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Biomedical subjects

J B Cooper

Publications and source records attributed to J B Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1994

3,4-Dehydroproline inhibits cell wall assembly and cell division in tobacco protoplasts.

We investigated the function of cell wall hydroxyproline-rich glycoproteins by observing the effects of a selective inhibitor of prolyl hydroxylase, 3,4-dehydro-L-proline (Dhp), on wall regeneration by Nicotiana tabacum mesophyll cell protoplasts. Protoplasts treated with micromolar concentrations of Dhp do not develop osmotic stability and do not initiate mitosis. The architecture of regenerated cell walls was examined using deep-etch, freeze-fracture electron microscopy of rapidly frozen tobacco cells. Untreated protoplasts assemble a dense fibrillar cell wall consisting of laterally associating subelementary fibrils. In contrast, treatment of protoplasts with Dhp alters the structure of the regenerated wall fibrils in several ways: first, the microfibrils are coated with globular knobs; second, some larger fiber bundles have an open ribbon-like appearance; and third, the smallest subelementary fibrils were not visible. Tobacco cells develop an abnormal morphology as a consequence of this abnormal cell wall structure. Thus, inhibition of prolyl hydroxylase results in the regeneration of a cell wall with abnormal structural and functional properties. These data provide experimental evidence that hydroxyproline-rich glycoproteins are important for the structural integrity of primary cell walls and for the correct assembly of other wall polymers, and that wall structure is an important regulator of cell division and cell morphology.

Cell Division↗
PubMed1994

A new proline-rich early nodulin from Medicago truncatula is highly expressed in nodule meristematic cells.

We cloned and characterized MtPRP4, a new member of the repetitive proline-rich protein gene family in Medicago truncatula. The sequence of MtPRP4 predicts a 62-kD protein consisting of a 22-amino acid N-terminal signal peptide and a 527-amino acid repetitive proline-rich domain composed of three repetitive pentapeptide motifs arranged into two decapeptide repeats: PPVEKPPVHK and PPVEKPPVYK. MtPRP4 is the largest PRP described to date and contains repeated motifs that have not previously been found together in a single polypeptide. RNA gel blot experiments detected MtPRP4 transcripts in symbiotic root nodules, but not in roots, hypocotyls, or leaves. Accumulation of MtPRP4 transcript was an early response to Rhizobium inoculation and did not depend on nodule infection. In situ hybridization experiments demonstrated that MtPRP4 was expressed early in the development of the nodule meristem and that expression was highest in the meristematic cells of mature indeterminate nodules. These data support the proposition that an important early response of legume host roots to Rhizobium involves remodeling the host extracellular matrix and that proline-rich wall proteins play an important role in this architectural modification.

Amino Acid Sequence↗
PubMed1994

Towards patient safety in anaesthesia.

The anaesthesia specialty has focused on the safety of the patient and examination of untoward outcomes. Serious injuries are now rare in medically advanced countries. Still, anaesthesia deaths and complications are important because the anaesthetic itself has no intended therapeutic effect. Safety is a never-ending battle that requires continued effort because many forces have the potential to diminish whatever progress is made. This paper describes the modern movement in anaesthesia patient safety--the reasons it started, the major foci and explanations for why anaesthesia seems now to be safer than at any time in history. The American legal system, critical incident studies, studies of malpractice claims and large-scale studies of anaesthesia outcomes played a role in increasing the awareness of the need to enhance anaesthesia safety. Many efforts are believed to have contributed to improvements in the safety of anaesthesia: improved training of anaesthesia clinicians, new pharmaceuticals, new technologies for monitoring (especially pulse oximetry and capnography), standards for monitoring and other aspects of anaesthesia care, safety enhancements in anaesthesia equipment and the implementation of quality assurance and risk management programmes. The creation of the Anesthesia Patient Safety Foundation in the United States and a similar organization in Australia have helped to bring about awareness of safety issues and to support study of patient safety. Ultimately, the motto of the Anesthesia Patient Safety Foundation should be the goal of all anaesthesia professionals: "That no patient shall be harmed by anaesthesia".

