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Summary Background Healthcare-associated infections (HCAIs) cause significant morbidity and mortality worldwide, and outbreaks are often only identified after they reach high levels. A wide range of data is collected within healthcare settings; however, the extent to which this information is used to understand HCAI dynamics has not been quantified. Aim To examine the use of spatiotemporal analyses to identify and prevent HCAI transmission in healthcare settings, and to provide recommendations for expanding the use of these techniques. Methods A systematic review of the literature was undertaken, focusing on spatiotemporal examination of infectious diseases in healthcare settings. Abstracts and full-text articles were reviewed independently by two authors to determine inclusion. Findings In total, 146 studies met the inclusion criteria. There was considerable variation in the use of data, with surprisingly few studies ( N = 22) using spatiotemporal-specific analyses to extend knowledge of HCAI transmission dynamics. The remaining 124 studies were descriptive. A modest increase in the application of statistical analyses has occurred in recent years. Conclusion The incorporation of spatiotemporal analysis has been limited in healthcare settings, with only 15% of studies including any such analysis. Analytical studies provided greater data on transmission dynamics and effective control interventions than studies without spatiotemporal analyses. This indicates the need for greater integration of spatiotemporal techniques into HCAI investigations, as even simple analyses provide significant improvements in the understanding of prevention over simple descriptive summaries.

SUMMARYThe highly remote pastoralist communities in Kaokoland, Namibia, have long been presumed to have high gonorrhoea prevalence. To estimate gonorrhoea prevalence and correlates of infection, we conducted a cross-sectional study of 446 adults across 28 rural villages. Gonorrhoea status was determined from urethral and vaginal swabs via qPCR assay. All participants answered a closed-ended interview about demographics, sexual behaviour and symptom history. Sixteen per cent of participants had high-level infections (⩾ID50dose) and 48% had low-level infections (50dose). Women had higher prevalence than men of both high- and low-level infections. High-level infections were regionally and seasonally clustered, occurring in young adults in the Ehama region during the winter. Low-level infections were distributed homogenously across demographic characteristics, season, and region. All low-level infections and most high-level infections (men 78%, women 95%) were asymptomatic and left untreated. The epidemic-like nature of high-level gonorrhoea cases suggests that intervention efforts can be focused on seasons of high social activity.

Four layer genetic stocks consisting of 3 Ottawa control strains (5, 7, and 10) and a commercial laying stock (CCS) were utilized to evaluate potential changes in behavioral profiles due to the effects of genetic selection through 2 production cycles. The Ottawa strains were started as random bred strains from the crosses of several popular commercial layers in 1950, 1959, and 1972, and the commercial strain used herein was from calendar year 1993, and its ancestors were involved in the formation of all of the random bred strains. The behavior study utilized 2 replicates from each strain that contained 4 cages, 6 hens/cage, for a total of 192 hens. Behavioral observations were recorded on 2 consecutive days beginning at 22 wk of age and every 28 d thereafter during the first production cycle, the molt period, and the second production cycle through 90 wk of age and periodic feather and Hansen's test scores recorded. Behavior profiles were similar between the control strains and the CCS, indicating that long-term genetic selection by commercial egg-type breeding firms to enhance production parameters has had no impact on laying strain behavior patterns. Appetitive behaviors were not affected by strain. During the molt, hens had reduced (P < 0.05) feeding and drinking frequencies in comparison with those observed during the first and second cycles. The data indicated that hens pecked inedible objects at a greater (P < 0.0001) frequency during the first cycle and molt than during the second cycle. Fearfulness scores were only influenced by production phase with the molt having the highest (P < 0.01) score of 3.46. Strain or production phase did not influence the frequency of aggressive and submissive acts.

The hypothesis was proposed that the improved embryonic livability observed when higher incubation temperatures were imposed on eggs stored for 15 d prior to setting might have basis in energy metabolism. To test the hypothesis, fertilized turkey eggs were incubated either for the first 2 wk of development (experiment 1) or only the first week of development (experiment 2) at 37.8 degrees C compared with controls incubated at 37.5 degrees C. In both experiments, eggs were stored for either 15 or 3 d prior to setting. Viable embryos were selected randomly from each storage-by-incubation period treatment combination at 25 to 28 d of incubation and were sampled for blood, heart, and skeletal muscle tissues. Tissues were weighed and assayed subsequently for glucose or glycogen content. In experiment 2, the randomly selected embryos from each treatment combination were sampled at 7, 14, 21, and 28 d of incubation. Embryos at 7 and 14 d were assayed on a whole body basis, whereas at 21 and 28 d the bodies were dissected, and heart, liver, and skeletal muscle tissues were weighed and assayed for glycogen and lactate. Blood samples were collected between 25 and 28 d of incubation as in experiment 1 and assayed for glucose, creatine kinase, lactate dehydrogenase, and thyroid hormone concentrations. In both experiments, accelerated development was noted due to higher temperature and enhanced embryonic carbohydrate metabolism, and elevated thyroid hormone concentrations were observed compared with controls. It was concluded that a possible mechanism for the improved livability of faster growing embryos observed after prolonged egg storage might be due to better utilization of carbohydrate.

Two commercial strains of Single Comb White Leghorn hens, HyLine W-36 and DeKalb XL, were reared separately as pullet flocks in an enclosed, environmentally controlled brood-grow house with three banks of quad-deck cages (310 cm 2 per bird). There were 1,800 hens of each strain, which were divided into two groups, control feed and a direct-fed microbial (DFM) feed treatment. During the pullet-rearing phase to 18 wk of age, the DeKalb birds had greater parameters of growth and overall feed cost than the HyLine birds. The overall feed cost of the DFM treatment was $0.02 per bird greater than controls. However, the DFM-treated feed improved the livability of the DeKalb birds by 2.68%. At 18 wk of age, 3,528 hens were transferred to an enclosed, mechanically ventilated layer house. The two strains were placed in two differently sized quad-deck layer cages with seven birds per cage; the cage sizes were 35.56 cm x 60.96 cm (2,267.73 cm 2 or 310 cm 2 per bird) and 14 cm x 32 cm (2,890.32 cm 2 or 413 cm 2 per bird). There were a total of 144 replications with each strain and DFM treatment combination made up of 36 replications equally divided between the high and low density cages. At 70 wk of age, hens receiving the DFM treatment exhibited greater mean egg weights (61.72 g) and percentages of extra large eggs (XLE, 52.06%) compared to that of controls (61.12 g and 48.98%, respectively). The treatment of 310 cm 2 /hen DFM produced the least (P ≤ 0.05) large eggs; however, this treatment group produced the most (P ≤ 0.05) XLE. The use of DFM resulted in a shift from smaller to larger eggs. Regardless of density, the DFM hens had lower (P ≤ 0.05) feed cost (FC) compared to FC of the controls (a savings of $0.46/bird between the DFM and control in the 310 cm 2 /hen treatment and a $0.83 savings/bird between the DFM and control in the 413 cm 2 /hen treatment). It was concluded that PrimaLac can improve egg size and lower feed costs, regardless of the bird density used in the present study.

