Association of salivary lactate dehydrogenase level with systemic inflammation in a Japanese population.

BACKGROUND AND OBJECTIVE: Salivary lactate dehydrogenase (LDH) was reported to be a useful parameter for the screening of periodontal disease. We performed a cross-sectional study to verify the usefulness of salivary LDH as a biomarker of periodontitis and to investigate the association of severity of periodontitis with systemic inflammation by measuring salivary LDH and serum high sensitive C-reactive protein (hs-CRP) levels in a community-based middle-aged and elderly population in Japan. MATERIAL AND METHODS: We recruited 644 men and 1171 women, aged 30-79 years, who participated in the Toon Health Study during 2011-15. Periodontal condition was assessed by full-mouth examination including mean value of probing depth, percentage of probing depth of ≥4 mm and ≥6 mm, and bleeding on probing. Saliva and blood serum samples were collected for measurement of salivary LDH level and hs-CRP, respectively. A linear trend across quartiles of salivary LDH was calculated using linear regression. Interaction of salivary LDH and overweight status (body mass index of ≥25 kg/m2 ) was tested using the cross-product term of log-transformed continuous salivary LDH and overweight status. RESULTS: Analysis of covariance adjusted for potential confounders revealed strong associations between salivary LDH level and the indicators of periodontal condition (P < .01) in both men and women. Sex- and age-adjusted mean values of hs-CRP according to salivary LDH quartiles were 0.40, 0.45, 0.45 and 0.50 mg/L (P for trend <.01). Although the association was attenuated after further adjustment for body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol intake, smoking status and physical activity. When stratified by overweight status, the association remained significant in overweight individuals (P = .03). The multivariable adjusted odds ratio of hs-CRP level of ≥1 mg/L for the highest vs lowest quartile of salivary LDH was 1.93 (95% CI, 1.01-3.69) in overweight individuals, but not significant in non-overweight individuals. CONCLUSION: Salivary LDH appears to be a promising biomarker for the mass screening of periodontitis in local community health settings. High salivary LDH levels, particularly in overweight individuals might contribute to prevention of cardiovascular disease, through measuring systemic inflammatory burdens as well as traditional cardiovascular risk factors.

Neuromuscular adaptations induced by adjacent joint training.

Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training.

Porphyromonas endodontalis reactivates latent Epstein-Barr virus.

AIM: To determine whether Porphyromonas endodontalis can reactivate latent Epstein-Barr virus (EBV). METHODOLOGY: The concentrations of short-chain fatty acids (SCFAs) in P. endodontalis culture supernatants were determined using high-performance liquid chromatography. A promoter region of BamHI fragment Z leftward open reading frame 1 (BZLF-1), which is a transcription factor that controls the EBV lytic cycle, was cloned into luciferase expression vectors. Then, the luciferase assay was performed using P. endodontalis culture supernatants. Histone acetylation using Daudi cells treated with P. endodontalis culture supernatants was examined using Western blotting. BZLF-1 mRNA and BamHI fragment Z EB replication activator (ZEBRA) protein were also detected quantitatively using real-time polymerase chain reaction (PCR) and Western blotting. Surgically removed periapical granulomas were examined to detect P. endodontalis, EBV DNA, and BZLF-1 mRNA expression using quantitative real-time PCR. Statistical analysis using Steel tests was performed. RESULTS: The concentrations of n-butyric acid in P. endodontalis culture supernatants were significantly higher than those of other SCFAs (P = 0.0173). Using B-95-8-221 Luc cells treated with P. endodontalis culture supernatants, the luciferase assay demonstrated that P. endodontalis induced BZLF-1 expression. Hyperacetylation of histones was also observed with the culture supernatants. BZLF-1 mRNA and ZEBRA protein were expressed by Daudi cells in a dose-dependent manner after the treatment with P. endodontalis culture supernatants. P. endodontalis and BZLF-1 in periapical granulomas were also detected. The expression levels of BZLF-1 mRNA were similar to the numbers of P. endodontalis cells in each specimen. CONCLUSIONS: n-butyric acid produced by P. endodontalis reactivated latent EBV.

