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Biomedical subjects

D L Harris

Publications and source records attributed to D L Harris.

At least 19 recordsLinked to original sources

Questions asked by family physicians who want to serve as medical student preceptors.

This article addresses the needs of family physician preceptors who teach medical students in their community-based practices. Responses are provided to 20 typical questions that a family physician might ask when considering whether to become a preceptor. Areas covered by the questions and responses include physician motivation for becoming a preceptor, characteristics of good preceptors, specific issues related to working with students in the office, what to teach students, how to give students feedback, evaluation of students, and relationships with the medical school.

Communication

Breeding for profit: synergism between genetic improvement and livestock production (a review).

Fifty years of research in animal breeding and genetics are examined from four perspectives: 1) genetic prediction, 2) animal testing and selection schemes, 3) dissemination of genetic improvement, and 4) definition of breeding objectives in economic form. Breeding in all classes of livestock has moved from a purebred appearance orientation to a performance (either purebred or crossbred) orientation. Unfortunately, the evolution from a performance orientation to an economic orientation is incomplete, especially for some livestock classes. Placing breeding objectives into a mathematical form on a sound economic basis is key to integrating modern developments in animal breeding into more purposeful industry programs. Procedures used to develop such objectives are reviewed with attention to common approaches. Where consensus is reached about a breeding objective (in economic form) for a class of livestock, this objective can be used in conjunction with genetic predictions to rank animals within a breeding population. Ranking without undue attention to herd of origin facilitates a pyramid-shaped hierarchy of animals that can be fundamental to the functioning of breeding enterprises contributing improvements to operations concerned with production. Genetic improvements should flow from proven genetically superior animals to improved production systems. The tiers of the pyramid need to be organized relative to animals with differing levels of economic evaluation.

Animal Husbandry

Principles and pitfalls in designing site-directed peptide ligands.

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints.

Bence Jones Protein

Mechanistic stoichiometry of mitochondrial oxidative phosphorylation.

P/O ratios of rat liver mitochondria were measured with particular attention to systematic errors. Corrections for energy loss during oxidative phosphorylation were made by measurement of respiration as a function of mitochondrial membrane potential. The corrected values were close to 1, 0.5, and 1 at the three coupling sites, respectively. These values are consistent with recent measurements of mitochondrial proton transport.

Adenosine Diphosphate

Binding of peptides to proteins: an exercise in molecular design.

Peptides coupled to solid supports were systematically tested for binding activity with a polyreactive immunoglobulin light chain dimer by the methods of Geysen and colleagues. Once identified, peptides of progressively increasing affinity for the dimer were synthesized in milligram quantities and diffused into crystals of the protein. The three-dimensional structures of the peptide-protein complexes were determined by X-ray analysis and crystallographic refinement. Criteria for the design of ligands to fill the binding cavity in incremental stages could be formulated from the combined results of peptide scanning and crystallographic analyses. Histidine proved to be an important substituent in the binding series. It was possible to manipulate the properties of this amino acid residue to alter the structures and binding patterns of the ligands. For example, if two beta-alanine residues were added to the carboxyl end of a tetrapeptide ligand, the terminal carboxyl group formed an intramolecular ion pair with the imidazolium group (N-3) of histidine. This interaction was accompanied by cleavage of the intra molecular hydrogen bond between N-1 of histidine and the amide group of a glutamine side chain. The shape of the ligand shifted from a compact to an extended form and the mode of binding changed from a lock-and-key to an induced-fit type. The direction of entry of dipeptides of histidine and proline into the binding cavity (normally amino end first) could be reversed (carboxyl end first) by protonation of the histidine ring.

Amino Acid Sequence

Computer simulation model of swine production systems: I. Modeling the growth of young pigs.

Theoretical concepts and relationships were used to develop a deterministic pig growth model. The model predicts, in a continuous form, growth and body composition of boars, barrows, and gilts according to genotype, diet, and management conditions. The model is aggregated at the whole-animal level with three main elements of body composition; total body DNA, total body protein mass (PT), and total body mass of lipids, with PT determining the secondary elements of ash and moisture. The primary factors regulating growth were associated with cellular hyperplasia and hypertrophy in agreement with the basic concepts described by Baldwin and Black (1979). Differential equations representing DNA accretion and protein synthesis and degradation were adapted from Oltjen et al. (1985). Normal pig protein growth was characterized from published data. Body PT was used to reflect several metabolic activities related to animal size and age, as in some prior models. Dietary energy and protein were used in sequence until requirements are satisfied, first for maintenance, then for protein growth, and finally for fat deposition. A comparison between experimental and simulated results illustrates that the model may simulate growth and body composition of young pigs adequately.

