ABSTRACT
INTRODUCTION: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear. METHODS: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (nâ¯=â¯17), and non-SM exposed individuals (nâ¯=â¯12). RESULTS: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (Pâ¯<â¯0.001 and Pâ¯=â¯0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter. CONCLUSIONS: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients.
Subject(s)
Alveolar Epithelial Cells/pathology , Bronchiolitis Obliterans/chemically induced , Chemical Warfare Agents/toxicity , Mustard Gas/toxicity , Pulmonary Surfactant-Associated Protein A/metabolism , Toll-Like Receptor 4/metabolism , Adult , Alveolar Epithelial Cells/immunology , Bronchiolitis Obliterans/drug therapy , Bronchiolitis Obliterans/immunology , Bronchiolitis Obliterans/pathology , Case-Control Studies , Gene Expression Profiling , Humans , Immunohistochemistry , Iran , Male , Middle Aged , Pulmonary Surfactant-Associated Protein A/analysis , Time Factors , Toll-Like Receptor 4/analysisABSTRACT
OBJECTIVE: Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV appears to be the most common cause of HCC in Iran. To date, no study has been carried out on the HBV genotype in Iranian HCC patients. This study was undertaken to determine the HBV genotype in Iranian patients with HCC. METHODS: Paraffin-embedded tissue samples from 40 patients (31 males and nine females) with HBV-associated HCC were collected from different pathology centers during 2000-2007. Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence. PCR products were sequenced, and the genotype of each HBV sequence was determined by comparison with sequences of known genotypes in the GenBank. A phylogenetic tree was constructed. RESULTS: Phylogenetic analysis revealed that all of the HBV isolates were clustered in genotype D. CONCLUSIONS: Our results concur with other reports from Iran, all showing that genotype D is the only detectable genotype in the different clinical forms of HBV infection in this country.
Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B virus , Hepatitis B/virology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/epidemiology , DNA, Viral/analysis , DNA, Viral/isolation & purification , Female , Genotype , Hepatitis B/epidemiology , Hepatitis B virus/classification , Hepatitis B virus/genetics , Humans , Iran/epidemiology , Male , Middle Aged , Phylogeny , Polymerase Chain Reaction/methods , Sequence Analysis, DNA , Young AdultABSTRACT
BACKGROUND: Recent studies have shown strong evidence that bronchiolitis obliterans is the major long-term sequelae of exposure to sulfur mustard (SM). This study is the first to examine the histopathologic spectrum of changes in a large number of surgical lung biopsies from patients exposed to SM. METHOD: Fifteen patients with chronic respiratory disease from mustard gas exposure were divided into severe (6 cases) and mild exposure (9 cases). All had surgical (open or thoracoscopic) lung biopsy, pulmonary function tests (PFTs) and chest high-resolution computed tomography scan (HRCT). RESULT: The mean age of the cases was 43.8+/-9.6 (range 33-65). All patients had dyspnea and cough as the two main complaints. Only one patient was a smoker. Thirteen patients had normal PFTs, while one had obstruction and one had mild restriction. Six (66.6%) patients in the mild exposure and 3 (50%) in the severe exposure group showed evidence of more than 25% air trapping on chest HRCT. Among the mild group, 3 had features of constrictive bronchiolitis and another had features suggestive of this (bronchiolectasis and mucus stasis). The next most common finding was a mild-to-moderate chronic cellular bronchiolitis (3 patients). Two among the 6 in the severe group showed constrictive bronchiolitis and one showed features suggestive of constrictive bronchiolitis. CONCLUSION: We conclude that about half of patients had diagnostic constrictive bronchiolitis, or bronchiolectasis and mucus stasis consistent with more proximal luminal compromise. The fact that there were no differences between the low- and high-dose groups suggests that effects of SM are not solely dependent on the severity of exposure. The results also indicate that the diagnosis of chronic lung disease due to SM may be difficult. Surgical lung biopsy may be helpful in difficult cases, as constrictive (obliterative) bronchiolitis can be present in symptomatic patients with normal PFTs and chest HRCT.
