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There are a few studies on gender differences in terms of reasons and motives for methamphetamine use. Purpose/Objectives: To examine gender differences in triggers of methamphetamine use Methods: ...

Adverse childhood experiences (ACEs) are distressing and/or traumatic events that occur during childhood that increase the risk of negative health outcomes in adulthood.This study estimated the prevalence of ACEs in a nationwide sample of Japanese methamphetamine users in prison and examined associations among ACEs, suicidal ideation, and non-suicidal self-injury.Participants were 636 inmates (418 male and 218 female) who were newly incarcerated in Japan for Stimulants Control Act violations.First, 699 participants completed an anonymous self-report questionnaire. Of these, 636 participants who did not have any missing responses were included in the analysis. After calculating descriptive statistics, the associations between ACEs and suicidal behaviors were assessed using binary logistic regression analyses.Results showed that 76.1 % of the participants reported at least one ACE before the age of 18, and female participants reported a significantly higher number of adversities than their male counterparts. The most common ACEs were parental death or divorce, followed by psychological abuse. Logistic regression analyses revealed that ACE scores significantly increased the risk of suicidal ideation (SI; adjusted odd ratio [AOR] = 1.18, p .001) and non-suicidal self-injury (NSSI; AOR = 1.18, p .001) after controlling for possible confounding variables.Findings suggest the importance of early prevention and intervention for traumatic experiences, and have implications for the recommendation of gender-responsive, trauma-focused interventions, especially for female inmates in the criminal justice system, to break the intergenerational chain of abuse. Future research directions and treatment are discussed.

To investigate optimal beam quality for chest flat panel detector (FPD) system by semi-quantitatively assessment using a realistic lung phantom. Chest FPD radiographs were obtained on a realistic lung phantom with simulated lung opacities using various X-ray tube voltage levels (90–140 kV) with/without copper filter. Entrance skin dose was set to maintain identical for all images (0.1 mGy). Three chest radiologists unaware of the exposure settings independently evaluated the image quality of each simulated opacity and normal structure using a 5-point scale (+ 2: clearly superior to the standard; + 1: slightly superior to the standard; 0: equal to the standard; − 1: slightly inferior to the standard; − 2: clearly inferior to the standard). The traditional FPD image obtained at a tube voltage of 120 kV was used as the standard. The scores of image quality were statistically compared using the Wilcoxon rank test with Bonferroni correction. FPD images using 90-kV shot with copper filter were superior to the traditional 120-kV shot without filter with respect to the visibility of vertebra, pulmonary vessels, and nodules overlapping diaphragm and heart (p

This study aimed to examine the relationship between methamphetamine (MA) use and high-risk sexual behavior among newly incarcerated prisoners in Japan. We conducted a secondary analysis using cross-sectional survey data, which constituted a nationwide prison sample surveyed between July and November 2017. In total, 699 participants (462 male and 237 female prisoners), who completed the self-administered questionnaire during imprisonment were recruited for the study. The prevalence of high-risk sexual behaviors was as follows: inconsistent condom use (78.4% male, 81.7% female), multiple sexual partners (61.3% male, 41.3% female), history of sexually transmitted diseases (14.1% male, 23.6% female), and trading sex for drugs (15.6% male, 17.7% female). A logistic regression analysis showed that MA use during sex increased the likelihood of high-risk sexual behavior in both male (adjusted odds ratio [AOR] = 5.86; 95% confidence interval [CI] = 3.41-10.07) and female prisoners (AOR = 2.58; 95% CI = 1.33-5.00). Additionally, in female prisoners, a history of sharing MA injection (AOR = 1.60; 95% CI = 1.06-2.42) increased high-risk sexual behavior. Our results indicate that harm reduction programs tailored according to the specific necessities of each gender to reduce high-risk sexual behaviors among MA users should be included in Japanese drug policies.

To evaluate the usefulness of the CT temporal subtraction (TS) method for the detection of the lung cancer with predominant ground-glass opacity (LC-pGGO). Twenty-five pairs of CT and their TS images in patients with LC-pGGO (31 lesions) and 25 pairs of those in patients without nodules were used for an observer performance study. Eight radiologists participated and the statistical significance of differences with and without the CT-TS was assessed by JAFROC analysis. The average figure-of-merit (FOM) values for all radiologists increased to a statistically significant degree, from 0.861 without CT-TS to 0.912 with CT-TS (p < .001). The average sensitivity for detecting the actionable lesions improved from 73.4 % to 85.9 % using CT-TS. The reading time with CT-TS was not significantly different from that without. The use of CT-TS improves the observer performance for the detection of LC-pGGO. • CT temporal subtraction can improve the detection accuracy of lung cancer. • Reading time with temporal subtraction is not different from that without. • CT temporal subtraction improves observer performance for ground-glass/subsolid nodule detection.

