Tracheobronchial Nodes Research Articles

The spread of metastatic lymph nodes to the mediastinum from left upper lobe cancer: results of superior mediastinal nodal dissection through a median sternotomy

This study endeavored to clarify the location, frequency, and prognostic value of metastatic lymph nodes in the mediastinum among patients with left upper lung cancer who underwent complete dissection of the superior mediastinal lymph node through a median sternotomy. Forty-four patients with left upper lobe cancer underwent extended radical mediastinal nodal dissection (ERD), all of whom were analyzed in this retrospective study. The group comprised 12 females and 32 males, with ages ranging from 28 to 70 years (median age, 60 years). Mediastinal nodal status was assessed according to the systems of Mountain/Dresler 7 and Naruke 8. The clinicopathological records of each patient were examined for prognostic factors, including age, sex, histology, tumor size, c-N number, preoperative serum CEA level, metastatic stations and distribution of metastatic nodes according to Naruke's system 8. The superior mediastinal lymph nodes which cannot be dissected through a left thoracotomy (bilateral #1 and #2, #3, right #3a, and right #4 according to Naruke's map 8 were defined as extra-superior mediastinal nodes for left lung cancer (ESMD). Fourteen patients had one or more metastases to mediastinal lymph nodes, among whom the most common metastatic station was the aortic nodes: 71.4% had metastasis to #5 or #6 (57.1% to #5 and 50% to #6). The next most common metastatic station was the left tracheobronchial nodes (42.8%). Metastasis to the ESMD occurred in 7 of the 44 study subjects (16%), representing a 50% rate of occurrence (7/14) among those with mediastinal nodal involvement. Univariate analysis found that CN factor and aortic nodal involvement (#5, #6) were significant predictive factors for ESMD metastasis. Multivariate analysis determined that only aortic nodal involvement was significant (p = 0.008). Furthermore, ESMD metastasis was rare (5.8%) in the absence of aortic node metastasis. The overall survival rate at 5 years was 50% among the patients without ESMD metastasis. However, the survival rate was 32% at 3 years and 0% at 5 years among the seven patients with ESMD metastasis. The aortic lymph node is the most common site of metastasis from left upper lobe cancer. Multivariate analysis demonstrated that aortic nodal involvement was a significant predictive factor for ESMD metastasis. Based upon the rates of metastasis and the post-operative prognosis in our study patients, dissection of aortic nodes and left tracheobronchial nodes may be important for patients with left upper lobe cancer. Whether ESMD dissection has a beneficial effect on prognosis remains controversial.

Tuberculosis (Mycobacterium tuberculosis) in a pregnant baboon (Papio cynocephalus)

Old World monkeys are considered more susceptible to tuberculosis (TB) than New World monkeys. Several cases of TB in baboons are described in the literature. The data regarding baboon reaction to the tuberculin skin test (TST) are controversial. Some authors described anergy in this species, while the others documented a positive reaction. An 8-year-old clinically healthy pregnant female baboon (Papio cynocephalus anubis) developed positive TST after 3 years of negative tests in captivity while not pregnant. Thoracic radiographs demonstrated three nodular densities in the lung. Histological examination of tracheobronchial lymph nodes revealed multiple coalescing pyogranulomas filled with caseonecrotic debris and mineralized foci with numerous large foreign body-type and Langhans-type multinucleated giant cells. The bacterial culture contained a slow growing Mycobacterium tuberculosis complex. We describe, to the best of our knowledge, the first case of a positive TST in a wild caught, pregnant baboon with latent infection after 3 years in captivity.

Comparison of results of computed tomography and radiography with histopathologic findings in tracheobronchial lymph nodes in dogs with primary lung tumors: 14 cases (1999–2002)

