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At least 307 records · Page 17Linked to original sources
PubMed2006

Breaking the (un)sound barrier: filaggrin is a major gene for atopic dermatitis.

We have recently shown that loss-of-function mutations in the filaggrin gene, carried by about 10% of people of European ethnicity, cause ichthyosis vulgaris and are strong predisposing factors for atopic dermatitis and asthma secondary to atopic dermatitis. These results demonstrate a prominent role for the epidermal barrier in atopic disease and have important implications for the study of complex traits.

Child↗
PubMed1978

Characterization of the papain active centre by using two-protonic-state electrophiles as reactivity probes. Evidence for nucleophilic reactivity in the un-interrupted cysteine-25-histidine-159 interactive system.

1.2,2'-Dipyridyl disulphide (2-Py-S-S-2-Py) and n-propyl 2-pyridyl disulphide (propyl-S-S-2-Py) were used as two-protonic-state reactivity probes to investigate the active centre of papain (EC 3.4.22.2).2. The existence of a striking rate optimum at pH approx. 4 in the reaction of papain not only with the symmetrical probe but also with the unsymmetrical probe is shown to constitute compelling evidence that the thiolate ion component of the cysteine-25-histidine-159 interactive system of papain possesses appreciable nucleophilic character. It is not a necessary requirement that the probe reagent should engage the imidazolium ion of histidine-159 in hydrogen-bonding for the sulphur atom of the interactive system to display nucleophilic character. The single proton-binding site of propyl-S-S-2-Py cannot simultaneously interrupt the active-centre ion pair and provide for rate enhancement as the pH is lowered towards 4. The possible implication of this for the mechanism of papain-catalysed hydrolysis is discussed. 3. The suspected difference in the active centres of papain and ficin (EC 3.4.22.3), which could be a lack in ficin of a carboxy group conformationally equivalent to that of aspartic acid-158 of papain is confirmed. The reactivity of the papain thiol group towards both probe reagents is controlled by two ionizations with pKa close to 4 that are positively co-operative. 4. In the reaction of papain with 2-Py-S-S-2-Py. the reactivity appears to be controlled also by an addition ionization with pKa approx. 5. Possible origins of this additional ionization are discussed. K. The spectral and ionization characteristics of propyl-S-S-2-Py are reported. 6. The reagent reacts rapidly with thiol groups at the sulphur atom distal from the pyridyl ring to provide, at pH values below 9, stoicheiometric release of 2-thiopyridone. This property, together with the ability of the reagent markedly to increase its electrophilicity consequent on protonation, suggests alkyl-2-pyridyl disulphides in general as valuable two-protonic-state reactivity probes with exceptional specificity for thiol groups.

2,2'-Dipyridyl↗
PubMed2004

Factors associated with (un)willingness to be an organ donor: importance of public exposure and knowledge.

BACKGROUND: Transplantation is increasingly limited by the supply of donor organs. Identifying subgroups that do not support organ donation will allow targeted efforts to increase organ donation. METHODS: A total of 185 non-acutely ill outpatients visiting a community physician's office voluntarily completed a survey designed to capture views and general knowledge/misconceptions about cadaveric organ donation/transplantation. RESULTS: Of 185 patients, 86 were willing to donate, 42 were unwilling, and 57 were unsure. Willingness to donate was significantly associated with: having discussed the topic with family; having known a cadaveric organ donor; age 55 yr; having graduated high school; recognizing the organ shortage as the primary problem in transplantation; having received a post-high school degree; having seen public information within 30 d; and having a family member in health care (all p</=0.05). Not significant were: gender; race; religious affiliation or regular church attendance; knowing a transplant recipient or wait-listed patient; and having easy internet access. Those unwilling/unsure more often thought: organ allocation is based on race/income; organ donation is expensive for the donor family; designated donors may not receive full emergency room care; a brain-dead person can recover. CONCLUSIONS: Intense efforts to improve public awareness and knowledge about organ donation/transplantation are necessary to maximize donation and the overall success of transplantation.

Adult↗