L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

AIM: To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. METHODOLOGY: Human teeth were sectioned transversely into 600-µm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. RESULTS: Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with L-mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 levels (P < 0.05). CONCLUSIONS: The prolyl hydroxylase inhibitor L-mimosine increased VEGF production via HIF-1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.

[Congenital and other myopathies]. / Kongenitale und andere Myopathien.

The myopathies presented here fall into two groups: Congenital myopathies and protein aggregate myopathies. These genetic conditions often require all modern diagnostic investigations, including histology, enzyme histochemistry, immunohistochemistry and electron microscopy to pave the way to an adequate individual molecular analysis and diagnosis. This is necessary to provide the patient and his or her family information about disease-characteristics or even disease-specific features. Distal myopathies, although caused by mutations in different genes, and toxic myopathies as acquired neuromuscular conditions largely provide non-specific morphological features a correct nosological interpretation of which only succeeds with additional non-morphological data.

Macrophagic myofasciitis plus (distinct types of muscular dystrophy).

Macrophagic myofasciitis (MMF) is a well-known lesion following vaccination with aluminium-containing vaccines. It has abundantly been reported in adults and several times in children, often in single patients or in rather small cohorts. Only few of these published reports on children have shown distinct myopathology of another neuromuscular disease except for MMF. Indications for biopsy often were nondescript clinical features in children, such as hypotonia or delay in motor development but, apparently, never that of suspected MMF. Thus, in previous reports as well as in our two patients, encountering MMF in the biopsied tissue specimens was coincidental. Our two unrelated patients with MMF also had two separate types of muscular dystrophy, a merosinopathy and dystrophinopathy, showing a combination of myopathologically well-defined neuromuscular diseases, muscular dystrophies and MMF. Detecting such a combination of two separate conditions may, in the future, be rare when non-invasive techniques, e. g., genetic, will have replaced muscle biopsy in ascertaining hereditary neuromuscular conditions, especially in children.

Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques.

AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL, METHODS: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.

Inflammatory infiltrates in the spinal cord of patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is defined as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) of the peripheral nervous system. Reports on central nervous system involvement in patients with GBS are rare and the histopathological analysis was usually restricted to conventional staining techniques. We were able to investigate four cases with GBS at autopsy in respect to the inflammatory infiltrates and histopathological changes in the spinal cord by immunohistochemistry using a panel of antibodies recognizing lymphocytes and different macrophage-activation antigens. There were increased inflammatory cell infiltrates comprising lymphocytes and macrophages in the spinal cord of two cases. In one of these two cases, GBS predominantly affecting the motor system similar to acute motor axonal neuropathy (AMAN) developed following hepatitis B vaccination; in the second one, GBS developed rapidly 4 days after onset of intravenous purified GM1-ganglioside application affecting the motor as well as the sensory system, resembling acute motor sensory axonal neuropathy (AMSAN). Impairment of the spinal anterior horn cells with their axons was suggested to be responsible for prolonged motor symptoms and the predominantly axonal type of neuropathy at least as a late-stage feature in these two cases with fatal outcome. Insignificant cellular infiltrates in the spinal cord were noted in the other two GBS cases. Focal cellular infiltration of spinal nerve roots and meninges was similar in all cases.

Acute onset of hemorrhagic leukoencephalomyelitis (Hurst) in the spinal cord.

Acute hemorrhagic leukoencephalomyelitis is considered to be a rare autoimmune disorder. The present case, a 34-year-old male, developed non-specific symptoms 3 weeks after surgical removal of his meniscus and following an inconspicuous infection of the upper respiratory tract. The spinal cord was the first to be affected, followed by symptoms of headache, nausea and fever which reached 39.4 degrees C. Autopsy revealed acute hemorrhagic leukoencephalomyelitis with marked involvement of the spinal cord. Diagnosis was established by histopathological examination of the brain and spinal cord. This is the first description of the onset of this disease in the spinal cord.

Dominantly inherited myopathy with novel tubular aggregates containing 1-21 tubulofilamentous structures.

