Search

The thymus, the organ that is the most sensitive to stress, presents acute involution as a result of exposure to strong stress in childhood. Thymic involution is thus often considered evidence of child abuse/neglect in forensic autopsies. A portion of the thymic epithelial cells express leptin receptor, and leptin showed a thymo-protective function against stress-induced thymic involution in an animal model. Leptin receptor-expressing thymic epithelial cells (LR-TECs) may play a key role in the thymic remodeling provoked by a stressful environment. Here, we sought to clarify the changes of histopathological findings and human LR-TECs in stressful environment. We examined human thymus specimens obtained from 40 forensic autopsy cases (26 male, 14 female; age 21 to 3221 days). We divided the cases into stressor-positive (SP, n = 29) and stressor-negative (SN, n = 11) groups. Cases were classified according to the histological classification of thymic involution and investigated by leptin receptor immunostaining. The results revealed that (1) the SP group showed obvious histological thymic involution (p

The annual number of suicides in Japan totaled around 23,000 in 1997 and abruptly increased to around 31,000 in 1998. This figure has remained high since then. This abrupt increase in the number of suicides was primarily due to an increase in suicides occasioned by economic concerns. The association between various economic factors and suicide must be studied in detail and over the long term in order to ascertain the association between economic concerns and suicide. This study examined the relative poverty rate and the suicide rate in Japan over 30 years and discussed the association between those two rates. The results suggest that the relative poverty rate may be associated with the suicide rate for both sexes. This association is true for men in particular. The organizations and professionals involved in implementing suicide prevention measures should be cognizant of the current findings and consider formulating additional specific measures.

Estimation of postmortem interval (PMI) is an important goal in judicial autopsy. Although many approaches can estimate PMI through physical findings and biochemical tests, accurate PMI calculation by these conventional methods remains difficult because PMI is readily affected by surrounding conditions, such as ambient temperature and humidity. In this study, Sprague-Dawley (SD) rats (10 weeks) were sacrificed by suffocation, and blood was collected by dissection at various time intervals (0, 3, 6, 12, 24, and 48 h; n = 6) after death. A total of 70 endogenous metabolites were detected in plasma by gas chromatography-tandem mass spectrometry (GC-MS/MS). Each time group was separated from each other on the principal component analysis (PCA) score plot, suggesting that the various endogenous metabolites changed with time after death. To prepare a prediction model of a PMI, a partial least squares (or projection to latent structure, PLS) regression model was constructed using the levels of significantly different metabolites determined by variable importance in the projection (VIP) score and the Kruskal-Wallis test (P < 0.05). Because the constructed PLS regression model could successfully predict each PMI, this model was validated with another validation set (n = 3). In conclusion, plasma metabolic profiling demonstrated its ability to successfully estimate PMI under a certain condition. This result can be considered to be the first step for using the metabolomics method in future forensic casework.

In Japan, there are increasing reports of death by poisoning following butane abuse. To determine the specific cause of death in such cases, it is important to confirm the presence of fuel gas components in the body, although careful analysis is required because of their volatile properties. In most reported cases, the subject died suddenly during or immediately after butane aspiration. Thus, the butane concentration in the samples from the deceased should be relatively high. Herein, we present a case of an 18-year-old man found with cardiopulmonary arrest, who then exhibited hypoxic encephalopathy for 16days in a hospital. At autopsy, we detected hypoxic encephalopathy, pneumonia, and ischemia-reperfusion injury of the myocardium, while the cause of cardiac arrest remained unclear. Toxicological analysis was then performed for fuel gas components in several specimens collected at autopsy. Results showed that n-butane and isobutane were detected in the adipose tissue at 16days after inhalation, indicating a role of butane gas inhalation as the cause of death. These data suggest that adipose tissue may be the most appropriate analysis sample to be collected at postmortem in cases where involvement of volatile and fat-soluble gas inhalation is suspected.

