Prevalence and correlation of multiple chemical sensitivity and electromagnetic hypersensitivity with age, sex, and depression in the Japanese population: a retrospective study.

BACKGROUND: In Japan, there are currently no definitive conclusions regarding the characteristics of multiple chemical sensitivity (MCS) and electromagnetic hypersensitivity (EHS). This study aimed to determine the prevalence and correlation of MCS and EHS with age, sex, and depression in the Japanese population. METHODS: An anonymous self-report questionnaire was distributed to 2,007 participants. Variables such as MCS, EHS, depression score, and demographic characteristics were individually evaluated using the U-test, chi-squared test, and correlation analyses. Moreover, we performed a covariance structure analysis to build a structural equation model. RESULTS: Older individuals and women were more likely to exhibit MCS and EHS symptoms. Moreover, depression was correlated with MCS and EHS. CONCLUSIONS: Although MCS and EHS are strongly correlated, they exhibit distinct characteristics and symptoms, indicating that they can be regarded as separate conditions.

Two Cases of Multiple Chemical Sensitivity Successfully Treated With Kampo Medicine.

CONTEXT: Multiple chemical sensitivity (MCS) is a chronic disorder in which minimal but sustained exposure to particular chemicals causes headaches, vertigo, and multiple other symptoms. Up to 10% of cases are clinically unresponsive to treatment. Kampo medicines include multiple crude components with many applications for organ disorders. OBJECTIVE: The research team aimed to assess the efficacy of goreisan, a Japanese Kampo medicine, for 2 patients diagnosed with intractable cases of MCS. DESIGN: The research team conducted case studies with 2 female patients. SETTING: The study took place at the Kampo clinic in the Department of Gynecology and Obstetrics at the Japanese Red Cross Maebashi Hospital in Maebashi, Gunma, Japan. PARTICIPANTS: The participants were patients at the clinic. INTERVENTION: The first participant received the Kampo formula goreisan for her headaches and keigairengyoto for her mucosal discomfort; the second received goreisan for her headaches and kakkonto to reduce her shoulder-muscle stiffness. The participants received Kampo treatments for one month. OUTCOME MEASURES: The first participant's MCS symptoms were evaluated with the Quick Environment Exposure Sensitivity Inventory questionnaire (QEESI); the second using a numeric rating scale (NRS). RESULTS: After the Kampo treatments, the first participant's QEESI scores for chemical intolerance, symptom severity, and life impact were reduced from 47, 92, and 76 to 37, 39, and 55 points, respectively. The second participant's NRS scores were likewise reduced from 6, 8, and 8 out of 10 to 1, 2, and 1 out of 10. Symptoms were relieved in both patients, and didn't recur. CONCLUSIONS: These results highlight the potential benefits of Kampo medicine for the treatment of intractable MCS. Further investigations will be needed to confirm the mechanism of action, thereby improving the understanding of the effectiveness of Kampo medicine for MCS therapy.

Development and evaluation of an electromagnetic hypersensitivity questionnaire for Japanese people.

The purpose of the present study was to evaluate the validity and reliability of a Japanese version of an electromagnetic hypersensitivity (EHS) questionnaire, originally developed by Eltiti et al. in the United Kingdom. Using this Japanese EHS questionnaire, surveys were conducted on 1306 controls and 127 self-selected EHS subjects in Japan. Principal component analysis of controls revealed eight principal symptom groups, namely, nervous, skin-related, head-related, auditory and vestibular, musculoskeletal, allergy-related, sensory, and heart/chest-related. The reliability of the Japanese EHS questionnaire was confirmed by high to moderate intraclass correlation coefficients in a test-retest analysis, and high Cronbach's α coefficients (0.853-0.953) from each subscale. A comparison of scores of each subscale between self-selected EHS subjects and age- and sex-matched controls using bivariate logistic regression analysis, Mann-Whitney U- and χ(2) tests, verified the validity of the questionnaire. This study demonstrated that the Japanese EHS questionnaire is reliable and valid, and can be used for surveillance of EHS individuals in Japan. Furthermore, based on multiple logistic regression and receiver operating characteristic analyses, we propose specific preliminary criteria for screening EHS individuals in Japan. Bioelectromagnetics. 37:353-372, 2016. © 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.

