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Biomedical subjects

J M Moore

Publications and source records attributed to J M Moore.

At least 55 records · Page 3Linked to original sources
PubMed1998

Premedication with fentanyl and midazolam decreases the reliability of intravenous lidocaine test dose.

UNLABELLED: This study was performed to determine whether premedication with midazolam and fentanyl prevents reliable detection of an i.v. lidocaine test dose. Thirty ASA physical status I or II patients received either 3 mL of saline or 1.5 mg of midazolam (1.5 mL) plus 75 microg of fentanyl (1.5 mL) i.v. in a randomized, double-blind fashion. Five minutes later, lidocaine 1 mg/kg was injected i.v. At 1.5 min before and every minute after lidocaine administration, each subject was questioned regarding the presence of four symptoms of systemic lidocaine toxicity. Any new tinnitus, perioral numbness, metallic taste, or light-headedness within 5 min after lidocaine administration was considered a positive response. All 15 patients in the saline group (100% sensitivity) had a positive response to i.v. lidocaine, but only 9 of 15 patients in the sedation group had a positive response (60% sensitivity; P = 0.017). We conclude that midazolam and fentanyl premedication decreases the reliability of subjective detection of i.v. lidocaine. IMPLICATIONS: Anesthesiologists often rely on subjective symptoms to prevent local anesthetic toxicity while performing regional anesthesia. Sedatives are often administered during the administration of regional anesthesia. This study demonstrates that typical sedation decreases the reliability of detection of local anesthetic toxicity by subjective symptoms.

Adult↗
PubMed1998

Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block.

UNLABELLED: The incidence and clinical significance of hemidiaphragmatic paresis after supraclavicular block of the brachial plexus is unknown. Eight healthy volunteers received a supraclavicular block with a standard technique using 30 mL of 1.5% lidocaine. Respiratory function was assessed with ultrasound of the diaphragm, respiratory inductive plethysmography (RIP), and pulmonary function tests (PFT) every 20 min. Sensory block was assessed with pinprick and motor block with isometric force dynamometry every 20 min. Four of eight subjects demonstrated hemidiaphragmatic paresis on both ultrasound and RIP. No subject experienced changes in PFT values or subjective symptoms of respiratory difficulty. Motor and sensory blockade outlasted hemidiaphragmatic paresis. These results are contrasted to the often symptomatic, 100% incidence of hemidiaphragmatic paresis seen after interscalene block. In this study of healthy volunteers, supraclavicular block was associated with a 50% incidence (95% confidence interval 14-86) of hemidiaphragmatic paresis that was not accompanied by clinical evidence of respiratory compromise. IMPLICATIONS: Interscalene block is always associated with diaphragmatic paralysis and respiratory compromise. The significance of these side effects after supraclavicular block is unknown. Using sensitive measures of respiratory function, we determined that diaphragmatic paralysis occurs less often with the supraclavicular approach and is not associated with respiratory difficulties in healthy subjects.

Adult↗
PubMed1997

A simple perfusion technique for isolation of maternal intervillous blood mononuclear cells from human placentae.

A noninvasive perfusion method for the recovery of maternal placental (intervillous) blood for use in immunologic assays is described. 60% of the perfused blood samples tested for fetal red blood cell (RBC) contamination were found to be pure maternal blood; in the remainder, fetal RBC contamination, with a single exception, was less than 6%. The intervillous mononuclear cells (IVBMC) isolated from this blood were of predominantly maternal origin as demonstrated by a polymerase chain reaction-based DNA typing technique. The number of IVBMC obtained was within the range of 9 to 55 X 10(6) cells. Phenotypic analysis of IVBMC surface antigens revealed that 61% of the cells were CD3 + T-cells and 18% were CD19 + B-cells. The CD4 + and CD8 + T-lymphocyte subsets accounted for 28 and 26% of the IVBMC, respectively. The IVBMC were functionally competent as evidenced by in vitro lymphoproliferation and cytokine production in response to mitogen and PPD stimulation. This technique allows for rapid and safe isolation of large numbers of IVBMC which are functionally active up to 12 h post-delivery, thus representing a significant improvement over previously described methods. It should facilitate more vigorous research in the study of uteroplacental immunity and infectious disease research, particularly in field settings where sample collection and laboratory facilities are distant.