The incidence of pancreatic injury after blunt abdominal trauma is extremely low. A timely and accurate diagnosis is important, as a delay could be life-threatening. In this case, a 70-year-old driver crashed a car into a concrete wall at low speed. He was transported to the emergency hospital but died about 9.5h later with the cause of death unknown. An autopsy revealed that his pancreas was lacerated in the coronal plane and there was mesenteric contusion. Cause of death was determined to be blood loss resulting from pancreatic and mesenteric contusion. The mechanism of the injury was considered to be a very rare "degloving," caused by the impact from the steering wheel. It is therefore important to keep in mind possible pancreatic damage when examining blunt trauma to the abdomen, especially in traffic accident cases.

Objective To determine the incidence of potential medical adverse events among patients undergoing forensic autopsy, and to present the characteristics of potential medical adverse events. Design Retrospective review of consecutive autopsy records. Setting Department of Forensic Medicine, the Jikei University School of Medicine, Tokyo, Japan. Participants A total of 3355 forensic autopsy cases between 1983 and 2006. Main outcome measures Incidence of potential medical adverse events identified in decedents undergoing forensic autopsy, classified by actual occurrence as ‘confirmed’, ‘equivocal’ and ‘negative’ cases; proportion of potential diagnostic, performance and system errors among potential medical adverse events. Results Of 291 autopsies (8.7%) with potential medical adverse events, 66 cases (22.7%) were confirmed, 42 cases (14.4%) were negative and 183 cases (62.9%) were equivocal. Confirmed cases consisted of potential diagnostic errors in 49 cases (74.2%) and performance errors in 17 cases (25.8%). Equivocal cases included 99 cases associated with potential diagnostic errors (54.1%) and 60 cases associated with potential system errors (32.8%). In 38 of the confirmed cases (57.5%), serious exacerbation of patient condition occurred outside the medical facility. Conclusions Potential medical adverse events are not uncommon in decedents undergoing forensic autopsy. They are particularly associated with potential diagnostic errors. Forensic autopsy may provide information that could be used to improve care and reduce deaths due to potential medical adverse events.

Class II alcohol dehydrogenase (pi-ADH), encoded by alcohol dehydrogenase (ADH4), is considered to contribute to ethanol (EtOH) oxidation in the liver at high concentration. Four single nucleotide polymorphisms (SNPs) were found in the promoter region of this gene. Analysis of genotype distribution in 102 unrelated Japanese subjects revealed that four loci were in strong linkage disequilibrium and could be classified into three haplotypes. The effects of these polymorphisms on transcriptional activity were investigated in HepG2 cells. Transcriptional activity was significantly higher in cells with the -136A allele than in those with the -136C allele. To investigate whether this difference in transcriptional activity caused a difference in EtOH elimination, previous data on blood EtOH changes after 0.4 g/kg body weight alcohol ingestion were analyzed. When analyzed based on aldehyde dehydrogenase-2 gene (ALDH2) (487)Glu/Lys genotype, the significantly lower level of EtOH at peak in subjects with -136C/A and -136A/A genotype compared with subjects with -136C/C genotype indicated that -136 bp was a suggestive locus for differences in EtOH oxidation. This effect was observed only in subjects with ALDH2 (487)Glu/Glu. These results suggested that the SNP at -136bp in the ADH4 promoter had an effect on transcriptional regulation, and that the higher activity of the -136A allele compared with the -136C allele caused a lower level of blood EtOH after alcohol ingestion; that is, individuals with the -136A allele may consume more EtOH and might have a higher risk for development of alcohol dependence than those without the -136A allele.

Background: The aim of the present study is to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, Japan, and to discuss the prevention of the suicidal influences in elderly patients. Methods: We investigated all inquest records during the 14-year period 1989‐2002 in cooperation with the First Department of Criminal Investigation of Mie Prefectural Police Headquarters. From all cases classified as suicides, we extracted data on age, sex and background, and we focused on suicide in the elderly group. Results: During the test period, there were 5048 suicides (3276 male and 1772 female suicides) of which 1513 (691 male and 822 female) were in the elderly group. The rate of suicide in the elderly group was approximately 30% of the total in all age groups. The rate of female suicides in the elderly group was approximately 46.3%. The major causative factors of suicide among the elderly were ‘suffering from physical illness’, and ‘psychiatric disorders’. ‘Physical diseases’ were not negligible backgrounds in middle and elderly groups. Among physical diseases, the number of malignant neoplasm was clearly less than the other diseases. Notably, ‘cardiovascular disease’ and ‘orthopedic disorders’ were most frequent causative factors of suicide other than malignant neoplasm. Conclusion: It is consequently concluded that improvements in the system of home nursing and health care should be involved in the suicidal prevention of the elderly who ‘suffer from physical illness’. The patients who ‘suffer from physical illness’ should be given physical and mental support. In order to prevent suicide, not only psychiatrists but also general practitioners as well as medical staff and general public should be provided with education regarding depression among ‘psychiatric disorders’.

