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Biomedical subjects

M K Johnson

Publications and source records attributed to M K Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Electrophysiological brain activity and memory source monitoring.

To investigate brain mechanisms involved in identifying the origin of memories, event-related potentials (ERPs) were recorded as participants discriminated previously presented (old) from new items or identified their earlier source (picture, word, or new). Differences in ERPs between old-new recognition and source identification were focused at frontal sites. For source identification, prominent negative deflections at occipital or frontal sites occurred depending on encoding task. These results support a model in which memory attributes are distributed neocortically and the frontal lobes are critical for source monitoring.

Discrimination Learning↗
PubMed1997

Redox-dependent structural changes in the nitrogenase P-cluster.

The structure of the nitrogenase MoFe-protein from Azotobacter vinelandii has been refined to 2.0 A resolution in two oxidation states. EPR studies on the crystals indicate that the structures correspond to the spectroscopically assigned oxidized (P(OX)/M(OX)) and the native or dithionite-reduced (P(N)/M(N)) forms of the enzyme. Both MoFe-protein structures are essentially identical, with the exception of the P-cluster. The MoFe-protein P-cluster in each state is found to contain eight Fe and seven S atoms. Interconversion between the two redox states involves movement of two Fe atoms and an exchange of protein coordination for ligands supplied by a central S atom. In the oxidized P(OX) state, the cluster is coordinated by the protein through six cysteine ligands, Ser-beta188 O gamma, and the backbone amide of Cys-alpha88. In the native P(N) state, Ser-beta188 O gamma and the amide N of Cys-alpha88 no longer coordinate the cluster due to movement of their coordinated Fe atoms toward the central sulfur. Consequently, this central sulfur adopts a distorted octahedral environment with six surrounding Fe atoms. A previously described model of the P-cluster containing 8Fe-8S likely reflects the inappropriate modeling of a single structure to a mixture of these two P-cluster redox states. These observed redox-mediated structural changes of the P-cluster suggest a role for this cluster in coupling electron transfer and proton transfer in nitrogenase.

Aspergillus↗
PubMed1997

Confabulation, memory deficits, and frontal dysfunction.

This paper explores potential cognitive deficits underlying confabulation of patient, G.S., following an anterior communication artery aneurysm. G.S.'s performance on tasks assessing memory for temporal duration, temporal order, and speaker identification is examined as is his recollection of autobiographical events. We compare G.S. with three nonconfabulating patients matched with him for age, education, and neuropsychological measures of memory and frontal deficits and with three age- and education-matched control subjects. Like frontal control patients, G.S. underestimated temporal durations and showed poor source monitoring (speaker identification). In addition, G.S. showed an even more pronounced deficit in recall of autobiographical memories and relatively more detailed reports of laboratory-induced memories for imagined events. We suggest that this configuration of deficits rather than any single factor accounts for G.S.'s tendency to confabulate.

Amnesia↗
PubMed1997

Prematurely condensed chromosomes and meiotic abnormalities in unfertilized human oocytes after ovarian stimulation with and without gonadotropin-releasing hormone agonist.

OBJECTIVE: To investigate the incidence of meiotic abnormalities, aneuploidy, and prematurely condensed sperm chromosomes in failed fertilized oocytes after controlled ovarian hyperstimulation (COH). DESIGN: Retrospective analysis of air-dried preparations of unfertilized oocytes. SETTING: University hospital-based infertility clinic. PATIENT(S): Thirty-three patients undergoing IVF having only tubal factor as the cause of infertility. Twelve patients (13 cycles) underwent treatment with hMG alone (-GnRH agonist [GnRH-a]), and 21 patients (24 cycles) underwent treatment with leuprolide acetate (LA) and hMG (+GnRH-a group). INTERVENTION(S): Standard IVF-ET treatment cycle for ovarian stimulation using hMG with or without LA. MAIN OUTCOME MEASURE(S): The meiotic stage, ploidy, and the presence of prematurely condensed sperm chromosomes were determined in 161 air-dried preparations of unfertilized oocytes. RESULT(S): Significantly more unfertilized oocytes were at metaphase II in the -GnRH-a group as compared with the +GnRH-a group, with significantly fewer exhibiting meiotic aberrations. Aneuploidy rates did not differ between groups. However, significantly more oocytes in the +GnRH-a group revealed prematurely condensed sperm chromosomes than in the -GnRH-a group. CONCLUSION(S): The use of GnRH-a for COH does not have an impact on aneuploidy rates in failed fertilized oocytes. However, the higher incidence of meiotic aberrations and prematurely condensed sperm chromosomes in the unfertilized population indicates that some retrieved oocytes exhibit incomplete nuclear and cytoplasmic maturation after the use of this agonist.

