Andreas Mohr

Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect

Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24−/−) have indicated a role for Zmpste24 in the processing of CAAX-type prenylated proteins. Here, we report the pathologic consequences of Zmpste24 deficiency in mice. Zmpste24−/− mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures—akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in Zmpste24−/− mice. Zmpste24−/− mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated CAAX protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle weakness in Zmpste24−/− mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.

Brodie abscess: another type of chronic posttraumatic osteomyelitis

distal humerus pain. No other symptoms or physical findings were found at the initial evaluation. The results of laboratory tests, including hematocrit concentration, sedimentation rate, leukocyte count, and serum blood chemistry profiles, were normal. The anteroposterior and lateral radiographs showed a rounded osteolytic diaphyseal lesion surrounded by an important sclerotic reaction and associated with mild L E T T E R T O T H E E D I T O R

Value Of Micro-Ct As An Investigative Tool For Osteochondritis Dissecans: A preliminary study with comparison to histology

Purpose: To evaluate micro computed tomography (micro-CT) for the assessment of osteochondritis dissecans in comparison with histology. Material and Methods: Osteochondritis dissecans lesions of 3 patients were evaluated using micro-CT (0.125 mA, 40 keV, 60 μm slice thickness, 60 μm isotropic resolution, entire sample) and light microscopy (toluidine blue, 3–5 μm slice thickness). The methods were compared regarding preparation time, detectability of tissue types and morphologic features of bone and cartilage. Results: Non-destructive micro-CT imaging of the entire sample was faster than histologic preparation of a single slice for light microscopy. Morphologic features of bone and cartilage could be imaged in a comparable way to histology. It was not possible to image cells or different tissue types of bone and cartilage with micro-CT. Conclusion: Micro-CT is a fast, non-destructive tool that may be a supplement or, if detailed histologic information is not necessary, an alternative to light microscopy for the investigation of osteochondritis dissecans.

Phenotypic characterization of skeletal abnormalities of Osteopotentia mutant mice by micro-CT: a descriptive approach with emphasis on reconstruction techniques.

PurposeThe novel protein osteopotentia (Opt) has recently been described as an essential regulator of postnatal osteoblast maturation and might possibly be responsible for some of the rarer types of osteogenesis imperfecta. Our aim was the evaluation of micro CT for the qualitative morphological assessment of skeletal abnormalities of Osteopotentia-mutant mice in comparison to radiography and histology.Materials and methodsFour homozygous mice with insertional mutations in the Opt gene and three wild-type controls were examined ex vivo using radiography and micro-CT. Two of the homozygous animals were evaluated histologically (trichrome reagent). For the micro-CT evaluation three-dimensional (3D) surface reconstructions and two-dimensional (2D) multiplanar reformations (MPRs) were applied.ResultsThe Opt-homozygous mice exhibited severe growth. The radiographic examinations showed osteopenia and fractures with hypertrophic callus formation and pseudarthroses of the forelimbs and ribs. Micro-CT confirmed these findings and was able to demonstrate additional fractures especially at smaller bones such as the metacarpals and phalanges. Additional characterization and superior delineation of cortices and fracture fragments was achieved by 2D MPRs. Histological correlation verified several of these imaging findings.ConclusionMicro-CT is able to screen Opt-mutant mice for osseous pathologies and furthermore characterize these anomalies. The modality seems superior to conventional radiography, but is not able to demonstrate cellular pathology. However, histology is destructive and more time- and material-consuming than micro-CT. Additional information may be gathered by 2D MPRs.

Micro-CT of Carotid Arteries: A Tool for Experimental Studies

Micro-computed tomography (micro-CT) is a high-resolution, nondestructive tool for two- and three-dimensional imaging and quantification. The ability of this technique to assess atherosclerosis of the carotid artery was evaluated in three human cadaver samples based on the original axial acquisitions, multiplanar reconstructions and volume rendering techniques. Quantitative analysis included the calculation of: (1) the original lumen perimeter, original lumen area, plaque area, residual lumen area, calcified area and gross sectional area reduction of the vascular lumen from two-dimensional slices; (2) the total tissue volume, soft tissue volume and calcified tissue volume from the three-dimensional data set. This preliminary study demonstrates the potential of micro-CT as a supplementary method for the two- and three-dimensional ex vivo evaluation of carotid atherosclerosis.

Imaging in rheumatology

Almost 60 contributors collaborated with the editors to produce this first edition on imaging of the rheumatic diseases. The great majority of the contributors are from the UK, with most of them working in departments of rheumatology. The aim is to provide the rheumatologist as well as the radiologist with a comprehensive review of the currently available imaging modalities. The editors’ purpose was to outline how these methods are used to investigate rheumatic symptoms and in the long term management of patients with diverse diseases of joints, muscles, and bones. There are three sections. The first six chapters focus on modes of imaging and provide the reader, especially the non-radiologist, with a background of knowledge of the available methods. The five chapters …