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J B Cooper

Publications and source records attributed to J B Cooper.

At least 127 records · Page 7Linked to original sources
PubMed1989

X-ray studies of aspartic proteinase-statine inhibitor complexes.

The conformation of a statine-containing renin inhibitor complexed with the aspartic proteinase from the fungus Endothia parasitica (EC 3.4.23.6) has been determined by X-ray diffraction at 2.2-A resolution (R = 0.17). We describe the structure of the complex at high resolution and compare this with a 3.0-A resolution analysis of a bound inhibitor, L-364,099, containing a cyclohexylalanine analogue of statine. The inhibitors bind in extended conformations in the long active-site cleft, and the hydroxyl of the transition-state analogue, statine, interacts strongly with the catalytic aspartates via hydrogen bonds to the essential carboxyl groups. This work provides a detailed structural analysis of the role of statine in peptide inhibitors. It shows conclusively that statine should be considered a dipeptide analogue (occupying P1 to P1') despite lacking the equivalent of a P1' side chain, although other inhibitor residues (especially P2) may compensate by interacting at the unoccupied S1' specificity subsite.

Amino Acids↗
PubMed1989

High-resolution X-ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor: the analysis of the inhibitor binding and description of the rigid body shift in the enzyme.

The conformation of the synthetic renin inhibitor CP-69,799, bound to the active site of the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6), has been determined by X-ray diffraction at 1.8 A resolution and refined to the crystallographic R factor of 16%. CP-69,799 is an oligopeptide transition--state analogue inhibitor that contains a new dipeptide isostere at the P1-P1' position. This dipeptide isostere is a nitrogen analogue of the well-explored hydroxyethylene dipeptide isostere, wherein the tetrahedral P1' C alpha atom has been replaced by trigonal nitrogen. The inhibitor binds in the extended conformation, filling S4 to S3' pockets, with hydroxyl group of the P1 residue positioned symmetrically between the two catalytic aspartates of the enzyme. Interactions between the inhibitor and the enzyme include 12 hydrogen bonds and extensive van der Waals contacts in all the pockets, except for S3'. The crystal structure reveals a bifurcated orientation of the P2 histidine side chain and an interesting relative rotation of the P3 phenyl ring to accommodate the cyclohexyl side chain at P1. The binding of the inhibitor to the enzyme, while producing no large distortions in the enzyme active site cleft, results in small but significant change in the relative orientation of the two endothiapepsin domains. This structural change may represent the action effected by the proteinase as it distorts its substrate towards the transition state for proteolytic cleavage.

Aspartic Acid Endopeptidases↗
PubMed1989

Chronic hoarseness secondary to gastroesophageal reflux disease: documentation with 24-h ambulatory pH monitoring.

Gastroesophageal reflux (GER) has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. To study this relationship, we used 24-h ambulatory intraesophageal or dual pharyngoesophageal pH monitoring in 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. Twenty-six of the patients (78.8%) had pH evidence of severe GER, being at least three times greater than the upper limit of normal. In contrast to 19 patients with proven esophagitis, this GER was worse in the upright position. Of 15 patients with both pharyngeal and esophageal probes, three had esophagopharyngeal reflux, and two had atypical unexplained pharyngeal decreases in pH to below 4.0. Less than half of the 33 patients had the typical symptoms of GER, and standard esophageal tests usually yielded normal findings. Occult GER, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness, who have laryngeal lesions suggestive of GER. The causative mechanisms are not clear. The 24-h esophageal pH monitor is useful in screening this potentially treatable problem.

Adult↗
PubMed1989

Postanesthesia care unit standards for anesthesiologists. Board of Directors of the American Society of Post Anesthesia Nurses.

The following article describes postanesthesia care unit standards for anesthesiologists as developed by the Harvard Anesthesia Department's Risk Management Committee, Harvard Medical School. The standards were endorsed by the ASPAN Board of Directors, April 10, 1988. It is hoped that publication of these standards will assist PACU nurses in evaluating the anesthesia support they receive in their respective settings.

Anesthesiology↗
PubMed1987

Effects of information feedback and pulse oximetry on the incidence of anesthesia complications.

