Distinct inflammatory properties of late-activated macrophages in inflammatory myopathies.

Distinct mechanisms such as humeral immunity in dermatomyositis (DM) and T-cell-mediated cytotoxicity in polymyositis (PM) contribute to the pathology of inflammatory myopathies. In addition, different subsets of macrophages are present in both diseases. Herein, the characteristics of 25F9-positive macrophages in skeletal muscle inflammation are outlined. Muscle biopsies of subjects with DM and PM were studied by immunohistochemical multi-labelling using the late-activation marker 25F9, together with markers characterizing macrophage function including IFN-gamma, iNOS, and TGF-beta. In PM, a robust expression of IFN-gamma, iNOS, and TGF-beta was observed in inflammatory cells. Double- and serial-labelling revealed that a subset of 25F9-positive macrophages in the vicinity of injured muscle fibres expressed iNOS and TGF-beta, but not IFN-gamma. In DM, IFN-gamma, iNOS and TGF-beta were also expressed in inflammatory cells in the endomysium. Double- and serial-labelling studies in DM indicated that 25F9-positive macrophages expressed TGF-beta and to a lesser degree iNOS, but not IFN-gamma. In conclusion, our data suggest that late-activated macrophages contribute to the pathology of inflammatory myopathies.

TorsinB expression in the developing human brain.

Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein, which is restricted to neuronal cells and present in all brain regions by the age of 2 months has been described recently in human developing brain. TorsinB is a member of the same family of proteins and is highly homologous with its gene adjacent to that for torsinA on chromosome 9q34. TorsinA and torsinB share several remarkable features suggesting that they may interact in vivo. This study examined the expression of torsinB in the human brain of fetuses, infants and children up to 7 years of age. Our results indicate that torsinB protein expression is temporarily and spatially regulated in a similar fashion as torsinA. Expression of torsinB protein was detectable beginning at four to 8 weeks of age in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia and was predominantly restricted to neuronal cells. In contrast to torsinA, torsinB immunoreactivity was found more readily in the nuclear envelope. High levels of torsinB protein were maintained throughout infancy, childhood and adulthood suggesting that torsinB is also needed for developmental events occurring in the early postnatal phase and is necessary for functional activity throughout life.

[The Pediatric Musculoskeletal Functional Health Questionnaire. A function assessment questionnaire for detection of illnesses of the locomotor system in children and adolescents--initial results of validating a German version]. / Pediatric Musculoskeletal Functional Health Questionnaire. Ein Funktionsfragebogen zur Erfassung von Erkrankungen des Stütz- und Bewegungsapparates bei Kindern und Jugendlichen--Erste Ergebnisse der Validierung einer deutschen Version.

AIM: It was the purpose of this investigation to create a German version of the Pediatric Musculoskeletal Functional Health Questionnaire and to test its reliability, practicability and acceptance in children and adolescents with musculoskeletal disorders. METHODS: In a first step, the Pediatric Musculoskeletal Functional Health Questionnaire was translated into the German language. Then 147 patients with musculoskeletal disorders or respectively, their parents were asked to fill in the questionnaire, in order to test the reliability, the internal consistency, the practicability, and the acceptance of this instrument. RESULTS: The test-retest reliability for the subscales was high, it ranged between r = 0.56 and 0.93. Concerning the internal consistency of items and subscales we found only moderate results. The acceptance of the Questionnaire was high in patients or, respectively, their parents with 92%. Furthermore, the instrument has shown to be practicable and economical. CONCLUSION: With the German version of the Pediatric Musculoskeletal Functional Health Questionnaire a multidimensional instrument is now available that reliably measures health status as well as therapeutic effects in children and adolescents with musculoskeletal disorders.