New criteria for multiple chemical sensitivity based on the Quick Environmental Exposure and Sensitivity Inventory developed in response to rapid changes in ongoing chemical exposures among Japanese.

BACKGROUND & OBJECTIVES: The Quick Environmental Exposure and Sensitivity Inventory (QEESI) developed by Miller and Prihoda in the USA is used as a questionnaire for patients with multiple chemical sensitivity (MCS) in >10 countries. We developed a Japanese version of QEESI, assessed its reliability and validity, and defined original cut-off values for screening Japanese patients with MCS in 2003. Our recent study revealed that opportunities for exposure to various chemicals had increased for people in Japan, while subjective symptoms of MCS in patients had increased in severity. In this study, we considered new cut-off values that combined QEESI subscale scores based on the current situation in Japan. METHODS: The questionnaire used was a Japanese version of QEESI. The survey was conducted from 2012 to 2015. Participants were 111 patients with MCS (mean age: 46 ± 20, 81% female) initially diagnosed by physicians, and 444 age- and gender-matched controls not diagnosed with MCS by doctors. The discriminatory validity of QEESI scores of patients and controls were evaluated by logistic regression and receiver operating characteristic analyses when considering interactions of the Masking Index (ongoing chemical exposure). New combined cut-off values were then set. RESULTS: New combined cut-off values (meeting conditions of Chemical Intolerances ≥ 30, Symptom Severity ≥ 13, and Life Impacts ≥ 17) showed high sensitivity (82.0%) and specificity (94.4%). Using new criteria when considering ongoing chemical exposure, study participants were categorized as: Very suggestive, Somewhat suggestive, Problematic, and Not suggestive. Participants classified as Very suggestive included 25 (5.6%) controls. CONCLUSIONS: We have set new criteria with combined cut-off values based on current Japanese conditions. Such new criteria can be used for screening and as a diagnostic aid for Japanese patients with MCS and suggest approximately 6% of the Japanese general population may be classified as "Very suggestive people with MCS".

Clinical characteristics of physician-diagnosed patients with multiple chemical sensitivity in Japan.

Multiple chemical sensitivity (MCS), a syndrome in which multiple symptoms occur with low-level chemical exposure, has not been clarified in detail. The aim of our study was to clarify the clinical characteristics of physician-diagnosed MCS patients in Japan. We analyzed patient characteristics based on the medical records of 106 patients diagnosed with MCS according to the 1999 Consensus and the Japanese diagnostic criteria for MCS. We evaluated subjective symptoms using the Quick Environment Exposure Sensitivity Inventory (QEESI) and compared the QEESI scores with those of four MCS patient groups in the US reported by Miller and Prihoda [Miller, C.S., Prihoda, T.J., 1999b. A controlled comparison of symptoms and chemical intolerances reported by Gulf War veterans, implant recipients, and persons with multiple chemical sensitivity. Toxicol Ind Health 15, 386-397]. Female patients accounted for 74.0%. Most male patients were in their 30s, whereas female ages ranged widely from 10 to 65 years. Among estimated onset factors, those seen in males tended to be workplace related, while female patients showed a variety of factors. Co-morbid allergic disease was present in 84.0% of patients. A significant difference in the QEESI score between male and female patients was found in only one item out of 10 in symptom severity and life impact. However, all 10 items in chemical intolerance were significantly higher in females than in males. The mean QEESI score in the patient group in our study was lower than those in any of the four self-reported patient groups in the US.

Survey on changes in subjective symptoms, onset/trigger factors, allergic diseases, and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity.

