Peripheral Blood CD64 Levels Decrease in Crohn's Disease following Granulocyte and Monocyte Adsorptive Apheresis

Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn's disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI). The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores

Local comparison of protein structures highlights cases of convergent evolution in analogous functional sites

We performed an exhaustive search for local structural similarities in an ensemble of non-redundant protein functional sites. With the purpose of finding new examples of convergent evolution, we selected only those matching sites composed of structural regions whose residue order is inverted in the relative protein sequences

Decreased olfactory discrimination is associated with impulsivity in healthy volunteers

In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identifcation). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and detection threshold predicted low inhibitory control (SST; increased motor impulsivity). These fndings extend clinical observations to support the hypothesis that defcits in olfactory ability are linked to impulsive tendencies within the healthy population. In particular, the relationship between olfactory abilities and behavioural inhibitory control (in the SST) reinforces evidence for functional overlap between neural networks involved in both processes. These fndings may usefully inform the stratifcation of people at risk of impulse-control-related problems and support planning early clinical interventions

Biomonitoring of complex occupational exposures to carcinogens: The case of sewage workers in Paris

<p>Abstract</p> <p>Background</p> <p>Sewage workers provide an essential service in the protection of public and environmental health. However, they are exposed to varied mixtures of chemicals; some are known or suspected to be genotoxics or carcinogens. Thus, trying to relate adverse outcomes to single toxicant is inappropriate. We aim to investigate if sewage workers are at increased carcinogenic risk as evaluated by biomarkers of exposure and early biological effects.</p> <p>Methods/design</p> <p>This cross sectional study will compare exposed sewage workers to non-exposed office workers. Both are voluntaries from Paris municipality, males, aged (20–60) years, non-smokers since at least six months, with no history of chronic or recent illness, and have similar socioeconomic status. After at least 3 days of consecutive work, blood sample and a 24-hour urine will be collected. A caffeine test will be performed, by administering coffee and collecting urines three hours after. Subjects will fill in self-administered questionnaires; one covering the professional and lifestyle habits while the a second one is alimentary. The blood sample will be used to assess DNA adducts in peripheral lymphocytes. The 24-hour urine to assess urinary 8-oxo-7, 8-dihydro-2'-deoxy-Guanosine (8-oxo-dG), and the in vitro genotoxicity tests (comet and micronucleus) using HeLa S3 or HepG2 cells. In parallel, occupational air sampling will be conducted for some Polycyclic Aromatic Hydrocarbons and Volatile Organic Compounds. A weekly sampling chronology at the offices of occupational medicine in Paris city during the regular medical visits will be followed. This protocol has been accepted by the French Est III Ethical Comitee with the number 2007-A00685-48.</p> <p>Discussion</p> <p>Biomarkers of exposure and of early biological effects may help overcome the limitations of environmental exposure assessment in very complex occupational or environmental settings.</p

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types