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Biomedical subjects

J M Moore

Publications and source records attributed to J M Moore.

At least 73 records · Page 4Linked to original sources
PubMed1994

Nocturnal orthopaedic operating: can we let sleeping orthopaedic surgeons lie?

A 12-month retrospective study of emergency orthopaedic operations in a district general hospital was performed. There were 962 emergency admissions of whom 272 (17.7%) underwent emergency operation. The largest group consisted of those undergoing operation for femoral neck fractures (37.6% of the total). Despite 58.8% of the patients presenting to the accident and emergency (A&E) department between 0800 and 1700 hours, the majority (66.2%) were operated on 'out-of-hours'. Those patients undergoing emergency operation out-of-hours were allocated to one of three categories (emergency, urgent, or scheduled) depending on the nature and severity of their presenting condition. In the authors' opinion, 81.9% of the patients could have been appropriately classified as scheduled cases and that all out-of-hours operating in this group of patients could have been deferred until the following morning. This would have reduced the number of orthopaedic operations performed out-of-hours from 182 to 33. The operating time at night would have been reduced from 126.9 h to 15.8 h. The implications of this study are important in view of the currently proposed changes in the hours worked by surgical trainees, the CEPOD findings, and the Government's proposals outlined in Achieving a Balance.

Adolescent↗
PubMed1993

15N NMR relaxation studies of the FK506 binding protein: backbone dynamics of the uncomplexed receptor.

Backbone dynamics of the major tacrolimus (FK506) binding protein (FKBP-12, 107 amino acids) have been studied using 15N relaxation data derived from proton-detected two-dimensional 1H-15N NMR spectroscopy. 15N spin-lattice relaxation rate constants (R1), spin-spin relaxation rate constants (R2), and heteronuclear NOEs were determined for over 85% of the backbone amide 15N nuclei. A model free formalism [Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559; Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4559-4570] was used to derive values for the generalized order parameter (S2), the effective correlation time for internal motions (tau e), and the chemical exchange line width (Rex) for each N-H bond vector. The final optimized overall correlation time (tau m) was 9.2 ns. The average order parameter (S2) describing the amplitude of motions on the picosecond time scale was found to be 0.88 +/- 0.06. Motions on the picosecond time scale are restricted at the N and C termini, consistent with previous NMR structural studies indicating well-defined beta-strands in these regions. With the exception of the flap region from resides 82 to 87, no regions appear to be significantly disordered on the picosecond time scale. Residues in several regions of the protein exhibit high Rex terms, indicating possible motions on the millisecond to microsecond time scale due to chemical exchange and/or conformational averaging effects. Possible effects of tacrolimus (FK506) binding on FKBP-12 dynamics are discussed in the context of previously determined solution structures for FKBP-12 in the uncomplexed [Michnick et al. (1991) Science 252, 836-839; Moore et al. (1991) Nature 351, 248-250] and complexed [Meadows et al. (1993) Biochemistry 32, 754-765] states.

Amides↗
PubMed1993

Femtogram on-column detection of nicotine by isotope dilution gas chromatography/negative ion detection mass spectrometry.

A gas chromatographic method, utilizing detection by negative chemical ionization (NCI) mass spectrometry, is presented for the detection of nicotine. The method incorporates derivatization with heptafluorobutyric anhydride/pyridine to yield the ring-opened addition product, 1-[4-(3'-pyridyl)-4-heptafluorobutyryloxybutyl]-1- methylheptafluorobutanamide. The resulting heptafluorobutanamide is both relatively stable and an excellent electron scavenger. This methodology provides for the detection of nicotine at femtogram on-column levels, the measurement of nicotine over three orders of magnitude, and the minimization of contamination due to environmental nicotine.

Chromatography, Ion Exchange↗
PubMed1993

The application of capillary gas chromatography-electron capture detection in the comparative analyses of illicit cocaine samples.

