Evaluation of the Pulmonary Toxicity of Ambient Particulate Matter From Camp Victory, Iraq.

Anecdotal reports in the press and epidemiological studies suggest that deployment to Iraq and Afghanistan may be associated with respiratory diseases and symptoms in U.S. military personnel and veterans. Exposures during military operations were complex, but virtually all service members were exposed to high levels of respirable, geogenic dust. Inhalation of other dusts has been shown to be associated with adverse health effects, but the pulmonary toxicity of ambient dust from Iraq has not been previously studied. The relative toxicity of Camp Victory dust was evaluated by comparing it to particulate matter from northern Kuwait, a standard U.S. urban dust, and crystalline silica using a single intratracheal instillation in rats. Lung histology, protein levels, and cell counts were evaluated in the bronchoalveolar lavage fluid 1-150 d later. The Iraq dust provoked an early significant, acute inflammatory response. However, the level of inflammation in response to the Iraq dust, U.S. urban dust, and Kuwait dust rapidly declined and was nearly at control levels by the end of the study At later times, animals exposed to the Iraq, U.S. urban, or Kuwait dusts showed increased small airway remodeling and emphysema compared to silica-exposed and control animals without evidence of fibrosis or premalignant changes. The severity and persistence of pulmonary toxicity of these three dusts from the Middle East resemble those of a U.S. urban dust and are less than those of silica. Therefore, Iraq dust exposure is not highly toxic, but similar to other poorly soluble low-toxicity dusts.

Myocardial mechanisms causing heart failure early after cardiac transplantation.

Early after heart transplantation, some patients have heart failure (HF) with preserved left ventricular ejection fraction (LVEF), in the absence of rejection. The purpose of this study was to define the mechanisms causing HF early after transplantation and to determine whether these mechanisms involve changes that occur in active or passive myocardial properties. Eleven consecutive patients 1 week after heart transplantation underwent right heart catheterization and echocardiography with an endomyocardial biopsy. Hemodynamic measurements were obtained at spontaneous heart rate, and then were repeated at three atrially paced rates increased in 20-bpm increments above spontaneous heart rate. At baseline, 5 patients (group 1) had clinical HF and a pulmonary capillary wedge pressure (PCWP) > or = 16 mmHg, and 6 patients (group 2) had no clinical evidence of HF and a PCWP < 16 mmHg. LVEF was normal in all 11 patients. The relationships between cardiac index versus heart rate (HR) and PCWP versus HR were normal in all 11 patients. These normal function-versus-frequency relationships suggested that there were no significant abnormalities in the active myocardial processes of contraction or relaxation. In group 1 patients, the PCWP was significantly increased but the left ventricular end diastolic dimension was normal, suggestive of diastolic stiffness. Early after transplantation, there was a significant increase in LV wall thickness in group 1 patients as compared with preexplantation values despite myocardial biopsies in all 11 patients, showing no evidence of rejection, cardiomyocyte hypertrophy, or interstitial fibrosis thus suggestive of myocardial edema.

Myofibroblast induction and microvascular alteration in scleroderma lung fibrosis.

OBJECTIVE: Scleroderma (SSc) is an autoimmune connective tissue disorder characterized by progressive fibrosis of the skin and internal organs. The leading cause of death in SSc patients is pulmonary dysfunction as a result of interstitial fibrosis and pulmonary vasculopathy. Our objective was to evaluate histopathological abnormalities associated with the development of pulmonary fibrosis in SSc. METHODS: Postmortem SSc lung tissue from various stages of fibrosis and tissue from normal lung were analyzed by Masson's trichrome staining and immunohistochemistry. Monoclonal antibodies against smooth muscle-alpha actin (myofibroblast marker), von Willebrand Factor, platelet endothelial cell adhesion molecule-1 (endothelial cell markers), or caldesmon (smooth muscle cell marker) were employed. RESULTS: We found that in the early active stages of SSc lung fibrosis two major types of cellular abnormalities occur. One is the induction of a large number of smooth muscle alpha-actin-positive myofibroblasts in interstitia. The other is the excessive formation of alveolar capillaries (hypervascularity) accompanied by an increase in the number of microvascular endothelial cells. The vascular abnormality also involves the development of microvessels that are irregular in size and shape. However, the population of myofibroblasts and capillary endothelial cells decline as the fibrosis progresses to its most marked, later stages. CONCLUSION: We conclude that the induction of myofibroblasts and the overdevelopment of capillary microvessels characterize the progression of lung fibrosis in SSc. Using these histological alterations as criteria, therefore we have divided the fibrosis formed in the SSc lungs into four pathological stages. These results suggest that both fibroblast overproliferation and vascular abnormality play an important role in the pathogenesis of lung fibrosis in SSc.

