Identification of protein pattern in kidney cancer using ProteinChip arrays and bioinformatics

Tumor biology of renal cell carcinoma (RCC) is not very well understood, although many studies on molecular and cellular biology have been performed. It is accepted now that cancer research has to be performed also with proteomic tools, because proteins are the real actors in the genesis and progression of cancer. Therefore, we used a ProteinChip System(R) (SELDI) which is able to detect minute amounts of protein and moreover to analyze a complex protein pattern. We analyzed 37 cases of clear cell RCC as a training set including corresponding normal tissue. From all samples protein lysates were made and spotted directly on different chip surfaces (SAX2, WCX). After a washing procedure the arrays were analyzed in the ProteinChip Reader. All profiles were subjected to a bioinformatical analysis including normalization, clustering, rule extraction and rating. Defined rules (markers) were evaluated using a test set of 24 samples (13 tumor tissues and 11 normal kidney tissues). The generated rule base for the SAX2 surface showed a sensitivity of 100% and a specificity of 97.3%. For the WCX arrays the optimal rule base showed worse results. A combined rule base for SAX2 and WCX did not result in a higher sensitivity or specificity. Using the optimal rule base for the SAX2 chip in the test set, sensitivity and specificity reached 76.9% and 100%, respectively. The ProteinChip System represents a key technology for the rapid detection of cancer specific proteomic patterns. It is possible to identify clear cell renal cancer with high sensitivity and specificity from minimal amounts of cells.     

Establishment and characterization of an Epstein-Barr virus transformed cell line with strong phagocytic activity

An immunoglobulin M (IgM)-positive cell line, Ms 28, apparently spontaneously transformed by Epstein-Barr virus (EBV) was established from peripheral blood cells of a patient with immature myeloblastic leukemia. It has been characterized according to phenotype, cytochemistry, and membrane antigen pattern. The cell line expresses lymphoid markers like CD 19, CD 22, and CD 30 and synthesizes and secretes IgM. Monocyte markers CD 11c, CD 14, and CD 15 are absent. Neither interleukin-1 (IL-1), nor tumor necrosis factor (TNF-alpha) are produced. But Ms 28 cells show strong phagocytic activity and engulf Latex particles and sheep RBCs (SRBCs) that need not to be opsonized. The phagocytic activity can be inhibited by chloroquine. Both phagocytosis and EBV nuclear-antigen (EBNA) expression can be observed in one and the same cell. Ms 28 cells might be useful to study immunologic activities like antigen processing and presentation.     

Veränderung einer Stichprobe ≥60-jähriger Krankenhauspatienten nach 5 Jahren: Ergebnisse der ELDERMEN-Study

METHOD: The ELDERMEN Study, which was funded by the German Research Association, comprises baseline assessment during 1994-1997 and a second assessment during 2000-2002. A total of 261 in-patients participated in an extensive examination at baseline assessment and were contacted again five years later. RESULTS: Five years after baseline assessment, 135 former participants had deceased, 29 newly fulfilled exclusion criteria. Of the 97 individuals who matched the study's inclusion criteria at the second assessment, 74 participated in the second evaluation. Baseline assessment revealed no significant differences between participants at second assessment and those persons who refused the second participation. However, participants in the extensive examination and longitudinal design were a positive selection when compared to the whole baseline sample. DISCUSSION: Because of increasing morbidity and mortality, longitudinal gerontological studies have to deal with the problem of selective diminishment of the sample, which can endanger the validity and generalizability of results. The problem has to be dealt with by careful documentation and evaluation of selectivity effects.We focus on the problems of longitudinal studies in gerontologic research and examine the longitudinal development of a sample of geriatric in-patients aged > or = 60 years.     

Proteomic profiling in microdissected hepatocellular carcinoma tissue using ProteinChip technology

At present, the molecular mechanisms of hepatocellular carcinogenesis are not well understood. It is known, however, that cancer development and progression are accompanied by profound changes at the cellular and subcellular level, involving RNA/DNA and protein structure and function. Therefore, high-throughput, proteomic techniques targeting these biological molecules may provide novel insights into HCC genesis and prognosis. We characterized tissue protein profiles from 10 HCC patients using ProteinChip technology (SELDI) which is able to detect minute amounts of proteins and moreover to analyze complex protein pattern. Therefore, after histopathological examination, proteins from kryostat sections of non-tumorous hepatic tissue as well as from central and peripheral tumor areas were isolated from complete histological sections or from selected and microdissected tissue areas. Analysis on the SAX and WCX ProteinChip Arrays revealed 14-26, and 25-29 differentially expressed peaks respectively, which characterized non-tumorous and tumor tissue (p< or =0.05). One feature which allows differentiation between central tumor and peripheral tumor regions could only be detected in microdissected tissue. Using ProteinChip technology in combination with tissue microdissection it is possible to investigate complex changes at the protein level in hepatocellular cancer associated with tumor development and progression.     

Pyoderma gangrenosum in a patient with autoimmune haemolytic anaemia and complement deficiency

About 50% of cases of pyoderma gangrenosum (PG) are associated with a variety of systemic diseases. We describe a patient with severe PG on both legs who suffered from an autoimmune haemolytic anaemia in association with a congenital deficiency of complement factors C2 and C4. To the best of our knowledge, this constellation has not been previously reported.     

Die Physiologie der tierischen Form

Ohne Zusammenfassung     

Eine neue Widerlegung der mechanistischen Lebenstheorie

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