Anesthesia↗
PubMed1993

Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors.

Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme homologous to renin. Crystal structures of inhibitor-bound complexes have provided invaluable insight regarding the three-dimensional structure of the aspartic proteinase family of enzymes, as well as the steric and polar interactions that occur between the proteins and the bound ligands. Beyond this, subtleties of binding have been revealed, including multiple subsite binding modes and subsite interdependencies. This information has been applied in the design of novel potent renin inhibitors and in the understanding of structure-activity relationships and enzyme selectivities.

Amino Acid Sequence↗
PubMed1993

Crystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors.

The aspartic proteinase from yeast vacuoles, proteinase-A, has been crystallized with and without non-hydrolysable transition-state analogue inhibitors. The native enzyme crystals belong to the space group I2(1)2(1)2(1), with two molecules per asymmetric unit. The inhibitor complex crystals are trigonal with space group P3(2)21 and with one molecule in the asymmetric unit. Preliminary X-ray analysis of both native enzyme and its complexes indicate that the complexes diffract to higher resolution than the native crystals. This is probably due to reduced flexibility in the enzyme-inhibitor complex.

Aspartic Acid Endopeptidases↗
PubMed1993

The use of protein homologues in the rotation function.

The success of molecular replacement depends, in part, on the degree of similarity of the target and search molecules. We have systematically investigated this effect in cross-rotation functions for members of the aspartic proteinase family of enzymes. The influence of various parameters on peak heights was investigated for six search models using magnitude of F(obs) data for two target enzymes. The beneficial effects of high-resolution data and a large radius of integration are most pronounced when target and search molecules have high-percentage identities. Correction for small differences in domain-domain orientation (typically 4-8 degrees) between search and target structures leads to only a marginal improvement in the rotation-function peak height. There is an almost linear relationship between the structural distance, D, a parameter used in cluster analysis to define differences between three-dimensional protein structures, and the height of the cross-rotation-function peaks.

Aspartic Acid Endopeptidases↗
PubMed1993

X-ray-crystallographic studies of complexes of pepstatin A and a statine-containing human renin inhibitor with endothiapepsin.

H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds).

Amino Acid Sequence↗
PubMed1993

Algorithm to identify components of arterial blood pressure signals during use of an intra-aortic balloon pump.

Existing bedside cardiovascular monitors often inaccurately measure arterial blood pressure during intra-aortic balloon pump (IABP) assist. We have developed an algorithm that correctly identifies features of arterial pressure waveforms in the presence of IABP. The algorithm is adaptive, functions in real-time, and uses information from the electrocardiographic (ECG) and arterial blood pressure signals to extract features and numeric values from the arterial blood pressure waveform. In its current form, it requires reliable ECG beat detection and was not intended to operate under conditions of extremely poor balloon timing. The algorithm was evaluated by an expert (P.F-C.) on a limited data set, which consisted of 12 1-minute epochs of data recorded from 6 intensive care unit patients. A criterion for selection of patients was that the ECG beat detector could detect ECG beats correctly from the waveforms. The overall sensitivity and positive predictivity for beat detection were 94.04% and 100%, respectively. For feature identification, the overall sensitivity was greater than 89%, positive predictivity was 100%, and the false-positive rate was 0%. The performance measures may be biased by the criteria for patient selection. This approach to identifying waveform features during IABP improves the accuracy of measurements. The utility of using 2 sources of information to improve measurement accuracy has been demonstrated and should be applicable to other physiologic signal-processing applications.

Algorithms↗
PubMed1993

A mass balance model for the Mapleson D anaesthesia breathing system.