Adult↗
PubMed1997

False recollection induced by photographs: a comparison of older and younger adults.

Looking at photographs constitutes an important everyday memory activity for older adults. The authors found that reviewing photographs of events seen earlier in a videotape increases the likelihood that both older and younger adults remember specific details from the reviewed event (W. Koutstaal, D. L. Schacter, M. K. Johnson, K. E. Angell, & M. S. Gross, 1977). In the present study, the authors report 2 experiments demonstrating that photo review can also produce false recollection in elderly adults: After reviewing photos of events that had not been shown earlier in a videotape, older but not younger adults were later more likely to "remember" that those events had been shown in the videotape. False recollection induced by photo review appears to reflect an age-related deficit in source-monitoring abilities.

Adolescent↗
PubMed1997

Effects of relatedness and number of distractors on attribute judgments in Alzheimer's disease.

Participants made judgments about the relative salience of category exemplars (e.g., fruit: apple or grape) or parts (e.g., plane: wings or seats). Mildly affected Alzheimer's disease (AD) patients were as accurate but slower than normal controls, and their response times increased more for related (e.g., apple, grape, or fig) than unrelated (e.g., apple, gym, bandit) choices as the number of alternatives was increased from 2 to 3. Performance (accuracy and response times) of moderate-severely affected patients was poorer still, but number of distractors and relatedness did not interact. In combination with previous findings (e.g., M. K. Johnson, A. M. Hermann, & J. L. Bonilla, 1995), these results suggest that the reflective processes necessary for deciding among competing alternatives show disruption early in the disease process. Such processing deficits would compound any difficulties arising from a degrading semantic structure.

Aged↗
PubMed1997

The verbal overshadowing effect: why descriptions impair face recognition.

Three experiments explored the verbal overshadowing effect, that is, the phenomenon that describing a previously seen face impairs recognition of this face. There were three main results: First, a verbal overshadowing effect was obtained both when subjects were provided with and when they generated a description of an earlier seen face. Second, instructing subjects at the time of test to be aware of potentially competing memories did not improve, and may even have worsened, recognition performance when the subjects had generated a description of the target face. However, these instructions improved performance and eliminated the verbal overshadowing effect when subjects were provided with someone else's description of the target face. Third, recognition of the target face was disrupted when subjects described a completely different face, such as their parent's face or a face of the opposite sex. The results are discussed in relation to two potential mechanisms: source confusion between previously encoded visual and verbal representations of the face and a shift in processing of the test faces at recognition.

Analysis of Variance↗
PubMed1997

Evaluating characteristics of false memories: remember/know judgments and memory characteristics questionnaire compared.

Subjects hearing a list of associates to a nonpresented lure word later often claim to have heard the lure (Deese, 1959; Roediger & McDermott, 1995). To examine the characteristics of such false memories, subjects completed a memory characteristics questionnaire (MCQ; Johnson, Foley, Suengas, & Raye, 1988) or made remember/know (RK; Gardiner & Java, 1993) judgments for previously heard theme associates and nonpresented lures. MCQ ratings indicated that false memories for lures had less auditory detail and less remembered feelings and reactions than memories for presented words. In addition, rates of false recognition for lures were significantly lower than rates of correct recognition when items from various themes were intermixed instead of blocked at acquisition and subjects made MCQ ratings instead of RK judgments. This demonstrates that false memories can be affected both by how they are acquired and by how extensively they are examined at retrieval.

Adult↗
PubMed1997

Metabolism and disposition of the HIV-1 protease inhibitor ritonavir (ABT-538) in rats, dogs, and humans.