Animals

Computer simulation model of swine production systems: II. Modeling body composition and weight of female pigs, fetal development, milk production, and growth of suckling pigs.

Theoretical concepts and relationships used to develop a deterministic computer simulation model of female pigs during their reproductive life are described. The model predicts, in a continuous form, body composition and weight of female pigs, fetal development, sow milk yield, and growth of suckling pigs according to genotype, diet, and management conditions. The model simulates growth of adult female pigs. Dietary nutrients are used first for maintenance and second for fetal growth or milk production. Any surplus is retained in the body. Energy and protein body reserves are mobilized when a nutrient deficit occurs during gestation or lactation. However, the rates of body protein and fat accretion as well as the fat/protein ratio are limited by boundaries, the values of which depend on the nutritional and physiological status of the pig. The model's ability to simulate sow body weight changes and composition, fetal growth, milk production, and suckling pig's growth is illustrated.

Animals

Computer simulation model of swine production systems: III. A dynamic herd simulation model including reproduction.

A dynamic herd simulation model for a swine production unit has been developed. The model is discrete and stochastic and the appropriate random distributions have been defined from the literature or empirically estimated. Theoretical concepts and relationships presented previously are used to simulate growth and the overall life cycle of individual animals. Simulated animals are young pigs (from birth to slaughter age), gilts, and sows. Animal events are farrowing, weaning, mating, end-nursery (transfer from nursery to the growing-finishing facility), and slaughter and are processed individually using a next-event scheduling orientation package. Animals within the herd are culled for different health and reproductive reasons. Genetic parameters, diet composition, and herd management are input variables chosen by the user. The effects of nutrition, genetics, season, and other factors on several reproductive parameters are considered. Model evaluation is performed by studying the output of the model under specified herd situations. The herd model adequately simulates animal flow and dynamics of the herd.

Animal Nutritional Physiological Phenomena

Genetic improvement programs in livestock: swine testing and genetic evaluation system (stages).

Genetic evaluations for the U.S. swine industry are conducted by the eight purebred associations of the National Association of Swine Records. Within-herd evaluations of the growth traits (days to 105 kg [market] and backfat depth) were first reported in 1986. Analyses of the maternal traits (litter size at birth and weaning, and litter 21-d weight) were inaugurated in 1987. Expected progeny differences (EPD) are reported for all traits and for general, paternal, and maternal bioeconomic indexes. A sow productivity index combining only maternal traits is available. All records are adjusted according to National Swine Improvement Federation (NSIF) guidelines for effects such as number of pigs transferred at crossfostering and age at recorded observation prior to the BLUP evaluation. Within-herd analyses of individual contemporary groups are conducted immediately on receipt of performance records at each breed association office. All parents in the herd and the young pigs in the current group are evaluated. A report is returned to the breeder for use in herd selection and the EPD are placed in the pedigree file. The genetic base of each herd is defined as the first n tested pigs or litters, where n is the number of pigs registered annually within the herd. Change in mean EPD between groups is indicative of genetic trend. Periodic across-herd analyses are used to update interim within-herd analyses and a national sire summary is published.

Animals

The current and future need for minority medical faculty.

Little progress has been made in increasing the number of minority faculty members at US medical schools. From 1975 through 1989, underrepresented minority medical faculty increased only 0.3%--from 2.7% to 3.0%. In the field of medicine in general, only 3% of physicians are African-American and 3% are Hispanic, while the African-American and Hispanic populations are approximately 12% and 7%, respectively, of the total US population. A number of factors have caused the persistent underrepresentation of minority health professions trainees: inadequate or inappropriate career counseling, admissions policies, relatively high attrition rates after matriculation, substantial costs of education, and lack of appropriate mentors and role models. Helping minority students overcome these obstacles requires providing them with appropriate information, preparation, motivation, and opportunities at all stages of the educational process. Attention must focus on recruiting minority students into the scientific, academic professions if an increase is to occur in numbers of underrepresented minorities in all specialties of medicine. The Health Resources and Services Administration and private foundations have committed to providing funds to educational institutions to help encourage minority students to pursue academic careers. Leadership at these institutions must also commit to increasing the numbers of underrepresented minority faculty and senior administrators.

Ethnicity