To compare results of computed tomography (CT) and radiography with histopathologic findings in tracheobronchial lymph nodes (TBLNs) in dogs with primary lung tumors. Retrospective case series. 14 client-owned dogs. Criteria for inclusion were diagnosis of primary lung tumor, use of thoracic radiography and CT, and histologic confirmation of TBLN status. Medical records were reviewed for signalment; history; and physical examination, clinicopathologic, radiographic, CT, surgical, and histopathologic findings. Tracheobronchial lymphadenopathy was not identified via radiography in any dogs. Tracheobronchial lymphadenopathy was diagnosed in 5 dogs via CT. Six dogs had histologic confirmation of metastasis to TBLNs. Radiographic diagnosis yielded 6 false-negative and no false-positive results for tracheobronchial lymphadenopathy. Computed tomography yielded 1 false-negative and no false-positive results. Sensitivity of CT for correctly assessing TBLN status was 83%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 89%. Dogs with lymphadenopathy via CT, histologic confirmation of TBLN metastasis, or primary tumors with a histologic grade > 1 had significantly shorter survival times than their counterparts. Results of CT evaluation of TBLN status were in agreement with histopathologic findings and more accurate than use of thoracic radiography for evaluating TBLNs in dogs with primary lung tumors. Computed tomography imaging should be considered as part of the staging process to more accurately assess the TBLNs in dogs with primary lung tumors.

Combination Exposure to Zidovudine plus Sulfamethoxazole-Trimethoprim Diminishes B-Lymphocyte Immune Responses toPneumocystis murinaInfection in Healthy Mice

We have previously shown that zidovudine plus sulfamethoxazole-trimethoprim exposure decreases immune cell populations in the bone marrow of healthy mice by inducing apoptosis. The hypothesis of the current work was that this toxicity would have an adverse impact on the immune response. To determine this, BALB/c mice were treated with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only (control) via oral gavage for 21 days. On day 4 after dosing completion, the mice were infected intratracheally with 1x10(7) Pneumocystis murina organisms. Immune cell populations (in lung digest, bronchoalveolar lavage fluid, tracheobronchial lymph node, and bone marrow samples), the lung Pneumocystis burden, and serum Pneumocystis-specific antibody titers were determined at days 6, 10, and 20 postinfection. While total bone marrow cellularity was recovered by day 6 postinfection in the combination exposure group, B-cell numbers did not recover until 10 days postinfection, primarily due to the persistent depletion of the late pre-B-cell phenotype. The numbers of CD4+ and CD8+ T cells, as well as the numbers of total B cells and activated B cells in tracheobronchial lymph nodes, were decreased at days 10 and 20 as a result of zidovudine plus sulfamethoxazole-trimethoprim exposure compared to the numbers in the control group. No significant differences in lung lavage or lung digest cell populations were observed. There was a trend of a delay in Pneumocystis clearance in the combination treatment group, and Pneumocystis-specific serum immunoglobulin G titers were reduced at day 20 postinfection. Together, these data indicate that the combination of zidovudine and sulfamethoxazole-trimethoprim adversely affects the humoral immune response to Pneumocystis.

Complete resection via medial sternotomy for non‐small cell lung cancer in the right upper lobe

Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. From 1995 to 2003, 48 patients aged < or = 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease (n = 18) was 42.6%, and the rate for p-N2 disease (n = 7) and p-N3 disease (n = 13) was 57.1% and 0%, respectively, using the Kaplan-Meier method. Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease.

Lungs: blood supply, lymphatic drainage and nerve supply

The pulmonary arteries, through their capillary plexus, are entirely concerned with alveolar gaseous exchange, while the nutrient supply of the lung parenchyma is provided by the bronchial arteries. The pulmonary vein tributaries derive partly from the capillaries of the bronchial and the pulmonary arteries. The bronchial veins drain the larger bronchi. The lymphatics of the lungs drain into the nodes lying at the bifurcations of the larger bronchi, then to the tracheobronchial nodes and then into the broncho-mediastinal lymph trunk on each side. These usually drain directly into the junction of the internal jugular and subclavian veins on each side, but may drain, on the right, into the right lymph trunk and, on the left, into the thoracic duct. If the subcarinal node is the site of secondary deposits it gives the typical bronchoscopic sign of widening of the carina. The principal function of the sympathetic (T2-4) supply to the lung is bronchodilatation, while the vagus fibres act as stretch receptors.

Pneumonitis and Multi-Organ System Disease in Common Marmosets (Callithrix jacchus) Infected with the Severe Acute Respiratory Syndrome-Associated Coronavirus

Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis.

