely monitored by knowledgeable medical and nursing staff. This case highlights the importance of preventing the accidental deaths of mentally retarded patients in nursing homes.

Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction.

Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400 mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldolase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (p < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction.

An autopsy case of sudden death in a boy with primary pulmonary hypertension: a case report.

We report a rare autopsy case of sudden death due to primary pulmonary hypertension. A seven-year-old boy, who had been diagnosed with primary pulmonary hypertension at the age of four years, died suddenly. Forensic autopsy and histopathologic examination revealed extensive obstruction of small muscular pulmonary arteries by plexiform lesions and concentric intimal thickenings, compatible with primary pulmonary hypertension. We concluded that plexiform lesions of pulmonary arteries produced right ventricular hypertrophy and dilatation, decreased the preload of the left ventricle and subsequently led to biventricular failure. This autopsy and histopathologic examination suggested a possible pathophysiologic mechanism of sudden death due to primary pulmonary hypertension in a child.

3. Sudden death due to pulmonary thromboembolism after car driving: a case report.

An autopsy case of sudden death due to pulmonary thromboembolism after a car trip is reported. A 56-year-old Japanese man with hypertension and atrial fibrillation suddenly died immediately after having driven for two and a half hours. At autopsy, the pulmonary arteries were found to be filled with dark-red, coiling thrombi consisting of fibrin and red blood cells. In the dilated right popliteal vein, a thrombus consisting of fibroblasts, a large number of collagen fibres, and newly formed capillaries was attached to the vessel wall. The cause of death was determined to be pulmonary embolism due to the thrombus of the right popliteal vein. Two and a half hours of prolonged sitting while driving a car encouraged thrombus formation. We believe that this case, the first autopsy case of fatal pulmonary thromboembolism after a car trip to be reported, highlights the importance of predicting venous thrombosis of the leg or fatal venous thromboembolism after a car trip.

[Sudden death while bathing].

We describe the epidemiologic and pathophysiologic features of sudden death while bathing. The leading cause of death is cardiovascular disease (60.4%), followed by cerebrovascular disease (18.7%) and drowning (11.2%). Because hydrostatic pressure, autonomic nervous reflexes or endocrine system reflect on hemodynamic changes while bathing, the elderly persons or patients with cardiovascular disease are often suffered from fatal cardiac events. To find the detail pathophysiologic changes while bathing, exact cause of death should be examined by autopsies. Furthermore, elderly or handicapped persons should be supervised by their families for preventing drowning.