PubMed Health⌕ Search

Biomedical subjects

J B Cooper

Publications and source records attributed to J B Cooper.

10 recordsLinked to original sources
PubMed1992

Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.

The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.

Binding Sites↗
PubMed1992

Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases.

We report the X-ray analysis at 2.0 A resolution for crystals of the aspartic proteinase endothiapepsin (EC 3.4.23.6) complexed with a potent difluorostatone-containing tripeptide renin inhibitor (CP-81,282). The scissile bond surrogate, an electrophilic ketone, is hydrated in the complex. The pro-(R) (statine-like) hydroxyl of the tetrahedral carbonyl hydrate is hydrogen-bonded to both active-site aspartates 32 and 215 in the position occupied by a water in the native enzyme. The second hydroxyl oxygen of the hydrate is hydrogen-bonded only to the outer oxygen of Asp 32. These experimental data provide a basis for a model of the tetrahedral intermediate in aspartic proteinase-mediated cleavage of the amide bond. This indicates a mechanism in which Asp 32 is the proton donor and Asp 215 carboxylate polarizes a bound water for nucleophilic attack. The mechanism involves a carboxylate (Asp 32) that is stabilized by extensive hydrogen bonding, rather than an oxyanion derivative of the peptide as in serine proteinase catalysis.

Amino Acid Sequence↗
PubMed1992

Predicting body weight and wither height in Holstein heifers using body measurements.

Relationships between body weight, wither height, and various other body traits, including heart girth, body length, and hip width, were studied using data from six experiments with 2625 observations. Body weight and wither height were regressed on the other body traits. Regressions of body weight including the linear, quadratic, and cubic effects of a single independent variable (heart girth, wither height, hip width or body length) indicated that each measurement would be useful in predicting body weight (R2 > .95); the regression of body weight on heart girth had the highest R2, followed by hip width. Similarly, regressions of wither height on heart girth, wither height, hip width, or body length, including linear, quadratic, and cubic effects, yielded R2 > .99. Regressions considering multiple traits as independent variables showed that the addition of a second body trait added little to the already high multiple correlations found with a single variable. In management situations for which body weight or wither height cannot be measured, various other traits can be used to estimate these body measurements accurately.

Animals↗
PubMed1992

Multidisciplinary cycles for protein engineering: site-directed mutagenesis and X-ray structural studies of aspartic proteinases.

The specificity and pH profile of aspartic proteinases have evolved to include not only pepsin with a broad specificity and an optimal activity in acid media, but also renin, with high specificity for angiotensinogen and activity close to neutral pH. Comparisons of the structures and catalytic activities of aspartic proteinases provide helpful clues for engineering new activity profiles. We illustrate an approach that involves recombinant DNA techniques, biochemistry, structure determination and biocomputing. We use the 3-D structures of inhibitor complexes of several aspartic proteinases to define likely intermediates and specificity sub-sites. The multidisciplinary research is organised as cycles, in which each cycle tests a design hypothesis proposed in the previous cycle. We use one member of the aspartic proteinase family, chymosin, to illustrate these ideas in engineering enzymes with altered pH optima and specificities.

Amino Acid Sequence↗
PubMed1978

A new anesthesia delivery system.

A prototype anesthesia delivery system has been developed to test the appropriateness of new technological design approaches. The objectives were to eliminate human-factors problems associated with present anesthesia apparatus and to lay a suitable technical foundation for the development of new techniques in anesthesia management. This prototype performs all the functions of a conventional anesthesia machine, as well as many monitoring and surveillance tasks. Eventual incorporation of new teaching functions, and additional monitoring and record-keeping activities, are intended. The system is fundamentally electronic with few moving parts. Reliability, safety, and clarity of operation were the primary criteria in selection and application of the specific technologies employed. The result is a promising first step in the development of a system oriented toward supporting rather than preoccupying the anesthestist.

