Genetic effects of demographic bottleneck and recovery in Kinkazan Island and mainland populations of Japanese macaques (Macaca fuscata).

Populations of Japanese macaques were significantly reduced in most areas from the 1900s to the 1960s and then recovered mainly in the northeastern part of Honshu. A drastic reduction in population size reduces genetic variability through a bottleneck effect. Demographic expansion after the reduction that accumulates new mutations can reduce the bottleneck effects or drive the recovery of genetic variability. We examined the genetic status of a small island population (Kinkazan Island) and a larger mainland population (southern Tohoku) of Japanese macaques that experienced recent demographic bottlenecks and recovery using eight microsatellite loci. The two populations were significantly genetically different from each other. The Kinkazan population exhibited lower genetic variability, remarkable evidence of bottleneck (i.e., significant heterozygosity excess and lower frequency of rare alleles), and a considerably smaller effective population size based on genetic data than based on the current census size. These results indicate that the genetic status has not completely recovered from the demographic bottleneck despite a full recovery in census size on Kinkazan Island. New mutations might rarely have accumulated because of the small carrying capacity of the island. Therefore, the genetic variability of the population would have been restrained by the severe bottleneck size, small carrying capacity, and long-term isolation. On the other hand, the bottleneck effect seems to be limited in the southern Tohoku population considering higher genetic variability, non-significant heterozygosity excess in many mutation conditions, and the highest frequency of rare alleles.

Evaluation of a novel immunochromatographic device for rapid and accurate clinical detection of Porphyromonas gingivalis in subgingival plaque.

UNLABELLED: An important goal for the improved diagnosis and management of infectious and inflammatory diseases, such as periodontitis, is the development of rapid and accurate technologies for the decentralized detection of bacterial pathogens. The aim of this prospective multicenter study was to evaluate the clinical use of a novel immunochromatographic device with monoclonal antibodies for the rapid point-of-care detection and semi-quantification of Porphyromonas gingivalis in subgingival plaque. Sixty-three patients with chronic periodontitis and 28 periodontally healthy volunteers were subjected to clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis using a novel immunochromatography based device DK13-PG-001, designed to detect the 40k-outer membrane protein of P. gingivalis, and compared with a PCR-Invader method. In the periodontitis group, a significant strong positive correlation in detection results was found between the test device score and the PCR-Invader method (Spearman rank correlation, r=0.737, p<0.0001). The sensitivity, specificity, and positive and negative predictive values of the test device were 96.2%, 91.8%, 90.4% and 96.7%, respectively. The detection threshold of the test device was determined to be approximately 10(4) (per two paper points). There were significant differences in the bacterial counts by the PCR-Invader method among groups with different ranges of device scores. With a cut-off value of ≥0.25 in device score, none of periodontally healthy volunteers were tested positive for the subgingival presence of P. gingivalis, whereas 76% (n=48) of periodontitis subjects were tested positive. There was a significant positive correlation between device scores for P. gingivalis and periodontal parameters including probing pocket depth and clinical attachment level (r=0.317 and 0.281, respectively, p<0.01). The results suggested that the DK13-PG-001 device kit can be effectively used for rapid, chair-side detection and semi-quantification of P. gingivalis in subgingival plaque. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000011943.

Ten-year incidences of self-reported non-vertebral fractures in Japanese patients with rheumatoid arthritis: discrepancy between disease activity control and the incidence of non-vertebral fracture.

UNLABELLED: Despite improvements in rheumatoid arthritis disease activity of in the past 10 years, the incidence of self-reported non-vertebral fractures did not decrease in our cohort of 9,987 patients. This study may indicate that osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the rheumatoid arthritis disease activity. INTRODUCTION: Although rheumatoid arthritis (RA) is a risk factor for osteoporosis and fractures, few studies have described the association between disease activity and the fracture incidence in patients with RA. This study aimed to investigate changes in the non-vertebral fracture incidence between 2001 and 2010 in our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. METHODS: The IORRA is a prospective observational cohort study of Japanese RA patients. A total of 9,987 patients with RA were enrolled in this cohort from 2000 to 2010. The clinical parameter and non-vertebral fracture occurrence data were collected biannually through self-reported questionnaires. Incidences of self-reported non-vertebral fractures were also analyzed via standardization according to gender, age, and disease activity during each 2-year period. RESULTS: From 2001 to 2010, the percentage of patients with 28-joint disease activity score remission increased from 7.8 to 39.7%, prednisolone intake decreased from 51.4 to 41.3%, and bisphosphonate intake increased from 5.0 to 23.4%. The non-vertebral fracture incidence rates were 24.6/1,000 person-years in 2001 and 35.5/1,000 person-years in 2010, with no apparent change even after standardization. The overall non-vertebral fracture incidence was significantly higher in the autumn/winter than in the spring/summer (p = 0.02). CONCLUSION: Despite improvements in disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in our patients with RA. Osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the disease control in patients with RA.

