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Objectives　This study aimed to develop scales for evaluating the level of implementation of community practices and explore the perception of public health nurses in municipalities regarding their community practices.Methods　Draft scales were developed based on a literature review and interviews with municipal public health nurses. Subsequently, a questionnaire survey was conducted with municipal public health nurses across Japan in response to these draft scales. Respondents were recruited based on the municipality population size. Questionnaires were distributed to 2,074 individuals from 52 municipalities ensuring representation from diverse municipalities. Exploratory factor analysis was performed to determine the number of factors, while confirmatory factor analysis was performed to determine the factor structure. The reliability of the scales was assessed by calculating Cronbach's alpha coefficients, and their validity was tested by examining correlations with existing scales, namely the Moral Competence Scale for Public Health Nurses and the Professional Identity Scale for Public Health Nurses, and years of experience as a public health nurse.Results　A total of 721 (34.8%) valid respondents were included in the analysis. Three scales, methods of community practices (three factors, nine items), perceptions of public health nurses toward community residents through community practices (three factors, 10 items), and organizational environment supporting community practices (two factors, 11 items) were developed as indicators of the implementation of public health nurses' community practices. Cronbach's alpha coefficients for the three scales were 0.896, 0.913, and 0.868, respectively. As hypothesized, each subfactor exhibited a positive correlation with the existing scales. However, certain subfactors did not demonstrate any correlation with years of experience.Conclusion　The three scales developed in this study were individually examined for reliability and validity. These scales can be used independently or in combination, allowing public health nurses to select the most suitable scale(s) based on their objective.　A notable contribution of this study is the establishment of concrete indicators for evaluating community practices, addressing the previously vague nature of this evaluation. By incorporating the scale items into daily health practices, we anticipate that these indicators can be employed to evaluate community practices at the organizational and individual levels.

Cervical cancer is prevalent among women, with a reported 604,127 cases in 2020 worldwide. The incidence of cervical cancer has been mitigated in most high-income countries by promoting the human papilloma virus (HPV) vaccine. However, in Japan, cervical cancer is still a leading cause of mortality and the most prevalent cancer among women aged between 15 and 39. This can be attributed to the 7-year suspension of HPV vaccination recommendations by the Japanese government. A decline in vaccination coverage followed this suspension, caused by a small number of reported adverse events, resulting in a steep decline in vaccination coverage from over 70% to less than 1%. However, there have been indications of a change in trend in Japan. In 2020, a group of volunteer doctors initiated awareness-raising activities through social networking services and other platforms, and the target population that received at least one dose of the vaccine in 2020 increased to 15.9%. Additionally, in July 2020, the Japanese government approved the updated 9-valent HPV vaccine and resumed recommendations in November 2021. As a result, 30.1% of those eligible for routine HPV vaccination received at least one dose of the vaccine from April to September, 2022. However, the HPV vaccine coverage in Japan is still far from the 90% recommended by the World Health Organization, and continued communication and education on the vaccines benefits are necessary to achieve optimal coverage., Competing Interests: Dr. Tanimoto reported personal fees from Medical Network Systems Inc. and Bionics co. ltd., outside the submitted work. No other disclosures were reported., (2023, National Center for Global Health and Medicine.)

Objectives　The purpose of this study was to define the terminology used in community health activities by systematically establishing agreement among public health nurses and related professionals, to aid them in effectively cooperating with other professionals.Methods　We extracted the major terms described in "Guidelines for Public Health Nurses' Activities in the Region," which was issued by the Director of Health Bureau, Ministry of Health, Labor and Welfare; and conducted 2 iterations on the proposed definition of the terms using the Delphi method. The survey targeted 800 stakeholders from the following 4 professions: public health nurses in managerial positions in local governments, clerical staff in local governments, public health nursing professors at educational institutions, and social welfare council staff. Respondents indicated their degree of agreement with the definition of the terms using a 4-point Likert scale. We tallied the answers indicating "I agree" or "Mostly agree." A 70% term agreement was considered "conformed." A free text box for each proposed definition was also available so that respondents could share their opinions and offer alternatives.Results　The first survey received 231 responses. The conformity of their definitions ranged from 83.9%-96.9% (mean=91.5%). Although all definitions exceeded the consensus level, we examined their adequacy with reference to the definitions and opinions from the free text. Various opinions were obtained from those engaged in each occupation. The second round included 117 consenting stakeholders from the first survey, yielding 90 responses. Their degree of conformity ranged from 86.7%-98.9% (mean=94.6%). Therefore, we determined the definitions had reached a robust agreement. We revised the definitions of some terms with reference to the opinions from the free texts and finalized the definitions. Finally, we defined 23 terms-such as region, community diagnosis, and policy.Conclusion　All terms had a conformity of more than 85%, thus bringing into alignment those community health terms that had varying interpretations among related occupations earlier. By including the opinions of those from the related occupations who collaborate with public health nurses, the definitions of these terms could be established and shared. These definitions can be used in public health nursing practice, education, service, and research-among those in involved these related occupations.

In this study, we aimed to investigate the standard method used for quantification of norovirus in oysters in Japan for the provisional adaptation of the method as an alternative to ISO 15216-1:2017, to conduct a Japan baseline survey of norovirus in oysters. For this purpose, the method provided by the Japan Committee for Standardization of Virus Detection in Food was subjected to an interlaboratory study to determine the performance characteristics of the standard method used in Japan. As a result, the theoretical limit of quantification for norovirus GI and GII in oysters by the standard method used in Japan was expected to be 1.92 and 1.85 log 10 copies/g, respectively. The repeatability standard deviations (S r ) were 0.26 and 0.30 log 10 copies/g for GI and GII, respectively, and the reproducibility standard deviations (S R ) were 0.47 and 0.44 log 10 copies/g for GI and GII, respectively. Through the interlaboratory study, we specified several critical points to obtain scientifically reliable results by using the standard method used in Japan. Especially, necessity for application of using process control virus was the most crucial point that needed to be improved. In addition, there are many participating laboratories that could not handle dilution of standard and quantify or detect the viruses in the test samples. To ensure scientifically reliable test result, capacity building of laboratories and implementation of proficiency testing should be considered for future tasks in combination with an application of process control materials in the method. On the assumption that the problems revealed in this study will be solved, the standard method used in Japan would be suitable for use in Japan baseline survey of norovirus in oysters, which will contribute to the international action against norovirus in oysters, led by the EU.

Objective: This study identified the radiological content required for PHNs and public health nursing students based on PHNs' experiences caring for people affected by the 2011 Fukushima Daiichi nuclear power plant accident., Design: We used qualitative research, interviews, and content analysis., Sample: Participants were eight PHNs employed by local governments in Fukushima and neighboring prefectures., Results: Six content themes regarding the nuclear disaster were identified: (a) basic knowledge about radiation, (b) public health nursing activities in emergency exposure situations, (c) management in emergency exposure situations, (d) consultation to support residents affected by the nuclear disaster, (e) activities in the existing exposure situations, and (f) disaster preparedness in the planned exposure situations. Necessary content shifted depending on the phase of the nuclear disaster recovery., Conclusions: The use of the experiences of PHNs after the nuclear power plant accident to inform PHNs and public health nursing students will enable PHNs to respond appropriately and support people without difficulties. Comprehensive radiation content is needed to address the range of situations caused by nuclear disaster., (© 2020 Wiley Periodicals, Inc.)

