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M Carson

Publications and source records attributed to M Carson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Ultrastructure of spared dopamine terminals in caudate-putamen nuclei of adult rats neonatally treated with intranigral 6-hydroxydopamine.

Residual dopamine terminals in the dorsal striatum, caudate-putamen nuclei (CPN), of adult rats neonatally lesioned with 6-hydroxydopamine (6-OHDA) sustain a relatively high level of dopamine release. We examined whether there were morphological differences in the spared dopamine terminals that might correlate with this increased efficacy. Postnatal male rat pups from 50 litters were pretreated with desmethylimipramine (DMI) to protect from non-specific monoamine damage, then given unilateral intranigral injections of 6-OHDA or vehicle. Coronal sections through the CPN and substantia nigra of the surviving adult animals from each litter were co-processed for immunoautoradiographic or immunoperoxidase localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH). Quantitative ultrastructural analysis established that in animals showing maximal (greater than 90%) depletions in immunoautoradiographic labeling for TH, the number of TH-labeled axons in the CPN ipsilateral to the 6-OHDA injections was reduced to one third of the number seen in the contralateral, unlesioned hemisphere, or the CPN from vehicle-injected animals. The ultrastructural features of residual terminals ipsilateral to 6-OHDA lesions were morphologically similar to those of the contralateral side or in vehicle-injected animals. However, in comparison with controls, these TH-labeled terminals had significantly larger mean cross-sectional diameters. When subdivided into groups according to size, there were significantly fewer small (0.0-0.1 micron 2) and more large (0.41-0.50 micron 2) TH-immunoreactive profiles in lesioned versus unlesioned CPN. The remaining TH-labeled terminals ipsilateral to the 6-OHDA lesions also appeared to be more often in direct contact with unlabeled soma and proximal dendrites as opposed to dendritic spines in the unlesioned CPN. These results suggest that the enhanced activity of dopamine neurons innervating the CPN after nigral 6-OHDA lesions may contribute to changes in size and target of their terminals. Alternatively, the observed large size of remaining dopamine terminals may reflect selective vulnerability of smaller axons to 6-OHDA toxicity.

Aging↗
PubMed1992

Structure of scorpion toxin variant-3 at 1.2 A resolution.

The crystal structure of the variant-3 protein neurotoxin from the scorpion Centruroides sculpturatus Ewing has been refined at 1.2 A resolution using restrained least-squares. The final model includes 492 non-hydrogen protein atoms, 453 protein hydrogen atoms, eight 2-methyl-2,4-pentanediol (MPD) solvent atoms, and 125 water oxygen atoms. The variant-3 protein model geometry deviates from ideal bond lengths by 0.024 A and from ideal angles by 3.6 degrees. The crystallographic R-factor for structure factors calculated from the final model is 0.192 for 17,706 unique reflections between 10.0 to 1.2 A. A comparison between the models of the initial 1.8 A and the 1.2 A refinement shows a new arrangement of the previously poorly defined residues 31 to 34. Multiple conformations are observed for four cysteine residues and an MPD oxygen atom. The electron density indicates that disulfide bonds between Cys12 and Cys65 and between Cys29 and Cys48 have two distinct side-chain conformations. A molecule of MPD bridges neighboring protein molecules in the crystal lattice, and both MPD enantiomers are present in the crystal. A total of 125 water molecules per molecule of protein are included in the final model with B-values ranging from 11 to 52 A2 and occupancies from unity down to 0.4. Comparisons between the 1.2 A and 1.8 A models, including the bound water structure and crystal packing contacts, are emphasized.

Amino Acid Sequence↗
PubMed1992

Structure of a diubiquitin conjugate and a model for interaction with ubiquitin conjugating enzyme (E2).

Covalent ligation of multiubiquitin chains targets eukaryotic proteins for degradation. In such multiubiquitin chains, successive ubiquitins are linked by an isopeptide bond involving the side chain of Lys48 and the carboxyl group of Gly76. The crystal structure of a diubiquitin conjugate has been determined and refined at 2.3-A resolution. The molecule has internal approximate 2-fold symmetry with multiple hydrophobic and hydrophilic contacts along the 2-fold axis. The structure of the diubiquitin conjugate suggests determinants for recognition of multiubiquitin chains. A model for the interaction of diubiquitin and a ubiquitin conjugating enzyme (E2) is proposed.

Amino Acid Sequence↗
PubMed1992

Crystal structure of peroxynitrite-modified bovine Cu,Zn superoxide dismutase.

