Long-Term Health Effects of PCBs and Related Compounds: A Comparative Analysis of Patients Suffering from Yusho and the General Population.

Yusho, which refers to a mass poisoning caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans, was first reported in October 1968 in Japan. Yusho patients suffer from various symptoms; however, after 40 years, some emerging symptoms have been attributed to aging. The prevalence of symptoms and diseases among Yusho patients and the general population was compared in this study. The data obtained from the survey among Yusho patients (1131 patients) by the Ministry of Health, Labour, and Welfare of Japan in 2008 were compared with the data from a survey conducted among the general population. When selecting the comparison group, the age and residential area (prefecture) were taken into account to match the baseline characteristics of Yusho patients. A logistic regression analysis was performed to identify the association between Yusho and the prevalence of symptoms and was adjusted for various potential confounding factors (age, sex, body mass index, cigarette smoking, frequency of drinking, and walking time). Skin pigmentation and acneiform eruption were found to be characteristic symptoms of Yusho and were more prevalent in these patients. Other symptoms and diseases associated with Yusho included orthostatic hypotension, hypohidrosis, dysgeusia, Basedow's disease, hoarseness, cardiac insufficiency, tachycardia, eczema, and hair loss. Symptoms related to aging, such as general fatigue, arthralgia, and numbness in the extremities, were significantly higher in Yusho patients after adjusting for age and lifestyle. This study demonstrated that, 40 years after the outbreak of Yusho, the prevalence of various symptoms and diseases in Yusho patients, including age-related diseases, was higher than that in the general population.

Yusho and its latest findings-A review in studies conducted by the Yusho Group.

The Yusho incident is an unprecedented mass food poisoning that occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations associated with systemic, ophthalmological, and mucosal symptoms for a long period of time. The Study Group of Yusho (the Yusho Group) has been conducting annual medical check-ups on Yusho victims for more than 45years. Since 2002, when concentrations of dioxins in the blood of Yusho patients started to be measured, the pharmacokinetics of dioxins, relationship between blood levels of dioxins and symptoms/signs in patients directly exposed to dioxins, and the adverse effects on the next generation have become dramatically clear. Herein we review recent findings of studies conducted by the Yusho Group to evaluate chronic dioxin-induced toxicity to the next generation as well as Yusho patients in comparison with a similar food mass poisoning, the Yucheng incident. Additionally, we summarized basic studies carried out by the Yusho Group to re-evaluate the mechanisms of dioxin toxicities in experimental models and various functions of the aryl hydrocarbon receptor (AhR), known as the dioxin receptor, pathway.

Association between first airborne cedar pollen level peak and pollinosis symptom onset: a web-based survey.

Cedar pollinosis in Japan affects nearly 25 % of Japanese citizens. To develop a treatment for cedar pollinosis, it is necessary to understand the relationship between the time of its occurrence and the amount of airborne cedar pollen. In the spring of 2009, we conducted daily Internet-based epidemiologic surveys, which included 1453 individuals. We examined the relationship between initial date of onset of pollinosis symptoms and daily amount of airborne cedar pollen to which subjects were exposed. Approximately 35.2 % of the subjects experienced the onset of pollinosis during a one-week interval in which the middle day coincided with the peak pollen count. The odds ratio for this one-week time interval was 4.03 (95 % confidence interval: 3.34-4.86). The predicted date of the cedar pollen peak can be used to determine the appropriate date for initiation of self-medication with anti-allergy drugs and thus avoid development of sustained and severe pollinosis.

Residual inhibition of tinnitus induced by 30-kHz bone-conducted ultrasound.

Sounds at frequencies of >24-kHz are classified as ultrasound which cannot be heard by humans if presented by air conduction, but can be perceived if presented by bone conduction. Some research studies involving ultrasonic hearing have reported that tinnitus is masked by bone-conducted ultrasound (BCU). However, little is known about residual inhibition (RI), which is a continuous reduction or disappearance of tinnitus after presentation of BCU. This study investigated whether RI could be induced by BCU. Five types of the masker sounds were used to measure RI in 21 subjects with tinnitus. A bone-conducted 30-kHz pure tone was used as a BCU, and an air-conducted 4-kHz pure tone, narrow-band noise, white noise, and a bone-conducted 4-kHz pure tone were used as controls of audible sounds. The masker intensities of the 30-kHz BCU and audible sounds were set at the minimum masking levels of tinnitus plus 3 and 10 dB, respectively, considering the narrow dynamic range of BCU. The duration of RI induced by the 30-kHz BCU was significantly longer than those induced by the 4-kHz sounds, but was not significantly different from that induced by the white noise. BCU activates the cochlear basal turn in response to the high frequency, which may broadly overlap with the frequency range that included the dominant tinnitus pitch in most of our subjects. The longer RI duration for the 30-kHz BCU was probably derived from this characteristic. These results suggested that the peripheral stimulation characteristic of BCU probably contributed to inducing long RI durations.

