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J K Johnson

Publications and source records attributed to J K Johnson.

At least 37 records · Page 2Linked to original sources

Detecting symmetric patterns in EEG data: a new method of analysis.

Theoretical models of higher cognitive function predict that cortical activity will exhibit families of spatial-temporal patterns of activity whose individual members are related to each other by specific symmetry transformations. In the trion model, it is suggested that these inherent symmetries play a vital role in how we think and reason. We have developed a method of analysis (SYMMETRIC analysis), which detects families of patterns in EEG data, and characterizes the symmetry relationships between members of those pattern families. Using this analysis, significant symmetry families have been found in EEG and single unit spike train data. If symmetry is a crucial aspect of brain function, it is possible that different pathologies are associated with specific types of symmetry relationships in brain activity that could be detected in EEG data by a SYMMETRIC analysis.

Electroencephalography↗

Initiation and propagation stages of beta-amyloid are associated with distinctive apolipoprotein E, age, and gender profiles.

Several recent studies have defined a relationship between apo-lipoprotein E (apoE) genotype and the risk of various neurodegenerative disorders. However, few studies have examined the influence of apoE on quantitative measures of beta-amyloid (Abeta) accumulation in a large population of autopsy cases. Using a multi-level analysis model, the interrelationships among apoE genotype, gender, age, and Abeta accumulation were investigated. In the population of these cases, there was a strong relationship between the presence of an epsilon4 allele and extent of Abeta in the frontal and entorhinal cortex. That is, when evaluating the presence or absence of significant Abeta (>1% Abeta load), subjects with one and two epsilon4 alleles were 1.9 and 3.5 times more likely to have significant Abeta accumulation than those with no epsilon4 alleles. These risks increased by a multiplicative factor of 1.014 for each year of age (at the time of death). In the subset of cases with significant Abeta (>1% Abeta load), the degree of Abeta load was best predicted by the presence of an epsilon2 allele and gender; females with no epsilon2 alleles had the highest Abeta loads (mean=12.3%), while males with one epsilon2 allele had the lowest amount of Abeta accumulation (mean=8.6%). Our results suggest that the presence of an epsilon4 allele predicts an earlier onset of Abeta deposition that is independent of gender. In contrast, once Abeta deposition has been initiated, the presence of an epsilon2 allele is associated with slower rates of accumulation, with males benefiting from the protective effect more than females.

Adult↗

Enhancement of spatial-temporal reasoning after a Mozart listening condition in Alzheimer's disease: a case study.

Several recent studies have investigated the effectiveness of various behavioral interventions on the cognitive performance of subjects with Alzheimer's disease (AD). Simulations of Shaw's structured model of the cortex led to the predictions that music might enhance spatial-temporal reasoning. A subsequent behavioral study in college students documented an improvement in scores on a spatial-temporal task after listening to a Mozart piano sonata. In this study, we investigated the enhancement of scores on a spatial-temporal task after a Mozart listening condition in a set of twins who are discordant for AD. After listening to an excerpt from a Mozart piano sonata, the AD twin showed considerable improvement on the spatial-temporal task when compared with pretest scores. Furthermore, no enhancement of scores was seen following either of the control conditions (i.e., silence or 1930s popular tunes). This finding suggests that music may be used as a tool to investigate functional plasticity in Alzheimer's disease and to better understand the underlying pathophysiology.

Aged↗

Early generation of glia in the intermediate zone of the developing cerebral cortex.