Chorionic Villi↗
PubMed1996

Dynamic NMR studies of ligand-receptor interactions: design and analysis of a rapidly exchanging complex of FKBP-12/FK506 with a 24 kDa calcineurin fragment.

Dynamic NMR methods, such as differential line broadening and transferred NOE spectroscopy, are normally reserved for the study of small molecule ligand interactions with large protein receptors. Using a combination of isotope labeling and isotope edited NMR, we have extended these techniques to characterize interactions of a much larger protein/drug complex, FKBP-12/ FK506 with its receptor protein, calcineurin. In order to examine this multicomponent system by dynamic NMR methods, the 93 kDa, tightly bound FKBP-12/FK506/Cn complex was replaced with a lower affinity, rapidly exchanging system consisting of FKBP-12/FK506 (13 kDa), recombinant calcineurin subunit B (CnB) (20 kDa), and a synthetic peptide (4 kDa) corresponding to the B binding domain (BBD) of calcineurin catalytic subunit A (CnA). Analysis of 1H-13C HSQC data acquired for the FKBP-12/ 13C-FK506 and FKBP-12/13C-FK506/CnB/BBD complexes indicates that FKBP-12/FK506 and CnB/BBD are in fast exchange in the quaternary complex. Comparison of proton line widths shows significant broadening of resonances along the macrocycle backbone at 13-CH, 13-OMe, 15-OMe, 18-CH2, 20-CH, 21-CH, and 25-Me, as well as moderate broadening on the macrocycle backbone at 17-Me, 24-CH, and the pyranose 12-CH2 protons. The tri-substituted olefin and cyclohexyl groups also show moderate broadening at the 27-Me, 28-CH, and 30-CH2 positions, respectively. Unexpectedly, little line broadening was observed for the allyl resonances of FK506 in the quaternary complex, although 13C longitudinal relaxation measurements suggest this group also makes contacts with calcineurin. In addition, intermolecular transfer NOE peaks were observed for the allyl 37-CH2, 21-CH, 30-CH2, 13-OMe, 15-OMe, 17-Me, 25-Me, and 27-Me groups, indicating that these are potential sites on the FK506 molecule that interact with calcineurin.

Amino Acid Sequence↗
PubMed1996

Immunodeficient mice as hosts for hemoparasitic infections.

Thiruchandurai Rajan, Julie Moore and Leonard Shultz here review the evolution of technology in murine xeno-lymphohemopoietic chimeras, produced by engraftment with xenogeneic (fetal or adult) progenitor cells or mature lymphohemopoietic tissues into immunodeficient mice, and their use as hosts for hemoprotozoan parasites. Particular attention is paid to the development of chimeras that house xenogeneic peripheral red blood cells (xeno-RBC). These chimeras are potentially invaluable models for hemoprotozoan parasites, such as Babesia and Plasmodium. There are, however, daunting limitations that have to be overcome before these models can become universally acceptable systems for the study of these parasitic agents.

Journal Article↗
PubMed1996

MMPI-A profiles of adolescent boys with a history of firesetting.

Firesetting in childhood and adolescence is associated with the more severe end of the conduct-disorder continuum and is considered to be prognostic of later pathology. The literature provides limited understanding of the pathology underlying firesetting in juveniles. This study compared the Minnesota Multiphasic Personality Assessment-Adolescent profiles of 28 psychiatric inpatient adolescent boys with a history of firesetting with the profiles of 96 psychiatric inpatient adolescent boys who do not have a history of firesetting. Using multivariate analyses, the firesetting group appeared more pathological than did the nonfiresetting group as reflected by significantly higher scores on three clinical scales: Psychasthenia (Pt), Schizophrenia (Sc), and Mania (Ma). The firesetting group also scored significantly higher than did the nonfiresetting group on eight of the content scales: Adolescent-Depression, Adolescent-Alienation, Adolescent-Bizarre Mentation, Adolescent-Anger, Adolescent-Conduct Problems, Adolescent-Family Problems, Adolescent-School Problems, and Adolescent-Negative Treatment Indicators. Taken together, these results suggest that the pathology associated with juvenile firesetting is more complex as well as more severe than that associated with nonfiresetting conduct disorder. The firesetting group's profiles suggest that their psychopathology is not merely a severe behavior disorder but rather is indicative of feelings of distress, alienation, depression, and thought disorder or poor reality testing. This degree of inner turmoil may be motivational impetus for the firesetting itself.

