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1.
The present study was designed to examine the effects of long-term ozone exposure on nasal epithelia and intraepithelial mucosubstances (IM) throughout the nasal airways of F344/N rats. Animals were exposed to 0 (controls), 0.12, 0.5, or 1.0 ppm ozone, 6 h/day, 5 days/wk, for 20 mo. Rats were killed 1 wk after the end of the exposure, and nasal tissues were processed for light and electron microscopy. Standard morphometric techniques were used to determine epithelial cell densities and the amounts of IM in the surface epithelium lining the nasal airways. No mucous cells or IM were present in the epithelia lining the nasal lateral meatus and maxillary sinus of rats exposed to 0 or 0.12 ppm ozone. In contrast, rats exposed to 0.5 or 1.0 ppm ozone had marked mucous cell metaplasia (MCM) with numerous mucous cells and conspicuous amounts of IM in the surface epithelium lining these upper airways. Ozone-induced increases in total epithelial cells (i.e., epithelial hyperplasia) were present only in rats exposed to 1.0 ppm. The results of this study indicate that rats chronically exposed to 1.0 or 0.5 ppm, but not 0.12 ppm, ozone can develop marked MCM with significant increases in IM in both proximal and distal nasal airways. The epithelial changes observed throughout the nasal passages of ozone-exposed rats may be adaptive responses in an attempt to protect the upper and lower respiratory tract from further ozone-induced injury.  相似文献   

2.
Acute pulmonary epithelial injury produced by short-term exposure to ozone varies by site within the tracheobronchial tree. To test whether this variability is related to the local dose of ozone at the tissue site or to local concentrations of glutathione, we exposed adult male rhesus monkeys for 2 h to filtered air or to 0.4 or 1.0 ppm ozone generated from 18O2. Following exposure, lungs were split into lobes and specimens were selected by microdissection so that measurements could be made on airway tissue of similar branching history, including trachea, proximal (generation one or two) and distal (generation six or seven) intrapulmonary bronchi, and proximal respiratory bronchioles. One half of the lung was lavaged for analysis of extracellular components. In monkeys exposed to filtered air, the concentration of reduced glutathione (GSH) varied throughout the airway tree, with the proximal intrapulmonary bronchus having the lowest concentration and the parenchyma having the highest concentration. Exposure to 1.0 ppm ozone significantly reduced GSH only in the respiratory bronchiole, whereas exposure to 0.4 ppm increased GSH only in the proximal intrapulmonary bronchus. Local ozone dose (measured as excess 18O) varied by as much as a factor of three in different airways of monkeys exposed to 1.0 ppm, with respiratory bronchioles having the highest concentration and the parenchyma the lowest concentration. In monkeys exposed to 0.4 ppm, the ozone dose was 60% to 70% less than in the same site in monkeys exposed to 1.0 ppm. Epithelial disruption was present to some degree in all airway sites, but not in the parenchyma, in animals exposed to 1.0 ppm ozone. The mass of mucous and ciliated cells decreased in all airways, and necrotic and inflammatory cells increased. At 0.4 ppm, epithelial injury was minimal, except in the respiratory bronchiole, where cell loss and necrosis occurred, and was 50% that found in monkeys exposed to 1.0 ppm ozone. We conclude that there is a close association between site-specific O3 dose, the degree of epithelial injury, and glutathione depletion at local sites in the tracheobronchial tree.  相似文献   

3.
To help assess acute health effects of summer air pollution in the eastern United States, we simulated ambient "acid summer haze" as closely as was practical in a laboratory chamber. We exposed young volunteers who were thought to be sensitive to this pollutant mixture on the basis of previous epidemiologic evidence. Specifically, we exposed 41 subjects aged 9-12 y to mixed ozone (0.10 ppm), sulfur dioxide (0.10 ppm), and 0.6-microm sulfuric acid aerosol (100 +/- 40 microg/m3, mean +/- standard deviation) for 4 h, during which there was intermittent exercise. Fifteen subjects were healthy, and 26 had allergy or mild asthma. The entire group responded nonsignificantly (p > .05) to pollution exposure (relative to clean air), as determined by spirometry, symptoms, and overall discomfort level during exercise. Subjects with allergy/asthma showed a positive association (p = .01) between symptoms and acid dose; in healthy subjects, that association was negative (p = .08). In these chamber-exposure studies, we noted less of an effect than was reported in previous epidemiologic studies of children exposed to ambient "acid summer haze."  相似文献   