Background: Previous studies on etiology of autism spectrum disorders (ASD) have shown strong contribution of hereditary factors. On the basis the heterogeneity in ASD symptoms, it is highly possible that each independent domain of ASD symptom is linked to a different set of genetic risk factors. However, few empirical investigations have been carried out to examine this hypothesis., Aims: The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in estrogen receptor genes, which several previous studies have identified as potential risk factors of ASD, and the severity of each independent aspect of ASD symptom within an Asian clinical sample., Method and Procedures: We investigated the association between severities of four ASD symptoms (Social Communication, Social Interaction, Stereotypies and Sensory Abnormalities, and Emotional Regulation) measured by childhood autism rating scale and SNPs in genes of estrogen receptor 1 and 2, ESR1 rs11155819 and ESR2 rs1152582, in 96 Japanese individuals with ASD., Outcomes and Results: The analysis revealed that severities in the impairment of social interaction and emotional regulation were linked to SNPs in ESR1 rs11155819 and ESR2 rs1152582, respectively. The effect of genotype was not observed for the other aspects of ASD symptoms., Conclusions and Implications: These findings support our contention that the severity of each ASD symptom domain is determined by a distinct set of genetic risk factors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The contamination of oysters with human norovirus (HuNoV) poses a human health risk, as oysters are often consumed raw. In this study, the effect of high pressure processing (HPP) on a wide variety of HuNoVs naturally present in aqua-cultured Japanese oysters was determined through a polymerase chain reaction-based method with enzymatic pretreatment, to distinguish between infectious HuNoV. Among five batches, genogroup I. genotype 1 (GI.1), GI.2, GI.3, and GI.8 HuNoV were detected from only one oyster not treated with HPP in the fifth batch, while genogroup II. genotype 1 to 4 (GII.1 to 4), GII.6, GII.8., GII.9, GII.13, GII.16, GII.17, and GII.22 HuNoV were detected from oysters not treated with HPP in all tested batches as determined by next-generation sequencing analysis. Neither GI nor GII HuNoV was detected in the oysters of any of the batches after HPP treatment. To our knowledge, this is the first study to investigate the effect of HPP on a wide variety of HuNoVs naturally present in aqua-cultured oysters.

Background: Delirium is known to be a poor prognostic factor in patients with acute decompensated heart failure (ADHF). The purpose of this study was to determine predictors of delirium on admission of ADHF patients, and to establish a scoring formula to identify patients at high risk for delirium., Methods and Results: We recorded the Intensive Care Delirium Screening Checklist (ICDSC) score in 120 ADHF patients during their stay in the coronary care unit (CCU). Patients with a highest ICDSC score of 4 or more were diagnosed with delirium. We examined independent candidate predictors of delirium using multivariate logistic regression analysis and developed the following scoring formula, the delirium prediction score (DPS), using independent predictors of delirium and their regression coefficients: DPS=inferior vena cava diameter+C-reactive protein (and additionally +10 for patients with a history of cerebral infarction). Receiver operating curve analysis indicated that evaluation using this scoring system at the time of admission was able to predict delirium with high accuracy (C-statistic: 0.885). In addition, the calculated scores had significantly positive correlations with duration of CCU stay and overall length of hospital stay., Conclusions: We established a novel scoring system to predict on admission the likelihood of development of delirium in ADHF patients; this system also predicts prolongation of intensive care and hospital stay., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives This study aimed to validate the function of community activities for mothers and examine the constructions of these functions. The relationships between these functions and the antecedent factors of mothers and community activity forms were investigated as well.Method Several items were selected, in accordance with a conceptual framework determined by a preliminary investigation, to measure the function of community activities, mothers' antecedent factors, and community activity forms. The target group was mothers of infants living in metropolitan areas who participated in community activities. The validity and reliability of the Community Activity Function Evaluation Scale for Mothers (CAFES), which includes five subscales, were examined by confirmatory factor analysis and Cronbach's reliability coefficient. Covariance structure analysis was also carried out. The construction of the five subscales was examined, and the relationships between the five functions, mothers' antecedent factors, and community activity forms were validated.Results Of the 405 responses (36.8% response rate), 379 (93.5%) were eligible for analysis. Confirmatory factor analysis confirmed the goodness of fit and reliability of the five subscales model. The five functions were correlated, per covariance structure analysis (CFI=0.858, RMSEA=0.060). Multiple regression analysis validated the relationships between the activity functions and mothers' antecedent factors and activity forms.Conclusion The community activities measured by CAFES worked mutually and were interrelated. The five activity functions showed relationships with mothers' antecedent factors (participation>10 times) and activity forms (mothers participate in half-day activities as administrators). Further studies are required in diverse community groups to refine CAFES for generalized use.

Exposure to environmental chemicals, such as dioxin, is known to have adverse effects on the homeostasis of gonadal steroids, thereby potentially altering the sexual differentiation of the brain to express autistic traits. Dioxin-like chemicals act on the aryl hydrocarbon receptor (AhR), polymorphisms, and mutations of AhR -related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship between AhR -related gene polymorphisms and autism susceptibility, we identified genotypes of them in patients and controls and determined whether there are different gene and genotype distributions between both groups. In addition, to clarify the relationships between the polymorphisms and the severity of autism, we compared the two genotypes of AhR -related genes (rs2066853, rs2228099) with the severity of autistic symptoms. Although no statistically significant difference was found between autism spectrum disorder (ASD) patients and control individuals for the genotypic distribution of any of the polymorphisms studied herein, a significant difference in the total score of severity was observed in rs2228099 polymorphism, suggesting that the polymorphism modifies the severity of ASD symptoms but not ASD susceptibility. Moreover, we found that a significant difference in the social communication score of severity was observed. These results suggest that the rs2228099 polymorphism is possibly associated with the severity of social communication impairment among the diverse ASD symptoms.

Purpose: Beta-defensins (BDs) and dendritic cells (DC) have been described as major effectors on host antimicrobial innate immunities. In the present study, the ability of DC to produce BDs was explored using DC from normal mice and full-thickness (FT)-burned mice., Methods: DCs were isolated from spleens of mice, and 1 × 10(6) cells/ml of them were cultured with LPS or SAC. Culture fluids harvested 24 h after cultivation were assayed for BD1 and BD3 and antibacterial activity (colony-counting, Pseudomonas aeruginosa). Also, DCs were tested for BD mRNAs by RT-PCR., Results: Sixty-five percent of the bacterial killing activity was shown by the culture fluids of splenic DC from normal mice, while only 15 % killing activity was shown by the culture fluids of splenic DC from FT-burned mice. X-irradiated NOD SCID IL-2rγ(null) mice inoculated with splenic DC from FT-burned mice showed increased susceptibility to P. aeruginosa infection compared to those from normal mice. Mice splenic DC expressed BD1 mRNA constitutively and expressed BD3 mRNA after stimulation. These BDs were produced by mice splenic DC. As compared with DC from normal mice, DC from FT-burned mice produced decreased amounts of BD1 and BD3 in their culture fluids., Conclusions: These results indicate that (1) DC from spleens of mice have an ability to produce BDs, and (2) the production of BDs by DC is influenced strongly by thermally injured stress. Since FT-burned mice are susceptible to P. aeruginosa infection, BDs produced by DC may play an important role on the host's antibacterial resistance.

Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed.

Introduction: The number and proportion of elderly persons in the general population have been increasing. Inevitably, the incidence of colorectal carcinoma has also increased. Although substantial evidence indicates that surgery is well tolerated in patients 80 years or older, studies in nonagenarians are not well documented., Methods: Consecutive nonagenarians and octogenarians who underwent elective laparoscopic-assisted colectomy (LAC) from September 2009 through October 2011 were studied. Data on medical history, ASA score, details of operations, and postoperative events were collected., Results: LAC was performed in nine nonagenarians and seven octogenarians. There were no complications related to laparoscopy. No patient required conversion from LAC to an open procedure or died postoperatively. Peristalsis was confirmed and oral intake was initiated on postoperative days 2.6 and 2.7, respectively., Conclusions: Laparoscopic surgery is considered an extremely useful treatment for very old patients because it has a low risk of postoperative complications, even in the presence of pre-existing diseases. We conclude that LAC may be indicated in nonagenarians., (© 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Cardiac surgery with cardiopulmonary bypass is associated with the development of a systemic inflammatory response that can often lead to dysfunction of major organs. We hypothesised that the highly selective α2-adrenergic agonist, dexmedetomidine, attenuates the systemic inflammatory response. Forty-two patients were randomly assigned to receive dexmedetomidine or saline after aortic cross-clamping). The mean (SD) levels of the nuclear protein plasma high-mobility group box 1 increased significantly from 5.1 (2.2) ng ml(-1) during (16.6 (7.3) ng ml(-1) ) and after (14.3 (8.2) ng ml(-1) ) cardiopulmonary bypass in the saline group. In the dexmedetomidine group, the levels increased significantly only during cardiopulmonary bypass (4.0 (1.9) ng ml(-1) baseline vs. 10.8 (2.7) ng ml(-1) ) but not after (7.4 (3.8) ng ml(-1) ). Dexmedetomidine infusion also suppressed the rise in mean (SD) interleukin-6 levels after cardiopulmonary bypass (a rise of 124.5 (72.0) pg ml(-1) vs. 65.3 (30.9) pg ml(-1)). These suppressive effects of dexmedetomidine might be due to the inhibition of nuclear factor kappa B activation and suggest that intra-operative dexmedetomidine may beneficially inhibit inflammatory responses associated with ischaemia-reperfusion injury during cardiopulmonary bypass., (© 2014 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Heatstroke is a life-threatening illness and causes high mortality due to multiple organ injuries. Thrombomodulin (TM) is an endothelial anticoagulant cofactor that plays an important role in the regulation of intravascular coagulation. In this study, we investigated the effect of TM on the inflammatory process, liver function, coagulation status, and mortality in experimental heatstroke., Methods: Male C3H/HeN (8-10 weeks) mice were randomly assigned to the TM-treated group (TG-Pre) or nontreated heatstroke group (HS). In group TG-Pre, mice were treated with recombinant soluble TM (1 mg/kg, intraperitoneally) before heat exposure. In some experiments, recombinant soluble TM was administrated during heat exposure (TG-Delay). Heatstroke was induced by exposure to ambient temperature of 38°C for 4 hours. After heat exposure, the levels of tumor necrosis factor-α, interleukin-6, and plasma high-mobility group box 1 (HMGB1), liver function, plasma aspartate aminotransferase and alanine aminotransferase concentrations, and immunohistochemical and histopathological characteristics of the livers were determined. The coagulation status, plasma protein C levels, and thrombin-antithrombin complex levels were also measured., Results: In group HS, plasma cytokines and HMGB1 concentrations increased after heat exposure. Plasma aspartate aminotransferase and alanine aminotransferase concentrations increased after heat exposure. In group HS livers, strong and extensive immunostaining for HMGB1 was observed. In addition, there was extensive hepatocellular necrosis and collapse of nuclei observed. In group HS, plasma protein C levels were suppressed and plasma thrombin-antithrombin complex levels increased. In group TG-Pre, plasma cytokines and HMGB1 concentrations were suppressed after heat exposure compared with group HS. Liver injury, coagulopathy, and mortality also improved in group TG-Pre. Furthermore, recombinant soluble TM treatment decreased mortality even with delayed treatment., Conclusions: This study demonstrated that recombinant soluble TM suppressed plasma cytokines and HMGB1 concentrations after heat exposure. Recombinant soluble TM also improved liver injury and coagulopathy. Recombinant soluble TM treatment improved mortality even with delayed treatment. Recombinant soluble TM may be a beneficial treatment for heatstroke patients.

Background: It has been demonstrated that proinflammatory mediators increase in patients with sepsis, trauma, and burns. These mediators are associated with the development of septic shock and organ dysfunction. Dexmedetomidine (DEX), a selective agonist of the α2-adrenergic receptors, is used in intensive care units for sedation. However, it still remains unclear whether DEX administration has any effects on the production of proinflammatory mediators. In this study, we investigated the effects of DEX on lipopolysaccharide (LPS)-induced production of tumor necrosis factor α, interleukin 6 (IL-6), IL-8, and high-mobility group box 1 protein in human whole blood., Methods: Human whole blood was cultured with LPS for up to 24 hours, and LPS-induced proinflammatory mediator production was measured. Next, we tested the effect of DEX on whole blood proinflammatory mediator production. Human whole blood was cultured with LPS and various concentrations of DEX for 12 hours. Then, we investigated the influence of yohimbine, an antagonist of the α2-adrenergic receptors, on the effects of DEX. The effect of DEX on necrosis factor κB (NFκB) activation was also investigated., Results: DEX suppressed tumor necrosis factor α, IL-6, IL-8, and high-mobility group box 1 protein production in human whole blood. The suppressing effects of DEX on proinflammatory mediator production were reversed by yohimbine. The results suggested that the mechanism for the suppressive effects of DEX on proinflammatory mediator production is meditated via α2-adrenergic receptors. These effects of DEX also include an inhibitory effect on NFκB activation., Conclusion: We demonstrate the suppressing effect of DEX on inflammatory mediator production in human whole blood after LPS stimulation. The mechanism for the suppressive effect of DEX on proinflammatory mediator production may be through the α2-adrenergic receptors and NFκB inhibition.

