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Background: Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents., Methods: A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6-15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires., Results: A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year., Conclusions: The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: The association between obesity and cardiovascular disease (CVD) remains unclear, particularly for those with established CVD risk factors. We analyzed follow-up data from the Aichi Workers' Cohort Study. We studied the association between the degree of obesity and risk of CVD and its subtypes specifically among individuals with hypertension, hyper-low-density lipoprotein (LDL)-cholesterolemia, or diabetes., Methods: Pooled data of 8972 adults (7076 men and 1896 women) who were recruited between 2002 and 2008 were used in the current analysis. We used multivariable Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the degree of obesity assessed with body mass index (BMI) and the risk of CVD and its subtypes, i.e., coronary heart disease (CHD) and stroke., Results: During a median of 12 years, there were 197 CVDs (80 CHDs and 117 strokes). BMI ≥ 27.5 compared to 21.0-22.9 kg/m 2 was positively and significantly associated with the risks of CVD, CHD, and total stroke. Hypertension, hyper-LDL-cholesterolemia, and diabetes mediated 15.9%, 5.8%, and 8.7% of obesity-CVD associations, respectively, and 28.3% by their combination. In the stratified analyses by the presence of risk factors, BMI ≥ 25.0 (overweight/obesity) compared to BMI < 25 kg/m 2 was associated with a higher risk of CVD in those with and without hypertension, but only with hyper-LDL-cholesterolemia, and without diabetes., Conclusions: Overweight/obesity was associated with the risk of CVD and its subtypes. About 30% of the risk was explained by hypertension, hyper-LDL-cholesterolemia, and diabetes, of which hypertension accounted for approximately the half of the explained risk. However, overweight/obesity increased the risk of CVD even in those without hypertension. These findings highlight the importance of controlling and preventing overweight/obesity regardless of chronic disease status., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Transplacental transport of maternal IgG via the neonatal Fc receptor (FcRn) provides babies with passive immunity. Several factors are reported to influence transport, including the avidity of antibodies (Abs) for their cognate antigens. Unfortunately, information on the role of antibody (Ab) avidity is limited. This study investigated if i) antibodies (Abs) with high avidity for 6 Plasmodium falciparum antigens and tetanus toxoid (TTx) were preferentially transferred to premature and term Cameroonian babies and ii) if Ab avidity was increased in babies whose mothers had placental malaria (PM), implicating the involvement of immune complexes., Methods: Total IgG (mg/ml) and Abs to malarial antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3, DBL5 of VAR2CSA) and TTx were measured in paired mother-cord samples obtained from premature and term deliveries in Cameroon. Half the women had PM at delivery. Avidity Indices (AIs) were determined by treating antigen-bound-Abs with different molar concentrations of NH 4 SCN and calculating 50% endpoints., Results: Total IgG and antigen-specific Abs increased in cord blood with gestational age; however, AIs did not. AIs in paired maternal-cord blood samples were strongly associated for all antigens (r = 0.77-0.96). However, no significant different in AIs was found between paired mother-cord blood samples for any of the antigens (p values > 0.05). Similarly, Ab avidity was not increased in cord blood of babies whose mothers had PM or hypergammaglobulinemia., Discussion: Overall, there was no evidence that higher avidity Abs to any of the malarial antigens or TTx were preferentially transferred to Cameroonian babies., Competing Interests: Declaration of competing interest All authors declare they have no real or perceived conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To examine associations among women's preferred locations for human papillomavirus (HPV) self-sampling in relation to their demographic, social, and health characteristics and their perceived benefits and concerns regarding this procedure., Design: Cross-sectional, descriptive survey., Setting: Online distribution between March 2022 and April 2022., Participants: People who were assigned female sex at birth and were eligible for cervical cancer screening (N = 367: cis-gender women, n = 364; another gender identity, n = 3)., Methods: We used quota sampling to obtain a racially and ethnically diverse sample. We conducted bivariate analyses to examine differences in participants' preferred locations for HPV self-sampling by sociodemographic and health characteristics. We used a multinomial logistic regression model to examine the associations between preferred HPV self-sampling location, characteristics of participants, and perceived benefits and concerns regarding this procedure., Results: In our sample, 43% (n = 158) of participants preferred HPV self-sampling at the office of a health care provider, 50% (n = 182) preferred HPV self-sampling anywhere (office or home), and 7% (n = 27) did not feel comfortable with HPV self-sampling anywhere. Participants 39 to 45 years of age were more likely to prefer HPV self-sampling anywhere (office or home) than participants 27 to 32 years of age, OR = 2.47, 95% confidence interval (CI) [1.21, 5.06]. Participants who preferred HPV self-sampling anywhere perceived greater benefit related to limited geographic access to a clinic compared to those who preferred office only, OR = 1.82, 95% CI [1.08, 3.07]. Participants who preferred HPV self-sampling anywhere had less concern related to performing the procedure accurately than those who preferred office only, OR = 0.44, 95% CI [0.31, 0.62]., Conclusion: HPV self-sampling is an alternative strategy to increase cervical cancer screening. As providers consider implementation of HPV self-sampling, our findings suggest that office and home-based collection strategies should be considered to increase access to cervical cancer screening., Competing Interests: Conflict of Interest Gregory Zimet has served as a consultant to Merck related to human papillomavirus vaccination and as an external advisory board member for Moderna (related to COVID-19 vaccination) and Pfizer (related to meningococcal vaccination). He received investigator-initiated research funding from Merck, which was administered through Indiana University. Holly B. Fontenot received investigator-initiated grant funding from Merck related to adolescent vaccination. Eunjung Lim and Masako Matsunaga were partially supported by Ola HAWAII (U54MD007691) and PIKO (U54GM13062) from the National Institutes of Health. Drs. Fontenot, Zimet, Lim, and Matsunaga confirm that their funding