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Thomas A Sporn

Publications and source records attributed to Thomas A Sporn.

17 recordsLinked to original sources
PubMed2006

Gene expression profiling of familial and sporadic interstitial pneumonia.

RATIONALE: Idiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown. OBJECTIVES: To evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma. METHODS: We profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray. RESULTS: Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-) mice demonstrating significantly less collagen deposition than C57BL/6(CXCR4+/+) mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia. CONCLUSIONS: Taken together, our findings indicate that differences in gene expression profiles between familial and sporadic IIPs may provide clues to the etiology and pathogenesis of IIP.

Adult↗
PubMed2005

Clinical and pathologic features of familial interstitial pneumonia.

RATIONALE: Several lines of evidence suggest that genetic factors and environmental exposures play a role in the development of pulmonary fibrosis. OBJECTIVES: We evaluated families with 2 or more cases of idiopathic interstitial pneumonia among first-degree family members (familial interstitial pneumonia, or FIP), and identified 111 families with FIP having 309 affected and 360 unaffected individuals. METHODS: The presence of probable or definite FIP was based on medical record review in 28 cases (9.1%); clinical history, diffusing capacity of carbon monoxide (DL(CO)), and chest X-ray in 16 cases (5.2%); clinical history, DL(CO), and high-resolution computed tomography chest scan in 191 cases (61.8%); clinical history and surgical lung biopsy in 56 cases (18.1%); and clinical history and autopsy in 18 cases (5.8%). RESULTS: Older age (68.3 vs. 53.1; p < 0.0001), male sex (55.7 vs. 37.2%; p < 0.0001), and having ever smoked cigarettes (67.3 vs. 34.1%; p < 0.0001) were associated with the development of FIP. After controlling for age and sex, having ever smoked cigarettes remained strongly associated with the development of FIP (odds ratio(adj), 3.6; 95% confidence interval, 1.3-9.8). Evidence of aggregation of disease was highly significant (p < 0.001) among sibling pairs, and 20 pedigrees demonstrated vertical transmission, consistent with autosomal dominant inheritance. Forty-five percent of pedigrees demonstrated phenotypic heterogeneity, with some pedigrees demonstrating several subtypes of idiopathic interstitial pneumonia occurring within the same families. CONCLUSIONS: These findings suggest that FIP may be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of idiopathic interstitial pneumonia.

Adult↗
PubMed2004

Giant cell tumor of rib masquerading as thymoma: a diagnostic pitfall in needle core biopsy of the mediastinum.

Giant cell tumor of bone is rarely seen in the rib, where it may present as a mediastinal mass. The diagnosis of giant cell tumor of bone is generally straightforward by fine-needle aspiration or needle core biopsy, but sampling problems may lead to confusion with other neoplasms or inflammatory processes. Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass in a 36-year-old man. Because of inadequate sampling and inaccurate clinical information, the tumor was initially mistaken for thymoma. When the mass failed to respond to conventional chemotherapy, additional tissue was obtained and a giant cell tumor was diagnosed. Consequently, definitive therapy was delayed. The case illustrates an important diagnostic pitfall in the biopsy of mediastinal masses.

Adult↗
PubMed2004

The spectrum of Kit (CD117) immunoreactivity in lung and pleural tumors: a study of 96 cases using a single-source antibody with a review of the literature.

CONTEXT: The development of successful chemotherapeutic agents directed against the Kit receptor tyrosine kinase protein has generated intense interest in the Kit (CD117) immunoreactivity of various neoplasms. Immunoreactivity for Kit in small cell lung carcinoma (SCLC) has been well established. However, data on Kit immunostaining in other lung tumors is limited. Likewise, while solitary fibrous tumors of the gastrointestinal tract have been examined for Kit expression, the Kit staining characteristics of their counterpart in the pleura, namely, localized fibrous tumor, are not well known. OBJECTIVE: To characterize the Kit immunohistochemical profiles of major types of lung and pleural tumors. DESIGN: We stained 60 lung carcinomas, including 11 SCLCs, 4 large cell neuroendocrine carcinomas, 22 squamous cell carcinomas, 23 adenocarcinomas, 11 pulmonary carcinoid tumors, 19 pleural malignant mesotheliomas, and 6 localized pleural fibrous tumors with a commonly used polyclonal Kit antibody. RESULTS: Small cell lung carcinomas demonstrated Kit staining in 82% of cases, nearly all of which demonstrated moderate to intense immunoreactivity. Immunostaining was observed in 25% of large cell neuroendocrine carcinomas. Focal staining was observed in 9% of squamous cell carcinomas and 17% of adenocarcinomas. None of the pulmonary carcinoid tumors were immunoreactive. Moderately intense immunostaining was present in 50% of localized fibrous tumors. Malignant mesotheliomas were nonimmunoreactive for Kit in 95% of cases. CONCLUSION: Non-small cell lung carcinomas showed very limited expression of Kit. Lung tumors with neuroendocrine differentiation exhibited a wide spectrum of Kit immunoreactivity, ranging from rare in pulmonary carcinoid tumors to frequent in SCLC. The high frequency of Kit immunostaining in SCLC has important potential therapeutic implications. Demonstration of Kit positivity in some localized fibrous tumors in this study contrasts with absent immunoreactivity in solitary fibrous tumors of the gastrointestinal tract. The paucity of Kit staining in malignant mesothelioma suggests these tumors are unlikely to respond to currently available tyrosine kinase inhibitors.