Objective:To determine whether 18F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS).Methods:We evaluated the in vitro binding of 3H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, 18F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD).Results:3H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher 18F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher 18F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism.Conclusions:18F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. 18F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder presenting variable combinations of parkinsonism, cerebellar ataxia, corticospinal and autonomic dysfunction. Alpha-synuclein (α-SYN)-immunopositive glial cytoplasmic inclusions (GCIs) represent the neuropathological hallmark of MSA, and tubulin polymerization promoting protein (TPPP)/p25 in oligodendroglia has been known as a potent stimulator of α-SYN aggregation. To gain insight into the molecular pathomechanisms of GCI formation and subsequent oligodendroglial degeneration, we ectopically expressed α-SYN and TPPP in HEK293T and oligodendroglial KG1C cell lines. Here we showed that TPPP specifically accelerated α-SYN oligomer formation and co-immunoprecipitation analysis revealed the specific interaction of TPPP and α-SYN. Moreover, phosphorylation of α-SYN at Ser-129 facilitated the TPPP-mediated α-SYN oligomerization. TPPP facilitated α-SYN-positive cytoplasmic perinuclear inclusions mimicking GCI in both cell lines; however, apoptotic cell death was only observed in KG1C cells. This apoptotic cell death was partly rescued by sirtuin 2 (SIRT2) inhibition. Together, our results provide further insight into the molecular pathogenesis of MSA and potential therapeutic approaches.

The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.

alpha-Synuclein is a major protein component deposited in Lewy bodies and Lewy neurites that is extensively phosphorylated at Ser(129), although its role in neuronal degeneration is still elusive. In this study, several apoptotic pathways were examined in alpha-synuclein-overexpressing SH-SY5Y cells. Following the treatment with rotenone, a mitochondrial complex I inhibitor, wild type alpha-synuclein-overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies, although cells overexpressing the S129A mutant, in which phosphorylation at Ser(129) was blocked, showed few aggregations. In wild typealpha-synuclein cells treated with rotenone, the proportion of phosphorylated alpha-synuclein was about 1.6 times higher than that of untreated cells. Moreover, induction of unfolded protein response (UPR) markers was evident several hours before the induction of mitochondrial disruption and caspase-3 activation. Eukaryotic initiation factor 2alpha, a member of the PERK pathway family, was remarkably activated at early phases. On the other hand, the S129A mutant failed to activate UPR. Casein kinase 2 inhibitor, which decreased alpha-synuclein phosphorylation, also reduced UPR activation. The alpha-synuclein aggregations were colocalized with a marker for the endoplasmic reticulum-Golgi intermediate compartment. Taken together, it seems plausible that alpha-synuclein toxicity is dependent on the phosphorylation at Ser(129) that induces the UPRs, possibly triggered by the disturbed endoplasmic reticulum-Golgi trafficking.

Background: The Oketani method is a program of breast massage and clinical counseling developed by the midwife Satomi Oketani. The purpose of this study is to examine the effects of the method on the quality of breast milk by determining the chemical composition of the milk before and after massage. Methods: Milk samples were obtained immediately before and after massage from healthy, exclusively breast-feeding Japanese mothers at two different periods of lactation one 3 months after parturition. Lipids, whey protein, casein, lactose, ash, and total solids in milk were measured in milk samples.The gross energy content of milk was estimated. Results: Breast massage significantly increased lipids in the late lactating period but not in the early lactating period. In the early lactating period casein was increased by breast massage but was not significantly affected in the late lactating period. Breast massage caused a significant increase in total solids from the first day to 11 months post partum. The gross energy in the late lactating period was significantly increased by breast massage but not in the early lactating period. Lactose was not significantly changed by breast massage. Conclusions: Breast massage improves the quality of human milk by significantly increasing total solids, lipids, and casein concentration and gross energy. The milk of mothers treated by Oketani breast massage may improve the growth and develop

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are immune-mediated peripheral neuropathies, and most of these cases were known to be associated with a preceding infection. Recent reports evidenced an increase in the number of infectious disease cases after the earthquake. The aim of this report is to investigate the incidence and clinical features of GBS and FS after the Great East Japan Earthquake. We found GBS and FS patients had markedly increased in 2011, the year of the earthquake. In regard to an antecedent illness, gastrointestinal infection was significantly increased in GBS patients after the earthquake. These results suggest environmental factors including infectious agents and stress caused by the earthquake might have been involved in the outbreak of the diseases.

