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Biomedical subjects

A C Martin

Publications and source records attributed to A C Martin.

11 recordsLinked to original sources

Molecular modelling and site-directed mutagenesis on a bovine anti-testosterone monoclonal antibody.

A three-dimensional (3D) molecular model of the antigen-combining site of a bovine anti-testosterone monoclonal antibody has been constructed. In the model, the CDRs, and a single heavy chain framework region residue (Trp47), associate to form a hydrophobic cavity large enough to accommodate a single molecule of testosterone. Tyr97 of CDR-H3 lies at the bottom of the cavity with its hydroxyl group exposed to solvent. Using the model and data from binding studies, we predicted that the cavity forms the antibody's paratope and on binding testosterone a hydrogen bond is formed between Tyr97 of CDR-H3 and the hydroxyl group on the D-ring of testosterone. This prediction has subsequently been tested by site-directed mutagenesis. An antibody with phenylalanine in place of tyrosine at position 97 in CDR-H3 has its affinity reduced by approximately 800 fold. The reduction in binding energy associated with the reduced affinity has been calculated to be 3.9 kcal/mol which is within the range (0.5-4.0 kcal/mol) expected for the loss of a single hydrogen bond. The model has been used to suggest ways of increasing the antibody's affinity for testosterone.

Amino Acid Sequence

Developing national guidelines for nurse practitioner education: an overview of the product and the process.

In 1988, the National Organization of Nurse Practitioner Faculties appointed an ad hoc education committee (AHEC) to review existing nurse practitioner (NP) education curricula and to formulate national guidelines. An overview of the new NP guidelines are presented along with the philosophy, content, objectives, and competencies that are viewed as the foundation for NP education today. The guidelines are presented within the structure outlined in Brykczynski's (1985) research about NP practice. Thus, as a "product" of the Advanced Nursing Practice: Nurse Practitioner Curriculum Guidelines (NPCG), a new NP graduate for the 1990s could be described as one who demonstrates beginning competencies in primary health care theory and research within the five domains of practice identified by Brykczynski.

Clinical Competence

Molecular modeling of antibody combining sites.

Each of the six CDRs of Gloop2 is shown with the modeled structure in. Overall, the results obtained using the combined algorithm are similar in accuracy to those achieved using the canonical method of Chothia et al. However, the canonical method is limited to those loops where the key residues identified by Chothia are present. With the number of antibody structures currently available, it is not possible to classify CDR-H3 into canonical ensembles. Additionally, a small percentage of examples in the remaining CDRs do not match the current canonical classifications and the protein engineer may well wish to mutate the key residues, precluding the use of Chothia's method for modeling the resulting conformation. Thus the best approach appears to be to use Chothia's method (at least to model the backbone conformation) when the loop to be modeled is represented in the database of canonical structures. Any other loops, either unrepresented among the known canonicals (including CDR-H3), or where mutations have been made to the key residues, may then be modeled by the combined algorithm presented here.

Algorithms

Effects of zinc sulfate concentration and feeding frequency on ruminal protozoal numbers, fermentation patterns and amino acid passage in steers.

Effects of zinc sulfate (0 vs 1,142 ppm supplemental zinc from zinc sulfate) and feeding frequency (1 x vs 12x daily) on ruminal protozoa numbers, fermentation patterns and amino acid passage were investigated using four ruminally and abomasally cannulated mature Jersey steers in a 4 x 4 Latin square experiment. Steers (530 kg) were fed a 50:50 roughage:concentrate diet at 1.5 times their NEm requirement. Experimental periods were 14 d in duration; ruminal, abomasal and fecal samples were collected at 6-h intervals during the last 3 d of each period. Protozoa numbers tended to be lowest (1.82 x 10(6)/ml) in steers fed zinc 1 x and tended to be highest (3.83 x 10(6)/ml) in steers fed zinc 12 x daily (P less than .10). Frequent feeding decreased ruminal pH .24 units and increased total VFA 20.7%, ammonia 22.7% and ruminal digestion of dietary amino acids (AA) 61.6% (P less than .05). Zinc supplementation decreased ruminal digestion of dietary AA 35.8% (P less than .05) and the abomasal passage of bacterial OM and AA 21.2% (P less than .05) and increased ruminal output of amino acids as a percentage of intake 15.1% (P less than .05). Although it increased escape of dietary AA, zinc sulfate decreased postruminal passage of bacterial AA and resulted in a net negative effect on total postruminal AA passage as a percentage of intake. The effects of zinc on ruminal AA digestion may be more closely related to an interaction of zinc with dietary CP rather than to an effect of Zn on ruminal microbial populations.