The gas chromatographic detection of manufacturing impurities in illicit cocaine can be enhanced by chemical derivatization and the use of an electron-capture detector. After derivatization of illicit cocaine hydrochloride samples with heptafluorobutyric anhydride, the isolated heptafluorobutyryl derivatives of the cocaine impurities were subjected to capillary gas chromatography-electron capture detection analysis. The on-column detection of cocaine impurities at low picogram levels was possible for compounds such as N-norcocaine and other N-demethylated impurities, amidic by-products, including N-benzoylnorecgonine methyl ester and tertiary amines possessing hydroxy functions. The latter compounds include the so-called hydroxycocaine impurities, believed to be new coca leaf alkaloids. This methodology is especially suited for sample comparison analyses.

Cocaine↗
PubMed1993

The anatomy of a cocaine comparison case: a prosecutorial and chemistry perspective.

Methodology used for the comparative chemical analyses of two illicit cocaine seizures, and its application in a successful criminal prosecution, is described. A description of events leading to the arrest of the defendant and an overview of the jury trial are provided. Illicit cocaine, found in the defendant's suitcase and wallet, was subjected to chemical derivatization and three distinct gas chromatographic methods for the detection and relative quantitation of cocaine manufacturing impurities/by-products. The cocaine impurities included cis- and trans-cinnamoylcocaine, the isomeric truxillines and the hydroxycocaines. Among the cocaine manufacturing byproducts detected were benzoylecgonine, ecgonine methyl ester, ecgonine, N-benzoylnorecgonine methyl ester and N-norcocaine. Chemical derivatization of the cocaine samples was accomplished using heptafluorobutyric anhydride and N,O-bis(trimethylsilyl)acetamide. The derivatized impurities/by-products were subjected to capillary gas chromatographic analysis using both flame ionization and electron-capture detectors. The comparative chemical analyses provided a positive correlation between the suitcase and wallet cocaine samples.

Chromatography, Gas↗
PubMed1992

Solution structure of FK506 bound to FKBP-12.

The complex of the immunosuppressant FK506 bound to FKBP-12 has been studied in solution using 1H and inverse-detected 13C NMR methods. The resonances of bound, 13C-labelled FK506 were assigned and a set of 66 intraligand NOE distance restraints were used to calculate the structure of the bound ligand by distance geometry and restrained molecular dynamics methods. The structure of bound FK506 in solution closely resembles that seen in the X-ray structure [17], except for the allyl region. The differences reflect the influence of intermolecular crystal contacts and have implications for interpretation of the interaction of the FK506/FKBP complex with its putative biological receptor.

Carrier Proteins↗
PubMed1992

Auditory responsiveness of premature infants utilizing visual reinforcement audiometry (VRA).

The purpose of this investigation was to study the relationship between visual reinforcement audiometry (VRA) performance and age (i.e., corrected and mental) with 60 premature infants. VRA performance was classified as unacceptable, marginal, or acceptable based on conditionability and number of responses obtained before habituation to the task. The results indicated that mental age and corrected age were significantly related to VRA performance. It was found that a corrected age of 8 mo and/or a mental age of 6 mo is typically required for acceptable performance using VRA. A lack of responsiveness to the VRA procedure at these ages would most likely be due to hearing loss as opposed to a general developmental delay. The data from this study would not support a large scale behavioral hearing screening program for premature infants below 8 mo corrected age or 6 mo mental age.

Acoustic Stimulation↗
PubMed1991

High-resolution solution structure of reduced French bean plastocyanin and comparison with the crystal structure of poplar plastocyanin.

