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Biomedical subjects

H S Koren

Publications and source records attributed to H S Koren.

At least 19 recordsLinked to original sources
PubMed2002

Attenuation and recovery of pulmonary injury in rats following short-term, repeated daily exposure to ozone.

Controlled human and epidemiology studies have demonstrated that during repeated exposure to ozone (O(3)) attenuation of lung function responses may occur. It is yet unknown whether inflammatory and biochemical effects in lower airways of humans, as observed upon single O(3) exposure, also show a diminutive response following repeated exposure to O(3). The aim of this study was to investigate inflammatory, permeability, and histopathological responses in lungs of rats following repeated daily O(3) exposure and to study the time course of attenuation and recovery of these effects using single O(3) challenges at various postexposure times. To aid in animal-to-human extrapolation, this study and a previously reported human study (Devlin et al., 1997) were designed with similar protocols. Wistar rats were exposed for 5 consecutive days to 0.4 ppm O(3) for 12 h/night. Subsequently, the time course of postexposure recovery was determined by a single challenge of 12 h to 0.4 ppm O(3) after a 5-, 10-, 15-, or 20-day recovery period. Bronchoalveolar lavage (BAL) examination and histopathology were performed 12 h after this O(3) challenge. To quantify the magnitude of the O(3) response, results were compared with a group exposed only once for 12 h to 0.4 ppm O(3) and sacrificed simultaneously. The results demonstrate that a single exposure of 0.4 ppm O(3) causes marked permeability and inflammatory responses in lower airways of rats, as evidenced by enhanced BAL fluid levels of proteins, fibronectin, interleukin (IL)-6, and inflammatory cells. However, 5 days of exposure to 0.4 ppm O(3) for 12 h/night resulted in a complete disappearance of these responses, resulting in BAL fluid values that were not different from those observed in unexposed controls. Postexposure analyses of pulmonary response to O(3) challenges demonstrated that these attenuated responses show a gradual recovery. The data indicate that with respect to BAL fluid levels of albumin, IL-6, and number of macrophages and neutrophils, the period for lung tissue to regain its full susceptibility and responsiveness to O(3) following a 5-day preexposure period is approximately 15-20 days. Remarkably, the total protein and fibronectin responses in BAL fluid still exhibited an attenuated response to an O(3) challenge at 20 days postexposure. Morphometry (number of BrdU-labeled cells in terminal bronchiolar epithelium, and number of alveolar macrophages) showed that after a recovery of 5-10 days following a 5-day preexposure the response to a challenge was identical to that after a single exposure. These results suggest that complete repair from lower airway inflammation caused by short-term, repeated exposure to O(3) may take longer than previously assumed.

Animals↗
PubMed2001

Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology.

A complex mixture of air pollutants is present in the ambient air in urban areas. People, animals, and vegetation are chronically and sequentially exposed to outdoor pollutants. The objective of this first of 2 studies is to evaluate by light and electron microscopy the lungs of Mexico City dogs and compare the results to those of 3 less polluted cities in MEXICO: One hundred fifty-two clinically healthy stray mongrel dogs (91 males/61 females), including 43 dogs from 3 less polluted cities, and 109 from southwest and northeast metropolitian Mexico City (SWMMC, NEMMC) were studied. Lungs of dogs living in Mexico City and Cuernavaca exhibited patchy chronic mononuclear cell infiltrates along with macrophages loaded with particulate matter (PM) surrounding the bronchiolar walls and extending into adjacent vascular structures; bronchiolar epithelial and smooth muscle hyperplasia, peribronchiolar fibrosis, microthrombi, and capillary and venule polymorphonuclear leukocytes (PMN) margination. Ultrafine PM was seen in alveolar type I and II cells, endothelial cells, interstitial macrophages (Mtheta), and intravascular Mtheta-like cells. Bronchoalveolar lavage showed significant numbers of alveolar macrophages undergoing proliferation. Exposure to complex mixtures of pollutants-predominantly particulate matter and ozone-is causing lung structural changes induced by the sustained inflammatory process and resulting in airway and vascular remodeling and altered repair. Cytokines released from both, circulating inflammatory and resident lung cells in response to endothelial and epithelial injury may be playing a role in the pathology described here. Deep concern exists for the potential of an increasing rise in lung diseases in child populations exposed to Mexico City's environment.