This study aims to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, and to discuss the prevention of the factors contributing to suicide in the elderly group. We obtained an agreement from the Mie Prefectural Police Headquarters and investigated all inquest records collected between 1996 and 2002 in Mie Prefecture and focused on suicide in the elderly group. During the test period, the number of suicides in the elderly group was 842. In causative factors, the two major causative factors of suicide were "suffering from physical illness" and "psychiatric disorders". In particular, the three most frequent physical illnesses were "cardiovascular disease", "orthopedic disorder", and "digestive organ disease", and these physical illnesses are mentally stressful, and thus have a psychiatric component, the same as psychiatric illnesses do. Consequently, it is concluded that improvements in the home nursing and mental health care should include the prevention of suicide in the elderly who "suffer from physical illness" and "psychiatric disorders" to prevent suicide. In addition, medical staff and the general public should be educated on the factors that can influence elderly persons' mental condition, and should be cautioned to observe elderly persons for suicidal signs and symptoms.

The diagnosis of the cause of sudden unexpected infant death (SUID) is often difficult work for forensic pathologists. Its misdiagnosis or misclassification is the cause of crucial epidemiological and medicolegal problems. During the sudden infant death syndrome (SIDS) epidemic, many reports described the risk factors of SIDS as well as mechanical suffocation during sleep. Meadow’s report has invited worldwide debate over whether the cause of SUID is attributable to SIDS or suffocation. On the basis of this background, the problems concerning causal diagnosis and risk factors, particularly the accidental suffocation of infants during sleep, and the specific pattern of suffocation, was reviewed from the forensic pathological viewpoint. The following tasks remain to be done for the future: (1) to avoid preventable SUIDs, the most effective measure worldwide is to identify high-risk factors for all SUIDs, including SIDS, accidental suffocation and undetermined causes, and then transmit this information to the public. (2) SIDS should be uniformly defined and diagnosed as strictly as possible to gain its reliability in the public health community and in a legal framework.

Die Entwicklung von “Real-time-imaging-Verfahren” mit drei- und vierdimensionalen Technologien ermoglicht „Virtual-reality-Ablaufe“. Obduktionen konnen nun nichtinvasiv durchgefuhrt werden. Die Dokumentationen konnen uber das Internet an fast alle Orte in der ganzen Welt ubertragen werden.

A 47-year-old Japanese woman died unexpectedly 11 days after admission due to acute cerebellar infarction. The patient had a history of Sjogren syndrome with long-term steroid therapy, hypertension, thalamic infarction and amphetamine psychosis. Multiple pseudoaneurysms in both the aorta and coronary artery were found at autopsy, and one located in the aortic root had ruptured into the pericardium resulting in sudden unexpected death. The detailed examination suggested that the pseudoaneurysms resulted from microbial infection to the arterial wall via the vasa vasorum. Immunosuppression induced by the long-term steroid therapy and abused drug injection could have influenced the formation of pseudoaneurysms.

The number of suicides in Japan has increased from approximately 22 000 per year from 1988 to 1997 to >30 000 per year since 1998. Likewise, the number of suicides has been increasing in Mie Prefecture. The purpose of the present study was to examine the incidence of and circumstances surrounding all suicide cases during 1996-2002 in Mie Prefecture and to compare the data with those from 1989 to 1995. In Mie Prefecture, the age-specific suicide rate during the second 7-year period included marked increases among men aged 50-59 and 60-69 years. Among women, the age-specific suicide rate increased with age during both 7-year periods. During the second period, psychiatric disorders as causative factors increased in all generations. They were especially important for women of the younger generation, whereas economic problems were the most common causative factor among men aged 40-64. Physical illness as a causative factor in suicide was high among the elderly, but among the other age groups this factor trailed behind economic difficulties for men and psychiatric disorders for women. To prevent suicide, social cooperation as well as a plenitude of visiting nurses and psychiatric care is required, and early detection and treatment are also important.