The crystal structure of bovine Cu,Zn superoxide dismutase modified with peroxynitrite (ONOO-) was determined by X-ray diffraction, utilizing the existing three-dimensional model of the native structure deposited in the Brookhaven Protein Data Bank (J. A. Tainer et al., J. Mol. Biol. 160, 181-217, 1982). The native structure and the modified derivative were refined to R factors of 19.0 and 18.7% respectively using diffraction data from 6.0 to 2.5 A. The major result after reaction with peroxynitrite was the appearance of electron density 1.45 A from a single epsilon carbon of Tyr-108, the only tyrosine residue in the sequence. Tyr-108 is a solvent-exposed residue 18 A from the copper atom in the active site. The electron density was consistent with nitration of Tyr-108 at one of the epsilon carbons to form 3-nitrotyrosine. We propose that the nitration occurs in solution by transfer of a nitronium-like species from the active site on one superoxide dismutase dimer to the Tyr-108 of a second dimer.

Animals↗
PubMed1992

HLA class II frequencies in celiac disease patients in the west of Ireland.

Restriction fragment length polymorphism analysis, using a single restriction enzyme TaqI-multiple-probe system for HLA-DRB1-DQB1 and -DQA1, was used to determine HLA-DR and -DQ frequencies in 56 unrelated celiac patients and 47 unrelated controls from the west of Ireland. In addition, HLA-DPB1 allelic frequencies were determined in the same group of patients and controls by using the technique of enzymatic DNA amplification of the polymorphic second exon of HLA-DPB1 genes in conjunction with sequence-specific oligonucleotide probing. The results suggest that HLA-DQ rather than HLA-DR is more important in conferring susceptibility to celiac disease. Furthermore, no association between HLA-DP and celiac disease was found in this study.

Adolescent↗
PubMed1991

Three-dimensional structure of recombinant human interferon-gamma.

The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques. Interferon-gamma, which is dimeric in solution, crystallizes with two dimers related by a noncrystallographic twofold axis in the asymmetric unit. The protein is primarily alpha helical, with six helices in each subunit that comprise approximately 62 percent of the structure; there is no beta sheet. The dimeric structure of human interferon-gamma is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions.

Amino Acid Sequence↗
PubMed1989

Effects of interocular blur suppression ability on monovision task performance.

Suppression of anisometropic blur induced by monovision contact lenses was examined in 18 presbyopic subjects. Suppression ability was quantified by reducing the contrast of a bright test target, viewed by subjects wearing a monovision correction, until the blurred image was suppressed. Subjective success with monovision was evaluated using a patient survey and no correlation to blur suppression ability was found. Objective success was evaluated in terms of performance at three near work tasks, each requiring a different level of stereoscopic localization. A significant correlation was found between card filing performance (requiring a moderate level of stereopsis) and blur suppression ability. Correcting either the dominant or non-dominant eye for near in the monovision correction did not significantly affect blur suppression ability. There was no evidence for adaptation to monovision in terms of increasing blur suppression ability over time.

Adult↗
PubMed1988

Polymorphonuclear leukocyte locomotion is insensitive to lowered cytoplasmic calcium levels.

Chemotactic factors stimulate the rate of locomotion of polymorphonuclear leukocytes (PMNs). To investigate the importance of cytoplasmic calcium we have examined the ability of the chemotactic peptide N-formylnorleucyl eucylphenalanine (FNLLP) to stimulate the locomotion of PMNs whose cytoplasmic calcium levels were reduced by incubation in EGTA or in EGTA plus the calcium ionophores, ionomycin or A23187. Locomotion was assayed by migration through micropore filters and by time-lapse videomicroscopy. Cells in EGTA exhibited similar or slightly reduced rates of locomotion compared to cells in Hanks' balanced salt solution (HBSS). The peptide dose dependence for the stimulation of locomotion was similar in medium containing calcium or EGTA. The presence of 1 microM ionophore plus EGTA had no effect on the stimulation of locomotion by peptide. The presence of ionophores (1 microM) plus external calcium inhibited locomotion.

Animals↗
PubMed1987

Substituted (aryloxy)alkanoic acids as antagonists of slow-reacting substance of anaphylaxis.

A series of compounds in which the 4-acetyl-3-hydroxy-2-propylphenoxy moiety of the standard SRS-A antagonist, FPL-55712, is linked by a polymethylene or a polyether chain to substituted (aryloxy)alkanoic acids was prepared. The compounds were evaluated for their ability to antagonize SRS-A-induced contractions of guinea pig ilea and LTE-induced bronchoconstriction in the guinea pig. The results showed that the compounds were all less potent than FPL-55712 in vitro, yet surprisingly, most were more potent by the inhalation route of administration. Some of the most potent analogues were selected for further pharmacological evaluation and, by inhalation, exhibited selective antagonism of leukotrienes as compared with PAF or histamine. In comparison to FPL-55712, compounds 28 and 37 were more potent against LTE (40- and 80-fold, respectively), LTD (4- and 3-fold, respectively), and LTC (27- and 20-fold, respectively) induced bronchoconstriction when tested by inhalation.

Animals↗
PubMed1987

Depression among alcoholics.