Vaccination against seasonal influenza is effective in Japanese patients with rheumatoid arthritis enrolled in a large observational cohort.

OBJECTIVE: To investigate the effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA) from a large practice-based cohort. METHOD: Patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires as part of the April IORRA surveys of 2001, 2002, 2003, and 2007, which included their influenza vaccination status and occurrence of an actual influenza attack. Vaccine coverage rate and attack rates were calculated in each season. Relative risks (RRs) of vaccination for an actual influenza attack were evaluated and risk factors for influenza infection were determined by multiple logistic regression analysis. RESULTS: Data from 3529, 4518, 4816, and 4872 patients in the 2000/01, 2001/02, 2002/03, and 2006/07 seasons, respectively, were analysed. Coverage rates were increased from 12.2% in the 2000/01 season to 38.7% in the 2006/07 season. For each season, the attack rates in vaccinated patients trended lower than the rates in unvaccinated patients but the differences were not significant; however, by combining these four seasonal results, the attack rate was significantly lower for vaccinated patients [RR 0.83, 95% confidence interval (CI) 0.71-0.95, p < 0.01]. Male gender [odds ratio (OR) 1.48, 95% CI 1.25-1.76, p < 0.001] was associated with increased risk whereas vaccination was associated with reduced risk for influenza attack (OR 0.76, 95% CI 0.63-0.91, p < 0.01). There were no associations between influenza attacks and RA disease activity, treatment with methotrexate (MTX) or corticosteroids. CONCLUSION: Influenza vaccination was effective in patients with RA regardless of disease activity or treatment.

Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis: a prospective observational cohort study.

UNLABELLED: Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture. INTRODUCTION: This study seeks to evaluate the association between potential risk factors and the occurrence of hip fractures in Japanese RA patients. METHODS: A total of 9,720 patients (82.1% female; mean age, 55.7 years) with RA were enrolled in a prospective observational study from 2000 to 2010. Self-reported hip fractures were verified using patient medical records. Cox proportional hazards models were used to analyze independent contributions of various risk factors to hip fracture occurrence. RESULTS: During a mean follow-up of 5.2 years, 152 patients reported 152 hip fractures. Among these patients, 97 hip fractures in 97 patients (15 males, 82 females) were verified with medical records. Japanese version of the Health Assessment Questionnaire (J-HAQ) disability score [per 1 score, hazard ratio (HR), 2.64; 95% confidence interval (CI), 1.94-3.58], age (per 10 years; HR, 1.53; 95% CI, 1.25-1.87), history of TKR (HR, 3.75; 95% CI, 1.57-8.96), and BMI (per 1 kg/m2, HR, 0.92; 95% CI, 0.86-0.99) were significantly associated with hip fractures. Among the scores on the eight domains of the J-HAQ, J-HAQ (arising) (HR, 1.74; 95% CI, 1.28-2.36) and J-HAQ (hygiene) (HR, 1.58; 95% CI, 1.11-2.24) were significantly correlated with the occurrence of hip fracture. CONCLUSIONS: High J-HAQ disability score, advanced age, history of TKR, and low BMI appear to be associated with the occurrence of hip fractures in Japanese RA patients. Among the eight domains of the J-HAQ, arising and hygiene disabilities appear to be correlated with the occurrence of hip fractures in this patient population.

Mortality and cause of death in Japanese patients with rheumatoid arthritis based on a large observational cohort, IORRA.