The isolation of differentially expressed genes in the nucleus accumbens (NA) from chronically ethanol-administered rats may help in understanding the underlying molecular mechanisms for the development and reinforcement of ethanol addiction. The differential display indicated that around 0.1-0.2% of mRNA could be considered to be affected by chronic ethanol-administration in the NA, regardless of whether ethanol directly affected gene expression in the NA or the gene alteration was secondary to changes in neuronal activity caused by ethanol. Forty-six clones were successfully reamplified, and screening by reverse Northern blot analysis resulted in the isolation of five up-regulated and three down-regulated genes. One of the up-regulated cDNAs was homologous to human TGFβ1 and its preferential expression was also observed in the cerebellum and locus coeruleus (LC). Since clone c10 displayed an extremely strong preferential expression in the ethanol-administered NA, its upstream sequence was analyzed by 5′ rapid amplification of DNA ends (5′RACE) but the coding sequence has not yet been isolated. c118 showed enrichment in the ethanol-administered NA and displayed strong homology to the mouse KH domain RNA binding protein QKI-5A. The 5′RACE analysis confirmed that this clone encoded rat QKI-5A. Since QKI proteins are considered to be regulators of myelination and their absence causes dysmyelination, its up-regulation may offer protection against ethanol-induced dysmyelination. Another 12 cDNAs were registered as expression sequence tags (ESTs) or novel with their functions unknown. It is considered important, however, that to their upstream sequences including coding regions and promoter sequences are identified not only to estimate the roles of these differentially expressed genes in ethanol addiction but also to clarify whether ethanol-dependent gene-regulation can occur or not.

The acid digestion method has been widely used for the diagnosis of death by drowning, but it is not always sensitive. However, there has been no definitive method to replace acid digestion until now. We speculate that bacteria are more useful markers than plankton for the diagnosis of death by drowning. In this study, from the preserved blood samples of 32 freshwater drowning cases, specific DNA fragments of Aeromonas sobria, one of the most common aquatic bacteria, were examined using PCR. The DNA fragments of the bacterium were detected from 27 of 32 cases with first round PCR or nested-PCR. The remaining 5 cases in which bacterial DNA was not detected had longer storage periods for the blood samples and shorter time intervals from drowning to death. These results indicate that the present method can be applied to the diagnosis of death by drowning.

The number of suicides in Japan has increased from approximately 22,000 per year in 1988–1997 to over 30,000 per year since then. The number has also increased in Mie Prefecture during this period. According to many reports, suicide attempts are one of the risk factors of suicide. In the present study, we investigated the incidences and circumstances of all suicide cases between 1996 and 2002, focusing in detail on the frequency of suicide attempts and general differences in the frequency of all suicide cases. During the 7 years, 1979 male and 969 female suicides were reported to Mie Prefectural Police Headquarters. During the test period, there were suicide attempts in 13.4% of all suicidal cases, 10.7% for men and 18.9% for women. The average age was 48.98 years (SD 17.68), 47.07 years (SD 16.32) for men, and 51.19 years (SD 18.89) for women. Among men, we discovered the risk factors of suicide attempts in completed suicides, which were “single time” of suicide attempts, “living with family” for the family constitution, and “visiting treatment” of the admission statuses. Among women, the risk factors were “living with family” and “visiting treatment”. We must pay attention to those risk factors.

