Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

Simple screening test for risk of falls in the elderly

Background:   The aim of this study is to construct a simple screening test for the risk of falls in community-dwelling elder persons.
Methods:   A total of 1378 community-dwelling people aged 65 years and older in five different communities in Japan were asked to answer a self rated questionnaire including 22 items covering physical, cognitive, emotional and social aspects of functioning and environmental factors. At a six-month follow-up, the outcome of fall occurrence and the number of falls was ascertained by social workers, health visitors or nurses.
Results:   Five out of 22 items were selected using a logistic regression model. Using this five-item version, a screening test was constructed, and at the best cut-off point, the sensitivity and specificity were 68% and 70%, respectively. The validity of this scale was tested on persons with cognitive dysfunction.
Conclusion:   The simplicity and the predictive validity of the screening test support the use of this test in health check ups or general outpatient facilities.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Electrogastrographic activity in patients who received proximal gastrectomy plus jejunal interposition or total gastrectomy plus jejunal interposition.

Electrogastrograms (EGGs) were recorded in patients both before and after receiving proximal gastrectomy plus jejunal interposition (PGJI) or just after receiving total gastrectomy plus jejunal interposition (TGJI). Intraluminal pressure was also recorded in some postoperative patients. The EGG 3 cpm component (2.5-4.9 cpm) remained after PGJI, but subsequently decreased with a significant reduction in the preoperative to postoperative ratio of the 3 cpm components (P<0.05). The mean frequency of the 3 cpm components increased significantly after PGJI (P<0.05) and its instability factor increased. The EGG 10 cpm components became relatively dominant compared to other frequency components in 2 out of 8 of patients having PGJI but the mean amplitude of 10 cpm decreased. In TGJI patients, only the 10 cpm component was conspicuous in EGG as in the case of total gastrectomy and Roux en Y anastomosis procedures. The spectral frequencies of intraluminal pressure in the interposed jejunum were similar to the EGG of 10 cpm components both in the case of PGJI and TGJI patients. In conclusion, surface EGG could record the electrical activities of the interposed jejunum more easily in patients having had TGJI than in PGJI.     

Changes in hepatic lymph vessels in endotoxaemia.

This study was undertaken into rats to investigate changes in the hepatic lymph vessels and the space of Disse in endotoxaemia and to examine their relationship with the development of endotoxin-induced hepatic injury. Lymph stasis, namely dilatation of the lymph vessels and oedema, developed rapidly in the medium-sized portal canals, the large portal canals, and the liver hilum after endotoxin injection, but not in the small portal canals. Such changes reached their maximum 4-8 h after endotoxin injection and had recovered markedly by 16 h after the injection. The space of Disse remained within normal limits during this period. These findings suggest that the intrahepatic lymph stasis in endotoxaemia may be caused by a reduction in the pumping activity of the extrahepatic and the intrahepatic large lymph vessels rather than by an increase of lymph formation in the liver lobules. There was no evidence suggesting a direct relationship between the disturbance of hepatic lymph flow and the development of hepatic injury in endotoxaemia.     

Pulmonary Mycobacterium avium complex infection: association with NRAMP1 polymorphisms.

The present study aimed to elucidate risk factors for nonimmunocompromised pulmonary Mycobacterium avium complex (MAC) infection. Epidemiological data and variations of candidate genes for mycobacterial diseases were analysed in 111 patients with pulmonary MAC infection. Four polymorphisms of the human natural resistance-associated macrophage protein (NRAMP)1 gene, the 5'(GT)n, 469+14 G/C, D543N and the 3'untranslated region (3'TGTG) insertion/deletion, were genotyped using PCR-based methods. Fok I and Taq I polymorphisms of the vitamin D receptor gene and -221 X/Y and codon 54 A/B polymorphisms of the mannose binding lectin gene were also evaluated. Females were more susceptible to MAC infection mainly affecting the right middle lobe or lingular segment of the lung. Patients' residence at the onset of the disease was distributed evenly irrespective of a waterfront or city water supply system. As compared with homozygotes for major alleles of the D543N and TGTG insertion/deletion polymorphism of the NRAMP1 gene, heterozygotes containing minor alleles were less often observed in MAC cases than in controls. This genetic effect was more significant in patients without comorbidity but not in patients with comorbidity. Other polymorphisms did not show any association with the MAC infection. The human natural resistance-associated macrophage protein 1 gene might be involved in susceptibility to pulmonary Mycobacterium avium complex infection.     

Effects of hyperbaric oxygen exposure on experimental hepatic ischemia reperfusion injury: relationship between its timing and neutrophil sequestration.

Recent studies have shown that hyperbaric oxygen therapy (HBOT) reduces neutrophil endothelial adherence in venules and also blocks the progressive arteriolar vasoconstriction associated with ischemia-reperfusion (I-R) injury in the extremities and the brain. In order to elucidate the effects of HBOT after I-R in digestive organs, particularly in the liver, we evaluated the following: 1) the relationship between timing of HBOT and tissue damage; and 2) HBOT's effects on neutrophil sequestration. Using a hepatic I-R (45 minute) model in male rats, survival rate, liver tissue damage, and neutrophil accumulation within the sinusoids in the HBOT-treated group (Group H) were compared to those in the nontreated group (Group C). For the HBOT-treated group, HBOT was administered as 100% oxygen, at 2.5 atm absolute, for 60 minutes. When HBOT was given 30 minute after I-R, the survival rate was much better in Group H than in Group C. HBOT performed within 3 hours of I-R markedly suppressed increases in the malondialdehyde level in tissues of the liver and lessened the congestion in the sinusoids. In addition, HBOT just after I-R caused decreased number of cells stained by the naphthol AS-D chloroacetate esterase infiltrating into the sinusoids. HBOT 3 hours after reperfusion, however, showed no clear effects upon neutrophil sequestration compared to Group C. These results indicate that HBOT performed within 3 hours of I-R alleviates hepatic dysfunction and improves the survival rate after I-R. Herein, we propose 1 possible mechanism for these beneficial effects: early HBOT given before neutrophil-mediated injury phase may suppress the accumulation of neutrophils after I-R. In conclusion, we believe that the present study should lead to an improved understanding of HBOT's potential role in hepatic surgery.     

Effects of diet with or without exercise on leptin and anticoagulation proteins levels in obesity.

Obesity is a risk factor for cardiovascular disease and thromboembolic events. We investigated the effects of weight reduction by a 12-week calorie-restricted diet with or without aerobic exercise (diet group and diet plus exercise group) on leptin and anticoagulation proteins levels. Forty-two obese nondiabetic individuals were evaluated for blood levels of leptin, protein C activity, free protein S antigen and for body fat area calculated on computerized tomography before and after intervention. Before intervention, serum levels of leptin and free protein S antigen correlated positively with several adiposity-related parameters. After the program, body weight and fat area were significantly decreased in both groups. Body mass index and leptin levels decreased in both groups, with a larger change in the diet plus exercise group than in the diet group. Although protein C activity levels did not change in both groups, free protein S antigen levels decreased significantly in the diet plus exercise group. In conclusion, the 12-week programs had significant effects on the initial weight reduction and body fat mass, decreasing lepin levels in obese nondiabetic individuals. To clarify whether aerobic exercise has additional or direct effects on the anticoagulation system, a study in a large number of individuals is needed.