Scalloped tongue is associated with nocturnal intermittent hypoxia among community-dwelling Japanese: the Toon Health Study.

Scalloped tongue is considered as a possible clinical finding of obstructive sleep apnoea (OSA). There are few evidence of the association between scalloped tongue and OSA. To examine the association between scalloped tongue and nocturnal intermittent hypoxia (NIH), a surrogate marker of OSA, among a general Japanese population. Study participants were 398 men and 732 women aged 30-79 years who participated in the Toon Health Study from 2011 to 2014. Scalloped tongue was classified into three categories: none, mild and moderate-to-severe. Moderate-to-severe NIH was defined as the 3% oxygen desaturation index of ≥15 events/h during sleep for one night with pulse oximetry. The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for moderate-to-severe NIH were calculated according to scalloped tongue categories using a logistic regression model. There were 69 (6·1%) moderate-to-severe NIH cases in this population. The multivariable-adjusted ORs (95% CIs) of moderate-to-severe NIH were 1·59 (0·85-2·95) for mild and 2·39 (1·10-5·17) for the moderate-to-severe scalloped tongue group compared with the group without scalloped tongues. When stratified by overweight status (BMI <25 or ≥25 kg m-2 ), the respective ORs (95% CIs) were 2·83 (1·06-7·55) and 4·74 (1·28-17·49) among overweight individuals, and 0·94 (0·40-2·70) and 1·52 (0·57-4·05) among non-overweight individuals. Scalloped tongue was associated with higher prevalence of moderate-to-severe NIH among the general Japanese population and this association was more evident in overweight individuals.

Functional status of the articularis genus muscle in individuals with knee osteoarthritis.

OBJECTIVES: To clarify the functional status of the articularis genus muscle (AGM) in individuals with knee osteoarthritis (OA) and to analyze the muscle's relationship with knee OA. METHODS: Fifty-two individuals with knee OA (mean age, 73.4 years), 50 elderly individuals without knee OA changes (mean age, 71.2 years) and 75 young individuals (mean age, 20.2 years) were observed the AGM using ultrasonography. The thickness of the AGM, the anteroposterior distance of the suprapatellar bursa, and moving distance of the muscle insertion were measured both at rest and during isometric contraction, and values during contraction were expressed as percentages of the values at rest (%Muscle-Increase, %Bursa-Increase). RESULTS: Muscle thickness at rest, %Muscle-Increase, %Bursa-Increase, and moving distance of the muscle insertion were significantly lower and anteroposterior distance of the suprapatellar bursa was significantly higher in the OA group than in the controls (p<0.001, all). In the OA group, these values for the AGM were significantly correlated with knee range of motion, knee pain, and Kellgren and Lawrence grade. CONCLUSIONS: Individuals with knee OA exhibited atrophic changes and dysfunctions of the AGM, and these were associated with symptoms. Atrophic changes and dysfunctions of the AGM may be specific changes associated with knee OA.

Tongue pressure production during swallowing in patients with mandibular prognathism.

UNLABELLED: Abnormalities of swallowing in patients with mandibular prognathism have not been evaluated quantitatively. The aim of this study was to compare tongue pressure production for bolus transfer between volunteers with normal occlusion and patients with mandibular prognathism. The control group had 10 female volunteers with normal occlusion, and the patient group had 10 women with mandibular prognathism. Tongue pressure was measured by a palatal sensor sheet at five sites on swallowing 4 mL of a tasteless and odourless jelly. RESULTS: The tongue pressure waveform differed between the control and patient groups. The incidence of a double-peak tongue pressure waveform was more frequent in the patient group. In both groups, the exertion of tongue pressure began at the anterior point of the sensor sheet, followed by the peripheral parts. Although the order of expression of tongue pressure was the same for the two groups, maximum tongue pressure at all parts of the sensor sheet was lower in the patient group than in the control group. Furthermore, swallowing time was longer in the patient group than in the control group at the peripheral parts of the palate. These results clearly show the difference in tongue pressure production during swallowing between patients with mandibular prognathism and volunteers with normal occlusion. The current findings suggest that maxillofacial morphology may affect tongue movement during swallowing.