The three-dimensional solution structure of reduced (CuI) plastocyanin from French bean leaves has been determined by distance geometry and restrained molecular dynamics methods using constraints obtained from 1H n.m.r. (nuclear magnetic resonance) spectroscopy. A total of 1244 experimental constraints were used, including 1120 distance constraints, 103 dihedral angle constraints and 21 hydrogen bond constraints. Stereospecific assignments were made for 26 methylene groups and the methyls of 11 valines. Additional constraints on copper co-ordination were included in the restrained dynamics calculations. The structures are well defined with average atomic root-mean-square deviations from the mean of 0.45 A for all backbone heavy atoms and 1.08 A for side-chain heavy atoms. French bean plastocyanin adopts a beta-sandwich structure in solution that is similar to the X-ray structure of reduced poplar plastocyanin; the average atomic root-mean-square difference between 16 n.m.r. structures and the X-ray structure is 0.76 A for all backbone heavy atoms. The conformations of the side-chains that constitute the hydrophobic core of French bean plastocyanin are very well defined. Of 47 conserved residues that populate a single chi 1 angle in solution, 43 have the same rotamer in the X-ray structure. Many surface side-chains adopt highly preferred conformations in solution, although the 3J alpha beta coupling constants often indicate some degree of conformational averaging. Some surface side-chains are disordered in both the solution and crystal structures of plastocyanin. There is a striking correlation between measures of side-chain disorder in solution and side-chain temperature factors in the X-ray structure. Side-chains that form a distinctive acidic surface region, believed to be important in binding other electron transfer proteins, appear to be disordered. Fifty backbone amide protons form hydrogen bonds to carbonyls in more than 60% of the n.m.r. structures; 45 of these amide protons exchange slowly with solvent deuterons. Ten hydrogen bonds are formed between side-chain and backbone atoms, eight of which are correlated with decreased proton exchange. Of the 60 hydrogen bonds formed in French bean plastocyanin, 56 occur in the X-ray structure of the poplar protein; two of the missing hydrogen bonds are absent as a result of mutations. It appears that molecular dynamics refinement of highly constrained n.m.r. structures allows accurate prediction of the pattern of hydrogen bonding.

Amino Acid Sequence↗
PubMed1991

Solution structure of the major binding protein for the immunosuppressant FK506.

The major FK506 binding protein (FKBP, relative molecular mass approximately 11,800; Mr 11.8K) and cyclophilin (Mr approximately 17K) belong to a class of proteins termed immunophilins. Although unrelated at the amino-acid sequence level, they both possess peptidyl-prolyl cis-trans isomerase activities which are inhibited by immunosuppressants that block signal transduction pathways leading to T-lymphocyte activation. FK506 and rapamycin strongly inhibit the peptidyl-prolyl cis-trans isomerase activity of FKBP, whereas cyclosporin A inhibits that of cyclophilin. The significance of this enzyme activity and the role of the immunophilins in immunoregulation is unknown. To understand better the function of the immunophilins and their interaction with inhibitors, we are investigating the solution structures of FKBP and FKBP-inhibitor complexes by multidimensional NMR methods. Here we report the solution conformation of FKBP, as generated by NMR, distance geometry and molecular dynamics methods. The regular secondary structure of FKBP is composed mainly of beta sheet (approximately 35%) with little helical structure (less than 10%). The hydrophobic core of the molecule, containing the buried side chains of six of the protein's nine aromatic amino acids, is enclosed by a five-stranded antiparallel beta sheet on one side, a loop and a short helix at residues 51-56 and 57-65, and an aperiodic loop at residues 81-95. Examination of the structure suggests a possible site of interaction with FK506.

Carrier Proteins↗
PubMed1991

A PAF receptor antagonist, BN 52021, attenuates thromboxane release and improves survival in lethal canine endotoxemia.

Platelet-activating (PAF) is a putative mediator in endotoxemia and sepsis. Administration of a PAF receptor antagonist prior to endotoxin improves survival in rats and attenuates the hypotension of endotoxemia. Both PAF and endotoxin stimulate eicosanoid production. We hypothesized that a PAF receptor antagonist, BN 52021, would alter the hemodynamic events, improve the survival and attenuate the eicosanoid release associated with endotoxemia in a resuscitated, but lethal, canine model. Male dogs were randomzied to two groups (n = 10 each). Group I received only E. coli endotoxin, 1 mg/kg IV, at time 0, while group II received BN 52021, 5 mg/kg IV, 30 min before and again 240 min after endotoxin treatment. During the 4-h study period, hemodynamics were measured and blood samples were taken at 0, 2, 60, 120, and 240 min. Survival was determined at 24, 48, and 72 h. All group I animals died before 24 h; all group II lived longer than 72 h (P less than 0.05). In group I, plasma TXB2 values increased from a baseline value of 0.26 +/- .04 ng/ml to 4.38 +/- 1.56 ng/ml at 120 min and then decreased to 2.64 +/- .96 ng/ml by 240 min. For group II, respective plasma TXB2 values were 0.35 +/- 0.13 ng/ml at baseline, 0.58 +/- 0.14 ng/ml at 120 min, and 0.39 +/- .09 ng/ml at 240 min. At the 120-min and 240-min time points, the groups differed at P less than 0.05. Heart rate tended to be less in group II, but MAP was unaffected. In group I, pH values were more acidotic than those observed in group II.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Energy need in childhood and adult-onset obese women before and after a nine-month nutrition education and walking program.

