A mechanism of melanogenesis mediated by E-cadherin downregulation and its involvement in solar lentigines.

OBJECTIVE: Intensive studies have revealed that pleiotropic melanocytic factors are associated with age-spot formation. Dysfunctional keratinocyte differentiation is thought to be an upstream cause of age-spot formation. Although it has been shown that keratinocyte differentiation is mediated by the cell-cell contact factor E-cadherin, its involvement in age-spot formation remains unknown. Thus, to determine the origin of age-spots and an integrated solution for the same, we focused on E-cadherin expression in the present study. METHODS: First, we assessed the solar lentigines in cutaneous and cultured cells by means of immunofluorescence staining. Following that, keratinocytes treated with siRNAs against E-cadherin were co-cultured with melanocytes, and the secreted factors were identified by means of proteomic analysis of the culture supernatants. We also performed quantitative PCR to assess melanogenesis activity and screen ingredients. For behavioural analysis of melanocytes, we performed time-lapse imaging using confocal laser scanning microscopy. RESULTS: E-cadherin expression was downregulated in the epidermis of the solar lentigines, suggesting its involvement in age-spot formation. E-cadherin knocked down keratinocytes not only promoted the secretion of melanocytic/inflammatory factors but also increased melanogenesis by upregulating the expression of melanogenesis factors. Furthermore, live-imaging showed that the downregulation of E-cadherin inhibited melanocyte dynamics and accelerated melanin uptake. Finally, we identified Rosa multiflora fruit extract as a solution that can upregulate E-cadherin expression in keratinocytes. CONCLUSION: Our findings showed that E-cadherin downregulation triggers various downstream melanocytic processes, such as the secretion of melanocytic factors and melanogenesis. Additionally, we showed that the Rosa multiflora fruit extract upregulated E-cadherin expression in keratinocytes.

OBJECTIF: Des études intensives ont révélé que les facteurs mélanocytaires pléiotropiques sont associés à la formation de taches de vieillesse. On pense que la différenciation des kératinocytes dysfonctionnels est une cause en amont de la formation des taches de vieillesse. Bien qu'il ait été démontré que la différenciation des kératinocytes est médiée par le facteur de contact cellule-cellule E-cadhérine, son implication dans la formation des taches de vieillesse reste inconnue. Ainsi, pour déterminer l'origine des taches de vieillesse et une solution intégrée pour celles-ci, nous nous sommes concentrés sur l'expression de la E-cadhérine dans la présente étude. MÉTHODES: Tout d'abord, nous avons évalué les lentigines solaires dans les cellules cutanées et cultivées au moyen d'une coloration par immunofluorescence. Par la suite, les kératinocytes traités avec des siRNA contre l'E-cadhérine ont été co-cultivés avec des mélanocytes, et les facteurs sécrétés ont été identifiés au moyen d'une analyse protéomique des surnageants de culture. Nous avons également effectué une PCR quantitative pour évaluer l'activité de la mélanogénèse et dépister les ingrédients. Pour l'analyse comportementale des mélanocytes, nous avons réalisé une imagerie accélérée à l'aide de la microscopie confocale à balayage laser. RÉSULTATS: L'expression de l'E-cadhérine a été régulée à la baisse dans l'épiderme des lentigines solaires, suggérant son implication dans la formation des taches de vieillesse. Les kératinocytes dans lesquels l'E-cadhérine a été réduite non seulement ont favorisé la sécrétion de facteurs mélanocytaires/inflammatoires, mais ont également accru la mélanogenèse en régulant à la hausse l'expression de facteurs de mélanogenèse. De plus, l'imagerie en direct a montré que la régulation négative de l'E-cadhérine inhibait la dynamique des mélanocytes et accélérait l'absorption de la mélanine. Enfin, nous avons identifié l'extrait de fruit de Rosa multiflora comme une solution capable de réguler positivement l'expression de l'E-cadhérine dans les kératinocytes. CONCLUSION: Nos résultats ont montré que la régulation négative de la E-cadhérine déclenche divers processus mélanocytaires en aval, tels que la sécrétion de facteurs mélanocytaires et la mélanogénèse. De plus, nous avons montré que l'extrait de fruit de Rosa multiflora régulait à la hausse l'expression de l'E-cadhérine dans les kératinocytes.