Preferable sites and orientations of transgene inserted in the adenovirus vector genome: The E3 site may be unfavorable for transgene position.

The adenovirus vector (AdV) can carry two transgenes in its genome, the therapeutic gene and a reporter gene, for example. The E3 insertion site has often been used for the expression of the second transgene. A transgene can be inserted at six different sites/orientations: E1, E3 and E4 sites, and right and left orientations. However, the best combination of the insertion sites and orientations as for the titers and the expression levels has not sufficiently been studied. We attempted to construct 18 AdVs producing GFP or LacZ gene driven by the EF1α promoter and Cre gene driven by the α-fetoprotein promoter. The AdV containing GFP gene at E3 in the rightward orientation (GFP-E3R) was not available. The LacZ-E3R AdV showed 20-fold lower titer and 50-fold lower level of fiber mRNA than the control E1L AdV. Notably, we found four aberrantly spliced mRNAs in the LacZ-E3L/R AdVs, probably explaining their very low titers. Although the transgene expression levels in the E4R AdVs were about threefold lower than those in the E1L AdVs, their titers are comparable with that of E1L AdVs. We concluded that E1L and E4R sites/orientations are preferable for expressing the main target gene and a second gene, respectively.

Modification of the excess risk of coronary heart disease due to smoking by seafood/fish intake.

Seafood/fish intake has been regarded as a protective factor for coronary heart disease (CHD), while smoking is a strong risk factor. To examine whether associations between smoking and risk of CHD are modified by seafood/fish intake, we studied 72,012 Japanese men and women aged 45-74 years who completed 2 food frequency questionnaires, 5 years apart, during the period 1995-2009. After 878,163 person-years of follow-up, 584 incident cases of CHD (101 fatal and 483 nonfatal), including 516 myocardial infarctions, were documented. There was a clear dose-response association between smoking and CHD risk among subjects with a low seafood/fish intake (<86 g/day) but not among those with a high seafood/fish intake (≥86 g/day). Compared with never smokers, the multivariable hazard ratios in light (1-19 cigarettes/day), moderate (20-29 cigarettes/day), and heavy (≥30 cigarettes/day) smokers were 2.39 (95% confidence interval (CI): 1.60, 3.56), 2.74 (95% CI: 1.90, 3.95), and 3.24 (95% CI: 2.12, 4.95), respectively, among low seafood/fish eaters and 1.13 (95% CI: 0.64, 1.99), 1.29 (95% CI: 0.95, 2.04), and 2.00 (95% CI: 1.18, 3.51), respectively, among high seafood/fish eaters. Compared with heavy smokers with a low seafood/fish intake, light smokers with a high seafood/fish intake had substantially reduced risk of CHD (hazard ratio = 0.57, 95% CI: 0.32, 0.98). High seafood/fish intake attenuated the positive association between smoking and risk of CHD.

Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants.

Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi-surface dust in 182 single-family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2-butoxyethyl) phosphate was detected in all samples (median value: 580 µg/g in floor dust, 111 µg/g in multi-surface dust). Tris(2-chloro-iso-propyl) phosphate (TCIPP) was detected at 8.69 µg/g in floor dust and 25.8 µg/g in multi-surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3-dichloro-2-propyl) phosphate in floor dust [per log10 -unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi-surface dust) and allergic rhinitis (OR: 2.55 in multi-surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia-Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status.

Quantum device designing (QDD) for future semiconductor engineering.