The effect of a 9-month nutrition education and walking program on total calorie need, resting metabolic rate (RMR), thermic effect of food (TEF), body composition, and activity level was determined in seven women (28-41 years of age) with childhood-onset obesity (CO) and eight women (29-42 years of age) with adult-onset obesity (AO). A 3-week testing period was conducted before and after the 9-month program during which all subjects were fed a controlled, weight-maintaining metabolic diet which was used to determine daily calorie need. Body composition, RMR, and TEF were measured during the second and third weeks of both 3-week testing periods. Body weight decreased significantly for CO (mean -5.7 +/- 9.3 kg) and AO (mean -3.3 +/- 6.2 kg), but fat-free mass (FFM) was unchanged. When comparing pre to post data, mean total calorie need increased by 2.9 percent for CO and 3.1 percent for AO (P greater than 0.05), RMR decreased 3.6 percent for CO and 2.8 percent for AO (P less than 0.05), and TEF increased 11 percent for CO and 50 percent for AO (P less than 0.05). Time spent in light and moderate level activity increased significantly from pre to post. The increase in activity and TEF more than compensated for the slight decrease in RMR (mean -55 kcal/day), contributing to an overall increase in daily energy need (mean = 74 kcal/day) at the end of the program, even for the six women who lost greater than 5 kg body weight.

Adult↗
PubMed1990

31P NMR studies of enzyme-bound substrate complexes of yeast 3-phosphoglycerate kinase: III. Two ADP binding sites and their Mg(II) affinity; effects of vanadate and arsenate on enzymic complexes with ADP and 3-P-glycerate.

31P nuclear magnetic resonance (NMR) measurements (at 121.5 MHz and 5 degrees C) were made on complexes of 3-phosphoglycerate kinase with ADP and 3-P-glycerate. Addition of Mg(II) to E.ADP shifts the alpha-P signal downfield by 3.8 ppm such that the alpha-P signal superimposes that for beta-P(E.MgADP). Such a shift is atypical among the Mg(II)-nucleotide complexes with other ATP-utilizing enzymes. This shift allowed the determination that enzyme bound ADP is saturated with Mg(II) for [Mg(II)]/[ADP] = 3.0--similar to that reported for ATP complexes with this enzyme (B.D. Ray and B.D. Nageswara Rao, Biochemistry 27, 5574 (1988]. This parallel behavior suggests that ADP binds at two sites on the enzyme as does ATP with disparate Mg(II) affinities. 31P relaxation times in E.MnADP.vanadate.3-P-glycerate and E.CoADP.vanadate.3-P-glycerate complexes indicate that these are long-lived, tightly bound complexes. 31P chemical shift measurements on diamagnetic complexes (with Mg(II] revealed three signals in the 2-5 ppm region (attributable to 3-P-glycerate) only upon addition of all the components necessary to form the E.MgADP.vanadate.3-P-glycerate complex. Subsequent sequestration of Mg(II) from the complex with excess EDTA reversed the Mg(II) induced effects on the ADP signals but did not cause coalescence of the three signals seen in the 2-5 ppm region. Addition of excess sulfate to dissociate these complexes from the enzyme resulted in a single resonance of 3-P-glycerate. The use of arsenate in place of vanadate yielded very similar results. These results suggest that, in the presence of MgADP, vanadate or arsenate, and 3-P-glycerate, the enzyme catalyzed the formation of multiple structurally distinguishable complexes that are stable on the enzyme and labile off the enzyme.

Adenosine Diphosphate↗
PubMed1989

Use of the partial farm budget technique to predict the economic impact of the flock management decision to use B-mode ultrasonographic pregnancy diagnosis.