OBJECTIVES: To investigate mortality, cause of death, and risk factors related to mortality in Japanese patients with rheumatoid arthritis (RA). METHODS: The IORRA cohort is a large observational cohort established in 2000 at the Institute of Rheumatology, Tokyo Women's Medical University. Essentially, all RA patients were registered and clinical parameters were assessed biannually. For patients who failed to participate in subsequent surveys, simple queries were mailed to confirm survival. Standardized mortality ratios (SMRs) were calculated and mortality risk factors were analysed using a Cox proportional hazard model. RESULTS: We analysed 7926 patients (81.9% females; mean age 56.3 ± 13.1 years; mean disease duration 8.5 ± 8.3 years) with RA who enrolled in IORRA from October 2000 to April 2007. During the observational period (35 443.0 person-years), 289 deaths were reported. Major causes of death included malignancies (24.2%), respiratory involvement (24.2%) including pneumonia (12.1%) and interstitial lung disease (ILD) (11.1%), cerebrovascular disease (8.0%), and myocardial infarction (7.6%). As death was not confirmed in all patients, the SMR was deduced to be between 1.46 [95% confidence interval (CI) 1.32-1.60] and 1.90 (95% CI 1.75-2.07) for all patients, between 1.45 (95% CI 1.22-1.70) and 1.70 (95% CI 1.45-1.97) for men, and between 1.46 (95% CI, 1.29-1.65) and 2.02 (95% CI 1.82- 2.24) for women. Factors associated with increased mortality included male gender, older age, worse physical disability, positive rheumatoid factor (RF), corticosteroid use, and presence of ILD. CONCLUSION: The mortality of Japanese RA patients is comparable to that in previous reports from western countries, even though the causes of death were significantly different.

Serological evidence of infection with hepatitis E virus among wild Yezo-deer, Cervus nippon yesoensis, in Hokkaido, Japan.

In this study, 520 serum samples from Yezo-deer in the Hidaka district, Hokkaido, Japan were examined by enzyme-linked immunosorbent assay to investigate whether the animals were infected with hepatitis E virus (HEV). The distribution of optical density values showed a bimodal pattern and 181 samples (34.8%) were deemed to be antibody-positive against HEV. At least five (2.8%) of the positive sera gave specific bands by Western blot analysis. An age-dependent increase in prevalence of the antibodies was found among the animals. These findings indicate that Yezo-deer are a possible host for HEV infection. To avoid the risk of becoming HEV infected, the consumption of raw Yezo-deer meat must be prohibited.

Low disease activity state with corticosteroid may not represent 'true' low disease activity state in patients with rheumatoid arthritis.

OBJECTIVE: Corticosteroids constitute one of the most common treatments of RA. The purpose of this study is to investigate whether long-term corticosteroid use suppresses the progression of disability in RA patients with low disease activity state. METHODS: Data collected from a large observational cohort of RA patients at our institution were analysed for 214 RA patients whose disease activity score (DAS) 28 and HAQ were available consecutively from October 2000 to October 2004. All 214 patients had average DAS 28 <3.2, meaning only those who had well-controlled RA disease activity were chosen as subjects. The subjects were divided into steroid users who received continuous corticosteroids every month and non-steroid users who did not receive consecutive corticosteroids continuously every month. RESULTS: Fifty-five patients (25.7%) were corticosteroid users and 159 (74.3%) were non-users. Average prednisolone for the former group was 4.2 mg/day. No significant differences were observed among baseline variables and RA disease activity variables. However, for steroid users, HAQ progressively worsened with time and for non-steroid users, HAQ progressively improved. CONCLUSIONS: Although DAS 28 and other variables may suggest well-controlled RA disease activity, functional capacity of patients on low-dose corticosteroids deteriorated. Thus, low disease activity state with corticosteroid may not represent the 'true' low disease activity state. Along with the achievement of a low disease activity state, long-term efficacy, prognosis, and the quality of remission need to be also considered in the tight control of RA activity.

Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients.