Separation of fine particulate matter emitted from gasoline and diesel vehicles using chemical mass balancing techniques.

Samples of fine particulate matter were collected in a roadway tunnel near Houston, TX over a period of 4 days during two separate sampling periods: one sampling period from 1200 to 1400 local time and another sampling period from 1600 to 1800 local time. During the two sampling periods, the tunnel traffic contained roughly equivalent numbers of heavy-duty diesel trucks. However, during the late afternoon sampling period, the tunnel contained twice as many light-duty gasoline-powered vehicles. The effect of this shift in the vehicle fleet affects the overall emission index (grams pollutant emitted per kilogram carbon in fuel) for fine particles and fine particulate elemental carbon. Additionally, this shift in the fraction of diesel vehicles in the tunnel is used to determine if the chemical mass balancing techniques used to track emissions from gasoline-powered and diesel-powered emissions accurately separates these two emission categories. The results show that the chemical mass balancing calculations apportion roughly equal amounts of the particulate matter measured to diesel vehicles between the two periods and attribute almost twice as much particulate matter in the late afternoon sampling period to gasoline vehicles. Both of these results are consistent with the traffic volume of gasoline and diesel vehicles in the tunnel in the two separate periods and validate the ability for chemical mass balancing techniques to separate these two primary sources of fine particles.

On-road measurement of carbonyls in California light-duty vehicle emissions.

Emissions of carbonyls by motor vehicles are of concern because these species can be hazardous to human health and highly reactive in the atmosphere. The objective of this research was to measure carbonyl emission factors for California light-duty motor vehicles. Measurements were made at the entrance and exit of a San Francisco Bay area highway tunnel, in the center bore where heavy-duty trucks are not allowed. During summer 1999, approximately 100 carbonyls were identified, including saturated aliphatic aldehydes and ketones, unsaturated aliphatic carbonyls, aliphatic dicarbonyls, and aromatic carbonyls. Concentrations were measured for 32 carbonyls and were combined with NMOC, CO, and CO2 concentrations to calculate by carbon balance emission factors per unit of fuel burned. The measured carbonyl mass emitted from light-duty vehicles was 68 +/- 4 mg L(-1). Formaldehyde accounted for 45% of the measured mass emissions, acetaldehyde 12%, tolualdehydes 10%, benzaldehyde 7.2%, and acetone 5.9%. The ozone forming potential of the carbonyl emissions was dominated by formaldehyde (70%) and acetaldehyde (14%). Between 1994 and 1999, emission factors measured at the same tunnel for formaldehyde, acetaldehyde, and benzaldehyde decreased by 45-70%. Carbonyls constituted 3.9% of total NMOC mass emissions and 5.2% of NMOC reactivity. A comparison of carbonyl emissions with gasoline composition supports previous findings that aromatic aldehyde emissions are related to aromatics in gasoline. Carbonyl concentrations in liquid gasoline were also measured. Acetone and MEK were the most abundant carbonyls in unburned gasoline; eight other carbonyls were detected and quantified.

MCMV induces neointima in IFN-gammaR-/- mice: intimal cell apoptosis and persistent proliferation of myofibroblasts.