Radial glia are present at the earliest stage of cerebral cortical development, and later they transform into astrocytes. Other glial cells including astrocytes and oligodendrocytes are thought to appear only after neuron generation is complete and the cortical layers are formed. Little is known of when and where microglia enter the central nervous system and proliferate. We addressed the question of the origin of these three glial cell types in the developing ferret cerebral cortex. We assessed the temporal pattern of glial cell division by administering [3H]thymidine to label cells in S phase, and by using survival periods of 1-2 h to label dividing cells in situ. Labeled cells were identified in the developing intermediate zone of the ferret cerebral wall. These cells were present at E28, and reached a maximum number at P1. Double labeling experiments identified these cells as astrocytes, oligodendrocytes or microglia. None of the dividing cells expressed neuronal markers. These data show that all three types of glia are generated in the developing subcortical white matter, and that glial progenitors are present in the intermediate zone as soon as it becomes a recognizable structure. These data also show that the period of glial generation overlaps extensively with the period of neuron generation, since neuron generation is not complete until the end of the second postnatal week in the ferret.

Animals↗

A transient phase of cell death in the developing medial forebrain of the perinatal ferret.

A transient bilateral population of cells immediately rostral to the ferret corpus callosum was examined at weekly intervals between embryonic day 28 and postnatal day 7. This region is tentatively identified as the medial forebrain apoptosis zone (MFAZ) because of the specific nature of cell death, and the limited area or zone in which it was observed. No other region within the brain or retina exhibited a similar pattern or amount of cell death. Only scattered apoptotic cells were found throughout the remainder of the brain-including the cerebral cortical plate, subplate, and white matter-with the exception of the ventricular zone of the lateral ventricles which contained a significant population of apoptotic cells. This study addressed three questions about apoptosis in the MFAZ: (1) does apoptotic cell death in this region signal the appearance of phagocytic macrophages, (2) does cell degeneration and phagocytosis in this region lead to the formation of an extracellular space analogous to the cavum septi pellucidi of rodents, and (3) what is the duration of degeneration, or clearance rate, of cell death in this defined region. The MFAZ was first found to contain apoptotic nuclei and macrophages late in gestation, at E34. Numbers of apoptotic nuclei and macrophages peaked one week later at birth in this area, but disappeared early in postnatal life. During this period, formation of a space rostral to the corpus callosum due to the removal of apoptotic cells was not observed. Finally, presence of apoptotic cells in the MFAZ over a period of > or = 9 days suggests a clearance rate of many hours. The close spatiotemporal correlation of the distribution of apoptotic cells and their removal by macrophages suggests that these are interrelated, and perhaps interdependent events.

Animals↗

Distribution of calcium-binding proteins within the parallel visual pathways of a primate (Galago crassicaudatus).

Bush babies possess three distinct parallel pathways to striate cortex (V1 or area 17). The calcium-binding proteins parvalbumin (PV) and calbindin (CB) typically show complementary regional distributions in the brain, often associated with specific aspects of functionally related groups of cells. We asked whether PV+ and CB+ immunoreactivity differentiate central visual parallel pathways in this species. Results show that PV and CB cell and neuropil staining is strongly complementary in the lateral geniculate nucleus (LGN) and is associated with separate parallel pathways. CB+ immunoreactivity is dense, but cytochrome oxidase (CO) staining is light in the paired koniocellular layers. PV+ and CO+ immunoreactivity is most dense in the parvocellular and magnocellular layers. Combined analyses of cell size, retrograde labeling, and double labeling have confirmed that all PV+ and CB+ LGN cells are geniculocortical relay cells; none was found to be gamma-aminobutyric acid (GABA)ergic. In V1, dense PV+ neuropil closely matches the expression of CO in layer 4 and in the blobs of layer 3. CB+ staining is most dense in layers 2 and 3A and is not strongly expressed within the CO interblobs. Finally, PV and CB are not found in related parallel pathway components in the LGN and V1 (e.g., in V1, CO blobs exhibit dense PV+ neuropil, yet they are targets of the small K geniculocortical relay cells that are CB+ in the LGN). Our findings support the view that three functionally distinct visual pathways project to V1 from the LGN. However, the differences in the patterns of localization of PV and CB in the LGN and in V1 suggest that these proteins may be utilized in different ways in these two visual areas.