Anesthesia↗
PubMed1978

Preventable anesthesia mishaps: a study of human factors.

A modified critical-incident analysis technique was used in a retrospective examination of the characteristics of human error and equipment failure in anesthetic practice. The objective was to uncover patterns of frequently occurring incidents that are in need of careful prospective investigation. Forty-seven interviews were conducted with staff and resident anesthesiologists at one urban teaching institution, and descriptions of 359 preventable incidents were obtained. Twenty-three categories of details from these descriptions were subjected to computer-aided analysis for trends and patterns. Most of the preventable incidents involved human error (82 per cent), with breathing-circuit disconnections, inadvertent changes in gas flow, and drug-syringe errors being frequent problems. Overt equipment failures constituted only 14 per cent of the total number of preventable incidents, but equipment design was indictable in many categories of human error, as were inadequate experience and insufficient familiarity with equipment or with the specific surgical procedure. Other factors frequently associated with incidents were inadequate communication among personnel, haste or lack of precaution, and distraction. Results from multi-hospital studies based on the methodology developed could be used for more objective determination of priorities and planning of specific investments for decreasing the risk associated with anesthesia.

Accident Prevention↗
PubMed1976

The effect of protein and dietary energy levels and housing regime on production and reproduction parameters of turkey hens.

Two experiments were conducted using 960 Large Board Breasted White turkey hens to measure the effect of diet and confinement housing versus range pens on egg production, fertility and hatchability. A 2 X 3 factorial arrangement of diets provided protein levels of 15 and 18% with metabolizable energy levels of 2666, 2893, and 3101 kcal. per kg. of diet. The hens were randomized into 24 range pens and 24 pens in an open-sided house. Dietary protein levels had no effect on body weight, feed consumption, egg production, fertility or hatchability. Hens fed the higher energy diet produced larger eggs (P less than .05), but there was no difference in total egg production due to dietary energy level. As dietary energy level increased, feed consumption linearly decreased. Hens fed the 3102 kcal./M.E./kg. diet had significantly higher fertility (P less than .05) than hens fed the intermediate energy level diet with no differences between the lowest energy level and either of the other two levels. Fertile eggs from hens fed the intermediate energy level diet had lower hatchability (P less than .05) than those from hens fed either the lower or higher dietary energy levels. Type of housing and no effect on average body weight or feed consumption on a hen-day basis. Housing treatment had no effect on percent fertility or hatchability. Hens housed in the range pens produced more and larger eggs (P less than .05) and more eggs per kg. of feed than hens penned in the house.

Animals↗
PubMed1976

Light intensity and housing for pigeons.

Four light intensities were used in completely enclosed pigeon housed for 14 hours per 24 hours. Open front pens with only natural light were also used. There were four pens per treatment and five pairs of young, breeding age, White Carneaux per pen for 420 days. Results per treatment, 16, 30, 44 and 61 lumens per sq. m. and open pens, were respectively as follows for each objective: squabs raised-252, 220, 288, 203, and 212 with no significant differences except for the 44 lumen treatment which was higher than all others except 16; body wt./squab in g.-522, 526, 522, 508, and 531 at four weeks of age with no significant differences; feed per squab in kg.-4.7, 5.3, 4.5, 5.5, and 5.1 with only a significant difference between treatments 44 and 61 lumens; percent hatchability-89.7, 82.1, 89.6, 78.0, and 82.9 with no significant differences; percent squabs raised-93.7, 88.7, 97.9, 91.0, and 89.5 with no significant differences. The average number of squabs raised per treatment for all enclosed artifically lighted pens was 241 compared to 212 for the open pens with only natural light.

Animals↗
PubMed1976

Twin pigeon embryos.

Twin pigeon embryos were found on incubation day 18 in a pipped egg. The egg was pipped at the small end. The embryos were dead. Removal of a portion of the shell allowed removal of one embryo and revealed the second one. Both appeared normal in development and size.

Animals↗