BACKGROUND: CMV infections have been linked to vasculopathies like atherosclerosis and Scleroderma. CMV infects vascular endothelium with intermittent shedding of the virus and the development of latency. METHODS: We adopted a model of arteritis, developed by Presti et al. (1998), triggered by murine cytomegalovirus (MCMV) infection. Our studies focused on neointima formation. Groups of mice include: 1) immunocompetent 129S, 2) immunocompetent 129S receiving whole body irradiation and MCMV, 3) IFN-gammaR-/- receiving MCMV, and 4) IFN-gammaR-/- receiving MCMV and whole body irradiation. RESULTS: Mice were inoculated with MCMV (5 x 10(4) or 1 x 10(5) PFU's) by i.p. injection; hearts and abdominal aortas were collected and histopathology evaluated. Infected immunocompetent animals exhibited widespread perivascular inflammation, which subsided by 8 weeks. Intimal pathology was not observed in any control group. Immunocompetent animals receiving MCMV and irradiation developed mild to moderate intimal lesions associated with medial and adventitial inflammation. IFN-gammaR-/- mice infected for 4 months and receiving whole body irradiation 2 months after infection developed pathology characterized by extensive adventitial and medial infiltrate and significant neointima, suggesting that infection and immunosuppression were co-requisites of neointima formation. Immunohistochemical analysis revealed myofibroblasts as a major component of neointima. The disease is characterized by up-regulation of growth factors (TGF-beta1, PDGF-A and B). Apoptosis was detected in the intimal layer of affected aortas. Active proliferation of myofibroblasts and infiltrating cells was also detected. CONCLUSION: These results indicate that CMV infections may lead to intimal injury that results in the formation of neointima characteristic of autoimmune vasculopathies.

A fuel-based assessment of off-road diesel engine emissions.

The use of diesel engines in off-road applications is a significant source of nitrogen oxides (NOx) and particulate matter (PM10). Such off-road applications include railroad locomotives, marine vessels, and equipment used for agriculture, construction, logging, and mining. Emissions from these sources are only beginning to be controlled. Due to the large number of these engines and their wide range of applications, total activity and emissions from these sources are uncertain. A method for estimating the emissions from off-road diesel engines based on the quantity of diesel fuel consumed is presented. Emission factors are normalized by fuel consumption, and total activity is estimated by the total fuel consumed. Total exhaust emissions from off-road diesel equipment (excluding locomotives and marine vessels) in the United States during 1996 have been estimated to be 1.2 x 10(9) kg NOx and 1.2 x 10(8) kg PM10. Emissions estimates published by the U.S. Environmental Protection Agency are 2.3 times higher for both NOx and exhaust PM10 emissions than estimates based directly on fuel consumption. These emissions estimates disagree mainly due to differences in activity estimates, rather than to differences in the emission factors. All current emission inventories for off-road engines are uncertain because of the limited in-use emissions testing that has been performed on these engines. Regional- and state-level breakdowns in diesel fuel consumption by off-road mobile sources are also presented. Taken together with on-road measurements of diesel engine emissions, results of this study suggest that in 1996, off-road diesel equipment (including agriculture, construction, logging, and mining equipment, but not locomotives or marine vessels) was responsible for 10% of mobile source NOx emissions nationally, whereas on-road diesel vehicles contributed 33%.

Localization and expression of tissue kallikrein and kallistatin in human blood vessels.

Tissue kallikrein releases kinins by specific proteolysis, an activity inhibited by kallistatin. In this study, kallikrein and kallistatin were localized to endothelial and smooth muscle cells of large, medium, and small normal blood vessels by immunohistochemical techniques. Immunostaining for both proteins was strong in the endothelium of all sizes of blood vessels and was more intense in medial smooth muscle cells of small and medium-sized blood vessels than in elastic arteries. The sites of synthesis by endothelial and smooth muscle cells were demonstrated in normal blood vessels of all sizes by in situ hybridization histochemistry. Kallikrein and kallistatin levels were measured by immunoassays in homogenates of human aorta, vena cava, and iliac artery and vein. Tissue kallikrein and kallistatin transcripts were identified in human blood vessels by RT-PCR followed by Southern blot analysis with specific oligonucleotide probes. The results demonstrated the expression and co-localization of tissue kallikrein and kallistatin in human vessels and suggest a potential role of kallistatin in regulating tissue kallikrein in blood vessels.

Cellular localization of kallistatin and tissue kallikrein in human pancreas and salivary glands.

