Genetic Mechanisms of Tumourigenesis in von Hippel-Lindau-Associated Tumours with the Emphasis on Capillary Hemangioblastoma

The von Hippel-lindau (VHL) disease is a dominantly inherited neoplastic disorder which predisposes patients to multiple tumours including capillary haemangioblastomas (CHBs), pheochromocytomas (PCCs), renal cell carcinomas (RCCs). CHBs are the most common manifestations of VHL disease, occurring sporadically or as a manifestation of VHL disease. Inactivation of the VHL gene at 3p25-26 is believed to cause both familial and sporadic VHL-associated tumours and germ-line mutation of the VHL gene have been detected in 100% of the CHBs studied. However, a limited number of sporadic CHBs, PCCs display VHL inactivation. Other molecular alterations involved in tumourigenesis of sporadic CHBs, PCCs remain largely unknown. The purpose of the present work was to search for genetic alterations, or other mechanisms of inactivation, in addition to the VHL gene, that may be important in the development of VHL-associated tumours. Though less satisfactory than cure, prevention and early detection are the most promising and feasible means reducing cancer morbidity and mortality. This work is based on the view that increasing knowledge about the molecular events underlying tumour development will eventually aid in early detection and lead to improved treatment. We evaluated a large set of VHL-associated patients, searched for a clinical and radiologic signs of the disease. We succesfully performed a germ-line mutation analysis and characterised three patient groups, VHL, suspect VHL and sporadic, a germ-line mutation analysis revealed a 50% mutation rate only in the VHL groups, no sporadic or suspect cases displayed any mutation. We also utilized comparative genomic hybridization (CGH) to screen for DNA copy number changes in both sporadic and VHL-associated CHB. Our analysis revealed (27%) DNA copy number losses. The most common finding was loss of chromosomal arm 6q, seen in (23%) cases, No differences were noted between VHL-associated and sporadic tumours. Furthermore a loss of heterozygosity (LOH) study on chromosome 3p and 6q was done with the purpose to determine allele losses not observable by CGH, and to uncover the location of putative tumour suppressor genes important in CHB and PCC tumourigenesis. We identified loss of chromosome 6q and a minimal deleted area at 6q23-24 in CHBs. We also showed LOH at 6q23-24 in PCCs and identified the ZAC1 (6q24-25) as a candidate gene, ZAC1 is a maternally imprinted tumour suppressor gene with anti proliferative properties. To study further the role of ZAC inactivation in CHBs, we investigated LOH, promoter hypermethylation and expression status of the ZAC1 gene in mainly sporadic CHBs. Our LOH analysis revealed that the majority of the tumours with allele loss. The gene promoter methylation analysis similarly detected predominance of the methylated ZAC sequence in almost all tumours. Immunohistochemistry exhibited a strongly reduced expression of ZAC in stromal cells of all CHBs studied. Our current results indicate that the absence of the unmethylated, ZAC1 promoter sequence was highly concurrent with LOH for the ZAC1 region or 6q loss. This observation together with lack of ZAC expression, points to preferential loss of the non imprinted, expressed ZAC allele in CHB, in summary, our series of studies reveal a new chromosomal region 6q, emphasizes the importance of ZAC1 gene in the development of CHB and PCC, particularly in non-VHL associated cases.

Outdoor portrait of Erich von Kahler.

Digital Image

Historian Herbert Strauss with CDU Mayor of West Berlin, Richard von Weizsacher.

Digital Image

Eine Erinnerung an den Geburtstag von Frau Sobernheim (in memory of Mrs. Sobernheim's birthday); Wiesbaden Portraits Groups Women

Image 200 participants include Erna Behr, Lenka Bederheimer, Paula Arendt, Elsa Trum, Hedwig Trum, Ruth Rosenau, Johanna Schoenmann and Martha Bruchfeld

Dr. Curt Bejach, Stadtarzt von Berlin-Kreuzberg 1922-1933 portraits men

Dr. Curt Bejach was town physician of Berlin-Kreuzberg 1922 - 1933. He was born on Dec. 20, 1890, and died in Auschwitz in 1944

[Gedichte von Else Bergmann] 1930-1948

Photocopies of poems

[Testament von Selig Rosenthal und dessen Ehefrau Regine Rosenthal, geb. Michael].