In semiconductor device history, a trend is observed where narrowing and increasing the number of material layers improve device functionality, with diodes, transistors, thyristors, and superlattices following this trend. While superlattices promise unique functionality, they are not widely adopted due to a technology barrier, requiring advanced fabrication, such as molecular beam epitaxy and lattice-matched materials. Here, a method to design quantum devices using amorphous materials and physical vapor deposition is presented. It is shown that the multiplication gain M depends on the number of layers of the superlattice, N, as M = kN, with k as a factor indicating the efficiency of multiplication. This M is, however, a trade-off with transit time, which also depends on N. To demonstrate, photodetector devices are fabricated on Si, with the superlattice of Se and As2Se3, and characterized using current-voltage (I-V) and current-time (I-T) measurements. For superlattices with the total layer thicknesses of 200 nm and 2 µm, the results show that k200nm = 0.916 and k2µm = 0.384, respectively. The results confirm that the multiplication factor is related to the number of superlattice layers, showing the effectiveness of the design approach.

Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

BACKGROUND: There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. OBJECTIVE: To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. RESULTS: Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. CONCLUSION: Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Body mass index, weight change and risk of stroke and stroke subtypes: the Japan Public Health Center-based prospective (JPHC) study.

OBJECTIVE: The Japan Public Health Center-based prospective Study examined the association of body mass index (BMI) and weight change with incident stroke in Japanese individuals, for whom BMI levels are generally low. METHODS: We used initial data from 1990 to 1994 and 5-year follow-up surveys from 1995 to 1999. We calculated weight change over a 5-year period for 32,847 men and 38,875 women, aged 45-74 years, with no history of cardiovascular disease or cancer. Subjects were followed from the 1995-1999 survey to the end of 2005, and hazard ratios of self-reported BMI levels and weight change for incident stroke were estimated using Cox's proportional hazard models adjusted for potential confounders. RESULTS: During the follow-up period (median 7.9 years) there were 2019 incident strokes, including subtypes. Multivariable-adjusted hazard ratios for all stroke events by BMI levels of 27.0-29.9 and ≥ 30 kg m(-2) versus 23.0-24.9 kg m(-2) were 1.09 (95% confidence interval 0.88, 1.36) and 1.25 (0.86, 1.84) in men (P for trend=0.22), and 1.29 (1.01, 1.65) and 2.16 (1.60, 2.93) in women (P for trend <0.001), respectively. A weight change of ≥ 10% in the previous 5 years was associated with total strokes and ischemic strokes in women. CONCLUSION: Higher BMI levels and a weight gain of ≥ 10% over 5 years were associated with an increased risk of stroke in women, whereas this association was weak in men.

Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome.

Polymerase chain reaction has been used to detect increased levels of EBV DNA in salivary gland (SG) biopsies and PBL from patients with Sjogren's syndrome (SS). These results suggest that EBV, which has a normal site of latency in a small number of SG epithelial cells, may be reactivated in SS patients and provide a target for immune attack. The great sensitivity of polymerase chain reaction (PCR) and the ability to analyze very small tissue biopsies (37) make this technique well suited for clinical diagnosis. Specific methods to prevent artefactual contamination of tissue biopsy DNA with viral DNA of other samples (i.e., lyophilization of samples before DNA extraction) and the use of an internal positive control (i.e., inclusion of primers for a single copy human gene) during PCR amplification are presented. Since EBV reactivation occurs with markedly increased frequency in patients with lymphoproliferative and immunodeficiency diseases, as well as transplant recipients receiving cyclosporin A (10), rapid methods of viral detection such as PCR may allow better monitoring of medications and early detection of EBV-related lymphomas that may arise in these patients.

Association between indoor exposure to semi-volatile organic compounds and building-related symptoms among the occupants of residential dwellings.