We previously demonstrated that long-term pretreatment of rat FRTL-5 thyroid cells with TSH or cAMP-generating reagents potentiated IGF-I-dependent DNA synthesis. Under these conditions, cAMP treatment increased tyrosine phosphorylation of a 125-kDa protein (p125) and its association with a p85 regulatory subunit of phosphatidylinositol 3-kinase (p85 PI3K), which were suggested to mediate potentiation of DNA synthesis. This study was undertaken to identify p125 and to elucidate its roles in potentiation of DNA synthesis induced by IGF-I. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis revealed p125 to be a rat ortholog of human XB130, which we named PI3K-associated protein (PI3KAP). cAMP treatment elevated PI3KAP/XB130 mRNA and protein levels as well as tyrosine phosphorylation and interaction with p85 PI3K leading to increased PI3K activities associated with PI3KAP/XB130, supporting the role of PI3KAP/XB130 in DNA synthesis potentiation. Importantly, PI3KAP/XB130 knockdown attenuated cAMP-dependent potentiation of IGF-I-induced DNA synthesis. Furthermore, c-Src was associated with PI3KAP/XB130 and was activated in response to cAMP. Addition of Src family kinase inhibitors, PP1 or PP2, during cAMP treatment abolished tyrosine phosphorylation of PI3KAP/XB130 and its interaction with p85 PI3K. Finally, introduction of PI3KAP/XB130 into NIH3T3 fibroblasts lacking endogenous PI3KAP/XB130 enhanced IGF-I-induced DNA synthesis; however, a mutant Y72F incapable of binding to p85 PI3K did not show this response. Together, these data indicate that cAMP-dependent induction of PI3KAP/XB130, which is associated with PI3K, is required for enhancement of IGF mitogenic activities.

Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with dementia. Current pharmacological approaches to treatment are inadequate, despite the availability of serotonergic agents to ameliorate anxiety, one of the symptoms of BPSD. The herbal medicine yokukansan has been demonstrated to improve BPSD in a randomized, single-blinded, placebo-controlled study. However, the mechanisms of the anxiolytic effect of yokukansan have not been clarified. There are also no reports on the anxiolytic effect of yokukansan in cerebrovascular ischemia models. In this study, we examined whether rats subjected to repeated cerebral ischemia exhibited anxiety-like behavior in a plus-maze task, a light/dark box test and an open-field task. We then investigated the effect of yokukansan on anxiety-like behavior in ischemic rats. Repeated ischemia was induced by the four-vessel occlusion method in which a 10-min ischemic episode was repeated once after 60 min. Yokukansan was orally administered once a day for 14 days from 7 days before ischemia induction. The last administration was performed 1 h before the behavioral experiments. The ischemic rats showed anxiety-like behavior in all three tasks, suggesting that this rat may be a good model for anxiety in cerebrovascular dementia. Yokukansan exhibited anxiolytic effects on the anxiety-like behavior in rats subjected to repeated cerebral ischemia, and exerted antagonistic effects on the wet-dog shakes induced by 1-(2,5-dimethoxy-4-indophenyl)-2-amino propane, a serotonin receptor (5-HT(2A)) agonist. This study revealed that yokukansan shows anxiolytic effects not only in normal animals but also in cerebrovascular model rats.

Background: The gastrointestinal mucosa is an important route of entry for microbial pathogens. The immune cells of Peyer's patch (PP) compartments contribute to the active immune response against infection. Although local anesthetics are widely used in clinical practice, it remains unclear whether local anesthetics such as lidocaine affect PP T cell functions., Methods: The aim of this study was to examine if lidocaine has any effects on mouse PP T cell functions. To test this, freshly isolated mouse Peyer's patch T cells were incubated with lidocaine. The effects of lidocaine on concanavalin A-stimulated PP T cell proliferation and cytokine production were assessed. The effect of lidocaine on PP T cell mitogen-activated protein kinase (MAPK) activation was also assessed., Results: The results indicate that lidocaine suppresses cell proliferation, cytokine production, and MAPK activation in PP T cells. Furthermore, we found that the chronic in vivo exposure to lidocaine increases bacterial accumulation in PP., Conclusion: The enhanced immunosuppressive effects of lidocaine on PP T cell functions could contribute to the host's enhanced susceptibility to infection., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Citidine-5-diphosphocholine or citicoline (CDP-choline) is used as a neuroprotective and memory-enhancing drug in cerebral stroke, Alzheimer's disease, and other neurovascular diseases. Non-clinical studies have demonstrated the neuroprotective effects of CDP-choline in ischemic animal models. However, the relationship between the neuroprotective effect and the memory enhancing effect of CDP-choline is still unknown. No studies have demonstrated the ameliorative effect on impaired spatial memory and the suppressive effect on neuronal cell death of CDP-choline in the same model. In this study, we examined the effect of CDP-choline on impaired spatial memory and hippocampal CA1 neuronal death in rats subjected to repeated cerebral ischemia, and we compared the mechanism of CDP-choline to that of donepezil. Seven days post administration of CDP-choline (100, 300, 1000 mg/kg per day, p.o.) or donepezil increased correct choices and reduced error choices in an eight-arm radial maze task in a dose-dependent manner. Neuronal cell death of caspase-3 protein-positive neurons in the hippocampus were reduced by repeated administration of CDP-choline at the highest dose. These results suggest that CDP-choline has ameliorative effects on the impairment of spatial memory via hippocampal neuronal cell death in a rat model of cerebral ischemia.

Silver particles (Ag particles) were synthesized by the photoreduction of silver perchlorate (AgClO(4)) in water-in-ionic liquid (IL) microemulsions consisting of nonionic surfactant Tween 20, water, and ionic liquids, [1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF(4)]) or 1-octyl-3-methylimidazolium tetrafluoroborate ([OMIm][BF(4)])], mixed with a high-pressure (25 MPa) CO(2). The time evolution of the Ag particle formation by photoreduction was investigated by UV-Vis, cryo-TEM, extended X-ray absorption fine structure (EXAFS), and small-angle X-ray scattering (SAXS) measurements. In the particle formation process, aggregation and precipitation of Ag particles were suppressed under high-pressure CO(2). The average diameters of the metallic Ag particles prepared in water-in-[BMIm][BF(4)] and water-in-[OMIm][BF(4)] microemulsions were estimated from TEM to be 3.2 and 3.7 nm, respectively. SAXS analysis shows that the average diameters of the water droplets, which consisted of ionic precursors of AgClO(4) and Ag particles (or Ag aggregates), were estimated to be about 30-40 nm. In the process of Ag particle formation, the water droplet size under high-pressure CO(2) is more effectively regulated than that under ambient air, thereby preventing Ag particles from aggregating and precipitating., (2009 Elsevier Inc. All rights reserved.)

Background: Neutrophils play an essential role in innate immunity and against infection. Mitochondria are organelles that produce energy in the form of adenosine triphosphate (ATP), which is required for maintaining the function and structure of cells and organs. Although local anesthetics (LAs) are widely used in clinical practice, it remains unclear whether LAs such as lidocaine, ropivacaine, and bupivacaine affect neutrophil mitochondrial functions. The aim of this study was to examine whether LAs have any effects on human neutrophil mitochondrial functions., Methods: Freshly isolated human neutrophils were incubated with lidocaine, ropivacaine, or bupivacaine. The oxidative burst and phagocytic activity of neutrophils and apoptotic rate of neutrophils were measured to assess the effect of LAs on neutrophil functions. The ATP concentration, mitochondrial transmembrane potential (Deltapsim), and neutrophil mitochondrial morphology were also measured to evaluate the effect of LAs on mitochondrial functions., Results: Lidocaine (400 microm) induced a reduction in the oxidative burst and phagocytosis activity of neutrophils by approximately 20%. The ATP concentration was significantly lower in lidocain-treated neutrophils compared with control neutrophils (876 +/- 25 vs. 1,332 +/- 76 pmol/10(6) neutrophils; p < 0.05). Mitochondrial transmembrane potential (Deltapsim) was also significantly lower in lidocaine-treated neutrophils compared with control neutrophils (p < 0.05). Lidocaine also induced mitochondrial structural changes and induced apoptosis of neutrophils. Ropivacaine and bupivacaine had no effect on neutrophil functions including mitochondrial function. Furthermore, the study of mitochondrial function depletion demonstrated that neutrophil function requires active mitochondrial function., Conclusions: Although ropivacaine and bupivacaine had no effect on neutrophil and mitochondrial functions, lidocaine suppressed neutrophil function, inhibited ATP synthesis, reduced mitochondrial membrane potential, and induced apoptosis.