Age Distribution↗
PubMed2001

Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology.

The principal objective of this study is to evaluate by light and electron microscopy (LM, EM) the heart tissues in stray southwest and northeast metropolitan Mexico City (SWMMC, NEMMC) dogs and compare their findings to those from 3 less polluted cities (Cuernavaca, Tlaxcala, and Tuxpam). Clinically healthy mongrel dogs, including 109 from highly polluted SWMMC and NEMMC, and 43 dogs from less polluted cities were studied. Dogs residing in cities with lower levels of pollutants showed little or no cardiac abnormalities. Mexico City and Cuernavaca dogs exhibited LM myocardial alterations including apoptotic myocytes, endothelial and immune effector cells, degranulated mast cells associated with scattered foci of mononuclear cells in left and right ventricles and interventricular septum, and clusters of adipocytes interspersed with mononuclear cells. Vascular changes included scattered polymorphonuclear leukocytes (PMN) margination and microthrombi in capillaries, and small venous and arteriolar blood vessels. Small veins exhibited smooth muscle cell hyperplasia, and arteriolar blood vessels showed deposition of particulate matter (PM) in the media and adventitia. Unmyelinated nerve fibers showed endoneural and epineural degranulated mast cells. EM examination of myocardial mast cells showed distended and abundant rough endoplasmic reticulum with few secretory granules. Myocardial capillaries exhibited fibrin deposition and their endothelial cells displayed increased luminal and abluminal pinocytic activity and the formation of anemone-like protrusions of the endothelium into the lumen. A close association between myocardial findings, lung epithelial and endothelial pathology, and chronic inflammatory lung changes was noted. The myocardial changes described in dogs exposed to ambient air pollutants may form the basis for developing hypothesis-driven mechanistic studies that might explain the epidemiological data of increased cardiovascular morbidity and mortality in people exposed to air pollutants.

Air Pollutants↗
PubMed2001

Dose response for UV-induced immune suppression in people of color: differences based on erythemal reactivity rather than skin pigmentation.

Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation and UVR sensitivity were evaluated using Fitzpatrick classifications, minimal erythemal dose (MED), slope of the erythemal dose response curve (sED), baseline pigmentation and tanning response. To assess immune responses dinitrochlorobenzene (DNCB) was applied to irradiated buttock skin 72 h after irradiation. Two weeks later DNCB was applied to the inside upper arm. Skin thickness was measured before and after challenge. Dose response was modeled (to obtain a regression line) for the entire group of 185 subjects. With the exception of sED none of the above-mentioned pigmentation indicators contributed significantly to variability around the regression line. Thus, differences in sensitivity for multiple skin types based on Fitzpatrick classification or MED were not observed. However, differences in immune sensitivity to UVR were detected between subjects with steep erythemal dose response curves and those with moderate or flat responses. For subjects with steep erythemal responses the dose calculated to suppress the immune response by 50% was 114 mJ/cm2. This group included individuals with Fitzpatrick skin types I-V, MED for these subjects ranged from 30 to 80 mJ/cm2. The 50% suppression dose for subjects with weak or no erythemal response could not be computed (the dose response was flat). This resistant group included subjects with skin types IV-VI and MED for these subjects ranged from 41 to > 105 mJ/cm2. This study provides a human dose response for UVR suppression of contact sensitivity that will be useful in risk assessment. It is the first study to provide this information using the FS sun lamp and is the first study to include people of color. The sED appears to be a new variable for identifying sensitive subjects at risk of UVR-induced immune suppression.

Adolescent↗
PubMed2000

Exposure to air pollution is associated with lung hyperinflation in healthy children and adolescents in Southwest Mexico City: a pilot study.

