Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism

The development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.     

Urban legends series: oral manifestations of HIV infection

Human immunodeficiency virus‐related oral lesions (HIV‐OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV‐OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy‐to‐use diagnostic techniques have been recently introduced likely restricting the importance of HIV‐OLs in diagnosis. (iii) The 1993 EC‐Clearinghouse classification of HIV‐OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV‐OL case definitions were updated in 2009 to facilitate the accuracy of HIV‐OL diagnoses by non‐dental healthcare workers in large‐scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV‐OLs has been reported for OC and OHL.     

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy

TRACK‐HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3‐Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross‐sectional data from this large well‐characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene‐positive subjects (120 PreHD and 119 early HD) from the TRACK‐HD study were included. Using voxel‐based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti‐saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment

Background  

It has been suggested that intrasphincteric injection of botulinum toxin (BTX) may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP) and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection).     

Establishment and characterization of an Epstein-Barr virus transformed cell line with strong phagocytic activity

An immunoglobulin M (IgM)-positive cell line, Ms 28, apparently spontaneously transformed by Epstein-Barr virus (EBV) was established from peripheral blood cells of a patient with immature myeloblastic leukemia. It has been characterized according to phenotype, cytochemistry, and membrane antigen pattern. The cell line expresses lymphoid markers like CD 19, CD 22, and CD 30 and synthesizes and secretes IgM. Monocyte markers CD 11c, CD 14, and CD 15 are absent. Neither interleukin-1 (IL-1), nor tumor necrosis factor (TNF-alpha) are produced. But Ms 28 cells show strong phagocytic activity and engulf Latex particles and sheep RBCs (SRBCs) that need not to be opsonized. The phagocytic activity can be inhibited by chloroquine. Both phagocytosis and EBV nuclear-antigen (EBNA) expression can be observed in one and the same cell. Ms 28 cells might be useful to study immunologic activities like antigen processing and presentation.     

Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT‐HD study, we use statistical shape analysis with deformation markers obtained through “Large Deformation Diffeomorphic Metric Mapping” of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico‐basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. Hum Brain Mapp 35:792–809, 2014. © 2012 Wiley Periodicals, Inc.