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1.
Human immune function undergoes adverse changes with aging. The T cells, which have a central role in cellular immunity, show the largest age-related differences in distribution and function, with thymus involution as the apparent underlying cause. The immune responses to acute exercise and training have not been studied extensively in the elderly. The natural killer (NK) cell response to a single exercise challenge is normal in older individuals, but immediately after exercise the elderly subjects manifest less suppression of phytohemagglutinin (PHA)-induced lymphocyte proliferation than younger individuals. In contrast, a strenuous exercise seems to induce a more sustained postexercise suppression of cellular immunity in older individuals than in their young peers. A few cross-sectional comparisons of immune status between physically fit elderly individuals and young sedentary controls suggest that habitual physical activity may enhance NK cell activity, checking certain aspects of the age-related decline in T cell function, such as reduced mitogenesis in response to plant lectins and decreases in the production of certain types of cytokine. The clinical implications, however, remain to be clarified by future study.  相似文献   

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Cell adhesion molecules (CAM) have a key role in the inflammatory response. Selectins, integrins and immunoglobulin (Ig) gene superfamily adhesion receptors mediate the different steps of the migration of leucocytes from the blood-stream towards inflammatory foci. The activation of endothelial cells (EC) upregulates the expression of several CAM and triggers the interaction of these cells with leucocytes. Selectins are involved in the initial interactions (tethering/rolling) of leucocytes with activated endothelium, whereas integrins and Ig superfamily CAM mediate the firm adhesion of these cells and their subsequent extravasation. During rolling, leucocytes are activated through the intracellular signals generated by CAM and chemokine receptors. Blockade of the function or expression of CAM has emerged as a new therapeutic target in inflammatory diseases. Different drugs are able to interfere with cell adhesion phenomena. In addition, new antiadhesion therapeutic approaches (blocking monoclonal antibodies, soluble receptors, synthetic peptides, peptidomimetics, etc.) are currently in development.  相似文献   

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Different adhesion molecules are implicated in the pathogenesis in glomerulonephritis. Leukocyte adhesion molecules play a critical role in causing renal damage in a variety of glomerulonephritic conditions. In order to understand the mechanisms by which distinct adhesion molecules are involved in human glomerulonephritis, it is necessary to have an overview of their function in maintenance of tissue architecture, morphogenesis, immunosurveillance, inflammation, tumor growth, etc. Thus, this review addresses the role of cadherins, selectins, integrins, and members of the immunoglobulin supergene family in developing, normal, and diseased kidney with special attention to glomerulonephritis and possible new therapeutic approaches.  相似文献   

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Adhesion molecules play an important role in organogenesis, would healing, inflammation, and progression of malignant tumors. Three major classes of adhesion molecules may be discriminated by function: (a) calcium-dependent homotypic adhesion molecules (e.g. cadherins), (b) substrate adhesion molecules (e.g. integrins) and (c) heterotypic adhesion molecules (e.g. ICAM-1). Molecules of each of the three classes have been identified in urologic tumors. Results of research on substrate adhesion molecules and heterotypic adhesion molecules have not yet led to new clinical concepts. In contrast, loss of E-cadherin in tumors of the bladder and prostate has been clearly associated with de-differentiation of tumors and diminished survival of patients. Loss of another adhesion molecule, C-CAM, has been observed in prostate cancer. This has led to new therapeutic approaches, which are in an experimental stage at present. It may be expected that, in the future, new therapeutic concepts will be based on research on adhesion molecules in urologic tumors.  相似文献   

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Cellular adhesion molecules (CAMs) are critical components in the processes of embryogenesis, tissue repair and organization, lymphocyte function, lymphocyte homing and tumor metastasis, as well as being central to the interactions between hemopoietic progenitors and bone marrow microenvironment, and between leukocytes and platelets with vascular endothelium. Expression of CAMs regulates normal hemopoiesis and migration and function of mature hemopoietic cells. CAMs are an important part of the inflammatory response and may regulate cytokine synthesis. In addition, CAM expression may be critical for tumorigenesis. Monoclonal antibodies to CAMs have been developed for clinical use; initial results suggest that these agents have great potential in the prevention and treatment of inflammation, thrombosis, reperfusion injury, and graft rejection.  相似文献   

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The rosette-forming cell (RFC) response of mice immunized with varying doses of Toxoplasma gondii was studied by immunocytoadherence (ICA). The specificity of ICA in the present system was tested by passive sensitization with hyperimmune serum in vivo and in vitro. A slight increase in RFC was observed with the latter. Prior treatment of spleen cells from immunized animals with rabbit anti-mouse immunoglobulin resulted in total inhibition of ICA. During the primary and the secondary response after 10 days, the number of RFC rose rapidly to reach the peak on the 3rd day. With secondary immunization 30 days later, the peak shifted to the 2nd day. Mice infected with a lower dose of Toxoplasma had a greater number of RFC during the secondary response after 10 days than with a larger dose.  相似文献   