Glyceraldehyde-derived advanced glycation end-products are associated with left ventricular ejection fraction and brain natriuretic peptide in patients with diabetic adverse cardiac remodeling.

Objectives: Glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs) have a strong binding affinity for their cognate receptor and elicit oxidative stress and inflammation. However, it remains unknown whether the levels of Glycer-AGEs correlate with the severity of cardiac function and heart failure in patients with diabetic adverse cardiac remodeling (DbCR). Fourteen heart failure patients with type 2 diabetes mellitus (DM) without other cardiac disorders (DbCR group) were enrolled. Another 14 patients with idiopathic dilated cardiomyopathy (DCM) without DM were served as a control (DCM group). All patients were assessed for serum Glycer-AGEs, nitrotyrosine (NT), and tumor necrosis factor alpha (TNFα) and for plasma brain natriuretic peptide (BNP). The left ventricular ejection fraction (LVEF) was evaluated by echocardiography. Results: The mean serum levels of Glycer-AGEs, NT, and TNFα in the DbCR group were significantly higher than those in the DCM group (for Glycer-AGEs, p = .0073; for NT, p = .005; for TNFα, p < .0001, respectively). In the patients with DbCR, the levels of serum Glycer-AGEs and TNFα were closely associated with LVEF and BNP values. Conclusions: Both Glycer-AGEs and TNFα showed close associations with LVEF and the levels of BNP in patients with DbCR. Glycer-AGEs and TNFα may play a pathological role in the development of DbCR.

Nutri-pharmacogenomics of warfarin anticoagulation therapy: VKORC1 genotype-dependent influence of dietary vitamin K intake.

Warfarin is the most widely prescribed oral anticoagulant, but large interindividual variations exist in the dose required to achieve comparable therapeutic effects. Several clinical and genetic variables have been identified that influence warfarin dosing. However, interactions between genotype and nutrition remain uncertain in terms of dietary vitamin K intake. To investigate genotype-nutrient interactions in warfarin anticoagulation therapy, 202 consecutive outpatients (M/F = 142/60, mean age, 69 years) undergoing treatment with warfarin were enrolled. Prevalent single nucleotide polymorphisms in VKORC1 and CYP2C9 were genotyped, and dietary vitamin K intake during the week preceding the blood sampling was quantitatively estimated by a dietitian-assisted questionnaire. Patients were classified according to low, medium, or high vitamin K intake. The mean daily warfarin dose in subjects with a VKORC1-1639 A/A genotype was significantly smaller than that with a -1639A/G genotype (2.74 vs. 3.91 mg/day, respectively, p < 0.0001). Dose requirements did not differ between subjects with a CYP2C9 *1/*3 genotype versus a CYP2C9 *1/*1 genotype. In subjects with a variant VKORC1-1639 G allele, the mean daily warfarin dose was significantly attenuated by low vitamin K intake compared with medium and high intake after adjustment for covariates (3.4 vs. 5.0 vs. 4.0 mg/day, respectively, p = 0.028). No such genotype effects were observed in homozygous patients for the VKORC1-1639 A allele. The results of the present study suggest that the capacity of dietary vitamin K intake to influence warfarin dose requirements during anticoagulation therapy is VKORC1 genotype-dependent, at least in part.

Digital clock drawing test reflects visuospatial ability of older drivers.

Objectives: To keep older drivers safe, it is necessary to assess their fitness to drive. We developed a touch screen-based digital Clock Drawing Test (dCDT) and examined the relationship between the dCDT scores and on-road driving performance of older drivers in a community-setting. Methods: One hundred and forty-one community-dwelling older drivers (range; 64-88 years old) who participated in this study were included in the analysis. Participants completed the dCDT, the Mini-Mental State Examination-Japanese (MMSE-J), and an on-road driving assessment. We examined the relationship between dCDT scores using the method by Rouleau et al. (maximum 10 points) and the on-road driving performance based on a driving assessment system originally developed by Nagoya University. Results: Multiple regression analyses showed that errors in the driving test were associated with dCDT score for the items "confirmation," "turning left" and "maintains driving lane position". Discussion: This study confirmed the relationship between the dCDT score and driving errors, such as confirmation, turning left and maintaining driving lane position. The increase in these errors indicates a decline in visuospatial ability while driving. The dCDT score may reflect older drivers' visuospatial abilities while driving.

Guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance in Japan: A tiered approach for the assessment of clinically meaningful driving impairment.

In December 2022, the Ministry of Health, Labour and Welfare (MHLW) of Japan issued and implemented the guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance. This guideline recommends the use of a tiered approach to assess clinically meaningful driving impairment. It is noted that adverse events cannot be solely explained by pharmacokinetics, as the onset and duration of these events vary. Among these adverse events, those affecting alertness, such as drowsiness caused by psychotropic drugs on driving performance, are more frequently observed during initial treatment stages and dose escalation. Hence, when evaluating the effects of psychotropic drugs on driving performance, it becomes crucial to assess the persistence of clinically meaningful impairment. Therefore, the MHLW guideline, developed by the authors, emphasizes the need to assess the temporal profile of adverse events affecting driving in all clinical trials. Additionally, the guideline states that when conducting driving studies, the timing of multiple dosing should consider not only the pharmacokinetics of the investigational drug but also its tolerance.

10-year outcome trajectories of people with mental illness and their families who receive services from multidisciplinary case management and outreach teams: protocol of a multisite longitudinal study.

INTRODUCTION: Individuals with mental illness and their families often undergo their recovery process in their communities. This study explored the long-term outcome trajectories of individuals and families who received case management services provided by multidisciplinary outreach teams in a community setting. The primary objective of this study was to determine whether trajectories of subjective quality of life (QoL) related to personal recovery were linked to those clinical and societal outcomes and changes in outreach service frequency. METHODS AND ANALYSIS: The protocol of this 10-year multisite cohort study was collaboratively developed with individuals with lived experience of psychiatric disorders who had received services from participating outreach teams, and with family members in Japanese family associations. The participants in the study include patients and their key family members who receive services from 23 participating multidisciplinary outreach teams. The participant recruitment period is set from 1 October 2023 to 30 September 2025. If necessary, the recruitment period may be extended and the number of participating teams may be increased. The study will annually evaluate the following outcomes after participants' initial utilisation of services from each team: QoL related to personal recovery, personal agency, feelings of loneliness, well-being and symptom and functional assessments. The family outcomes encompass QoL, well-being, care burden and family relationships. Several meetings will be held to monitor progress and manage issues during the study. Multivariate analyses with repeated measures will be performed to investigate factors influencing changes in the patients' QoL scores as the dependent variable. ETHICS AND DISSEMINATION: The study protocol was approved by the ethical committee of the National Center of Neurology and Psychiatry (no. A2023-065). The study findings will be reported in peer-reviewed publications and presented at relevant scientific conferences. TRIAL REGISTRATION NUMBER: UMIN-CTR, No. UMIN000052275.

The new guideline for evaluating effects of psychotropic drugs on the performance to drive a motor vehicle in Japan: Comparison with US FDA guideline.

In December 2022, the new guideline for evaluating the effect of psychotropic drugs on the performance to drive a motor vehicle was issued by the Ministry of Health, Labour and Welfare (MHLW) and implemented in Japan. Of the safety information, information on the influence of medications on driving performance is particularly important because it can be relevant to the social functioning of patients. In principle, the package inserts of medications are designed based on evidence and provide precautions regarding the operation of heavy machinery such as automobiles in Japan, the United States, and Europe. The effects of medications on driving performance are generally evaluated in a tiered approach involving nonclinical and clinical studies. Because of the wide variety of functional domains involved in automobile driving, the selection of evaluation methods for a given medication depends on their characteristics, which is a complicated method. Therefore, to evaluate the effects of psychotropic drugs on driving performance efficiently and appropriately, we developed the MHLW guideline that specifically defines the evaluation methods used in pharmacological studies, the neuropsychological tests used in pharmacodynamic studies, and the situations in which driving studies are necessary. Regarding the planning of appropriate drug development strategies, we review the background of the MHLW guideline and its differences from the US Food and Drug Administration (FDA) guideline.

Assessment of senior drivers' internal state in the event of simulated unexpected vehicle motion based on near-infrared spectroscopy.

