Effect of space environment on man's response to infection A review of literature and annotated bibliography

Review of literature on effects of space environment on human response to infectio

Short-Term Exposure to Tobacco Toxins Alters Expression of Multiple Proliferation Gene Markers in Primary Human Bronchial Epithelial Cell Cultures

The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(b)fluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions

Nontuberculous mycobacteria: II: Nested-cohort study of impact on cystic fibrosis lung disease

The prevalence of nontuberculous mycobacteria (NTM) is high (approximately 13%) in sputum of patients with cystic fibrosis (CF), but the impact on lung disease is unknown. We followed 60 incident NTM-positive and 99 culture-negative patients with CF for 15 months and assessed clinical impact of NTM by FEV1 and high-resolution computed tomography (HRCT) of the chest. Mycobacterium avium complex was seen in 75% of NTM-positive subjects. The annual rate of decline in FEV1 was not different among control versus NTM-positive subjects who did not, or did, meet American Thoracic Society microbiologic criteria for NTM disease (3 ± 1, 3 ± 2, and 5 ± 2%, respectively). More subjects with three or more positive cultures for NTM had two or more characteristic findings on entry HRCT (60%, 9/15) as compared with subjects with two positive cultures or less (32%) or negative cultures (19%; p < 0.02). All subjects with three or more positive cultures and exit HRCTs (n = 6) showed progression of HRCT findings, whereas only 17% of subjects with two positive cultures or less had progression (p = 0.0006). In summary, no significant short-term effect on FEV1 was detected in patients with multiple positive NTM cultures, but an abnormal HRCT was predictive of progression. Patients with CF and multiple positive NTM cultures, characteristic HRCT findings, and progression of HRCT changes should be monitored closely and considered for antimycobacterial therapy

Endobronchial chondromatous hamartoma in an infant

No abstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35322/1/2085_ftp.pd

Measuring diffuse metabolic activity on FDG-PET/CT: new method for evaluating Langerhans cell histiocytosis activity in pulmonary parenchyma

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cause of interstitial lung disease characterized by formation of nodules in the active phase of the disease that evolve into nonactive cystic lesions later on. To evaluate PLCH activity in patients, we developed a new method for measuring diffuse metabolic activity on fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT) using a lung-to-liver activity ratio. Material and Methods: We retrospectively studied a series of 4 FDG-PET and 23 FDG-PET/CT scans from 7 patients with PLCH and analyzed a sample of 100 randomly chosen FDG-PET/CT studies free from any known lung or hepatic diseases. Maximum standardized uptake value (SUVmax) in a spherical volume (6–8 cm in diameter) in the right lung was put into relation with SUVmax in a spherical volume (9–10 cm in diameter) in the reference liver parenchyma to set up the SUVmaxPULMO/SUVmaxHEPAR index. The index values were compared to the disease course in each patient. Results: In patients with PLCH, a close correlation between the index value and the disease course was found in all seven subjects, where the increasing index values indicated disease activity, while decreasing index values were observed after therapy administration. In the group of 100 healthy control subjects, we found index values lower than 0.3 in 80% and lower than 0.4 in 96%. Conclusion: Measuring SUVmaxPULMO/SUVmaxHEPAR values and their time-trend monitoring represent simple, noninvasive screening tools allowing an early diagnosis and treatment response follow-up assessment in patients with PLCH

Mycobacterium abscessus and Children with Cystic Fibrosis

We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS

Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections among Cystic Fibrosis Patients, Israel

A multicenter cross-sectional study showed prevalence appears to be increasing

The Dual Role of TNF in Pulmonary Edema

—Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema

Danger‐associated molecular patterns ( DAMPs ) in acute lung injury

Danger‐associated molecular patterns ( DAMPs ) are host‐derived molecules that can function to regulate the activation of pathogen recognition receptors ( PRRs ). These molecules play a critical role in modulating the lung injury response. DAMPs originate from multiple sources, including injured and dying cells, the extracellular matrix, or exist as immunomodulatory proteins within the airspace and interstitium. DAMPs can function as either toll‐like receptor ( TLR ) agonists or antagonists, and can modulate both TLR and nod‐like receptor ( NLR ) signalling cascades. Collectively, this diverse group of molecules may represent important therapeutic targets in the prevention and/or treatment of acute lung injury ( ALI ) and its more severe form, acute respiratory distress syndrome ( ARDS ).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94713/1/path4124.pd