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There is a high incidence of infections in athletes undergoing intense, prolonged training or participating in endurance races (e.g., the marathon), in particular, upper respiratory tract infections. Prolonged, exhaustive exercise can lower the plasma level of the amino acid, glutamine, which is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. This could therefore be an important factor in the event of an impaired response of immune cells to opportunistic infections. The effects of feeding glutamine to sedentary individuals and to marathon and ultramarathon runners before and after prolonged, exhaustive exercise has been investigated in a series of studies that monitored the incidence of infections and some acute-phase response markers. Oral glutamine, compared with a placebo, appeared to have a beneficial effect on the incidence of infections reported by runners after a marathon.  相似文献   

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The secretory immune response in humans infected with Giardia lamblia was studied by using saliva samples and a membrane-rich protein fraction. The membrane fraction, studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed 24 antigen bands, ranging from 170 to 14 kDa. Saliva samples from giardiasis patients showed a heterogeneous response against the membrane fraction when they were assayed by immunoblotting. Among the antigens recognized by patient saliva samples, those of 170, 105, 92, 66, 32, 29, and 14 kDa stood out. These antigens were not recognized by saliva samples from healthy individuals. They may be of importance in future studies of protection from or diagnosis of G. lamblia infections.  相似文献   

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High-force eccentric exercise induces neuromuscular dysfunction and may augment the cardiovascular response to exercise. This investigation sought to determine whether changes in strength and sense of force following high-force eccentric exercise alter heart rate and blood pressure responses during isometric contractions. Subjects (4F,6M) performed 50 maximum resistance eccentric actions with one arm (ECC arm). Contractions at 10% of the ECC arm maximum were held for 7 min on two pre-exercise days. The force output perceived to be the same as 10% of the pre-exercise maximum was determined using a force matching task. This force, 35.6, 27.2, and 21.1% lower on days 1, 3, and 5 post-exercise, was held during isometric contractions on these days, respectively. Despite a lowering of absolute contraction force, heart rate (P < 0.05) and blood pressure (P < 0.001) responses during contractions using the ECC arm were consistently elevated relative to the control arm. However, subjects perceived that they were exerting forces similar to those achieved before eccentric exercise-induced neuromuscular dysfunction. These findings suggest that perceived effort following strength loss induced by mechanically stressful exercise dictates the cardiovascular responses during isometric contractions.  相似文献   

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The response to trauma begins in the immune system at the moment of injury. The loci are the wound, with activation of macrophages and production of proinflammatory mediators, and the microcirculation with activation of endothelial cells, blood elements, and a capillary leak. These processes are potentiated by ischemia and impaired oxygen delivery and by the presence of necrotic tissue, each exacerbating the inflammatory response. Hemorrhage alone may be a sufficient stimulus. Inflammation once was considered to be a host reaction to bacteria or other irritants. This concept was expanded by the discovery of autoimmune diseases, and we are now aware that some illnesses are the result of the body's response to an invader rather than the direct effect of the invader itself. The discoveries about the response to trauma described here add another dimension, showing inflammation to be a fundamental life process that begins at the molecular level at the moment of injury and that, depending on the severity of the stimulus and the effectiveness of initial treatment, may spread to include every cell, tissue, and organ in the body, for good or ill. An important part of these expanding concepts is the notion that all noxious stimuli activate the cytokine system as a final common pathway. Sepsis, hemorrhage, ischemia, ischemia-reperfusion, and soft tissue trauma all share an ability to activate macrophages and produce proinflammatory cytokines that may initiate the SIRS. Second-message compounds and effector molecules mediate the observed clinical phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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Nickel is the major cause of allergic contact dermatitis, and to increase our understanding of this immune reaction we studied changes in the expression of adhesion molecules on mononuclear cells during nickel stimulation in vivo and in vitro. Nickel-induced lymphocyte cultures were used in vitro, the cells being examined with monoclonal antibodies (Mabs) and by flow cytometry. Mononuclear cells from skin biopsies of in vivo cutaneous nickel reactions were studied with Mabs and immunohistochemistry. The expression of adhesion molecules in vitro was differential: the number of cells carrying CD11c, CD29, CDw49b, CDw49d, CDw49e, CDw49f, CD54, CD56 and ELAM-1 being significantly overrepresented among the nickel-induced lymphoblasts whereas the number of blasts carrying CD44 was underrepresented and those of CD11a, CD18, CD58 and LAM-1 remained unchanged. CD4+ cells gained adhesion molecules during nickel-induced blast transformation whereas CD8+ cells lost most of their adhesion molecules. The in vivo results were in agreement with the in vitro ones except that CDw49b, CDw49f, CD56 and ELAM-1 could not be detected in a 96-hour nickel reaction in vivo. In conclusion, the nickel allergic reaction favors the expression of certain adhesion molecules, and this expression is induced on CD4+ cells while CD8+ cells tend to lose such molecules. The changes were more sensitively detected with the in vitro method.  相似文献   