Amino Acids

Antibody-combining sites: prediction and design.

For maximum value, a predicted model of an antibody-combining site should have an accuracy approaching that of an X-ray structure (1.6-2.7 A). In addition, the method by which the combining site is modelled should make no demands on the user of a sort that require arbitrary or subjective decisions to be made during the process. We have made substantial progress towards this objective and some recent results are reviewed. In addition, we describe how the modelling protocols developed can aid in the design of novel features within the antibody-combining site. The particular design example reported here suggests an approach for the introduction of metal-binding sites to create metallo-antibodies. This type of modification may be useful in the design of immunobiosensors, the induction of catalytic activity or simply as an alternative to metal chelates in the preparation of antibodies for imaging.

Algorithms

Adult survivors of parental alcoholism: implications for primary care.

Alcoholism has a significant impact on families. In fact, there are between 28 million and 34 million children and adults in America who are members of alcoholic families. There are many emotional and interpersonal consequences for adult children of alcoholics (ACAs), who often suffer from health problems complicated by unresolved emotional issues related to their families of origin. This article describes the family dynamics that affect the ACA's ability to deal with life stresses, outlines the general characteristics of adults who have a history of family alcoholism, discusses assessment techniques and describes resources available to assist the ACA toward recovery. Also described is the role of the primary health care provider in the treatment of ACAs.

Adult

Modeling antibody hypervariable loops: a combined algorithm.

To be of any value, a predicted model of an antibody combining site should have an accuracy approaching that of antibody structures determined by x-ray crystallography (1.6-2.7 A). A number of modeling protocols have been proposed, which fall into two main categories--those that adopt a knowledge-based approach and those that attempt to construct the hypervariable loop regions of the antibody ab initio. Here we present a combined algorithm requiring no arbitrary decisions on the part of the user, which has been successfully applied to the modeling of the individual loops in two systems: the anti-lysozyme antibody HyHel-5, the crystal structure of which is as a complex with lysozyme [Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C. & Davies, D. R. (1987) Proc. Natl. Acad. Sci. USA 84, 8075-8079], and the free antigen binding fragment (Fab) of the anti-lysozyme peptide antibody, Gloop2. This protocol may be used with a high degree of confidence to model single-loop replacements, insertions, deletions, and side-chain replacements. In addition, it may be used in conjunction with other modeling protocols as a method by which to model particular loops whose conformations are predicted poorly by these methods.

Algorithms

Managing common marital stresses.

Marital conflict and divorce are problems of great magnitude in our society, and nurse practitioners are frequently asked by patients to address marital problems in clinical practice. "Family life cycle theory" provides a framework for understanding the common stresses of marital life and for developing nursing strategies to improve marital satisfaction. If unaddressed, marital difficulties have serious adverse consequences for a couple's health, leading to greater dysfunction and a decline in overall wellness. This article focuses on identifying couples in crisis, assisting them to achieve pre-crisis equilibrium or an even higher level of functioning, and providing appropriate referral if complex relationship problems exist.

Adult

Mental health problems in primary care: a study of nurse practitioners' practice.

The purpose of this study was to explore whether NPs see clients for mental health problems in the primary care setting and the strategies NPs use to manage such problems. The results of a survey of 110 nurse practitioners suggest that NPs regularly encounter clients with mental health problems, use a wide variety of individual and family-focused strategies in caring for such clients and typically refer clients who have multiple problems/diagnoses.

Counseling

Improving marital relationships: strategies for the family physician.

BACKGROUND: Marital conflict and divorce are prevalent in our society, and patients frequently ask family physicians to assist them with marital difficulties. These difficulties are often associated with a decline in health, resulting in additional stress to the marital unit. METHODS: A MEDLINE search was undertaken using the key words "family medicine," "marital therapy," "marital counseling," "brief psychotherapy," and "short-term psychotherapy." The bibliographies of generated articles were searched for additional references. The authors used the resources of their individual behavioral science libraries, as well as their clinical experiences. RESULTS AND CONCLUSIONS: With adequate training, many family physicians can include marital counseling skills in their clinical repertoires. Family life cycle theory provides a framework for understanding the common stresses of marital life and also guides the family physician in recommending strategies to improve marital satisfaction. The physician's role is twofold: (1) to identify couples in crisis, and (2) to provide preventive strategies geared to assist couples in achieving pre-crisis equilibrium or higher levels of functioning. For physicians whose practices do not include marital counseling, an understanding of the basic techniques can be beneficial in effectively referring appropriate couples for marital therapy.

Counseling