A murine model of dual infection with cytomegalovirus and Pneumocystis carinii: Effects of virus-induced immunomodulation on disease progression

Despite the use of antimicrobial prophylaxis, cytomegalovirus (CMV) and Pneumocystis carinii ( PC) pneumonia (PCP) are both leading causes of morbidity and mortality in immunocompromised patients. It has previously been reported that CMV infection modulates host immune responses with a variety of mechanisms which include the suppression of helper T cell functions and antigen presenting cell (APC) functions, both of which are critical for PCP resolution. However, the mechanisms of these interactions and other possible immune regulatory effects are not clearly understood. In this study, we investigated the impact of murine CMV (MCMV) induced immunomodulation on the progression of PCP in a co-infection model. Initial results show that dually infected mice had evidence of more severe PC disease, which include a greater loss of body weight, an excess lung PC burden and delayed clearance of PC from lungs, compared to mice with PC infection alone. At day 7 post-infection, dually infected mice had reduced numbers of MHC-II expressing cells in the lung interstitium and lymph nodes and reduced migration of CD11c + cells to both the tracheobronchial lymph nodes and alveolar spaces. Dual infected mice showed elevated numbers of specific CD8 responses concomitant with a decrease in activated CD4 + T cells in both the lymph nodes and in alveolar spaces when compared to mice infected with MCMV alone. These data suggest that MCMV infection inhibits the immune responses generated against PC which contribute to the delayed clearance of the organism.

Utility of Rapid On-Site Evaluation of Transbronchial Needle Aspirates

Background: Rapid on-site evaluation has been proposed as a method to improve the yield of transbronchial needle aspiration. Objectives: This study investigated whether on-site analysis facilitates routine diagnostic bronchoscopy in terms of sampling, yield and cost. Methods: Patients with lesions accessible for transbronchial needle aspiration on computed tomography were investigated. A cytopathologist screened the needle aspirates on site for the presence of diagnostic material. The bronchoscopic sampling process was adjusted according to the results. In 90 consecutive patients with neoplastic disease (n = 70; 78%), non-neoplastic disease (n = 16; 18%) or undiagnosed lesions (n = 4; 4%) we aspirated 162 lung lesions (paratracheal tumours or lymph nodes: 7%; tracheobronchial lymph nodes: 68%; other: 25%). Results: The diagnostic yield of needle aspiration was 77 and 25% in patients with neoplastic and non-neoplastic lesions, respectively. Sampling could be terminated in 64% of patients after needle aspiration had been performed as the only diagnostic modality, and on-site analysis identified diagnostic material from the first site aspirated in 50% of patients. Only in 2 patients (2%) diagnostic aspirates were not recognized on site. On-site analysis was cost effective due to savings for disposable diagnostic tools, which exceeded the extra expense for the on-site cytology service provided. Conclusions: Rapid on-site analysis of transbronchial aspirates is a highly useful, accurate and cost-effective addition to routine diagnostic bronchoscopy.

Is tryptophan catabolism increased under indoleamine 2,3 dioxygenase activity during chronic lung inflammation in pigs?

In a preliminary study we observed that piglets suffering from chronic lung inflammation induced by an intravenous injection of complete Freund adjuvant showed a marked decrease in plasma tryptophan (Trp) concentration suggesting increased Trp utilisation. During the inflammatory process, a cytokine-induced enzyme called indoleamine 2,3-dioxygenase (IDO) has been shown to catabolise Trp into kynurenine (Kyn). Yet, during inflammation, increased Trp catabolism may decrease Trp availability for other functions such as growth. This metabolic pathway has never been studied in pigs. So, the objectives of this study were to measure IDO activity in pigs and to determine if the decrease in plasma Trp concentrations previously observed in piglets suffering from chronic lung inflammation could be explained by the induction of IDO activity. In order to do so, we compared IDO activity measured in the tracheo-bronchial lymph nodes and in the lungs of 7 piglets, injected with complete Freund adjuvant (CFA), to 7 pair-fed littermate healthy controls. Blood samples were taken at 0, 2, 5, 7 and 10 days following CFA injection in order to measure plasma Trp, Kyn and haptoglobin concentrations. Indoleamine 2,3-dioygenase activity in the tracheo-bronchial lymph nodes (P < 0.05), in the lungs (P < 0.07) and plasma haptoglobin (P < 0.01) were higher in pigs with lung inflammation than in the controls. Plasma Trp and Kyn were not significantly affected by CFA injection. Our data showed that IDO is activated under chronic lung inflammation in pigs. The impact of IDO activation on plasma Trp concentration and its availability is discussed according to the amount of Trp provided by the diet.