4.
One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.  相似文献   

5.
BACKGROUND: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. OBJECTIVE: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. METHODS: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed-PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. RESULTS: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/beta-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects (P =. 0424, P =.0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells (r = 0.506, P =.0023) and the histamine content (r = 0.480, P =.0040). CONCLUSIONS: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose.  相似文献   

6.
Longitudinal behavior and achievement outcomes of traumatic brain injury (TBI) were investigated in 53 children with severe TBI, 56 children with moderate TBI, and 80 children with orthopedic injuries not involving brain insult. Measures of preinjury child and family status and of postinjury achievement skills were administered shortly after injury. Assessments were repeated 3 times across a mean follow-up interval of 4 years. Results from mixed model analysis revealed persisting sequelae of TBI. Recovery of math skills was observed in the severe TBI group but only for children from less stressed families. Social disadvantage in children with TBI predicted more adverse behavioral sequelae and less favorable changes in some outcome measures. The findings suggest that pediatric TBI has long-term effects on behavior and achievement but that postinjury progress is influenced by the family environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

7.
We reviewed 30 patients at an average of 7.4 years after acute repair of the anterior cruciate ligament augmented with a loop of iliotibial tract. A noncontact twisting had been the mechanism of injury in 18 of these patients, with 28 having been injured in sports. At followup, 25 patients had not experienced symptoms of instability and 23 were able to return to unrestricted athletic activity; only 5 had been unable or unwilling to return to sporting activity at all. There had been no swelling in 23 patients; however, 17 suffered from pain on exertion. The average Lysholm score was 93.2. Joint laxity was assessed and anteroposterior tibial translation quantified with a KT-1000 arthrometer. Eighteen patients had a normal or 1+ Lachman test and 27 had an absent or 1+ pivot shift. When compared with the results of a similar study performed on this group of patients at 2 years after surgery, there had been little subjective change in knee function. However, objectively there had been significant deterioration of the anteroposterior stability of the knees at 7 years, suggesting failure of the integrity of the repaired ligament with time. An associated medial collateral ligament injury had a significant adverse effect both on the integrity of the anterior cruciate ligament repair and the incidence of postoperative stiffness.  相似文献   

8.
Longitudinal neuropsychological outcomes of traumatic brain injury (TBI) were investigated in 53 children with severe TBI, 56 children with moderate TBI, and 80 children with orthopedic injuries only. Neuropsychological functioning was assessed at baseline, at 6- and 12-month follow-ups, and at an extended follow-up (a mean of 4 years postinjury). Mixed model analyses revealed persistent neuropsychological sequelae of TBI that generally did not vary as a function of time postinjury. Some recovery occurred during the first year postinjury, but recovery reached a plateau after that time, and deficits were still apparent at the extended follow-up. Further recovery was uncommon after the first year postinjury. Family factors did not moderate neuropsychological outcomes, despite their demonstrated influence on behavior and academic achievement after childhood TBI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

9.
Ozone and the oxides of sulfur are common environmental pollutants. The acute pulmonary lesions caused by ozone and sulfuric acid mist in rats and guinea pigs have been characterized. Rats are not affected by sulfuric acid mist in concentrations up to 100 mg/m3 except for reduced body weight at the higher doses. A true alveolitis develops in guinea pigs exposed to more than 20 mg/m3 sulfuric acid mist. The ozone lesion is primarily confined to the terminal bronchioles and proximal alveoli. In combination studies with up to 2 ppm ozone and up to 10 mg/m3 sulfuric acid mist, the pulmonary lesion and lung/body weight data were essentially the same as in exposure to ozone alone, and the number of statistically significant synergistic effects in rats and guinea pigs was about what one would expect to observe by chance alone.  相似文献   

10.
Identified predictors of couples' response to marital therapy at termination and 4 yrs posttreatment for 55 couples receiving either behavioral or insight-oriented marital therapy. Couples were more likely to remain maritally distressed at termination if either spouse reported high levels of negative marital affect or depressive symptomatology at intake. Couples were more likely to be divorced or maritally distressed 4 yrs after completing therapy if spouses' intake measures reflected high levels of negative marital affect, poor problem-solving skills, low psychological resilience, high levels of depression, low emotional responsiveness, or if neither spouse was employed at a semiskilled or higher level position. Termination measures of negative marital affect and poor communication skills also predicted couples' status at 4-yr follow-up. Joint contingency tables relating predictors to outcome were constructed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