A mathematical model is described which calculates the alveolar concentration of CO2(FACO2) in a patient breathing through a Mapleson D anaesthesia system. The model is derived using a series of mass balances for CO2 in the alveolar space, dead space, breathing system limb volume and reservoir. The variables included in the model are tidal volume (VT), respiratory rate, fresh gas flow rate (Vf), dead space volume, I:E ratio, and expiratory limb volume (Vl) time constant of lung expiration, and carbon dioxide production rate. The model predictions are compared with measurements made using a mechanical lung simulator in both spontaneous and controlled ventilation. Both the model and the experimental data predict that at high fresh gas flow rates and low respiratory rates, FACO2 is independent of Vf; at low fresh gas flow rates and high respiratory rates, FACO2 is independent of respiratory rate. The model and the data show that the VT influences FACO2, independent of minute ventilation alone, during both partial re-breathing and non-rebreathing operation. Therefore, describing the operation in terms of minute ventilation is ambiguous. It is also shown that Vl influences FACO2 such that, for any combination of patient and breathing-system variables, there is a Vl that minimizes the Vf required to maintain FACO2. In addition, expiratory resistance can increase the fresh gas flow rate required to maintain a given FACO2. The respiratory patterns observed with spontaneous and controlled ventilation are responsible for the difference in Vf required with each mode of ventilation.

Anesthesiology↗
PubMed1993

Perioperative monitoring with pulse oximetry and late postoperative cognitive dysfunction.

In a randomized, blinded clinical study, we have used objective and subjective measures to determine if perioperative monitoring with pulse oximetry--by virtue of its potential to lessen hypoxaemia--would decrease late postoperative cognitive dysfunction. We investigated 736 adult patients undergoing elective procedures (other than cardiac, neurosurgical or for cancer) under regional or general anaesthesia, allocated randomly to undergo (group I) or not to undergo (group II) pulse oximetry monitoring in the operating theatre and recovery room. Cognitive function was evaluated using the Wechsler memory scale (WMS) and continuous reaction time (RT) test the day before surgery, and on the 7th day after operation or at discharge if that occurred before postoperative day 7. A questionnaire sent 6 weeks after surgery elicited patients' subjective perceptions regarding cognitive abilities. There were no significant differences between the two groups in either the total WMS score, the score for each WMS subtests or RT test. The questionnaire revealed that 7% in group I and 11% in group II believed cognitive abilities had decreased (ns). For the 40 patients whose WMS scores were 10 points less after than before operation, a follow-up study was undertaken 3 months after surgery. At that time, the median WMS score had returned to the preoperative value. We conclude that, for these 736 patients, subjective and objective measures did not indicate less postoperative cognitive impairment after perioperative monitoring with pulse oximetry.

Adolescent↗
PubMed1993

Randomized evaluation of pulse oximetry in 20,802 patients: I. Design, demography, pulse oximetry failure rate, and overall complication rate.

BACKGROUND: Although pulse oximetry is currently in widespread use, there are few data documenting improvement in patient outcome as a result of the use of oximetry. The authors describe the study design, patient demographic findings, data validation, pulse oximetry failure rate, and overall postoperative complication rates in the first large prospective randomized multicenter clinical trial on perioperative pulse oximetry monitoring. METHODS: In five Danish hospitals, by random assignment, monitoring did or did not include pulse oximetry for patients 18 yr of age and older, whether scheduled for elective or emergency operations, or for regional or general anesthesia, except during cardiac and neurosurgical procedures. Operational definitions were established for perioperative events and postoperative complications. The data were collected preoperatively, during anesthesia, in the postanesthesia care unit, and until the day of discharge from the hospital or the seventh postoperative day. RESULTS: Of 20,802 patients, 10,312 were assigned to the oximetry group and 10,490, to the control group. In general, the demographic data, patient factors, and anesthetic agents used were distributed evenly. A slight intergroup difference was found in the distribution of age, duration of surgery, some types of surgery, and some types of anesthesia. The total failure rate of the oximetry was 2.5%, but it increased to 7.2% in patients with American Society of Anesthesiologists physical status 4 (P < 0.00001). In 14.9% of the patients, one or more events occurred in the operating room and 13.5% in the postanesthesia care unit. The overall postoperative complication rate was 9.7%. The total rates of cardiovascular and respiratory complications were 2.78% and 3.50%, respectively. Within the first seven postoperative days, 0.47% of the patients died. Anesthesia was not thought to have been solely responsible for any death, but in 7 patients (1 per 3,365), it was a possible contributory factor. CONCLUSIONS: Despite the finding of a few significant inter-group differences, the randomization was well balanced with a high validity of data. The overall postoperative complication rate was similar to that in other recent morbidity and mortality studies.