Unusual Metastasis of Malignant Aortic Body Tumor to &lt;i&gt;Multiple&lt;/i&gt; Bones in a Dog

Unusual metastasis of malignant aortic body tumor to multiple bones was detected in a 5-year-old female English Setter dog. Radiographs exhibited an abnormal mass in the base of heart and osteolytic lesions in the bodies of T11 and L2 vertebrates, body of right femur, right proximal humoral epiphysis and infraspinous fossa near to the neck of right scapula. At necropsy, multiple tumor masses of various sizes were observed also in the bones as well as the heart base and tracheobronchial lymph node. Tumor masses of L2 and T11 protruded into the vertebral canal and compressed corresponding sites of spinal cord, leading to paraplegia. Histopathologically, the tumor cells, arranged in sheets or nests, were polyhedral, lightly eosinophilic, finely granular cytoplasm with mostly round to oval nucleus and had scattered bizarre giant cells. Ultrastructural study revealed the characteristic findings that tumor cells contained a large number of small, electron-dense, membrane-limited secretory granules in cytoplasm. This is thought to be an extremely rare case having multiple bone metastases of a malignant aortic body tumor.

Integration of clinical data, pathology, and cDNA microarrays in influenza virus-infected pigtailed macaques (Macaca nemestrina).

For most severe viral pandemics such as influenza and AIDS, the exact contribution of individual viral genes to pathogenicity is still largely unknown. A necessary step toward that understanding is a systematic comparison of different influenza virus strains at the level of transcriptional regulation in the host as a whole and interpretation of these complex genetic changes in the context of multifactorial clinical outcomes and pathology. We conducted a study by infecting pigtailed macaques (Macaca nemestrina) with a genetically reconstructed strain of human influenza H1N1 A/Texas/36/91 virus and hypothesized not only that these animals would respond to the virus similarly to humans, but that gene expression patterns in the lungs and tracheobronchial lymph nodes would fit into a coherent and complete picture of the host-virus interactions during infection. The disease observed in infected macaques simulated uncomplicated influenza in humans. Clinical signs and an antibody response appeared with induction of interferon and B-cell activation pathways, respectively. Transcriptional activation of inflammatory cells and apoptotic pathways coincided with gross and histopathological signs of inflammation, with tissue damage and concurrent signs of repair. Additionally, cDNA microarrays offered new evidence of the importance of cytotoxic T cells and natural killer cells throughout infection. With this experiment, we confirmed the suitability of the nonhuman primate model in the quest for understanding the individual and joint contributions of viral genes to influenza virus pathogenesis by using cDNA microarray technology and a reverse genetics approach.

Uranium deposition and retention in a USTUR whole body case.

This report describes a whole body donation from a person with a documented occupational intake of uranium. USTUR Case 1002 was an adult male who died from an acute cerebellar infarct at the age of 83. He worked as a power operator, utility operator, and metal operator for 28 years in a facility that processed and handled radioactive materials. Although he suffered a number of burns from hot metal and acids, cuts, abrasions, and puncture wounds during his many years of work, there were no corresponding health physics or medical records to indicate that these occurrences needed or required excision or decontamination due to the suspicion of the deposition of radioactive material. Over the course of his employment, USTUR Case 1002 submitted numerous urine samples for uranium, plutonium, and fission product analysis. The highest single uranium value measured during this time period was approximately 30 microg L(-1) recorded during the second year of his employment. A urinary bioassay sample taken before termination of employment measured 4.3 microg L(-1). The mean urinary uranium concentration per liter per year calculated from the employee's bioassay records covering the first eleven years of monitoring averaged less than 3 microg L(-1). The ratio of 234/238U activity in the lung tissue was about 1, the same as that found in natural uranium. The highest concentration of uranium was found in a tracheobronchial lymph node. The uranium content in the various tissues of the body followed a rank order lung > skeleton > liver > kidney. Concentration of uranium in the kidney tissue was approximately 1.98 ng g(-1), about 3 orders of magnitude less than the generally accepted threshold level for permanent kidney damage of 3 microg U g(-1) and roughly equal to the 1.4 ng g(-1) reported for Reference Man. The autopsy disclosed findings not uncommon in the aged: severe atherosclerosis, areas of sclerotic kidney glomeruli with stromal fibrous scarring, and moderate to severe arterionephrosclerosis. Lung sections contained parenchymal areas of acute vascular congestion and a mild degree of anthracosis.