Antibodies↗
PubMed2003

Exposure to brake dust and malignant mesothelioma: a study of 10 cases with mineral fiber analyses.

OBJECTIVES: A large number of workers in the USA are exposed to chrysotile asbestos through brake repair, yet only a few cases of malignant mesothelioma (MM) have been described in this population. Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers. We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens. METHODS: Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure. Lung fiber analyses were performed using scanning electron microscopy (SEM) in all cases for which formalin-fixed or paraffin-embedded lung tissue was available. RESULTS: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose in the pleura and one in the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our upper limit of normal (range 0-20 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos fiber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysotile and non-commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers. CONCLUSIONS: Brake dust contains exceedingly low levels of respirable chrysotile, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM.

Aged↗
PubMed2003

Beryllium detection in human lung tissue using electron probe X-ray microanalysis.

Chronic berylliosis is an uncommon disease that is caused by the inhalation of beryllium particles, dust, or fumes. The distinction between chronic berylliosis and sarcoidosis can be difficult both clinically and histologically, as both entities can have similar presentations and exhibit nonnecrotizing granulomatous inflammation of the lungs. The diagnosis of chronic berylliosis relies on a history of exposure to beryllium, roentgenographic evidence of diffuse nodular disease, and demonstration of beryllium hypersensitivity by ancillary studies, such as lymphocyte proliferation testing. Additional support may be gained by the demonstration of beryllium in lung tissue. Unlike other exogenous particulates, such as asbestos, detection of beryllium in human lung tissue is problematic. The low atomic number of beryllium usually makes it unsuitable for conventional microprobe analysis. We describe a case of chronic berylliosis in which beryllium was detected in lung tissue using atmospheric thin-window energy-dispersive X-ray analysis (ATW EDXA). A woman with a history of occupational exposure to beryllium at a nuclear weapons testing facility presented with progressive cough and dyspnea and a nodular pattern on chest roentgenograph. Open lung biopsy showed nonnecrotizing granulomatous inflammation that was histologically indistinguishable from sarcoidosis. Scanning electron microscopy and ATW EDXA demonstrated particulates containing beryllium within the granulomas. This application of EDXA offers significant advantages over existing methods of beryllium detection in that it is nondestructive, more widely available, and can be performed using routine paraffin sections.

Adult↗
PubMed2003

Human parainfluenza virus giant cell pneumonia following cord blood transplant associated with pulmonary alveolar proteinosis.

Giant cell pneumonia secondary to human parainfluenza virus 3 has been reported only rarely in immunocompromised hosts. The few cases documented after bone marrow transplant have resulted in significant morbidity and mortality. To our knowledge, this entity has not been described following umbilical cord blood transplant. Pulmonary alveolar proteinosis, a rare condition that has been reported with increasing frequency in association with immunocompromise and infections, has not been documented in the setting of either umbilical cord blood transplant or human parainfluenza viral infection. We report what we believe is the first documented case of giant cell pneumonia caused by human parainfluenza virus 3 in an umbilical cord blood transplant recipient. To our knowledge, a unique associated feature of this case, a pulmonary alveolar proteinosis-like reaction, has not been reported previously in association with human parainfluenza virus pneumonia.

Cord Blood Stem Cell Transplantation↗
PubMed2002

Oxidative stress and inflammation contribute to lung toxicity after a common breast cancer chemotherapy regimen.