Thyroid hormone responses in embryonic avian species are of two types, developmental and metabolic. Many studies have characterized the developmental function of the turkey embryonic thyroid, but few have characterized the metabolic function. Therefore, the purpose of this study was to describe the response of turkey embryonic thyroid hormones to three environmental factors. We proposed that embryonic thyroids from different genetic backgrounds would respond differently to changes in maternal diet and incubation temperature. Lines of turkeys known to have different embryonic growth and survival were examined in the current study. These eggs differ in egg weight, eggshell conductance, hatchling weight and organ maturity at the time of hatching. Eggs were produced throughout a 20 wk laying period and embryos were sampled at monthly intervals. Half of the hens producing the eggs were fed additional iodide in their diets, then, subsequently, half of each dietary treatment and line combination were incubated at either 36.8 C or 37.5 C to prolong the incubation period. Embryos were sampled during the final week of incubation when thyroid hormones become elevated to effect maturation and survival functions in turkey embryos. Embryonic thyroxine (T4) and triiodothyronine (T3) levels were assayed by RIA and compared among the treatments. Line, diet, and incubation period interacted to affect the levels of T4, T3 and T3 to T4 ratios in the turkey embryonic during late incubation. It was concluded that environmental factors can affect circulating thyroid hormone levels in turkey embryos, thus affecting metabolic functions, and the possibility exists to manipulate these circulating levels using environmental incubation conditions to improve hatchability.

An experiment was designed to examine a mechanism to improve embryonic survival following maternal thyroid hormone manipulation. Commercial turkey breeder hens were fed diets containing supplemental iodide to mimic changes in the maternal thyroid output during an egg production cycle (32 to 48 wk of age). Dietary iodide treatment depressed maternal blood thyroxine (T4) concentrations in a time-dependent manner. Dietary iodide depressed maternal blood 3, 5, 3’-triiodothyronine (T3) levels across all times examined. The maternal dietary treatment increased embryonic blood concentrations of T4 at 25 to 28 d of incubation but depressed blood concentrations of T3 only at 27 d of incubation. In a second trial, the same response was noted in maternal blood when the hens were fed additional iodide with no corresponding effects on T3 concentrations. The iodide treatment decreased embryonic T4 concentrations in the second trial as well but in a time-dependent manner. Iodide accelerated the increase in T4 concentrations coincidental with earlier pipping in eggs from iodide-fed dams compared with controls. The data indicate that the embryonic thyroid function during hatching is dependent upon the maternal thyroid in turkey dams, even though the embryo develops outside the maternal body.

Leishmania major (Lm) infection in mice is a prototypical model for the role of immune deviation in disease resistance. Resistant strains of mice develop a Th1 response to Lm infection, distinguished by secretion of IL-12 and interferon γ. In contrast, susceptible strains display sustained IL-4 expression characteristic of a Th2 response. However, when mechanisms of cell death are blocked, mice display a susceptible phenotype even in the presence of a strong Th1 response, suggesting that cell death, and not cytokine bias, may be an importnt factor in disease resistance. Here, we investigated this hypothesis by comparing lymphocyte cellularity, cell death and Fas expression in resistant CBA and susceptible BALB/c mice during the course of Lm infection. We found that delayed onset of cell death and late Fas induction correlated with massive lymphocyte accumulation and susceptibility to leishmaniasis, while early cell death and rapid Fas induction occurred in resistant mice.

Functional eggshell qualities, thyroid hormones, and carbohydrate metabolism of chick embryos at the end of incubation were compared between a modern (Arbor Acres line) and a randombred control population (Athens-Canadian Randombred). Embryos from the Arbor Acres genetic line developed in larger eggs with more albumen and less yolk than Athens Canadian Randombred lines. Percentage shell and functional eggshell properties measured as eggshell conductance constants did not differ between genetic lines. On a relative basis, hearts were generally smaller and livers heavier in Arbor Acres than in Athens-Canadian Randombred birds. Heart and liver glycogen concentrations were greater in Athens-Canadian Randombred than in Arbor Acres embryos. However, blood glucose was greater in Randombred than in Arbor Acres embryos only at internal pipping, a time of hypoxia and hypercapnia. Blood plasma concentrations of thyroxine did not differ significantly between the modern and Randombred embryos at any stage examined. Modern broiler chick embryos possessed greater concentrations of triiodothyronine as well as greater triiodothyronine to thyroxine ratios than Randombred embryos at external pipping and hatching. It can be inferred from the data that chick embryos differ in their use of carbohydrate during late development between modern and Randombred genetic lines.

A flock of 520, 11-wk-old breeder Pekin ducklings was raised in 20 floor pens in a curtain-sided poultry house under decreasing day lengths. At 22 wk of age, the ducklings were photostimulated (16 h of light/day) with a combination of natural daylight and artificial light. After dusk, half of the ducklings were exposed to 10 lx of incandescent (IN) light and the other half were maintained under 172 lx of high-pressure sodium (HPS) light. In addition, each light treatment consisted of an equal number of pens with two different sex ratios, 22 hens:4 drakes (15% males) and 21 hens:5 drakes (19% males). Egg production, egg quality characteristics, and fertility were monitored from 22 to 52 wk of age. Ducklings housed under 172 lx of HPS light exhibited significantly (P ≤ .05) greater egg production between 23 and 34 wk of age. Egg weight, shell weight, and shell thickness were not consistently affected by the different light treatments or sex ratios. The sex ratios did not affect percentage egg fertility, but fertility was significantly (P ≤.05) higher in the HPS light treatment during the last 15 wk of the study. It was concluded that HPS light of 172 lx can enhance egg production in breeder Pekin ducklings prior to peak production (37 wk), and HPS light can improve fertility following the peak egg production period. Furthermore, this study indicated that a breeder duckling flock with 15% males was adequate to achieve optimum fertility.

