Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.     

Identification of tumor suppressor loci on the long arm of chromosome 15 in primary small cell lung cancer

Small cell lung cancer (SCLC) frequently shows a loss of heterozygosity (LOH) on chromosome 15q. In order to define the commonly affected region on chromosome 15q, we tested 23 primary SCLCs by microsatellite analysis. By analyzing 43 polymorphic microsatellite markers located on chromosome 15q, we found that 14 (60.8%) of 23 tumors exhibited a LOH in at least one of the tested microsatellite markers. Two (14.3%) of the 14 tumors were found to have more than a 50% LOH on chromosome 15q. LOH was observed in five commonly deleted regions on 15q. Of those regions, LOH from D15S1012 to D15S1016 was the most frequent (47.8%). LOH was also observed in more than 20-30% of tumors at four other regions, from D15S1031 to D15S1007, from D15S643 to D15S980, from D15S979 to D15S202, and from D15S652 to D15S642. Four of the 23 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.2% (29 of 914) of the loci tested. Our data suggests the presence of at least five tumor suppressor loci on chromosome 15q in SCLC, and further that these may play an important role in SCLC tumorigenesis.     

Identification of mutations in the Bruton's tyrosine kinase gene,including a novel genomic rearrangements resulting in large deletion,in Korean X-linked agammaglobulinemia patients

Mutations in the Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion including BTK exons 11–18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation, and a point mutation in a splicing acceptor site (IVS7−9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations.     

Scoring system for risk stratification of viral reactivation during prophylactic antiviral treatment in Korean patients with hepatitis B undergoing anticancer chemotherapy: A multicenter study

Prophylactic antiviral therapy is recommended for hepatitis B virus (HBV)‐infected patients with malignancies who are undergoing systemic chemotherapy. In the current study, we aimed to develop a risk scoring system to guide the selection of prophylactic antiviral agents. In this retrospective analysis, we included consecutive chronic hepatitis B patients who received antiviral prophylaxis for chemotherapy of solid or hematologic malignancies at three large‐volume hospitals in Korea. The primary endpoint was HBV reactivation. The inverse probability treatment weighting method was used to minimize selection bias in terms of antiviral assignments. A total of 419 patients were enrolled: 129 patients received lamivudine (LAM), 216 received telbivudine (LdT), and 74 received entecavir (ETV), respectively. Of these, 36 patients developed on‐treatment HBV reactivation (LAM, 17; LdT, 18; ETV, 1). Multivariate analysis identified three independent predictors for reactivation: hepatitis B e‐antigen positivity, HBV DNA level, and type of malignancy. Accordingly, a risk scoring system was developed wherein one point was assigned for each of the risk factors. HBV reactivation occurred more frequently in the high‐risk group (score ≥ 2) than in the low‐risk group (hazards ratio, 14.17; P < 0.001). ETV exhibited superior prophylactic efficacy over LdT or LAM in the high‐risk group, whereas no significant difference was noted in the low‐risk group. The prognostic scoring system was useful for risk stratification of chemotherapy‐related HBV reactivation. High genetic barrier agents appear to be vital for high‐risk patients, whereas cost‐effectiveness may be more relevant for low‐risk patients.     

Topical anti-inflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis

Background

The placenta is a reservoir enriched with growth factors, hormones, cytokines and minerals. While several beneficial effects of placenta extracts on wound healing, anti-aging and anti-inflammatory responses have been reported, relatively limited mechanistic exploration has been conducted to date. Here, we provide compelling evidence of anti-inflammatory and anti-oxidative activities of porcine placenta extracts (PPE) against contact dermatitis in vivo.

Methods

A contact dermatitis mouse model was established by sensitizing the dorsal skin of BALB/c mice using the contact allergen, 2,4-dinitrochlorobenzene (DNCB), and molecular consequences of topical application of PPE were investigated. PPEs were pre-sterilized via γ-irradiation, which is a milder but more effective way of sterilizing biomolecules relative to the conventional autoclaving method.

Results

DNCB-induced skin lesions displayed clear contact dermatitis-like symptoms and topical application of PPE dramatically alleviated both local and systemic inflammatory responses. Inflammatory epidermal thickening was completely abrogated and allergen-specific serum IgE levels significantly reduced in the presence of PPE. Moreover, anti-oxidative activities of PPE were observed both in vitro and in vivo, which may lead to attenuation of inflammatory responses. Prolonged treatment with PPE strongly inhibited production of DNCB-induced reactive oxygen species (ROS) and subsequently prevented oxidative degradation of hyaluronic acid (HA), which triggers innate inflammatory responses.

Conclusion

Our findings supply valuable insights into the mechanisms underlying the anti-inflammatory effects of PPE and provide a functional basis for the clinical application of PPE in inflammatory diseases.

     

Attachment insecurity as a mediator of the relationship between childhood trauma and adult dissociation

This study aimed to investigate whether attachment insecurity mediates the relationship between childhood trauma and adult dissociation, specifically with regard to individual forms of childhood maltreatment. Psychiatric outpatients who visited a specialized trauma clinic (n = 115) participated in the study. Data were collected via the Childhood Trauma Questionnaire, Revised Adult Attachment Scale, and Dissociative Experience Scale. Structural equation modeling and path analysis were performed to analyze the mediating effects of attachment insecurity on the relationship between childhood trauma and adult dissociation. Greater childhood trauma was associated with higher dissociation, and the relationship between them was fully mediated by attachment anxiety. In path analysis of trauma subtypes, the effects of emotional abuse, physical abuse, and physical neglect as a child on adult dissociation were found to be fully mediated by attachment anxiety. The effect of sexual abuse on dissociation was mediated by a synergistic effect from both attachment anxiety and attachment avoidance. Regarding emotional neglect, a countervailing interaction was discovered between the direct and indirect effects thereof on dissociation; the indirect effect of emotional neglect on dissociation was partially mediated by attachment insecurity. Specific aspects of attachment insecurity may help explain the relationships between individual forms of childhood trauma and adult dissociative symptoms. Tailored treatments based on affected areas of attachment insecurity may improve outcomes among patients with dissociative symptoms and a history of childhood trauma.     

Spinal cholinergic mechanism of the relieving effects of electroacupuncture on cold and warm allodynia in a rat model of neuropathic pain

This study was performed to determine whether spinal cholinergic systems mediate the relieving effects of electroacupuncture (EA) on cold and warm allodynia in a rat model of neuropathic pain. For neuropathic surgery, the right superior caudal trunk was resected at the level between the S1 and S2 spinal nerves innervating the tail. Two weeks after the injury, the intrathecal (i.t.) catheter was implanted. Five days after the catheterization, the rats were injected with atropine (non-selective muscarinic antagonist, 30 μg), mecamylamine (non-selective nicotinic antagonist, 50 μg), pirenzepine (M₁ muscarinic antagonist, 10 μg), methoctramine (M₂ antagonist, 10 μg) or 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (M₃ antagonist, 10 μg). Ten minutes after the injection, EA was applied to the ST36 acupoint for 30 min. The cold and warm allodynia were assessed by the tail immersion test [i.e., immersing the tail in cold (4°C) or warm (40°C) water and measuring the latency of an abrupt tail movement] before and after the treatments. The i.t. atropine, but not mecamylamine, blocked the relieving effects of EA on cold and warm allodynia. Furthermore, i.t. pirenzepine attenuated the antiallodynic effects of EA, whereas methoctramine and 4-DAMP did not. These results suggest that spinal muscarinic receptors, especially M₁ subtype, mediate the EA-induced antiallodynia in neuropathic rats. J. H. Park and S. K. Kim have contributed equally to this work.