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Of 5,500 newborn infants whose family histories were screened, 900 were found to have anamnestic risk. Cord-blood IgE was evaluable in 4,677 of these newborns, of which 394 had levels > or = 1 IU/mL; 84 infants had both anamnestic risk and elevated cord-blood IgE levels. Parents of infants with anamnestic risk were informed of their child's risk of atopy. Additionally, for 391 infants at two of the three participating hospitals, a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life, with maternal diet restricted to no more than 200 dL of cow milk per day, no more than one egg per week, and no tomato, fish, shellfish, nuts, or foods allergenic to the mother. Only soy formula was recommended, and introduction of solid foods was also carefully prescribed. Furthermore, doctors recommended against exposure to tobacco smoke, animal allergens, and early entrance into daycare. Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life (13.3%, n = 158) than infants whose parents had ignored the prescribed diet (54.7%, n = 86) or infants whose parents were offered no dietary recommendations (28.9%, n = 218). Differences between the compliant group and the two groups with unrestricted diets were significant, indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life.  相似文献   

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We studied the response in left ventricular (LV) internal dimensions and posterior wall thickness during the performance of sudden strenuous exercise without warm-up (SSE) and sudden strenuous exercise with warm-up (SSEw) in 15 healthy, untrained college-aged males (26 +/- 5.0 yr). Measurements of left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), stroke dimension (SD = LVEDD-LVESD), fractional shortening (FS = SD/EDD) and posterior wall thickness (PWT) were obtained from continuous 2-D targeted on M-mode echocardiography. Continuous EKG and blood pressure were obtained at rest and during the final 10 s of SSE (30 s of upright leg cycle ergometry of 400 W at 80 rpm). SSEw was preceded by warm-up exercise (6 min of graded leg cycle exercise of 2-min stages initial load 30 W, increasing in 30-W increments at 60 rpm, followed immediately by SSE). Our findings revealed that there were no significant differences in the LV internal dimensions (LVEDD, LVESD, FS, PWT), HR max, RPP max, ECG, and MAP max between SSE and SSEw. Sudden strenuous exercise without warm-up is not associated with a reduced LV function. The results of this study are contradictory to previous findings that have suggested that SSE is associated with transient global left ventricular (LV) dysfunction.  相似文献   

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Opioid receptor subtype antagonists differentially alter food intake under deprivation (24 h), glucoprivic (2-deoxy-D-glucose, 500 mg/kg, i.p.) or palatable (10% sucrose) conditions with mu (beta-funaltrexamine) and kappa (nor-binaltorphamine), but not delta1 ([D-Ala2,Leu5,Cys6]enkephalin) opioid antagonists reducing each form of intake following ventricular microinjection. Both mu and kappa opioid antagonists microinjected into either the hypothalamic paraventricular nucleus or the nucleus accumbens reduce intake under deprivation and glucoprivic conditions. Palatable intake is reduced by both antagonists in the paraventricular nucleus, but only mu antagonists are active in the accumbens. Food intake is stimulated by mu and delta, but not kappa, opioid agonists microinjected into the ventral tegmental area. The present study examined whether food intake under either deprivation, glucoprivic or palatable conditions was altered by bilateral administration of general (naltrexone), mu, kappa, delta1 or delta2 (naltrindole isothiocyanate) opioid antagonists into the ventral tegmental area. Deprivation (24 h)-induced feeding was significantly reduced by high (50 microg), but not lower (10-20 microg) doses of naltrexone (21%), and by delta2 (4 microg, 19%) antagonism in the ventral tegmental area. 2-Deoxy-D-glucose (500 mg/kg, i.p.)-induced hyperphagia was significantly reduced by high (50 microg), but not lower (20 microg) doses of naltrexone (64%), and by delta2 (4 microg, 27%) antagonism in the ventral tegmental area. Sucrose (10%) intake was significantly reduced by naltrexone (20-50 microg, 25-39%) and delta2 (4 microg, 25%) antagonism in the ventral tegmental area. Neither mu, kappa nor delta1 antagonists were effective in reducing any form of intake following microinjection into the ventral tegmental area. These data indicate that the ventral tegmental area plays a relatively minor role in the elicitation of these forms of food intake, and that delta2, rather than mu, kappa or delta1 opioid receptors appear responsible for mediation of these forms of intake by this nucleus.  相似文献   

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