Experimental acute sinusitis was induced in 21 New Zealand hybrid rabbits by occluding the ostium and inoculating them with Streptococcus pneumonia. While a group of rabbits with sinusitis was left untreated, two other groups were administered parenteral sodium nitroprussid (SNP) and oral levofloxacin for ten days. While staphylococci species, non-hemolytic streptococcus and contaminated flora were isolated from the sinuses of controls, Streptococcus pneumonia was re-isolated in two of six untreated rabbits, in one of six SNP administered rabbits and none of the levofloxacin treated rabbits. Serum and maxillary sinus mucosal nitric oxide (NO) levels were correlated. While the mean maxillary sinus NO level of controls was significantly higher than that of untreated rabbits, the mean maxillary sinus and serum NO levels were significantly higher in SNP administered rabbits than in the others. Although goblet cell hyperplasia and squamous cell metaplasia were detected in some slides, edema and neutrophil infiltration were the prominent findings. The most severe inflammatory changes were found in the untreated sinusitis group on the third and fifth days. The earliest improvement was observed in the levofloxacin treated rabbits. It was concluded that NO level is decreased during acute sinusitis and that SNP administration hastens the bacteriological and histological recovery.
Acute Disease ; Animals ; Bacterial Infections ; Maxillary Sinus/*metabolism/pathology ; Maxillary Sinusitis/blood/*metabolism/microbiology/pathology ; Nitric Oxide/blood/*metabolism ; Rabbits ; Respiratory Mucosa/*metabolism/pathology

Retinoic acid receptor- (RAR-beta) is induced by and mediates the growth-inhibitory and apoptotic effects of retinoic acid (RA), suggesting that loss of RAR-betaexpression may be one of the critical events involved in the carcinogenesis/ progression of non-small cell lung cancer (NSCLC) and in the responsiveness to retinoid chemotherapy. However, recent contradictory reports that the expression of RAR-beta is associated with poor clinical outcome, and the fact that treatment of serum-deprived type 2 alveolar cells with RA leads to a stimulation of cell proliferation, require the verification of RAR-beta as a biomarker of chemoprevention or prognosis. The expression status of RAR-beta in cancer cells and adjacent normal appearing bronchial epithelium from 39 patients, diagnosed as stage I NSCLC and undergone a curative lung resection, was analyzed in paraffin-embedded tissue sections by IHC staining. The normal appearing bronchial epithelium of 14 out of 33 (42.4%) specimens expressed RAR-beta, whereas 22 out of the 39 (56.4%) stage I NSCLC specimens expressed RAR-beta. RAR-beta was more frequently expressed in the adenocarcinoma (72.7%) than in the squamous cell carcinoma (31.3%) (p=0.026). Neither the expression status in normal appearing adjacent tissue nor that in the tumor tissue had prognostic implications. The higher expression of RAR-beta in cancer tissue, the focal and uneven distribution in normal appearing adjacent bronchial epithelium, and inconsistency with the corresponding tumor tissue, suggest that the expression status of RAR-beta as a biomarker for chemoprevention/early diagnosis or the prognosis of NSCLC requires further consideration.
Adult ; Aged ; Bronchi/metabolism/pathology ; Carcinoma, Non-Small-Cell Lung/*metabolism/pathology ; Down-Regulation ; Female ; Human ; Immunohistochemistry ; Lung Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Receptors, Retinoic Acid/*metabolism ; Respiratory Mucosa/*pathology ; Tumor Markers, Biological/*metabolism

OBJECTIVETo investigate the relationship of BCL-10 protein and API2-MALT1 fusion gene in MALT lymphoma.

METHODSSpecimens from 86 cases of MALT lymphoma were studied by immunohistochemical staining for BCL-10. RT-PCR was used to detect the transcripts of API2-MALT1 fusion gene.

RESULTSIn all 10 cases of Hashimoto thyroiditis only cytoplasmic BCL-10 expression in lymphoid cells was observed. In 86 MALT lymphoma cases, 42 cases (48. 8%) exhibited BCL-10 expression in both nucleus and cytoplasm. API2-MALT1 fusion gene was detected in 35 cases (40. 7%) of MALT lymphoma. BCL-10 nuclear expression was correlated with API2-MALT1 fusion gene transcript (r = 0. 374,P = 0. 000).