Animals↗

Molecular basis of the medium-chain fatty acyl-CoA dehydrogenase-catalyzed "oxidase" reaction: pH-dependent distribution of intermediary enzyme species during catalysis.

In a previous paper, we demonstrated that the medium-chain fatty acyl-CoA dehydrogenase-catalyzed (MCAD-catalyzed) reductive half-reaction of indolepropionyl-CoA proceeds via formation of a chromophoric intermediary species "X" (absorption maximum = 400 nm) and proposed that the decay of this species might limit the overall rate of the "oxidase" reaction [Johnson, J. K., & Srivastava, D. K. (1993) Biochemistry 32, 8004-8013]. During this latter reaction, the buffer-dissolved O2 served as an electron acceptor [Johnson, J. K., Wang, Z. X., & Srivastava, D. K. (1992) Biochemistry 31, 10564-10575]. To ascertain whether the intrinsic stability of X influences the oxidase activity, we undertook a detailed kinetic investigation of this enzyme at different pH values. The time-resolved spectra for the reductive half-reaction (obtained via the rapid-scanning stopped-flow method) at different pH values reveal that the amplitude of the intermediary (X) spectral band is more pronounced at a lower pH (pH 6.4) than at a higher pH (pH 9.0). Single-wavelength transient kinetic data for the reductive half-reaction (in both the forward and the reverse direction) at all pH values are consistent with fast (1/tau 1) and slow (1/tau 2) relaxation rate constants. Of these, whereas the fast relaxation rate constant for the reaction in the forward direction (1/tau 1f) decreases with an increase in pH, the corresponding slow relaxation rate constant (1/tau 2f) increases with an increase in pH. The pH-dependent steady-state kinetic data reveal that, like 1/tau 2f, kcat for the MCAD-catalyzed oxidase reaction increases with an increase in the pH of the buffer media.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl-CoA Dehydrogenase↗

Computed tomography detection of a cerebral calcific embolus following coronary catheterization.

A 77-year-old man underwent coronary artery angiography quite well. However, several attempts were required to pass the pigtail catheter across a calcified stenotic aortic valve. On return to the floor, motor aphasia and right hemiparesis developed and improved steadily within a few days. Computed tomography (CT) of the head revealed a calcific density in the left middle cerebral artery. The authors believe the calcific plaque originated from the calcified aorta and aortic valve. The patient was discharged within 48 hours with minimal neurological signs. Spontaneous calcified emboli to cranial vessels from calcific aortic stenosis or other sources are rare. CT detection of a calcific plaque in a cranial vessel following coronary vessel catheterization is well documented in this patient.

Aged↗

Peptides associated with monensin resistance in sporozoites of Eimeria tenella (Coccidia).

Resistance to monensin in the sporozoites of a laboratory strain (WIS) of Eimeria tenella was amplified by treating free sporozoites with increased monensin levels in vitro, followed by propagation of these treated sporozoites in chickens. The parent strain of WIS and its subsequent lines developed from the treatment of monensin at 1, 5, or 25 micrograms/ml were designated as WIS(0), WIS(1), WIS(5), or WIS(25), respectively. The penetration rate of sporozoites into primary chicken kidney cell cultures showed that the sensitivity of sporozoites to the treatment of monensin at 1 and 5 micrograms/ml was significantly reduced in the WIS(25) line in comparison with the WIS(0) line. When native polyacrylamide gel electrophoresis (PAGE) was conducted, a change in the relative mobility of a protein band was found in the protein samples of these coccidial lines. Sodium dodecyl sulfate PAGE revealed that 2 peptides with molecular weights of approximately 50.0 and 31.4 kDa were present in the sporozoites of resistant lines but undetectable in their WIS-parent sporozoites. Derivation of the resistant lines from a drug-sensitive parent line gave strong support to a link between the appearance of the peptides and resistance to ionophores in this strain of E. tenella.