Tubular aggregates (TAs) in skeletal muscle fibers have been observed as a nonspecific finding in a number of different conditions such as periodic paralysis, myotonic disorders, hyperaldosteronism, chronic use of drugs, and alcoholism. However, TAs were also found more specifically in well-defined muscle disorders, e.g., exercise-induced cramps, myasthenic syndromes, and even in dominantly or recessively inherited familial myopathies. We report on a presumably dominantly inherited familial myopathy with late onset characterized morphologically by the presence of three types of TAs in type II muscle fibers identified in three affected members of one family (a 86-year-old man and his two sons). The first, novel type was characterized by tubules, 30-200 nm in thickness which included 1-21 tubulofilamentous structures 14-18 nm in diameter. The second type of TAs corresponded to previously well-described tubules and were derived from terminal cisternae, which were rather irregularly arranged or widened, and filled with material of medium electron density. The third type of TAs were occasional, hexagonally arranged TAs of the usual type [type Ib and Ic]. Rare annulate lamellae were also seen. Our findings support the evidence of tubular aggregates as the major finding in certain dominantly inherited myopathies. Tubules of the first type, to the best of our knowledge, have not been recorded in any other myopathy. It is therefore suggested that these tubules characterize a novel type of a benign, slowly progressive myopathy with late onset, muscle pain, cramps, and stiffness.

Hereditary motor and sensory neuropathy with absence of large myelinated fibers due to absence of large neurons in dorsal root ganglia and anterior horns, clinically associated with deafness, mental retardation, and epilepsy (HMSN-ADM).

Hereditary motor and sensory neuropathy (HMSN) with autosomal recessive inheritance represents a genetically heterogeneous group of disorders with variable clinical, pathologic and electrophysiologic manifestations. A new variant of autosomal recessive HMSN, clinically defined by sensorimotor polyneuropathy associated with deafness and mental retardation, has recently been described. We report on the first autopsy case with this type of HMSN: a girl of non-consanguineous parents with a presumably autosomal recessive type of motor and sensory neuropathy clinically associated with deafness, mental retardation, and epilepsy. The autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves corresponding to a lack of large neurons in dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of the cerebellum. Molecular genetic analyses in our case revealed neither genetic alterations in the survival motor neuron gene nor in the PMP-22 gene.

[The chemical composition of "zymosans" from yeasts]. / Uber die chemische Zusammensetzung von "Zymosanen" aus Bäckerhefe.

The chemical composition of "Zymosanes" (complex cell-wall-polysaccharides), prepared by different methods from Baker's yeast, were analyzed by classical and modern techniques, e.g. GLC and TLC. They are very complex natural products consisting of a basic structure of polysaccharides, which proteins and different lipids are bound to. Higher purified zymosanes seem to be free from nucleic acids and do not contain sialic acid.

[Pilar tumor of the scalp. Case report and study of 59 cases]. / Pilartumor der Kopfhaut. Fallbericht und Studie über 59 Fälle.

The pilar tumor occurs mainly in elderly women. It is a solitary lesion, localized on the scalp in most cases. In spite of the usually long course of the disease, pilar tumors very rarely metastasize. Small tumors look like "sebaceous cysts", large and very large tumors are diagnosed as squamous cell carcinomas. In these cases one could directly come to the right diagnosis if sex, age and localization do correspond. Microscopic examination reveals interlacing lobules of squamous eqithelium that undergo in their center abrupt keratinization of pilar or trichilemmal cysts. The pilar tumor, therefore, keratinizes like the middle portion of the outer root sheath. Our own case shows the typical above-mentioned clinical and histological signs of the pilar tumor.

[Morphea resembling pseudoxanthoma elasticum in progressive scleroderma]. / Pseudoxanthoma elasticum-artige Morphaea bei progressiver Sklerodermie.

Lesions of circumscribed scleroderma clinically appeared as pseudoxanthoma elasticum. The histological structure, however, revealed circumscribed scleroderma. The sclerodactyly, Raynaud's phenomenon, acrosclerosis and the laboratory results suggested systemic sclerosis.