Genetic analysis of immunomodulating factors in sporadic Parkinson's disease.

Immunomodulating factors have been shown to play a role in the pathogenesis of Parkinson's disease (PD) by biochemical methods. In order to investigate functionally important genes of the tumor necrosis factor alpha (TNFalpha) pathway we studied the frequency of DNA polymorphisms in the interleukin 6 (IL6), the TNFalpha, and the TNFalpha receptor 1 (TNFR1) genes in 264 sporadic German PD patients and in 183 age and sex matched German healthy controls. Analyzing the TNFalpha-308 polymorphism we found heterozygous individuals carrying alleles 1 and 2 more frequently in patients with a relative risk of 1.56 (p = 0.046, p(c) = 0.13, chi2 = 3.98). In contrast, the frequency of the B/2 haplotype described by the TNFR1-609 and TNFRI+36 polymorphisms was significantly decreased in our PD patients group (p = 0.0097, p(c) = 0.048, chi2 = 6.69) with a relative risk reduced to 0.52. Our results suggest an involvement of immunomodulating factors in the pathogenesis of sporadic PD as revealed by a molecular genetic approach.

Increased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, alpha-synuclein (alpha-SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of alpha-SYN and apolipoprotein E, which is a major risk factor for late-onset Alzheimer's disease, prompted us to investigate the influence of different alpha-SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the alpha-SYN gene (NACP-Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apo epsilon4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early-onset PD patients (age at onset, <50 years) than in late-onset PD. Regarding the combination of the Apo epsilon4 allele and allele 1 of the alpha-SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8-fold increased relative risk for developing PD during their lives.

[Idiopathic multicentric osteolysis and the delimitation of the cranio-carpal-tarsal-osteolysis syndrome]. / Idiopathische multizentrische Osteolyse und die Abgrenzung des cranio-carpo-tarsalen Osteolyse-Syndroms.

It is shown in the example of a 36 year old female patient with progressive but mainly carpotarsal osteolysis to analyse the radiological and clinical delimitation to other osteolysis-syndromes. Over 35 years during infancy and adolescence the clinical picture was incorrectly related to the "Freeman-Sheldon-Syndrome" and was twice the cause for fruitless attempts to classify. Although no standardized classification or rather grouping of the osteolysis exist, now with means of systematically radiological diagnostic and by long clinical follow-up of over 35 years a definite enrollment of the case represented, proved to be an extreme rare form of idiopathic multicentric osteolysis with nephropathy. It can be listed now as the 13th case in the literature.

[Synovial sarcoma in childhood. A case report]. / Synoviales Sarkom im Kindesalter. Ein kasuistischer Beitrag.

Synovial sarcomas or malignant synovialomas are among the soft-tissue sarcomas rarely encountered in children. The few cases described in the literature are reviewed and a case observed by the authors is presented together with the differential-diagnostic, histological and therapeutic problems it posed.

[Myositis ossificans following extensive burns]. / Myositis ossificans nach ausgedehnter Verbrennung.

A report on a case of myositis ossificans following 50-60% burns (second to third-degree) on the trunk and extremities with periarticular localization of the ossification at the hip and knee joints. In terms of its extent and localization the ossification is primarily similar to post-paraplegic ossification of soft tissues.

Glass-ceramic coated implants. A simple model for a loaded hip prosthesis with a bioactive interface.

The favorable histological results at the bone-implant-interface of glass ceramic material are well-known. The mechanical properties of the solid material limit it's application for implants. Therefore metallic hip implants had been coated by glass ceramic granules, by a special technique, to transfer the bioactive property of the glass ceramic on to the metal stem. The following loaded experiments in rabbits with a simple model of a hip endoprosthesis showed a direct and tight bonding between implant surface and surrounding new bone formation. These findings demonstrate a possibility to anchor a joint endoprosthesis without the use of bone cement.

[Multiple cartilaginous exostoses with polyposis of stomach and colon: a new, hereditary combination different from Gardner's syndrome (author's transl)]. / Multiple kartilaginäre Exostosen bei Kolon- und Magen-Polypose. Mitteilungen einer neuen, vom Gardner-Syndrom abweichenden erblichen Kombinationserkrankung

Multiple cartilaginous exostoses were found in a 41-year-old man and his two sons, aged 11 and 15 years. The older boy had extensive polyposis of the sigmoid colon and gastric antrum, his brother had radiological changes suspicious of sigmoid polyposis, while there was no radiological evidence of polyposis in the father. None of them had any symptoms of polyposis. The described combination of findings suggests a separate entity from Gardner's syndrome, perhaps on the basis of a combined dominant gene inheritance. In case of multiple exostoses radiological and endoscopic examination of the gastro-intestinal tract for polyposis are indicated.