Adult↗
PubMed1993

Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative events and postoperative complications.

BACKGROUND: The authors describe the effect of pulse oximetry monitoring on the frequency of unanticipated perioperative events, changes in patient care, and the rate of postoperative complications in a prospective randomized study. METHODS: The study included 20,802 surgical patients in Denmark randomly assigned to be monitored or not with pulse oximetry in the operating room (OR) and postanesthesia care unit (PACU). RESULTS: During anesthesia and in the PACU, significantly more patients in the oximetry group had at least one respiratory event than did the control patients. This was the result of a 19-fold increase in the incidence of diagnosed hypoxemia in the oximetry group than in the control group in both the OR and PACU (P < 0.00001). In the OR, cardiovascular events were observed in a similar number of patients in both groups, except myocardial ischemia (as defined by angina or ST-segment depression), which was detected in 12 patients in the oximetry group and in 26 patients in the control group (P < 0.03). Several changes in PACU care were observed in association with the use of pulse oximetry. These included higher flow rate of supplemental oxygen (P < 0.00001), increased use of supplemental oxygen at discharge (P < 0.00001), and increased use of naloxone (P < 0.02). The rate of changes in patient care as a consequence of the oximetry monitoring increased as the American Society of Anesthesiologists physical status worsened (P < 0.00001). One or more postoperative complications occurred in 10% of the patients in the oximetry group and in 9.4% in the control group (difference not significant). The two groups did not differ significantly in cardiovascular, respiratory, neurologic, or infectious complications. The duration of hospital stay was a median of 5 days in both groups (difference not significant). An equal number of inhospital deaths were registered in the two groups. Questionnaires, completed by the anesthesiologists at the five participating departments, revealed that 18% of the anesthesiologists had experienced a situation in which a pulse oximeter helped to avoid a serious event or complication and that 80% of the anesthesiologists felt more secure when they used a pulse oximeter. CONCLUSIONS: This study demonstrated that pulse oximetry can improve the anesthesiologist's ability to detect hypoxemia and related events in the OR and PACU and that the use of the oximeter was associated with a significant decrease in the rate of myocardial ischemia. Although monitoring with pulse oximetry prompted a number of changes in patient care, a reduction in the overall rate of postoperative complications was not observed.

Adult↗
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

X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins.

X-ray analyses have defined the three-dimensional structures of crystals of mouse and human renins complexed with peptide inhibitors at resolutions of 1.9 and 2.8 A, respectively. The exquisite specificity of renin arises partly from ordered loop regions at the periphery of the binding cleft. Although the pattern of main-chain hydrogen bonding in other aspartic proteinase inhibitor complexes is conserved in renins, differences in the positions of secondary structure elements (particularly helices) also lead to improved specificity in renins for angiotensinogen substrates.

Amino Acid Sequence↗
PubMed1992

Crystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.

Porphobilinogen deaminase, the polymerase that catalyses the synthesis of preuroporphyrinogen, the linear tetrapyrrole precursor of uroporphyrinogen III, has been crystallized from sodium acetate buffer with polyethylene glycol 6000 as precipitant. The crystals are orthorhombic and the space group is P2(1)2(1)2, with unit cell dimensions a = 88.01 A, b = 75.86 A, c = 50.53 A and alpha = beta = gamma = 90 degrees, indicating a single molecule of 34 kDa in the asymmetric unit. The crystals grow to dimensions of 1 mm x 2 mm x 0.5 mm within two weeks in the dark and are stable in the X-ray beam for at least 40 hours. Diffraction data beyond 1.7 A resolution, observed with a synchrotron radiation source, indicate that a high resolution structure analysis is feasible.

Crystallization↗