Background: In 1988, the first survey of child abuse in Japan was conducted in Osaka Prefecture as a joint effort between medical, health and welfare agencies. Ensuing surveys in 1988 revealed that infant abuse had a death rate of 10% in Health Center. Methods: In 1996 and 1999, surveys were performed on 130 and 215 abused children under 18 years of age. They were studied in terms of their activity of Health Center, including help, means of involvement by health visitors. Results: Fifty-five percent of children were detected via health centers. In 69% of cases, health visitors listened to parents and promptly contacted other agencies. Ninety-five percent of cases had home visits. The concerted effort of the health centers with allied disciplines in Osaka Prefecture yielded the following changes: the mortality rate decreased from 9.8% in 1988 to 2.3% in 1996, and institutionalized cases tripled from 13.7% in 1988 to 39.5% in 1999. The rate of admission to day care centers increased from 22.4% in 1988 to 58.7% in 1999. Along with the constant support of health visitors, day care centers provided secure support and protection for parents and infants. Conclusions: Effective prevention and treatment become possible only when treatment of the child’s physical and psychological health, mental care for parents and tangible support for childrearing and daily life were undertaken in a concerted way. To this end, a systematic commitment of all child agencies, child guidance centers, as well as medical, health educational, welfare and other allied disciplines is required.

activator inhibitor, von Willebrand factor antigen and multimers together with several other laboratory parameters. Healthy human volunteers, who served as their own controls, were randomly assigned to ingest a moderate dose of red wine (or water) with or without an evening meal. The aim was to find out the possible beneficial effects of alcohol on SIPA and other parameters of the haemostatic and fibrinolytic systems in healthy human volunteers during fasting and after the ingestion of a standard evening meal. Abstract — Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled condition s on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether th e subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willeb rand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcoho l. Excretion of the platelet thromboxane A2 metabolites 11-dehydrothromboxane B2 and 2,3-dinorthromboxane B2, as well as the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F 1α , into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.

Background and Purpose —The aim of this study was to investigate the frequency, possible predictive factors, and prognosis of deteriorating ischemic stroke in 4 clinical categories according to the classification of the Oxfordshire Community Stroke Project (OCSP). Methods —A total of 350 patients with first-ever ischemic stroke who presented within 24 hours of onset were enrolled. Based on the OCSP criteria, cerebral infarctions were divided into the following 4 clinical categories: total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar infarcts (LACI), and posterior circulation infarcts (POCI). Clinical deterioration was defined as a decrease of ≥1 points in the Canadian Neurological Scale (CNS) (in TACI, PACI, and LACI) or Rankin Scale (RS) (in POCI) during 7 days from the onset. In each clinical category, deteriorating (D) and nondeteriorating (ND) patients were compared in terms of their background characteristics, risk factors, vital signs, laboratory data, and cranial CT at the time of hospitalization. The acute-phase mortality and functional outcome were also compared. Results —The subjects comprised 86 patients (24.6%) with TACI, 63 (18.0%) with PACI, 141 (40.3%) with LACI, and 60 (17.1%) with POCI. Overall, 90 patients (25.7%) deteriorated. The frequency was very high in TACI (41.9%), followed by LACI (26.2%) and POCI (21.7%), whereas it was very low in PACI (6.3%). There were some clinical variables that differed significantly between D and ND groups. In the patients with TACI, early abnormalities of the cranial CT and significant stenoses in corresponding arteries were more frequent in the D than the ND group. In those with LACI, the CNS and hematocrit were lower in the D than the ND group. In those with POCI, cerebral atrophy was more severe and significant stenoses in vertebrobasilar arteries were more frequent in the D than ND group. The mortality of the D groups of patients with TACI and POCI exceeded 35%, and the functional outcome was worse in the D group than in the ND group of patients with TACI, LACI, and POCI. Conclusions —The frequency of deterioration in acute ischemic stroke significantly differed among the OCSP subgroups, and deterioration worsened the prognosis. There were some factors that could predict deterioration: early CT findings in TACI, large-artery atherosclerosis in TACI and POCI, and stroke severity in LACI. Further research to find sophisticated radiological and chemical markers appears to be needed.

Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T cells and macrophages. The clinical characteristics associated with this disease result from overproduction of Th1 cytokines including interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). In this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was detected in plasma in all patients (mean peak value, 30.0 ± 5.0 pg/mL), while IFN-γ was massively produced in nine patients (mean peak value, 79.2 ± 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma IL10 levels were elevated in all patients (mean peak value, 2,698.0 ± 3,535.0 pg/mL). There was a positive correlation between the levels of IFN-γ and IL-10 (P < .01). The plasma concentrations of these cytokines were initially high, before decreasing after the acute phase. However, the decrease in IL-10 levels was slower than that of IFN-γ. Although the concentration of IL-12 was high at the acute phase, in some patients, a peak in the level was delayed until the chronic phase. Thus, in HLH, production of cytokines that promote development of Th1 cells appears to be predominant over that for Th2 cell development. Overproduction of IL-10 was also observed indicating that a mechanism suppressing hyperactivation of Th1 cells and monocytes/macrophages functions in patients with this disease.

Many administrative agencies in Japan are encouraging installation of household rainwater-storage tanks for more effective use of natural rainwater. Water samples were collected periodically from 43 rainwater tanks from 40 households and tested for the presence of Legionella species and the extent of heterotrophic bacteria in Azumino city, Nagano prefecture, Japan. PCR assays indicated the presence of Legionella spp. in 12 (30%) of the 43 tank water samples. Attempts were made to identify correlations between PCR positive samples, topography, pH, chemical oxygen demand (COD), atmospheric temperature and the numbers of heterotrophic bacteria. Between June and October, 2012, the numbers of heterotrophic bacteria in rainwater tanks and the values of COD positively correlated with the presence of Legionella species. In most of the Legionella-positive cases, heterotrophic bacterial cell counts were10(4) CFU/mL. Moreover, Legionella species were less frequently detected when the COD value was5 mg KMnO(4)/L. Therefore, at least in Azumino, Japan between June and October 2012, both heterotrophic bacterial counts and COD values may be considered index parameters for the presence of Legionella cells in rainwater tanks. Much more accumulation of such data is needed to verify the accuracy of these findings.

Cases of child abuse identified by a hot-line telephone service and by a survey of health and welfare agencies are reported. Many consultations to the telephone hot-line were from mothers concerned about maltreating their own children. In such cases, the extent of abuse was often mild to moderate, and many of those mothers were troubled about child care in the relatively segregated context of the nuclear family. In only a few cases did the callers indicate that the children's life was in danger. In the administrative survey, however, deaths occurred in 5% of the cases, and the abused children frequently had physical and psychological symptoms. There were also more frequent and more serious family problems in the administrative survey compared to the telephone consultation cases. The findings of these surveys suggest that many children and parents are suffering from child abuse in Japan, that many cases are currently not being identified by health and welfare agencies, and that a wide range of measures, from protection of severely abused children to prevention of abuse, are necessary.

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD.

A 68-year-old male underwent a partial hepatectomy for hepatocellular carcinoma located in S5 close to the confluence of the anterior and posterior Glisson's sheath. Thereafter, bile leakage developed from the drain on postoperative day (POD) 2. Endoscopic nasobiliary drainage of the biliary tree and percutaneous drainage of the biloma proved ineffective, and the bile leakage continued at a constant volume of 40 mL per day. A fistulogram on POD 62 demonstrated an enhancement of the isolated bile duct. Ethanol injection into the isolated bile duct was attempted to ablate biliary epithelium but this was unsuccessful because it was impossible to insert the tube into the isolated bile duct. Ethanol was injected into the liver parenchyma surrounding the isolated bile duct via the percutaneous transhepatic approach under sonographic guidance on POD 78 in order to eliminate the production of bile juice by destroying both the biliary epithelium and liver parenchyma. The bile leakage decreased one day following the ethanol injection, although the patient experienced a prolonged fever for a week, and he was discharged on POD 100. This is the first report of ethanol injection into the liver parenchyma by a percutaneous transhepatic approach, instead of into the bile duct, to treat intractable bile leakage.

Hyposmia in Parkinson's disease (PD) was evaluated by using neuroimaging techniques. It is well known that olfactory impairments are one of the cardinal non-motor symptoms in PD. However, all smell tests used in previous studies depend on subjective answers by examinees and on sniffing of odorants, the latter of which may be impaired in PD as a consequence of motor impairments. We developed an fMRI system, which can visualize brain activation by olfactory stimuli during natural breathing. Although 7 age-matched controls demonstrated significant activations in various brain areas including precentral gyrus (BA6/6) and middle temporal gyrus (BA19/39) by the odorant stimuli, 9 patients with PD showed little activations by the same stimuli. These data suggest that the olfactory dysfunction in PD is not a simple reflection of impaired sniffing. Recent epidemiological studies demonstrate that the olfactory impairments may precede the onset of motor symptoms. Moreover, several pathological studies suggest that amygdala is one of the most frequently affected regions and is closely related to hyposmia in PD. Further brain imaging studies of hyposmia will shed light on the early pathological changes in PD.

