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71.
Bensafi M Porter J Pouliot S Mainland J Johnson B Zelano C Young N Bremner E Aframian D Khan R Sobel N 《Nature neuroscience》2003,6(11):1142-1144
Neural representations created in the absence of external sensory stimuli are referred to as imagery, and such representations may be augmented by reenactment of sensorimotor processes. We measured nasal airflow in human subjects while they imagined sights, sounds and smells, and only during olfactory imagery did subjects spontaneously enact the motor component of olfaction--that is, they sniffed. Moreover, as in perception, imagery of pleasant odors involved larger sniffs than imagery of unpleasant odors, suggesting that the act of sniffing has a functional role in creating of olfactory percepts. 相似文献
72.
Calcineurin B1 is essential for positive but not negative selection during thymocyte development 总被引:6,自引:0,他引:6
During development, discrete cell fates often result from variation in the intensity of a particular signal. The mechanisms underlying these seemingly analog-to-digital switches are not understood. In developing T lymphocytes, low-intensity signals through the antigen receptor result in positive selection while more intense signals give rise to negative selection. By deleting the genetic locus encoding the regulatory B1 subunit of calcineurin specifically in thymocytes, we found an absolute requirement for calcineurin in positive selection. In contrast, calcineurin activity was dispensable in several models of negative selection. Unexpectedly, we found that removal of calcineurin activity from thymocytes results in inefficient ERK activation at the double-positive stage of thymocyte development, when selection occurs. These studies clarify the mechanism by which graded signals are converted to discrete outcomes in T cell development and further indicate that the developmental roles of calcineurin likely contribute to immunosuppression by calcineurin inhibitors. 相似文献
73.
Joel D. Schiff Norbert I. A. Overweg 《Pflügers Archiv : European journal of physiology》1980,389(1):75-79
The effects of changing bathing medium osmolality on tension generation in smooth muscle were studied on potassium-depolarized segments of rat ileum. Increasing the tonicity of the medium evokes a transient relaxation of the smooth muscle; restoration of isotonicity evokes a transient contraction of similar amplitude and time course. While immersed in hypertonic media of less than 1.3 times normal tonicity, the smooth muscle slowly increases its isometric tension; in media of nearly twice normal tonicity, the smooth muscle loses tension. All of these effects occur whether the medium is made hypertonic with added NaCl or sucrose. 相似文献
74.
75.
Thomas L. Patterson Lawrence W. Smith Tom L. Smith Joel Yager Igor Grant 《Journal of behavioral medicine》1992,15(2):113-125
Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical-correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes.This work was supported by Award SA 325 from the Medical Research Service of the Department of Veterans Affairs. 相似文献
76.
Academic medical centers face barriers to training physicians in systems- and practice-based learning competencies needed to function in the changing health care environment. To address these problems, at the University of Virginia School of Medicine the authors developed the Clinical Health Economics System Simulation (CHESS), a computerized team-based quasi-competitive simulator to teach the principles and practical application of health economics. CHESS simulates treatment costs to patients and society as well as physician reimbursement. It is scenario based with residents grouped into three teams, each team playing CHESS using differing (fee-for-service or capitated) reimbursement models. Teams view scenarios and select from two or three treatment options that are medically justifiable yet have different potential cost implications. CHESS displays physician reimbursement and patient and societal costs for each scenario as well as costs and income summarized across all scenarios extrapolated to a physician's entire patient panel. The learners are asked to explain these findings and may change treatment options and other variables such as panel size and case mix to conduct sensitivity analyses in real time. Evaluations completed in 2003 by 68 (94%) CHESS resident and faculty participants at 19 U.S. residency programs preferred CHESS to a traditional lecture-and-discussion format to learn about medical decision making, physician reimbursement, patient costs, and societal costs. Ninety-eight percent reported increased knowledge of health economics after viewing the simulation. CHESS demonstrates the potential of computer simulation to teach health economics and other key elements of practice- and systems-based competencies. 相似文献
77.
Elliott DE Setiawan T Metwali A Blum A Urban JF Weinstock JV 《European journal of immunology》2004,34(10):2690-2698
Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells. 相似文献
78.
The intercellular adhesion molecule (ICAM) family of proteins 总被引:8,自引:0,他引:8
Macromolecular adhesive associations between cells are important for transmitting spatial and temporal information that is
critical for immune system function. One such group of proteins, the intercellular adhesion molecules (ICAMs), has grown as
newly identified members are revealed. In addition, the functions of the ICAMs, in general, have begun to be better understood,
including intracellular signaling events. This information has led to the design of novel therapeutic agents that may prove
effective in a variety of disease states. 相似文献
79.
Molecular alterations in atypical adenomatous hyperplasia occurring in benign and cancer-bearing lungs. 总被引:1,自引:0,他引:1
Joel F Gradowski Geeta S Mantha Jennifer L Hunt Sanja Dacic 《Diagnostic molecular pathology》2007,16(2):87-90
Atypical adenomatous hyperplasia (AAH) is considered to be a precursor lesion of the lung adenocarcinoma. Several genetic abnormalities have been reported in AAH associated with adenocarcinoma, but little is known about AAH associated with benign lung lesions. To address this we compared the molecular characteristics of AAH present in benign conditions to those coexisting with carcinoma. Seven cases of AAH from resected non-neoplastic lungs (AAH-B) and 12 cases from lungs resected for primary lung carcinoma (AAH-M) were analyzed for loss of heterozygosity (LOH) using 21 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes on chromosomes 3p, 5q, 7p, 9p, 10q, and 17p. Direct DNA sequencing for K-ras mutation was also performed. There was a broad range of LOH in both groups. No LOH was identified in 3 cases (25%) of AAH-M, but all cases of AAH-B showed LOH (P=0.26). Six cases (50%) of AAH-M and 3 cases (43%) of AAH-B showed loss at 1 marker (P=0.99). LOH at 2 or more markers was identified in 3 (25%) cases of AAH-M and 4 (57%) cases of AAH-B (P=0.32). LOH was most frequently detected on chromosomes 3p and 10q in both groups. The difference in overall fractional allelic loss between the 2 groups did not reach statistical significance. K-ras mutations were not identified in either group. Our results showed a significant overlap in LOH patterns between AAH with or without coexistent lung malignancy. Therefore, AAH may represent a smoking induced low-grade neoplastic lesion that may be a precursor lesion of only a subset of invasive lung adenocarcinoma. 相似文献
80.
Zoref-Shani E Bromberg Y Hirsch J Feinstein S Frishberg Y Sperling O 《Molecular genetics and metabolism》2003,78(2):158-161
We identified a novel point mutation (I137T) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) encoding gene, in a patient with partial deficiency of the enzyme (variant of Lesch-Nyhan syndrome). The mutation, ATT to ACT, resulting in substitution of isoleucine to threonine, occurred at codon 137 (exon 6), which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). We suggest the mechanism by which the mutation-induced structural alteration of HPRT reduced the affinity of the enzyme for PRPP. 相似文献