In order for a patient and a family to be able to return to the region comfortably and to lead the life of their own, ascertaining and multi-occupational participation of the support to the patient and family needs to be inquired (joint conference) at the early stage of hospitalization. Before discharged from the hospital, it is essential for the patient and family to know a key person and have useful social resources, so that we can pull out their self care abilities at home and eventually link to a comfortable homecare support. By our intervention in the early stage of hospitalization, a family's uneasiness of taking care of the patient at home has changed to a confidence and led to shortening of hospital stay. Sharing the information with the staffs of many occupational disciplines and to have a homecare support that meets the patient and his family's needs will lead to an elevation of the services and staff motivation.

Hair follicle regeneration involves epithelial-mesenchymal interactions (EMIs) of follicular epithelial and dermal papilla (DP) cells. Co-grafting of those cellular components from mice allows complete hair reconstitution. However, regeneration of human hair in a similar manner has not been reported. Here, we investigated the possibility of cell-based hair generation from human cells. We found that DP-enriched cells (DPE) are more critical than epidermal cells in murine hair reconstitution on a cell number basis, and that murine DPE are also competent for hair regeneration with rat epidermal cells. Co-grafting of human keratinocytes derived from neonatal foreskins with murine DPE produced hair follicle-like structures consisting of multiple epidermal cell layers with a well-keratinized innermost region. Those structures expressed hair follicle-specific markers including hair keratin, and markers expressed during developmental stages. However, the lack of regular hair structures indicates abnormal folliculogenesis. Similar hair follicle-like structures were also generated with cultured human keratinocytes after the first passage, or with keratinocytes derived from adult foreskins, demonstrating that epidermal cells even at a mature stage can differentiate in response to inductive signals from DP cells. This study emphasizes the importance of EMI in follicular generation and the differentiation potential of epidermal keratinocytes.

Background: Previously, we have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD14 and HLA-DR expression decreased soon after the start of surgery under general anaesthesia. This study was designed to investigate the effects of epidural anaesthesia on surgical stress-induced immunosuppression in patients undergoing upper abdominal surgery., Methods: After having obtained informed consent, patients were randomly allocated to receive general anaesthesia (Group G) or general anaesthesia with epidural anaesthesia (Group E). Perioperative changes in neutrophil phagocytic activity, neutrophil respiratory burst activity, monocyte mCD14 and HLA-DR expression, plasma IL-10 concentration, and the LPS-induced TNF-alpha production in whole blood were measured., Results: Surgical stress rapidly depressed neutrophil phagocytic activity, monocyte mCD14 and HLA-DR expression, and LPS-induced TNF-alpha production ex vivo (P < 0.05 vs preoperation) in both Group G and Group E. In contrast, the plasma IL-10 concentration increased significantly 2 h after the start of surgery (P < 0.05) in both groups. There were no significant differences between the two groups. The neutrophil respiratory burst activity did not change during the operation in either group., Conclusion: This study showed that the innate immune system is suppressed from the early period of upper abdominal surgery. Subgroup analysis suggested that epidural anaesthesia to T4 dermatome as well as general anaesthesia may not protect patients from this immunosuppression. These results in part explain the impairment of host-defense mechanisms seen in the perioperative period.

To evaluate the efficacy of imatinib in a practical setting, we registered 43 patients with newly diagnosed chronic myelogenous leukemia (CML) (group I) and 56 patients with previously diagnosed CML (group II) at 11 hematology centers in Nagasaki prefecture, Japan, from December 2001 to July 2005 and analyzed the molecular responses. Cytopenia, fluid retention, and skin rash were major adverse events, along with elevation in creatine phosphokinase levels. With a follow-up of approximately 3.5 years, imatinib treatment led to 88.7% overall survival (OS) and 85.2% progression-free survival (PFS) rates for group I, and 79.8% OS and 76.6% PFS rates for group II; the rates were not significantly different despite a lower average imatinib dose in group II. The rates of complete cytogenetic response at 30 months and major molecular response at 24 months were 86.1% and 62.5%, respectively, in group I, and 77.9% and 58.3% in group II; the rates were not significantly different. As has been reported by other groups, these results demonstrate that imatinib treatment can provide excellent clinical and molecular effects for not only newly diagnosed but also previously treated CML patients in practical settings that cover a wider variety of patients than clinical trials.

Migration of bisphenol A (BPA) and benzophenones, i.e., benzophenone (BZ), 4-(dimethylamino)benzophenone (DMAB), Michler's ketone (MK) and 4,4'-bis(diethylamino)benzophenone (DEAB), from 21 paper and paperboard products (15 recycled paperboard boxes and 6 virgin paper products) used in contact with food was examined. Migration levels of compounds from recycled paperboard were compared under various food-simulating conditions. BPA showed the highest migration into 20% ethanol and benzophenones into 95% ethanol. No compounds migrated from virgin paper products, but compounds did migrate into food simulants from recycled paperboard food boxes. BPA migrated into 20% ethanol from all recycled paperboard food boxes between 1.0 and 18.7 ng/mL. Into 95% ethanol, migration of BZ was observed in 8 samples (1.0-18.9 ng/mL), DMAB in 12 samples (1.2-3.7 ng/mL), MK in 13 samples (1.9-9.0 ng/mL), and DEAB in 13 samples (1.0-10.6 ng/mL). The highest migration level was 27.2 ng/mL and most of the migration levels were below 10 ng/mL. These values are sufficiently low compared with the TDI and NOAEL levels. Moreover, the amount of food in daily meals that comes into contact with paperboard products is relatively small. Consequently, it was concluded that there was no safety concern regarding the tested compounds in recycled paperboard food boxes.

Levels of eight harmful elements, i.e., antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium, were investigated in 45 baby toys and 10 paints, which were mainly made of polyvinyl chloride. All samples contained barium at levels of 0.3-3,700 mg/kg, several samples contained cadmium (0.2-26 mg/kg), chromium (0.5-280 mg/kg) and lead (1.5-1,300 mg/kg), and one sample contained antimony (5.3 mg/kg). They might have been used as colorants of the toy materials and paints. They were then evaluated using the migration test of ISO 8124-3, in which samples were ground up, and then soaked in 0.07 mol/L HCl at 37 degrees C for two hours. Barium, cadmium, chromium and lead migrated from some of the samples, but at levels lower than the migration limits required by ISO 8124-3. Compared with the Japanese official method, the ISO method resulted in higher migration, but there are significant differences in the migration limits, test method, and so on between them. Further investigation is needed in this area.