BACKGROUND: Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago. METHODS: The new survey was conducted from 2012 to 2015 and the old survey was independently conducted from 1999 to 2003, meaning it was not a follow-up study. Patients were initially diagnosed by physicians at five medical institutions with MCS specialty outpatient services, with 111 and 103 patients participating in the new and old surveys, respectively. The controls were a general population living in Japan, with 1313 and 2382 participants in the new and old surveys, respectively. Subjective symptoms and ongoing chemical exposure were evaluated using a quick environmental exposure sensitivity inventory. Additionally, from clinical findings recorded by an attending physician, the prevalence of allergic diseases and presumed onset/trigger factors were evaluated. Differences between new and old surveys were analyzed using logistic regression analyses and significance tests. RESULTS: Compared with ten years ago: (1) Regarding factors affecting patients with ongoing chemical exposures, the proportion of patients affected decreased significantly for two items only (insecticides and second-hand smoke). The proportion of controls showing ongoing exposure to 8 out of 10 items changed significantly. (2) In patients, scores for chemical intolerances, other intolerances, and life impacts increased significantly. (3) In terms of the prevalence of allergic diseases among patients with MCS, bronchial asthma (adjusted odds ratio [AOR]: 5.19), atopic dermatitis (AOR: 3.77), allergic rhinitis (AOR: 5.34), and food allergies (AOR: 2.63) increased significantly, while hay fever (AOR: 0.38) and drug allergies (AOR: 0.40) decreased significantly. (4) With regard to construction and renovation, which was the presumed predominant onset/trigger factor for MCS 10 years ago, this decreased from 68.9% to 35.1%; in contrast, electromagnetic fields (0.0%-26.1%), perfume (0.0%-20.7%), and medical treatment (1.9%-7.2%) increased significantly, confirming the diversification of onset/trigger factors. CONCLUSION: Compared to ten years ago, for patients with MCS, an increase in avoidance behavior toward chemical substance exposures, which were presumed to be aggravating factors for symptoms, was confirmed. It has been suggested that the ongoing chemical exposure of the general population in Japan has largely changed. In addition, for patients with MCS, chemical intolerances and life impacts have become severe, the prevalence of the main allergic diseases has increased, and onset/trigger factors have become diversified.

[Relationship between fetal lead exposure and birth weight--evaluation using deciduous incisor enamel].

OBJECTIVE: The purpose of this study was to examine the relationship between fetal lead exposure and birth weight, using deciduous incisor enamel as a biomarker and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for analysis of lead. METHODS: We asked dental clinics (n=11) and kindergartens (n=11), mainly in the Tokyo metropolitan area and Miyagi Prefecture, and parents to enroll donors of exfoliate deciduous incisors. Donors who consented to this study voluntarily sent deciduous incisors and questionnaires to the authors between March and October, 2003. The Pb/Ca ratios of inner enamel samples were determined by LA-ICP-MS. The relationship between the lead-to-calcium ratio in the enamel and the birth weight was evaluated by stepwise multiple linear regression analysis. RESULTS: One hundred forty-one subjects (male, 72; female, 69) were enrolled in this study. The mean Pb/Ca ratio in the enamel was as low as 0.24 mg-Pb/kg-Ca (SD=0.17). Stepwise multiple linear regression analysis extracted the following maternal variables with a positive coefficient with birth weight: gestational age (p < 0.01), weight gain during pregnancy (p < 0.01), prepregnancy BMI (body mass index, p < 0.01), and parity (p < 0.05). Lead concentration in the enamel was significantly negatively associated with birth weight (p < 0.05). CONCLUSIONS: Our study indicated that lead concentration in the enamel was inversely related to birth weight. This association was found in a population of which the mean blood lead level was estimated to be as low as about 1 microg/dl. We concluded that in utero low lead exposure decreased birth weight, within the normal range of birth weight.

Evaluation of subjective symptoms of Japanese patients with multiple chemical sensitivity using QEESI(c).