source(s) have had no involvement in the conduct of this work. The other authors report no conflicts of interest or relevant financial relationships., (Copyright © 2023 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes insipidus (DI) is a well-known complication of transsphenoidal surgery. However, the risk factors for DI remain controversial., Methods: We conducted a retrospective study of patients who underwent endoscopic transsphenoidal surgery for pituitary adenoma at our institution during a 5-year period. The patients were divided into a DI group and a non-DI group. Logistic regression analyses were used to identify risk factors for postoperative DI. In subgroup analysis, the DI group was divided into transient DI and permanent DI groups, and perioperative factors were compared between groups., Results: Of 101 patients, 58 were in the non-DI group (57.4%) and 43 were in the DI group (42.6%). Permanent DI occurred in 7 patients (6.9%). In univariate analyses, statistically significant risk factors were suprasellar extension, tumor functionality, and intraoperative cerebrospinal fluid leaks by Esposito grade. In multivariate logistic regression analysis, Esposito grade was the only statistically significant risk factor (P = 0.015). The frequency of DI increased as the Esposito grade increased (P = 0.0002 for the trend). In subgroup analysis, postoperative nadir sodium concentration was lower in the permanent DI group (128.1 ± 2.78 mmol/L) than in the transient DI group (135 ± 1.22 mmol/L; P = 0.035), and the optimal cutoff value was 124.5 mmol/L, with a sensitivity of 57.1% and a specificity of 91.7% (area under the curve = 0.76, P = 0.034)., Conclusions: Intraoperative cerebrospinal fluid leak by Esposito grade is associated with postoperative DI. These data can be applied to help identify high-risk patients who need more aggressive follow-up and fluid management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup., Methods: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin., Results: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups., Conclusions: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To examine whether laughter yoga (LY), i.e., simulated laughter, alters cortisol and dehydroepiandrosterone (DHEA) levels and cortisol/DHEA (C/D) ratios., Methods: In a randomized controlled trial, 120 healthy university students were allocated to experiencing LY, watching a comedy movie (spontaneous laughter), or reading a book. Salivary cortisol and DHEA levels were measured immediately before, immediately after, and 30 min after the intervention., Results: Cortisol levels and C/D ratios significantly decreased by time in the LY and comedy movie groups. Significant group*time interactions were found between these two groups for cortisol levels and C/D ratios. DHEA levels did not change by time in the LY group., Conclusions: LY decreased cortisol levels and C/D ratios but did not affect DHEA levels. Simulated and spontaneous laughter differently affected the dynamics of cortisol levels and C/D ratios. Effect of spontaneous laughter on the cortisol dynamics lasted longer than that of simulated laughter. (UMIN000019409)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Dual (oxygen and nitrogen) isotopic composition of the museum archived nitrates from the United States of America, South Africa and Australia was studied. The analyzed specimens were collected in middle 19th to early 20th centuries, and represent world-wide acquisition of the Smithsonian Institution Natural Museum of Natural History (Washington, D. C., USA) and the Natural History Museum (London, UK). The samples consist of transparent to semi-transparent aggregates of minute nitrate, euhedral crystallites which imply precipitation from percolating fluids under ample space and dry regimes. The major nitrate chemistry is saltpetre (KNO 3 ) with minor nitratine (NaNO 3 ). A binary plot of δ 15 N vs. δ 18 O of almost all nitrates indicates a trend, reflecting microbial origin through nitrification of ammonium. The diagram excludes the contribution of meteoric origin formed by mass-independent, photochemical reaction of NO with ozone in stratosphere. Calculated paleo-ambient fluid compositions responsible for microbial nitrification imply extreme evaporative concentration of relevant fluids under dry climatic regimes in the Northern Cape Province (South Africa) and in the Northern Territory (central Australia), and even throughout the United States of America. The dual isotopic characterization provides direct evidence to the origin of the museum archived nitrates., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report the case of a 12-year-old girl who developed Guillain-Barré syndrome (GBS) and optic neuritis (ON) following Mycoplasma pneumoniae infection. Her symptoms, including bilateral vision impairment and tingling in her hands and right foot, were resolved after methylprednisolone pulse therapy. Serum anti-galactocerebroside (Gal-C) IgM antibodies were detected in our patient. This is the first report of a child with GBS and ON associated with M. pneumoniae infection., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Dietary indexes to assess accordance with the Dietary Approaches to Stop Hypertension (DASH) dietary pattern are useful tools in studies with health-related outcomes. However, scoring algorithms of the dietary index can affect the range of its applications., Objective: The purposes of this study were to develop a DASH dietary index with calorie-based standards in equivalent units and to evaluate the validity and reliability of the index., Methods: Calorie-based standards for nine components were determined based on recommended intakes in the DASH eating plan and dietary intakes estimated from two 24-hour dietary recalls of adult participants in the National Health and Nutrition Examination Survey 2007-2008, 2009-2010 (n=9,720). Evaluation tests included descriptive analyses of index scores among US adults stratified by sex and smoking status. Spearman's rank correlations were used to examine the relationships among components and total scores. The developed index was compared with two DASH dietary indexes that use different scoring algorithms to examine the association between total scores and blood pressure status through multivariable regression models., Results: The newly developed index consisted of seven food group and two nutrient components. The mean and median of total scores among US adults were 42.3 (95% CI 41.6 to 43.0) and 41.6 of 90 points, respectively. The mean total scores among adult women and non-current smokers were higher than their counterparts (P<0.001). The absolute correlation coefficients among the components and between each component and the sum of other components were ≤0.33 and ≤0.35, respectively. After adjusting for age and race/ethnicity, an association between total scores and blood pressure status was found in adult women (P<0.001), but not in adult men. The same pattern was