The metabolism and disposition of [14C]ritonavir (ABT-538, NOR-VIR), a potent, orally active HIV-1 protease inhibitor, were investigated in male and female Sprague-Dawley rats, beagle dogs, and HIV-negative male human volunteers. Rats and dogs received a 5 mg/kg iv, 20 mg/kg oral or 20 mg/kg intraduodenal dose, whereas humans received a single 600-mg liquid oral dose. Ritonavir was cleared primarily via hepatobiliary elimination in all three species. After iv or oral dosing in either rats or dogs, > 92% of the dose was recovered in rat and dog feces and < or = 4% was recovered in the urine. Humans excreted 86.3% of the oral dose in feces and 11.3% in urine over 6 days. Bile-exteriorized rats and dogs excreted 85.5% and 39.8%, respectively, of the iv dose in bile, with < 3% recovered in urine. Radio-HPLC analysis of bile, feces, and urine from all three species indicated extensive metabolism of ritonavir to a number of oxidative metabolites, some being species-specific, and all involving metabolism at the terminal functional groups of the molecule. Glucuronide metabolites were observed in dog only. Plasma radioactivity consisted predominantly of unchanged parent drug in all three species. M-2, the product of hydroxylation at the methine carbon of the terminal isopropyl moiety of ritonavir, was the only metabolite present in human plasma and made up 30.4% of the total dose recovered in human excreta over 6 days. Tissue distribution of ritonavir in rat was widespread, with good distribution into lymphatic tissue but low CNS penetration. Plasma protein binding of ritonavir was high (96-99.5%) in all species and was nonsaturable in humans at concentrations up to 30 micrograms/ml. Partitioning into the formed elements of whole blood was minimal.

Adult↗
PubMed1996

Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster.

The five cysteines closest to the carboxyl terminus of human ferrochelatase have been individually mutated to serine, histidine, or aspartate residues in an attempt to identify the protein ligands to the [2Fe-2S] cluster. Mutations of cysteines at positions 403, 406, and 411 (C403D, C403H, C406D, C406H, C406S, C411H, and C411S mutants) all resulted in inactive enzyme that failed to assemble the [2Fe-2S] cluster as judged by whole-cell EPR studies. In contrast, mutation of the cysteines at positions 360 and 395 to serines (C360S and C395S mutants) did not affect the enzymatic activity, and the resulting enzyme assembled a [2Fe-2S] cluster that was spectroscopically indistinguishable from the wild-type enzyme. The results indicate that three of the conserved cysteines in the 30-residue C-terminal extension of mammalian ferrochelatase are involved in ligating the [2Fe-2S] cluster. Resonance Raman and variable-temperature magnetic circular dichroism studies of heme-free preparations of human ferrochelatase are reported, and the spectra are best interpreted in terms of one non-cysteinyl, oxygenic ligand for the [2Fe-2S] cluster. Such anomalous coordination could account for the cluster lability compared to similar clusters with complete cysteinyl ligation and hence may be intrinsic to the proposed regulatory role for this cluster in mammalian ferrochelatases.

Amino Acid Sequence↗
PubMed1996

Electrophysiological brain activity and memory source monitoring.

To investigate brain mechanisms involved in identifying the origin of memories, event-related potentials (ERPs) were recorded as participants discriminated previously presented (old) from new items or identified their earlier source (picture, word, or new). Differences in ERPs between old-new recognition and source identification, were focused at frontal sites. For source identification, prominent negative deflections at occipital or frontal sites occurred depending on encoding task. These results support a model in which memory attributes are distributed neocortically and the frontal lobes are critical for source monitoring.

Adult↗
PubMed1996

The function and properties of the iron-sulfur center in spinach ferredoxin: thioredoxin reductase: a new biological role for iron-sulfur clusters.