The relationships of cognition, health status, and age to depression among alcoholics were studied. Eighty male alcoholics in an alcohol treatment unit were rated on health status and given a battery of psychological tests and scales. These included the Hooper VOT (cognition) and several self-rated depression indices: MMPI-Depression, MCMI-Dysthymic, BDI-Total (BDI-Somatic and BDI-Psychological), and the Geriatric Depression Scale (GDS). Results showed that depression was present in this sample at mild clinical levels. Regression analyses showed that age was the most influential factor on the MMPI-D and BDI-Somatic. Age also was most influential on the GDS, with health status contributing. However, except for somatic depression, the amount of explained variance was small. Despite this, it is argued that age is a contributing factor to depression among alcoholics, especially the somatic elements of depression.

Adult↗
PubMed1986

An actin-nucleating activity in polymorphonuclear leukocytes is modulated by chemotactic peptides.

We examined the actin-nucleating activity in polymorphonuclear leukocyte lysates prepared at various times after chemotactic peptide addition. The actin nucleation increases two- to threefold within 15 s after peptide addition, decays to basal levels within 90 s, and is largely independent of cytoplasmic calcium fluxes. The peptide-induced nucleation sites behave as free barbed ends and therefore may increase the level of polymerized actin in vivo. The new nucleation sites may also determine the cellular sites of actin polymerization. This localization of actin polymerization could be important for the directional extension of lamellipodia during chemotaxis.

Actin Cytoskeleton↗
PubMed1984

Prediction of sulfamethoxazole-trimethoprim synergistic action against members of the family Enterobacteriaceae with a two-plate agar dilution breakpoint MIC system.

Synergy between sulfamethoxazole (SMZ) and trimethoprim (TMP) was predicted by a two-plate agar dilution breakpoint MIC system. Comparison of the results of this new system with those of the disk diffusion system (P.M. Waterworth, Postgrad. Med. J. Suppl. 45:21-27, 1969) after tests with 1,518 Enterobacteriaceae isolates showed an overall correlation of 99.8%, a sensitivity of 99.7%, and a specificity of 100%. The method involves spot inoculation of 10(3) organisms onto each of two plates, one containing 160 micrograms of SMZ per ml and the other 8 micrograms of TMP per ml (in Oxoid IsoSensitest medium with 3% agar supplemented with 7% saponin-lysed horse blood), and then incubation overnight at 37 degrees C in air. All but three organisms for which SMZ-TMP was found to be synergistic by disk testing were inhibited on both plates. Three isolates of Proteus mirabilis, which failed to correlate with disk testing by this new system, all showed SMZ MICs of 1,000 micrograms/ml. The SMZ-TMP combination was falsely predicted to be nonsynergistic against these three organisms. There were no false synergy predictions by the breakpoint MIC system. Laboratories should report susceptibility to the SMZ-TMP combination only when there is synergy between the constituents. This simple, reliable agar dilution technique enables laboratories to accurately report synergy between SMZ and TMP.

Drug Resistance, Microbial↗
PubMed1983

Dependence of the shape of the plasma fibronectin molecule on solvent composition. Ionic strength and glycerol content.

Fibronectin has been purified to apparent homogeneity according to measurements of molecular weight and diffusion constant from light scattering and sedimentation in the analytical ultracentrifuge. This gives two estimates of molecular weight close to 500,000. (The difference with the gel electrophoretic value of 440,000 may indicate the presence of some material of molecular weight higher than that of the monomer.) The (corrected) diffusion constant is found to decrease with ionic strength, much more rapidly in 30% glycerol than in water. A corresponding change occurs when the glycerol content is varied from 0 to 30% at moderate ionic strength, but at very low ionic strength the diffusion constant does not depend on glycerol content. It is concluded that fibronectin can occur in two extreme conformations: the open form, in 30% glycerol at moderate ionic strength, should correspond to the extended shapes visualized by others by electron microscopy of samples prepared from solutions containing glycerol, while the closed form occurs under more physiological conditions. The Stokes radii of these forms, 14.5 and 9.6 nm, respectively, have been compared with calculated Stokes radii of chains of beads of overall length 140 nm having varying stiffness, simulated by a Monte Carlo procedure. These have a Stokes radius of 14.5 nm when made relatively extended to where the distance between chain ends averages 90 nm, as observed in the electron micrographs. When these chains are made very flexible, the Stokes radius reaches a limit of about 10 nm, apparently a lower limit to which a randomly coiled molecule of this size and volume may collapse in a disordered fashion. These results and electron micrographs obtained at low ionic strength suggest a tangled model of the compact form, rather than the ordered model recently proposed by others. Finally, some speculation is offered in regard to a possible physiological role of a conformation change of fibronectin.

Fibronectins↗
PubMed1983

(E)-3-(4-Oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents.

A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduction of the side chain double bond, or reduction of the quinazoline ring resulted in substantial loss of activity. Among the analogues that exhibited oral activity in the PCA test, (E)-3-[6-(methylthio)-4-oxo-4H-quinazolin-3-yl]-2-propenoic acid (5i) was the most potent.

Animals↗