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Biomedical subjects

H H Neumann

Publications and source records attributed to H H Neumann.

At least 19 recordsLinked to original sources

Complement factor H and hemolytic uremic syndrome.

Factor H is a 150 kDa single chain plasma glycoprotein that plays a pivotal role in the regulation of the alternative pathway of complement. Primary sequence analysis reveals a structural organization of this plasma protein, in 20 homologous units, called Short Consensus Repeats (SCRs), each about 60 amino acids long. Biochemical and genetic studies show an association between factor H deficiency and human diseases, including Systemic Lupus Erythematosus, susceptibility to pyogenic infection and a form of membranoproliferative glomerulonephropathy. More recently, factor H deficiency has also been associated with susceptibility to Hemolytic Uremic Syndrome (HUS), a disease consisting of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, caused by platelet thrombi which mainly, but not exclusively, form in the microcirculation of the kidney. In this review, we summarize recent genetic and biochemical data, which indicate a critical role for factor H in the pathogenesis of HUS and suggest an important role of the most C-terminal domain, i.e. SCR 20, in the disease. In addition, we discuss the physiological consequences of these findings, as novel functional data show a particular essential role of SCR 20 of factor H as the central discriminatory and regulatory site of this multidomain, multifunctional plasma protein.

Complement Factor H↗

Target volume definition and target conformal irradiation technique for breast cancer patients.

The aim of this study was to present the target volume and irradiation technique in the most complex situation where the breast or chest wall and the locoregional lymphatics (mammaria interna lymph nodes, axillary and supraclavicular lymph nodes) have to be irradiated. The study comprised 125 breast cancer patients treated with curative intent after primary surgery in the last two years at our institute. In 62 cases the target volume included the breast or chest wall and the locoregional lymphatics, which were treated using our irradiation technique. The target conformal irradiation technique is a multiple non-opposed beams one isocenter technique developed to protect the heart and lungs. This technique, consisting of several rotation beams modulated with wedge filters and individual lung absorbers as well as additional fixed beams, was used in our study to apply a homogeneous dose of 46 to 56 Gy to the target volume; the irradiation technique was optimized by means of dose-volume histograms. After pre-localization, the patients underwent computerized tomographic scanning, with sections at 1.0 cm intervals. Contouring of target volume and organs at risk was carried out with a MULTIDATA workstation for regions of interest (mammaria interna and/or axillary and/or supraclavicular lymphatics and the breast or chest wall) as well as the organs at risk, such as heart and lung parenchyma. Planning target volume coverage was examined by three-dimensional isodose visualization for all CT axial sections for each patient. To determine the incidence of acute or late side effects on the lung parenchyma, conventional chest x-rays and CT studies were carried out at 1 month, 3 months and 6 months after completion of radiotherapy. Dose-volume histogram analysis revealed that this irradiation technique permits the application of a homogeneous dose to the target volume, conforming to the ICRU norms. The maximum dose applied to the ipsilateral lung parenchyma was less than 50-70% of the prescribed dose in the target volume. For left-located primaries, the highest dose applied to the myocardium is less than 30-50% of the dose in the target volume. Acute side effects, such as radiation pneumonitis, were noted in 8% (5/62) of the treated patients. Late side effects (grade I) in the lung were observed in 6.4% of the patients (4 patients) and occurred only in areas that had received more than 70% of the prescribed dose. We conclude that it is possible to apply a homogeneous dose distribution with a one isocenter multiple beams irradiation technique to the most complex target volume, such as the breast or chest wall and the locoregional lymphatics, with a minimum of side effects guaranteed.

Adult↗

Cytogenetic and fluorescence in situ hybridization studies on sporadic and hereditary tumors associated with von Hippel-Lindau syndrome (VHL).

We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel-Lindau [correction of Landau] disease. Four of five renal cell carcinomas with detectable alterations showed clones with chromosome 3 alterations. These changes led to loss of genetic material visible with cytogenetic resolution: either an unbalanced translocation involving 3p or loss of a whole homolog 3, resulting in monosomy of 3p. We have previously mapped the VHL gene to chromosomal region 3p25-p26. We applied FISH using the single copy probes cA233 and cA479, sequences close to the VHL gene, in a search for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were located within bands 3p25-26. FISH with single copy probes for interphase cytogenetics detected four subclones with deletions in the VHL region in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, especially helpful in detecting tumor subclones in benign and slowly growing tumors.

Adrenal Gland Neoplasms↗

Legalingo.

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Jurisprudence↗