Animals↗

Microscopic pathway for the medium-chain fatty acyl CoA dehydrogenase catalyzed oxidative half-reaction: changes in the electronic structures of flavin and CoA derivatives during catalysis.

In a previous communication, we demonstrated that the medium-chain fatty acyl CoA dehydrogenase (MCAD) catalyzed conversion of 3-indolepropionyl CoA (IPCoA) to trans-3-indoleacryloyl CoA (IACoA) proceeds via the formation of an intermediary species X that possesses the electronic properties of reduced flavin and highly conjugated CoA product. Since the steady-state turnover of the enzyme-catalyzed dehydrogenation reaction precisely matches with the rate of formation of X [Johnson, J. K., & Srivastava, D. K. (1993) Biochemistry 32, 8004-8013], the latter species appeared to be the likely site for the transfer of electrons to external electron acceptors (e.g., ferricenium hexafluorophosphate, FcPF6). To probe the microscopic pathway for the oxidative half-reaction, we employed a sequential mixing stopped-flow technique utilizing IPCoA as the enzyme substrate and FcPF6 as the electron acceptor. The time-dependent changes in absorption at 450, 415, and 367 nm were measured upon mixing FcPF6 with previously mixed and aged solutions of MCAD-FAD+IPCoA in the stopped-flow syringes. The kinetic traces show an increase (1/tau 1) followed by a decrease (1/tau 2) in absorption at 450 and 415 nm, and a lag (corresponding to the time regime of 1 u 1) followed by an increase in absorption (1/tau 2) at 367 nm. The relaxation rate constants (1/tau's) thus measured remain unaffected, with variations in the aging time; however, the amplitudes of these phases increase up to the aging time of 5 s, after which the amplitudes attain maxima. For an aging time of 5 s, 1/tau 1 and 1/tau 2 show a linear and a hyperbolic dependence on the FcPF6 concentration, respectively. These, coupled with the complementary studies involving butyryl CoA as a nonchromophoric substrate for this enzyme, lead us to propose the following sequence of events during the MCAD-catalyzed oxidative half-reaction: (1) The enzyme-catalyzed oxidative half-reaction proceeds via the formation of a collision complex between X and FcPF6 during the fast (1/tau 1) relaxation phase. (2) The reduced flavin moiety of X is oxidized via (rapid) transfer of electrons to FcPF6 within the collision complex, without formation of a detectable (metastable) flavin semiquinone intermediate. (3) The transfer of electrons is accompanied by changes in the electronic structures of both the flavin and IACoA moieties within the enzyme-IACoA complex. The electronic structure of this newly formed complex is exactly the same as that formed upon isomerization of the MCAD-FAD-IACoA complex [Johnson, J. K., Wang, Z. X., & Srivastava, D. K. (1992) Biochemistry 31, 10564-10575].(ABSTRACT TRUNCATED AT 400 WORDS)

Acyl Coenzyme A↗

Detection and identification of a chromophoric intermediate during the medium-chain fatty acyl-CoA dehydrogenase-catalyzed reaction via rapid-scanning UV/visible spectroscopy.