OBJECTIVE: A driver's internal state is a critical factor influencing driving performance, especially in cases of surprise or shock in response to unexpected incidents while driving. This study was designed to investigate the brain activity of a senior driver in response to simulated unexpected vehicle motion, compared with a relaxed state and normal driving. METHODS: To accomplish this, we created a driving simulator paradigm wherein participants were involved in one of the following three scenarios: sitting down and relaxing, normal driving around the city with traffic signals and other vehicles, and the exiting of a parking area. In the scenario where the driver was to exit the parking area, the gear was switched automatically by the CarMaker software without the driver being notified, leading to an unexpected condition. The driver's internal states were classified by artificial intelligence, based on information obtained through four-channel near-infrared spectroscopy. RESULTS: Significant differences were observed between the hemodynamic responses obtained in the three conditions. Ultimately, this method can be used to update advanced driver assistance systems, with a view to preventing future traffic accidents, by activating in-vehicle safety functions based on the driver's condition. CONCLUSIONS: A driver's internal states in a panic situation while driving can be detected using near-infrared spectroscopy and artificial intelligence.

Expressions of rod and cone photoreceptor-like proteins in human epidermis.

Previous reports have suggested the existence of photoreceptors for visible radiation at the surface of the human body. Rhodopsin is a well-known photosensitive protein found in the rod cells of the retina and detects light/dark contrast. Cone opsins are also photosensitive receptors in the cone cells of the retina and detect colour. Here, we describe immunochemical studies using anti-rhodopsin and anti-opsin antibodies on human skin. Both mouse retina and human epidermis showed clear immunoreactivity with each antibody. Interestingly, immunoreactivity against longer-wavelength opsin antibody was observed in the basal layer of the epidermis, while immunoreactivity against rhodopsin and shorter-wavelength opsin was observed in the upper layer. PCR analysis confirmed the expression of rhodopsin-like and opsin-like genes in human retina and the skin. These results suggest that a series of proteins, which play a crucial role in visual perception, are expressed in human epidermis.

Possibly Late-Onset Arrhythmogenic Right Ventricular Cardiomyopathy: Unique Triglyceride Deposition by Analysis of Lipid Contents.

We presented an unusual arrhythmogenic right ventricular cardiomyopathy (ARVC) case of a late-60s elderly man's death, due to severe pericardial/pleural effusion and ascites, and arrhythmic events, with unique pathological features. The hypertrophic heart grossly displayed yellowish to yellow-whitish predominantly in the variably thinned wall of the dilated right ventricle. Microscopic findings showed diffuse fatty/fibrofatty replacement in not only the right but left ventricular myocardium, together with an outer lymphoplasmacytic infiltrate. According to the lipid contents analysis, the triglyceride content, but not the cholesterol content, in our patient's right and left ventricular cardiac muscle was much higher than that in the control subject. We propose that this unique triglyceride deposition in our possibly late-onset ARVC case might be one of new clues to understand its enigmatic cause. Further prospective studies are needed to validate the presence and significance of a greater volume of triglyceride deposit, after collecting and investigating a larger number of early and late-onset ARVC cases examined.

SmartEye and Polhemus data for vestibulo-ocular reflex and optokinetic reflex model.

In this data article, this dataset included raw data of head and eye movement that collected by Polhemus (Polhemus Inc) and SmartEye (Smart Eye AB) equipment. Subjects who have driver license participated in this experiment. The experiment was conducted with a driving simulator that was controlled by CarSim (Mechanical simulation Co., Anna Arbor, MI) with the vehicle motion. This data set not only contained the eye and head movement but also had eye gaze, pupil diameter, saccades, and so on. It can be used for the parameter identification of the vestibulor-ocular reflex (VOR) model, simulation eye movement, as well as running other analysis related to eye movement.

A Novel Method for Classifying Driver Mental Workload Under Naturalistic Conditions With Information From Near-Infrared Spectroscopy.