The purpose of this study is to clarify the characteristics of sensory-motor, verbal and cognitive abilities of preschool boys with attention-deficit/hyperactivity disorder (ADHD) in order to provide information for their treatment and education at preschool age by teachers and professionals. For this purpose, 46 Japanese boys with ADHD-combined type (ADHD-C) whose ages ranged from 45 to 72 months were examined using the Japanese version of the Miller Assessment for Preschoolers (JMAP), and were compared with 46 Japanese boys matched for age and gender in the normative samples that served as the standardizations for the JMAP. The results showed that the ADHD-C group was significantly lower than the normative sample group both on the Total score and on each Index score (P < 0.01) with the exception of the Non-verbal Index. In particular, the number of boys with ADHD-C scoring below the 5th percentile on the Foundation Index (i.e. fundamental sensory-motor tests) was the highest among all index scores. The ADHD-C group had significantly lower scores than the normative sample group in equilibrium, postural control, fine motor of hand and tongue, motor praxis, articulation, memory related to the comprehension of long sentences, and visual construction. Because fundamental sensory-motor abilities were notably lower in the ADHD-C group than in the normative sample group, it is suggested that preschool boys with ADHD-C should be examined and treated for sensory-motor disabilities.

Previous studies of physiological responses to music showed inconsistent results, which might be attributable to methodological differences. Heart rate variability has been used to assess activation of the sympathetic and the parasympathetic nervous systems. The present study aimed to examine heart rate variability with repetitive exposure to sedative or excitative music. The participants were 13 undergraduate or graduate students who were each exposed to three conditions sedative music (SM), excitative music (EM), and no music (NM) on different days. Each participant underwent four sessions of one condition in a day. Sedative music and no music each induced both high relaxation and low tension subjectively. However, excitative music decreased perceived tension and increased perceived relaxation as the number of sessions increased. The low-frequency (LF) component of heart rate variability (HRV) and the LF/HF (high-frequency) ratio increased during SM and EM sessions but decreased during NM sessions. The HF component of HRV during SM was higher than that during EM but the same as that during NM. These findings suggest that excitative music decreased the activation of the parasympathetic nervous system.

Unlabelled: We previously reported that a platelet-activating factor receptor (PAFR) antagonist (TCV-309) suppressed lipopolysaccharide (LPS)-induced mortality and tumor necrosis factor (TNF) production in mice. However, the effect of TCV-309 on cytokine production induced by Staphylococcus enterotoxin B (SEB) or live bacteria has not been reported. In this study we investigated the effect of TCV-309 on cytokine production in human whole blood induced by LPS, SEB, and both Gram-positive and -negative bacteria. Human whole blood diluted 5:1 (980 microL) was placed in the wells of a 24-well plate. Ten microliters of LPS, SEB, Escherichia coli O18 K(+), or Staphylococcus aureus were added to each well. After incubation at 37 degrees C for 6 h, TNF, interleukin (IL)-6, and IL-8 in the culture medium were measured. TCV-309 did not affect the growth of either E. coli or S. aureus bacteria in the culture medium for the 6 h incubation. LPS, SEB, and both E. coli and S. aureus induced TNF, IL-6, and IL-8 in human whole blood. TCV-309 significantly inhibited the production of TNF, IL-6, and IL-8 induced by LPS, SEB, and bacteria. A PAFR antagonist suppressed cytokine production induced by LPS, SEB, and both Gram-positive and -negative bacteria in human whole blood. A PAFR plays an important role of producing proinflammatory cytokines induced by both toxins and live bacteria., Implications: The platelet-activating factor receptor plays an important role in producing proinflammatory cytokines induced by bacterial toxins, such as lipopolysaccharide,Staphylococcus enterotoxin B, and live Gram-positive and Gram-negative bacteria.

The etiology of nocturia in 70 patients with benign prostatic hyperplasia (BPH) who had nocturia of two or more times were examined based on frequency volume charts (FVC). Nocturia was classified into four groups: nocturnal polyuria, low capacity, combined nocturia, and no evidence of abnormality. Nearly half of the cases had nocturnal polyuria only. A little under 70% of patients had associated nocturnal polyuria (nocturnal polyuria+combined nocturia). Naftopidil was administered for three months to the patients with BPH who had nocturia with a urinary frequency of two or more times. Clinical efficacy was evaluated in 32 patients based on FVC and naftopidil was shown to improve nocturia. The improvement in nocturia was determined by the increment in voided volume.

Unlabelled: It has been demonstrated that local anesthetics have several effects on the immune system. Monocytes and macrophages are essential components of the host response to microbial infection; however, the effect of local anesthetics on monocyte surface receptor expression remains unclear. We designed this study to investigate the effects of local anesthetics on monocyte mCD14 and human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced or staphylococcal enterotoxin B (SEB)-induced tumor necrosis factor (TNF)-alpha production. Blood samples were obtained from 10 healthy volunteers. The effects of local anesthetics on LPS- or SEB-induced TNF-alpha production were determined by using an enzyme-linked immunosorbent assay. After different doses of local anesthetics were added, the blood was stimulated with LPS (10 ng/mL) or SEB (10 micro g/mL) for 4 h. The effects of local anesthetics on monocyte mCD14 and HLA-DR expression were measured by dual monoclonal antibody staining and flow cytometry. Local anesthetics showed no effect on LPS- or SEB-induced TNF-alpha production in human whole blood. Local anesthetics suppressed monocyte HLA-DR expression in a dose-dependent manner (P < 0.05) but had no effect on monocyte mCD14 expression. This study demonstrated that local anesthetics suppress HLA-DR expression on the surface of human monocytes., Implications: Monocyte surface receptors have a crucial role in the host response to microbial infection. We investigated the effects of local anesthetics on monocyte mCD14 and human leukocyte antigen (HLA)-DR expression. Our results show that local anesthetics suppress HLA-DR expression on the surface of human monocytes.

A new World Health Organization classification was recently proposed. However, classification of peripheral T-cell lymphomas remains to be clarified. Particularly, unspecified type was considered as a heterogeneous category. Here we studied the expressions of chemokine receptors, Th1-associated CXCR3 and CCR5 and Th2-associated marker ST2(L), and activated T-cell receptor OX40/CD134 in 185 patients with nodal T-cell lymphoma, and evaluated the relationship to prognosis. Their expression patterns correlated with the specific subtype of nodal T-cell lymphoma, such as angioimmunoblastic T-cell lymphoma (AILD), anaplastic large cell lymphoma (ALCL), and in peripheral T-cell lymphoma (PTCL), unspecified. In AILD, almost all cases were immunoreactive for OX40/CD134 (96%) and for CXCR3 (89%). In ALCL, all cases were immunonegative for OX40/CD134, and only a few cases (24%) were immunoreactive for CXCR3, whereas almost all cases (94%) were positive for ST2(L). Cases of PTCL, unspecified, were divided into 2 groups; group 1 (cases positive for either ST2(L), CCR5, or CXCR3) tended to show favorable prognosis compared with group 2 (cases negative for ST2(L), CCR5, and CXCR3). Our results indicate that further subtyping of PTCL, unspecified, into groups 1 and 2 could be significant for evaluating prognosis and understanding the functional role of these tumors.

