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Immunohistochemistry of tumour samples is increasingly used in the triage of families where hereditary non-polyposis colorectal cancer (HNPCC) due to mismatch repair defects is suspected. Usually, this is undertaken in tumours that are a recognised part of the spectrum of HNPCC-related cancers e.g. colon or endometrial cancers. Although breast cancers are not classed as part of this spectrum, this study examined the extent to which some breast tumours do arise by the mismatch repair pathway in these families. This may have clinical utility in families where an individual with a ‘classic HNPPC-related’ tumour is not available for evaluation. Immunohistochemistry of a breast tumour may identify an individual in whom germline mutation testing is worthwhile. [ABSTRACT FROM AUTHOR]

Investigations into Drosophila mutants with impaired vision due to mutations in the transient receptor potential gene ( trp) initiated a systematic search for TRP homologs in other species, finally leading to the discovery of a whole new family of plasma membrane cation channels involved in multiple physiological processes. Among the recently discovered TRP cation channels two homologous proteins, TRPM6 and TRPM7, display unique domain compositions and biophysical properties. These remarkable genes are vital for Mg2+ homeostasis in vertebrates and, if disrupted, lead to cell death or human disease. [ABSTRACT FROM AUTHOR]

At least two separate genetic pathways of carcinogenesis in sporadic colon cancer involving the accumulation of mutations at various genetic loci have been described. About 15% of sporadic colorectal carcinomas arise via a mechanism associated with microsatellite instability (MSI) and mutations in transforminggrowth factorβ receptor II (TGFβRII), insulin-like growth factor II receptor (IGFIIR) and BAX, whilst the remaining 85% are associated with aneuploidy and gross chromosomal rearrangements. An 81-year-old woman had a sigmoid colon carcinoma resected and 18 months later developed two additional carcinomas of the caecum and transverse colon. To investigate whether there was a common genetic mechanism of carcinogenesis for the three lesions, MSI status was assessed, TGFβRII, IGFIIR and BAX were analysed for mutations and protein expression of transforming growth factor β1 (TGFβ1) and p53 were studied using immunohistochemistry. The caecal and transverse colonic carcinomas were both MSI positive but different mutations were identified in each lesion. No genetic abnormalities were identified in the sigmoid colonic carcinoma. This suggests that each carcinoma arose via a separate genetic mechanism of carcinogenesis. [ABSTRACT FROM AUTHOR]

To study the role of endothelial ATP-sensitive K+ channels in the regulation of vascular tone we examined the intracellular calcium concentration ([Ca2+]i) in coronary capillaries consisting only of endothelial cells. Coronary capillary fragments were isolated enzymatically from the guinea-pig heart and [Ca2+]i was determined by microfluorometry of fura-2 loaded cells. Low concentrations of the K+ channel opener diazoxide, which caused pronounced glibenclamide-sensitive hyperpolarization in capillaries, induced a rapid, transient rise in [Ca2+]i followed by a sustained elevation of [Ca2+]i (19 of 40 experiments). [Ca2+]i in the endothelial cells increased from 32 ± 7 nM at rest to 66 ± 11 nM at the peak ( n = 19). One third of the [Ca2+]i-transients showed irregular oscillations of [Ca2+]i. No significant difference in the [Ca2+]i-response induced by 100 nM or 1 μM diazoxide was found. Similar results were obtained with the K+ channel opener rilmakalim. Simultaneous measurements of the membrane potential and [Ca2+]i with fluorometric methods indicated that the hyperpolarization but not the [Ca2+]i-transient could be repeatedly induced in a single capillary by the K+ channel openers. Electrophysiological recordings of the membrane potential using the ”perforated patch” method ( n = 4), showed that rilmakalim (1 μM) induced hyperpolarization of capillaries towards the K+ equilibrium potential, confirming our fluorometric measurements. In conclusion, for the first time, these data indicate that K+ channel openers induce [Ca2+]i-transients in microvascular endothelial cells. This raises the possibility that these drugs not only act as synthetic vasoactive factors via hyperpolarizing smooth muscle cells but also via NO release of microvascular endothelial cells. Interestingly, only 100 nM diazoxide was sufficient for a maximal response, suggesting the expression of a new type of KATP-channel in coronary capillaries characterised by high sensitivity to diazoxide. [ABSTRACT FROM AUTHOR]

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Copyright of Archiv für Orthopädische und Unfall-Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archiv für Gewerbepathologie und Gewerbehygiene is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A letter to the editor is presented in response to the article "Long-term remission after CD34+ -selected PBSCT in a patient with advanced intra-abdominal desmoplastic small round-cell tumor" in the August 31, 2009 issue.

Copyright of Archiv für Orthopädische und Unfall-Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)