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A R Davidson

Publications and source records attributed to A R Davidson.

At least 19 recordsLinked to original sources
PubMed1998

A model for the nucleotide-binding domains of ABC transporters based on the large domain of aspartate aminotransferase.

ABC transporters are a large superfamily of integral membrane proteins involved inATP-dependent transport across biological membranes. Members of this superfamily play roles in a number of phenomena of biomedical interest, including cystic fibrosis (CFTR) and multidrug resistance (P-glycoprotein, MRP). Most ABC transporters are predicted to consist of four domains, two membrane-spanning domains and two cytoplasmic domains. The latter contain conserved nucleotide-binding motifs. Attempts to determine the structure of ABC transporters and of their separate domains are in progress but have not yet been successful. To aid structure determination and possibly learn more about the domain boundaries, we set out to model nucleotide-binding domains (NBDs) of ABC transporters based on a known structure. Previous attempts to predict the 3D structure of NBDs were based solely on sequence similarity with known nucleotide-binding folds. We have analyzed the sequences of a number of nucleotide-binding domains with the algorithm THREADER, developed by D.T. Jones, and a possible fold was found in the structure of aspartate aminotransferase. We present a model for the N-terminal NBD of CFTR, based on the large domain of the A chain of aspartate aminotransferase. The model is refined using multiple sequence alignment, secondary structure prediction, and 3D-1D profiles. Our model seems to be in good agreement with known properties of nucleotide-binding domains and has some appealing characteristics compared with the previous models.

ATP-Binding Cassette Transporters↗
PubMed1997

Injectable contraceptive discontinuation and subsequent unintended pregnancy among low-income women.

OBJECTIVES: This study investigated rates of discontinuation of the recently introduced injectable contraceptive depot medroxyprogesterone acetate (DMPA) and postdiscontinuation rates of unprotected intercourse and unintended pregnancy. METHODS: A sample of 402 low-income, urban, minority women were interviewed when they initiated DMPA use and 12 months later. RESULTS: The 12-month life-table discontinuation rate was 58%, with half of the discontinuers stopping after only one injection. Menstrual changes and other side effects were the most frequently cited reasons for discontinuation. Approximately half of the discontinuers at risk for unintended pregnancy either did not make the transition to another contraceptive or used contraception only sporadically. The cumulative unintended pregnancy rate by 9 months postdiscontinuation was 20%. CONCLUSIONS: DMPA initiators were at substantial risk for unintended pregnancy because most quickly discontinued use and did not make the transition to consistent use of another contraceptive.

Adolescent↗
PubMed1996

Beliefs about Depo-Provera among three groups of contraceptors.

This article examines the beliefs about Depo-Provera held by three groups of contraceptors utilizing urban family planning clinics in the United States (n = 836). Patients choosing Depo-Provera, oral contraceptives, and Norplant were asked about their beliefs regarding Depo-Provera in the following four domains: effectiveness in preventing pregnancy, convenience, side-effects, and risk to health; and also for their perceptions regarding the physical discomfort and cost associated with the method. Findings reveal that patients choosing the pill and Norplant give Depo-Provera significantly lower ratings for both convenience and effectiveness than do Depo-Provera acceptors. Given the documented effectiveness of Depo-Provera, this is a potential cause for concern. Moreover, Norplant and pill choosers are most likely to hold inaccurate beliefs regarding both the cost of Depo-Provera, and certain side-effects associated with its use. Although more than half of all patients believe the Depo-Provera would cause menstrual changes and weight gain, it is noteworthy that the proportions are not higher, given their known association with the method. Knowledge about the likelihood of these side-effects is essential, particularly for those choosing Depo-Provera. Implications for physicians, counselors, and other family planning professionals are discussed.

Adolescent↗
PubMed1996

Sequence space, folding and protein design.

Protein design efforts are beginning to yield molecules with many of the properties of natural proteins. Such experiments are informed by and contribute to our understanding of the sequence determinants of protein folding and stability. The most important design elements seem to be the proper placement of hydrophobic residues along the polypeptide chain and the ability of these residues to form a well packed core. Buried polar interactions, turn and capping motifs and secondary structural propensities also contribute, although probably to a lesser extent.

Amino Acid Sequence↗
PubMed1996

A pathway for targeting soluble misfolded proteins to the yeast vacuole.