11.
Synapses of optic afferents (optic synapses) in the suprachiasmatic nucleus of hooded rats were morphometrically evaluated after exposing the animals to 12 h, 14 days, 2 months, and 8 months of constant light (light rats) and darkness (dark rats). Compared with dark rats, optic synapses from light rats have larger boutons with larger mitochondria, more clear vesicles, fewer dense-core vesicles and front-line vesicles, smaller presynaptic dense projections, a smaller amount of postsynaptic density material, a smaller relative number of Gray-type I (asymmetric) junctions, a greater relative number of Gray-type II (symmetric) junctions, as well as more and larger mitochondria in the postsynaptic dendrites. Junctions of optic synapses are mostly straight, but the small number of positively curved contacts are more flattened in light rats than in dark rats. An age-related increase in the size of presynaptic dense projections was also observed. There are no changes in the sizes of clear and dense-core vesicles, in the size of synaptic junctions and their numerical density in area, and in the unspecific contact area between pre- and postsynaptic elements. The changes in optic boutons are characteristic for activated and relatively disused synapses with a slow, tonic firing rate. It appears that (1) the amount of postsynaptic density material is proportional to the strength of Gray-type I synapses, and that (2) some excitatory optic synapses become inhibitory after long-term activity, whereas some inhibitory synapses turn into excitatory contacts after long-term disuse.  相似文献   

12.
Coping and adaptation theory is used to synthesis existing data concerning psychological recovery from acute spinal cord injury. Psychological reactions to spinal cord trauma are similar to those of mourning and other situations of severe loss. Each reaction plays a specific role in fostering or hindering recovery depending upon when it occurs. Premorbid personality and the influence of significant others play a central role in coping with injury. These factors partly explain why some patients cope better than others to equally serious disability. A critique of research methodologies and suggestions for new studies are provided.  相似文献   

13.
This multifaceted study involved a combined biochemical and cellular analysis of oxidant metabolism by a lung cell at risk from injury by endogenous and environmental oxidants, the pulmonary alveolar type II epithelial cell. Within the framework of this study, a method was developed for effectively delivering antioxidant enzymes and alpha-tocopherol to the intracellular compartment of alveolar epithelial cells. Alveolar type II cells are key sources of pulmonary surfactant phospholipids and apoproteins and serve as progenitors of type I alveolar epithelium, thus playing an important role in the re-epithelialization of the lung alveolus after exposure to pulmonary oxidants. The type I and II pulmonary epithelium also play an essential collaborative role in maintaining the integrity of the air-blood barrier of the lung. Because of these critical properties of the alveolar epithelium and their recognized sensitivity to oxidant stress derived from diverse sources, such as activated inflammatory cells, hyperoxia, the environmental oxidants and nitrogen dioxide, and surgical procedures, such as cardiopulmonary bypass and lung transplantation, we endeavored to understand more about the oxidant metabolism and antioxidant pharmacology of these cells. In our experiments, we made the observation that loss of differentiated oxidant generation and antioxidant properties of type II cells occurs very rapidly in vitro. For example, we observed a 50% to 75% reduction in the specific activities of type II cell superoxide dismutase, catalase, and glutathione peroxidase, all critical scavengers of cell superoxide and hydrogen peroxide and key enzymes in the attenuation of hydroxyl radical formation. Although the differentiated characteristics of the type II cell antioxidant defenses changed in vitro, they may have become more reflective of type I alveolar epithelial cells. The type I cell is the most vulnerable for oxidant damage in the alveolus because of its large surface area and the possibility of a reduced antioxidant capacity compared to type II alveolar epithelium. In spite of this limitation, we were able to culture type II cells and study their adaptive and toxic responses to exogenously administered oxidant stress. We also observed that a significant source of self-generated oxidants in type II cells was the enzyme xanthine oxidase. Normal rates of oxidant production by this enzyme had an inhibitory effect on incorporation of biosynthetic precursors into surfactant phospholipids; these effects were eliminated by the xanthine oxidase inhibitor, allopurinol.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

