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Last updated: 13
|Expression of beta-defensin-2 in human gastric tumors: a pilot study|
Exp Oncol. 2005 Jun;27(2):130-5
The present work was AIMED on the study of patterns of human beta-defensin-2 (hBD-2) expression in human gastric tumors. MATERIALS AND METHODS: 17 samples of surgically resected human gastric adenocarcinoma paired with respective normal tissue controls have been analyzed for the expression of hBD-2 by semi-quantitative RT-PCR and by immunohistochemical analysis using anti-hBD-2 monoclonal antibodies (mAbs) generated against recombinant hBD-2 by standard hybridoma technology. RESULTS: The hyperexpression of hBD-2 on mRNA and protein levels was registered in 6 from 17 gastric tumor samples compared to respective controls; however, hBD-2 expression patterns seems not be related to the differentiation grade and stage of tumors and the presence of anti-Helicobacter pylori-antibodies in the blood serum of the patients. CONCLUSION: In human gastric adenocarcinomas expression of hBDs possesses heterogeneic character; the research on larger cohort of the patients with gastric cancer should be further performed.
|Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract|
J Clin Pathol. 2005 Jul;58(7):687-94
BACKGROUND: Upper gastrointestinal tract intestinal metaplasia (IM) is termed Barrett's oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on its location. BO and GIM are associated with chemical exposure resulting from gastro-oesophageal reflux and chronic Helicobacter pylori infection, respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic granules, are found in a subset of IM at these sites, but histology may not accurately detect them. AIM: To determine human defensin 5 (HD5; an antimicrobial peptide produced by PCs) expression in BO and GIM, and to investigate its association with H pylori infection. METHODS: Endoscopic biopsies from 33 patients with BO and 51 with GIM, and control tissues, were examined by routine histology and for H pylori infection and HD5 mRNA and protein expression. RESULTS: In normal tissues, HD5 expression was specific for PCs in the small intestine. Five patients with BE and 42 with GIM expressed HD5, but few HD5 expressing cells in IM had the characteristic histological features of PCs. Most HD5 positive specimens were H pylori infected and most HD5 negative specimens were not infected. CONCLUSIONS: HD5 immunohistochemistry was often positive in IM when PCs were absent by conventional histology. Thus, HD5 immunohistochemistry may be superior to histology for identifying metaplastic PCs and distinguishing GIM from BO. The higher frequency of HD5 expression in GIM than in BO is associated with a higher frequency of H pylori infection, suggesting that in IM PCs may form part of the mucosal antibacterial response.
|Expression of alpha-defensin-1 in chronic hyperplastic candidosis|
J Oral Pathol Med. 2005 Jul;34(6):347-51
BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic opportunistic candida infection. We clarified the presence, localization and participation of alpha-defensin-1 in host response against chronic candidal stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria and in the epithelium, in part in intraepithelial microabscesses. Staining intensity of individual neutrophils varied and was associated with peri- and extracellular staining, in particular in the superficial epithelial cell layers. In controls only very few homogeneously staining neutrophils were detected intravascularly without any extracellular alpha-defensin-1 deposition. CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation and release of alpha-defensin-1 to peri- and extracellular matrix. This together with the epithelial cell migration from the basal layer to epithelial surface leads to alpha-defensin-1 rich protective shield in the most superficial epithelial cell layers.
|Effects of Lactobacillus GG on genes expression pattern in small bowel mucosa|
Dig Liver Dis. 2005 May;37(5):320-9
BACKGROUND AND AIMS: Probiotics have been used for cure and prevention of several clinical conditions. However, further insights into the mechanism of action are needed to understand the rationale of their use. The aim of this study was to investigate the influence of Lactobacillus GG on the genetic expression patterns in the small bowel mucosa. METHODS: Six male patients (38+/-5 years) with endoscopically proven oesophagitis were enrolled. All patients were treated for 1 month with esomeprazole and randomised to receive Lactobacillus GG or placebo. After 1 month of treatment, upper endoscopy was repeated. Biopsies of the duodenal mucosa were taken prior to and after the treatment, and the genes expression patterns were assessed using GeneChip Human U133A array. Genes with significant expression changes were selected and analysed to identify specific cellular pathways modified by Lactobacillus GG. To support the array data, 10 target genes were studied using Syber-Green PCR. RESULTS: Microarray analysis showed that Lactobacillus GG administration determined the up- and down-regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the reliability of the analysis. Lactobacillus GG mainly affected the expression of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell growth and cell differentiation (cyclins and caspases, oncogenes), cell-cell signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription and transduction. CONCLUSIONS: These data indicate that administration of Lactobacillus GG is associated with a complex genetic response of the duodenal mucosa, reflected by the up- and down-regulation of several genes involved in specific cellular pathways.
|Differential gene expression of human beta-defensins (hBD-1, -2, -3) in inflammatory gingival diseases.|
Oral Microbiol Immunol. 2005 Jun;20(3):186-90.
Antimicrobial peptides, like human beta-defensins, play an important role in the epithelial innate defense response. The aim of the present study was to investigate the quantitative expression of human beta-defensin-1, -2, and -3 in inflammatory gingival diseases. Gingival biopsies were obtained from patients with healthy gingiva (n = 10), patients with gingivitis (n = 10), and patients with periodontitis (n = 10). The clinical diagnosis was verified by histology. Gingival tissues were used for RNA extraction followed by reverse transcription. Gene expression was quantified by real-time polymerase chain reaction (normalization with GAP-DH). Comparing the tissues with different clinical stages of health and disease, no significant differences in mRNA expression were found for any of the beta-defensins studied. Similar levels of expression were found in healthy gingiva, whereas in gingivitis samples there was a significantly higher expression of hBD-2 compared to hBD-1 (P = 0.004) and hBD-3 (P = 0.016). Likewise, in periodontitis samples, hBD-2 expression was significantly higher than hBD-1 (P = 0.016); however, hBD-2 expression was comparable to hBD-3. In conclusion, the results of the present study showed a differential expression of human beta-defensins (hBD-1, -2, -3) in tissues with inflammatory gingival disease.
|Human beta-defensin (hBD-1, -2) expression in dental pulp.|
Oral Microbiol Immunol. 2005 Jun;20(3):163-6.