CONCLUSIONBCL-10 nuclear expression is correlated with API2-MALT1 fusion gene expression in MALT lymphoma.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; B-Cell CLL-Lymphoma 10 Protein ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Female ; Follow-Up Studies ; Gastric Mucosa ; metabolism ; pathology ; Hashimoto Disease ; genetics ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoid Tissue ; metabolism ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Respiratory Mucosa ; metabolism ; pathology ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To study the expression of epidermal growth factor receptor (EGFR), C-erbB-2 and its relationship with cell proliferation in nasopharyngeal carcinoma. METHOD: Expression of C-erbB-2, EGFR and proliferating cell nuclear antigen (PCNA) were detected with immunohistochemical staining in 32 nasopharyngeal carcinoma samples and 12 chronic inflammatory nasopharyngeal tissue samples. RESULT: The positive rate of EGFR,C-erbB-2, and PCNA expression in nasopharyngeal carcinoma was 65.6%, 37.5%, and (42.5 +/- 22.6)%, respectively, which was significantly higher than that in chronic inflammatory nasopharyngeal tissue (P < 0.05). There were positive correlations between the positive rate of EGFR, C-erbB-2, and PCNA expression and histopathological stage. The co-expression of C-erbB2 and EGFR was found in 62.5% (20/32) nasopharyngeal carcinoma samples. There was a positive correlation between C-erbB-2 and EGFR expression (r = 0.38, P < 0.05). The highest percentage of PCNA expression was found in carcinoma samples with co-expression of C-erbB and EGFR. CONCLUSION C-erbB-2, EGFR might have synergetic effect in the development and progress of nasopharyngeal carcinoma. The co-expression of C-erbB-2 and EGFR closely correlates with cell proliferation status.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Proliferation ; ErbB Receptors ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Proliferating Cell Nuclear Antigen ; metabolism ; Receptor, ErbB-2 ; metabolism ; Respiratory Mucosa ; metabolism ; Young Adult

OBJECTIVETo investigate the role of dual oxidase-1 (DUOX-1) inducing airway hyperresponsiveness in human bronchial epithelium.

METHODSThe human bronchial epithelial cells were divided into several groups: control group, tumor necrosis factor-α (TNF-α) group, methyl-β-cyclodextrin (M-β-CD)+TNF-α group, desipramine (DES)+ TNF-α group, diphenylene iodonium (DPI) + TNF-α group and apocynin (APO)+TNF-α group. Fractionation was performed by sucrose gradient centrifugation and the protein DUOX-1 was measured by western blotting. The lipid raft clusters and its colocalization with DUOX-1 were confocal analysed. The intracellular reactive oxygen species (ROS) accumulation was measured by fluorescence of reactive oxygen probe of intracellular measurement. Sigmastat 3.02 software was used to analyze the data.

RESULTS(1) Detection of ROS, control group: 1.00 ± 0.00; TNF-α group: 1.95 ± 0.16; M-β-CD+TNF-α group: 0.91 ± 0.16; DES+TNF-α group: 1.49 ± 0.20; DPI+TNF-α group: 1.03 ± 0.16; APO+TNF-α group: 1.47 ± 0.26. The difference was statistically significant (F = 3.83, P < 0.05). (2) Extracts in rafts to lipid rafts region represents the ratio of total protein, protein content DUOX-1 each group, control group: 0.21 ± 0.02; TNF-α group: 0.49 ± 0.04; M-β-CD+TNF-α group: 0.08 ± 0.02; DES+TNF-α group: 0.09 ± 0.03; the difference was statistically significant (F = 3.96, P < 0.05). (3) DUOX-1 protein fluorescence values, control group: 1.72 ± 0.21; TNF-α group: 8.11 ± 1.23; M-β-CD+TNF-α group: 1.51 ± 0.32; DES+TNF-α group: 1.43 ± 0.11; the difference was statistically significant (F = 4.87, P < 0.05). (4) DUOX-1 gene detection, control group: 1.00 ± 0.00 ScrRNA+TNF-α group: 1.75 ± 0.04; DUOX-1siRNA+TNF-αgroup: 1.15 ± 0.02; the difference was statistically significant (F = 4.19, P < 0.05).

CONCLUSIONTNF-α can induce DUOX-1 expression increasing in lipid raft, then the DUOX-1 can be activated to increase reactive oxygen species level; acidic sphingomyelinase inhibitor desipramine can inhibit this process, the results disclose that the process will depend on the ceramide of lipid raft.

Cells, Cultured ; Ceramides ; metabolism ; Dual Oxidases ; Epithelial Cells ; metabolism ; Humans ; Hypersensitivity ; metabolism ; pathology ; Membrane Microdomains ; metabolism ; NADPH Oxidases ; metabolism ; Reactive Oxygen Species ; metabolism ; Respiratory Mucosa ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).

METHODSMice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.

RESULTSPCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.

CONCLUSIONSRSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.

Amino Acids, Branched-Chain ; metabolism ; Animals ; Female ; Gas Chromatography-Mass Spectrometry ; Intestinal Mucosa ; metabolism ; Intestine, Large ; metabolism ; pathology ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Pneumonia, Viral ; metabolism ; Respiratory Syncytial Virus Infections ; metabolism

OBJECTIVETo study the alternative expression and sequence of human elongation factor-1 delta (human EF-1 delta p31) during malignant transformation of human bronchial epithelial cells induced by cadmium chloride (CdC12) and its possible mechanism.