found when the two indexes were used, but the strength of the association varied across the three indexes., Conclusions: The developed index appeared to measure accordance with the DASH dietary pattern based on the dietary data from US adults. Further studies are warranted for various applications of the index., (Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Coronary heart disease (CHD) and stroke have common risk factors, but some of these differ in the magnitude or direction of associations between CHD and stroke. We assessed whether the impact of each risk factor differed between CHD and stroke mortality in Asians., Methods: In total, 104 910 subjects aged 40-79 years without histories of cancer, CHD and stroke at baseline were followed between 1988 and 2009. Competing-risks analysis was used to test for differences in the associations of each risk factor with two endpoints (CHD and stroke). Population attributable fractions (PAFs) were also calculated for these endpoints to estimate the population impact of each risk factor., Results: During a median 19.1-year follow-up, 1554 died from CHD and 3163 from stroke. The association of hypertension with CHD was similar to that with stroke in terms of the magnitude and direction (multivariable-adjusted hazard ratio for CHD: 1.63 vs. stroke: 1.73 in men and 1.70 vs. 1.66 in women). Conversely, the magnitude of these associations differed for smoking (CHD: 1.95 vs. stroke: 1.23 in men and 2.45 vs. 1.35 in women) and diabetes (1.49 vs. 1.09 in men and 2.08 vs. 1.39 in women). The highest PAF for CHD was caused by smoking in men and by hypertension in women; that for stroke was caused by hypertension in both sexes., Conclusions: Hypertension associations and PAFs were consistent between CHD and stroke, but not for other risk factors. These findings may be useful to optimize public health intervention strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We previously showed that salmon milt nucleoprotein (NP) promotes thermotolerance in Caenorhabditis elegans; however, the active component and physiological mechanism of this effect has remained unclear. l-arginine (AR) is a major component of protamine and thus it has been proposed as the possible active component of NP. In this study, the viability of C. elegans treated with AR under heat stress was assessed and AR was shown to extend the survival term of the heat-stressed organisms. Additionally, AR was shown to restore the thrashing movement of the worms that is suppressed by heat stress. Treatment with AR was furthermore shown to promote thermotolerance in a DAF-16- and SIR-2.1-dependent manner, where DAF-16 and SIR-2.1 are homologs of FoxO and SirT1, respectively. Taken together, these data suggest that AR is one of the active components of NP and promotes thermotolerance via the activation of DAF-16 and SIR-2.1., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Although the Palliative Prognostic Index (PPI) is a reliable and validated tool to predict the survival of terminally ill cancer patients, all clinicians cannot always precisely diagnose delirium., Objectives: The primary aim of this study was to examine the predictive value of a simplified PPI. In the simplified PPI, a single item from the Communication Capacity Scale was substituted for the delirium item of the original., Methods: This multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Palliative care physicians recorded clinical variables at the first assessment and followed up patients six months later., Results: A total of 2425 subjects were recruited; 2343 had analyzable data. The C-statistics of the original and simplified PPIs were 0.801 and 0.800 for three week and 0.800 and 0.781 for six-week survival predictions, respectively. The sensitivity and specificity for survival predictions using the simplified PPI were 72.9% and 67.6% (for three week) and 80.3% and 61.8% (for six week), respectively., Conclusion: The simplified PPI showed essentially the same predictive value as the original PPI and is an alternative when clinicians have difficulties in diagnosing delirium., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: To examine the association of intrahepatic fat with homeostasis model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, in Japanese adults, and whether intrahepatic fat is associated with insulin resistance independent of waist circumference and other measures of obesity., Methods: Fifty-three individuals aged 37-69 were studied. Spectrum obtained using a 3-T magnetic resonance imager was analysed with LCModel to quantify intrahepatic fat. Blood levels of insulin, glucose and other biochemical markers were obtained after 8h or more fasting. Percent body fat was estimated by a bioelectrical impedance analyzer. HOMA-IR and intrahepatic fat content were log-transformed in the analysis., Results: We found a positive correlation between intrahepatic fat and HOMA-IR, which was independent of the anthropometric measures of obesity. In contrast, significant and positive correlations of body mass index, percent body fat, and waist circumference with HOMA-IR were largely explained by their associations with intrahepatic fat. Intrahepatic fat was positively associated with alanine transaminase and triglycerides even after adjustment for HOMA-IR., Conclusion: Intrahepatic fat was associated with insulin resistance independent of age, sex, and measures of obesity in Japanese adults. Hypertriglyceridemia and liver injury may directly occur subsequent to intrahepatic fat accumulation., (Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Mycotic aneurysms of the coronary artery are extremely uncommon and can be very difficult to diagnose. We report a unique case of a mycotic aneurysm of the left anterior descending coronary artery with a history of two-vessel off-pump coronary artery bypass graft surgery 9 months previously. The aneurysmectomy was successful., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The effects of anticipated threat situations and the valence of the stimuli on the deceleration of the phasic heart rate (HR) were investigated in a single experiment using an S1-S2 paradigm. There were certain S1 cues that were always expected to be followed by neutral pictures (S2 stimuli), and uncertain S1 cues that had a 50% probability of being followed by neutral or unpleasant pictures (S2 stimuli). Greater phasic HR deceleration was observed for S2 stimuli following uncertain S1 cues than for S2 stimuli following certain S1 cues, regardless of the valence of the S2 stimuli. This result suggests that an anticipated threat situation in which participants anticipate facing potentially unpleasant stimuli leads to the allocation of more attentional resources. Additionally, correlation analyses revealed that highly anxious individuals tended to show greater HR deceleration in response to unpleasant stimuli, possibly reflecting maladaptive attentional bias for threat stimuli., (2010 Elsevier B.V. All rights reserved.)