DeKalb XL chicks were given a beak trim at 6 d of age (6DP) with a 2.8-mm gauge and a beak trim at 11 wk (11WB) with a block cut approximately 2 mm anterior to the nasal openings. Corticosterone (CS) levels of the 6DP treatment were (P < or = 0.01) elevated above nontrimmed CS levels at 2 h posttrim; and BW and feed consumption (FC) of the 6DP were depressed until 8 wk of age. At 11 wk of age, CS of the 11WB treatment was (P < or = 0.02) elevated above controls at 1, 2, 8, and 5 wk posttrim. The 11WB treatment resulted in a decrease in FC and a reduction in BW at 12, 14, and 16 wk of age, whereas there were no differences among treatments in livability during the pullet phase. At 72 wk of age, FC of the nontrimmed controls was greater than both beak trimmed treatments, and both beak trimmed treatments had greater hen housed eggs, percentage hen day egg production, and percentage livability. Both beak trimmed treatments resulted in better egg income, feed cost per hen, and net income (NI). The 6DP and 11WB beak trim treatments resulted in an improvement of NI per hen of 1.48 dollars and 1.86 dollars, respectively. In addition, both beak trimmed treatments exhibited better feather score and Hansen's test (fearfulness). It was concluded that pullets and hens could adapt to the physiological stress of beak trimming and out perform, during a lay phase, controls whose beaks were not trimmed.

Two commercial strains, Hy-Line W-36 and DeKalb XL, were moved to a laying house at 18 wk of age. They were housed 6 hens/layer cage at 2 densities (361 and 482 cm2/bird) with 2 replications each per strain/density combination. The high-density treatment contained 24 hens/replication and the low-density treatment contained 18 hens/replication for a total of 168 hens. Production parameters were measured during the first egg production cycle, the molt period, and the first 4 wk of the second lay cycle (20 to 68 wk of age). Behavioral observations were taken during 2 consecutive d at 26, 34, 43, 51, 62, 64, and 68 wk of age to examine behavioral patterns. Modified Hansen's tests were conducted concurrently to provide indication of the fearfulness levels of hens at the various stages of production. The production characteristics were similar for both strains. The hens kept at the higher density had lower (P < 0.01) hen-day production and (P < 0.05) daily egg mass. Appetitive behaviors were not affected by strain or density but were affected by the age of the hen and by molting. During the molt, feeding and drinking behavioral acts were fewer (P < 0.05) at 0.018 and 0.013 acts per bird/min, respectively, and standing behavior was highest. The results indicated that the frequencies of pecking inedible objects during the molt period were similar to the frequencies at 26 and 34 wk. Hens performed more acts of standing, and crouching and had lower frequency of movement during the molt. Those kept at a low density performed more movement acts. Feather pecking decreased as hens aged and increased when they molted but was not affected by strain or density. The frequency of aggression and submissive acts was significantly lower during the molt period. Behaviors were affected by strain, density, bird age, and molting; however, the patterns and number of aggressive acts did not increase to compromise the welfare status of the hens. Behaviors during the molt appeared consistent with mechanisms for conservation of body reserves.

The hypothesis was proposed that shorter incubation periods and faster growth rates for long-stored eggs would improve embryonic survival and poult hatchling quality. Increased incubation temperatures were tested for their efficacy in improving embryonic livability in fertilized eggs stored for 15 d prior to setting in the incubator compared to controls stored for only 3 d. Two temperature treatments were applied. In experiment 1, a 37.8 degrees C set point for dry bulb temperature was used to accelerate development for the initial 2 wk compared to the controls at 37.5 degrees C. Following treatment, the accelerated embryos were returned to the same machine as the controls. In experiment 2, higher temperature exposure was only for the initial week of incubation. The temperature and storage treatments were in a completely random 2 × 2 factorial arrangement of treatments. At the completion of 28 d of incubation, survival rates of all treatments were determined by opening all nonhatching eggs to differentiate truly fertilized eggs from unfertilized. Hatchability was determined by dividing the total number of poults on a hatching tray by the number of fertilized eggs on a tray. Incubator trays were the experimental unit. Tissues were sampled in both experiments to verify treatment effects on growth and metabolism. Hatching times were observed at 4-h intervals during the actual hatching process beginning at 25 d of incubation. It was concluded that delayed growth and depressed metabolism of fertilized turkey eggs stored for 15 d can be compensated for by exposure to higher incubation temperatures for the initial 1 or 2 wk of incubation.

Objectives To add to the knowledge base concerning confined placental mosaicism for trisomy 2. Methods Cytogenetic study of a late CVS referred for hyperechogenic bowel and raised AFP, and cytogenetic and molecular genetic study of a follow-up amniocentesis. Ultrasound monitoring at regular intervals following the CVS result. Results All cells examined from direct and cultured CVS showed a 47,XY,+2 karyotype. Amniocentesis showed a mosaic 47,XY,+2[8]/46,XY[81] karyotype. Uniparental disomy (UPD) studies on the amniotic fluid showed normal biparental inheritance. The pregnancy developed oligohydramnios and IUGR and resulted in a 26-week liveborn male infant with a 46,XY karyotype, which died after 3 days because of complications of severe prematurity. Placental villi post delivery showed only the 47,XY,+2 cell line. Conclusions This case represents a further example of confined placental mosaicism (CPM) for trisomy 2 associated with oligohydramnios, IUGR and poor pregnancy outcome. Copyright © 2003 John Wiley & Sons, Ltd.

High mortality occurred in two flocks of ducklings: 20% and 50% by 4 and 7 days of age, respectively. The feeds were found to contain 300 to 1176 ppb of deoxynivalenol (DON), 4.5 ppm of fumonisin, and 10 ppb of aflatoxin B1. No other mycotoxins were detected. Pathological analysis indicated that the ducklings were dehydrated with no feed in the gastrointestinal tract. Histopathology revealed no significant lesions. A necropsy diagnosis indicated a condition similar to starve-outs and feed refusal. An infectious cause of mortality was not suspected.

Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.

Four commercial table egg genetic stocks consisting of the Ottawa Control Strains 5, 7, and 10 (CS5, CS7, and CS10) and the 1993 H&N "Nick Chick" (CCS) were housed in the same environment and compared for production characteristics. These birds were housed in an environmentally controlled laying facility with trideck cages. Feed consumption, egg production, and mortality were monitored daily and compiled every 28 d. The study was conducted for two egg production cycles, including the molt period. Body weight was progressively lower for the more modern strains with CS5 being the heaviest and CCS maintaining the smallest body weight throughout the production periods. The CCS had the highest (P < 0.0001) hen-day production rate, which resulted in the greatest daily egg mass among the strains. The CCS consumed the greatest amount of feed and exhibited the highest gross egg income among the strains. We concluded that genetic selection has improved production parameters in commercial layers as determined by measurements in this study.

Leishmania major (Lm) infection in mice is a prototypical model for the role of immune deviation in disease resistance. Resistant strains of mice develop a Th1 response to Lm infection, distinguished by secretion of IL-12 and interferon gamma. In contrast, susceptible strains display sustained IL-4 expression characteristic of a Th2 response. However, when mechanisms of cell death are blocked, mice display a susceptible phenotype even in the presence of a strong Th1 response, suggesting that cell death, and not cytokine bias, may be an important factor in disease resistance. Here, we investigated this hypothesis by comparing lymphocyte cellularity, cell death and Fas expression in resistant CBA and susceptible BALB/c mice during the course of Lm infection. We found that delayed onset of cell death and late Fas induction correlated with massive lymphocyte accumulation and susceptibility to leishmaniasis, while early cell death and rapid Fas induction occurred in resistant mice.

Two commercial strains of 18-wk-old Single Comb White Leghorn (SCWL) hens, HyLine W-36 and DeKalb XL, were housed six hens per cage in layer cages at two densities (361 and 482 cm2 per bird) with two replications each per strain and density combination. The high density treatment contained 24 hens per replication, and the low density treatment contained 18 hens per replication. Egg production was measured during the first egg production cycle, a molt (fast) period, and the first 4 wk of the second lay cycle (20 to 68 wk of age). Blood samples were obtained from six hens from each replicate in each strain and density combination (total of 48) at 20, 26, 34, 43, 51, 62, 64, and 68 wk of age. In addition, blood samples were obtained in a random order from hens in each cage, and the sequence of sampling was recorded (1 to 6). Blood smears were made, from which heterophil to lymphocyte ratios (H:L) were determined. Radioimmunoassays were conducted to determine levels of plasma corticosterone (CS), 3,5,3'-triiodothyronine (T3), and thyroxine (T4). The results indicated that strain did not affect percentage hen-day egg production (%HDP). Strain and cage density did not affect H:L, T3, T4, or CS. However, these parameters were affected by bird age, which was related to the egg production cycle. Plasma CS significantly (P < or = 0.001) increased during peak %HDP at 26 wk and 64 wk during the molt (fast), and H:L significantly (P < or = 0.001) increased during the molt (fast) at 64 wk. The sequence in which blood samples were obtained, from hens within a cage in sampling order, also increased plasma CS. The CS was significantly (P < or = 0.001) elevated in the third, fifth, and sixth hens from which blood samples were drawn. Plasma T3 and T4 changed during the production cycle. The T3 was significantly (P < or = 0.0001) depressed during peak egg production at 26 wk and during the molt (fast) at 64 wk when compared with the other time periods. Plasma T4 was depressed (P < or = 0.0001) at 51 wk and was elevated (P < or = 0.0001) at 64 wk during the molt (fast). The physiological and metabolic parameters of the different hen strains and cage densities were similar during egg production. However, CS, T3, T4, and H:L changed with age in relation to the egg production cycle. In addition, the physiological demands of peak egg production and molt (fast) appeared to be similar.

Coxsackievirus B3 (CVB3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. C57BL/6 mice, which inherently lack major histocompatibility complex (MHC) class II IE antigen, develop minimal cardiac lesions despite high levels of virus in the heart. The present experiments evaluate the relative roles of class II IA and IE expression on myocarditis susceptibility in four transgenic C57BL/6 mouse strains differing in MHC class II antigen expression. Animals lacking MHC class II IE antigen (C57BL/6 [IA + IE − ] and AB o [IA − IE − ]) developed minimal cardiac lesions subsequent to infection despite high concentrations of virus in the heart. In contrast, strains expressing IE (AB o Eα [IA − IE + ] and Bl.Tg.Eα [IA + IE + ]) had substantial cardiac injury. Myocarditis susceptibility correlated to a Th1 (gamma interferon-positive) cell response in the spleen, while disease resistance correlated to a preferential Th2 (interleukin-4-positive) phenotype. Vγ/Vδ analysis indicates that distinct subpopulations of γδ + T cells are activated after CVB3 infection of C57BL/6 and Bl.Tg.Eα mice. Depletion of γδ + T cells abrogated myocarditis susceptibility in IE + animals and resulted in a Th1→Th2 phenotype shift. These studies indicate that the MHC class II antigen haplotype controls myocarditis susceptibility, that this control is most likely mediated through the type of γδ T cells activated during CVB3 infection, and finally that different subpopulations of γδ + T cells may either promote or inhibit Th1 cell responses.

The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha), derived from macrophages and other cells, may promote mononuclear cell inflammation and fibrosis in pulmonary silicosis. C3H/HeN mice were exposed to control air or to an aerosol of 70 mg/m3 cristobalite silica for 5 h/d for 12 days and examined at 2 and 16 weeks after exposure. This exposure resulted in murine silicosis, as manifested by focal mononuclear cell accumulations, diffuse interstitial fibrosis, lymphoid tissue enlargement, recruitment of inflammatory cells into BAL fluid, and increased total lung collagen. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) with designed primers and membrane hybridization with biotinylated cDNA probes were used to assess the abundance of IL-1beta and TNFalpha mRNA. In situ hybridization with digoxigenin-labeled cDNA probes was used to localize gene expression. Persistent overexpression of both IL-1beta and TNFalpha were found at 2 and 16 weeks in the lungs of silica-exposed mice compared with air-sham control mice. IL-1beta and TNFalpha expression localized to individual mononuclear cells in the alveolar spaces, groups of cells within the aggregate lesions, and scattered mononuclear cells in BALT and lymphoid nodules. Thus, cells producing IL-1beta and TNFalpha appear to be intimately associated with the evolving lesions of silicosis, and the lymphoid tissue of the lung may be important in driving the pathogenesis of this disease.