No standard outcome measures exist to evaluate the effect of interventions intended to improve the quality of anesthesia care. The authors established a clinically practical definition of outcome, and used it to assess the effect of feedback of information about complications and the effect of pulse oximetry on the rate and severity of important anesthesia-related problems encountered in the operating room (OR) and recovery room (RR). On admission to the RR, the patient's anesthetist documented Recovery-Room-Impact Events (RRIE), defined as an "unanticipated, undesirable, possibly anesthesia-related effect that required intervention, was pertinent to recovery-room care, and did or could cause at least moderate morbidity." Following a control period with no feedback of data, intense feedback of grouped (anonymous) RRIE rates was provided. Later, pulse oximeters were introduced to all anesthetizing locations. Among 12,088 patients (71% of all RR admissions), 18% had at least one RRIE in the OR or RR. The most common RRIEs were hypotension (4.4%), arrhythmia (3.9%), hypertension (1.5%), intubation difficulties (0.8%), hypoventilation (0.8%), and hypovolemia (0.6%). Feedback of information produced no demonstrable change in the rate of RRIEs. Although significantly fewer patients experienced RRIEs (15.6% vs. 12.4%, P less than 0.0001), hypotensive RRIEs (5.2% vs. 3.8%, P = 0.0003), and hypovolemic RRIEs (0.88% vs. 0.42%, P = 0.0017) following the introduction of pulse oximetry in the OR, confounding factors prevent establishment of a cause-and-effect relationship. Quality assurance may require more direct intervention and individual feedback to be effective. Still, the RRIE measure requires minimal effort at low cost and encourages improved transmission of information at the time of admission to recovery-room care.

Anesthesia↗
PubMed1986

Effects of an ATP site affinity analog on some conformational and enzymatic properties of the canine kidney (Na+ + K+)-ATPase.

We have shown previously that the canine kidney Na+,K+ pump [Na+ + K+)-ATPase) reacts with the ATP affinity analog p-fluorosulfonylbenzoyladenosine (FSBA). At 20 degrees C, we find the time-course of this reaction to be that predicted for a first-order reaction accompanied by competing solvolysis of the reagent. The FSBA-inactivated (Na+ + K+)-ATPase retains the ability to move between the E1 and E2 conformations that predominate in Na+ and K+ medium, respectively. Therefore, FSBA reaction with the enzyme does not interfere significantly with either its alkali metal cation binding or its conformational freedom. The ability of ATP to influence the enzyme's conformation by binding to the high-affinity nucleotide site is decreased, however, in proportion to the degree of inhibition of enzyme activity by FSBA. In addition, the ability of the enzyme to shift from the E1 to the E2 conformation through the (ATP + Na+)-dependent phosphorylation cycle is inhibited by FSBA treatment, as shown by the decreased ability of these substrates to stimulate the K+-dependent p-nitrophenylphosphatase activity. Both of these effects are consistent with specific reaction of FSBA with the ATP binding site of the enzyme. An additional effect of FSBA treatment is that it causes loss of p-nitrophenylphosphatase activity, but to a lesser extent than (Na+ + K+)-ATPase or Na+-ATPase activity. Binding of p-nitrophenylphosphate to the enzyme is apparently unaffected by FSBA treatment, since the Km for p-nitrophenylphosphate is not changed.

4-Nitrophenylphosphatase↗
PubMed1986

Supplemental niacin for lactating cows during summer feeding.

Five herds with 240 cows were used to determine the response to feeding 6 g/d of supplemental niacin during the summer months. Diets consisted of corn silage, hay crop silage, hay, or pasture as the forage and concentrate. Cows in each herd were paired by lactation number and stage of lactation and randomly assigned to either a control or niacin group and fed niacin once daily for 84 d (July 3 to September 25). Cows averaged 143 d postpartum with a total of 121 and 119 cows on control and niacin groups. Using milk weight and composition prior to initiating the trial as a covariate, least squares means for all cows for control and niacin were milk, 24.5, 25.4 kg/d; milk fat, 3.72, 3.70%; milk fat, .91, .94 kg/d; milk protein, 3.35, 3.34%; and fat-corrected milk, 23.5, 24.3, kg/d. Yields of milk and fat-corrected milk were significantly higher for niacin-supplemented cows. Cows in first lactation and second lactation and greater had a similar response to niacin. Cows producing greater than 34 kg milk produced 2.4 kg more milk with supplemental niacin. Results indicate that feeding 6 g/d supplemental niacin during the summer increased yield of milk and fat-corrected milk but had no effect on milk composition.