We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN-gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-gamma production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma production results in accumulation of IFN-gamma mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.

The fatty acid composition of samples of breast milk obtained from well-nourished Nigerian and Japanese women was determined by gas chromatography. The cultural differences in dietary intake was reflected in the fatty acid composition of breast milk samples. The milk of Nigerian women contained a significantly higher percentage of saturated fatty acids (48.75%) than that of Japanese women (46.65%). Nigerian milks were also richer in arachidonic (20:4 n-6), eicosatrienoic (20:3 n-6), and docosatetraenoic (22:4 n-6) acids. Conversely, the milk of Japanese woman contained significantly higher percentages of monoun-saturates as palmitoleic, heptadecenoic, oleic, and polyunsaturates of n-3 series as alpha-linolenic, eicosapentaenoic, and docosahexaenoic acid.

Background Peroxisome proliferator-activated receptor γ (PPAR-γ) expression has not been evaluated in bronchoalveolar lavage (BAL) cells from allergic asthmatic patients. Objective To determine whether inappropriate down-regulation of PPAR-γ in alveolar macrophages may contribute to persistent airway inflammation in allergic asthma. Methods We used segmental allergen challenge as a model of in vivo experimental allergic asthmatic exacerbation and airway inflammation. PPAR-γ gene expression was evaluated at baseline and 24 hours later in asthmatic patients and controls using real-time polymerase chain reaction. Immunofluorescence was used to determine cellular location of the PPAR-γ protein. Results We demonstrate for the first time to our knowledge that PPAR-γ messenger RNA and protein, which are highly expressed in alveolar macrophages of healthy individuals, are significantly reduced in asthmatic patients after segmental allergen challenge. In allergic asthmatic patients (n = 9), PPAR-γ gene expression decreased significantly from baseline to postchallenge BAL (median decrease, 45%; P = .008). Furthermore, immunofluorescence staining demonstrated that PPAR-γ protein was associated with alveolar macrophages and not with inflammatory eosinophils and neutrophils. Conclusion Results implicate down-regulation of PPAR-γ in BAL cells as a potential factor in dysregulation of lung homeostasis in asthmatic patients. The present findings suggest that PPAR-γ agonists could have a future role in asthma therapy and warrant further study.

Background Patients with Duchenne muscular dystrophy (DMD) are at risk of the development of dilated cardiomyopathy and heart failure, thus making early identification of high-risk patients necessary. Myocardial strain imaging (MSI) can be used for quantitative analysis of wall motion of the left ventricle (LV). The aim of this study was to determine whether MSI could detect early changes in myocardial properties in presymptomatic DMD patients with normal LV function. Methods and results Two-dimensional echocardiographic and tissue Doppler examinations were performed in 13 DMD patients (age range, 11 to 20 years) with normal LV function and in 10 healthy controls. MSI was obtained from tissue Doppler information. In control subjects, strain values in both inner and outer layers of the myocardium were positive at the short-axis image showing the radial systolic thickening. In 10 of the 13 DMD patients, however, myocardial strain showed a negative strain value in systole in the outer layer of the posterolateral wall at the parasternal short-axis image for each cardiac cycle. In 5 of these 10 patients, the timing of the peak systolic velocity at the inferoposterior wall was delayed more than 60 ms than that at the posterolateral wall (mean 80.0±17.5 ms). Conclusions In some DMD patients with normal LV function, myocardial strain profiles at the posterolateral wall of the LV were different from those in healthy controls, suggesting abnormal myocardial contraction. MSI appears to detect early changes in myocardial features in DMD patients before the onset of overt cardiomyopathy.

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, which may be responsible for enlargement of alveoli in chronic obstructive pulmonary disease (COPD) and remodeling of pulmonary tissue associated with chronic asthma. Here, we provide novel evidence that MMP-12 is expressed and secreted by normal human bronchial epithelial cell cultures (NHBECs) and reveal the regulation of MMP-12 gene expression by tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), and interferon gamma (IFN-gamma). Reverse transcription-polymerase chain reaction analyses demonstrated MMP-12 mRNA presence in unstimulated differentiated NHBEC cultures. Cultures stimulated independently with EGF or IFN-gamma failed to alter MMP-12 mRNA abundance, while TNF-alpha, TNF-alpha+EGF, or TNF-alpha+IFN-gamma elicited relatively early (6 h) peak increases in MMP-12 mRNA levels. Western blot analyses specifically indicated the presence of MMP-12 in differentiated NHBEC-conditioned media. These findings indicate that the bronchial epithelium may be an important source of elastolytic activity in COPD and tissue remodeling in chronic asthma.