Recent studies in psychoneuroimmunology have indicated that proinflammatory cytokines cause several diseases and behaviors that overlap symptomatically with depression. It is known that the endogenous opioid peptide beta-endorphin regulates proinflammatory cytokine secretion from peripheral immune cells via mu-opioid receptor-dependent mechanisms. Therefore, it is possible that the functional polymorphism of the mu-opioid receptor gene (OPRM1, SNP: A118G) influences peripheral circulating proinflammatory cytokine levels and the health-related quality of life (QOL) even in healthy populations. In this study, we compared the serum concentrations of several proinflammatory cytokines (interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma)) and the health-related QOL between OPRM1 genotypes. Interestingly, serum concentrations of IL-6, TNF-alpha, and IFN-gamma were significantly lower and the general health score was significantly higher in carriers of the G allele, who show a strong binding of beta-endorphin to the mu-opioid receptor as compared to individuals without the G allele. Correlation analysis indicated that the general health score was negatively correlated with the IL-6 serum concentration. These results suggest that the sensitive endogenous opioid system in carriers of the G allele may suppress proinflammatory cytokine secretion from peripheral immune cells; consequently, it may influence the health perception.

Recent studies demonstrated that an acute psychological stressor elicited transient changes in lymphocyte redistribution. Earlier studies had established that CD3-CD16+CD56+ natural killer cells (NK cells) increased remarkably in peripheral blood circulation and that the amount of lymphocyte redistribution in NK cells was dependent on the CD62L expression density. Specifically, CD62L- cells were mobilized more pronouncedly than were CD62L+ cells. These results led us to hypothesize that such different reactivity causes different temporal characteristics between CD62L+ and CD62L- lymphocyte subsets. The present study was conducted to examine this issue. Ten female participants experienced a 10-minute baseline period and performed a 10-minute mental arithmetic task as an acute psychological stressor. Blood samples for measuring the proportions of CD62L+ or CD62L- NK cells and CD62L+ or CD62L- T cells were obtained immediately after each period and every 2 min during the task. As expected, CD62L+ and CD62L- NK cells showed different reactivity in response to the stressor and showed different temporal characteristics. That is, the elevation of CD62L- NK cells reached a significant level at 1 min after the initiation of the stressor, while CD62L+ NK cells took 8 min to show a tendency of elevation. Although CD3+ T cells showed different reactivity between CD62L cell types, they did not show different temporal characteristics. These findings suggest that the expression of CD62L modulates not only the amount of redistribution but also the temporal characteristics of the redistribution of NK cells.

