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Biomedical subjects

V Barrett

Publications and source records attributed to V Barrett.

18 recordsLinked to original sources

Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation.

Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT(1B/1D) receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. This molecule also has significant activity against 5HT(1F) receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.

Administration, Oral↗

Dental implants. 7. Basic restorative techniques.

Some restorative techniques for implant supported restorations will be familiar to dentists used to providing conventional crown and bridgework. The differences and principles involved when using implants are identified.

Dental Abutments↗

Reproductive health in the American workplace.

Helping workers understand their risk of reproductive and developmental hazard exposure can be demanding for the occupational health nurse. The lack of conclusive information about most suspected hazards, as well as concern over job security and advancement, make this issue doubly challenging. Further research is needed to verify or rule out the suspected toxic effects of a hazard. The occupational health nurse must make every effort to keep abreast of new research findings and federal or state requirements related to reproductive hazards. The key to promoting the reproductive health of American workers is primary prevention (Bernhardt, 1990). Educating and counseling workers about reproductive hazards so that they can make informed decisions about their reproductive health, along with implementing engineering controls or ergonomic changes to reduce the risk of exposure, should be the goal of all occupational health programs.

Female↗

Market testing. What am I bid?

Walsall's experience of marketing testing for urology services was that it is a difficult, time-consuming but thoroughly worthwhile process. We believe that a much improved level of service will be available to Walsall residents, representing excellent value for money. Turning the spotlight on to this particular specialty resulted in local provider trusts showing increased willingness to address the clinical management and quality issues about which the HA had expressed concern.

Competitive Bidding↗

A primary care nursing model in long-term care facilities: evaluation of impact on affect, behavior, and socialization.

A primary care model of delivery of nursing aide care was implemented and evaluated in one small, rural nursing home and one large, urban facility. Experimental unit residents received primary care consisting of permanent assignment of nursing aide, a team approach and enhanced communication. The urban experimental residents improved significantly in behavior and affect as measured across several sources, while the comparison group declined or remained the same. Significant improvements in behavior and social activities were observed among the experimental rural nursing home residents as contrasted with the comparison group after implementation of primary care nursing. It was concluded that primary care nursing as applied to nursing attendants in long-term care is beneficial to residents in terms of decreasing disturbed behavior and improved affect.

Affect↗

Calmodulin increases Ca-dependent inhibition of the Na,K-ATPase in human red blood cells.

Proteins in human red cell hemolysate were purified to determine which of them increase inhibition of the Na,K-ATPase in the presence of 2 microM free Ca. Samples purified 600,000-fold inhibited the Na,K-ATPase of human red cells in a Ca-dependent manner and stimulated the (Ca+Mg)-ATPase. These samples contained two proteins as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): calmodulin (18,000 Mr), which comprised most (greater than 90%) of the total protein, and an unidentified protein of approximately 13,000 Mr. Both proteins were a distinctive light yellow when stained with silver. Calmodulin from bovine testes also inhibited the Na,K-ATPase and stimulated the (Ca+Mg)-ATPase. This preparation also contained two proteins as analyzed by SDS-PAGE: calmodulin (95 to 99% of the total protein) and another protein of approximately 13,000 Mr (1 to 5% of the total protein). Both were light yellow when stained with silver. Since the amount of red cell protein was limited, the remainder of the study was carried out with the bovine testes preparation. Heating the testes preparation decreased, but did not abolish, inhibition of the Na,K-ATPase and reduced stimulation of the (Ca+Mg)-ATPase. When corrected for denatured calmodulin, both heated and unheated proteins increased inhibition of the Na,K-ATPase to the same extent. The Na,K-ATPase was inhibited at 2 microM free Ca in a dose-dependent manner over a range of 15 to 100 nM calmodulin. To establish if the inhibition was due to the calmodulin or the 13,000 Mr protein, both were electroeluted after SDS-PAGE. Electroeluted calmodulin stimulated the (Ca+Mg)-ATPase and increased Ca inhibition of the Na,K-ATPase. Electroeluted amounts of the smaller Mr protein slightly stimulated the (Ca+Mg)-ATPase, but had no effect on the Na,K-ATPase. This protein was digested with cyanogen bromide, partially sequenced, and thereby identified as a fragment of calmodulin. We conclude that intact calmodulin increases inhibition of the Na,K-ATPase at 2 microM free Ca. We suggest that calmodulin is part of a mechanism mediating the effects of physiological free Ca on the Na,K-ATPase.

Amino Acid Sequence↗

On the origins of tandemly repeated genes: does histone gene copy number in Drosophila reflect chromosomal location?

Widely regarded beliefs about Drosophila histone gene copy numbers and developmental requirements have been generalized from fairly limited data since studies on histone gene arrangements and copy numbers have been largely confined to a single species, D. melanogaster. Histone gene copy numbers and chromosomal locations were examined in three species: D. melangaster, D. hydei and D. hawaiiensis. Quantitative whole genome blot analysis of DNA from diploid tissues revealed a tenfold variability in histone gene copy numbers for these three species. In situ hybridization to polytene chromosomes showed that the histone DNA (hDNA) chromosomal location is different in all three species. These observations lead us to propose a relationship between histone gene reiteration and chromosomal position.

Animals↗

Home health care and quality of life of patients with Alzheimer's disease.

BACKGROUND: Little is known about the quality of life (QOL) of people with Alzheimer's disease (AD). The formal home care sector plays an increasingly large role in care for this population, but home care agencies do not routinely collect QOL information or use this information in care planning. METHODS: A series of roundtable discussions with representatives of the home care industry were held to document current practices by home care providers regarding the elicitation, recording, and use of QOL information; to derive indicators of QOL in AD patients; and to develop standardized procedures for using QOL information. Results from this investigation were incorporated into an epidemiological investigation of community-dwelling AD patients, comparing formal sector home attendants to family caregivers regarding efforts to enhance patient QOL. RESULTS: Twenty representatives of the home care industry met over three sessions to discuss these issues. Patient QOL indicators were derived, showing divergence of patient and caregiver perspectives. A survey of 240 AD patients compared family and formal home attendant caregivers and showed that home attendants underutilize opportunities to enhance patient QOL, as referenced by patient participation in activities that require supervision. CONCLUSIONS: Collaboration with home care agencies allowed a better understanding of quality of life for this vulnerable patient population. More research will be required to refine QOL outcomes and develop quality assurance tools for dementia care. Medical Subject Headings (MeSH): Alzheimer's disease, quality of life, home care, paraprofessional care.

Aged↗