Adolescent↗
PubMed1995

Maintenance of the human malarial parasite, Plasmodium falciparum, in scid mice and transmission of gametocytes to mosquitoes.

The study of human malaria has been hampered by the lack of small animal models for the human-infecting malarial parasites. To approach this problem, the erythrocytic stages of the human malarial parasite Plasmodium falciparum were adapted to in vitro growth in the presence of ascites fluid from mice homozygous for the severe-combined immunodeficiency (scid) mutation. Human red blood cells (hRBCs) infected with these adapted parasites were then injected i.p. into nonobese diabetic scid/scid (NOD/LtSz-scid) mice. With daily supplemental intraperitoneal boosts of uninfected hRBCs, parasites were detected in the peripheral circulation of these mice for an average of 7 d after injection. Splenectomy of NOD/LtSz-scid mice increased both the level and duration of parasitemia in the periphery, and it also promoted the circulation of mature sexual stage parasites (gametocytes). When Anopheline mosquitoes were allowed to feed on the splenectomized mice, the gametocytes were ingested by the mosquitoes and developed into oocysts in the mosquito midguts. To our knowledge, these results are the first demonstration of human malarial parasite propagation in mice and transmission of these parasites to the invertebrate vector.

Animals↗
PubMed1995

The circum-Chryse region as a possible example of a hydrologic cycle on Mars: geologic observations and theoretical evaluation.

The transection and superposition relationships among channels, chaos, surface materials units, and other features in the circum-Chryse region of Mars were used to evaluate relative age relationships and evolution of flood events. Channels and chaos in contact (with one another) were treated as single discrete flood-carved systems. Some outflow channel systems form networks and are inferred to have been created by multiple flood events. Within some outflow channel networks, several separate individual channel systems can be traced to a specific chaos which acted as flood-source area to that specific flood channel. Individual flood-carved systems were related to widespread materials units or other surface features that served as stratigraphic horizons. Chryse outflow channels are inferred to have formed over most of the perceivable history of Mars. Outflow channels are inferred to become younger with increasing proximity to the Chryse basin. In addition, outflow channels closer to the basin show a greater diversity in age. The relationship of subsequent outflow channel sources to the sources of earlier floods is inferred to disfavor episodic flooding due to the progressive tapping of a juvenile near-surface water supply. Instead, we propose the circum-Chryse region as a candidate site of past hydrological recycling. The discharge rates necessary to carve the circum-Chryse outflow channels would have inevitably formed temporary standing bodies of H2O on the Martian surface where the flood-waters stagnated and pooled (the Chryse basin is topographically enclosed). These observations and inferences have led us to formulate and evaluate two hypotheses: (1) large amounts of the sublimated H2O off the Chryse basin flood lakes precipitated (snowed) onto the flood-source highlands and this H2O was incorporated into the near surface, recharging the H2O sources, making possible subsequent deluges; and (2) ponded flood-water in Chryse basin drained back down an anti basinward dipping subsurface layer accessed long the southern edge of the lake, recharging the flood-source aquifers. H2O not redeposited in the flood-source region was largely lost to the hydrologic cycle. This loss progressively lowered the vitality of the cycle, probably by now killing it. Our numerical evaluations indicate that of the two hypotheses we formulated, the groundwater seep cycle seems by far the more viable. Optimally, approximately 3/4 of the original mass of an ice-covered cylindrical lake (albedo 0.5, 1 km deep, 100-km radius, draining along its rim for one quarter of its circumference into substrata with a permeability of 3000 darcies) can be modeled to have moved underground (on timescales of the order of 10(3) years) before the competing mechanisms of sublimation and freeze down choked off further water removal. Once underground, this water can travel distances equal to the separation between Chryse basin and flood-source sites in geologically short (approximately 10(6) year-scale) times. Conversely, we calculate that optimally only approximately 40% of the H2O carried from Chryse can condense at the highlands, and most of the precipitate would either collect at the base of the highlands/lowlands scarp or sublimate at rates greater than it would accumulate over the flood-source sites. Further observations from forthcoming missions may permit the determination of which mechanisms may have operated to recycle the Chryse flood-waters.