Driver cognitive distraction is a critical factor in road safety, and its evaluation, especially under real conditions, presents challenges to researchers and engineers. In this study, we considered mental workload from a secondary task as a potential source of cognitive distraction and aimed to estimate the increased cognitive load on the driver with a four-channel near-infrared spectroscopy (NIRS) device by introducing a machine-learning method for hemodynamic data. To produce added cognitive workload in a driver beyond just driving, two levels of an auditory presentation n-back task were used. A total of 60 experimental data sets from the NIRS device during two driving tasks were obtained and analyzed by machine-learning algorithms. We used two techniques to prevent overfitting of the classification models: (1) k-fold cross-validation and principal-component analysis, and (2) retaining 25% of the data (testing data) for testing of the model after classification. Six types of classifier were trained and tested: decision tree, discriminant analysis, logistic regression, the support vector machine, the nearest neighbor classifier, and the ensemble classifier. Cognitive workload levels were well classified from the NIRS data in the cases of subject-dependent classification (the accuracy of classification increased from 81.30 to 95.40%, and the accuracy of prediction of the testing data was 82.18 to 96.08%), subject 26 independent classification (the accuracy of classification increased from 84.90 to 89.50%, and the accuracy of prediction of the testing data increased from 84.08 to 89.91%), and channel-independent classification (classification 82.90%, prediction 82.74%). NIRS data in conjunction with an artificial intelligence method can therefore be used to classify mental workload as a source of potential cognitive distraction in real time under naturalistic conditions; this information may be utilized in driver assistance systems to prevent road accidents.

A multicenter, retrospective, observational study of the clinical outcomes and risk factors for relapse of ulcerative colitis at 1 year after leukocytapheresis.

BACKGROUND: Extracorporeal leukocytapheresis (LCAP) is effective for inducing remission of ulcerative colitis (UC). This retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse of UC after LCAP. METHODS: Patients with active UC treated with LCAP between 2010 and 2012 were enrolled from 54 medical facilities in Japan. Clinical data evaluated at 1 year after the last LCAP session included the incidence of relapse, 1-year cumulative relapse-free rate, risk factors for relapse, and history of re-induction treatment following relapse. Relapse was defined by the addition of treatment to induce remission. The primary endpoint was the 1-year cumulative relapse-free rate. Secondary endpoints were risk factors for relapse and outcomes of re-induction treatment after relapse. RESULTS: For 314 patients, the 1-year cumulative relapse-free rate was 63.6%. Following LCAP, a Lichtiger clinical activity index (CAI) of 3 or 4 and high leukocyte count (cut-off value: 7790/mm3) were associated with a greater risk of relapse. Intensive LCAP (≥4 sessions within the first 2 weeks) was associated with favorable long-term outcomes in corticosteroid-refractory patients. The response rate was 85.1% among 30 patients who required re-treatment with LCAP. CONCLUSIONS: The majority of patients (>60%) with UC treated with LCAP achieved clinical remission within 1 year and remained relapse-free. A higher Lichtiger CAI and leukocyte count following LCAP were risk factors for relapse. Re-induction therapy with LCAP was effective for relapse of UC.

Virtual-reality-Based 3D navigation training for emergency egress from spacecraft.

BACKGROUND: Astronauts have reported spatial disorientation and navigation problems inside spacecraft whose interior visual vertical direction varies from module to module. If they had relevant preflight practice they might orient better. This experiment examined the influence of relative body orientation and individual spatial skills during VR training on a simulated emergency egress task. METHOD: During training, 36 subjects were each led on 12 tours through a space station by a virtual tour guide. Subjects wore a head-mounted display and controlled their motion with a game-pad. Each tour traversed multiple modules and involved up to three changes in visual vertical direction. Each subject was assigned to one of three groups that maintained different postures: visually upright relative to the "local" module; constant orientation relative to the "station" irrespective of local visual vertical; and "mixed" (local, followed by station orientation). Groups were balanced on the basis of mental rotation and perspective-taking test scores. Subjects then performed 24 emergency egress testing trials without the tour guide. Smoke reduced visibility during the last 12 trials. Egress time, sense of direction (by pointing to origin and destination) and configuration knowledge were measured. RESULTS: Both individual 3D spatial abilities and orientation during training influence emergency egress performance, pointing, and configuration knowledge. Local training facilitates landmark and route learning, but station training enhances sense of direction relative to station, and, therefore, performance in low visibility. CONCLUSIONS: We recommend a sequence of local, followed by station, and then randomized orientation training, preferably customized to a trainee's 3D spatial ability.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND: Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS: Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS: The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS: Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

Prediction of all-cause death using (11)C-hydroxyephedrine positron emission tomography in Japanese patients with left ventricular dysfunction.

