ABSTRACT
We encountered two patients with acute pandysautonomia who subacutely exhibited extensive autonomic dysfunction after antecedent infections. Although these patients had been suffering from autonomic disturbance for several months, they both had a good clinical course after plasma exchange and intravenous immunoglobulin therapy. Thin-layer chromatography (TLC)-immunostaining did not demonstrate any antibodies against gangliosides, but immunoblot analysis showed antibodies against a neuroblastoma cell line, SH-SY5Y, in serum samples. Furthermore, ganglionic acetylcholine receptor autoantibodies were detected in one patient. These findings suggest that neuronal antibodies against the autonomic nervous system play an important role in the pathogenesis of acute pandysautonomia.
Subject(s)
Autoantibodies , Autoimmune Diseases of the Nervous System/immunology , Autonomic Nervous System Diseases/immunology , Neurons/immunology , Aged , Autoimmune Diseases of the Nervous System/therapy , Autonomic Nervous System Diseases/therapy , Humans , Immunoblotting , Immunoglobulins, Intravenous/therapeutic use , Male , Plasma Exchange , Receptors, Cholinergic/immunologyABSTRACT
The life span of osteoclasts is critically regulated by various cytokines, and therapeutics such as bisphosphonates act directly on osteoclasts and induce apoptosis of the cells. This article will focus on the molecular mechanism of osteoclast apoptosis and summarize the recent advances in this field with an emphasis on the role of intracellular signaling pathways.
Subject(s)
Osteoclasts/cytology , Osteoclasts/physiology , Animals , Apoptosis , Cell Death , Cell Survival , Homeostasis , Humans , Signal TransductionABSTRACT
Glucocorticoid (GC) excess often elicits serious adverse effects on the vascular system, such as hypertension and atherosclerosis, and effective prophylaxis for these complications is limited. We sought to reveal the mechanism underlying GC-induced vascular complications. Responses in forearm blood flow to reactive hyperemia in 20 GC-treated patients were significantly decreased to 43+/-8.9% (mean+/-SEM) from the values obtained before GC therapy (130+/-14%). An administration of vitamin C almost normalized blood flow responses. In human umbilical vein endothelial cells (HUVECs), production of hydrogen peroxide was increased up to 166.5+/-3.3% of control values by 10(-7) mol/L dexamethasone (DEX) treatment (P<0.01). Concomitant with DEX-induced hydrogen peroxide production, intracellular amounts of peroxynitrite significantly increased and those of nitric oxide (NO) decreased, respectively (P<0.01). Immunoblotting analysis using anti-nitrotyrosine antibody showed that peroxynitrite formation was increased in DEX-treated HUVECs. Using inhibitors against metabolic pathways for generation of reactive oxygen species (ROS), we identified that the major production sources of ROS by DEX treatment were mitochondrial electron transport chain, NAD(P)H oxidase, and xanthine oxidase. These findings suggest that GC excess causes overproduction of ROS and thereby perturbs NO availability in the vascular endothelium, leading to vascular complications in patients with GC excess.