14.
Examines the effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on contextual fear conditioning in 48 female rats. Freezing behavior served as the measure of conditioning. Unlesioned control Ss showed reliable conditional freezing in the testing chamber when observed both immediately and 24 hrs after footshocks. In contrast, Ss with amygdala or ventral PAG lesions exhibited a significant attenuation in freezing both immediately and 24 hrs after the shocks. Dorsal PAG lesions had no effect on freezing at either time. Ss with hippocampal lesions displayed robust freezing behavior immediately following the shock, even though they showed a marked deficit in freezing 24 hrs after the shock. These results indicate that there are anatomically dissociable short- and long-term conditional fear states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

15.
In a liquid environment, at high dilutions, fertility of bull sperm is maintained for 3-5 days when stored at ambient temperatures (10-21 degrees C), after which time it steadily declines at a rate of 3-6% per day. This decline in fertility occurs irrespective of whether the sperm are stored at 5 degrees C or at 15 degrees C, but the rate is greater once storage temperatures exceed 25 degrees C. Sperm motility can be maintained for extended periods in an environment where the extracellular oxidative stress is minimized by reducing the oxygen tension, by addition of antioxidants and chelating agents; however, this will not prevent a significant drop in fertility after five days of storage at ambient temperature. The requirement of energy by the sperm-motility apparatus demands a high level of respiratory activity. This system is very active and the free radicals produced in vivo during this process could lead to chromatin damage. As no internal repair mechanism exists in sperm, an extraneous supply of protectants, or an environment where damage is minimized, is essential to maintain its fertilizing potential. The lack of extended storage potential of sperm, even in the presence of antioxidants, seems to suggest that although oocyte-penetrating ability of the sperm could still be intact, the high rate of intracellular metabolic activity could lead to mitochondrial DNA damage and chromosomal abnormalities that would compromise the viability of the resulting conceptus.  相似文献   

16.
52 Long-Evans male water-deprived rats were given 150 licks of a 10% sucrose solution, followed 4 sec later by 30 sec of low-intensity electrical brain stimulation applied in the dorsal hippocampus, amygdala, or lateral hypothalamus. Retention of the licking experience was then tested either 90 sec of 24 hrs after the lick experience by measuring the number of licks taken on an empty drinking tube. Ss that received hippocampal stimulation licked the empty tube less than the 17 controls did during the 24-hr, but not during the 90-sec, retention test. Data suggest that the hippocampus may be critically involved in processes (e.g., consolidation) mediating long-term, but not short-term, memory. Compared with controls, Ss that received amygdala stimulation did not exhibit any changes in licking at either retention test. Ss given lateral hypothalamic stimulation showed more licking compared with controls during the 90-sec, but not the 24-hr, test. Subsequent tests suggest that facilitation of short-term memory may have been influenced by stimulation-induced motivational changes. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

17.
PURPOSE: Biostatistical models predicting the risk of recurrence after radical prostatectomy for clinically localized prostate cancer are necessary. Identifying these high risk patients shortly after surgery, while tumor burden is minimal, makes them candidates for possible adjuvant therapy and/or investigational phase II clinical trials. This study builds on previously proposed models that predict the likelihood of early recurrence after radical prostatectomy. MATERIALS AND METHODS: In our analysis we evaluate age, race, prostatic acid phosphatase and nuclear grade with the established prognostic variables of pretreatment prostate specific antigen, postoperative Gleason sum and pathological stage. RESULTS: After multivariable Cox regression analysis using only statistically significant variables that predicted recurrence we developed an equation that calculates the relative risk of recurrence (Rr) as: Rr = exp[(0.51 x Race) + (0.12 x PSAST) + (0.25 x Postop Gleason sum) + (0.89 x Organ Conf.). These cases are then categorized into 3 distinct risk groups of relative risk of recurrence of low (< 10.0), intermediate (10.0 to 30.0) and high (> 30.0). Kaplan-Meier survival analysis of these 3 risk groups reveals that each category has significantly different risks of recurrence (p < 0.05). This model is validated with an independent cohort of radical prostatectomy patients treated at a different medical center by multiple primary surgeons. CONCLUSIONS: This model suggests that race, preoperative prostate specific antigen, postoperative Gleason sum and pathological stage are important independent prognosticators of recurrence after radical prostatectomy for clinically localized prostate cancer. Race should be considered in future models that attempt to predict the likelihood of recurrence after surgery.  相似文献   