OBJECTIVE: A bi-allelic polymorphism on the promoter region, -1612 ins/del A, was found to influence the production of MMP-3. Since MMP-3 plays a particularly pivotal role in joint destruction, the MMP-3 gene is thought to be an interesting target gene of disease severity in RA. We attempt to determine whether the MMP-3 promoter polymorphism is associated with serum titre of MMP-3, disease activity and severity in Japanese RA patients. METHODS: DNA samples were obtained from 1504 RA patients as part of the Institute of Rheumatology Rheumatoid Arthritis observational cohort study. From the 2006 spring data, serum MMP-3 levels of 820 patients were available by enzyme immunoassay. Joint damage score at 5-yr disease duration could be measured using the Sharp/van der Heijde method in 162 patients. Genotyping of -1612 ins/del A was performed using fluorescent-labelled fragment analysis. Differences in serum MMP-3 level and joint damage score among genotypes of -1612 ins/del A polymorphism were analysed by linear regression analysis. RESULTS: No significant differences were found among MMP-3 genotypes on patient characteristics including disease activity score (P = 0.51) or health assessment questionnaire (P = 0.99). A significant effect of risk allele on serum MMP-3 level was observed (P = 0.038), while no significant effect was observed on radiographic joint damage (P = 0.47). CONCLUSION: We conclude that MMP-3 functional polymorphism is associated with serum MMP-3 titre, but is not a direct predictor for outcome measures in Japanese RA patients.

Efficient management of rheumatoid arthritis significantly reduces long-term functional disability.

OBJECTIVES: The aim of this study was to examine the effect of efficient management of rheumatoid arthritis (RA) in relation to disability levels in a large cohort of patients with RA over a period of 3 years. METHODS: We studied 2775 patients with RA who had continuous enrolment for at least 3 years from 7511 patients with RA enrolled in an observational cohort study (Institute of Rheumatology, Rheumatoid Arthritis (IORRA)) from October 2000 to April 2005. The 28-joint Disease Activity Scores (DAS28) were calculated at 6 month intervals for all the patients and a value <2.6 was considered as a tight control. We have set up a new variable for each patient, "Avg-Dscore", based on the transition of each patient's DAS28 value, taking the threshold level of 2.6 into consideration. The "Avg-DAS28" is the average of DAS28 values over all the phases. Functional disability status was assessed by J-HAQ, the validated Japanese version of the Health Assessment Questionnaire (HAQ). The relationship of "Avg-Dscore" and "Avg-DAS28" with the functional disability level was determined using Spearman correlation coefficients and multiple linear regression models. RESULTS: The baseline features of these 2775 patients were: female 83.7%, mean age 56.8 years, mean RA duration 9.5 years, mean initial DAS28 4.0, mean initial J-HAQ score 0.79, and mean final J-HAQ score 0.86. There was a statistically significant correlation between "Avg-DAS28" and final J-HAQ score (r = 0.57, p<0.001), indicating that tighter disease control has significant association with lower disability levels. A similar relationship was observed between "Avg-Dscore" and final J-HAQ score (r = 0.47, p<0.001). Multiple linear regression analysis, after adjusting for all the covariates, revealed that "Avg-Dscore" and "Avg-DAS28" were the most significant factors contributing to final J-HAQ score, and confirmed the strong relationship between disease activity and functional disability. CONCLUSIONS: In patients with RA efficient disease management, by maintaining the DAS28 values at a level under 2.6, has significant association with improving functional capability. The threshold DAS28 level of 2.6 may be useful in developing targeted treatment guidelines for patients with RA.

What's in season for rheumatoid arthritis patients? Seasonal fluctuations in disease activity.

OBJECTIVES: To examine whether a seasonal fluctuation exists with rheumatoid arthritis (RA) activity and to analyse seasonal effects of varying components that express disease activity in RA patients. METHODS: A group of 1665 RA patients (mean age 57.2 yrs, mean disease duration 9.9 yrs) whose data were available for 10 consecutive phases from a large observational cohort study conducted at our institution from October 2000 to April 2005, bi-annually, were evaluated. Ten criteria were analysed to assess RA disease activity. RESULTS: All criteria revealed decrease in disease activity during fall and increase in disease activity during spring, except for the physician's global assessment of disease activity in which significant differences were not observed between the two seasons. CONCLUSIONS: We found definite seasonal differences in RA patients, both subjectively and objectively. RA disease activity was higher in spring and lower during fall. Seasonal changes may play an important role in evaluating disease activity of RA patients and should be taken into account when examining these patients.

Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan.

