Frequent loss of heterozygosity targeting the inactive X chromosome in melanoma.

After previous preliminary observations of paradoxical deletion events affecting the inactive X chromosome in melanoma, we have surveyed the X chromosome for deletions using 23 polymorphic microsatellite markers in 28 informative (female XX) metastatic melanomas. Ten tumors (36%) showed at least one loss of heterozygosity (LOH) event, and in two cases an entire chromosome showed LOH at all informative loci. Four distinct X chromosome smallest regions of overlap can be resolved. An 18.6-Mb region on the p arm involving 9 of 28 (32%) samples lies between the markers DXS1061 and DXS1068. An equally frequently deleted smallest region of overlap straddled the centromere, bounded by DX1204 on the p arm and DXS983 14.6 Mb away in Xq11-12. One tumor potentially defines this region more tightly to a 10.6-Mb smallest region of overlap bounded by DXS1190 and DXS981 that contains the androgen receptor (AR) gene. A 6.2-Mb deleted region can be defined between the markers DXS8051 and DXS9902 in 8 of 28 (28%) tumors. An additional, less frequently deleted region of 25.7 Mb was found on distal Xq between the markers DXS1212 and DXS1193 in 5 of 28 (18%) tumors. X inactivation analysis of five tumors with LOH, using the AR exon 1 CAG repeat, showed that in each case, the inactive, hypermethylated allele was the one deleted. Analysis of copy number in this region by quantitative PCR showed restoration to disomy and, in one case, trisomy at AR.     

Medicine and art.: Alan EH Emery, Marcia LH Emery. (122 pages, {pound}40.) Royal Society of Medicine Press Ltd, 2003. ISBN 1-85315-501-2.

Alan and Marcia Emery have given the reader a book of considerableerudition and insight into the relationship between medicineand society over the past 2000 years. Many will get great pleasuresimply from dipping in and out of this book. Their choice ofover 50 images of     

Evaluation of the behaviour of a thermal diffusion sensor in a high field strength magnetic resonance system: an experimental study.

Patients with acute brain pathology requiring ferromagnetic bio-medical implants for on-going invasive monitoring are largely excluded from the benefits of MRI scanning. We evaluated the behaviour of a thermal diffusion cortical blood flow (TD-CBF) sensor both in vitro (phantom gelatin model) and in vivo environments in a high field strength MRI system.Two baboons underwent cranial subdural implantation of 2 TD-CBF sensors/hemisphere and a single left parietal sensor was implanted subcortically to determine any deleterious effects. Using standard MRI sequences, artefact size, thermal effects, current generation, movement and reliability of recordings were assessed during scanning.The deflection forces were negligible, no observable thermal effects were demonstrated, while wide fluctuations in cerebral blood flow recordings were recorded. Mean image artefact size for implanted sensors was 6 times larger than in vitro. Patients with an implanted TD-CBF sensor may be safely imaged provided the device is disconnected. The MRI images obtained are of an acceptable quality.     

Rapid isolation and characterization of 118 novel C2H2-type zinc finger cDNAs expressed in human brain

C2H2-type zinc finger genes comprise one of the largest genefamilies in the human genome. These proteins are involved ingenetic regulation and development and are quite conserved throughoutevolution. The finger domains commonly contain the small linkerpeptide TGEKP between some finger units. Here, we report theisolation of 133 human zinc finger cDNAs, of which 118 are novel.These clones were isolated from human brain cDNA libraries usingoligonucleotide hybridization followed by expressed sequencetag (EST) analysis, sequencing from the conserved linker regionusing degenerate oligonucleotide primers. This directed partialsequencing approach to cDNA isolation and characterization,signature sequencing, combines the speed of EST automatic sequencingwith the focus of specific cDNA family analysis. Signature sequencingminimizes the generation of less informative random EST sequencesand provides a unique relative position for sequence comparison.We also show that there is an even distribution of these RNA5from this brain cDNA library, and that these cDNAs contain N-terminaldomains found in other zinc finger genes. This rapid focusedsequencing approach should be applicable to any family of cDNAscontaining short conserved signature peptide sequences.     

Percutaneous nephrolithotomy directlythrough an angiomyolipoma

We present a patient with tuberous sclerosis and bilateral angiomyolipomaswith a right partial staghorn calculi in which the calculi was managed with a percutaneous nephrolithotomy. Despite the inherent risk of hemorrhage with a percutaneous approach compounded by the fact that this was done directly through a tumor, we were able to render the patient stone free with no intraoperative bleeding, complications, or the need for postoperative blood transfusion. To our knowledge, this is the first reported case of percutaneous nephrolithotomy directly through a renal angiomyolipoma.