Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate

The goals of this study were to (1) determine the effects of repeated inhalation of relatively insoluble nickel oxide (NiO) and highly soluble nickel sulfate hexahydrate (NiSO4.6H2O) on lung particle clearance, (2) investigate the effects of repeated inhalation of NiO or NiSO4 on the pulmonary clearance of subsequently inhaled 85Sr-labeled microspheres, (3) correlate the observed effects on clearance with accumulated Ni lung burden and associated pathological changes in the lung, and (4) compare responses in F344 rats and B6C3F1 mice. Male F344/N rats and B6C3F1 mice were exposed whole-body to either NiO or NiSO4.6H2O 6 hr/day, 5 days/week for up to 6 months. NiO exposure concentrations were 0, 0.62, and 2.5 mg NiO/m3 for rats and 0, 1.25, and 5.0 mg NiO/m3 for mice. NiSO4.6H2O exposure concentrations were 0, 0.12, and 0.5 mg NiSO4.6H2O/m3 for rats and 0, 0.25, and 1.0 mg NiSO4.6H2O/m3 for mice. After 2 and 6 months of whole-body exposure, groups of rats and mice were acutely exposed nose-only to 63NiO (NiO-exposed animals only), 63NiSO4.6H2O (NiSO4.6H2O-exposed animals only), or to 85Sr-labeled polystyrene latex (PSL) microspheres (both NiO- and NiSO4.6H2O-exposed animals) to evaluate lung clearance. In addition, groups of rats and mice were euthanized after 2 and 6 months of exposure and at 2 and 4 months after the whole-body exposures were completed to evaluate histopathological changes in the left lung and to quantitate Ni in the right lung. Repeated inhalation of NiO results in accumulation of Ni in lungs of both rats and mice, but to a greater extent in lungs of rats. During the 4 months after the end of the whole-body exposures, some clearance of the accumulated Ni burden occurred from the lungs of rats and mice exposed to the lower, but not the higher NiO exposure concentrations. Clearance of acutely inhaled 63NiO was also impaired in both rats and mice, with the extent of impairment related to both exposure concentration and duration. However, the clearance of acutely inhaled 85Sr PSL microspheres was not impaired. The repeated inhalation of NiO resulted in alveolar macrophage (AM) hyperplasia with accumulation of NiO particles in both rats and mice, chronic alveolitis in rats, and interstitial pneumonia in mice. These lesions persisted throughout the 4-month recovery period after the NiO whole-body exposures were terminated. In contrast, repeated inhalation of NiSO4.6H2O did not result in accumulation of Ni in lungs of either rats or mice and did not affect the clearance of 63NiSO4.6H2O inhaled after either 2 or 6 months of NiSO4.6H2O exposure. Clearance of the 85Sr-labeled microspheres was significantly impaired only in rats exposed to the microspheres after 2 months of exposure to NiSO4.6H2O. Histopathological changes in rats were qualitatively similar to those seen in NiO-exposed rats. Only minimal histopathological changes were observed in NiSO4.6H2O-exposed mice. These results suggest that repeated inhalation of NiO at levels resulting in AM hyperplasia and alveolitis may impair clearance of subsequently inhaled NiO. The potential effects of repeated inhalation of soluble NiSO4.6H2O on the clearance of subsequently inhaled poorly soluble particles are less clear.     

The human REC2/RAD51B gene acts as a DNA damage sensor by inducing G1 delay and hypersensitivity to ultraviolet irradiation