Recent studies on psychoneuroimmunology have indicated that positive psychological events are related to immune functions; however, limited information is available regarding associations among the central nervous, endocrine, and immune systems when positive emotions are elicited. In the present study, we demonstrated associations among these systems by simultaneously recording brain, endocrine, and immune activities when positive emotions were evoked in participants as they watched films featuring their favorite persons. Interestingly, the activity of peripheral circulating natural killer cells and the peripheral dopamine level were elevated while participants experienced positive emotions, and these values were positively correlated. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, hypothalamus, subcallosal gyrus, posterior cingulate cortex, superior temporal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with endocrine and immune activities. These results suggest that while an individual experiences positive emotions, the central nervous, endocrine, and immune systems may be interrelated and attraction for favorite persons may be associated with the activation of the innate immune function via the dopaminergic system.

Several studies reported that redistribution of lymphocyte subsets, especially CD3-CD16+CD56+ natural killer (NK) cells, was elicited by acute psychological stress tasks. It is known that lymphocyte redistribution was regulated based on active or passive emotional coping strategies, which can be elicited dependent on controllability of a stressor. Controllability can be evaluated gradually by learning of a contingency between actions and outcomes. Therefore, lymphocyte redistribution can be determined by learning of the contingency. To examine this issue, we used a stochastic learning task as an acute stress task and divided twenty healthy participants into reinforcement or yoked groups. Between the two groups, only whether they could learn the contingency was manipulated. As a result, patterns of changes in the NK cell numbers differed between the groups; NK cells remarkably increased at first and then gradually decreased to the baseline in the reinforcement group while the yoked group showed a moderate but sustained increase of NK cells. These patterns of changes in the NK cells were completely parallel with changes of the cardiovascular parameters but not with secretion of catecholamines. The present results suggest that cardiovascular and immune reactivity can be modulated along with progresses of adaptation for an acute stressor.

Oxidative stress and DNA oxidation play important roles in the induction of ischemic neuronal cell death. However, the subcellular source of oxidized DNA detected by 8-hydroxy-2'-deoxyguanosine (8-OHdG) after ischemia has not been clarified although it is known to increase in the brain after ischemia. One-hour transient ischemia of the middle cerebral artery was induced in mice utilizing an intraluminal filament. The occurrence of superoxide anion as an ethidium (Et) signal, 8-OHdG, cytochrome c release and neuronal cell death were examined using immunohistological and biochemical techniques in sham-operated control (0h) and 1, 3, 6, 24, or 96h after reperfusion. Et signals were prominent in the cortical neurons of ipsilateral hemisphere 3h after reperfusion. Strong 8-OHdG immunoreactivity was observed 3-6h after reperfusion. Immunoassays after cell fractionation revealed a significant increase of 8-OHdG in mitochondria 6h after reperfusion. Immunohistochemistry revealed that the 8-OHdG immunoreactivity colocalized with a neuronal marker, microfilament 200 and a mitochondrial marker, cytochrome oxidase subunit I. Cytochrome c rose in cytoplasm at 6h and TUNEL-positive neurons noted 6-24h after ischemia. The present results suggest the possibility that the mitochondrial damage including mitochondrial DNA oxidation might be responsible for the induction of ischemic neuronal cell death.

Marked fluctuation of dopamine concentration in the striatum following long-term L-DOPA administration contributes to the development of L-DOPA-induced motor complications including L-DOPA-induced dyskinesias and wearing-off in patients with Parkinson's disease. We have shown that pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A (5-hydroxytryptamine) receptor agonist, alleviates fluctuation of dopamine levels in the dopamine-denervated striatum of 6-hydroxydopamine-lesioned (hemiparkinsonian) rats after L-DOPA treatment. To determine whether co-administration of 8-OH-DPAT with L-DOPA prevents L-DOPA-induced motor complications, we examined rotation behavior and levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the striatum of 6-hydroxydopamine-lesioned rats treated with L-DOPA alone or L-DOPA + 8-OH-DPAT, twice daily, for 2 weeks. Co-administration of 8-OH-DPAT inhibited an increase of rotation behavior to L-DOPA and L-DOPA-induced increases in levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the dopamine-denervated striatum, both of which are established indices of L-DOPA-induced motor complications. These results suggest that pharmaceutical products that stimulate 5-HT1A receptors could prove useful in prevention of the development of L-DOPA-induced motor complications in patients with Parkinson's disease.

Background: It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1)., Objective: To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis., Methods: A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy., Results: The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002)., Conclusion: This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.

Salmon milt DNA hydrogel beads were synthesized by an inverse suspension polymerization of acrylamide in the continuous phase of cyclohexane. These DNA hydrogel beads in water medium are stable, more than 82% (w/w) of the DNA can be retained in the hydrogel after a sufficient soaking in water. Comparing with normal adsorbents such as activated carbon and alumina, this DNA matrix showed a selective adsorptivity for the dioxin derivatives with planar structure such as dibenzo-p-dioxin (DD), dibenzofuran (DF) and biphenyl (BP). Rinsing with hexane can regenerate the DNA beads after adsorption by the dioxin derivatives, even the adsorption-regeneration process repeated four times, no significant decrease in the dioxin removal capacity was observed.