Experimental silicosis allows study of the mechanisms of lung injury, inflammation, and fibrosis. Inbred mice are an attractive species in which to study these mechanisms because of recent progress in murine immunology, molecular biology, and genetics. We exposed mice to an aerosol of silica and examined the effects of exposure dose, the evolution of disease features over time, and the variation in responses among four inbred strains. In C3H/HeN mice incremental cumulative exposure doses of cristobalite silica caused increased initial lung dust burden 12 to 16 weeks post-exposure, progressively intense pathological responses, and increased total lung collagen (hydroxyproline). The histopathological changes and total lung collagen increased progressively over time after exposure. We compared the features of silicosis in four strains of inbred mice selected for common use or immunologic reactivity 16 weeks after aerosol inhalation exposure to crystalline cristobalite silica (70 mg/m3, 5 hours/day, 12 days). C3H/HeN mice demonstrated histopathological silicotic lesions and enlarged intrapulmonary lymphoid tissue, and increased lung wet weight, bronchoalveolar lavage (BAL) recovery of macrophages, lymphocytes, and neutrophils, and total lung collagen (hydroxyproline). BALB/c mice developed slight pulmonary lesions; MRL/MpJ mice demonstrated prominent pulmonary infiltrates with lymphocytes; New Zealand Black mice developed extensive alveolar proteinaceous deposits, inflammation, and fibrosis. Our findings demonstrate orderly dose-time-response relationships, and a substantial variation of responses among inbred strains of mice. This model should prove valuable for future experimental interventions into the mechanisms of silicosis.

We have investigated the level of mitochondrial DNA (mtDNA) damage and deletions in bronchoalveolar lavage tissues from smokers and nonsmokers using quantitative, extra-long PCR and a "common" mtDNA deletion assay. Smokers had 5.6 times the level of mtDNA damage, 2.6 times the damage at a nuclear locus (beta-globin gene cluster), and almost 7 times the level of a 4.9-kb mtDNA deletion compared to nonsmokers, although the latter increase was not significant. Although both genomes (mitochondrial and nuclear) showed significantly increased levels of DNA damage in smokers (mtDNA P = 0.00072; beta-globin P = 0.0056), the relative differences were greatest in the mtDNA. Damage to the mtDNA may inhibit oxidative phosphorylation and, therefore, potentially cause or contribute to chronic lung disease and cancer. Consequently, the mtDNA may be a sensitive biomarker for environmentally induced genetic damage and mutation.

Eggshell conductance was measured and eggshell conductance constants were calculated for eggs from ostriches. In addition, egg water, yolk, albumen, shell, and total solids were measured in an effort to determine the maternal investment of ostrich eggs. The results of the study suggest that the optimal incubator humidity for ostrich eggs is less than 25% to allow a 15% loss of initial egg mass during the 45-d incubation period. This low humidity does not preclude increasing humidity during the actual hatching process. In addition, incubation temperatures need to be adjusted to allow a longer development time for the embryo to attain an adequate level of maturity to survive the plateau stage in oxygen consumption or to prevent the use of limited energy of the yolk to survive the anoxia of tucking and internal pipping. The optimal incubation temperature of ostrich eggs appears to be between 36.1 and 36.9 C.

The cumulative effects (CE) model explains free-operant choice by the ratio of total numbers of responses and reinforcements, a probability-like variable. Williams (1994) argues that the model is vulnerable to experiments that disprove melioration, a local probability model. The authors note critical differences between the nonlocal CE model and local probability models that allow the CE model to handle some data with which they are incompatible. All models are simplifications of reality; hence, a model's failures are as revealing as its successes. Williams suggests that simple models may need to be abandoned in favor of a "representational" account. The authors point out that representations must be both acquired and acted on. Acquisition requires processing of responses and reinforcers; action requires decision rules. Models are simply testable suggestions for what these rules and processes might be.

A study was undertaken to assess the role of sex and age on the adrenal cortical response of turkey poults during the time period associated with idiopathic poult mortality. Three and 14-day-old tom and hen turkey poults were subjected to the following treatments: saline injection (control), cool water immersion (20 C) for 1 min, cold water immersion (5 C) for 1 min, and 1 IU/kg adrenocorticotrophic hormone (ACTH) injection. Blood was collected 1 and 4 h posttreatment for plasma corticosterone (CS) assay. Temperature treatments did not affect plasma CS in either age or sex. Plasma CS was increased by ACTH after 4 h postinjection in both sexes and at both ages. The hypothalamic-pituitary-adrenal cortical axis of the turkey poult was functional but appeared to be insensitive to temperature stress.

A new flux-transfer technique has been used to measure the total neutron flux to an accuracy of 5% at the Army Pulse Radiation Facility (APRF) fast pulse reactor. Use is made of 239Pu-loaded fission chambers developed by the National Bureau of Standards (NBS) and calibrated against a 252Cf source at NBS. Advantages of the method are that it uses a standard source for calibration, that it is independent of errors in fission foil masses and that the effects of cross-section errors are minimized by the need to use only cross-section ratios. Therefore, the method can serve as a calibration procedure that is readily amenable to interlaboratory comparison. The results show that previous dosimetry is 18% too high in the APRF in-core irradiation facilities, and 21% too high at core surface. Flux calibrations have also been made by using 237Np, several uranium isotopes, and the 32S(n,p)32P reaction. Fluxes from all measurements agree to 7%. The (>10 keV/>3 Mev) flux ratios determined for the glory holes and leakage spectra are 8.4 ± 0.6 and 7.3 ± 0.5, respectively.