HsRec2/Rad51B is a 350-amino acid protein with a molecular mass of 38,300 Da that appears to be involved in cell cycle regulation and UV-induced apoptosis. The mouse and human genes were isolated based on their homology to a recombinational repair gene from Ustilago maydis and contain functional domains to hRAD51 and hLIM 15 (M. C. Rice et al., Proc. Natl. Acad. Sci. USA, 94: 7417-7422, 1997). Here, we report the results of studies on the behavior of CHO cells containing a plasmid encoding a wild-type hsRec2/Rad51B, a full-length protein with a single mutation at residue 163, which lies in the putative src site, and a truncated version of hsRec2/Rad51B, containing only the first 100 amino acids at the NH2 terminus. Using fluorescence-activated cell sorting analysis to follow the progression of cells through the cell cycle, we find that stable transfectants constitutively overexpressing the wild-type human Rec2/Rad51B protein exhibit a G1 delay. In addition, when irradiated with UV at a dose of 15 J/m2, CHO cells transfected with the various hREC2/RAD51B vectors exhibited different responses. Cells expressing the wild-type human Rec2/Rad51B underwent apoptosis, with the greatest cell death occurring 24 h after irradiation. The control cells, which contained an empty vector, and the cells expressing truncated hsRec2/Rad51B or the full-length Rec2 with a mutation at residue 163 did not. In summary, these findings of cell cycle slowing and UV-induced apoptosis in CHO cells constitutively expressing the human Rec2/Rad51B protein suggest that hsRec2/Rad51B plays a role in a DNA damage surveillance pathway.     

Use of dialectical behavior therapy in a partial hospital program for women with borderline personality disorder

One of the difficulties of surgical treatment of pulmonary atresia with patent septum by unifocalisation resides in the accurate diagnosis of the different collateral vessels to the lung in order to optimise the surgical approach: anterior or posterolateral thoracotomy, and to determine the type of operation: one or two stages repair. Conventional angiography, even using different views, cannot always give an accurate representation of the anatomy of the different collateral vessels, especially their relationship to the bronchial structures. The authors report the contribution of spiral angioscanner with three dimensional reconstruction in the determination of the operative strategy of a case of pulmonary atresia with patent septum.     

Epidemiology of and risk factors for pancreatic cancer

In the United States, incidence of and mortality from pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in blacks than in whites and higher in men than in women. Cigarette smoking increases the risk of pancreatic cancer, while alcohol consumption largely shows no relationship, coffee consumption shows little, if any, association, and a number of occupational exposures seem to be associated but the results are not fully consistent. Finally, human studies have suggested positive associations with meat consumption and carbohydrate intake and a protective effect of dietary fiber and consumption of fruits and vegetables. Thus, much progress has been made in the last two decades in identifying risk factors, but much epidemiologic work is needed to identify and reduce putative exposures.     

An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.     

Communication in reactive multiagent robotic systems

Multiple cooperating robots are able to complete many tasks more quickly and reliably than one robot alone. Communication between the robots can multiply their capabilities and effectiveness, but to what extent? In this research, the importance of communication in robotic societies is investigated through experiments on both simulated and real robots. Performance was measured for three different types of communication for three different tasks. The levels of communication are progressively more complex and potentially more expensive to implement. For some tasks, communication can significantly improve performance, but for others inter-agent communication is apparently unnecessary. In cases where communication helps, the lowest level of communication is almost as effective as the more complex type. The bulk of these results are derived from thousands of simulations run with randomly generated initial conditions. The simulation results help determine appropriate parameters for the reactive control system which was ported for tests on Denning mobile robots.     

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.     

The striatum in the system of the central mechanisms of biorhythm control

BACKGROUND: This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital inpatients and to identify variables associated with long-term smoking cessation following hospitalization. METHODS: One hundred eighty-five patients were randomly assigned to one of three smoking cessation interventions: (1) A Minimal Care (MC) condition, consisting of a brief physician-delivered motivational message to stop smoking, (2) a Counseling + Active Nicotine Patch (CAP) condition in which patients received the motivational message, a 6-week supply of nicotine patches, and extended bedside and telephone counseling, and (3) a Counseling + Placebo Patch (CPP) condition identical to the CAP condition except the supplied patches contained no nicotine. RESULTS: At 6-month follow-up, abstinence rates for the three treatments were 4.9, 6.5, and 9.7% for the MC, CPP, and CAP treatments, respectively. These differences were not statistically significant. Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis. The nicotine patch was well tolerated by hospital inpatients. CONCLUSIONS: The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses. Our study provided no evidence of the superiority of nicotine patches versus placebo, but this does not preclude the possibility that future research using larger samples might detect differences between patch groups. Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease.