IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis

Immunologic Research - Low levels of IgM auto-antibodies have been reported in health and disease. IgM anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in patients with...     

Expression of sialic acids in human adult skeletal muscle tissue

Investigations mostly in animal models have shown a role of sialic acid in the morphology and functionality of skeletal muscle during development and adult life. Several studies in humans have been performed regarding changes in sialic acid expression in a particular pathology, hereditary inclusion body myopathy, leading to muscular weakness and atrophy, with a similar phenomenon appearing also in sarcopenia of aging. In this study the expression of monomeric and polymeric sialic acids was evaluated in human skeletal muscle during adult life. Surgical biopsies of the Quadriceps femoris muscle from men aged 18–25 years (young group; n = 8) and men aged 72–78 (elderly group; n = 10) were collected for analysis. Expression of sialic acids was evaluated using lectin histochemistry, associated with enzymatic and chemical treatments to characterize monomeric and polymeric sialic acids. The polysialic acid expression was also evaluated by immunohistochemistry. Various types of sialic acid in the muscle tissue, in different amounts in the study groups, were detected. Monomeric sialic acids decreased in the elderly group compared with the young group, whereas polysialic acid increased. Sialic acid acetylation was present only in the young group. These findings demonstrated that changes in the expression of sialic acids in skeletal muscle tissue may be related to morphofunctional modifications occurring during aging.     

Progress in restorative neurosurgery: human fetal striatal transplantation in Huntington's disease. Review

The purpose of this paper was to offer a review of the rationale, methods, biological and clinical results of human fetal striatal transplantation (HFST) in the treatment of Huntington's disease (HD). HD is a heritable neurodegenerative disease in which degeneration of neurons in the striatum leads to motor, psychiatric and cognitive deficits. The disease is progressive and inexorably lethal. At present there are no curative treatments for HD. A restorative therapy based on the intrastriatal transplantation of striatal neuroblasts taken from human fetus is currently being explored as potential treatment in selected HD patients. Pilot clinical trials of HFST have been started in few neurosurgery restorative centres. Results demonstrated that HFST is feasible and safe without relevant adverse effects; grafted neuroblasts survive, grow without evidence of neoplasia or teratoma, build new tissue with striatal-like imaging features, and move into the host brain towards short and long-distance cortical and sub-cortical targets. HFST delays disease progression and provides a period of improvement and stability. Even though larger-scale studies are still necessary to establish the true value of such a treatment, at this time, HFST represents a promising experimental therapy for patients with HD and one of the most interesting clinical application of restorative neurosurgery.     

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves' disease. In isolated human thyrocytes, tumor necrosis factor (TNF)alpha demonstrates a potent synergistic effect on interferon (IFN)gamma-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNgamma and TNFalpha and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor gamma agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFNgamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappaB (NF-kappaB). In human thyrocytes, the synergistic effect of TNFalpha with IFNgamma on CXCL10 secretion is due to the upregulation of IFNgamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFalpha-induced upregulation of the IFNgamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappaB translocation, without affecting IFNgamma receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.     

Development of human striatal anlagen after transplantation in a patient with Huntington's disease

Replacement of damaged neuronal population by fetal tissue transplantation represents a potential treatment for neurodegenerative diseases. Consistent success has been achieved with fetal striatal transplantation in Huntington's disease animal models and patients. We report the neo-generation of metabolically active tissue with striatum-like imaging features after transplantation of striatal primordia in a patient with Huntington's disease. This study represents the first “in vivo” demonstration that a human striatal anlagen, transplanted into the adult human brain, is able to progress in its development and to generate a new anatomical structure in the host, without evidence of neoplasia or teratoma.     

Alteration of Polymeric Immunoglobulin Receptor and Neonatal Fc Receptor Expression in the Gut Mucosa of Immunodeficiency Virus‐Infected Rhesus Macaques

Polymeric immunoglobulin receptors (pIgR) and neonatal Fc receptors (FcRn) are crucial immunoglobulin (Ig) receptors for the transcytosis of immunoglobulins, that is IgA, IgM and IgG, the levels of which in mucosal secretions were altered in both HIV‐ and SIV‐infected individuals. To gain an insight into the changes of pIgR and FcRn expression after immunodeficiency virus (SHIV/SIV) infection, real‐time RT‐PCR methods were established and the mRNA levels of pIgR and FcRn in normal and SHIV/SIV‐infected rhesus macaques were quantitatively examined. It was found that the levels of pIgR mRNA were within a range of 10⁷ copies per million copies of GAPDH mRNA in the gut mucosa of rhesus macaques, which were up to 55 times higher than that in the oral mucosa, the highest among the non‐gut tissues examined. Levels of FcRn mRNA were generally lower than that of pIgR, and the levels of FcRn mRNA in the gut mucosa were also lower than that in most non‐gut tissues examined. Notably, the levels of pIgR mRNA in the duodenal mucosa were positively correlated with that of IL‐17A in normal rhesus macaques. Both pIgR and FcRn mRNA levels were significantly reduced in the duodenal mucosa during acute SHIV infection and in the jejunum and caecum during chronic SHIV/SIV infection. These data expanded our knowledge on the expression of pIgR and FcRn in the gastrointestinal tract of rhesus macaques and demonstrated altered expression of pIgR and FcRn in SHIV/SIV, and by extension HIV infections, which might have contributed to HIV/AIDS pathogenesis.     

Limited motor performance and minor neurological dysfunction at school age

Aim: To investigate the relationship between motor performance and minor neurological dysfunction (MND) at school age. Methods: Two hundred and fifty‐three children (158 boys, 95 girls; mean age 8 years and 7 months) of whom 167 children received mainstream education and 86 children special education were neurologically examined according to Touwen. Special attention was paid to the severity of MND (simple or complex form) and type of dysfunction. Motor performance was assessed with the Movement Assessment Battery for Children (MABC), a parental questionnaire (Developmental Coordination Disorder Questionnaire; DCD‐Q) and a teacher’s questionnaire (Motor Observation Questionnaire for Teachers; MOQ‐T). Results: Total scores of MABC, DCD‐Q and MOQ‐T were strongly related to the severity of MND and to dysfunctional coordination and fine manipulation. Mild dysfunction in posture and muscle tone was only weakly related to limited motor performance. Children with a MABC score < 5th percentile showed significantly more often complex MND than children with scores between the 5th and 15th percentile or >15th percentile (54% vs 17% and 10%). Conclusion: Limited motor performance is related to the severity and type of MND. Coordination problems and fine manipulative disability are strongly related to poor motor performance, mild dysfunctions of posture and muscle tone to a lesser extent.