Disasters↗
PubMed1995

Novel chlorinated tropanes derived from the treatment of cocaine with sodium hypochlorite.

Several novel chlorinated tropanes were produced when cocaine was treated with aqueous sodium hypochlorite. Two of these, 2'- and 3'-chlorobenzoyloxy-2-carbomethoxypseudotropine (that is, ortho- and meta-chlorococaine), were characterized by synthesis and gas chromatography/mass spectrometry. Four other new chlorinated tropanes (endo-6- and 7-chlorococaine, exo-6- or 7-chlorococaine and N-chlorobenzoylnorecgonine methyl ester) were also tentatively identified via their gas chromatography retention data and mass spectra. The results are of potential use in cocaine signature and comparative analysis.

Chlorine↗
PubMed1994

Solution structure of FK506 bound to the R42K, H87V double mutant of FKBP-12.

The binding of the FK506/FKBP-12 complex to calcineurin (CN), its putative target for immunosuppression, involves recognition of solvent-exposed regions of the ligand as well as FKBP-12 residues near the active site. The R42K, H87V double mutation of FKBP-12 decreases the CN affinity of the complex by 550-fold [Aldape, R. A., Futer, O., DeCenzo, M. T., Jarrett, B. P., Murcko, M. A., & Livingston, D. J. (1992) J. Biol. Chem. 267, 16029-16032]. This work reports the solution structure of 13C-labeled FK506 bound to R42K, H87V FKBP-12. Assignments and NOE measurements at three mixing times were made from inverse-detected 1H-13C NMR experiments. Structures were calculated by several different methods, including distance geometry, restrained molecular dynamics, and molecular dynamics with time-averaged restraints. The NMR structures of the ligand are very well defined by the NOE restraints and differ slightly from the X-ray structure in regions that are involved in crystal packing. Comparison with the NMR structure of FK506 bound to wild-type FKBP-12 reveals that the R42K, H87V mutation causes the ligand backbone near C16 to move by 2.5 to 4.5 A, reorients 15-MeO by 90 degrees, and shifts 13-MeO by approximately 1.5 A. FK506 appears to undergo a concerted, mutationally induced shift in the binding pocket, with the greatest changes occurring in the effector region of the drug. The altered effector conformation of mutant-bound FK506 may perturb interactions between the drug and CN, thus accounting for the effect of the double mutation upon the CN inhibitory activity of the complex.

Calcineurin↗
PubMed1994

Pristane retards clearance of particulate materials from the peritoneal cavity of laboratory mice.

The effect of intraperitoneal pristane on the movement of India ink particles and water-based radio-opaque dye injected into the peritoneal cavity of mice was examined. There was a marked difference between pristane-treated mice and unmanipulated controls in terms of particle retention; unmanipulated mice cleared India ink particles via lymphatic drainage within 24 h following injection, whereas pristane-treated mice retained particles for as long as 22 days post-injection. In contrast, all mice displayed similar kinetics of removal of radio-opaque dye. We conclude that the movement of particulate matter from the peritoneal cavity is retarded in pristane-treated mice whereas removal of water-based materials is unaffected. The implications for generation of ascites using hybridoma cells in pristane-primed mice is discussed.

Animals↗
PubMed1994

In-depth chromatographic analyses of illicit cocaine and its precursor, coca leaves.