Traumatic cerebellar hemorrhagic contusions are infrequent, and the pathogenic mechanism involves a coup injury that is associated with motor vehicle accidents in most cases. Traumatic basal subarachnoid hemorrhage (TBSAH) is commonly reported after blunt trauma to the neck or unrestricted movement of the head, and the source of the hemorrhage is most frequently identified in the vertebrobasilar arteries. A 55-year-old woman who was addicted to alcohol was found dead in her bed. She had a bruise on the left side of her posterior parietal region, and autopsy revealed massive subarachnoid hemorrhage at the base of the brain; the hematoma was strongly attached to the right lower surface of the cerebellar hemisphere. No ruptured cerebral aneurysms, arteriovenous malformations or vertebrobasilar artery leakage were detected. Hemorrhagic cerebellar contusions were regarded as the source of the TBSAH. This is the first report of TBSAH suspected to have been caused by contrecoup cerebellar contusions.

In Japan, the medical examiner system was enforced only in three large cities, Tokyo metropolitan, Osaka and Kobe Cities. In other areas without this system, autopsy rates are much lower than in the areas with the system. Since the population of the aged (>/=65 years old) has been increasing recently, the subjects for medicolegal investigations seem to be also increasing. In the present study, between Mie Prefecture and those three Medical Examiner's Offices in Japan, the inquest results during the 5-year-period from 1996 to 2000, especially on the aged, were compared. The aged accounted for approximately 50% of all inquest cases in those areas. Autopsy rates for the aged were 16, 24 and 75% in Tokyo, Osaka and Kobe, respectively. Seventy-five to eighty percent was classified in deaths due to disease. Seventy to seventy-five percent of death due to disease was subclassified in circulatory diseases. The highest incidence of vascular diseases was observed in Kobe whose autopsy ratio was the highest. On the contrary, ambiguous causes of deaths, e.g. heart failure or unknown, were still frequent in Mie Prefecture.

Human class I ADH is a dimmer formed by the random association of three types of subunits (alpha, beta and gamma) encoded by ADH1A, ADH1B, and ADH1C, respectively. Different kinetic properties were reported due to polymorphisms of ADH1B Arg47His and ADHIC Ile349Val. Besides these polymorphisms in the coding region, various mutations in the promoter region and 3' untranslated (UTR) region, which possibly affect expression and degradation rate, were recently reported. In this study, to asses the involvement of each genotype in alcohol metabolism in humans, our previously collected data set of blood EtOH and AcH changes were reanalyzed with regard to the ALDH2 Glu487Lys genotype. The effects of genotypes and haplo-types on transcriptional activity were also examined by a luciferase reporter assay by cloning the promoter region and 3' UTR corresponding to each polymorphism and transfecting into HepG2 cells. Among the nine polymorphisms, including ADH1B Arg47His and ADH1C Ile349Val, blood EtOH levels were significantly affected by polymorphisms ADH1B -451GT, ADH1B +52AG, ADH1B +531GA, ADH1B +1176AGdel. and ADH1A -55CT in ALDH2 Glu/Glu subjects. In the ALDH2 Glu/Lys genotype background, only ADH1C -254GC and ADH1B His47Arg showed significant effects on blood EtOH. These five loci (and the two loci which had significant effect on blood EtOH in ALDH2 Glu/Glu and Glu/Lys subjects) also showed strong linkage disequilibrium. In comparison to the in vivo study on alcohol metabolism, significantly higher transcriptional activities in ADH1B -451T (rather than C) promoter and ADH1C-254 G (rather than C) promoter were observed in a luciferase assay in HepG2 cells. In conclusion, polymorphisms in the untranslated regions of ADH class I genes were demonstrated to clearly affect individual differences in alcohol metabolism. Especially, ADH1B -451GT, ADH1C-254GC polymorphisms were suggested to have functional significance with regard to transcriptional activity to the linkage equilibrium of polymorphisms ADH1B His47Arg and ADH1C Ile349Val.