We have investigated the medium-chain fatty acyl-CoA dehydrogenase (MCAD)-catalyzed reaction via rapid-scanning stopped-flow (RSSF) UV/vis spectroscopy, combined with the single-wavelength stopped-flow technique, utilizing 3-indolepropionyl-CoA (IPCoA) and trans-3-indoleacryloyl-CoA (IACoA) as chromophoric pseudosubstrates. The RSSF spectral data reveal that formation of an intermediary species with an absorbance maximum at 400 nm and a broad charge-transfer band around 600 nm accompanies the reduction of MCAD-FAD by IPCoA. In the presence of high concentrations of enzyme ([MCAD] >> [IPCoA]) the intermediary spectral band at 400 nm remains unperturbed, whereas in the presence of low concentrations of enzyme ([MCAD] << [IPCoA]) it slowly shifts to an absorption band with an absorbance maximum at 370 nm. Appearance and disappearance of this intermediary species coincides with the appearance and disappearance of the charge-transfer band. Single-wavelength stopped-flow studies, performed under similar high and low enzyme conditions, were consistent with one (1/tau 1) and two (1/tau 1 > 1/tau 2) relaxation rate constants, respectively. These findings, combined with relaxation studies performed in the reverse directions as well as substrate and product binding studies with the oxidized and reduced forms of the enzyme, have allowed us to conclude the following: (1) the intermediary species possesses the properties of reduced flavin and highly conjugated reaction product IACoA (absorbance maximum = 400 nm); (2) this intermediary species collapses into an MCAD-FADH2-IACoA complex (absorbance maximum = 370 nm) in the presence of excessive concentrations of IPCoA; the collapse is being driven by the competitive binding of IPCoA with the reduced form of the enzyme; (3) the 400-nm absorption band and the charge-transfer band are given by the same intermediary species formed during the enzyme-catalyzed reaction pathway. The role of protein conformational changes in modulating the substrate/product structures during the MCAD-catalyzed reaction is discussed.

Acyl Coenzyme A↗

Efficacy of semduramicin and salinomycin against different stages of Eimeria tenella and E. acervulina in the chicken.

The efficacy of a new ionophore, semduramicin, was compared with salinomycin in a series of in ovo and in vivo trials. Semduramicin was more efficacious than salinomycin against Eimeria tenella sporozoites as judged by oocyst production in embryonated eggs. When the two drugs were given in ovo at 93 h post inoculation (PI), both drugs exerted some effect against late schizogonous stages of E. tenella. In three battery studies, semduramicin (25 ppm) and salinomycin (60 and 66 ppm) were tested against E. tenella and E. acervulina. Medicated feed was withdrawn at 24-h intervals PI to study the stage of action of the anticoccidials. In E. tenella infected chickens, both anticoccidials exerted their maximum effect on weight gain and feed:gain ratio through the first 72 h PI. Semduramicin was more effective than salinomycin in controlling E. tenella lesions and coccidiosis mortality. With E. acervulina, both drugs acted similarly on early life cycle stages and no improvement in performance was recorded when medicated feed was given for longer than 72 h. Semduramicin was more effective than salinomycin in controlling E. acervulina lesions.

Animals↗

Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester.

Cytoadherence to HB3 and FC27 strains of Plasmodium falciparum-parasitized red blood cells (PRBC) was studied under shear conditions to elucidate the pathways of adherence to microvascular endothelial cells (MEC). HB3 PRBC bound exclusively to MEC CD36 and intercellular adhesion molecule-1 (ICAM-1) receptors. FC27 PRBC bound to CD36 and another unidentified pathway but not to ICAM-1. Down-regulation of CD36 and ICAM-1 expression by phorbol 12,13-dibutyrate abolished HB3 PRBC adherence. Selective up-regulation of CD36 with interferon-gamma (IFN-gamma) increased PRBC adherence. Conversely, selective up-regulation of ICAM-1 with tumor necrosis factor did not elevate cytoadherence. These data have defined the relative contributions of both CD36 and ICAM-1 to PRBC binding to MEC and have provided evidence for the presence of a novel adhesion mechanism. Furthermore, in addition to antibody blocking of cell adhesion molecules, anti-IFN-gamma antibody therapy or pharmacologic manipulation of endothelial cell receptor expression may reduce PRBC sequestration and ameliorate the events associated with human cerebral malaria.

Antigens, CD↗

Outcome of treating thyrotoxic patients with a standard dose of radioactive iodine.