Thioredoxin reduction in chloroplasts is catalyzed by a unique class of disulfide reductases which use a [2Fe-2S]2+/+ ferredoxin as the electron donor and contain an Fe-S cluster as the sole prosthetic group in addition to the active-site disulfide. The nature, properties, and function of the Fe-S cluster in spinach ferredoxin:thioredoxin reductase (FTR) have been investigated by the combination of UV/visible absorption, variable-temperature magnetic circular dichroism (MCD), EPR, and resonance Raman (RR) spectroscopies. The results indicate the presence of an S = 0 [4Fe-4S]2+ cluster with complete cysteinyl-S coordination that cannot be reduced at potentials down to -650 mV, but can be oxidized by ferricyanide to an S = 1/2 [4Fe-4S]3+ state (g = 2.09, 2.04, 2.02). The midpoint potential for the [4Fe-4S]3+/2+ couple is estimated to be +420 mV (versus NHE). These results argue against a role for the cluster in mediating electron transport from ferredoxin (Em = -420 mV) to the active-site disulfide (Em = -230 mV, n = 2). An alternative role for the cluster in stabilizing the one-electron-reduced intermediate is suggested by parallel spectroscopic studies of a modified form of the enzyme in which one of the cysteines of the active-site dithiol has been alkylated with N-ethylmaleimide (NEM). NEM-modified FTR is paramagnetic as prepared and exhibits a slow relaxing, S = 1/2 EPR signal, g = 2.11, 2.00, 1.98, that is observable without significant broadening up to 150 K. While the relaxation properties are characteristic of a radical species, MCD, RR, and absorption studies indicate at least partial cluster oxidation to the [4Fe-4S]3+ state. Dye-mediated EPR redox titrations indicate a midpoint potential of -210 mV for the one-electron reduction to a diamagnetic state. By analogy with the properties of the ferricyanide-oxidized [4Fe-4S] cluster in Azotobacter vinelandii 7Fe ferredoxin [Hu, Z., Jollie, D., Burgess, B. K., Stephens, P. J., & Münck, E. (1994) Biochemistry 33, 14475-14485], the spectroscopic and redox properties of NEM-modified FTR are interpreted in terms of a [4Fe-4S]2+ cluster covalently attached through a cluster sulfide to a cysteine-based thiyl radical formed on one of the active-site thiols. A mechanistic scheme for FTR is proposed with similarities to that established for the well-characterized NAD(P)H-dependent flavin-containing disulfide oxidoreductases, but involving sequential one-electron redox processes with the role of the [4Fe-4S]2+ cluster being to stabilize the thiyl radical formed by the initial one-electron reduction of the active-site disulfide. The results indicate a new biological role for Fe-S clusters involving both the stabilization of a thiyl radical intermediate and cluster site-specific chemistry involving a bridging sulfide.

Chloroplasts↗
PubMed1996

Characterization of the mononickel metallocenter in H134A mutant urease.

A mutant form of Klebsiella aerogenes urease possessing Ala instead of His at position 134 (H134A) is inactive and binds approximately half the normal complement of nickel (Park, I.-S., and Hausinger, R. P.(1993) Protein Sci. 2, 1034-1041). The crystal structure of the H134A protein was obtained at 2.0-A resolution, and it confirms that only Ni-1 of the two nickel ions found in the native enzyme is present. In contrast to the pseudotetrahedral geometry observed for Ni-1 in native urease (where it is liganded by His-246, His-272, one oxygen atom of carbamylated Lys-217, and a water molecule at partial occupancy), the mononickel metallocenter in the H134A protein was found to possess octahedral geometry and was coordinated by the above protein ligands plus three water molecules. The nickel site of H134A urease was probed by UV-visible, variable temperature magnetic circular dichroism, and x-ray absorption spectroscopies. The spectroscopic data are consistent with the presence of Ni(II) in octahedral geometry coordinated by two histidylimidazoles and additional oxygen and/or nitrogen donors. These data underscore the requirement of Ni-2 for formation of active urease and demonstrate the important role of Ni-2 in establishing the proper Ni-1 coordination geometry.

Binding Sites↗
PubMed1996

Cysteine ligand swapping on a deletable loop of the [2Fe-2S] ferredoxin from Clostridium pasteurianum.

The [2Fe-2S] ferredoxin from Clostridium pasteurianum is unique among ferredoxins, both by its sequence and by the distribution of its cysteine residues (in positions 11, 14, 24, 56, and 60). In previous investigations, a combination of site-directed mutagenesis and of spectroscopic techniques showed that cysteines 11, 56, and 60 are ligands of the [2Fe-2S] cluster in the wild type protein and that cysteine 14 is not, but the status of cysteine 24 remained unclear. New mutated forms of this ferredoxin have been obtained and characterized. The data show that cysteine 24 is a ligand of the cluster in the wild type protein. When cysteine 24 is mutated into alanine, it is replaced as a cluster ligand by cysteine 14. The fourth ligand of the cluster can also be a cysteine residue newly introduced in position 16 when both cysteines 14 and 24 are replaced by alanine. These results suggest that the region encompassing cysteines 14 and 24 is a solvent-exposed flexible loop, in agreement with structure predictions. A number of nondeleterious deletions of variable length (3-14 residues) have been performed in the region of residues 17-32. The deletions were found to modify only marginally the spectroscopic properties of the [2Fe-2S] cluster but resulted in variations of its redox potential over a range of nearly 100 mV. This is the first instance of ligand swapping in a [2Fe-2S] protein, and the first time in any ferredoxin that a large loop has been excised from the structure without preventing the assembly of the iron-sulfur chromophore. Some of the molecular variants described here also highlight the similarities between the C. pasteurianum [2Fe-2S] ferredoxin and the 25 kDa subunit of the proton-translocating NADH: ubiquinone oxidoreductase of Paracoccus denitrificans.