OBJECTIVE: To determine the risk for tuberculosis infection in patients with rheumatoid arthritis before the anti-cytokine era in Japan. PATIENTS AND METHODS: A database of a single-institute-based large observational cohort study for rheumatoid arthritis at the Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, was analysed. Information on the history of tuberculosis infection was collected by patient self-reporting during April and October 2003. The age-adjusted incidence rate and relative risk for tuberculosis infection were investigated. RESULTS: Among 5044 patients with rheumatoid arthritis, 483 (9.6%) patients claimed to have a history of tuberculosis infection before October 2002. The frequency of history of tuberculosis increased according to the age of the patient. Four cases of new-onset tuberculosis were identified among 5544 patients with rheumatoid arthritis during 1 year. The age-adjusted incidence of tuberculosis was 42.4/100,000 patients. The relative risk for tuberculosis was 3.21 (95% confidence interval (CI) 1.21 to 8.55), and that of men and women was 10.59 (95% CI 3.42 to 32.78) and 1.41 (95% CI 0.2 to 10), respectively. CONCLUSION: There was an increased risk of tuberculosis infection in Japanese patients with rheumatoid arthritis, especially in male patients before the introduction of anti-tumour necrosis factor treatment. These data should form the basis for the risk management of anti-cytokine treatment in Japan.

Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population.

OBJECTIVE: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a member of the PTPs that negatively regulate T-cell activation. A missense single nucleotide polymorphism (SNP) in the PTPN22 gene known as R620W was recently reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA). The association was confirmed repeatedly in the populations of North European ancestry. However, the SNP was reported to be non-polymorphic in the Asian populations. Because the gene confers an impact on autoimmune diseases, we attempt to explore an association between PTPN22 gene and RA in a Japanese population without restricting to the SNP, R620W. METHODS: We studied 1128 RA patients and 455 controls. In addition to the SNP, R620W, we selected eight testing SNPs spanning 45 kb over the PTPN22 gene using the International HapMap Project. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay. Associations between RA and each of the SNPs were estimated by the Fisher's exact test. Haplotype was constructed using the expectation-maximization algorithm. RESULTS: R620W was not polymorphic enough in both the patients and the controls, and was therefore excluded from further analysis. Each allele frequency for the eight other SNPs in both groups was compared and no association was detected. Haplotype analysis also revealed that PTPN22 gene was not associated with RA in a Japanese population. CONCLUSION: We found no association between PTPN22 and RA in a Japanese population. The result suggests that the PTPN22 gene is associated with RA only in a specific ethnic group.

Signal intensity changes in T2-weighted MR image of the human trapezius muscle upon cold pressor stimulation.

OBJECTIVE: The ability to measure hemodynamics of skeletal muscle proper is one of the major goals for muscle pain researchers. The aim of the present study was to evaluate the ability of signal intensity (SI) in T2-weighted trapezius muscle magnetic resonance imaging (MRI) to detect intramuscular hemodynamic changes during cold pressor stimulation (CPS). MATERIALS AND METHODS: Fifteen healthy volunteers (mean age, 25.9+/-2.1 years) participated in this study. T2-weighted MRI was acquired using a 1.5 tesla MR unit with a body array coil. The slice level was set perpendicular to the muscle long axis at the mid-point of the horizontal portion of the right trapezius muscle. Cold pressor stimulation (4 degrees C) was applied to each subject's right foot and ankle for 2 min. The SI changes were recorded continuously for 7 min before, 2 min during, and 6 min after withdrawal of cold pressor stimulation. Six of these subjects also underwent a mock-CPS trial. RESULTS: The mean SI level in T2-weighted trapezius muscle MRI significantly increased during CPS (P<0.0001, one way repeated measure ANOVA) and returned to the baseline level after cold pressor withdrawal. No statistically significant signal changes were observed across the mock-CPS trial subjects. These findings are identical to the cold pressor-induced hemodynamic changes documented in the trapezius muscle by near-infrared spectroscopy evaluation. CONCLUSIONS: SI measurement in T2-weighted trapezius muscle MRI is sufficiently sensitive to detect intramuscular hemodynamic changes during CPS.

Spirituality in nursing from a Japanese perspective.

The purpose of this study was to explore the concept of spirituality and its expression among persons in a Japanese farming community. It was found that spirituality was described as "living in harmony with nature and surrounding people." Common expressions of this spirituality were through faith and ways of worship, prayer, search for inner peace, hope and thanksgiving, including spiritual well-being. The latter was defined as showing thanks to nature, ancestors, and people; caring for surrounding people; and peacefully embracing the concept of death. To provide congruent spiritual care, it was suggested that nurses need to expand their own knowledge and understanding of spirituality; integrate spirituality in their nursing care; and improve communication with their clients and their families.