OBJECTIVES: The aim of this study was to determine whether (11)C-hydroxyephedrine ((11)C-HED) can predict adverse events including all-cause death in Japanese patients with left ventricular (LV) dysfunction. BACKGROUND: Although (11)C-HED PET has been used to assess cardiac sympathetic innervation in various disease conditions, data on their prognostic value are limited. METHODS: Sixty patients (mean LVEF, 42 ± 14 %) with LV dysfunction (42 ischemic and 18 non-ischemic heart disease) underwent (11)C-HED PET. Myocardial retention was calculated for (11)C-HED PET as a measure of cardiac sympathetic neuronal integrity. Statistical analysis was performed using Cox proportional hazards regression and log-rank test. RESULTS: Thirteen deaths (7 cardiac and 6 non-cardiac deaths) occurred during a mean follow-up period of 33 ± 23 months. The patients with death were associated with significantly lower (11)C-HED retention (7.1 ± 2.1 vs 9.0 ± 2.4, p = 0.015) than those without death. The hazard ratio for global (11)C-HED retention per unit (/min) was 0.762 (p = 0.039), which remained significant in multivariate analysis. When the patients were divided into the high (≥8.5) and low (<8.5) (11)C-HED retention groups, the low (11)C-HED retention group was associated with significantly poorer survival than the high (11)C-HED retention group (p = 0.004). CONCLUSION: The low global (11)C-HED retention is a marker of poor overall survival in patients with LV dysfunction in this study.

Chronic total occlusions of the right coronary and left anterior descending coronary arteries in a young adult patient with antiphospholipid syndrome.

A 36-year-old male appeared to have an old myocardial infarction on electrocardiogram, and coronary angiography (CAG) was performed. The CAG showed total occlusions of the right coronary artery and left anterior descending artery. He was successfully treated with drug-eluting stent implantation for both occluded coronary arteries. Such serious coronary lesions are uncommon for his young age. The patient was diagnosed as having antiphospholipid syndrome (APS) based on elevation of anticardiolipin antibody and anti-ß2 glycoprotein I antibody. Two years after stent implantation, the patient was well without ischemia or thrombosis. APS should be considered a potential cause of serious coronary disease in young adults. .

Upregulation of the IFN-gamma-stimulated genes in the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De.

DNA microarray hybridization was used to measure the changes of mRNA levels over time during the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De. Upregulation of a number of interferon (IFN)-gamma-stimulated genes was detected in delayed pigmented lesions, suggesting that IFN-gamma may play a pivotal role in the development of delayed pigmented spots in this model. Upregulation of these genes was further supported by the increased protein expression level of IFN-gamma in the lesions. Epidermal infiltration of CD8(+) T lymphocytes and mast cell accumulation in the dermis were observed in delayed pigmented spots. Genes encoding chemokines such as monocyte chemoattractant protein-2 (MCP-2), IFN-inducible protein 10 (IP-10), and monokine induced by IFN-gamma (MIG) were among those upregulated by IFN-gamma. We hypothesize that chemokines produced in the epidermis induce migration of inflammatory cells, such as T lymphocytes, mast cells, and macrophages, to the vicinity of melanocytes. Keratinocytes, T lymphocytes, mast cells, and macrophages would become involved in an interactive network, providing a suitable local environment for melanocyte activation. In this environment, melanocytes are exposed to an extensive array of secreted mediators. Reciprocal activation among these cells to maintain this interactive network results in constitutive melanocyte activation and chronic melanin synthesis in delayed pigmented lesions.

The effect of the configuration and the interior design of a virtual weightless space station on human spatial orientation.

In a virtual weightless environment, subjects' orientation skills were studied to examine what kind of cognitive errors people make when they moved through the interior space of virtual space stations and what kind of visual information effectively decreases those errors. Subjects wearing a head-mounted display moved from one end to the other end in space station-like routes constructed of rectangular and cubical modules, and did Pointing and Modeling tasks. In Experiment 1, configurations of the routes were changed with such variables as the number of bends, the number of embedding planes, and the number of planes with respect to the body posture. The results indicated that spatial orientation ability was relevant to the variables and that orientational errors were explained by two causes. One of these was that the place, the direction, and the sequence of turns were incorrect. The other was that subjects did not recognize the rotation of the frame of reference, especially when they turned in pitch direction rather than in yaw. In Experiment 2, the effect of the interior design was examined by testing three design settings. Wall colors that showed the allocentric frame of reference and the different interior design of vertical and horizontal modules were effective; however, there was a limit to the effectiveness in complicated configurations.