[It can not be healthy not to be ill]. / Gar ned krank is a ned g'sund.

This article is written in remembrance of Karl Valentin's 70th anniversary of his death. He was a comedian and song writer suffering from vegetative dystonia and depression lifelong. This hypochondriac developed extreme self observation and had anxiety to get ill permanently. As one year old, his brother died of diphteria and he was close to death himself. After jumping in an ice cold river in Munich as a young man he caught a pneumonia. From that day he had a undefined long lasting lung disease. His performances and pieces of literature in Bavarian dialect are characterized by critical thoughts about the world in general and human vulnerability including his own in a philosophical way. His sarcastic view of the world, which was rarely pleasant for the counterpart still induced admiration of many audiences and was satisfying for Karl Valentin's egocentrism. He has been the most famous Bavarian comedian during world war II and during the early days of the Republic of Germany.

"Essentially" pure trisomy 3q27 --> qter: further delineation of the partial trisomy 3q phenotype.

Partial duplication 3q is a well defined clinical entity characterized by growth retardation, cryptorchism, microcephaly, and characteristic dysmorphisms. Most patients present with large duplications or are associated with a second chromosomal imbalance, which makes the definition of the phenotype difficult. Here, we report on a 4-year and 8-month-old girl with pre- and postnatal measurements in the high normal range, developmental delay, minor dysmorphic features, and a de novo unbalanced 3/4 translocation with trisomy 3q27 --> qter and monosomy of the subtelomeric region of 4p. Conventional karyotyping, FISH with probes from the Wolf-Hirschhorn syndrome critical region and chromosome 4p locus-specific probes, microsatellite marker-based haplotyping, and SNP microarray copy number analysis revealed a terminal 4p deletion of less than 500 kb with a breakpoint distal to the Wolf-Hirschhorn syndrome critical region, a chromosome 3q duplication of around 15.3 Mb, with origin of the rearrangement in paternal meiosis. Thus, our case clearly characterizes the phenotype of pure partial duplication 3q more exactly, and moreover, indicates that small chromosome rearrangements might lead to growth in the upper normal range or even cause overgrowth.

Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis.

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury.

The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis.

BACKGROUND: Non-Wilsonian hepatic copper toxicosis includes Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and the non-Indian disease known as idiopathic copper toxicosis (ICT). These entities resemble the hepatic copper overload observed in livers of Bedlington terriers with respect to their clinical presentation and biochemical and histological findings. We recently cloned the gene causing copper toxicosis in Bedlington terriers, MURR1, as well as the orthologous human gene on chromosome 2p13-p16. AIM: To study the human orthologue of the canine copper toxicosis gene as a candidate gene for ICC, ETIC, and ICT. METHODS: We sequenced the exons and the intron-exon boundaries of the human MURR1 gene in 12 patients with classical ICC, one patient with ETIC, and 10 patients with ICT to see whether these patients display any mutations in the human orthologue of the canine copper toxicosis gene. RESULTS: No mutations in the MURR1 gene, including the intron-exon boundaries, were identified in a total of 23 patients with non-Wilsonian hepatic copper toxicosis. CONCLUSIONS: Our results demonstrate that copper toxicosis in Bedlington terriers is not an animal model for the non-Wilsonian hepatic copper toxicosis described in this study.