Air pollution produces adverse health effects. The consequences of lifelong daily exposures to atmospheric pollutants upon the respiratory apparatus of healthy children are of considerable clinical importance. We investigated the association between exposure to a highly polluted urban environment with a complex mixture of air pollutants-ozone and particulate matter the predominant ones-and chest x-ray abnormalities in 59 healthy Mexican children who are lifelong residents of Southwest Metropolitan Mexico City (SWMMC), with a negative history of tobacco exposure and respiratory illnesses. Their clinical results and x-ray findings were compared to those of 19 Mexican control children, residents of a low-pollution area, with a similar negative history of tobacco exposure and respiratory illnesses. Ozone concentrations in SWMMC exceeded the U.S. Environmental Protection Agency (U.S. EPA) National Ambient Air Quality Standard (NAAQS) for O(3): 0.08 ppm as 1-h maximal concentration, not to be exceeded more than 4 times a year, on 71% of days in 1986 and 95% in 1997, with values as high as 0.48 ppm. Ozone maximal peaks are usually recorded between 2 and 5 pm coinciding with children's outdoor physical activities. Children in the control group reported no upper or lower respiratory symptomatology. Every SWMMC child complained of upper and/or lower respiratory symptoms, including epistaxis, nasal dryness and crusting, cough, shortness of breath, and chest discomfort. Children aged 7-13 yr had the most symptomatology, while 5- to 6-year olds and adolescents with the lowest number of statistically significant outdoor exposure hours had less respiratory symptoms. Bilateral symmetric mild lung hyperinflation was significantly associated with exposure to the SWMMC atmosphere (p = .0004). Chronic and sustained inhalation of a complex mixture of air pollutants, including ozone and particulate matter (PM), is associated with lung hyperinflation, suggestive of small airway disease, in a population of clinically healthy children and adolescents. Small airways are a target of air pollutants in SWMMC children, with ozone and PM being most likely responsible, based on experimental animal, controlled-chamber, and epidemiological data available. Our main concern is the potential likelihood for the development of chronic lung disease in this highly exposed population.

Adolescent↗
PubMed1999

Inflammatory response in humans exposed to 2.0 ppm nitrogen dioxide.

Nitrogen dioxide (NO2) is a common indoor air pollutant, especially in homes with unvented combustion appliances. Epidemiological studies suggest that children living in homes with unvented heating sources are more prone to respiratory infections than children living in homes with lower levels of NO2. However, experimental studies in which human volunteers were exposed acutely to moderate levels of NO2 (0.5-2.0 ppm) have shown little evidence of lung inflammation or decreased host resistance capacity. In the study reported here, 8 healthy volunteers were exposed to 2.0 ppm NO2 and to filtered air for 4 h while undergoing intermittent moderate exercise. Bronchoalveolar lavage was performed the following morning. The lavage was divided into a predominantly bronchial washing (first 20 ml of lavage; BL) and a predominantly alveolar washing (BAL). In the BL, NO2 exposure caused increases in polymorphonuclear neutrophils (PMNs), interleukin 6 (IL-6), IL-8, alpha1-antitrypsin, and tissue plasminogen activator, and decreases in epithelial cells. In the BAL, there were no NO2-induced changes in either cell numbers or soluble mediators. On the other hand, alveolar macrophages from BAL showed a decrease in the ability to phagocytose unopsonized Candida albicans and a decrease in superoxide production. No difference in susceptibility to virus infection was found between the NO2- and air-exposed macrophages. No changes in lung function were observed, but the aerosol bolus recovery technique revealed a statistically significant (p <.05) decrease in the fraction of aerosol recovered following nitrogen dioxide exposure, which is suggestive of small obstructive changes induced by NO2.

Adolescent↗
PubMed1999

Compartmentalization of the inflammatory response to inhaled grain dust.

Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 grain handlers 6 h after experimental inhalation of saline or an aqueous corn dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1beta (> 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn dust extract, the expression of messenger RNA (mRNA) for IL-1beta and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF-alpha mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1beta was 11-fold higher in BAL cells; and TNF-alpha and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1beta and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled grain dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.

Adolescent↗
PubMed1999

Cellular and biochemical response of the human lung after intrapulmonary instillation of ferric oxide particles.

Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 microm-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. Our findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles. These findings may have relevance to the acute health effects associated with increased levels of ambient particulate air pollutants.