Shared feed as a means of deer-to-deer transmission of Mycobacterium bovis.

To determine the ability of experimentally inoculated white-tailed deer (Odocoileus virginianus) to transmit Mycobacterium bovis to naïve deer through the sharing of feed, four deer were intratonsillarly inoculated with 4 x 10(5) colony-forming units of M. bovis. On a daily basis, feed not consumed by inoculated deer after approximately 8 hr was offered to four naïve deer maintained in a separate pen, where direct contact, aerosol transmission, or transmission through personnel were prevented. After 150 days, naïve deer were euthanized and examined. All naïve deer had lesions consistent with tuberculosis and M. bovis was isolated from various tissues. The most commonly affected tissues were lung, tracheobronchial lymph nodes, and mediastinal lymph nodes. This study demonstrates the potential for indirect transmission of M. bovis through the sharing of feed. Intentional or unintentional feeding of deer by wildlife or agricultural interests in regions where M. bovis infection is endemic should be avoided because both direct and indirect transmission through sharing of feed are enhanced.

限局型と診断された豚の抗酸菌症例における病変と抗酸菌の分布調査

Thirty-three pigs were investigated which were diagnosed with the localized-type of mycobacteriosis. The gross lesions (caseous necrosis) were recognized only in mesenteric and/or mandibular lymph nodes during routine meat inspection of all cases. Lymph nodes from seven locations, including the mesentery and mandible, and organs (lungs and spleen) were examined; and lesion and bacteria distributions were histopathologically and bacteriologically surveyed. These methods authenticated only 8 animals (15.2%) as proven instances of the localized-type.Mycobacterium avium (M. avium) and/or granulomatous lesions were demonstrated in the lungs and the tracheobronchial and digestive lymph nodes of 21 animals (63.6%). Neither lesions norM. aviumwas demonstrated in the spleen of any animal. These results indicate the possibility thatM. aviumspreads over the lungs through the respiratory tract. Granulomatous lesions in the iliac and inguinal lymph nodes orM. aviumisolates from these organs were recognized only in female pigs, indicating the suspection of sexual influence onM. aviumdistribution differences.

Coccidioidomycosis in Przewalski's horses (Equus przewalskii).

Coccidioidomycosis is a rare, often subclinical infection in domestic animals caused by the fungus Coccidioides immitis. Because of an apparent high incidence of coccidioidomycosis in Przewalski's horses (Equus przewalskii) housed at a single facility, necropsy records and biomaterials from animals that died between 1984 and 2000 were reviewed (n = 30, 15 males, 15 females). Coccidioidomycosis was the leading cause of death (33%) in this population with lesions in the lungs and tracheobronchial lymph nodes of all animals and variable involvement of the skeletal muscle, heart, kidney, liver, skin, brain, spinal cord, spleen, as well as other regional lymph nodes. At the time of death, affected horses tended to be younger than unaffected animals, were from multiple lineages, and males were over represented. During the same time period, no other exotic equids (n = 76) housed at the same facility were diagnosed with coccidioidomycosis, suggesting that environmental factors are not the sole cause of the high incidence in E. przewalskii. Numbers of the lymphocyte subsets (CD3, CD4, CD5, CD8, CD21+ cells) quantified by flow cytometry were similar between Przewalski's horses and domestic horses (Equus caballus). Although responses of lymphocyte blastogenesis assays were similar between Przewalski's (n = 5) and domestic horses (n = 5) in response to the T cell mitogen concanavalin A, lymphocytes from two of the Przewalski's horses failed to proliferate in response to Coccidioides. One of these horses had systemic disease and the second developed coccidioidomycosis 2 yr later. These results suggest that the immune system of some Przewalski's horses fails to respond appropriately to Coccidioides.