Chromatographic methodology used for the in-depth alkaloid analyses of coca leaves and for the characterization of alkaloidal impurities and manufacturing by-products in illicit refined cocaine samples is reviewed. This includes liquid-liquid partition and liquid-solid adsorption column chromatography, packed- and capillary-column gas chromatography with flame-ionization, electron-capture, nitrogen-phosphorous and mass spectrometric detection, and high-performance liquid chromatography with ultraviolet detection. The rationale supporting the presence and determination of processing impurities/by-products in cocaine samples is discussed, and chromatographic methodology used for the development of drug impurity signature profiles is presented.

Alkaloids↗
PubMed1994

15N NMR relaxation studies of the FK506 binding protein: dynamic effects of ligand binding and implications for calcineurin recognition.

Backbone dynamics of the ligand- (FK506-) bound protein FKBP-12 (107 amino acids) have been examined using 15N relaxation data derived from inverse-detected two-dimensional 1H-15N NMR spectra. A model free formalism [Lipari & Szabo (1982) J. Am. Chem. Soc. 104, 4546-4559] was used to derive the generalized order parameter (S2), the effective correlation time for internal motions (tau e), and the chemical-exchange line width (R(ex)) based on the measured 15N relaxation rate constants (R1, R2) and 1H-15N heteronuclear NOEs. The final optimized overall correlation time (tau m) was 9.0 ns. The average order parameter (S2) describing the amplitude of motions on the picosecond time scale was found to be 0.88 +/- 0.04, indicating that internal flexibility is restricted along the entire polypeptide chain. In contrast to results obtained for uncomplexed FKBP, the 80's loop (residues 82-87) surrounding the ligand binding site was found to be rigidly fixed, indicating that internal motions at this site are damped significantly due to stabilizing noncovalent interactions with the FK506 molecule. Structural implications of these differences in picosecond mobility as well as possible implications for calcineurin recognition are discussed.

Binding Sites↗
PubMed1994

Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves.

Methodology is described for the detection and/or determination of cocaine and minor alkaloids in South American coca as well as in greenhouse- and tropical-cultivated field coca of known taxonomy. Coca leaf from Bolivia, Peru, Ecuador and Colombia were subjected to the determination of cocaine, cis- and trans-cinnamoylcocaine, tropacocaine, hygrine, cuscohygrine and the isomeric truxillines. The greenhouse samples were cocaine-bearing leaves of the genus Erythroxylum and included E. coca var. coca, E. novogranatense var. novogranatense and E. novogranatense var. truxillense, and the alkaloids determined were cocaine, ecgonine methyl ester, cuscohygrine, tropacocaine and the cinnamoylcocaines. The tropical-cultivated coca were E. novogranatense var. novogranatense and E. coca var. coca. Cocaine and minor alkaloids were isolated from basified powdered leaf samples using a toluene extractant, followed by acid-Celite column chromatography. The isolated alkaloids were determined by capillary gas chromatography with flame ionization or electron-capture detection. Methodology is also presented for the isolation and mass spectral analysis of numerous trace-level coca alkaloids of unknown structure.

Alkaloids↗
PubMed1994

Detection and determination of pseudococaine in coca leaves and illicit cocaine samples.

Methodology is presented for the isolation, identification and determination of pseudococaine in coca leaves and illicit cocaine. Coca leaves, crude cocaine base (coca paste), refined cocaine base and refined cocaine hydrochloride, all derived from the same geographic location in Bolivia, were examined. Pseudococaine and other coca alkaloids were isolated from leaf samples using toluene extraction followed by acid/Celite trap and ion-pair column chromatography, and from crude and refined cocaine samples by acid/Celite column ion-pairing chromatography. Mass spectral analysis of coca leaf isolates confirmed the presence of pseudococaine. Pseudococaine was quantified by capillary gas chromatography with flame ionization detection at levels of 0.0001-0.035% (relative to cocaine) in refined illicit cocaine and coca leaves.

Chromatography, Gas↗