Aims: To assess the effect of the −360G/A polymorphism in the promoter region of the human aldehyde dehydrogenase-2 (ALDH2) gene on its transcription, basal and acetaldehyde/ethanol-induced gene expression was examined by in vivo and in vitro experiments. Methods: Human peripheral blood leukocytes were collected before and after alcohol ingestion (0.4 g/kg body weight) in 21 healthy young Japanese volunteers with a deficient phenotype of ALDH2 (487Glu/Lys), and the levels of ALDH2 mRNA were quantified by real-time RT-PCR. The transcriptional activity of the ALDH2 promoter was investigated by a reporter assay using HepG2 cells in the presence or absence of acetaldehyde/ethanol. Results: The basal level of ALDH2 mRNA was significantly higher in −360A heterozygous subjects than in −360G homozygous subjects. In all subjects, regardless of the genotype, ALDH2 mRNA increased following ethanol ingestion. The promoter activity of a reporter plasmid for −360G was significantly lower than that of a reporter plasmid for −360A. Exposure to acetaldehyde induced a significant increase in the transcriptional activity of the −360G reporter, but not the −360A reporter. Conclusions: In vivo and in vitro experiments showed that the −360G allele has lower basal transcriptional activity than the −360A allele, whereas acetaldehyde/ethanol-induced gene expression, in general, seems to be more enhanced in individuals homozygous for the −360G allele than in those with the −360A allele. Thus, the promoter polymorphism may be involved in individual differences in acetaldehyde elimination.

Background: The polymorphism of human aldehyde dehyrogenase-2 (ALDH2) Glu487Lys is well known to be a crucial factor underlying the genetic background for alcohol sensitivity in Asian populations. Subjects with the inactive Lys487 allele show a marked increase in blood acetaldehyde level after alcohol intake, which results in facial flushing and various cardiovascular-related symptoms. However, other polymorphisms related to catecholaminergic systems that tightly regulate the activity of the sympathetic nervous system may also influence the physiological changes after acute alcohol intake. Methods: We investigated whether, together with the ALDH2 Gly487Lys and ADH1B Arg47His genotype, putative functionally important polymorphisms, including 9 loci in 7 human genes, were associated with changes in blood catecholamine levels and cardiovascular measures after alcohol ingestion. Forty-nine young Japanese males were subjected to blood catecholamine analysis after alcohol ingestion. Among them, 28 were also subjected to heart rate variability and blood pressure analysis. The contribution of polymorphisms to the alcohol-induced response was analyzed by multiple regression analysis. Results: Among the polymorphisms examined in this study, haplotypes of the phenylethanolamine N-methyltransferase (PNMT) promoter [(−182bpG/A)_(−387bpG/A)] and catechol-O-methyltransferase (COMT) exon 4 [(Ex4 + 119bpC/G)_(Ex4 + 138bpG/A), Leu136Leu_Val158Met] are suggested to have functionally important effects on alcohol-induced cardiovascular symptoms by affecting blood catecholamine levels. The neuropeptide Y (NPY) promoter C-1450T genotype is also suggested to be involved in the individual differences in regulation of catecholamine secretion. Conclusions: This study suggested that these common polymorphisms of genes related to catecholaminergic systems, as well as those of the alcohol metabolizing system, are significant for understanding the basis of individual differences in alcohol sensitivity.

The EditorSir,The number of suicides in Japan has increased from about 22000 per year between 1988 to 1997 to over 30 000 per yearsince then. Mie Prefecture, in central Japan, has also seen anincrease in suicide. We believe suicide victims express sui-cidal signs before they act. According to a report by Yoshio-ka for the Ministry of Education, Culture, Sports, Scienceand Technology of Japan, which presented a statistical analy-sis of suicides in Mie Prefecture between 1989 to 1995, theprefecture showed intermediate levels of suicide and patternsof suicide similar to those of Japan as a whole (1). Therefore,the Mie Prefecture suicide data were analyzed as a reflectionof the national problem. In the present report, the authorsinvestigated the incidence and the circumstances surroundingall suicide cases from 1996 to 2002 in cooperation with thefirst department of criminal investigation of the MiePrefectura police headquarters. Pre-suicide signs were alsoexamined in detail. All data in the records were completelyanonymous after encoding.Pre-suicide signs were determined by psychiatric spe-cialists and divided into four stages: direct linguistic signs,indirect linguistic signs, direct action signs and indirect ac-tion signs. Direct linguistic signs are direct expressions ofsuicidal thoughts, such as