OBJECTIVES: The Quick Environment Exposure Sensitivity Inventory (QEESI(c)) has been used as a questionnaire to evaluate subjective symptoms of patients with multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerance, in Japan. However, no cutoff value for Japanese subjects has yet been established. We designed this study to establish a cutoff value for Japanese subjects using QEESI(c) for screening of MCS patients. METHODS: A questionnaire using the QEESI(c) was administered to 103 MCS patients and 309 healthy control subjects matched for age and sex. QEESI(c) scores of the two groups were compared using logistic regression analysis, receiver operating characteristic analysis, and the Mann-Whitney test. RESULTS: Cutoff values for Japanese subjects were determined for the Chemical Intolerance subscale (40), Symptom Severity subscale (20), and Life Impact subscale (10). The subjects whose scores exceeded the cutoff values in any two subscales accounted for 88.4% of the patients but only 14.5% of the controls. CONCLUSIONS: Our results suggest that subjects meeting two out of three subscale criteria can be screened as "patients suffering from a low level of environmental chemicals such as MCS" in Japan.

A bifunctional enzyme with L-fucokinase and GDP-L-fucose pyrophosphorylase activities salvages free L-fucose in Arabidopsis.

Monomeric sugars generated during the metabolism of polysaccharides, glycoproteins, and glycolipids are imported to the cytoplasm and converted to respective nucleotide sugars via monosaccharide 1-phosphates, to be reutilized as activated sugars. Because L-fucose (L-Fuc) is activated mainly in the form of GDP derivatives in seed plants, the salvage reactions for L-Fuc are expected to be independent from those for Glc, Gal, L-arabinose, and glucuronic acid, which are activated as UDP-sugars. For this study we have identified, in the genomic data base of Arabidopsis, the gene (designated AtFKGP) of a bifunctional enzyme with similarity to both L-fucokinase and GDP-L-Fuc pyrophosphorylase. Recombinant AtFKGP (rAt-FKGP) expressed in Escherichia coli showed both L-fucokinase and GDP-L-Fuc pyrophosphorylase activities, generating GDP-L-Fuc from L-Fuc, ATP, and GTP as the starting substrates. Point mutations in rAtFKGPs at either Gly(133) or Gly(830) caused loss of GDP-L-Fuc pyrophosphorylase and l-fucokinase activity, respectively. The apparent K(m) values of L-fucokinase activity of rAtFKGP for L-Fuc and ATP were 1.0 and 0.45 mm, respectively, and those of GDP-L-Fuc pyrophosphorylase activity for L-Fuc 1-phosphate and GTP were 0.052 and 0.17 mm, respectively. The expression of AtFKGP was detected in most cell types of Arabidopsis, indicating that salvage reactions for free L-Fuc catalyzed by AtFKGP occur ubiquitously in Arabidopsis. Loss-of-function mutants with tDNA insertion in AtFKGP exhibited higher accumulation of free L-Fuc in the soluble fraction than the wild-type plant. These results indicate that AtFKGP is a bifunctional enzyme with L-fucokinase and GDP-L-Fuc pyrophosphorylase activities, which salvages free L-Fuc in Arabidopsis.

Properties and physiological functions of UDP-sugar pyrophosphorylase in Arabidopsis.

UDP-sugar pyrophosphorylase catalyzes the conversion of various monosaccharide 1-phosphates to the respective UDP-sugars in the salvage pathway. Using the genomic database, we cloned a putative gene for UDP-sugar pyrophosphorylase from Arabidopsis. Although relatively stronger expression was detected in the vascular tissue of leaves and the pollen, AtUSP is expressed in most cell types of Arabidopsis, indicating a housekeeping function in nucleotide sugar metabolism. Recombinant AtUSP expressed in Escherichia coli exhibited broad specificity toward monosaccharide 1-phosphates, resulting in the formation of various UDP-sugars such as UDP-glucose, -galactose, -glucuronic acid, -xylose and -L-arabinose. A loss-of-function mutation in the AtUSP gene caused by T-DNA insertion completely abolished male fertility. These results indicate that AtUSP functions as a UDP-sugar pyrophosphorylase in the salvage pathway, and that the generation of UDP-sugars from monosaccharide 1-phosphates catalyzed by AtUSP is essential for pollen development in Arabidopsis.