Objective: To study early cognitive processes and hemispheric differences in the primary auditory cortex during selective attention., Methods: We measured auditory evoked magnetic fields (AEFs) to 400 and 4000 Hz tone pips that were randomly presented at the right or left ear. Subjects paid attention to target stimuli during pitch (high or low) or laterality (left or right) discrimination tasks. In the control session, 400 or 4000 Hz tone alone was presented at the left or right ear. We calculated the location and strength of N100m dipole for 400 and 4000 Hz tones, based on the AEFs obtained from the hemisphere contralateral to the stimulated ear., Results: N100m amplitude increased in both hemispheres in pitch or laterality discriminating conditions. N100m latency also shortened during selective attention. The N100m dipole distance between 400 and 4000 Hz tones was enlarged, especially in the right auditory cortex during pitch discrimination task, but was unchanged during the laterality discrimination task., Conclusions: We conclude that these dynamic changes in the N100m dipole reflect short-term plastic changes in the primary auditory cortex, supporting early selection models., Significance: This work is the first to disclose short-term plastic changes during pitch discrimination in the human auditory cortex based on the analysis of magnetoencephalography.

The nutritional benefits of nucleoprotamine (NP), the main component of fish soft roe, have been rarely addressed. In the present study, the preventive effect of oral supplements of nucleoprotamine and its derivatives, DNA and protamine (PT), extracted from salmon soft roe, on survival rate and hippocampal cell death induced by transient brain ischemia, was evaluated in mice. Artificially formulated nucleoprotamine-free (NF) diet with/without nucleoprotamine, DNA or protamine was fed orally. One week after commencement of respective diets, animals were subjected to transient brain ischemia, which was performed by common carotid artery (CCA) occlusion for 25 (severe) or 15 min (mild). After severe ischemia, the survival rate of the NF group was lower than that in the group fed standard diet or NP. Morphological changes in the hippocampal CA1 region were estimated 48 h after mild ischemia. The NP and PT groups significantly decreased the neuronal damage compared with the NF group. The number of cell death in the DNA group, however, was affected similar to that of the NF group. Our data suggests that the nucleoprotamine content in salmon soft roe could be a useful nutritional resource for the prevention of cell damage caused by ischemia such as those occurring with cerebral and/or heart infarction.

In the present study, a dialytic method that uses a DNA aqueous solution to remove and enrich dioxins from polluted water was proposed. Circular dichroism (CD) and fluorescent spectra indicated that dibenzo-p-dioxin (DD), dibenzofuran (DF) and biphenyl (BP), which are dioxin derivatives, form complexes with DNA. Their experimental dialytic sorption coefficients were measured by quantifying the concentrations of DD, DF, and BP in aqueous solutions before and after dialysis of the DNA solution, and the values were 2.1x10(5), 1.3x10(5), and 1.5x10(7), respectively. As a simulated water treatment model, DNA solution was dialyzed in an aqueous mixture of DD, DF, and BP for 96h, the HPLC studies showed that the dioxin derivatives have been concentrated in the DNA solution about 200 times. The dialyzed DNA solution was reusable by an extraction with hexane.

Objective: To investigate spatiotemporal features of the isofrequency bands for 400 and 4000 Hz tones in human auditory cortex and on the hemispheric differences in the arrangement of isofrequency bands., Methods: We recorded auditory evoked magnetic fields (AEFs) to 400 or 4000 Hz tone pips presented at right or left ear from 31 normal subjects. The dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear., Results: In the right hemisphere, the current sources for 400 and 4000 Hz moved toward the anterolateral direction before the N100m peak, showing parallel arrangement of the isofrequency bands (4000 Hz in medial location). In the left hemisphere, the movement direction of 400 Hz dipoles was anterolateral, while that of 4000 Hz dipoles was lateral., Conclusions: This difference in the organization of isofrequency bands between right and left auditory cortices reflects distinct functional roles in auditory information processing such as pitch vs. language discrimination., Significance: This work is the first to disclose isofrequency bands in human auditory cortex based on the analysis of magnetoencephalography.

Background: The postoperative opioid-sparing effects of systemic L-type calcium channel blockers are controversial. We investigated whether the postoperative analgesic effect of epidural fentanyl was enhanced by i.v. infusion of diltiazem at a rate that would minimize any cardiovascular depressant effect., Methods: After elective lower abdominal gynaecological surgery, 30 patients were randomized to receive continuous i.v. diltiazem 1 micro g kg(-1) min(-1) (diltiazem group) or the same volume of saline (control group) for 24 h. Cumulative postoperative epidural fentanyl consumption, visual analogue scale (VAS) scores and verbal rating scores (VRS) at rest and during mobilization, sedation scores, incidence of side-effects and overall patient satisfaction were assessed., Results: There was no significant difference in cumulative epidural fentanyl consumption between the groups at any period. Although there were no statistically significant differences in VAS scores, VRS, sedation scores, incidence of side-effects and overall patient satisfaction, there was a trend to an increased incidence of nausea in the diltiazem group., Conclusions: Continuous i.v. infusion of diltiazem did not reduce epidural fentanyl consumption when administered at dosages having minimal haemodynamic depressant effects.

Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clear this central issue, mice that were gene deficient in IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1-h transient middle cerebral artery occlusion (tMCAO). Expression levels of IL-1beta and IL-1 receptor I (IL-1RI) were then examined. Generation of peroxynitrite and the expression of mRNAs for nitric oxide synthase (NOS) subtypes were also determined. Immunostaining for IL-1beta was increased from 6 h and peaked at 24 h after tMCAO in the microglia and macrophage. The immunoreactivities of IL-1RI were increased progressively in the microvasculature and neuron-like cells of the ipsilateral hemisphere. Infarct volumes were significantly lower in IL-1 KO mice compared with wild-type mice 48 h after tMCAO (P<0.01). The immunoreactivities of 3-nitro-L-tyrosine were determined in the neurons and microvasculature 24 h after tMCAO and were significantly decreased in the IL-1 KO mice compared to wild-type mice. In addition, expression levels of NOS mRNA in IL-1 KO mice were lower than that measured in wild-type mice. These results indicate that IL-1 is up-regulated and may play a role in neurodegeneration by peroxynitrite production during ischemia.

Two novel haplotypes of CYP2D6 were found in Japanese subjects. One haplotype of the human CYP2D6 gene, newly designated as CYP2D6(*)44 allele, had both a novel single nucleotide polymorphism (SNP) of 2950G>C in intron 6 donor splice junction and a known SNP (82CG, -1235A>G, -740C>T, -678G>A, and a gene conversion with CYP2D7 gene in intron 1 associated with CYP2D6(*)21. Both CYP2D6(*)44 and CYP2D6(*)21B alleles would cause a splicing error or a frameshift with impaired drug metabolizing function mediated by CYP2D6.

Premature infants often present metabolic acidosis without protein load in the early neonatal period, around days 4-6. In order to elucidate the cause of acidosis, we investigated urinary acidification of infants in the early neonatal period. Urine pH, fractional excretion of HCO(3)(-) (FEHCO(3)), excretion of HCO(3)(-) and NH(4)(+) of the appropriate-for-date infants were measured on days 0-2 and on days 4-6 of life. Extremely low birth weight (ELBW) infants showed higher urine pH than more than 1500 g birth weight infants. FEHCO(3) and HCO(3)(-) excretion were of high values in ELBW infants on days 0-2, but decreased on days 4-6. Urine NH(4)(+) excretion rate was lower in ELBW infants than in birth weight more than 1000 g on days 0-2 of life and still remained at a low rate on days 4-6. These data indicated that insufficiency of NH(4)(+) excretion is the main cause for metabolic acidosis of ELBW infants in the early neonatal period.

To elucidate the relevance of metabotropic glutamate receptors (mGluRs) to the selective vulnerability of motor neurons in the spinal cord in patients with amyotrophic lateral sclerosis (ALS), we investigated the distribution of mRNAs coding mGluR1-5 in the normal human spinal cord. The mRNAs for mGluR1, 4 and 5 were observed in the spinal gray matter, whereas mGluR2 mRNA was absent in the spinal cord and mGluR3 mRNA was displayed only on glial cells in the white matter. Signals for mGluR1 and mGluR5 were enriched in the dorsal horn, while mGluR4 mRNA was abundant in the ventral horn. Since agonists to group I mGluRs (mGluR 1 and 5) have been demonstrated to have neuroprotective effects on spinal motor neurons, less expression of mRNAs coding mGluR1 and mGluR5 in the ventral horn than in the dorsal horn may be implicated in the selective susceptibility of spinal motor neurons in ALS.

Objectives: To investigate effects of aging on peripheral and central somatosensory conduction, and evaluate onset-to-onset and peak-to-peak measurements of each component and central conduction time (CCT) in somatosensory evoked potentials (SEPs)., Methods: We recorded SEPs with non-cephalic reference from the Erb's point, the posterior (cv 6) and anterior neck, and scalp (Fz and P4) after left median nerve stimulation in 138 normal subjects aged between 20 and 78 years. We determined onset or peak latencies of the Erb's potential (N9), the spinal N13-P13 in cv 6-to-anterior neck montage and the N20-P20 in scalp leads. Onset CCT was defined as a transit time from N13-P13 onset to N20-P20 onset. In each subject, interpeak latencies of the 'N13' component in cv 6-to-Fz montage and the N20-P20 in P4-to-Fz montage were also defined as conventional peak CCT., Results: Using multiregression analysis, we found that the onset or peak latencies of each SEP component were correlated with the subject's height and age. So were the onset CCTs: Onset CCT (in ms) = 2.549+2.041x(height in meters) + 0.005 x (age in years) (P<0.0001). The conventional peak CCTs as well as onset-to-peak durations of the N20-P20 were correlated with the subject's age but not height: Peak CCT(in ms) = 5.458+0.012x (age in years) (P<0.0005)., Conclusion: Conductive function is affected by normal aging in the central as well as peripheral somatosensory pathways. The peak CCT is more affected by aging than the onset CCT. However, the onset-to-peak duration of the N20-P20 increased by 0.8 ms between the 4th and 7th decades, suggesting that the peak CCT increase in older people reflects the age-related changes in N20-P20 profile but not in the fastest central conduction. We therefore conclude that the onset CCT measurement is preferable to the peak CCT measurement when assessing the central somatosensory conduction.