This is a report of an audit exercise that was designed to study the effectiveness of treating thyrotoxic patients with a standard dose--370 MBq--of radioactive iodine (131l). This treatment was received by 183 patients in one centre between 1977 and 1989. The results were assessed from the answers to 114 questionnaires that had been completed by the patients' general practitioners. The patients were aged between 28 and 85 years; 86% were female; 42% had been treated previously with anti-thyroid drugs. Ninety-five of the patients (83%) became euthyroid after a single dose of 131l; 18 required one further dose; and one required two further doses. At the time of the survey, 32 (28%) were euthyroid, while 82 patients (72%) had become hypothyroid and required treatment with thyroxine. Within five years of treatment, 85% of the patients had become hypothyroid. These results are compared with those from two other centres.

Adult↗

The nitrate contamination of private well water in Iowa.

The State-Wide Rural Well-Water Survey was conducted between April 1988 and June 1989. About 18% of Iowa's private, rural drinking-water wells contain nitrate above the recommended health advisory level (levels of NO3-N greater than 10 mg/L); 37% of the wells have levels greater than 3 mg/L, typically considered indicative of anthropogenic pollution. Thirty-five percent of wells less than 15 m deep exceed the health advisory level, and the mean concentration of nitrate-nitrogen for these wells exceeds 10 mg/L. Depth of well is the best predictor of well-water contamination. Individually, NO3-N levels of more than 10 mg/L occurred alone in about 4% of the private wells statewide; pesticides were present alone in about 5%. Total coliform positives occurred alone at 27% of the sites. In a cumulative sense, these three contaminants were detected in nearly 55% of rural private water supplies.

Enterobacteriaceae↗

Mechanistic investigation of medium-chain fatty acyl-CoA dehydrogenase utilizing 3-indolepropionyl/acryloyl-CoA as chromophoric substrate analogues.

The CoA derivative 3-indolepropionyl-CoA (IPCoA) serves as a competent pseudosubstrate for the medium-chain fatty acyl-CoA dehydrogenase (MCAD)-catalyzed reaction. The reaction product trans-3-indoleacryloyl-CoA (IACoA) exhibits a characteristic UV-vis absorption spectrum with lambda max = 367 nm and epsilon 367 = 26,500 M-1 cm-1. The chromophoric nature of IACoA allows us to measure the direct conversion of substrate to product (at 367 nm) without recourse to absorption signals for either the enzyme-bound flavin or the coupling electron acceptors, as well as probe the enzyme site environment. The interaction of IACoA with medium chain fatty acyl-CoA dehydrogenase (MCAD)-FAD is characterized by resultant (spectra of the mixture minus the individual components) absorption peaks at 490, 417, and 355 nm. These absorption peaks increase in magnitude as the pH of the buffer media decreases. Transient kinetic analysis for the interaction of MCAD-FAD with IACoA suggests that the formation of the enzyme-IACoA complex proceeds in two steps. The first (fast) step involves the formation of an E-IACoA collision complex, which [formula: see text] is isomerized (concomitant with changes in the protein structure) to an E*-IACoA complex in the second (slow) step. We have studied the effect of pH on Kc, k2, and k-2. While Kc shows practically no dependence on pH (within a 2-fold variation between pH 6.0 and 9.5), k2 and k-2 show a strong dependence on pH. Both k2 and k-2 exhibit a sigmoidal dependence on the pH of the buffer media, with pKa's of 7.53 and 8.30, respectively. In accordance with the model presented herein, the pKa of 7.53 represents an enzyme site group which is involved in the interaction with IACoA within the E-IACoA collision complex. This pKa is perturbed to 8.30 upon isomerization of the collision complex. The pH-dependent changes in k2 and k-2 are such that the equilibrium distribution between E-IACoA and E*-IACoA is favored to the latter complex (by about 20-fold) at lower pH than at higher pH. A cumulative account of the spectral, kinetic, and thermodynamic properties of the enzyme-IACoA complexes has allowed us delineate the microscopic pathway by which the E-IACoA isomerization (presumably via protein conformational changes) is coupled to the proton equilibration steps.

Acyl Coenzyme A↗