[Relationship between half-lives of blood dioxins and possible metabolic mechanism].

Blood levels of dioxins in Yusho patients have been measured for 10 years. The purposes of this study were to determine the half-lives of dioxins on the basis of the data obtained from Yusho patients and to compare the half-lives of the compounds. Linear regression analysis was performed using the binary logarithmic value of each dioxin level as the dependent variable and the year of measurement as the independent variable. The linear coefficient obtained from this linear regression analysis was the reciprocal number of the half-life. The relationship between the blood dioxin levels estimated in 2004 and the reciprocal number of half-life was evaluated. Of the studied dioxins, the concentrations of some compounds were strongly correlated with that of 2,3,4,7,8-PeCDF. For 2 such compounds, the correlation coefficient of the reciprocal numbers of half-life were greater than the correlation coefficient of the logarithmic values of the estimated concentrations. Of these 2 compounds, the concentration of 3,3,4,4,5,5-HxCB was at least 50 times less than that of the 2,3,4,7, 8-PeCDF in rice oil: however, their current concentrations are equivalent. Patients with high levels of 2,3,4,7,8-PeCDF also showed high levels of 3,3,4,4,5,5-HxCB. Yusho patients may have a disease-specific mechanism to supply 3,3,4,4,5,5-HxCB.

Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event.

BACKGROUND: The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination. METHODS: Medical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses. RESULTS: Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum gamma-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho. CONCLUSION: After Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.

[Average of the PCDFs value in blood in patients with Yusho in the 2001 to 2003 fiscal year and comparison between the clinical features and PCDFs].

BACKGROUND: Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth, general fatigue, headaches, and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001. SUBJECTS AND METHODS: The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15 years previously. RESULTS AND DISCUSSION: The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well, the blood PeCDF level was related to PCB level, hexachlorobiphenyl level, urinary sugar, erythrocyte sedimetation rate (ESR) (2-hour), thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988. However, PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions.

[Relationship between blood dioxin levels and present/past clinical symptoms in Kanemi Yusho patients].

BACKGROUND: Kanemi Yusho was a food poisoning incident caused by rice bran oil that occurred in western Japan, particularly in northern Kyushu, in 1968. It is difficult to determine the symptoms in patients after many years since the occurrence. Techniques for measuring blood dioxins have advanced recently. More accurate data measurement has now become possible, and techniques for mass data analysis, such as data mining, have also advanced. It has also become possible to find unknown characteristics, even in an object group with elusive characteristics, by checking all the combinations in all the patients. AIM: There are already several reports on the incidence of symptoms in Yusho patients. These reports are limited to symptoms in a single period, and there has been no analysis taking into account the time that has elapsed. Here, we evaluated the relationship between recent and past symptoms and 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) levels in the same subject patient, in order to demonstrate the correlation between PeCDF levels and symptoms at a time point close to the incident. METHODS: Subjects were examined for symptoms of Yusho and had blood PeCDF levels measured, both recently and in the past. Combinations were extracted using association analysis of data mining technique for comparison, which had strong correlations between the presence or absence of symptoms in the medical examination, tests including blood test, dermatological examination, dental examination and ophthalmologic examination in recent years (2001-2004) and the blood PeCDF levels and those between the presence or absence of past (1986-1989) symptoms and recent blood PeCDF levels. RESULTS: Subjects with higher PeCDF levels were more likely to present with pigmentation, a symptom included in the diagnostic criteria for Yusho. Pigmentation was a commonly found symptom in the past. Past pigmentation was a common symptom in the present. DISCUSSION: PeCDF levels were measured recently and therefore should not be compared directly with past symptoms. However, among the symptoms included in the diagnostic criteria, past symptoms tended to have a stronger relationship with PeCDF levels than did recent symptoms. We suggest that the present PeCDF level is strongly related to the past symptoms since the present PeCDF level is correlated with the past PeCDF level due to constant emission rate. More specifically, if the past PeCDF level is strongly related to the past symptoms, it can indirectly be concluded that the present PeCDF level is also strongly related to the past symptoms. Thus, the present PeCDF level cannot be related to the past symptoms directly but can indirectly. CONCLUSIONS: Combining recent and past symptoms further demonstrated that clinical symptoms are strongly related to PeCDF toxicity. This may have resulted from the increase in symptoms with aging, however, it was demonstrated that the symptoms of each patient were relieved and become obscure.