We have evaluated the fate of misfolded protein domains in the Saccharomyces cerevisiae secretory pathway by fusing mutant forms of the NH2-terminal domain of lambda repressor protein to the secreted protein invertase. The hybrid protein carrying the wild-type repressor domain is mostly secreted to the cell surface, whereas hybrid proteins with amino acid substitutions that cause the repressor domain to be thermodynamically unstable are retained intracellularly. Surprisingly, the retained hybrids are found in the vacuole, where the repressor moiety is degraded by vacuolar proteases. The following observations indicate that receptor-mediated recognition of the mutant repressor domain in the Golgi lumen targets these hybrid fusions to the vacuole. (a) The invertase-repressor fusions, like wild-type invertase, behave as soluble proteins in the ER lumen. (b) Targeting to the vacuole is saturable since overexpression of the hybrids carrying mutant repressor increases the fraction of fusion protein that appears at the cell surface. (c) Finally, deletion of the VPS10 gene, which encodes the transmembrane Golgi receptor responsible for targeting carboxypeptidase Y to the vacuole, causes the mutant hybrids to be diverted to the cell surface. Together these findings suggest that yeast have a salvage pathway for degradation of nonnative luminal proteins by receptor-mediated transport to the vacuole.

Amino Acid Sequence↗
PubMed1996

Beliefs about Norplant implants among low income urban women.

This study documents the counseling experiences and beliefs about Norplant implants that are held by an ethnically diverse sample of low income clinic patients in the United States. Virtually all implant acceptors, but only about half of those choosing other contraceptives, receive information about the Norplant system during clinic-based counseling. Exposure to group counseling and to a film regarding Norplant implants are associated with high levels of knowledge among acceptors. Several important patterns emerge in comparing the beliefs of patients choosing the Norplant system with those of patients choosing other methods of birth control. Substantial proportions of the latter group adhere to several inaccurate beliefs about the method, associating its use with: long-term health problems, problems for future babies, future fertility problems, infection, and high cost. These outcomes in particular, as well as several others described, should be systematically addressed and reviewed in contraceptive counseling.

Adult↗
PubMed1995

Cooperatively folded proteins in random sequence libraries.

The structural properties of proteins recovered from random sequence libraries can be used to investigate the relationship between folding and sequence information. Here, we show that helical proteins displaying cooperative thermal denaturation transitions can be easily recovered from a library containing 80-residue proteins predominantly composed of glutamine, leucine, and arginine, with an average hydrophobicity level similar to that of natural proteins. The native structure of one of these proteins has a stability and oligomeric form similar to that of many natural proteins but differs in having no slowly exchanging amide hydrogens.

Amino Acid Sequence↗
PubMed1994

Folded proteins occur frequently in libraries of random amino acid sequences.

A library of synthetic genes encoding 80- to 100-residue proteins composed mainly of random combinations of glutamine (Q), leucine (L), and arginine (R) has been expressed in Escherichia coli. These genes also encode an epitope tag and six carboxyl-terminal histidines. Screening of this library by immunoblotting showed that 5% of these QLR proteins are expressed at readily detectable levels. Three well-expressed QLR proteins were purified and characterized. Each of these proteins has significant alpha-helical content, is largely resistant to degradation by Pronase, and has a distinct oligomeric structure. In addition, one protein unfolds in a highly cooperative manner. These properties of the QLR proteins demonstrate that they possess folded structures with some native-like properties. The QLR proteins differ from most natural proteins, however, in being remarkably resistant to denaturant-induced and thermal-induced unfolding and in being relatively insoluble in the absence of denaturants.

Amino Acid Sequence↗
PubMed1993

Treatment of active Crohn's disease by exclusion diet: East Anglian multicentre controlled trial.

Elemental diet is as effective in producing remission of Crohn's disease (CD) as is corticosteroid treatment, but most patients relapse soon after resumption of a normal diet. We have investigated the efficacies of dietary modification and oral corticosteroids in maintaining remission achieved with elemental diet. In a multicentre trial, 136 patients with active CD were started on elemental diet and other treatment was withdrawn. 43 (31%) declined to continue elemental diet for 14 days, but 78 (84%) of the remaining 93 achieved remission and were randomly assigned corticosteroids (38) or diet (40). Corticosteroid treatment started at 40 mg prednisolone daily, which was tapered and stopped after 12 weeks; that group received dietary advice on healthy eating. The diet group received "tapered" placebo and were instructed to introduce one new food daily, excluding any that precipitated symptoms. Assessment of progress for up to 2 years was made by physicians unaware of group assignment. Intention-to-treat analysis showed median lengths of remission of 3.8 (interquartile range 5.0) months in the corticosteroid group and 7.5 (15.3) months on diet, and relapse rates at 2 years, adjusted for withdrawals, of 79% and 62%, respectively (p = 0.048). Clinical improvement in the diet group was associated with significant changes in plasma albumin and alpha 1-antichymotrypsin concentrations and erythrocyte sedimentation rate. Food intolerances discovered were predominantly to cereals, dairy products, and yeast. Diet provides a further therapeutic strategy in active Crohn's disease.