Potential of magnetic resonance lymphography with intrapulmonary injection of gadopentetate dimeglumine for visualization of the pulmonary lymphatic basin in dogs: preliminary results.

To evaluate a new approach of magnetic resonance (MR) lymphography with intraalveolar injection of a conventional extracellular contrast agent (gadopentetate dimeglumine) for imaging lymphatic basin draining from specific portions of the lung. Three-dimensional T1-weighted spoiled gradient-recalled echo MR sequence images were acquired serially before and for 40 minutes after intraalveolar injection of gadopentetate dimeglumine in a total of 14 anesthetized beagle dogs. Six of these dogs received 1 mL undiluted and low-concentration (75%) contrast agent into the same portion of the right caudal lobe during a 7-day interval. In all dogs, including these 6 dogs, MR lymphography was repeated with injection of the low-concentration contrast agent into different lung regions at 7-day intervals to evaluate the differences of the visualized draining lymphatic station. Lymphatic enhancement was quantified by percent increases of signal intensity against precontrast. Postmortem examination of the lymphatic anatomy was performed in 7 of these animals. In all dogs, the lymphatic station draining from the injection sites was visualized within 5 minutes after contrast injection. The maximum percent increase of signal intensity of the same middle tracheobronchial lymph nodes was significantly greater with a low-concentration (75%) contrast agent than with an undiluted one in the same 6 dogs (n = 6, 247.6 +/- 30.5% vs. 204.2 +/- 33.8%; P < 0.01). Different lymphatic stations draining from the different injection sites were visualized in all dogs. In a total of 12 MR studies that showed extended nodal enhancement after injection of the low-concentration contrast agent, the enhancement peak of the most proximal nodes (n = 12) from the injection sites appeared earlier than that of their distant nodes (n = 12), with a maximum percent increase of signal intensity of 249.8 +/- 42.4%. The visualized lymph nodes were found in the appropriate locations postmortem, with significant correlation for nodal sizes (r = 0.965; P < 0.0001). MR lymphography with low-concentration gadopentetate dimeglumine can quickly and sufficiently visualize the drainage lymphatic station from specific lung portions, and may have the potential of sentinel node mapping in lung cancer.

Blastomycosis in nondomestic felids.

Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.

Trachea, lung, and tracheobronchial lymph nodes are the major sites where antigen-presenting cells are detected after nasal vaccination of mice with human papillomavirus type 16 virus-like particles.

Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4(+) T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.

Development of a Respiratory Allergy Model in Male Brown Norway Rats: Pulmonary Immune and Gene Expression Studies

The aim of these studies is to develop a respiratory allergy model in Brown Norway (BN) rats using ovalbumin (Ova) as the antigenic stimulus. Specifically, we are interested in studying the mechanisms underlying the development of pulmonary T helper type 2 (Th2) responses following Ova sensitization and inhalation challenge. We have previously reported on the development of an active pulmonary inflammatory response characterized by the presence of eosinophils and measurement of serum immunoglobulin E levels in Ova-sensitized but not in alum-treated, Ova-challenged or sham control rats. In the current study, we have used cDNA microarray technology to assess the gene expression in tracheobronchial, mesenteric and submaxillary lymph nodes, as well as in pulmonary cells and tissues of Ova-sensitized, alum-sensitized or sham control BN rats. Preliminary cDNA microarray results of lung tissue from BN rats exposed to ova–ova (Ova-sensitized, Ova-challenged) 4 or 24 h after ova challenge did not show up-regulation (relative to sham controls) of mRNA for interleukin-4 (IL-4) or IL-5 but did show up-regulation of eotaxin (4 h), intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAMs), which are likely to be prerequisites for eosinophilic pulmonary inflammatory responses measured at 24 and 48 h post Ova inhalation exposure. In addition, reverse transcriptase–polymerase chain reaction analysis of lung tissue from BN rats exposed to ova–ova 4 and 24 h after challenge demonstrated up-regulation of mRNA for IL-10 (Th2 response). Studies are ongoing to identify the time course and anatomic location of Th2 responses related to the development of Ova-induced respiratory allergy responses in BN rats.