ABSTRACT
OBJECTIVES: To determine the frequency of familial focal and segmental dystonias in a large patient cohort with primary dystonia from north-western Germany. MATERIALS AND METHODS: In this study, 130 patients with focal or segmental dystonia were examined and a family history was obtained. Whenever possible, affected relatives were examined (a total of 789 first-degree relatives). Data on disease duration, age at disease onset and age of the patients were investigated by Student's t-test and a segregation analysis was performed by Weinberg's proband method. RESULTS: Age at onset of disease was significantly later in the blepharospasm group. Only in the writer's cramp group were women outnumbered by men. A positive family history was found in 15 of the 130 index patients (11.5%). None of 102 index patients tested carried the GAG deletion in the DYT1 gene. CONCLUSIONS: In accordance with previous series our study provides evidence that primary focal dystonia may have a genetic etiology, most probably caused by an autosomal dominant trait with reduced penetrance.
Subject(s)
Carrier Proteins/genetics , Dystonic Disorders/genetics , Dystonic Disorders/pathology , Molecular Chaperones , Adult , Age of Onset , Aged , Aged, 80 and over , Cohort Studies , Dystonic Disorders/epidemiology , Female , Gene Deletion , Genetic Predisposition to Disease , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Pedigree , Sex FactorsABSTRACT
Polymorphonuclear neutrophils (PMN) are part of the innate immune system and are first-line effector cells in acute inflammatory responses. On activation PMNs secrete cytokines and oxygen metabolites that might be involved in the regulation of the acquired immune response. We show here that peripheral blood PMNs constitutively express a B7-1-like molecule as detected by immunostaining with several B7-1 antibodies. Reverse transcriptase-polymerase chain reaction using three sets of primers spanning different regions of B7-1 indicate dissimilarities at the mRNA level. B7-1 mRNA is expressed in bone marrow cells and lipopolysaccharide (LPS)-stimulated but not in unstimulated PMNs. The B7-1-like molecule is localized to the cytoplasmic granules and translocated to the cell surface after stimulation with LPS or interleukin-12 in some donors. Binding of CTLA4-Ig suggests that the B7-1-like molecule can interact with functional B7 ligand and might be important in the immunobiology of PMNs.
Subject(s)
B7-1 Antigen/biosynthesis , Neutrophils/metabolism , Antibodies, Monoclonal , Antigens, CD/biosynthesis , Antigens, CD/blood , Antigens, CD/cerebrospinal fluid , Antigens, CD/genetics , Antigens, Surface/biosynthesis , B7-1 Antigen/blood , B7-1 Antigen/cerebrospinal fluid , B7-1 Antigen/genetics , B7-2 Antigen , Cells, Cultured , Humans , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/blood , Membrane Glycoproteins/cerebrospinal fluid , Membrane Glycoproteins/genetics , Meningitis, Bacterial/blood , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/immunology , Meningitis, Bacterial/metabolism , Neutrophil Activation/immunology , Neutrophils/drug effects , RNA, Messenger/biosynthesis , RNA, Messenger/metabolism , Staining and Labeling/methodsABSTRACT
The examination of cerebrospinal fluid (CSF) continues to play an important role in the diagnosis of inflammatory diseases of the central nervous system (CNS). Immunocytochemistry and flow cytometry are the most commonly used methods for analysis of surface markers on CSF cells. We here compared these methods in the examination of CSF cells from a total of 68 patients with acute and chronic inflammatory CNS diseases. Expression of costimulatory molecules CD80 (B7-1) and CD86 (B7-2) as activation markers that are present at low density on the cell surface was analyzed in comparison to CD22 (B-cells) and CD4 (T-cell subset), that show high staining intensities. For CD22 and CD4, the results obtained with both methods were similar and reliable. Using flow cytometry, CD80 expression was detected in 6% of CSF cells in patients with chronic inflammatory CNS disease, as compared to 2% using immunocytochemistry, where the reliability of the data was found to be higher. We conclude that for examination of low-density surface markers on CSF cells, particularly with low cell counts, immunocytochemistry may be more reliable.
Subject(s)
Antigens, Surface/biosynthesis , Central Nervous System Diseases/pathology , Cerebrospinal Fluid/cytology , Flow Cytometry , Immunohistochemistry , Antigens, CD/biosynthesis , Central Nervous System Diseases/metabolism , Humans , Inflammation/metabolism , Inflammation/pathologyABSTRACT
The aberrant expression of B7 costimulatory molecules is involved in the pathogenesis of autoimmune diseases and overexpression of B7-1 was found in inflammatory multiple sclerosis (MS) lesions. We here report that costimulatory molecules B7-1 and B7-2 are expressed on cerebrospinal fluid (CSF) monocytes and B-lymphocytes from patients with MS, optic neuritis (ON) and other inflammatory central nervous system (CNS) diseases. In patients with ON but not MS, increased expression of B7-2 was detected as compared to non-inflammatory controls. The expression of B7-1 in MS and ON patients correlates with disease duration but not with relapses in patients with MS indicating a role in early disease but not as a reliable marker of disease activity at later stages of MS.
