S. Plusa

Mitochondrial DNA mutations in human colonic crypt stem cells

The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.

The quality of patient‐orientated internet information on colorectal cancer

Objective  The Internet provides an enormous amount of patient‐orientated information on colorectal cancer. This study examined its accessibility and quality.

Defects in multiple complexes of the respiratory chain are present in ageing human colonic crypts

Mitochondrial DNA (mtDNA) mutations accumulate in a number of ageing tissues and are proposed to play a role in the ageing process. We have previously shown that colonic crypt stem cells accumulate somatic mtDNA point mutations during ageing. These mtDNA mutations result in the loss of the activity of complex IV (cytochrome c oxidase (COX)) of the respiratory chain in the stem cells and their progeny, producing colonic crypts which are entirely COX deficient. However it is not known whether the other complexes of the respiratory chain are similarly affected during ageing. Here we have used antibodies to individual subunits of complexes I–IV to investigate their expression in the colonic epithelium from human subjects aged 18–84. We show that in ∼50% of crypts with any form of respiratory chain deficiency, decreased expression of subunits of multiple complexes is observed. Furthermore we have sequenced the entire mitochondrial genome of a number of cells with multiple complex defects and have found a wide variety of point mutations in these cells affecting a number of different protein encoding and RNA encoding genes. Finally we discuss the possible mechanisms by which multiple respiratory chain complex defects may occur in these cells.

Use of the internet by colorectal cancer patients

Objective  To identify the frequency of Internet use by colorectal cancer patients.

Anal sphincter fibrillation: is this a new finding that identifies resistant chronic anal fissures that respond to botulinum toxin?

Anal fissures can be resistant to treatment and some patients may undergo several trials of medical therapy before definitive surgery. It would be useful to identify predictors of poor response to medical therapy. This study assesses the role of anorectal physiological criteria to identify patients with anal fissure predicted to fail botulinum toxin (BT) treatment.