The number of suicides in Japan has increased from approximately 22,000 per year in 1988-1997 to over 30,000 per year since then. It has also increased in Mie prefecture during that period. In the present study, we investigated the correlation between annual suicide rates in Mie prefecture, Japan from 1996-2002 and the annual unemployment rate in Japan from 1996-2002 among males. Among the results, annual suicide rates in total correlated with the unemployment rate in Japan, but the relation was not statistically significant: r(7)=0.76, r(2)(7)=0.58, p=0.05 (y=3.54x+6.37); the rates in males, however, correlated significantly with the unemployment rate in Japan: r(7)=0.85, r(2)(7)=0.73, p=0.01 (y=5.72x+4.49). In addition, we found that annual suicide rates in total correlated significantly with the male unemployment rates. When a patient is unemployed and in a bad situation, the medical staff and the family should be aware of the correspondence between suicide rates and unemployment. Language: en

The number of suicides in Japan has increased from approximately 22,000 per year from 1988 to 1997 to over 30,000 per year since then; this increase is among the most important problems facing Japan. Moreover, the unemployment rate in Japan has increased rapidly since 1998. In this study, we examined the total number of suicides and both the suicide and unemployment rates in Japan from 1978 to 2004. We also focused on the correlation between annual suicide rates in Japan and the annual unemployment rates during the study period. During that period, 455,357 males and 225,012 females committed suicide in Japan, and the suicide rates by sex were 27.8 males and 13.3 females per 100,000 population (P

The deficiency in activity of aldehyde dehydrogenase-2 (ALDH2), commonly found in Asians, is due to a mutation at position 487 in exon 12, encoded by the ALDH2*2 allele, which is a crucial factor for deficient ability to acetaldehyde (AcH) oxidation. In addition to this locus, polymorphism in -361 G/A mutation of this gene at 5'flanking region, commonly found in multi-racial populations, is one of the suggestive polymorphisms which may affect on the enzyme activity because it has been reported to affect on the transcriptional activity in hepatoma cells. We aimed to examine the individual differences in alcohol metabolism in Japanese population based on the genotypes of both ALDH2 exon 12 and -361 G/A promoter region. Following genotyping of 2 loci, subject groups based on the promoter genotype was defined as variant A carrier (A+; A/A and G/A) or not (A-; G/G). Under the condition with 0.4 g/kg body weight of alcohol ingestion, significant differences in AcH peak levels, that reached at 30 or 60 minutes in most subjects, was not detected between promoter A+ and A- groups both in exon 12 ALDH2*1/*1 and ALDH2*1/*2 subjects. Furthermore, we developed a real-time RT-PCR method to detect and quantitate the ALDH2 mRNA levels in easily accessible peripheral blood leukocytes (PBLs) to examine whether this promoter mutation affects on the amount of ALDH2 mRNA in normal human tissue at pre- and post-alcohol ingestion phase in ALDH2*1/*1 subjects. Significant increase of mRNA was observed only in A- group at 2 hours after alcohol ingestion. Maximal changing rates of mRNA in PBLs within 3 hours after alcohol intake were +48 % and +17 % in A and A' groups, respectively. These results suggest that the individual differences in ALDH2 enzyme activity may be intricately regulated by the common polymorphisms in these two loci in Asian populations.

Acute promyelocytic leukemia (APL) is associated with severe hemorrhagic coagulopathy induced by the release of procoagulant, plasminogen, and protease from leukemic cells. The case described in this report is of a 15-year-old male who unexpectedly died due to a cerebral hemorrhage caused by underlying APL within 12 h after presentation. This case suggests that underlying APL should be considered as a differential diagnosis when sudden death occurs with a fatal spontaneous hemorrhage, although it is rare.

The number of suicides in Japan increased from about 22,000 per year during the period 1988 to 1997 to over 30,000 since 1998. The number of suicides has also been increasing in Mie Prefecture. In the present study we examined the incidence and the circumstances for all suicidal cases during the seven-year period, 1996-2002, that were reported to Mie Prefectural Police Headquarters. In Mie Prefecture, the number of suicides per year averaged 421 cases: from a minimum of 319 in 1997 to a maximum of 501 in 1998. The most frequent month for suicides was July, while the lowest number occurred in February. Suicide was most common in the 50-59 year age group in men, and in the 70-79 year group in women. Regarding the means of suicide, hanging was the most frequent (61.6%) in both sexes. Psychiatric disorders were the most serious causative factors in all generations, accounting for 23.8% in general but being especially prevalent in the younger generation of people under 39 years. Further reasons for suicide were economic problems for the 40-64 age-group in men and suffering from illness for the elderly age-groups in both sexes. In order to prevent suicide, urgent strategies for effective medical treatments and improved working circumstances are required.