The purpose of this study was to investigate the expression of human beta-defensins (hBD-1, -2) in dental pulps by reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The mRNA transcripts of human beta-defensin-1 and human beta-defensin-2 could be detected by performing RT-PCR. With immunohistochemical staining of pulp tissue using antisera to hBD-1 and -2 it was possible to demonstrate cytoplasmic expression in odontoblasts. The results demonstrate that not only oral keratinocytes at the epithelial surface but also odontoblasts express human beta-defensins. Thus odontoblasts take part in the innate immune system and human beta-defensins may play an important role in the innate host defense of human dental pulp.
|Distribution of human beta-defensin polymorphisms in various control and cystic fibrosis populations|
Genomics. 2005 May;85(5):574-81
Human beta defensins contribute to the first line of defense against infection of the lung. Polymorphisms in these genes are therefore potential modifiers of the severity of lung disease in cystic fibrosis. Polymorphisms were sought in the human beta-defensin genes DEFB1, DEFB4, DEFB103A, and DEFB104 in healthy individuals and cystic fibrosis (CF) patients living in various European countries. DEFB1, DEFB4, and DEFB104 were very polymorphic, but DEFB103A was not. Within Europe, differences between control populations were found for some of the frequent polymorphisms in DEFB1, with significant differences between South-Italian and Czech populations. Moreover, frequent polymorphisms located in DEFB4 and DEFB104 were not in Hardy Weinberg equilibrium in all populations studied, while those in DEFB1 were in Hardy Weinberg equilibrium. Sequencing of a monochromosomal chromosome 8 mouse-human hybrid cell line revealed signals for multiple alleles for some loci in DEFB4 and DEFB104, but not for DEFB1. This indicated that more than one DEFB4 and DEFB104 gene was present on this chromosome 8, in agreement with recent findings that DEFB4 and DEFB104 are part of a repeat region. Individual DEFB4 and DEFB104 PCR amplification products of various samples were cloned and sequenced. The results showed that one DNA sample could contain more than two haplotypes, indicating that the various repeats on one chromosome were not identical. Given the higher complexity found in the genomic organization of the DEFB4 and DEFB104 genes, association studies with CF lung disease severity were performed only for frequent polymorphisms located in DEFB1. No association with the age of first infection by Pseudomonas aeruginosa or with the FEV1 percentage at the age of 11-13 years could be found.
|Elevated serum beta-defensins concentrations in patients with lung cancer.|
Anticancer Res. 2004 Nov-Dec;24(6):4051-7.
BACKGROUND: Beta-defensins (HBDs) are expressed in lung epithelial cells and act as antimicrobial agents. Most lung cancers that originate from pulmonary epithelial cells may produce HBDs. MATERIALS AND METHODS: We measured serum HBD-1 and HBD-2 levels in healthy subjects (HS), patients with lung cancer and patients with pneumonia by radioimmunoassay. RESULTS: Serum HBD-1 levels were higher in patients with lung cancer than HS and patients with pneumonia. Serum HBD-2 levels were higher in patients with lung cancer than HS. When cut-off values for positive HBD-1 were set at mean + 2SD of HS, the sensitivity and specificity of HBD-1 for the whole group of patients with lung cancer were 76.4 and 94.0%, respectively, and the proportion of patients with HBD-1-positive lung cancer and clinical stage I was 69.2%. CONCLUSION: Serum HBDs levels were high in patients with lung cancer and the serum HBD-1 level could be used as an auxiliary diagnostic tool for lung cancer.
|Association of defensin beta-1 gene polymorphisms with asthma|
J Allergy Clin Immunol. 2005 Feb;115(2):252-8
BACKGROUND: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. OBJECTIVE: We characterized the genetic diversity in the defensin beta-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. METHODS: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. RESULTS: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5' genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma ( P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion ( P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted ( P = .04) and was more prominent in female subjects ( P = .007). CONCLUSION: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.
|Expression and activity of beta-defensins and LL-37 in the developing human lung|
J Immunol. 2005 Feb 1;174(3):1608-15
Immaturity of innate immunity contributes to the increased susceptibility of human neonates to infection. The lung is a major portal of entry for potential pathogens in the neonate, and human beta-defensins (HBDs) and LL-37 participate in pulmonary innate immunity. We hypothesized that these antimicrobial factors would be developmentally regulated, expressed by neonatal pulmonary tissues, and participate in neonatal innate immunity. We found HBD-2 to be the predominant beta-defensin in human neonatal lung. HBD-2 mRNA expression was developmentally regulated, induced by the proinflammatory factor IL-1beta, and decreased by dexamethasone. Additionally, HBD-2 abundance in neonatal tracheal aspirates increased as a function of gestational age. HBD-1 had a lower level of expression compared with HBD-2 and was induced by dexamethasone. HBD-3 and LL-37 messages were not detected in airway epithelial cultures. Additionally, each antimicrobial peptide exhibited a unique spectrum of antimicrobial activity and salt sensitivity against bacteria commonly causing sepsis in the neonate. Lower levels of HBD-2 may be one factor contributing to the increased susceptibility of premature infants to pulmonary infections.