Helena Svensson

Annoyance due to single and combined sound exposure from railway and road traffic.

Environmental noise is a growing and well recognized health problem. However, in many cases people are exposed not to a single noise source-for example, road, railway, or aircraft noise-but to a combination of noise exposures and there is only limited knowledge of the effects on health of exposure to combined noise sources. A socio-acoustic survey among 1953 persons aged 18-75 years was conducted in residential areas exposed to railway and road traffic noise with sound levels ranging from L(Aeq,24h) 45-72 dB in a municipality east of Gothenburg, Sweden. The objectives were to assess various adverse health effects, including annoyance, and to elucidate the impact of exposure to single and combined noise sources. In areas exposed to both railway and road traffic, the proportion annoyed by the total traffic sound environment (total annoyance) was significantly higher than in areas with one dominant noise source (rail or road traffic) with the same total sound exposure (L(Aeq,24h,tot)). This interaction effect was significant from 59 dB and increased gradually with higher sound levels. Effects of the total sound exposure should be considered in risk assessments and in noise mitigation activities.

Accumulation of CCR4+ CTLA-4hi FOXP3+CD25hi Regulatory T Cells in Colon Adenocarcinomas Correlate to Reduced Activation of Conventional T Cells

Background Colorectal cancer usually gives rise to a specific anti-tumor immune response, but for unknown reasons the resulting immunity is not able to clear the tumor. Recruitment of activated effector lymphocytes to the tumor is important for efficient anti-tumor responses, while the presence of regulatory T cells (Treg) down-modulate tumor-specific immunity. We therefore aimed to determine homing mechanisms and activation stage of Treg and effector T cell infiltrating colon tumors compared to cells from the unaffected mucosa in patients suffering from colon adenocarcinoma. Methodology/Principal Findings Lymphocytes were isolated from unaffected and tumor mucosa from patients with colon adenocarcinoma, and flow cytometry, immunohistochemistry, and quantitative PCR was used to investigate the homing mechanisms and activation stage of infiltrating Treg and conventional lymphocytes. We detected significantly higher frequencies of CD25highFOXP3+CD127low putative Treg in tumors than unaffected mucosa, which had a complete demethylation in the FOXP3 promotor. Tumor-associated Treg had a high expression of CTLA-4, and some appeared to be antigen experienced effector/memory cells based on their expression of αEβ7 (CD103). There were also significantly fewer activated T cells and more CTLA-4+ conventional T cells susceptible to immune regulation in the tumor-associated mucosa. In contrast, CD8+granzyme B+ putative cytotoxic cells were efficiently recruited to the tumors. The frequencies of cells expressing α4β7 and the Th1 associated chemokine receptor CXCR3 were significantly decreased among CD4+ T cells in the tumor, while frequencies of CD4+CCR4+ lymphocytes were significantly increased. Conclusions/Significance This study shows that CCR4+CTLA4hi Treg accumulate in colon tumors, while the frequencies of activated conventional Th1 type T cells are decreased. The altered lymphocyte composition in colon tumors will probably diminish the ability of the immune system to effectively attack tumor cells, and reducing the Treg activity is an important challenge for future immunotherapy protocols.

CCL28 Is Increased in Human Helicobacter pylori-Induced Gastritis and Mediates Recruitment of Gastric Immunoglobulin A-Secreting Cells

ABSTRACT Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for the development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of immunoglobulin A (IgA)-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori-infected volunteers mounted a B-cell response in the gastric mucosa. To identify the signals for recruitment of gastric IgA-secreting cells, we investigated the gastric production of CCL28 (mucosa-associated epithelial chemokine) and CCL25 (thymus-expressed chemokine) in H. pylori-infected and uninfected individuals and the potential of gastric B-cell populations to migrate toward these chemokines. Gastric tissue from H. pylori-infected individuals contained significantly more CCL28 protein and mRNA than that from uninfected individuals, while CCL25 levels remained unchanged. Chemokine-induced migration of gastric lamina propria lymphocytes isolated from patients undergoing gastric resection was then assessed using the Transwell system. IgA-secreting cells and IgA+ memory B cells from H. pylori-infected tissues migrated toward CCL28 but not CCL25, while the corresponding cells from uninfected patients did not. Furthermore, IgG-secreting cells from H. pylori-infected patients did not migrate to CCL28 but instead to CXCL12 (SDF-1α). However, chemokine receptor expression did not correlate to the migratory pattern of the different B-cell populations. These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals.

