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Biomedical subjects

A G Shearer

Publications and source records attributed to A G Shearer.

7 recordsLinked to original sources
PubMed2001

Beliefs that support the behavior of people with asthma: a qualitative investigation.

Differences between patients' knowledge and behavior in relation to asthma may account for continuing morbidity in theface of professional and public asthma education campaigns. We conducted a qualitative study of beliefs that support asthma-related behavior, obtaining data from interviews with 70 adult patients. Analysis identified four clear subgroups, or "streams," of adults with asthma: an "anonymous" stream, who doubt that they have asthma and manage symptoms outside the organized health system; an "isolated" stream, who feel dependent on bronchodilators and do not understand the potential of preventive therapy; a "suboptimal" stream, who are confident that they are managing their asthma effectively but who are excessively reliant on bronchodilators; and an "optimal stream," who have high expectations of outcomes and participate actively in a partnership with a doctor. Characteristics of the doctor and the doctor-patient relationship are important elements in altering asthma-related behavior in ways that may facilitate the best health outcomes.

Adolescent↗
PubMed2001

In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation.

Ubiquitination is used to target both normal proteins for specific regulated degradation and misfolded proteins for purposes of quality control destruction. Ubiquitin ligases, or E3 proteins, promote ubiquitination by effecting the specific transfer of ubiquitin from the correct ubiquitin-conjugating enzyme, or E2 protein, to the target substrate. Substrate specificity is usually determined by specific sequence determinants, or degrons, in the target substrate that are recognized by the ubiquitin ligase. In quality control, however, a potentially vast collection of proteins with characteristic hallmarks of misfolding or misassembly are targeted with high specificity despite the lack of any sequence similarity between substrates. In order to understand the mechanisms of quality control ubiquitination, we have focused our attention on the first characterized quality control ubiquitin ligase, the HRD complex, which is responsible for the endoplasmic reticulum (ER)-associated degradation (ERAD) of numerous ER-resident proteins. Using an in vivo cross-linking assay, we directly examined the association of the separate HRD complex components with various ERAD substrates. We have discovered that the HRD ubiquitin ligase complex associates with both ERAD substrates and stable proteins, but only mediates ubiquitin-conjugating enzyme association with ERAD substrates. Our studies with the sterol pathway-regulated ERAD substrate Hmg2p, an isozyme of the yeast cholesterol biosynthetic enzyme HMG-coenzyme A reductase (HMGR), indicated that the HRD complex discerns between a degradation-competent "misfolded" state and a stable, tightly folded state. Thus, it appears that the physiologically regulated, HRD-dependent degradation of HMGR is effected by a programmed structural transition from a stable protein to a quality control substrate.

Animals↗