There are currently two main interpretations proposing mechanisms underlying tactile extinction: sensory and attention deficit hypotheses. Kinsbourne proposed an opponent processor model to support the attention deficit hypothesis. He insisted that bilateral hemispheres interact reciprocally through contralaterally oriented vectors, and in patients presenting extinction, balance is impaired, causing inattention. From Kinsbourne's point of view, extinction is not caused by sensory disturbance but inattention, therefore even in extinction patients, simultaneous bilateral stimuli should reach the bilateral primary sensory cortices (SI). Using functional magnetic resonance imaging (fMRI), tactile stimuli were administered to both hands of healthy subjects as well as a tactile extinction patient. The patient with tactile extinction extinguished right palm stimuli following simultaneous palm stimulation. During the fMRI study, we gave tactile stimuli to the right palm, the left palm, and simultaneously to both palms. In normal subjects, simultaneous bilateral stimuli activated the bilateral SI and bilateral secondary sensory cortices (SII). In the patient with right tactile extinction, simultaneous bilateral stimuli activated the bilateral SI along with the bilateral SII and right superior parietal lobule. Our study suggests that activation of SI is insufficient to engender an awareness of sensory stimuli. From the view point of Kinsbourne, stimulus driven activity in one hemisphere suppresses activity in the other hemisphere via callosal connections. Our results support the notion that an undamaged superior parietal lobule in the patient with tactile extinction suppresses the damaged parietal lobe function and causes extinction.

While interleukin-4 (IL-4) and interleukin-13 (IL-13) can utilize a common receptor, composed of IL-4Ralpha and IL-13Ralpha1, IL-4 can also signal through a receptor with IL-4Ralpha and the common gamma chain (gammaC) as its subunits. IL-4 and IL-13 have been reported to elicit similar biological effects in a number of settings, including stimulating Ig isotype switching to IgE and inducing chemokines and cytokines in a variety of cell types whereas, depending on the receptor expression on responder cells, differential effects such as induction of type II helper T cell differentiation by IL-4 but not by IL-13 are also well documented. Recent data suggest distinct roles for these two cytokines in the 'in vivo' pathology of airway inflammatory diseases such as asthma. In this study, we examined the possibility of differential signaling by IL-4 and IL-13 on cells of the airway, by comparing expression of receptor chains and activation of different Signal Transducer and Activator of Transcription (STAT) family members. Five primary cultured cell lines representing four non-immune human lung tissue cell types (smooth muscle, epithelium, endothelium, and fibroblast) were utilized. While we readily detected expression of IL-4 Ralpha and IL-13Ralpha1 in all five cell lines, gammaC was not detectable in any of these cell lines. Consistent with previous reports, we detected STAT-6 activation in all five airway tissue cell lines examined in response to both cytokines. In addition, we also consistently detected STAT-1 activation in all of these cells. This observation was extended to include lymphoid as well as myeloid cells that express also gammaC chain. In conclusion, while the study found no differences in STAT activation in response to the two cytokines, the data show that in addition to STAT-6 activation, STAT-1 activation is also a part of the integral signaling pathways utilized by IL-4 and IL-13.

A 54-year-old woman presented choreic movements in left face and extremities for three months. Cerebral angiography revealed occlusions of bilateral internal carotid arteries (right: after the furcation of posterior communicating artery; left: after the furcation of opthalmic artery) and net-like collaterals around the basal ganglia region (Moyamoya vessels). Haloperidol rapidly resolved the choreic movements and no recurrence was observed. PET demonstrated misery perfusion at bilateral temporo-parietal cortices. Especially, right peri-sylvian region showed the most severe ischemia. MRI demonstrated no infarcts. Therefore, ischemia of the right striatum was suspected to be the cause of the left-sided hemichorea. Previously, Moyamoya disease presenting chorea was infrequently reported in young people of less than 20 years of age. This is the first report of the aged patient of Moyamoya disease presenting with hemichorea and severe misery perfusion.