Three trials were conducted to investigate plasma corticosterone (B) levels in Large White turkey hens in response to adrenocorticotropic hormone (ACTH) injections at different ages, doses, and routes of administration. In Trial 1, hens were subjected to one of the following treatments at 10, 15, and 20 wk of age: cold water immersion (5 C for 1 min), ACTH injection (10 IU/kg), or saline injection. The plasma B responses to ACTH and cold water immersion followed the same general pattern in all three age groups. Plasma B levels of hens in the ACTH treatment were depressed below control B levels until 6 h postinjection, when they became elevated. Plasma B levels of hens in the cold water treatment were either similar to or increased above those of controls by 2 h posttreatment and were depressed below control levels at .5 h posttreatment at 10 and 15 wk of age. In Trial 2, three dose levels of ACTH (1, 5, and 10 IU/kg) were injected either intramuscularly (IM) or intravenously (IV) in 10-wk-old hens. There was both a dose and route of administration effect. Of the IM-injected hens, only those in the 1-IU ACTH treatment group had significantly (P less than .05) increased plasma B levels and this occurred 4 h postinjection. However, plasma B levels of the 1 and 5-IU IV-ACTH treatment hens were significantly (P less than .05) elevated at .5 h postinjection. Plasma B of the 10-IU IM and IV-ACTH treatments were consistently, but not significantly, lower than controls through 4 h postinjection.(ABSTRACT TRUNCATED AT 250 WORDS)

Emerging chick limb-buds at first grow only in length, not width. The growth parameters of limb mesoderm – cell shapes, distributions, division patterns and cleavage orientations – are incompatible with representations of this tissue as an elongating solid composed of proliferating but immobile cells. We observe that samples of both early limb mesoderm and also surrounding flank mesoderm round up like liquid droplets in organ culture. Therefore, liquid-like tissue rearrangments, including cell shuffling movements and neighbor exchanges, may occur in limb and flank mesoderm during in vivo limb budding. If so, differences in limb-flank surface tension properties would have to be present to keep these two fluid cell populations segregated into distinct tissues and properly positioned underneath limb and flank ectoderm. Previous studies have shown that tissue surface tensions are reflected in the spreading behavior of fused pairs of cell aggregates. To determine whether or not they possess differing surface tension properties, we pair excised pieces of early leg-bud, wing-bud or intervening flank mesoderm with pieces of heart or liver in hanging drop cultures. For more rapid determinations of relative liquid-tissue cohesiveness than can be obtained in conventional, long-term experiments, aggregate pairs are fixed shortly after fusion. Since partial-envelopment configurations depend upon relative aggregate sizes as well as their tissue surface tensions, new procedures are used to deduce relative aggregate cohesiveness from cross-sections of these briefly fused aggregate pairs. The envelopment tendencies of aggregates fixed 6–9 h after fusion are similar to those fixed 15–19 h after fusion: heart tends to surround leg; heart and wing surround each other with similar frequencies, but flank tends to surround heart. Also, liver tends to surround leg and wing, but flank tends to surround liver. When the effects of relative aggregate size are taken into account, these non-random, tissue-specific patterns of aggregate envelopment indicate that the relative cohesiveness of these tissues falls into the sequence: leg > heart ≃ wing > liver > flank. The in vitro behavior of early limb-bud and neighboring flank mesoderm in these studies suggests that they are not simply mechanically identical portions of a single liquid tissue. We have previously proposed that early limb-bud mesoderm may act like a non-dispersing, cohesive liquid droplet which is embedded within a less cohesive fluid layer of flank tissue (and which is molded distally into paddle-shaped conformations by solid-like limb ectoderm and/or subjacent extracellular matrix). This proposal is not only compatible with the growth parameters of limb-bud mesoderm in vivo, but is also consistent with our observation that flank mesoderm surrounds tissues which surround limb mesoderm in these aggregate-fusion experiments. Our model suggests that differences in the surface tension properties of limb vs. flank mesoderm may combine with differential cell proliferation, and possibly with active limb ectoderm expansion, to generate initial proximodistal limb outgrowth.

In each of two trials, plasma corticosterone (B) was measured in Large White turkey torn poults after the following treatments were applied: 1) .9% saline injected; 2) cold water immersion, and 3) adrenocorticotropic hormone (ACTH) injected (10 IU/kg body weight). Poults were treated at 3- to 4-day intervals from the day of hatching to 21 days of age. Plasma samples were obtained at 1, 2, 3, 4, and 6 hr posttreatment. In both trials, there was a depression in B levels within the first 3 hr following ACTH or cold water immersion treatment. Significant increases in plasma B levels of the cold water treatment occurred at 4 hr posttreatment in Trial 1 in 7-day-old poults and in Trial 2 in 21-day-old poults. A significant adrenal cortical response to ACTH injection was observed in 3- and 7-day-old poults at 6 hrs posttreatment in Trial 2. Plasma B concentrations were also measured in three groups of nontreated Large White torn poults on the day of hatching at a commercial hatchery. Plasma samples were obtained from poults in incubators at 1000 hr, immediately following commercial processing procedures at 1030 hr, and at poult placement at 1330 hr. Plasma B levels of poults sampled in the incubator and after processing were similar. However, B levels of poults sampled at placement were increased significantly above the other two groups.

The study examined the relationship between plasma corticosterone (CS) levels and early mortality in Large White tom turkey poults. Trial 1 was conducted to compare the plasma CS levels of 3-day-old poults that subsequently lived or died during the first 2 wk posthatch. Blood samples were obtained from 100 poults at 3 days of age. By 2 wk of age 9% mortality had occurred. Plasma CS of poults that lived (7.1 ng/mL) was significantly greater (P less than .05) than in poults that died (3.2 ng/mL) between 3 and 14 days of age. A second trial was conducted to test the effects of feed-induced elevation of plasma CS on poult performance under stressful conditions. This trial consisted of three treatment groups: 1) control (C), poults placed immediately after removal from the hatcher with feed and water; 2) control-held (CH), poults held without feed and water at 28.9 C for 3 days posthatch; and 3) 40 mg CS/kg feed-held (40H), poults held without feed and water at 28.9 C for 3 days posthatch then fed 40 mg CS/kg feed. Mortality was monitored daily and body weights, feed consumption, and plasma CS levels were measured at 1 and 2 wk of age. The only performance parameter that was significantly affected was body weight; a significant reduction occurred at 2 wk of age in poults given the 40H treatment. It was concluded that poult death is associated with low plasma CS levels, but diet-induced increases in plasma CS did not significantly improve livability following a stressful condition.