Animal Feed↗
PubMed1985

A developmentally regulated hydroxyproline-rich glycoprotein from the cell walls of soybean seed coats.

In soybean seeds the level of hydroxyproline is regulated in a developmental and tissue-specific manner. The seed coat contains approximately 77% of the total hydroxyproline in the seed at all stages of development. We determined the ratio of hydroxyproline to dry weight in a number of tissues within the seed; however, only the seed coat shows an increase in this ratio during development. Within the many cell layers of the seed coat, hydroxyproline is most abundant in the external layer. The hydroxyproline is present as an hydroxyproline-rich cell wall glycoprotein. The protein is rich in hydroxyproline (36%), lysine (11%), proline (10%), histidine (9%), tyrosine (9%), and serine (8%). The carbohydrate portion is 90 mole% arabinose and 10 mole% galactose. The arabinose residues are attached to hydroxyproline mostly in the form of trisaccharides. The apparent molecular weight of this glycoprotein is 100,000 daltons.

Journal Article↗
PubMed1984

An analysis of major errors and equipment failures in anesthesia management: considerations for prevention and detection.

Adaptations of the critical-incident technique were used to gather reports of anesthesia-related human error and equipment failure. A total of 139 anesthesiologists, residents, and nurse-anesthetists from four hospitals participated as subjects in directed or open-ended interviews, and 48 of them functioned as "trained observers." A total of 1,089 descriptions of preventable "critical incidents" were collected. Of these, 70 represented errors or failures that had contributed in some way to a "substantive negative outcome." From these incidents, ten potential strategies were developed for prevention or detection of incidents. Overall patterns observed in this wider study were similar to those of our earlier report. The incidents most frequently reported included breathing circuit disconnections, drug-syringe swaps, gas-flow control errors and losses of gas supply. Only 4% of the incidents with substantive negative outcomes involved equipment failure, confirming the previous impression that human error is the dominant issue in anesthesia mishaps. Among the broad categories of key strategies for mishap prevention were additional technical training, improved supervision, improved organization, equipment human-factors improvements, and use of additional monitoring instrumentation. The data also suggest that less healthy patients are more likely to be affected adversely by errors. It is suggested that, in future studies of anesthesia mortality and morbidity, untoward events should be classified according to preventive strategy rather than outcome alone as an aid to those who wish to apply the experience of others to lessen the risk in their individual practice.

Accident Prevention↗
PubMed1984

Cross-linking of soluble extensin in isolated cell walls.

The extensin component of primary cell walls has generally been considered to be an intrinsically insoluble cell wall glycoprotein. Recent data have established that cell wall extensin is in fact secreted in a soluble monomeric form which slowly becomes insolubilized in the cell wall probably through the oxidative formation of isodityrosine cross-links. We now show that isolated cell walls from aerated root slices of Daucus carota have the capacity to insolubilize extensin through the formation of isodityrosine. This in vitro cross-linking is specific for the extensin glycoprotein, as other wall proteins are not cross-linked by the isolated wall system. Although extensin can be cross-linked in solution by peroxidase and H(2)O(2), dityrosine and not isodityrosine is the phenolic cross-link formed. Wall-catalyzed cross-linking of soluble extensin is inhibited by l-ascorbate, and both the initial rate and total extent of cross-linking are inhibited by acidic pH in the physiological range (pH 4 to 6). We suggest several mechanisms by which acid might inhibit cross-linking and propose that cytoplasmic factors (ascorbate and/or hydrogen ions) may regulate the solubility of extensin in vivo.

Journal Article↗
PubMed1983

Insolubilization of hydroxyproline-rich cell wall glycoprotein in aerated carrot root slices.

The hydroxyproline-rich glycoprotein of plant cell walls is secreted from the cytoplasm as a soluble monomer which slowly becomes insolubilized. A tyrosine derivative, isodityrosine, is formed in the cell wall during this insolubilization and could serve as a protein-protein crosslink. Glycoprotein insolubilization is inhibited by peroxidase inhibitors and free radical scavengers, the most effective of which is L-ascorbate. These data support a hypothesis that the hydroxyproline-rich cell wall glycoprotein forms a covalently crosslinked wall network under the control of an extracellular peroxidase/ascorbate oxidase system.

Biopolymers↗