Amino Acid Sequence↗
PubMed1996

Axial heme ligation in the cytochrome bc1 complexes of mitochondrial and photosynthetic membranes. A near-infrared magnetic circular dichroism and electron paramagnetic resonance study.

The combination of EPR and low-temperature near-IR magnetic circular dichroism spectroscopies have been used to investigate the axial ligation of the cytochromes in the cytochrome bc1 complexes from bovine heart mitochondria, Rhodobacter capsulatus, Rhodobacter sphaeroides, and Rhodospirillum rubrum, and the purified cytochromes c1 from bovine heart mitochondria, Rb. capsulatus and Rb. sphaeroides. The possibility of axial ligation of cytochrome c1 by the amino terminus of the polypeptide was also assessed by acetylating the N-terminus of Rb. capsulatus cytochrome c1 and comparing the properties of the acetylated and unmodified samples. The results are consistent with bis-histidine axial ligation for the high- and low-potential b-type cytochromes and histidine/methionine axial ligation for the c1-type cytochrome in the intact cytochrome bc1 complexes. Purified samples of cytochrome c1 are mixtures of two forms, one with histidine/methionine and the other with bis-histidine axial ligation. The form with bis-histidine axial ligation is also assembled in the M183L mutant of the Rb. capsulatus cyt bc1 complex in which the methionine residue coordinating cyt c1 is replaced by a leucine. The bis-histidine form appears to be an artifact of dissociation of cytochrome c1 from the cytochrome bc1 complex and is greatly enhanced particularly in the bacterial cytochromes c1 by sample handling and the addition of 50% (v/v) ethylene glycol or glycerol.

Amino Acid Sequence↗
PubMed1996

Function of the [2FE-2S] cluster in mammalian ferrochelatase: a possible role as a nitric oxide sensor.

Ferrochelatase (E.C. 4.99.1.1) is the terminal enzyme of the heme biosynthetic pathway, catalyzing the insertion of ferrous iron into protoporphyrin. In mammals the enzyme contains a labile [2Fe-2S] center. Although this cluster is absent in all prokaryotic, plant, and yeast ferrochelatases, its destruction or elimination from the mammalian enzyme results in loss of enzyme activity. In the current study we present data which clearly demonstrate that mammalian ferrochelatase is strongly inhibited by nitric oxide and that this effect is mediated via destruction of the [2Fe-2S] cluster. Carbon monoxide has no inhibitory effect, and yeast ferrochelatase, which lacks the [2Fe-2S] cluster, is not affected by NO (or CO). EPR and UV-visible absorption of purified recombinant human ferrochelatase provides evidence that NO is targeting the [2Fe-2S] center. UV-visible absorption spectroscopy of both human and murine recombinant ferrochelatase incubated with NO or the NO donor, S-nitroso-N-acetylpenicillamine (SNAP), indicate a rapid loss of the visible absorption spectrum of the [2Fe-2S] cluster. EPR studies of the resulting samples reveal the characteristic axial S = 1/2 resonance, g perpendicular = 2.033, and g parallel = 2.014 of a cysteinyl-coordinated monomeric iron-dinitrosyl cluster degradation product. Parallel spectroscopic studies of spinach ferredoxin, which also contains a [2Fe-2S] cluster, gave no indication of NO-induced cluster degradation under the same experimental conditions. Exposure of DMSO-induced murine erythroleukemia cells exposed to SNAP results in an initial decrease in heme production, suggesting that in vivo the cluster is rapidly destroyed. The potential physiological relevance of these data to the anemias that are found in individuals with chronic infections is discussed.

Animals↗
PubMed1996

Some problems with the process-dissociation approach to memory.

The process-dissociation framework (L. L. Jacoby, 1991) is a technique for deriving estimates of controlled (e.g., recollection) and automatic (e.g., familiarity) memory processes. The authors examined 3 assumptions of this framework. In Experiment 1, estimates of familiarity were affected by varying the proportion of old targets to old nontargets on the inclusion and exclusion tests and whether or not the tests were completed with full or divided attention, violating the assumption that familiarity's influence is automatic. In Experiment 2, the similarity of old targets and old nontargets was manipulated to show that source confusions (i.e., misrecollections) violate the assumption that the process of recollection is all-or-none. Source confusions also create an imbalance in the influence of recollection on the inclusion and exclusion tests, violating the consistency assumption. The source-monitoring framework is consistent with the present findings.

Attention↗