Delayed pulmonary toxicity syndrome after high-dose chemotherapy (HDC) and autologous hematopoietic support occurs in up to 64% of women with advanced-stage breast cancer. Using a similar, but nonmyeloablative, HDC treatment regimen in mice, we found both immediate and persistent lung injury, coincident with marked decreases in lung tissue glutathione reductase activity and accompanied by increases in lung oxidized glutathione, bronchoalveolar lavage (BAL) lipid peroxidation, and BAL total cell counts. Most interestingly, at 6 wk, BAL total cell counts had increased fourfold, with lymphocyte cell counts increasing >11-fold. A single supplemental dose of glutathione prevented early lung injury at 48 h but showed no lung-protective effects at 6 wk, whereas single doses of other thiol-sparing agents (Ethyol and glutathione monoethyl ester) showed no benefit. These data suggest that this HDC regimen results in acute and persistent lung toxicity, induced in part by oxidative stress, that culminates with an acute lung cellular inflammatory response. Continuous glutathione supplementation and/or attenuation of the delayed pulmonary inflammatory response may prove beneficial in preventing lung toxicity after the use of these chemotherapeutic agents.

Amifostine↗
PubMed2002

Outcome of lung transplantation in patients with mycetomas.

BACKGROUND: Lung transplantation has become an acceptable treatment option for many end-stage lung diseases. Pulmonary mycetomas are found in patients with end-stage lung diseases, especially sarcoidosis. The clinical course and long-term outcome of these patients after transplantation remains unknown. METHODS: We reviewed retrospectively the pathology reports of the explanted lungs from all lung and heart-lung transplantations performed at our institution between January 20, 1992, and June 26, 2000. Patients were included in our study if mycetomas were present on the specimens. Information on transplant date and type, diagnosis, information on antifungal therapy and fungal infections pretransplant and posttransplant, and clinical course after transplantation was recorded. RESULTS: Mycetomas were present in 3.0% of transplant recipients (9 of 303 patients). The underlying pulmonary diagnoses were sarcoidosis (six patients), and emphysema, idiopathic pulmonary fibrosis, and pneumoconiosis (one patient each). Seven patients received bilateral lung transplants, one patient received a heart/lung transplant, and one patient received a single lung transplant. Aspergillus was isolated from culture in five patients pretransplant and from five patients posttransplant. Six patients received treatment with itraconazole, or IV or inhaled amphotericin B prior to transplantation. All patients who survived transplantation received posttransplant antifungal therapy. Four patients died in the first month after transplantation. Two patients died at 17 months and 24 months posttransplant, respectively; one patient received a second transplant 30 months later; and two patients are alive and free from fungal infections 17 months and 18 months, respectively, after transplantation. All of the medium-term survivors received lengthy therapy with inhaled and systemic amphotericin B and itraconazole before and after transplantation. CONCLUSIONS: Lung transplant recipients with mycetomas have significantly reduced posttransplant survival. Careful selection of patients and aggressive antifungal therapies before and after transplantation have led to improved outcomes in patients with mycetomas. Additional research is needed to define the best therapeutic strategy for these patients during transplantation.

Adult↗
PubMed2002

Tremolite and mesothelioma.

BACKGROUND: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases. METHODS: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos. RESULTS: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background. CONCLUSIONS: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.

Aged↗
PubMedDate not supplied

Giant cell interstitial pneumonia associated with nitrofurantoin.

A case of giant cell interstitial pneumonia (GIF) that occurred in association with exposure to nitrofurantoin is presented. While the diagnosis of GIP is confirmed by histopathology, this diagnosis can be supported by the findings of bizarre multinucleated giant cells (MGC), elevated T lymphocytes, and a low T lymphocyte helper/suppressor ratio in the bronchoalveolar lavage fluid (BALF). Recognition of GIP as a rare manifestation of nitrofurantoin toxicity is important because prompt therapy may be associated with a favorable outcome.

Aged↗
PubMedDate not supplied

Multiple lung nodules in a woman with a history of melanoma.

A 61-year-old Caucasian female presented with a 6-week history of dry persistent cough. She had no shortness of breath, chest pain, fever, chills, or weight loss. She had been diagnosed with melanoma on the left thigh 6 months earlier. It was a spindle cell variant, Clark's grade III, with maximal thickness of 0.5 mm. At the time of diagnosis of melanoma, there was no evidence of metastasis on chest radiographs or computed tomography (CT) of the abdomen and pelvis. Treatment of her melanoma was limited to surgical excision with no subsequent radiation or chemotherapy. Other significant past medical history included hypertension, hypothyroidism, and bilateral breast augmentation. She had a 40 pack-year history of smoking.

Comorbidity↗