Objective: To evaluate the characteristics of high frequency (HF) components of the early cortical somatosensory evoked potentials (SEPs)., Methods: We recorded 8-channel SEPs from the frontal and left centro-parietal scalp after right median nerve stimulation with a wide band-pass (0.5-2000 Hz) and digitized at 40 kHz sampling rate in 12 healthy subjects. HF components were analyzed after digital band-pass filtering (300-1000 Hz). The power spectrum was obtained by a maximum entropy method., Results: HF oscillations (maximum power at 600-800 Hz) consisting of 5 to 8 peaks were discriminated from the preceding P14 far-field in all cases and their phases were reversed between the frontal and contralateral parietal regions. In addition, in subjects with a high amplitude central P22 potential in original wide-band recordings, a single HF oscillation with a maximum at the central region was present. Furthermore, this component showed no phase reversal over the centro-parietal area., Conclusion: We therefore conclude that HF oscillations are superimposed not only on the tangential N20-P20 but on the radial P22 potential, and are generated from both tangential (area 3b) and radial (area 1) current sources.

Cos 7 cells transfected with human atrial natriuretic polypeptide (hANP) gene with SV40 enhancer and replication origin sequences expressed hANP gene. The expressed RNA was indistinguishable from native hANP mRNA and the transcribed protein seemed to be properly processed to alpha-hANP and beta-hANP. This system provides a useful approach to investigate the processing of hANPs and the structure-function relationship of amino acid sequences of hANPs.

To investigate whether the human atrial natriuretic polypeptide (hANP) gene is responsive to glucocorticoid, we co-introduced the hANP gene (with SV40 enhancer) with HSV-tk gene into mouse tk- L cells. The transformants with hANP gene with SV40 enhancer expressed hANP specific RNAs. The administration of 1 microM dexamethasone reduced the expressed hANP specific RNAs, especially those that had a physiological initiation site. These results suggest that the hANP gene is really a glucocorticoid responsive gene and may be negatively regulated by glucocorticoid.

Reexamination of conditions for processing and storing blood for plasma renin assay confirmed that plasma can be stored at -20 degrees C for at least 4 weeks without significant changes in active renin level. The active renin concentration is increased by storage at 4 degrees C because of conversion from inactive renin.

Angiotensin converting enzyme (ACE) of vascular endothelial cells is suggested to control vascular wall tonus through the conversion of angiotensin I (AI) to angiotensin II (AII) and the degradation of bradykinin. To obtain more insight into the pathophysiological significance of ACE of vascular endothelial cells, we studied the regulation of ACE produced by cultured human umbilical vein endothelial cells (EC). Phorbol 12-myristate 13-acetate (PMA) increased the cellular and medium ACE activity, accompanied by a marked morphological change in EC. N'-O'-dibutylyladenosine 3';5'-cyclic monophosphate (db-cAMP) increased only the cellular ACE activity and not the medium ACE activity. The effect of isoproterenol with 0.1mM theophylline mimicked that of db-cAMP. These findings suggest that PMA and cAMP-related agents participate in the control of vascular wall tonus through the positive regulation of ACE produced by vascular endothelial cells.

Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL.

Thirty adult male Wister rats were pretrained to criterion on the moving belt test, and then made tolerant to ethanol by daily administration of increasing doses over a period of 3 weeks. After a one-month recovery period, they were divided into 3 groups, subjected to bilateral frontal polar cortical ablations, sham-operation and no operation respectively. After postoperative recovery, the cycle of ethanol treatment and testing was repeated. Only the lesioned group failed to reacquire tolerance. A pilot experiment showed that occipital cortical ablations also prevented tolerance. In a second experiment 32 rats, which had similarly undergone and then recovered from an initial period of ethanol tolerance, were divided into 4 groups which received daily treatment with sucrose plus cycloheximide (0.3 mg/kg), sucrose plus saline, ethanol plus cycloheximide, and ethanol plus saline respectively. Only the ethanol plus saline group re-acquired tolerance. Tt is concluded that frontal polar cortical lesions and cycloheximide can both block the development of tolerance to ethanol in animals previously shown to be capable of developing such tolerance.