18.
Measurement of cardiac output by Doppler echocardiography were compared to simultaneous measurements by thermodilution in 9 conscious horses. In the Doppler technique, mean blood flow velocities for estimation of cardiac output were recorded from the aorta and pulmonary artery. The flow area of each vessel was calculated from the vessel diameter, measured from a 2-dimensional ultrasound image. Differences in the site and method of measuring the vessel diameter altered the estimation of cardiac output by the Doppler method. Cardiac output was modified by the i.v. infusion of 4 micrograms/kg bwt/min dopamine and 4 micrograms/kg bwt/min dobutamine and by the i.v. administration of 10 micrograms/kg bwt detomidine and 20 micrograms/kg bwt butorphanol. Doppler measurements of cardiac output correlated closely with measurement by thermodilution. Measurements from the aortic outflow correlated more closely with thermodilution, than those from the pulmonary artery (r = 0.89 and r = 0.77, respectively). Doppler measurements when the mean flow velocity was recorded from the aorta and the flow area was measured from the ascending aorta using the leading edge method. There was no significant bias between the 2 techniques when Doppler flow velocities were recorded by this method and the limits of agreement were narrow (+/- 12.26 l/min). The differences between the 2 methods increased with increasing cardiac output. Doppler echocardiography is a safe noninvasive method of measuring cardiac output in horses. The agreement between Doppler echocardiography and thermodilution in this study is similar to that reported in man and is similar to that reported between thermodilution and other techniques in man.  相似文献   

19.
BACKGROUND: The urease-ammonia (NH4OH) system has been proposed to play a major role in the pathogenesis of the Helicobacter pylori-associated gastritis, but the mechanism of the mucosal damage has not been fully explained. This study was designed to examine possible adaptive cytoprotection and the adaptation of rat gastric mucosa to the irritant action of NH4OH and urease. METHODS AND RESULTS: Single application of NH4OH alone in various concentrations (15-500 mM) caused concentration-dependent mucosal damage starting with 30 mM and reaching a maximum at 250 mM NH4OH, similar to that obtained with 100% ethanol; it was accompanied by a decrease in gastric blood flow (GBF) to approximately 30% of the normal value. When the mucosa was first exposed to the low, non-damaging concentration (15 mM) of NH4OH and then insulted with 100% ethanol, the extent of ethanol damage was greatly attenuated as compared with that caused by ethanol alone. This adaptive cytoprotection was accompanied by the rise in GBF and reversed, in part, by the pretreatment with indomethacin, an inhibitor of prostaglandin (PG)-cyclooxygenase; with L-NAME, a blocker of NO-synthase; or with capsaicin deactivating the sensory nerves. Damaging concentrations of NH4OH (125 mM) caused widespread mucosal damage after the first application, but with repeated insults with 125 mM NH4OH a gradual reduction in the mucosal lesions, accompanied by enhanced mucosal cell proliferation and over-expression of epidermal growth factor (EGF) (using immunocytochemistry) and mRNA of EGF (using trans-reverse polymerase chain reaction), were observed. CONCLUSIONS: NH4OH alone damages gastric mucosa only at the concentration exceeding that found in H. pylori-infected stomachs, whereas at lower concentrations it acts as 'mild' irritant to induce adaptive cytoprotection. This adaptive cytoprotection appears to be mediated, in part, by endogenous PG, sensory nerves, and an arginine-NO-dependent pathway, and repeated applications of NH4OH induce gastric adaptation, probably mediated by enhanced expression of EGF and its receptors and by an increased cell proliferation.  相似文献   

20.
Reviewed the scientific evidence on the effectiveness of early childhood educational programs. Drawing upon the theory that intelligence and related complex human behaviors are probably always determined by myriad complex interactions of genes and environments, this meta-analytic study is based on the assumption that such behaviors can be both highly heritable and highly malleable. Integrating results across 35 preschool experiments and quasi-experiments, the primary findings were: (a) preschool effects on standardized measures of intelligence and academic achievement were statistically significant, positive, and large; (b) cognitive effects of relatively intense educational interventions were significant and very large, even after 5–10 years, and 7–8 of every 10 preschool children did better than the average child in a control or comparison group; and (c) cumulative incidences of an array of personal and social problems were statistically, significantly, and substantially lower over a 10- to 25- year period for those who had attended preschool (e.g., school drop out, welfare dependence, unemployment, poverty, criminal behavior). The need for a very large, well-controlled, national experiment to either confirm or refute these provocative, review-generated findings is discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   

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