To explore pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy, we developed cellular model for synucleinopathy. In this experimental model, alpha-synuclein was overexpressed in SH-SY5Y cells, which were then exposed to mitochondrial toxins. The data thus obtained suggested the followings. (1) By the treatment with rotenone, wild type alpha-synuclein overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies. (2) The aggregate formation of alpha-synuclein may be cytoprotective. (3) The catechol-derived quinones are candidate molecules to facilitate the oligomer formation of a-synuclein. (4) The cells overexpressing S129A mutant showed few aggregations. It is suggested that phosphorylation at serine 129 is essential for aggregate formation. (5) In wild-type alpha-synuclein cells treated with rotenone, unfolded protein response (UPR) markers were induced prior to the induction of mitochondrial disruption and caspase-3 activation. (6) On the other hand, the S129A mutant failed to activate these UPRs. Thus it seems plausible that alpha-synuclein toxicity is dependent on the phosphorylation at S129.

Depressive symptoms and personality traits 90+ years population were examined. Data were obtained from 33 aged people (mean 93 +/- 3.2 years old; range 90-105 years old) using the Hamilton Rating Scale for depression and a questionnaire for the evaluation of type A personality trait (devised by Dr. Maeda). Scores of > 11 in the Hamilton Rating Scale for depression were considered indicative of depression. This score was found in 39% of cases. There are four types of depressive symptoms among the 90+ years population: sleep disturbance and somatic complain type; depressive mood type; hypochodrical type; reference of ideas and obsessive-compulsive type. The usual distributions of symptoms is 43, 29, 21 and 7% respectively. According to the questionnaire for type A personality trait among the 33 cases, there were more people with type A personality (n = 18; 56%) than there were those with type B (n = 15; 44%). Of the total number of cases studied, there was a tendency high scores to be achieved items characteristic of type A personality, such as a thorough native, self-confidence and precision. On the other hand, there are also tendencies for flexibilities and "going-my-way" traints in the 90+ year population. There is a significant correlation between scores in Hamilton Rating Scale for depression and scores in the type A personality questionnaire.

The fifth allele, DNASE1*5, of human deoxyribonuclease I (DNase I) has been discovered. Polymerase chain reaction fragments containing exon 5 of the DNase I gene were screened for DNA polymorphism using single-strand conformation polymorphism (SSCP) analysis. DNAs from 114 unrelated Japanese and 81 German individuals were tested and a new variant was detected. By DNA sequencing analysis, this variant was found to be caused by a heterozygous G-A transition at nucleotide position 1227 that results in a Val to Met substitution at amino acid position 92 of the mature enzyme. The nucleotide substitution was also confirmed by mismatched polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Genotyping of the variant could be carried out by three independent reactions based on PCR amplification, and phenotyping by isoelectric focusing followed by immunostaining. The results supported the presence of the fifth codominant allele, DNASE1*5, which generates a new isozyme.

The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes are governed by the repertoire of expressed genes, and the levels and timing of expression, it is important to have experimental tools for the direct monitoring of large numbers of mRNAs in parallel. We have developed an approach that is based on hybridization to small, high-density arrays containing tens of thousands of synthetic oligonucleotides. The arrays are designed based on sequence information alone and are synthesized in situ using a combination of photolithography and oligonucleotide chemistry. RNAs present at a frequency of 1:300,000 are unambiguously detected, and detection is quantitative over more than three orders of magnitude. This approach provides a way to use directly the growing body of sequence information for highly parallel experimental investigations. Because of the combinatorial nature of the chemistry and the ability to synthesize small arrays containing hundreds of thousands of specifically chosen oligonucleotides, the method is readily scalable to the simultaneous monitoring of tens of thousands of genes.

We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 micrograms/ml

According to Health and Welfare Ministry figures (1985), 95% of pregnant women wished to breast-feed their baby, and the number of breast-fed newborns is increasing annually. Nevertheless, the Ministry reports that only 49.5% of one-month-old babies are still being breast-fed. In 1977, Ina Health Center established Mother-Baby Clinics, offering education about breast-feeding. The Center also started research in 1983, with the cooperation of the Kami-Ina Public Health Nurses' Association, into infant feeding styles. Since then, the local breast-feeding rate has risen well above the national average. This paper presents practical guidance toward encouraging successful breast-feeding. First, timely advice must be offered to pregnant women, to establish a correct understanding of the importance of breast-feeding. The mother's strong intention is a major factor, as is support from people around her--family, employer, health care professionals. The most important period for establishing breast-feeding is the first three months. Adequate milk secretion, good breast condition, and proper sucking are also crucial. Education and further research are still needed.

