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Previous research has not compared implicit affective responses to smoking-related stimuli in occasional (i.e., those who smoke less than one cigarette per day) and daily smokers (i.e., those who smoke at least once per day). In addition to assessing their motivations for smoking, implicit affective responses were measured using the Affect Misattribution Procedure (AMP) in occasional (n=19) and daily smokers (n=34) to smoking-related and neutral cues. Half of the cues depicted a human interacting with an object (i.e., active), whereas the remaining cues depicted objects alone (i.e., inactive). Results indicated that for the active cues, daily smokers responded more positively to smoking-related than to neutral cues, whereas occasional smokers showed no difference in their implicit responses. In addition to smoking frequency, relative differences in implicit responses to active cues were related to cognitive enhancement motivation. For inactive cues, implicit responses were related to cognitive enhancement as well as reinforcement. Because daily smokers have more positive implicit responses to active smoking-related cues than occasional smokers, these cues may play an important role in maintaining smoking behavior in daily smokers. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in cells by treatment with lipopolysaccharide (LPS) in vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo. Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP+/NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP+/NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock. [ABSTRACT FROM AUTHOR]

Flotillin microdomains, specialized lipid raft domains in cell membranes, serve as physical platforms for many different molecules important in crucial intracellular signaling pathways. Flotillin-2 (Flot2), together with flotillin-1, is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and has been implicated in the progression of cancer and metastasis formation. Based largely on studies in xenograft models, flotillin-2 has been implicated in the progression of multiple types of human tumors, including breast cancer. In our studies, we identified flotillin-2 as highly amplified in a high-throughput comparative genomic hybridization screen of human breast cancer cell lines and breast tumor samples. Short hairpin RNA-mediated reduction of flotillin-2 protein levels significantly reduced the tumorigenicity and metastatic capability of a human breast cancer cell line in vivo. We generated mice deficient for flotillin-2 and also found a reduction of flotillin-1 protein levels and complete absence of flotillin-specific membrane microdomains in these mice. To examine the role of Flot2 in mammary tumorigenesis and lung metastasis, we used an in vivo molecular genetics approach, crossing a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with gene-targeted Flot2−/− mice. Flotillin-2 deficiency lead to a striking reduction in the number of lung metastasis observed, but had no influence on primary tumor formation in this model. Our results indicate, using a novel in vivo animal model approach, that Flot2 is an important regulator of mammary tumor-derived lung metastasis. [ABSTRACT FROM AUTHOR]

Study Objectives: The present study introduces a method that has been developed to improve the remote collection and transportation of gas samples from the nose and lungs.Design: Assessment of agreement between two methods of clinical measurements.Setting: Noninvasive exhaled gas measurement at a respiratory research laboratory.Participants: Ten nonsmoking adult volunteers (median age, 44 years; age range, 33 to 53 years; men, 6; women, 4) were recruited.Measurements and Results: Exhaled nitric oxide (ENO) and nasal nitric oxide (NNO) outputs were measured directly (on-line) and remotely (off-line). With the velum closed, lung air was exhaled at fixed flows (ie, 6, 8, and 10 L/min) (ENO) or room-air was aspirated through the nose in series at one fixed flow (ie, 5 to 8 L/min) (NNO). The off-line nitric oxide (NO) measurements were achieved by a gas collection tube system, which consisted of a flow control unit, a tube reservoir with one-way valves at both ends, and an interrupter valve allowing the trapping of gas inside the tube and eliminating the inclusion of "dead space." After clamping, the reservoir may store and transport the gas samples for delayed analysis. The coefficient of variation of three consecutive NO measurements was < 3% for both on-line and off-line ENO and NNO. The correlations between on-line and off-line measurements in both ENO and NNO outputs were high (r = 0.99; R(2) = 0.99), and, unlike previous studies using bag-collection, the ENO outputs for on-line and off-line measurements were in good agreement (Bland-Altman test) at all flows tested.Conclusions: The tube gas collection system eliminates the dead space and contamination during the gas sampling and permits the cost-effective and reliable off-line collection of both nasal and exhaled gas samples. [ABSTRACT FROM AUTHOR]