The effects of alcohol intake on haemodynamics and heart rate variability were investigated with relation to genotypes of aldehyde dehydrogenase 2 (ALDH2), which were determined in 33 male Japanese volunteers (mean +/- s.e., 35.7 +/- 1.4 years) using the PCR-RFLP method. On the alcohol intake day, they consumed 660 ml of beer containing 33 ml of ethanol (0.3-0.5 g/kg of body weight) from 18.00 to 18.30. On the control day, they ingested the same amount of non-alcoholic beer. Ambulatory blood pressure, heart rate, and ECG R-R intervals were measured during a 24-h period with a portable recorder. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. Sixteen subjects were homozygotes for the normal ALDH gene (active ALDH2), only one was a homozygote for the mutant ALDH2 gene (inactive ALDH2), and the remaining 16 were heterozygotes (inactive ALDH2). Alcohol intake did not change 24-h average blood pressure (BP) either in the active ALDH2 group or in the inactive ALDH2 group. However, during the time interval from 18.30 to 0.00, alcohol intake significantly decreased diastolic BP in the active ALDH2 group and both systolic and diastolic BPs in the inactive ALDH2 group. In the active ALDH2 group, alcohol intake did not change heart rate, while in the inactive ALDH2 group, alcohol intake significantly increased 24-h average heart rate by 5.3 +/- 1.6 beats per minute (P < 0.01). In the active ALDH2 group, neither the LF nor the HF component was changed by alcohol intake, while in the inactive ALDH2 group, both the LF and the HF components were significantly decreased during the time interval from 18.30 to 0.00. These results demonstrate for the first time that ALDH2 genotypes modify the effects of intake of a small amount of alcohol on haemodynamics and heart rate variability in Japanese men.

To the Editor: The process of commercial coffee roasting releases large amounts of carbon monoxide (CO), which sometimes reach life-threatening levels. We report a case of a death due to CO poisoning sustained during commercial coffee roasting. Report of a Case. A 23-year-old employee of a roasting plant collapsed and lost consciousness soon after entering a storage tank (approximately 2 m in diameter and 2.7 m in height) to retrieve a tool that he had dropped into the tank. When removed from the tank 40 minutes later, he was found to be in a state of cardiopulmonary arrest and was transported to the hospital. Resuscitation attempts, including cardiac compression and administration of 100% oxygen, were unsuccessful. Five coworkers also were transported to nearby hospitals. Three of these had collapsed and lost consciousness when they went inside or approached the tank, while 2 others reported presyncopal symptoms. All 5 recovered soon or within a few hours, although 1 was hospitalized and given oxygen. The medicolegal autopsy of the deceased worker was performed in our department 17 hours after the death. A cherryred discoloration was seen on the back. Slight bruises were found on the left temporal area and the left forearm. Multiple petechial hemorrhages were observed in the pericardium and on lung surfaces. Both lungs showed severe edema and congestion. The concentration of CO hemoglobin (COHb) was 26% in the heart blood. No other toxic gases or drugs were detected. The cause of death was determined to be acute CO poisoning. According to the result of the subsequent forensic inspection, the company involved in this incident uses an extracting process on coffee beans that have already been roasted and ground. This process, which is widely used in the industry, involves adding water to ground beans in an extracting tank to produce a coffee extract that is then transferred to a storage tank. Air samples from storage tanks were collected throughout the roasting process for the determination of CO levels. In this case, the maximum levels of CO in the storage tank were found to be 10000 to 100000 ppm. An ambient CO concentration of 5000 to 10000 ppm can lead to a COHb saturation of as high as 75% (a lethal level) within a few minutes. Comment. Industrial coffee extraction may place workers at risk of CO poisoning. Workplace standards, improved industrial systems, and better worker education may help to reduce this risk.