The gastrointestinal (GI) tract is the most common site for the development of extranodal non-Hodgkin's lymphomas, with most cases having a diffuse architectural pattern. Follicular lymphoma (FL) of the stomach is a very rare disease, and little is known about the immuno-histochemical and molecular genetic characteristics of this type of lymphoma. Despite their rarity, FLs are an important consideration in the differential diagnosis of follicular hyperplasia of mucosa-associated lymphoid tissue (MALT), a relatively frequently encountered lesion with the potential to cause significant diagnostic difficulty, especially when assessment is based on scanty biopsy material. We report a 57-year-old woman with gastric FL, and describe the results of immunohistochemical and molecular genetic studies.

The stomach is a common site of extranodal malignant lymphoma. Here we examined the clinicopathological features of 317 gastric B-cell lymphomas and characterized the differences among low-grade mucosa-associated lymphoid tissue (MALT) lymphomas (LG), high-grade MALT lymphomas (HG), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DL). Cases included 126 DL, 71 HG, 98 LG, 10 FL, three Burkitt's lymphoma and nine of undefined type. The age range of patients was as follows: LG, 14-96 years (mean, 61.1); HG, 20-87 years (mean, 63.9); DL, 16-88 years (mean, 62.8); and FL, 54-76 years (mean, 65.5). There were no differences in age with respect to tumor type. There were more women patients with LG (female:male, 55:43), while males predominated among DL patients (54:72). The sexes were represented almost equally in HG cases (34:37). Histological findings, especially in DL tumors, correlated significantly to the gross appearance of mass formation. Dutcher bodies were encountered mainly in HG or LG cases. Our results showed no differences in age, sex or site of disease between LG, HG and DL tumors. However, the grade of malignancy correlated strongly to gross appearance. Dutcher bodies were important for the diagnosis of gastric MALT lymphoma.

Aims: Most primary gastrointestinal lymphomas are of B-cell origin and T-cell origin is very rare. Recent studies have suggested that human T-cell lymphotrophic virus type 1 (HTLV-1) may be involved in the development of primary gastric T-cell lymphoma. We analysed 31 patients with primary gastric T-cell lymphoma in south-west Japan, an area endemic for HTLV-1, and determined their phenotypes, genotypes, and HTLV-1 status., Methods and Results: Here we present 31 cases of primary gastric T-cell lymphoma in a HTLV-1-endemic area in Japan and analyse the clinical status, histology, phenotype and virus status. The median age at onset of primary gastric T-cell lymphoma was 57 years with a gender ratio of M:F = 1.58:1. Six of the 31 primary gastric T-cell lymphoma cases had HTLV-1 proviral DNA (five males, one female), nine of the 31 cases were positive for anti-adult T cell leukaemia antibody, without examination of HTLV-1 proviral DNA (five males, four females), eight were non-HTLV-1-associated primary gastric T-cell lymphoma (four males, four females) and the other eight cases were unknown. Primary gastric T-cell lymphoma usually presented as a large ulcerated tumour at the corpus to the antrum and histologically consisted of anaplastic large cell type (n = 2), pleomorphic large cell type (n = 3), pleomorphic medium and large cell type (n = 14), pleomorphic medium cell type (n = 11), and angioimmunoblastic T-cell lymphoma type (n = 1). There were no clear macroscopic and microscopic differences between HTLV-1-associated and non-HTLV-1-associated primary gastric T-cell lymphoma. Most patients died within 2 years of diagnosis, and both types of primary gastric T-cell lymphoma (with and without HTLV-1) were associated with poor prognosis. Cytotoxic marker analysis showed that HTLV-1-associated lymphomas were negative for TIA-1, while non-HTLV-1-associated lymphomas were positive for TIA-1., Conclusions: Our results suggest that in HTLV-1-endemic areas, patients with HTLV-1-associated primary gastric T-cell lymphoma should be managed carefully and that TIA-1 seems to be useful for identifying the aetiology of this lesion.

Introduction: Because pancreatic exocrine function testing methods are problematic, both imaging and functional tests are important in the diagnosis of chronic pancreatitis., Aim: To evaluate the usefulness of ultrasonographic monitoring of the main pancreatic duct after a secretin test., Methodology: A total of 70 subjects (30 control subjects, 26 patients with probable chronic pancreatitis, and 14 patients with definite chronic pancreatitis) were selected. The main pancreatic duct diameters were measured serially after an injection of secretin (100 IU/body). The relation between the magnitude of the duct dilation and exocrine pancreatic function on the secretin test was evaluated., Results: The main pancreatic duct dilated immediately after a bolus injection of secretin, showed a peak after 2-5 minutes, and recovered gradually. The response curve of the definite group had a flatter pattern than that of the other groups. For the maximal to basal duct diameter ratio, statistically significant differences were found between the control and definite groups and between the control and probable groups. In addition, the ratio correlated significantly with the maximal bicarbonate concentration and secretory volume on the secretin test., Conclusions: The results of the current study indicate that exocrine pancreatic function and the morphologic changes of the main pancreatic duct are significantly related. Dynamic ultrasonographic findings may reflect pancreatic function; consequently, this test may be a useful tool in the diagnosis of chronic pancreatitis.

Hodgkin disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. Various CXC and CC chemokines [e.g., interferon-gamma-inducible protein-10 (IP10), monokine induced by interferon-gamma (MIG) and TARC] are expressed on H&RS cells. Our study was designed to investigate the expression of MIG, IP10 and TARC on H&RS cells and their relations on lymphocyte infiltration. Immunohistochemical staining was performed using antibodies for CXCR3 (a specific receptor for IP10 and MIG), which is characteristic of Th1 helper phenotype and CCR3, CCR4 and ST2, which are features of Th2 cells. We studied 15 cases of HD [lymphocyte predominance (LP) type, 2; mixed cellularity (MC) type, 6; and nodular sclerosis (NS) type, 7]. All 6 MC cases contained TARC-, IP10- and MIG-expressing H&RS cells, however only 2 of 5 NS cases contained TARC-expressing H&RS cells, 3 of 7 NS contained MIG-expressing H&RS cells and only 1 of 7 NS contained IP10-expressing H&RS cells. Neither of the 2 LP cases contained HR&S cells that expressed these chemokines. The chemokines were more frequently expressed by MC than by NS and LP types. IP10-, MIG- and TARC-positive HD cases contained higher numbers of Th2 lymphocytes (ST2- CCR3- or CCR4-positive lymphocytes), compared to IP10-, MIG- and TARC-negative HD cases (p < 0.05 or <0.5). The number of CXCR3 (MIG and IP10 receptor)-positive lymphocytes (Th1 lymphocytes) was not different between MIG- and IP10-positive and -negative HD. Lymphocytes surrounding MIG- and IP10-positive H&RS cells were more frequently CXCR3-positive, however, compared to MIG- and IP10-negative cases. The CCR4 (TARC receptor)-positive lymphocytes, surrounding H&RS cells, were minority and the surrounding lymphocytes were not different between TARC-positive and negative cases. Our results indicate that MIG, IP10 and TARC chemokines influenced the response of Th2 cells in HD. It is possible, however, that IP10 and MIG may locally influence Th1 cells via cell migration., (Copyright 2002 Wiley-Liss, Inc.)