METHODSTotal RNA was isolated at different stages of transformed human bronchial epithelial cells (16HBE) induced by CdCl2 at a concentration of 5.0 microM. Special primers and probe for human EF-1 delta p31 were designed and expression of human EF-1 delta mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis.

RESULTSThe expressions of human EF-1 beta p31 at different stages of 16HBE cells transformed by CdCl2 was elevated (P < 0.01 or P < 0.05). Compared with their corresponding non-transformed cells, the overexpression level of EF-1 delta p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed cells and 7.2 folds in Cd-tumorigenic cells. No change was found n the sequence of overexpressed EF-1beta p31 at different stages of 16HBE cells transformed by CdCl2.

CONCLUSIONOverexpression of human EF-1beta p31 is positively correlated with malignant transformation of 16HBE cells induced by CdC12, but is not correlated with DNA mutations.

Cadmium Chloride ; Cell Line ; Cell Transformation, Neoplastic ; chemically induced ; metabolism ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Peptide Elongation Factor 1 ; genetics ; metabolism ; Respiratory Mucosa ; drug effects ; metabolism ; pathology ; Sequence Analysis, DNA

OBJECTIVEIt is supposed that bronchial epithelial cells responses to the environmental stimuli are different between asthmatic and non-asthmatic individuals, which contribute to the pathogenesis of asthma. These different responses produce different mediators. If differential gene expressions are found in bronchial epithelial cells of asthmatic and non-asthmatic individuals after the same stimuli in vitro, and these genes are overexpressed in asthmatic children in vivo, then it is concluded that these genes may be associated with asthma. Therefore the authors analyzed the differential gene expressions in the bronchial epithelium cells of asthmatic and non-asthmatic children after RSV infection in vitro. Among these genes, Galectine-7 (lectin, galactoside-binding, soluble, 7, Galectin-7) was 8 times up-regulated in asthmatic children. Galectine-7 was associated with skin keratinocyte apoptosis. The authors hypothesized that Galectin-7 may also be associated with bronchial epithelial cell apoptosis in asthmatic children. The aim of this study was to understand the role of Galectine-7 in bronchial epithelial cell apoptosis in asthma.

METHODSThe bronchial mucosae of one asthmatic child and one non-asthmatic child were obtained by biopsy and cultured in vitro. The bronchial epithelial cells were infected by RSV. The differential gene expressions were analyzed with micro array. Among those differentially expressed genes, Galectin-7 was 8 times up-regulated in asthmatic children. The bronchial mucosae from 10 asthmatic children and 17 non-asthma children were investigated for cell DNA break, Galectine-7 and mRNA expression, Caspase-3 expression by TUNEL, hybridization in situ and immunochemistry. Image analysis was used for quantitative assessment.

RESULTSGalectine-7 gene was 8 times up-regulated in bronchial epithelial cells from asthmatic children after RSV infection in vitro. Galectin-7 and mRNA were overexpressed in bronchial epithelial cells in asthma in vivo. Bronchial epithelial cell apoptosis increased in asthma in vivo.

CONCLUSIONGalectin-7 may be associated with bronchial epithelial cell apoptosis in asthma.

Adolescent ; Apoptosis ; genetics ; Asthma ; metabolism ; pathology ; Biopsy ; Bronchi ; metabolism ; pathology ; Bronchoscopy ; Caspase 3 ; genetics ; metabolism ; Cells, Cultured ; Child ; Child, Preschool ; Epithelial Cells ; metabolism ; pathology ; virology ; Female ; Galectins ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization ; In Situ Nick-End Labeling ; Infant ; Male ; RNA, Messenger ; Respiratory Mucosa ; cytology ; metabolism ; pathology ; virology ; Respiratory Syncytial Viruses ; pathogenicity ; Up-Regulation

No abstract available.
Air Pollutants/*toxicity ; Animals ; Biological Markers/metabolism ; Cell Proliferation/*drug effects ; Female ; Immunohistochemistry ; Inhalation Exposure ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/drug effects/pathology ; Ozone/*toxicity ; Proliferating Cell Nuclear Antigen/metabolism ; Respiratory Mucosa/*drug effects/metabolism/pathology ; Skin/*drug effects/metabolism/pathology

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.
Animals ; Antineoplastic Agents/*therapeutic use ; Bronchoalveolar Lavage Fluid/cytology ; Cytokines/biosynthesis ; Enzyme Activation ; Eosinophils/cytology ; Goblet Cells/pathology ; Inflammation/drug therapy/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/metabolism ; Respiratory Hypersensitivity/*drug therapy/etiology/metabolism ; Respiratory Mucosa/drug effects/pathology