Decreased T lymphocyte infiltration in bronchial bipsies of subjects with severe obstructive pulmonary disease

BACKGROUND: Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. OBJECTIVE: The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. METHODS: We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium. RESULTS: Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P < 0.012, P < 0.02 and P < 0.02, respectively) and control smokers (P < 0.015, P < 0.005 and P < 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P < 0.015 and r = 0.52, P < 0.032, respectively). CONCLUSIONS: Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation

RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression

Huntington’s Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD

Correction: RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression.

[This corrects the article DOI: 10.1371/journal.pone.0143563.]

The impact of psychopathological subtypes on retention rate of patients with substance use disorder entering residential therapeutic community treatment

A specific psychopathology of addiction has been proposed and described using the self-report symptom inventory (SCL-90), leading to a 5-factor aggregation of psychological/psychiatric symptoms: 'worthlessness and being trapped', 'somatic symptoms', 'sensitivity-psychoticism', 'panic-anxiety' and 'violence-suicide' in various populations of patients with heroin use disorder (HUD) and other substance use disorders (SUDs). These clusters of symptoms, according to studies that have highlighted the role of possible confounding factors (such as demographic and clinical characteristics, active heroin use, lifetime psychiatric problems and kind of treatment received by the patients), seem to constitute a trait rather than a state of the psychological structure of addiction. These five psychopathological dimensions defined on the basis of SCL-90 categories have also been shown to be correlated with the outcomes of a variety of agonist opioid treatments. The present study aims to test whether the 5-factor psychopathological model of addiction correlates with the outcome (retention rate) of patients with SUDs entering a therapeutic community (TC) treatment

Psychic Structure of Opioid Addiction: Impact of Lifetime Psychiatric Problems on SCL-90-based Psychopathologic Dimensions in Heroin-dependent Patients

Background: By applying a Principal Component Analysis (PCA) to the items of the SCL-90 checklist, we previously investigated the psychopathologic structure of individuals with heroin addiction, finding a 5-factor aggregation of psychological/psychiatric symptoms: "Worthlessness and Being trapped," "Somatic Symptoms," "Sensitivity-Psychoticism," "Panic-Anxiety," and "Violence-Suicide." Our studies on this subject did not, however, explore the possible impact of comorbid psychiatric conditions on 5 psychopathologic dimensions listed above. The aim of the present study is to verify whether there is any difference in these 5 dimensions between heroin-addicted patients with (PC-HA) or without (NPC-HA) known lifetime psychiatric problems. Methods: A total of 1195 patients with heroin dependence entering a residential therapeutic community treatment were assigned to one of the 5-factor solutions yielded by Principal Component Analysis on the basis of the highest z score obtained. Differences between NPC-HA and PC-HA patients in the frequency of the 5 psychopathologic dimensions and in their severity were then analyzed by means of univariate and multivariate analyses. Results: All the SCL-90 factor scores were, from a statistical viewpoint, significantly higher in PC-HA than in NPC-HA patients, but the only statistically significant differences in the frequency of the 5 psychopathological dimensions were those observed in the case of "Panic-Anxiety," which turned out to be higher in the PC-HA group. Stepwise discriminant analysis showed that the severity of "Somatic Symptoms" and "Panic-Anxiety" made these 2 factors the only ones that successfully discriminated between NPC-HA and PC-HA patients. The other SCL-90-based psychopathologic dimensions were unable to improve the value of the discrimination. Conclusions: On the basis of our results, the SCL-90-defined structure of opioid addiction may be considered to be only partly dependent on the presence of a "psychiatric" condition. This observation adds to the previous ones that go to show the stability of the above aggregations of symptoms, irrespectively of other demographic and clinical characteristics, as well as active involvement with heroin abuse or the kind of treatment chosen. When the available evidence is considered as a whole, it seems to support the trait-dependent, rather than state-dependent, nature of the proposed factorial dimensions of the psychopathology of opioid addiction