Two trials were conducted with turkey poults to examine the ontogeny of daily rhythmicity of plasma corticosterone (CS), and to determine the plasma CS response to adrenocorticotropic hormone (ACTH) injections and temperature stress at different times during a light-dark cycle. In Trial 1, CS levels were determined at 3-h intervals over a 24-h period in 3, 10, and 14-day-old tom and hen poults maintained on a 12 h light:12 h dark (12L:12D) light-dark cycle. Plasma CS levels of tom and hen poults were similar. A robust daily rhythm in plasma CS occurred by 10 days of age, with maximal levels of CS occurring during the scotophase. In Trial 2, daily variation in plasma CS sensitivity to cold treatment or ACTH in 2-wk-old toms was examined. Tom poults were exposed to cold water immersion (5 C for 1 min), porcine ACTH injection (1 IU/kg), or saline injection at 1100 h in midphotophase and at 2300 h in midscotophase. Treatments significantly increased plasma CS in both the photophase and scotophase, with the levels being significantly higher in the scotophase. At midphotophase cold or ACTH treatment induced, respectively, a 489 and 546% increase in plasma CS above that of controls. During midscotophase, 746 and 695% increases in CS above levels for controls were induced by cold stress or ACTH, respectively. Differences between percent changes for times of day were not significantly different. It was concluded that a daily rhythm in plasma CS in turkey poults grown under a 12L:12D light-dark cycle occurs between 3 and 10 days of age, with maximum levels occurring during the scotophase. A daily variation in the adrenal cortical response to exogenous ACTH or cold water treatment in excess of the normal plasma CS rhythm was not apparent.

This report demonstrates symptomatic coronary artery spasm at a site different from that of the previous percutaneous transluminal coronary angioplasty.

This article provides a review of Legionnaire's Disease, a bacterial pneumonia caused by Legionella species, and of Pontiac Fever, the flu-like illness caused by these microorganisms. The authors draw on their personal experience with major human outbreaks of Legionnaire's Disease and with animal models of Legionella pneumonia. Emphasis is placed on the sources in nature from which legionellosis is acquired, the means of dissemination of bacteria, the epidemiology of human infections, the pathogenetic mechanisms of disease and host defense, the clinical manifestations, and the treatment.

Inhalation of crystalline silica causes fibrotic pulmonary disease. The lung pathology of silicosis is well characterized and predictable, but the initial patterns of particle deposition and translocation are unknown. Scanning electron microscopy and backscattered electron imaging were utilized to quantify silica particle distribution in the distal air spaces of rats following a three-hour exposure to silica dust at a concentration of 100mg/m3. Lungs were perfused through the vasculature with 2% Karnovsky's fixative at a pressure of 15cm of water for 30 minutes. Blocks of tissue were dissected from five predetermined regions of the left lung and critical point dried. Mounted blocks were further dissected to reveal terminal bronchioles and their attached alveolar ducts. The tissue was sputter-coated with gold. Silica particles were visualized on the alveolar duct surfaces, then counted using negative backscattered electron imaging. The precise area of alveolar duct surfaces was calculated by using a standard magnification of 10,000X and a grid of 64cm2 over the viewing cathode ray tube. Thus, quantitation of silica particles could be expressed as number of particles per square micron. Our data show that there were fewer particles on the alveolar duct surfaces and in alveolar spaces of animals 8 hours after exposure when compared with animals 3 hours post-exposure.

We characterized the bronchoalveolar lavage (BAL) from healthy Vermont granite workers to investigate the pulmonary response to a chronic exposure to an injurious agent. Nine granite workers with 4 to 36 yr of employment in the industry and 27 unexposed volunteers were normal by history, physical examination, electrocardiogram, blood count, spirometry, and chest radiograph. Lavage cell recovery and percent neutrophils were not different. Lymphocyte recovery in BAL was increased in the granite-exposed population. Granite dust was present within the majority of alveolar macrophages from granite workers compared with those from control subjects, as determined by polarizing light microscopy and confirmed by scanning electron microscopy with X-ray energy spectrometry. There were no differences in phagocytic function or viability of macrophages from granite workers compared with those from unexposed volunteers. We conclude that in exposed populations, granite dust can be detected and semiquantitated in lavage specimens within the alveolar macrophages, macrophage function is preserved, and the response to this exposure involves an influx of lymphocytes.

Emerging chick limb-buds at first grow only in length, not width. The growth parameters of limb mesoderm--cell shapes, distributions, division patterns and cleavage orientations--are incompatible with representations of this tissue as an elongating solid composed of proliferating but immobile cells. We observe that samples of both early limb mesoderm and also surrounding flank mesoderm round up like liquid droplets in organ culture. Therefore, liquid-like tissue rearrangments, including cell shuffling movements and neighbor exchanges, may occur in limb and flank mesoderm during in vivo limb budding. If so, differences in limb-flank surface tension properties would have to be present to keep these two fluid cell populations segregated into distinct tissues and properly positioned underneath limb and flank ectoderm. Previous studies have shown that tissue surface tensions are reflected in the spreading behavior of fused pairs of cell aggregates. To determine whether or not they possess differing surface tension properties, we pair excised pieces of early leg-bud, wing-bud or intervening flank mesoderm with pieces of 5 3/4-day heart or liver in hanging drop cultures. For more rapid determinations of relative liquid-tissue cohesiveness than can be obtained in conventional, long-term experiments, aggregate pairs are fixed shortly after fusion. Since partial-envelopment configurations depend upon relative aggregate sizes as well as their tissue surface tensions, new procedures are used to deduce relative aggregate cohesiveness from cross-sections of these briefly fused aggregate pairs. The envelopment tendencies of aggregates fixed 6--9 h after fusion are similar to those fixed 15--19 h after fusion: heart tends to surround leg; heart and wing surround each other with similar frequencies, but flank tends to surround heart. Also, liver tends to surround leg and wing, but flank tends to surround liver. When the effects of relative aggregate size are taken into account, these non-random, tissue-specific patterns of aggregate envelopment indicate that the relative cohesiveness of these tissues falls into the sequence: leg greater than heart congruent to wing greater than liver greater than flank. The in vitro behavior of early limb-bud and neighboring flank mesoderm in these studies suggests that they are not simply mechanically identical portions of a single liquid tissue. We have previously proposed that early limb-bud mesoderm may act like a non-dispersing, cohesive liquid droplet which is embedded within a less cohesive fluid layer of flank tissue (and which is molded distally into paddle-shaped conformations by solid-like limb ectoderm and/or subjacent extracellular matrix). This proposal is not only compatible with the growth parameters of limb-bud mesoderm in vivo, but is also consistent with our observation that flank mesoderm surrounds tissues which surround limb mesoderm in these aggregate-fusion experiments. Our model suggests that differences in the surface tension properties of limb vs...