We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NKCF and NK-CIA activity are lost after 2 d at 37 degrees C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitor activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-gamma, and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-gamma suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-alpha or -beta was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodies specific for tumor necrosis factor (TNF), but not those specific for lymphotoxins, inhibit both NK-CIA and NKCF activity in the NK cell-derived supernatant. Recombinant TNF, in the range of concentrations corresponding to that of the cytotoxic activity on L-929 cells present in supernatants, mediated both NKCF and NK-CIA activity.(ABSTRACT TRUNCATED AT 400 WORDS)

We show that the cytotoxins tumor necrosis factor (TNF) or lymphotoxin (LT), at concentrations of approximately 10(-11) M induce monocytic differentiation of human myeloid cell lines. After 5 d of culture in the presence of rTNF and LT, a significant proportion of the myeloid cell lines express monocyte differentiation antigens and ANAE activity, and become able to reduce nitroblue tetrazolium (NBT) and mediate low levels of ADCC against tumor target cells. These markers of differentiation, however, are maximally induced when rIFN-gamma, at concentrations as low as 4 U/ml, is present simultaneously with the cytotoxins, and the two classes of cytokines act synergistically to induce terminal differentiation. The appearance of monocytic antigens is accompanied by acquisition of morphology and other functional properties of mature monocytic cells, such as chemiluminescence and phagocytosis, and by expression of FcR for monomeric IgG. A decrease in cell proliferation accompanies induced differentiation, and is not due to the cytotoxic properties of TNF or LT, as indicated in simultaneous analysis of surface phenotype and cell cycle. The lack of cytotoxicity of TNF on the HL-60 cell line is also demonstrated by the enhancing effect of TNF on HL-60 cell growth and nucleoside uptake in the first 2 d of culture. These data show that the cytotoxins TNF and LT mediate complex effects on cells of the myelomonocytic lineage and, in synergy with IFN-gamma, can fully induce immature myeloid cells to differentiate into cells with phenotypic, functional, and proliferative characteristics of terminally differentiated myelomonocytic cells.

We have shown that lymphocytes stimulated by PHA produce colony-forming unit of granulocyte/monocyte (CFU-GM)-stimulating and -inhibiting activities, IFN-gamma, and lymphotoxin (LT). IFN-gamma is necessary for inhibition of CFU-GM by PHA-conditioned medium (CM), as shown by experiments in which removal of IFN-gamma from PHA-CM abrogated inhibition. However, experiments in which rIFN-gamma was added to IFN-gamma-depleted PHA-CM revealed the presence, in PHA-CM, of other factors that act in synergy with IFN-gamma to inhibit CFU-GM. Fractionation of PHA-CM on a Sephadex G-100 column was used to separate IFN-gamma and LT. Colony-inhibiting activity was eluted in fractions that contained both IFN-gamma and LT activities, identifying LT as a factor present in PHA-CM that synergizes with IFN-gamma to inhibit CFU-GM. Treatment of PHA-CM with mAb against either IFN-gamma or LT completely abrogated the colony-inhibiting activity, demonstrating a requirement for both lymphokines in PHA-CM-induced inhibition of CFU-GM. Experiments using rIFN-gamma and preparations of purified LT confirmed that neither lymphokine alone, when added to bone marrow cells at the concentrations present in PHA-CM, strongly inhibited day 7 or day 14 CFU-GM, but that the two lymphokines, added together, behaved synergistically to inhibit CFU-GM by up to 70%. The inhibition observed using purified preparations of lymphokines shows that synergy between IFN-gamma and LT is sufficient to explain PHA-CM-induced inhibition of CFU-GM. Our findings suggest that activated T cells regulate hematopoiesis through the release of inhibitory as well as stimulatory factors, and that the simultaneous production of IFN-gamma and LT may represent a mechanism of suppression of hematopoiesis in the cases of bone marrow failure associated with the presence of activated T cells.

Phonetic letters in Japanese (Hiragana, 23 in number) written by 6 adults (Ws) were presented one by one and the S was asked to guess by which W it was written. Immediately after the S made the guess, the code of correct W was given on each trial. The Ss were Japanese housewives, students etc., 53 in number. Rate of correct identification increased during 23 × 6 trials, but only from 0.3 to 0.4 on the average. The learning transferred to the remaining 23 letters of the same kind but not to letters of the other kind (Katakana). On each trial, the S verbally described cues upon which the guess was made. When the data were separately analysed according to Ws, it was found that letters of the W who was most difficult to identify were most ‘diffused’ in characterization by the Ss. The relevance of the present experiment to study of concept identification in general was also discussed.