Cholecystektomie und experimentell erzeugtes Dickdarmcarcinom

Zusammenfassung Die experimentelle Studie gilt dem Coloncarcinom und dem Problem seiner möglichen Entstehung nach einer vorausgegangenen Cholecystektomie. Die Ergebnisse zeigen, daß die 1,2-Dimethylhydrazin (DMH) induzierte Dickdarmkanzerogenese der Maus durch die Entfernung der Gallenblase signifikant gesteigert werden kann. 70% der cholecystektomierten Tiere, denen 10mal 15 mg/kg DMH subcutan injiziert wurde, hatten nach 20 Wochen einen Dickdarmkrebs. Dagegen wiesen nur 16% der nichtoperierten Tiere (bei sonst gleichen Bedingungen) ein Coloncarcinom auf. Als Ursache des karzinogenen Einflusses der Cholecystektomie wird die verstärkte Bildung sekundärer Gallensäuren durch die Darmbakterien, sowie der Fortfall der Resorptionsständigkeit der Gallenblase für lebergängige Karzinogene diskutiert. Den klinischen Hintergrund für diese experimentelle Studie bildet die Tatsache, daß 10% aller Dickdarmkrebskranken in der chirurgischen Anamnese eine Cholecystektomie aufweisen.

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Cholecystectomy and experimental coloncarcinoma

Summary The influence of cholecystectomy on the development of carcinoma of the colon is investigated. The experimental results show a significant high rate of carcinoma of the colon induced by subcutaneous injection of 1,2-Dimethylhydrazin (DMH) in the mouse after cholecystectomy. After 10 weekly injections of 15 mg/kg DMH 70% of the animals with cholecystectomy developed carcinoma. Only 16% of the mice with similar treatment but without cholecystectomy had carcinoma. The cocarcinogenic effect of cholecystectomy is assumed to be due to the increased production of secondary bile salts by the colonic bacteria and the lacking of the resorptive function of the gall bladder for some carcinogenic substances passing through the liver. The background of this experimental studies is the clinical findings that 10% of patients with carcinoma of the large bowels had a cholecystectomy previously.

     

Zur Ultrastruktur der Nebennierenrindentumoren beim Cushing-Syndrom

Zusammenfassung Vier Nebennierenrindenadenome und ein Nebennierencarcinom bei einem Cushing-Syndrom wurden licht- und elektronenoptisch untersucht und mit hormonalen Parametern verglichen. Es lassen sich vorwiegend spongiocytäre Adenome, die durch einen hohen Gehalt an Liposomen gekennzeichnet sind, von kompaktzelligen Adenomen mit reichlicher Ausbildung Steroidhormon-produzierender Zellorganellen unterscheiden. Letztere entsprechen einem hohen Funktionsgrad, während die spongiocytären Adenome eher als Speicherformen anzusehen sind und sich durch ACTH stimulieren lassen. Die Ultrastruktur aller Adenomzellen zeigte bei Zunahme des granulären endoplasmatischen Reticulum und Pleomorphie der Mitochondrien deutliche Abweichungen von der normalen Fasciculata-Reticulariszelle und von der hyperplastischen Nebennierenrinde bei Cushing-Syndrom. Bei der Abgrenzung des Carcinoms vom Adenom ließen sich dagegen ultrastrukturell lediglich graduelle Unterschiede aufzeigen. Sowohl in kompakten Adenomzellen als auch im Nebennierencarcinom waren polymorphe Zellkerne mit vergrößerten, chromatindichten Nucleoli und Kerneinschlüsse nachweisbar. Die histologischen und ultrastrukturellen Merkmale zur Differentialdiagnose des Adenom und Carcinom der Nebennierenrinde werden erörtert.

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Ultrastructural study of the adrenal tumours in Cushing's syndrome

Summary Four adenomas and one carcinoma of the adrenal cortex associated with Cushing's syndrome were investigated by light and electron microscope. The structure was compared to their hormonal function. We differentiate predominantly clear cell adenomas, which are characterized by a large number of lipid vacuoles, from compact cell adenomas with well-developed steroid hormone-producing cytoplasmic organelles. The compact cell adenomas are considered the morphologic equivalent of a high functional state, whereas the clear cell adenomas represent a storage phase and can be stimulated by ACTH. Ultrastructurally the adenoma cells with increased granular endoplasmic reticulum and pleomorphic mitochondria showed marked differences from the cells of the fasciculate and reticular zone in normal and hyperplastic adrenal glands. Electron microscopy revealed only differences of degree between adrenal carcinoma and compact cell adenoma. In the carcinoma as well as in the compact cell adenomas pleomorphic nuclei with enlarged and hyperchromatic nucleoli and nuclear inclusions were observed. Histological and ultrastructural features which may be useful in the differential diagnosis of adrenal adenomas and carcinoma are discussed.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (Sonderforschungsbereich 34 — Endokrinologie).     

Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.     

Potential Occupational Exposures in the Reiss-Engelhorn-Museen Mannheim/Germany

The Reiss-Engelhorn-Museen in Mannheim, Germany requested support from a toxicological laboratory in evaluating occupational exposures before a cleanup and renovation period in 2006. Samples of dust and dirt and scrapings of exhibits were collected from several locations. Following toxicologically relevant compounds could be identified by gas chromatography – mass spectrometry (GC/MS) by comparison with a mass spectra library: dichlorodiphenyl trichloroethane (DDT) and its breakdown product dichlorodiphenyl dichloroethane (DDD) as well as dichlorodiphenyl dichlorethylene (DDE), methoxychlor, nicotine, and camphor. In recent times various insecticides have been used to protect museum artefacts against moths, woodborers and other insect pests. Caution has to be made because the presence of hazardous compounds can result in security problems for museum staff as well as for visitors.     

Multi-ethnic adolescents' attitudes toward smoking: a focus group analysis

PURPOSE: To explore young, multi-ethnic adolescents' attitudes and influences related to cigarette smoking for the purpose of developing and producing a youth-led, tobacco prevention drama. DESIGN: Focus groups and demographic surveys. SETTING: Island of Oahu, Hawaii. PARTICIPANTS: Fifty-four multi-ethnic youth, ranging in age from 10 to 14 years, participated. The study was promoted in schools with a large representation of Hawaiian, Filipino, and Pacific Islander students. METHODS: Each of five focus groups was audio-recorded, and an observer recorded extensive notes throughout the sessions. Content analysis consisted of coding focus group notes for recurrent themes and using the audio recording as confirmation. RESULTS: Just more than one quarter (n = 15) of the youth had tried smoking, and two-thirds (n = 35) currently lived with someone who smoked. Participants expressed the feeling of being surrounded by smoking influences at home, in their communities, and at school. Youth were negatively affected by family members' tobacco use, and they desired skills that could enable them to help family members stop using tobacco. CONCLUSION: Family influences may play an important role in youth attitudes toward tobacco use, especially given the cultural significance of extended family and of filial piety that are reflected in many traditional, Asian and Pacific Islander families. Interventions targeting youth in Asian and Pacific Islander communities should incorporate key cultural references to the extended family and to a respect for elders to establish relevance in the life experiences of young people in these population groups.