Selective Upregulation of Endothelial E-Selectin in Response to Helicobacter pylori-Induced Gastritis

ABSTRACT Helicobacter pylori is one of the most common bacterial pathogens, infecting up to 50% of the worlds population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect of H. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, in H. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to α5β1 integrins. Thus, endothelial E-selectin expression induced by H. pylori probably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected with cagPAI-positive H. pylori strains and may thereby contribute to tissue damage in these individuals.

Expression of the chemokine decoy receptor D6 is decreased in colon adenocarcinomas.

Abstract Recruitment of immune cells to tumors is a complex process crucial for both inflammation-driven tumor progression and specific anti-tumor cytotoxicity. Chemokines control the directed migration of immune cells, and their actions are partly controlled by nonsignaling chemokine decoy receptors. The role of the receptors such as D6, Duffy antigen receptor for chemokines and ChemoCentryx chemokine receptor in immunity to tumors is still unclear. Using real-time PCR, we detected significantly decreased expression of D6 mRNA in colon tumors compared to unaffected mucosa. D6 protein was expressed by lymphatic endothelium and mononuclear cells in the colon lamina propria and detected by immunohistochemistry in two out of six tissue samples containing high D6 mRNA levels, whereas no staining was observed in any tissue samples expressing low mRNA levels. When examining the density of lymphatic vessels in colon tumors, we detected a marked increase in vessels identified by the lymphatic endothelial marker Lyve-1, excluding passive regulation of D6 due to decreased lymphatic vessel density. In parallel, the Treg-recruiting chemokine CCL22, which is sequestered by D6, was threefold increased in tumor tissue. Furthermore, we could show that low D6 expression correlated to more invasive tumors and that tumor location influences D6 expression, which is lower in the more distal parts of the colon. The data support that regulation of D6 by colon tumors results in altered levels of proinflammatory CC chemokines, thereby shaping the local chemokine network to favor tumor survival. This may have implications for the design of future immunotherapy for colon cancer.

Dermoscopic rainbow pattern: A clue to diagnosing aneurysmal atypical fibroxanthoma

AAFX: aneurysmal atypical fibroxanthoma AFX: atypical fibroxanthoma ERG: ETS-related gene RP: rainbow pattern INTRODUCTION Atypical fibroxanthoma (AFX) is an uncommon spindle cell tumor of fibrous tissue most often located on the sun-damaged skin on the head and neck of elderly patients. It has a locally aggressive behavior and a tendency to recur after surgery but a low metastatic potential. Clinically, AFX presents as a rapidly growing solitary nodule, which sometimes becomes ulcerated. Several subentities exist, including the aneurysmal atypical fibroxanthoma (AAFX), which is the subject of this report. Dermoscopy of AFX usually shows a nonspecific pattern including slight pigmentation, reddish and whitish areas, and/or a polymorphic vascular pattern (eg, linear, dotted, hairpin, and highly tortuous vessels) irregularly distributed over the surface of the lesion. This pattern can also be seen in other clinically similar tumors, such as squamous cell carcinoma, angiosarcoma, Merkel cell carcinoma, and amelanotic melanoma. The dermoscopic term rainbow pattern (RP) is used for highly vascularized lesions with areas showing various colors of the rainbow on polarized dermoscopy. Hemosiderotic and aneurysmal variants of fibrohistiocytic tumors such as dermatofibromas have been described as presenting with a RP. RP has previously been reported in a case of AFX, but to the best of our knowledge, no cases of AAFX showing the dermoscopic RP have been reported.

Annoyance Due to Single and Combined Sound Exposure from Railway and Road Traffic

Environmental noise is a growing and well recognized health problem. However, in many cases people are exposed not to a single noise source—for example, road, railway, or aircraft noise—but to a combination of noise exposures and there is only limited knowledge of the effects on health of exposure to combined noise sources. A socio-acoustic survey among 1953 persons aged 18–75 years was conducted in residential areas exposed to railway and road traffic noise with sound levels ranging from LAeq,24h 45–72 dB in a municipality east of Gothenburg, Sweden. The objectives were to assess various adverse health effects, including annoyance, and to elucidate the impact of exposure to single and combined noise sources. In areas exposed to both railway and road traffic, the proportion annoyed by the total traffic sound environment (total annoyance) was significantly higher than in areas with one dominant noise source rail or road traffic with the same total sound exposure (LAeq,24h,tot). This interaction effect was significant from 59 dB and increased gradually with higher sound levels. Effects of the total sound exposure should be considered in risk assessments and in noise mitigation activities.