The tissue kallikrein-kinin system contributes to the regulation of local blood flow, vascular permeability, inflammatory responses, and ion transport. Tissue kallikrein is a serine proteinase which produces vasoactive kinin peptides. Kallistatin specifically binds to tissue kallikrein and inhibits its proteolytic activity. To investigate their anatomical relationship in the human pancreas and salivary glands, the expression and localization of kallistatin and tissue kallikrein were identified by immunoassays, immunohistochemistry, and in situ hybridization histochemistry. Human kallistatin and tissue kallikrein levels were measured by ELISA and radioimmunoassay, respectively, in pancreatic and salivary tissue extracts, and in pancreatic fluid and saliva. Immunoreactive kallistatin and kallikrein were colocalized in acinar cells of the human pancreas by immunohistochemistry. In situ hybridization histochemistry confirmed the presence of both mRNAs in pancreatic acini. In salivary glands, kallistatin and kallikrein mRNAs were also colocalized in serous acinar cells, and the kallikrein transcript was further localized to striated and interlobular ducts. Immunoreactive kallistatin was localized in serous acinar and demilune cells of salivary glands and kallikrein was localized to the epithelium of striated and interlobular ducts. The colocalization and/or coexpression of human tissue kallikrein and kallistatin in the pancreas and salivary glands suggest a role for kallistatin in the regulation of tissue kallikrein in these organs.

Reducing the risk of accidental death due to vehicle-related carbon monoxide poisoning.

Emissions of carbon monoxide (CO) from motor vehicles cause several hundred accidental fatal poisonings annually in the United States. The circumstances that could lead to fatal poisonings in residential settings with motor vehicles as the source of CO were explored. The risk of death in a garage (volume = 90 m3) and a single-family dwelling (400 m3) was evaluated using a Monte Carlo simulation with varying CO emission rates and ventilation rates. Information on emission rates was obtained from a survey of motor vehicle exhaust gas composition under warm idle conditions in California, and information on ventilation rates was obtained from a summary of published measurements in the U.S. housing stock. The risk of death ranged from 16 to 21% for a 3-hr exposure in a garage to 0% for a 1-hr exposure in a house. Older vehicles were associated with a disproportionately high risk of death. Removing all pre-1975 vehicles from the fleet would reduce the risk of death by one-fourth to two-thirds, depending on the exposure scenario. Significant efforts have been made to control CO emissions from motor vehicles with the goal of reducing CO concentrations in outdoor air. Substantial public health benefit could also be obtained if vehicle control measures were designed to take account of acute CO poisonings explicitly.

Respiratory reovirus 1/L induction of intraluminal fibrosis. A model for the study of bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a term that was first applied in 1985 to describe a long-observed but unclassified pattern of acute lung injury. BOOP lesions are characterized by fibrous extensions into the alveolar spaces in association with a peribronchiolar organizing pneumonia. Since 1985, an increasing number of reports of BOOP have appeared in the clinical literature, and it is now accepted that BOOP is a significant pulmonary syndrome. Although BOOP can be associated with a number of documented pulmonary insults, many cases are not associated with known causes and are thus classified as idiopathic. The lack of an appropriate small animal model that closely mimics the generation of BOOP lesions has been an impediment to basic studies of the pathogenic mechanisms responsible for the generation of BOOP in humans. In this report, we describe an animal model for BOOP in which CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions. These lesions closely resemble those seen in humans and occur in a well defined temporal sequence that proceeds from initial peribronchiolar inflammatory lesions to characteristic, fibrotic cellular BOOP lesions over a 3-week time course.

Fine-needle aspiration cytology of pleuropulmonary blastoma: case report and review of the literature.

This report describes the fine-needle aspiration (FNA) cytology of a case of pleuropulmonary blastoma in a 3-yr-9-mo-old male. Pleuropulmonary blastoma is considered by most authors to be distinct from pulmonary blastoma and is a rare malignant tumor of the intrathoracic cavity. FNA smears were cellular with numerous small ovoid to spindled cells with oval to elliptical nuclei exhibiting finely granular chromatin and inconspicuous nucleoli. The cytoplasm was scant and eosinophilic with indistinct borders. Focal chondroid material and blastema-like cells were noted. The differential diagnosis suggested by the cytologic findings included rhabdomysosarcoma, teratoma, neuroblastoma, malignant mesenchymoma, pleuropulmonary blastoma, and metastatic tumor. To our knowledge, this is the first report of the cytology of this tumor.

Silicone deposition in reconstruction scars of women with silicone breast implants.

