A novel HLA allele, HLA-A*02:393, identified in a two generation Italian family.

HLA-A*02:393 differs by a single nucleotide substitution from both A*02:26 (A524G) and from A*02:40:01 (T527A).

Forgoing life sustaining treatments: differences and similarities between North America and Europe.

BACKGROUND: As evidence exist that severe neurological damage or prolonged death after inappropriate CPR could occur, restraints and indications for CPR were perceived as necessary. The objective of this review is to examine policies and attitudes towards end-of-life decisions in Europe and North America and to outline differences and similarities. METHODS: A bibliographic database search from 1990 to 2006 was performed using the following terms: do-not-resuscitate orders, end-of-life decisions, withholding/withdrawal of life-sustaining treatments, medical futility and advanced directives. Eighty-eight articles, out of 305 examined, were analyzed and their data systematically reported and compared where possible. They consisted of studies, questionnaires and surveys answering the following questions: percentage of deaths of critical patients preceded by do-not-resuscitate orders, factors affecting the decision for do-not-resuscitate orders, people involved in this decision (patient, surrogates and medical staff) and how it was performed. RESULTS: There is an evident gap between the North American use of standard and formal procedures compared with Europe. Second, they diverge in the role acknowledged to surrogates in the decisional process, as in Europe, restraints and reserves to accept surrogates as decision makers seem still strong and a paternalistic approach at the end-of-life is still present. CONCLUSION: Incidentally, despite the predictable differences between Europe and North America, concerns do exist about the actual extent of autonomy wished by patients and surrogates. It is important to highlight these findings, as the paternalistic attitude, too often negatively depicted, could be, according to the best medical practice, justified and more welcomed in some instances.

Estradiol induction of cAMP in breast cancer cells is mediated by foetal calf serum (FCS) and sex hormone-binding globulin (SHBG).

Plasma sex hormone-binding globulin (SHBG or SBP), the specific carrier for estradiol and androgens, after binding to its membrane receptor (SHBG-R), causes a significant increase of cAMP in the presence of estradiol, in both breast (MCF-7) and prostate (LNCaP) cancer cells maintained in serum-free medium. On the other hand, it has been proposed that estrogens, in addition to the well-known nuclear receptor pathway, exert their biological effect inducing cAMP, as a consequence of a direct membrane action, in breast cancer and uterine cells. The aim of the present study was to clarify this controversial issue by verifying if the cAMP increase in MCF-7 cells was a direct effect of estradiol, or if it was mediated by FCS proteins, such as bovine sex hormone-binding globulin; and to reevaluate the effect of human SHBG on cAMP induction in the presence of FCS. MCF-7 cells were maintained in DCC-FCS (treated with DCC to remove steroids), in SHBG-FREE/DCC-FCS (treated with DCC and with a specific affinity chromatography to remove bovine sex hormone-binding globulin), or in serum-free medium (SFM). It was observed that estradiol determined a significant time-dependent increase of cAMP only in MCF-7 cells maintained in 10% DCC-FCS. When cells were maintained in 10% SHBG-FREE/DCC-FCS, estradiol had no detectable effect. However, its ability to increase cAMP was observed again after the addition of human SHBG, in doses ranging from 5 to 50 nM. Moreover, in the presence of 10% SHBG-FREE/DCC-FCS, SHBG, even in the absence of estradiol, caused a significant increase of cAMP. In conclusion, the data reported in the present study suggest that the ability of estradiol to induce cAMP in MCF-7 cells is not due to a direct membrane effect of the hormone, but rather it is mediated by FCS. SHBG is one of the serum factors mediating estradiol action. Lastly, it was proven that SHBG triggers the cAMP pathway in MCF-7 cells in a physiologic culture condition and at physiologic concentrations.