Levels of type III procollagen N-terminal peptide were immunoassayed in sera and bronchoalveolar lavage fluids from healthy volunteers and patients with idiopathic pulmonary fibrosis or sarcoidosis. Peptide levels normalized to protein were higher than corresponding serum levels in all groups, suggesting that the lung is a producer of this peptide. Levels were significantly elevated in both patient groups, suggesting increased rates of type III collagen synthesis. Values were highest in idiopathic pulmonary fibrosis samples. Correlation of peptide levels with clinical severity of disease and lavage cell profiles was poor, perhaps because the latter reflects aspects of the disease process other than that stage in which type III collagen synthesis is altered. Lavage analyses of procollagen peptides may provide an important index of altered collagen synthesis in interstitial lung disease.

We developed an animal model of Legionnaires' pneumonia to permit study of aerosol infection, pathogenesis, and pulmonary host defense mechanisms in this disease. Guinea pigs and rats were exposed in a nose-only inhalation facility for 30 min to an aerosol of Burlington serogroup 1 Legionella pneumophila. Lungs contained 10(3) to 10(4) L. pneumophila immediately after exposure. Both guinea pigs and rats developed pneumonia, with 100% infectivity by microbiologic, histologic, and serologic criteria. Guinea pigs demonstrated illness, fever, and 56% mortality; rats showed little illness and 11% mortality. In both species, diffuse patchy pneumonitis coalesced and consolidated as the disease progressed. Aerosol challenge with 3H-L. pneumophila showed exponential growth of the bacteria in the lungs of both species. Guinea pigs and rats can be infected by aerosol exposure to L. pneumophila to produce a disease that closely simulates human Legionnaires' pneumonia. Rapid initial intrapulmonary growth suggests that resident lung defense mechanisms are quite ineffective against L. pneumophila, and that recruited or immunospecific defenses may be more critical in the outcome of infection. The difference in severity of illness between guinea pigs and rats may be exploited for different experimental designs.

Subsegmental bronchoalveolar lavage of human subjects provides an accessible sample of cells and secretions from the lower respiratory tract for clinical and research study. Technical factors that may modify lavage results have received little attention. The effects of lavage volume on the patterns of recovered cells and biochemical components were studied by separately analyzing each of 4 sequential 60-ml syringes of saline instilled into a subsegment of the right middle lobe. Fourteen healthy normal subjects volunteered for lavage. Recovery of cells from both nonsmokers and smokers increased and then remained essentially constant in subsequent syringes, suggesting elution of adherent macrophages from the alveolar surface. Protein, carbohydrate, lipid, and potassium appeared in decreasing concentrations in sequential syringes, but different constituents followed separate patterns. Simple mixing models do not explain the observed results. Measured values for the components in a "small" 120-ml lavage may be substantially different from the values in a "large" 240-ml lavage. Further study of the kinetics of recovery of selected lavage components may provide better understanding of the origins and functions of these substances in the lung.

Day-old tom poults were exposed to one of the following light treatments: 1) continuous incandescent light (24LL), 2) 23L:1D incandescent light, 3) 12L:12D incandescent light, or 4) natural day lengths only. Mortality was recorded daily. At Weeks 1, 2, 4, 6, and 8, after poult placement, body weights and feed consumption were measured. At each of these times, 10 poults were sacrificed from each treatment group for evaluation of plasma corticosterone. Day lengths utilized in this study had no consistent effect on poult-performance parameters except from 0 to 2 weeks of age. During this time, poults in the 24LL and 23L:1D treatments consumed less feed but were similar in body weight to poults in the other treatments. Adrenal function was also not consistently affected by day length. However, in all treatment groups plasm a corticosterone was lowest during the first 2 weeks posthatching, when compared to hormone levels at 4, 6, and 8 weeks. The lower corticosterone that occurred during the first 2 weeks posthatching may be involved in early poult mortality.

The success or failure of pulmonary defense mechanisms largely determines the appearance of clinical lung disease. The lung is protected by interlucking systems of nonspecific and specific defenses. Inhaled substrances can be isolated by mechanical barriers or can be physically removed from the lung either by transport up the bronchial mucociliary escalator or by transport through interstitial and lymphatic channels leading to lymph nodes. Substances can be locally detoxified within the lung by interaction with secretory proteins, such as antibodies, or by neutralization and dissolution within phagocytic cells. The pulmonary alveolar macrophage is the central figure in the protection of the respiratory membrane, operating in all 3 of the nonspecific modes of defense and augmented by specific immunologic mechanisms as well. Alterations in macrophage function and physiology may be crucial in determining the effectiveness of pulmonary defense. Recent advances in the cell biology of the alveolar macrophage have led to a greater understanding of its complex funcition. The multiple origins of macrophages from local and circulating cell pools and the variability in their fate and lifespan reflect the multi-faceted role of this cell type. The importance of the interactions between macrophages, orther lung cells, and other defense mechanisms has become increasingly clear. As well as functioning as resident defender of the alveolus, the macrophage is an important effector of the pulmonary immune response and plays a key role in the pathogenesis of a wide variety of inflammatory, destructive, and fibrotic lung diseases. Humoral and cell-mediated immune responses amplify and direct lung defenses against infection and may also participate in protection against other agents. Immunoglobulin A and G, microbial neutralizing and opsonizing anti-bodies, and macrophage-stimulating T lymphocytes are the major immunospecific forms of lung defense. Infectious agents, cigarette smoke, air pollutants, industrial dusts, and a spectrum of coexistent disease states may impair pulmonary defense mechanisms and increase susceptibility to asute and chronic respiratory diseases. A thorough understanding of the ways in which the lung protects itself against the daily assault of infectious, toxic, and immunogenic materials should lead to a beter understanding of pathogenesis and consequences of lung disease and to better clinical care of the patient with respiratory disease.