A computer spreadsheet was developed to predict the economic impact of a management decision to use B-mode ultrasonographic ovine pregnancy diagnosis. The spreadsheet design and spreadsheet cell formulas are provided. The program used the partial farm budget technique to calculate net return (NR) or cash flow changes that resulted from the decision to use ultrasonography. Using the program, either simple pregnancy diagnosis or pregnancy diagnosis with the ability to determine singleton or multiple pregnancies may be compared with no flock ultrasonographic pregnancy diagnosis. A wide range of user-selected regional variables are used to calculate the cash flow changes associated with the ultrasonography decisions. A variable may be altered through a range of values to conduct a sensitivity analysis of predicted NR. Example sensitivity analyses are included for flock conception rate, veterinary ultrasound fee, and the price of corn. Variables that influence the number of cull animals and the cost of ultrasonography have the greatest impact on predicted NR. Because the determination of singleton or multiple pregnancies is more time consuming, its economic practicality in comparison with simple pregnancy diagnosis is questionable. The value of feed saved by identifying and separately feeding ewes with singleton pregnancies is not offset by the increased ultrasonography cost.

Animal Feed↗
PubMed1988

1H NMR studies of plastocyanin from Scenedesmus obliquus: complete sequence-specific assignment, secondary structure analysis, and global fold.

Two-dimensional 1H NMR methods have been used to make sequence-specific resonance assignments for the 97 amino acid residues of the plastocyanin from the green alga Scenedesmus obliquus. Assignments were obtained for all backbone protons and the majority of the side-chain protons. Spin system identification relied heavily on the observation of relayed connectivities to the backbone amide proton. Sequence-specific assignments were made by using the sequential assignment procedure. During this process, an extra valine residue was identified that had not been detected in the original amino acid sequence. Elements of regular secondary structure were identified from characteristic NOE connectivities between backbone protons, 3JHN alpha coupling constant values, and the observation of slowly exchanging amide protons. The protein in solution contains eight beta-strands, one short segment of helix, five reverse turns, and five loops. The beta-strands may be arranged into two beta-sheets on the basis of extensive cross-strand NOE connectivities. The chain-folding topology determined from the NMR experiments is that of a Greek key beta-barrel and is similar to that observed for French bean plastocyanin in solution and poplar plastocyanin in the crystalline state. While the overall structures are similar, several differences in local structure between the S. obliquus and higher plant plastocyanins have been identified.

Amino Acid Sequence↗
PubMed1988

Three-dimensional solution structure of plastocyanin from the green alga Scenedesmus obliquus.

The solution conformation of plastocyanin from the green alga Scenedesmus obliquus has been determined from distance and dihedral angle constraints derived by nuclear magnetic resonance (NMR) spectroscopy. Structures were generated with distance geometry and restrained molecular dynamics calculations. A novel molecular replacement method was also used with the same NMR constraints to generate solution structures of S. obliquus plastocyanin from the x-ray structure of the homologous poplar protein. Scenedesmus obliquus plastocyanin in solution adopts a beta-barrel structure. The backbone conformation is well defined and is similar overall to that of poplar plastocyanin in the crystalline state. The distinctive acidic region of the higher plant plastocyanins, which functions as a binding site for electron transfer proteins and inorganic complexes, differs in both shape and charge in S. obliquus plastocyanin.

Calorimetry↗
PubMed1987

Capillary gas chromatographic-electron capture detection of coca-leaf-related impurities in illicit cocaine: 2,4-diphenylcyclobutane-1,3-dicarboxylic acids, 1,4-diphenylcyclobutane-2,3-dicarboxylic acids and their alkaloidal precursors, the truxillines.

A method has been developed that allows for the detection of the eleven stereoisomers of diphenylcyclobutanedicarboxylic acid in illicit cocaine samples, including alpha-, gamma-, and epsilon-truxillic acids and beta- and delta-truxinic acids. These, and other carboxylic acids, were also detected as ester moieties of alkaloidal impurities in illicit cocaine as well as in alkaloids of the South American coca leaf, e.g., alpha- and beta-truxilline. After lithium aluminum hydride reduction of the acidic and basic extracts of a prepared sample, the reduced species were derivatized with heptafluorobutyric anhydride in the presence of pyridine. The heptafluorobutyryl derivatives of the reduced diphenylcyclobutanedicarboxylic compounds were easily detected on-column at low picogram levels using a moderately polar fused-silica capillary column in the splitless mode and interfaced with a 63Ni electron-capture detector.

Alcohols↗