Further evidence of linkage at 7p22 with familial hyperaldosteronism type II and exclusion of genetic defects in the RBAK coding regions

Once thought rare, primary aldosteronism (PAL) is now reported to be responsible for 5–10% of hypertension. Unlike familial hyperaldosteronism type I (FH-I), FH-II is not glucocorticoidremediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. At least five times more common than FH-I, FH-II is clinically indistinguishable from apparently sporadic PAL, suggesting an even higher incidence. Studies performed in collaboration with C Stratakis (NIH, Bethesda) on our largest Australian family (eight affected members) demonstrated linkage at chromosome 7p22. Linkage at this region was also found in a South American family (DNA provided by MI New, Mount Sinai School of Medicine, New York) and in a second Australian family. The combined multipoint LOD score for these 3 families is 4.61 (q = 0) with markers D7S462 and D7S517, providing strong support for this locus harbouring mutations responsible for FH-II. A newly identified recombination event in our largest Australian family has narrowed the region of linkage by 1.8 Mb, permitting exclusion of approximately half the genes residing in the originally reported 5 Mb linked locus. Candidate genes that are involved in cell cycle control are of interest as adrenal hyperplasia and adrenal adenomas are common in FH-II patients. A novel candidate gene in this linked region produces the retinoblastoma-associated Kruppel-associated box protein (RBaK) which interacts with the retinoblastoma gene product to repress the expression of genes activated by members of the E2F family of transcription factors.

Unexpected role of surface transglutaminase type II in celiac disease

Background & Aims: In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. Methods: Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, pα-9, and deamidated pα-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. Results: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. Conclusions: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases. © 2005 by the American Gastroenterological Association.

Clinical measurement in assessing obesity and the prediction of biomarkers in association to cardovascular diseases and type-II diabetes

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR CONSULTATION

Első- és másodfajú etikai kudarcok (Type I and type II ethical errors)

A cikkben a szerző a piac és a kormányzat kudarcaiból kiindulva azonosítja a közjó elérését célzó harmadik rendszer, az etikai felelősség kudarcait. Statisztikai analógiát használva elsőfajú kudarcként azonosítja, mikor az etikát nem veszik figyelembe, pedig szükség van rá. Ugyanakkor másodfajú kudarcként kezeli az etika profitnövelést célzó használatát, mely megtéveszti az érintetteteket, így még szélesebb utat enged az opportunista üzleti tevékenységnek. Meglátása szerint a három rendszer egymást nemcsak kiegészíti, de kölcsönösen korrigálja is. Ez az elsőfajú kudarc esetében általánosabb, a másodfajú kudarc megoldásához azonban a gazdasági élet alapvetéseinek átfogalmazására, az önérdek és az egydimenziós teljesítményértékelés helyett egy új, holisztikusabb szemléletű közgazdaságra van szükség. _______ In the article the author identifies the errors of ethical responsibility. That is the third system to attain common good, but have similar failures like the other two: the hands of the market and the government. Using statistical analogy the author identifies Type I error when ethics are not considered but it should be (null hypothesis is rejected however it’s true). She treats the usage of ethics to extend profit as Type II error. This misleads the stakeholders and makes room for opportunistic behaviour in business (null hypothesis is accepted in turn it’s false). In her opinion the three systems: the hand of the market, the government and the ethical management not only amend but interdependently correct each other. In the case of Type I error it is more general. Nevertheless to solve the Type II error we have to redefine the core principles of business. We need a more holistic approach in economics instead of self-interest and one-dimensional interpretation of value.

Conséquence du choc hypotonique sur le transport sodique des cellules épithéliales alvéolaires de type II

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Expression différentielle des récepteurs "scavenger" de classe B de type I (SR-BI) et de type II (SR-BII) dans le testicule de souris et de vison

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Relations entre la lipolyse adipocytaire, la périlipine et l'obésité dans une perspective de physiopathologie telle le diabète de type II

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Rôle de l'inositol polyphosphate 4-phosphatase de type II (Inpp4b) dans la différenciation et l'activité des ostéoclastes

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Conséquence du choc hypotonique sur le transport sodique des cellules épithéliales alvéolaires de type II

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.