UNLABELLED: The aim of this study was to evaluate the levels of semi-volatile compounds (SVOCs) in residential detached houses in Sapporo, Japan, and whether exposure to these SVOCs was associated with the development of building-related symptoms named 'sick house syndrome' (SHS). The definition of SHS is fundamentally the same as that of the sick building syndrome (SBS). The presence of symptoms of SHS was evaluated using a validated self-administered questionnaire. Surveys and samplings of air and house dust in 41 dwellings were performed from October 2006 to January 2007, and 134 occupants responded to questionnaires. Samples were analyzed to quantify the concentrations of eight plasticizers, eleven phosphate triester flame retardants, two alkyl phenols used as anti-oxidants, and one organochlorine synergist called s-421, by gas chromatography-mass spectrometry and gas chromatography-flame photometry. The compounds frequently detected were di-n-butylphthalate, di(2-ethylhexyl)phthalate (DEHP), and dibutylhydroxytoluene in air, and DEHP and tris(2-butoxyethyl)phosphate (TBEP) in dust. Tributylphosphate was strongly and directly associated with mucosal symptoms of SHS; s-421 was also directly associated with mucosal symptoms of SHS. On the contrary, some chemicals such as diethylphthalate and TBEP were inversely associated with SHS. In future studies, we plan to assess these associations in a larger population. PRACTICAL IMPLICATIONS: This study suggests that it may be possible to reduce building-related symptoms by altering exposure to certain SVOCs, such as tributylphosphate commonly found in ceiling and wall coverings and s-421 used as a synergist for pyrethroids. The association between SHS and s-421 suggested that use of pyrethroid insecticides could elicit symptoms of SHS. However, further studies are necessary to test the associations observed in the present study and to examine whether the SVOCs associated with symptoms are causative agents or simply surrogates for some other factor that is causing the symptoms.

Identification of alpha-fodrin as a candidate autoantigen in primary Sjögren's syndrome.

It is unclear whether organ-specific autoantigens are critical for the development of primary Sjögren's syndrome (SS). A 120-kilodalton organ-specific autoantigen was purified from salivary gland tissues of an NFS/sld mouse model of human SS. The amino-terminal residues were identical to those of the human cytoskeletal protein alpha-fodrin. The purified antigen induced proliferative T cell responses and production of interleukin-2 and interferon-gamma in vitro. Neonatal immunization with the 120-kilodalton antigen prevented the disease in mice. Sera from patients with SS reacted positively with purified antigen and recombinant human alpha-fodrin protein, whereas those from patients with systemic lupus erythematosus and rheumatoid arthritis did not. Thus, the immune response to 120-kilodalton alpha-fodrin could be important in the initial development of primary SS.

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Glia-synapse interaction through Ca2+-permeable AMPA receptors in Bergmann glia.

Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial cells in the cerebellum have Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) assembled without the GluR2 subunit. To elucidate the role of these Ca2+-permeable AMPARs, we converted them into Ca2+-impermeable receptors by adenoviral-mediated delivery of the GluR2 gene. This conversion retracted the glial processes ensheathing synapses on Purkinje cell dendritic spines and retarded the removal of synaptically released glutamate. Furthermore, it caused multiple innervation of Purkinje cells by the climbing fibers. Thus, the glial Ca2+-permeable AMPARs are indispensable for proper structural and functional relations between Bergmann glia and glutamatergic synapses.

Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study.

OBJECTIVES: We previously reported the therapeutic potential of Bifidobacterium breve A1 (B. breve A1) for preventing cognitive impairment in Alzheimer's disease model mice, which suggested that supplementation of the probiotics could be an effective therapeutic strategy for managing cognitive function in mild cognitive impairment (MCI). DESIGN AND SETTINGS: We conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on elderly with MCI in Aki Orthopedics Rehabilitation Clinic in Japan. PARTICIPANTS: 27 participants were screened by their Mini Mental State Examination (MMSE) scores. MEASUREMENTS: Cognitive function was assessed using MMSE and Digit Symbol Substitution Test (DSST) at baseline and every 8 weeks. Mental condition and quality of life for gastrointestinal symptoms were measured using the Profile of Mood States 2nd Edition (POMS2), and the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Of the 27 participants enrolled, 19 completed the study. MMSE scores were significantly increased during the intervention by mixed model Dunnett's test and Wilcoxon signed-rank tests (+1.7, P < 0.01). POMS2 and GSRS scores were significantly improved during intervention when analyzed by Wilcoxon signed-rank tests. CONCLUSION: The present study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function, thus suggesting the potential of B. breve A1 for improving cognitive function and maintaining quality of life of the elderly. Further randomized, double-blind placebo-controlled studies are worth conducting to examine the beneficial effect of B. breve A1.

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment.

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.