BACKGROUND: The possible association of silicone breast implants and disease is a subject of continuous debate and concern. OBJECTIVE: Our purpose was to examine microscopically and ultrastructurally the periprosthetic fibrous capsules and reconstruction scars of women with silicone breast implants. METHODS: Representative samples from the periprosthetic capsules and reconstruction scars from six women with silicone breast implants were examined by a variety of light microscopy techniques, transmission electron microscopy, and electron probe microanalysis. RESULTS: Silicone globules of various sizes were identified in every periprosthetic capsule and reconstruction scar. CONCLUSION: Extrusion and seeding of the incision tract during surgery most likely accounts for the presence of silicone in the reconstruction scar specimens. This observation suggests that the identification of silicone in the reconstruction scars of women with silicone breast implants does not necessarily implicate rupture of the silicone breast implant with systemic dissemination of silicone gel.

Fatal disseminated herpes simplex in pregnancy with maternal and neonatal death.

Disseminated herpes is rare in the adult and usually occurs in the immunocompromised. Twenty-one cases have been reported in which healthy women contracted life-threatening disseminated herpes simplex virus (HSV) infections in the third trimester of pregnancy. Most of these patients had nonspecific symptoms, and many did not have mucocutaneous lesions. On physical examination, they were usually febrile and anicteric and had markedly elevated aminotransferase values, without a corresponding elevation in bilirubin level. In our review of the literature, we found that prompt acyclovir therapy resulted in 100% survival. Those patients not receiving treatment or treated late in the terminal stages of their disease had a 63% mortality rate. We report a case of maternal disseminated HSV with subsequent maternal death at an estimated 31 weeks' gestation in which the diagnosis was made at the time of necropsy. The infant was started on acyclovir therapy but died of disseminated HSV.

Cellular localization of low-molecular-weight kininogen and bradykinin B2 receptor mRNAs in human kidney.

Kininogen is the precursor of the kinin peptide, which binds to kinin receptors and mediates a broad spectrum of physiological effects. To understand the function of kinin in the kidney, we have identified the cellular localization of the human low-molecular-weight (LMW) kininogen and bradykinin B2 receptor mRNAs in the human kidney by in situ hybridization histochemistry. Kininogen mRNA was found in the juxtaglomerular cells, mesangial areas, epithelium of parietal and visceral (podocytes) layers of Bowman's capsule, proximal and distal tubules, thin and thick segments of Henle's loop, collecting ducts, and the endothelial cells of the blood vessels. B2 receptor mRNA was colocalized with kininogen mRNA in the kidney except the podocytes. The most intense signals were observed in the distal tubules and collecting ducts for both kininogen and B2 receptor mRNAs. No signals were observed in the interstitial cells and macula densa. Control sections did not stain with either the kininogen or B2 receptor sense riboprobe. A Northern blot showed that the expression of LMW kininogen is in the liver and the kidney. Reverse transcription-polymerase chain reaction Southern blot showed expression of B2 receptor mRNA in the endothelial cells, renal proximal tubular cells, and kidney. Our results show the sites of action of kinin in the human kidney and provide further insight into the physiological role of the kallikrein-kinin system on renal function.

Respiratory-mucosal lymphocyte populations induced by reovirus serotype 1 infection.

Respiratory virus infections are a serious health challenge. While models exist to study immune mechanisms of the respiratory tract, they have not allowed analysis of the interaction of the lower respiratory tract with other components of the mucosal immune system. This study demonstrates that reovirus 1/Lang, an effective gut mucosal immunogen, also provides a useful model of respiratory mucosal infection. Intra-nasal infection of Balb/c mice resulted in severe viral bronchopneumonia. Major components of the cellular inflammatory response in the lung interstitium and alveolar spaces were CD8 lymphocytes. Lung lymphocyte populations exhibited lysis of reovirus-infected, but not uninfected target cells after in vitro culture. The GCT antigen, a germinal center B-cell and CD8 T-cell marker, was present on 21-60% of the inflammatory lymphocytes. A novel population of GCT-expressing CD4+ lymphocytes unique to reovirus-stimulated lung alveolar and interstitial lymphocyte populations was identified.

Mosaic vs. nonmosaic trisomy 9: report of a liveborn infant evaluated by fluorescence in situ hybridization and review of the literature.