Application of Quick Environment Exposure Sensitivity Inventory (QEESI) for Japanese population: study of reliability and validity of the questionnaire.

A standardized questionnaire has not been established for screening or diagnostic assessment of patients with multiple chemical sensitivity (MCS) in Japan. In the US, Miller and Prihoda (1999a,b) developed a questionnaire that could be used internationally, the Quick Environment Exposure Sensitivity Inventory (QEESI), to assist researchers and clinicians in evaluating patients and populations for chemical sensitivity. The Japanese version of QEESI was subsequently translated by Ishikawa and Miyata (1999). The present study was performed to investigate the reliability and validity of QEESI (Japanese version) for research purposes and for evaluation of patients with MCS in Japan. A total of 498 subjects were recruited from the general population of Miyagi prefecture, Japan. The factor structure in QEESI was analyzed with 40 items on four subscales except for the items in 'Masking' using principal components analysis with Promax rotation. The results showed that 30 items on three subscales, 'Chemical Inhalant Intolerances,' 'Symptom Severity,' and 'Life Impact' except for 'Other Intolerances' were consistent with those reported for the US population by Miller and Prihoda (1999a). Cronbach's alpha reliability coefficient ranged between 0.87 and 0.94 indicating high internal consistency in the 30 items on three subscales. Next, we compared the mean scores on three subscales of QEESI in two groups: 131 self-reported MCS group who were new outpatients at the Environmental Medical Center in Kitasato Institute Hospital, and 131 members of the general population (controls) who were matched for both gender and age with the self-reported MCS group. Mean scores on each subscale for the self-reported MCS group were significantly greater than those for controls (P <0.001). Mean scores on all of the 30 items on three subscales for the self-reported MCS group were also significantly greater than for the controls (P <0.001). These findings indicated that the 30 items on three subscales in QEESI can be used for surveys and for diagnostic assessment of patients with MCS as well as for comparative studies between patients in Japan and in other countries.

UDP-sugar pyrophosphorylase with broad substrate specificity toward various monosaccharide 1-phosphates from pea sprouts.

UDP-sugars, activated forms of monosaccharides, are synthesized through de novo and salvage pathways and serve as substrates for the synthesis of polysaccharides, glycolipids, and glycoproteins in higher plants. A UDP-sugar pyrophosphorylase, designated PsUSP, was purified about 1,200-fold from pea (Pisum sativum L.) sprouts by conventional chromatography. The apparent molecular mass of the purified PsUSP was 67,000 Da. The enzyme catalyzed the formation of UDP-Glc, UDP-Gal, UDP-glucuronic acid, UDP-l-arabinose, and UDP-xylose from respective monosaccharide 1-phosphates in the presence of UTP as a co-substrate, indicating that the enzyme has broad substrate specificity toward monosaccharide 1-phosphates. Maximum activity of the enzyme occurred at pH 6.5-7.5, and at 45 degrees C in the presence of 2 mm Mg(2+). The apparent K(m) values for Glc 1-phosphate and l-arabinose 1-phosphate were 0.34 and 0.96 mm, respectively. PsUSP cDNA was cloned by reverse transcriptase-PCR. PsUSP appears to encode a protein with a molecular mass of 66,040 Da (600 amino acids) and possesses a uridine-binding site, which has also been found in a human UDP-N-acetylhexosamine pyrophosphorylase. Phylogenetic analysis revealed that PsUSP can be categorized in a group together with homologues from Arabidopsis and rice, which is distinct from the UDP-Glc and UDP-N-acetylhexosamine pyrophosphorylase groups. Recombinant PsUSP expressed in Escherichia coli catalyzed the formation of UDP-sugars from monosaccharide 1-phosphates and UTP with efficiency similar to that of the native enzyme. These results indicate that the enzyme is a novel type of UDP-sugar pyrophosphorylase, which catalyzes the formation of various UDP-sugars at the end of salvage pathways in higher plants.