Importance of spatial activation of Cdc42 and rac small G proteins by frabin for microspike formation in MDCK cells.

BACKGROUND: Frabin is an actin filament (F-actin)-binding protein that shows GDP/GTP exchange activity for Cdc42 small G protein (Cdc42). Frabin furthermore induces indirect activation of Rac small G protein (Rac) in intact cells. We have recently shown that in nonepithelial cells, frabin induces the formation of both filopodia- and lamellipodia-like processes through the activation of Cdc42 and Rac, respectively. In epithelial cells such as MDCK cells, Cdc42 and Rac regulate cell-cell adherens junctions (AJs) via the accumulation of F-actin and E-cadherin, although neither Cdc42 nor Rac induces the formation of filopodia or lamellipodia. In this study, we have examined the effects of frabin on the reorganization of the actin cytoskeleton in MDCK cells. RESULTS: Frabin induces the formation of microspikes at the basal area of the lateral membranes through the activation of Cdc42 and Rac in MDCK cells, although a dominant active mutant of Cdc42 or Rac alone, or both, did not induce the formation of microspikes. Furthermore, frabin weakly increased the accumulation of F-actin and E-cadherin at cell-cell AJs and the formation of stress fibres through the activation of Cdc42 and Rac, under conditions where the dominant active mutant of Cdc42 or Rac markedly showed these effects. The Cdc42- and Rac-induced formation of stress fibres was dependent on the activation of Rho small G protein. CONCLUSION: These results indicate that the frabin-dependent spatial activation of Cdc42 and Rac is important for the formation of microspikes.

Development of bacterial expression system with high yield of CYP3A7, a human fetus-specific form of cytochrome P450.

In an E. coli expression system for human cytochrome P450 3A7 (CYP3A7), holo-CYP3A7 was not expressed as judged by CO-difference spectra, although apo-CYP3A7 was clearly detected by Western blot analysis. Unlike CYP3A7, CYP3A4 was expressed efficiently as a hemoprotein in E. coli transformed with a CYP3A4 expression plasmid. To achieve the high yield of the holo-CYP3A7 in E. coli, we examined a causal residue(s) preventing the expression of the holo-CYP3A7 using the chimeric gene of CYP3A4 with CYP3A7. It was found that the region between residues 405 and 503 of CYP3A7 was responsible for the prevention of the holo-CYP3A7 expression in E. coli. Among amino acids examined, substitution of Thr at position 485 in CYP3A7 with Pro, which is at the corresponding position of CYP3A4, resulted in an increase in the amount of holo-CYP3A7. The Thr residue was adjacent to the heme-binding region of CYP3A7. Thus, it appeared that the incorporation of heme into CYP3A7 was possibly affected by this particular amino acid residue. Moreover, holo-CYP3A7 was expressed efficiently when CYP3A7 was co-expressed with molecular chaperone GroEL, known to assist the correct folding of unfolded proteins. Dehydroepiandrosterone 16alpha-hydroxylation was catalyzed by CYP3A7 expressed in the presence of GroEL.

Low-cost soft-copy display accuracy in the detection of pulmonary nodules by single-exposure dual-energy subtraction: comparison with hard-copy viewing.

This study endeavored to clarify the usefulness of single-exposure dual-energy subtraction computed radiography (CR) of the chest and the ability of soft-copy images to detect low-contrast simulated pulmonary nodules. Conventional and bone-subtracted CR images of 25 chest phantom image sets with a low-contrast nylon nodule and 25 without a nodule were interpreted by 12 observers (6 radiologists, 6 chest physicians) who rated each on a continuous confidence scale and marked the position of the nodule if one was present. Hard-copy images were 7 x 7-inch laser-printed CR films, and soft-copy images were displayed on a 21-inch noninterlaced color CRT monitor with an optimized dynamic range. Soft-copy images were adjusted to the same size as hard-copy images and were viewed under darkened illumination in the reading room. No significant differences were found between hard- and soft-copy images. In conclusion, the soft-copy images were found to be useful in detecting low-contrast simulated pulmonary nodules.