The role of bcl 10, a recently cloned apoptosis-associated gene, in diffuse large B-cell lymphoma (DLBL) is unknown. Here we determined the role of bcl 10 gene rearrangement on prognosis. Bcl 10 rearrangement was examined by Southern blot. Bcl 10 rearrangement was detected in 20 of 137 (14.6%) samples of DLBL. The frequency of bcl 10 rearrangement was higher in extranodal (eight of 38 cases, 21%) than in nodal (12 of 99, 12%) DLBL. The survival rate in patients with bcl 10 rearrangement tended to be better than in those with germ-line bcl 10, albeit statistically insignificant probably due to the small population sample. The superior prognosis in patients with bcl 10 rearrangement might be due to bcl 10-induced enhanced apoptosis.

A rare subset of HIV lymphoma, known as primary effusion lymphoma (PEL), is a high-grade tumour carrying human herpes virus 8 (HHV-8). Very little is known about genomic aberration in PEL, and only a few HIV-negative PEL have been reported. Here we report the results of chromosomal analysis and comparative genomic hybridisation (CGH) conducted to detect regions of gain and loss, in five HIV-negative Japanese cases of HHV-8-negative PEL. All patients except one (35-year-old female) were elderly men and the morphologic examination showed large cell type. PEL expressed B-cell-associated and activation-associated antigens, and exhibited clonal immunoglobulin genes. No HHV-8 was detected in all four examined cases, but Epstein-Barr virus (EBV) was detected in one case. Genomic abnormalities and aberrations were identified in all HHV-8/HIV-negative PEL. CGH studies showed gain in 19 of 24 chromosomes. Gains of 3q13-27, 8q24, 10q21-23 and Yq were detected in two of the five cases, but other gains were noted in each case. Chromosomal analysis revealed complex abnormalities both in numbers and structures. Burkitt lymphoma-associated t(8;22) was detected in one case, but +8 chromosome and c-myc amplification were detected in the other three cases by Southern blot and/or fluorecence in situ hybridization (FISH). Abnormality of chromosome 8, which associates with c-myc, was detected in four of the five HHV-8/HIV-negative PEL. However, the other common genomic abnormalities of HHV-8/HIV-negative PEL were not detected in our study, but the complex abnormalities seemed to be true rather than the usual large B-cell lymphoma. Our results suggest that multi-step genomic abnormalities might be associated in HHV-8/HIV-negative PEL tumorigenesis.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. Several studies have confirmed the presence of a high apoptotic rate and proliferative state in the bone marrow of MDS. However, MDS is a heterogeneous disease from the point of view of prognosis. Some patients develop only anemia and show long survival with or without maintenance therapy, while others develop fatal pancytopenia or leukemic changes and therefore show a poor prognosis. This review focuses on the relationship between prognosis and apoptotic or proliferative processes affecting hematopoietic cells in the bone marrow of patients with MDS.

Purpose: To investigate the efficacy of S(+)-ketamine and R(-)-ketamine on staphylococcal enterotoxin B (SEB)-induced tumour necrosis factor (TNF)-, interleukin (IL)-6, and IL-8 production in human whole blood in vitro., Methods: After Ethics Committee approval and informed consent, blood samples were obtained from ten healthy volunteers and diluted with five volumes of RPMI 1640. After adding different doses of ketamine isomers (0-1000 microM), the blood was stimulated with SEB (10 ng x mL(-1)). After a six-hour incubation period, the plasma TNF- activity was determined by the L929 cell cytotoxic assay and IL-6 and IL-8 concentrations were measured using an enzyme-linked immunoassay., Results: Ketamine isomers significantly suppressed SEB-induced TNF- production at concentrations exceeding 50 microM. Ketamine isomers at concentrations exceeding 100 microM also significantly suppressed SEB-induced IL-6 production. Furthermore, ketamine isomers at concentrations exceeding 500 microM significantly suppressed SEB-induced IL-8 production. There were no significant differences between the suppressive effects of S(+)-ketamine and R(-)-ketamine on SEB-induced proinflammatory cytokine production., Conclusion: This study demonstrated that ketamine isomers suppressed SEB-induced TNF-, IL-6, and IL-8 production in human whole blood.

Diffuse large B-cell lymphoma (DLBL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 137 patients with de novo DLBL for rearrangements of the bcl-1, bcl-2, bcl-6 and c-myc oncogenes by Southern blot analysis. Structural alterations of bcl-1, bcl-2, bcl-6, and c-myc were detected in 21 of 137 (15.3%), 8 of 137 (5.8%), 22 of 137 (16.1%), 14 of 137 (10.2%) patients, respectively. Two cases showed a combination of bcl-1 and bcl-6 rearrangements. Chromosomal analysis was performed in 31 cases of the 137 DLBL. 27 of these showed karyotypic abnormalities, and two had translocations 3q27 involving bcl-6. However, one of two cases had no rearrangement of bcl-6. Patients with rearranged bcl-6 and c-myc tended to have poorer survival than patients with germ-line. Furthermore, bcl-1 and bcl-2 rearrangements tended to have a better outcome, although the above differences were not statistically significant. Rearrangements of the bcl-1, 2, 6, and c-myc gene correlated with the clinical outcome in DLBL and may thus serve as prognostic markers in patients with this form of malignant lymphoma. However, other genetic factors are probably involved in determining prognosis.

Mucosa-associated lymphoid tissue (MALT) lymphomas usually involve extranodal sites, especially the stomach, lung and salivary glands. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14) (p22;q32) in MALT lymphomas, and considered to be an apoptosis-associated gene, and involves a caspase recruitment domain (CARD)-containing protein that activates NF-kappaB. We investigated the role of Bcl10 in MALT lymphoma by analyzing its expression, rearrangement and somatic mutation, by immunostaining, reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot and PCR in 20 cases of MALT lymphoma. Expression of NF-kappaB was studied by immunostaining. Five cases of reactive lymphadenitis (RLA) were used as the control. Bcl10 rearrangement was detected in 8 of 20 (40%) MALT lymphomas, but in none of RLA. Significant Bcl10 mutation was detected only in 1 case (5%) with MALT, but not in RLA. RT-PCR showed higher density bands of Bcl10 in MALT lymphomas than in RLA. Immunostaining showed a weak Bcl10 expression in the germinal center and very weak expression in the marginal zone B-cells in RLA, which was limited to the cytoplasm. In contrast, Bcl10 was strongly expressed in MALT lymphomas, and was mainly detected in the cytoplasm, as well as in the nuclei. Bcl10 expression did not correlate with Bcl10 mutation and re-arrangements. NF-kappaB was expressed in nuclei of MALT lymphoma cells, but not in RLA. Bcl10 expression in MALT lymphoma correlated closely with NF-kappaB expression. Our results suggest that activation of Bcl10 and NF-kappaB may be important in MALT lymphomagenesis, and that nuclear localization of Bcl10 may be important in the progression of MALT.