Relationship between clinical features and blood levels of pentachlorodibenzofuran in patients with Yusho.

BACKGROUND: Yusho is a form of food poisoning that occurred in 1968, as a result of consuming rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins such as polychlorinated dibenzofurans (PCDFs). The victims of Yusho suffered from various dermatological, ophthalmological, and mucosal symptoms in addition to general fatigue, weight loss, anorexia, headache, paresthesia of the extremities, abdominal pain, cough and sputa, dysmenorrhea, and growth retardation in infants and children. We measured the blood levels of dioxins in the annual medical check-up of Yusho patients from 2001 to 2003. PURPOSE: To analyze the relationship between the concentrations of PCDFs/PCBs and the subjective/objective/laboratory findings of patients with Yusho. We also compared the present clinical findings with those collected in 1988. RESULTS AND DISCUSSION: The mean blood level of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in 359 patients with Yusho was 177.50 pg/g lipids, which was much higher than that of normal controls (15.2 +/- 8.9 pg/g lipids). The blood levels of PeCDF were significantly correlated with total PCB levels, hexachlorobiphenyl levels, urinary sugar, 2-h erythrocyte sedimentation rate, thymol turbidity test, and sodium levels. A significant correlation was also noted with dermatological findings (acneform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. The incidence and severity of most of the dermatological and ophthalmological symptoms decreased from 1988 to 2001-2003. In conclusion, high amounts of PCBs and PeCDF are still present in a number of patients with Yusho. The patients still suffer from various mucocutaneous and subjective symptoms.

[Evaluation of dermatological symptoms of Yusho patients in the annual examination in 2003-2004].

We evaluated the severity grades and the skin severity scores of the skin symptoms who visited the annual examinations of Fukuoka prefecture in 2003 and 2004. The severity of skin symptoms improved significantly in the first 20 years; nowadays, however, further improvement can hardly be observed. More than 36 years have passed since the Yusho incident, and about 60% of the patients currently present no skin symptoms. In contrast, in about 40% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could still be observed. Using Peason's correlation coefficient test and Spearman's correlation coefficient test, we analyzed correlation between "PCB pattern" and the blood PCB concentration, the skin severity grade and the skin severity scores. However, we could not find out any obvious correlation.

[Inter-laboratory evaluation studies for establishment of notified ELISA methods for allergic substances (buckwheat)].

Inter-laboratory evaluation studies were conducted for the ELISA methods for allergic substances (buckwheat). Extracts of snack, bun and udon spiked with buckwheat standard protein at a level of 5-20 ng/mL as sample solutions were analyzed in replicate at 10 laboratories. Coefficients of variation (CVs) of the ELISA methods using a Buckwheat Protein ELISA Kit (Buckwheat kit) and a FASTKIT Buckwheat ELISA kit (Buckwheat ELISA kit) were mostly below 10%. Mean recoveries of the buckwheat standard protein from the food extracts were over 40% in the two ELISA methods. Repeatability relative standard deviations of buckwheat standard protein in three food extracts were in the ranges of 6.8-78.5% and 5.0-33.9% for the Buckwheat kit and the Buckwheat ELISA kit, respectively. Reproducibility relative standard deviations of buckwheat standard protein in three food extracts were 11.9-69.5% and 16.5-34.1% for the Buckwheat kit and the Buckwheat ELISA kit, respectively. The detection limits of both ELISA methods were 1 ng/mL in sample solutions. These results suggest that the notified ELISA methods are reliable and reproducible for the inspection of buckwheat protein levels in extracts of snack, bun and udon.