Adrenal Cortex Hormones↗
PubMed1993

Long-term effect of tubal sterilization on menstrual indices and pelvic pain.

OBJECTIVE: To evaluate the long-term effect of tubal sterilization on menstrual indices and pelvic pain. METHODS: Five hundred women undergoing sterilization were interviewed before sterilization, 6-10 months after surgery, and 3-4.5 years later. Four hundred sixty-six non-sterilized comparison women were interviewed in parallel. The study population consisted of low-income, ethnically and regionally diverse women from three participating institutions. RESULTS: When women who were taking oral contraceptives were excluded, no long-term differences was found between sterilized and nonsterilized women in terms of menstrual cycles, bleeding between periods, prolonged or heavy flow, dysmenorrhea, or noncyclic pelvic pain. Hysterectomy was uncommon (3.2%), but statistically more prevalent among sterilized women (4.55%) than nonsterilized women (2.17%) (P = .019). CONCLUSIONS: Tubal sterilization has no long-term effect on menstrual indices or pelvic pain. An increase in severe dysmenorrhea, which emerged as a disturbing but nonsignificant trend at 6-10 months, did not progress over the next 3-4.5 years. Reasons for an increased rate of hysterectomy are not clear, but may be related to a lower threshold for choosing hysterectomy as a treatment option once a woman has been sterilized.

Adult↗
PubMed1992

Mutations abolishing the endonuclease activity of bacteriophage lambda terminase lie in two distinct regions of the A gene, one of which may encode a "leucine zipper" DNA-binding domain.

Bacteriophage lambda terminase is a multifunctional enzyme composed of two subunits which are the products of the phage-encoded Nu1 and A genes. The enzyme catalyzes the endonucleolytic cleavage of lambda DNA at a site known as cosN and mediates packaging of the phage DNA into empty heads. This work describes the characterization of mutations within the A gene which lead to the loss of terminase endonuclease activity without affecting the ability of the enzyme to package monomeric mature (cut) lambda DNA. The residues changed by these mutations lie in two distinct regions within the carboxy half of the A protein. One of these regions has sequence homology with a conserved region of DNA polymerases. The other region resembles the "leucine zipper" DNA binding domain (bZIP) found in eukaryotic transcription factors in that both a basic region and leucine heptad-repeat are present. This terminase domain may be involved in the recognition and/or cleavage of cosN.

Amino Acid Sequence↗
PubMed1992

Diagonal earlobe creases and atheromatous disease: a postmortem study.

The association between the grade of earlobe creases and degree of atheromatous disease was investigated in 376 postmortem examinations. Each earlobe crease was individually graded from 0 to 3. The risk of atherosclerosis as a cause of death was nearly doubled in men with grade 3 creases in both earlobes, and more than trebled in women with bilateral high-grade creases. The risk of death from myocardial infarction was 2.50 in men with high-grade creases and 3.70 in women. The earlobe crease is an important sign of atheromatous disease and it may be useful to include it in the clinical examination of patients.

Aged↗
PubMed1990

Coarctation of the aorta associated with a sinus venosus atrial septal defect presenting with endocarditis in middle age.

We report the case of a 44 year old man who presented with an infective endocarditis and was found to have a coarctation of the aorta associated with a sinus venosus atrial septal defect and a small ventricular septal defect. The association of coarctation with a sinus venous atrial septal defect presenting with endocarditis in an adult is extremely rare.

Abnormalities, Multiple↗
PubMed1989

Changes in menstrual symptoms among sterilized and comparison women: a prospective study.

Changes in menstrual parameters after tubal sterilization were analyzed in ethnically diverse, poor women from three geographic areas in the United States. Two large suitable comparison groups were similarly studied. Menstrual cycles, duration of menstrual flow, and bleeding between periods were unchanged in the sterilization and comparison groups. The prevalence of dysmenorrhea increased in 10.8% of sterilized women, compared with 2.1% in the comparison groups. This difference was even more significant--16.4 and -0.5%--when usage of oral contraceptives and intrauterine devices was discounted. There was a nonsignificant increase in noncyclic pelvic pain.

Adult↗
PubMed1987

Sarcoidosis of the stomach.

A 25-year-old housewife presented with an 8-month history of epigastric pain, vomiting and weight loss. This was found to be due to sarcoidosis of the stomach. Her condition improved remarkably on steroids.

Adult↗