We report on a newborn infant with multiple congenital anomalies and apparent nonmosaic trisomy 9 in the blood (by conventional cytogenetic studies) who died shortly after birth. Clinical observations at birth and autopsy are compared with phenotypes of mosaic and nonmosaic trisomy 9 cases reported previously. Unlike the initial cytogenetic analysis, fluorescence in situ hybridization (FISH) studies of metaphase and interphase blood cells and skin fibroblasts detected the presence of euploid and trisomy 9 cells. These results suggest that earlier reports of trisomy 9, which relied on conventional chromosome analysis of a few metaphase cells and/or only one tissue type, may not have excluded mosaicism, and that trisomy 9 may be viable only in the mosaic state.

Experimental reovirus serotype 1/strain Lang infection of the lung: a model for the study of the lung in the context of mucosal immunity.

A number of studies have examined the nature of the respiratory immune response to particular pathogens. Although many pathogens stimulate specific immunity in the lung, they frequently are not effective immunogens at other mucosal sites. Because the gastrointestinal tract is a major inductive site for mucosal immunity, a pathogen that is an effective respiratory and gut immunogen would allow studies of the interaction of the lung with gut mucosal immune system. Reovirus, a respiratory isolate that previously has been shown to be an effective gut mucosal immunogen, provides a potential model of the relationship of the lung to the gut mucosal immune system. In this report, we demonstrate that intranasal application of reovirus serotype 1/strain Lang (1/L) to CD-1 mice elicits an acute lymphocytic inflammatory infiltration of the lung and hyperplasia of the lung-associated lymph nodes. The initial inflammatory response occurs in the airspaces and interstitium of the lung. As the infection progresses, the initially diffuse cellular infiltrate becomes more focused around small bronchioles. Viral replication occurs predominantly during the first week of the infection, and infectious virions are eliminated during the second week. After the elimination of infectious virions, a secondary response consisting of the appearance of plasma cells adjacent to pulmonary arteries develops as the primary infiltrate organizes into peribronchiolar follicles, resembling the human inflammatory lung condition termed follicular bronchiolitis. These two infiltration patterns were also observed by immunohistochemical analysis of the the infected lung. Whereas CD4+ and CD8+ lymphocytes and Mac-1+ cells were found to be more closely associated with the primary infiltration process, B220+ lymphocytes were observed adjacent to pulmonary arteries. These results establish respiratory reovirus 1/L infection as a viable model for future investigations of the mucosal immune response in the lung and its relationship to the common mucosal immune system.

Talc slurry pleurodesis. Pleural fluid and histologic analysis.

Although talc slurry pleurodesis is effective for control of malignant pleural effusions and recurrent pneumothorax, the mechanisms of pleurodesis remain incompletely defined. We instilled 70 mg/kg of sterile asbestos-free talc slurry into the pleural space of New Zealand white rabbits and studied the inflammatory response at 1, 2, 3, 7, 15, 30, 60, 90, and 120 days by observing pleural fluid and histologic characteristics. Talc slurry caused mesothelial denudement and an exudative neurotrophilic pleural effusion that resolved after 48 h. A transient mononuclear vasculitis was seen within the lung at 1, 2, and 3 days after instillation. Pleural adhesions were minimal and did not increase in number over time. Talc was found outside of the pleural space in mediastinal lymph nodes (4 of 23 animals examined), kidney (1 of 6), and spleen (4 of 10). The predominant cause of pleurodesis with talc slurry instillation is an acute pleural injury similar to the tetracycline class agents.

Electron probe microanalysis of silicon and the role of the macrophage in proximal (capsule) and distant sites in augmentation mammaplasty patients.

Electron probe x-ray microanalysis was used to locate silicon (Si) within macrophages from 12 women who had previously undergone polymer prosthesis augmentation or reconstruction. Silicon was identified within macrophages and extracellularly in all fibrous breast capsules. In four women with arthritic joint pain and one woman with sclerodermatous skin lesions, silicon also was identified within macrophages residing in joint synovium and skin, respectively. It is suggested that the silicon-laden macrophages observed in the remote lesions may have accumulated silicon from other macrophages that had previously resided in the connective-tissue capsule around the silicone breast implants.