Adult↗
PubMed1998

Cell-specific differences in the susceptibility of potential cellular targets of human origin derived from blood and lung following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The induction of cytochrome P4501A (CYP1A1) enzyme activity is one of the best-studied direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and has been shown to be a sensitive biomarker of exposure to polycyclic aromatic hydrocarbons (PAH) in different experimental animal species as well as in humans. TCDD has also been shown to modulate cytokine gene expression in human keratinocytes, including IL-1 beta, TGF-alpha and TFG-beta 2. In the present studies, the aim was to determine whether different cellular targets of human origin differed in susceptibility to TCDD as measured by CYP1A1 activity and mRNA expression, and whether cytokine gene induction/suppression correlated with TCDD susceptibility. Human airway epithelial cells, alveolar macrophages (AM), peripheral blood monocytes and lymphocytes (PBL) were exposed to 10(-10)-10(-7) mol/L TCDD. CYP1A1 enzyme activity was determined by ethoxyresorufin-O-deethylase (EROD) activity, mRNA expression of CYP1A1 was measured by semiquantitative PCR assay. The secretion and/or gene expression of specific cytokines, including IL-6, IL-8, and IL-1 beta were also examined. Overall, there was a clear correlation between TCDD-induced enzyme activity and CYP1A1 mRNA levels, which were dose-dependently increased in the bronchoepithelial cells and PBL. The human airway epithelial cells (BEAS-S6 cell line and primary cells) appeared to be the most inducible cellular target, with up to 50-fold increases at 10(-8) mol/L TCDD with an EC50 of 3 x 10(-11) mol/L TCDD. The pokeweed mitogen-activated peripheral blood lymphocytes revealed approximately 5-fold less capacity in CYP1A1 activity, with high interindividual variabilities (EC50 3 x 10(-9) mol/L TCDD). In contrast, CYP1A1 enzyme activity in both AM and purified peripheral blood monocytes, which were costimulated with LPS and/or GM-CSF, could not be detected. CYP1A1 mRNA levels, however, were detectable and only marginally enhanced in response to TCDD. The ability of all these cells to express and produce the proinflammatory cytokines IL-6 and IL-8 was neither enhanced nor impaired by TCDD. These results indicate that cell types found in human lung and peripheral blood vary in susceptibility to TCDD, with the lung epithelium being highly susceptible and the alveolar macrophage being nonsusceptible. However, expression and production of specific cytokines such as IL-6 and IL-8, which may potentiate inflammatory processes and/or work as mitogens, does not appear to be influenced by TCDD.

Adolescent↗
PubMed1996

Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure.

Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE2) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAl fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE2, thromboxane B2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE2 levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time.

Adolescent↗
PubMed1996

Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes.

Inhalation of O3 causes airways neutrophilic inflammation accompanied by other changes including increased levels of cyclo-oxygenase products of arachidonic acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes decreased forced vital capacity (FVC) and forced expiratory volume after 1 s (FEV(1)), associated with cough and substernal pain on inspiration, and small increases in specific airway resistance (SRAW). The spirometric decrements are substantially blunted by pretreatment with indomethacin. Since the O3-induced decrement in FVC is due to involuntary inhibition of inspiration, a role for stimulation of nociceptive respiratory tract afferents has been suggested and cyclo-oxygenase products have been hypothesized to mediate this stimulation. However, the relation (if any) between the O3-induced neutrophilic airways inflammation and decreased inspiratory capacity remains unclear. We studied the effects of pharmacologic inhibition of O3-induced spirometric changes on the inflammatory changes. Each of ten healthy men was exposed twice (5-week interval) to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation 601*min(-1)). One-and-a-half hours prior to and midway during each exposure the subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized, double-blind fashion. Spirometry and body plethysmography were performed prior to drug administration, and before and after O3 exposure. Immediately following postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor PLA administration changed pre-exposure lung function. O3 exposure (with PLA) caused a significant 17 percent mean decrement in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1) (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4 percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by IBU as compared to PLA pretreatment. As expected, O3 exposure produced neutrophilia in BALF. There was, however, no effect of IBU on this finding. None of the major cell types in the BALF differed significantly between pretreatments. We found no association between post-exposure changes of BALF components and pulmonary function decrements. We conclude that IBU causes significant inhibition of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting of the spirometric response. This is consistent with the hypothesis that the products of AA metabolism mediate inhibition of inspiration. However, IBU did not alter the modest SRAW response to O3.

Adult↗
PubMed1996

2,3,7,8-TCDD induces cytochrome P450 enzyme activity but not proliferation or phenotypical changes in human peripheral blood lymphocytes.