Handwritten last will and testament (photocopy and typed transcript) of Selig Rosenthal and his wife Regine Rosenthal, née Michael, Gleicherwiesen (Thuringia, Germany), 1860.

Lernen im Team: Zusammenhänge zwischen Personen- und Teammerkmalen und der Leistung von Multiplikatoren [Learning in teams: Relationships between individual and team characteristics and the performance of multipliers]

The continuous mutual transfer of knowledge and skills within work teams is increasingly important for organizational practice. According to the situational and experience-based approaches of applied learning research, certain individual and social prerequisites have to be met for successful learning in teams. In a field study at an automobile production site, it was investigated which personal characteristics of multipliers and which characteristics of teams are related to the performance of multipliers in 31 teams with 291 coworkers. Using multi-level analyses (HLM), the amount of variance explained by the predictor variables in teaching success of multipliers and learning success of coworkers was examined. Results showed that multipliers' conscientiousness and team cohesion were related to teaching success of multipliers; extraversion and team cohesion were related to the learning success of coworkers. In closing, the scientific and practical implications for the investigation and promotion of work-based learning processes in teams are discussed.

Die Darstellung von Schwefeltetrafluorid aus den Elementen bei tiefer Temperatur in einem inerten Lösungsmittel

Schwefeltetrafluorid läßt sich in reiner Form in einer CCl3F-Lösung durch direkte Fluorierung von elementarem Schwefel bei -78°C in hoher Ausbeute darstellen.

Familiengeschichte und Lebenserinnerungen 1800-1937

Genealogy reaching back to his great-grandparents in 18th century; history of the family's wine business until its liquidation in 1931; primary and secondary education; military service; activities in various associations; president of the "Israelitische Oberkirchenbehoerde" (Federation of Wuerttemberg Jewish communities); information about Stuttgart Jewish community.

How do you like America? 1800-1940

The memoirs were written in 2000 in California and contains some of the author's diary entries during the years of the family's emigration and reminiscences of the author's father. Detailed description of family history going back to the early 19th century. The author's grandfather Moses Stern had a rawproduct business in Gelsenkirchen, Westphalia. His father Max Stern took his graduate exam (Abitur) at the Jacobsohn boarding school in 1904 and was sent to a business school in Brussles, Belgium. Work in the family business M. Stern AG. World War One and rise of the family business with branches throughout Germany and offices in New York, London, Milan and Stockholm. Due to political unrest at the end of the war the business administration moved to Essen. Description of the family background of Beate Herzberg, the author's mother. Courtship of his parents and marriage in 1922. Birth of his sister Annelore in 1923. Martin Stern was born in 1924. Description of the family household and domestic life in a well-to-do family the 1920s. Friday visits to the synagogue and celebration of Jewish holidays. Vacations at the North sea and skiinig in the Alps. Martin attended a Jewish elementary school. Rising National Socialism. After Hitler came to power in 1933 the author's father immediately started preparations for the family's emigration, but was persuaded to stay by his family. Life under National Socialism. Martin attended Gymnasium and was one of only two Jewish students in his class. Antisemitic incidents. Private lessons in piano and Hebrew. Bar Mitzvah in 1937. Recollections of performances of the Kulturbund.

In search of Gustav: The story of the Lilienfeld (later Lynfield) family covering the last 200 years 1800-1920

This is the first of three books about the history of Geoffrey Lynfield's family. It is about four Lilienfeld brothers--Geoffrey Lynfield's grandfather and his brothers. They were born in the Jewish enclave of Marburg and ended up in South Africa when and where the first diamonds were discovered. The manuscript also includes photographs and documents.