In contrast to the well documented immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans accidentally or occupationally exposed to dioxin. More recently, a dose-dependent decrease of specific subpopulations of mitogen-activated human peripheral blood lymphocytes (PBL), including helper-inducer/memory cells (CD4+CD29+) and B cells (CD20+), was reported after in vitro treatment with dioxin concentrations as low as 10(-12)-10(-14) M TCDD [1]. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied in more detail, in order to assess the availability of a sensitive indicator system for human dioxin exposure. PBL from healthy volunteers were stimulated with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (OKT3) and treated with 10(-7)-10(-14) M TCDD for 3-4 days. Cytochrome P450 (CYP1A1) enzyme induction was determined by the ethoxy-resorufin-O-deethylase (EROD) assay. Percentages of the different lymphocytes subsets, including CD2 (T cells), CD4, CD45 RA (suppressor-inducer/ virgin T cells), CD4, CD29, CD8, CD19 (B cells), as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (human leukocyte antigen HLA-DR) expression, were analyzed by flow cytometry. The proliferative activity was determined by 3H-thymidine uptake after 3-4 days of culture. In the present study, all stimulated lymphocyte cultures showed a significant increase of CYP1A1 activity at dioxin concentrations of 10(-7) and 10(-9) M. In contrast, alterations in surface antigen expression or suppression of proliferative responses did not occur in the mitogen-activated PBL over the whole concentration range of TCDD. These results clearly demonstrate that lymphoproliferation, as well as phenotypes of human PBL, are not affected by dioxin treatment and thus are not useful as sensitive biomarkers in human exposure studies.

Adolescent↗
PubMed1995

Results of ophthalmic examinations of 29 alpacas.

Analysis of the results of ophthalmic examinations of 29 alpacas (Lama pacos) revealed a direct relationship among coat color, iris color, and ocular fundus pigmentation. Alpacas with light-pigmented coats had iris color that included combinations of gray, blue, and brown, and had reduced pigmentation of the ocular fundi. Alpacas with dark coats had brown irides and pigmented ocular fundi. Eleven alpacas had evidence of ophthalmic conditions, including bilateral conjunctivitis (1); formation of a superficial corneal scar (1); formation of posterior synechiae and anterior cataracts (4); development of a deep corneal scar with anterior synechiae, buphthalmia, a subluxated lens, and cataracts (1); development of focal incipient primary cataracts (2); formation of vitreous opacities (1); and development of a unilateral optic nerve coloboma (1).

Animals↗
PubMed1995

Ozone-induced human respiratory dysfunction and disease.

Exercising volunteers exposed in chambers to as little as 80 ppb O3 for several hours exhibit impaired lung function and irritative lower airway symptoms. Comparable changes occur among children and young adults exposed to summer smog containing O3. Intensity of the response is reproducible but varies widely among individuals. The (reversible) decrements in vital capacity are due to involuntary inhibition of deep inspiration probably mediated by nociceptive bronchial C-fibers that may be stimulated by local prostaglandin release, and can be modulated by appropriate pharmacologic agents. A second characteristic response to low O3 levels is mucosal neutrophilic inflammation probably mediated by phospholipid-derived products and by epithelial cell-derived chemokines and cytokines, but poorly correlated with lung function changes. Fluctuations in ambient O3 levels are associated with acute respiratory health effects in exposed populations but concomitant acid aerosol pollution is an important confounder. Whether irreversible impairment of lung function occurs among residents of chronically high ozone-pollution areas is debated.

Adult↗
PubMed1995

Nasal cytokine production in viral acute upper respiratory infection of childhood.

Children in a day care center underwent serial nasal lavages in order to assess nasal cytokine expression during acute upper respiratory infections (URI). Interleukin (IL)-1 beta, IL-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were markedly elevated in nasal lavage fluid during acute URI compared to baseline, and all except TNF-alpha decreased significantly by 2-4 weeks later. Cytokine patterns in respiratory syncytial virus-positive and -negative illnesses did not differ significantly. A subgroup of children also underwent superficial mucosal biopsy under the inferior nasal turbinate. During acute URI, biopsy cells (90%-95% epithelial) showed increased transcripts for IL-1 beta, IL-8, and IL-6 in 7 of 9 subjects, suggesting that epithelial cells may be one source of cytokines during acute URI. The results show that inflammatory cytokines are elevated in nasal secretions during acute URI in preschool children. Thus, cytokines are likely to participate in regulation of respiratory virus-induced inflammation.

Acute Disease↗