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Michael J Taylor

Publications and source records attributed to Michael J Taylor.

At least 19 recordsLinked to original sources
PubMed2006

Modulating biochemical perturbations during 72-hour machine perfusion of kidneys: role of preservation solution.

This study documents renal biochemistry during hypothermic machine perfusion of kidneys. It is intended to demonstrate that a comprehensive evaluation of organ viability during ex-vivo preservation is needed to increase the number of organs available for transplantation and to reduce the current renal discard rate. Porcine kidneys were hypothermically machine perfused for 72 h with either Unisol-UHK or Belzer-Machine Perfusion Solution, (Belzer-MPS). Renal perfusate samples were periodically collected and biochemically analyzed. Significant differences were measured in the renal metabolic activity between the two experimental groups while similar values for traditional parameters such as renal flow rate and vascular resistance values were recorded. The effluent of UHK perfused kidneys showed strong metabolites and NH(4)(+) dynamics (P<0.05 vs. baseline), while the Belzer-MPS kidneys metabolic activity led to little or no change of the effluent biochemistry relative to baseline.

Animals↗
PubMed2006

Transient and executive function working memory in schizophrenia.

Transient working memory requires attention and temporary storage of information, whereas executive function working memory requires additional mental manipulation of that information. Working memory impairment is common in schizophrenia patients, but only some studies have found differential impairment in executive function working memory compared to transient working memory. We measured both types of working memory using the Digit Span forward (DF) and backward (DB) tasks in a large sample of schizophrenia patients (n=267) and normal comparison subjects (n=82); in the patients, we also examined associations between performance on the Digit Span tasks and Letter-Number Sequencing (LNS), a putative executive function working memory test. Compared to healthy subjects, the schizophrenia patients showed impairment in the medium effect size range on both DF (d=-0.55) and DB (d=-0.68). DB scores predicted LNS performance, whereas DF scores did not. Worse negative symptoms were associated with worse performance on DF, DB and LNS. These results do not reflect differential executive function working memory dysfunction in schizophrenia, but appear to support transient and executive function working memory as separable constructs.

Adult↗
PubMed2006

WAIS-III and WMS-III performance in chronic Lyme disease.

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects.

Adult↗
PubMed2006

Development of demographic norms for four new WAIS-III/WMS-III indexes.

Following the publication of the third edition Wechsler scales (i.e., WAIS-III and WMS-III), demographically corrected norms were made available in the form of a computerized scoring program (i.e., WAIS-III/WMS-III/WIAT-II Scoring Assistant). These norms correct for age, gender, ethnicity, and education. Since then, four new indexes have been developed: the WAIS-III General Ability Index, the WMS-III Delayed Memory Index, and the two alternate Immediate and Delayed Memory Indexes. The purpose of this study was to develop demographically corrected norms for the four new indexes using the standardization sample and education oversample from the WAIS-III and WMS-III. These norms were developed using the same methodology as the demographically corrected norms made available in the WAIS-III/WMS-III/WIAT-II Scoring Assistant.

Adolescent↗
PubMed2006

Demographically adjusted normative standards for new indices of performance on the Paced Auditory Serial Addition Task (PASAT).

The Paced Auditory Serial Addition Task (PASAT) is a complex cognitive test sensitive to neuropsychological disorders. Its traditional Total Correct score seemingly reflects multiple cognitive abilities, including attention, working memory, and processing speed. Snyder, Aniskiewicz, and Snyder (1993) modified scoring guidelines for the PASAT to give credit only for "dyads." This method emphasizes working memory operations and has been found superior to Total Correct scores at detecting cognitive impairments in several investigations. To date, normative standards are not available for the "dyad" scoring method, thus limiting its utility in clinical and research settings. The current investigation provides demographically adjusted normative data based on a sample of 500 healthy adults of varied age, education, sex, and race (African American and Caucasian) for various indices of performance on the PASAT, including "Total Dyads" obtained across the four PASAT trials. In addition, we describe and present normative data on four other indices designed to quantify various aspects of performance on the PASAT: invalid responding, effects of varied information processing speed demands, and tendency to omit responses and to make arithmetic errors.

Abstracting and Indexing↗
PubMed2005

Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors.

Nucleoside reverse transcriptase inhibitors (NRTIs) suppress human immunodeficiency virus (HIV) replication, but are often associated with mitochondrial toxicity. Although well studied outside of the central nervous system, no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV. The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria. N-acetylaspartate (NAA; sensitive to alterations in mitochondrial integrity) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and/or stavudine (two NRTIs likely to cause mitochondrial toxicity), 14 HIV+ individuals taking zidovudine and lamivudine, 16 HIV+ individuals not currently taking antiretrovirals, and 17 HIV- controls. The HIV+ groups were comparable on demographic measures, estimates of illness severity, and estimated length of HIV infection. Those taking didanosine and/or stavudine had a significant 11.4% decrease in concentrations of frontal white matter NAA compared to HIV- controls, whereas NAA levels of the other HIV+ groups were intermediate. Group differences in metabolites were not found in frontal gray matter. Lower levels of frontal white matter NAA were associated with longer periods of didanosine and/or stavudine treatment (r = -.41, P = .06). Levels of NAA were not related to length of zidovudine/lamivudine treatment (r = -.04, P = .44). Furthermore, taking more than one of stavudine, didanosine, and abacavir increased the likelihood of having reduced NAA. The results are consistent with previous studies finding HIV-related changes in neuronal integrity. However, because NRTIs can injure mitochondria, we propose that the observed reductions in NAA in individuals taking didanosine and/or stavudine may be the result of depleted brain mitochondria and/or alterations in cellular respiration. Measurement of brain metabolites sensitive to impairments in energy metabolism, including NAA, may aid in early detection of subclinical NRTI-mediated mitochondrial toxicity.

Adult↗
PubMed2005

Cryomacroscopy of vitrification, Part I: A prototype and experimental observations on the cocktails VS55 and DP6.

A new imaging device, termed a "cryomacroscope", is presented in this report. This device is designed to assist in exploring thermal and mechanical effects associated with large-scale vitrification and crystallization, with the current setup aimed at the range of 50 μm to 2 cm. The cryomacroscope is not intended as a substitute for the cryomicroscope, but as a complementary tool for the cryobiologist. A combination of cryomacroscopy and cryomicroscopy is suggested as a basis for multi-scale cryobiology studies. This report presents initial results on vitrification, crystallization, and fracture formation in the cryoprotectant cocktails DP6 and VS55. These results show some inconsistency in the tendency to form crystals, based on critical cooling and rewarming rates measured by means of a differential scanning calorimetric device (DSC) in parallel studies. This research is in its early stages, and comparative studies on biological materials are currently underway. Part II of this report (the companion paper) presents results for fracture formation in the cryoprotectant and discusses the mechanical stresses which promote these fractures. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

Journal Article↗
PubMed2005

Cryomacroscopy of vitrification, Part II: Experimental observations and analysis of fracture formation in vitrified VS55 and DP6.

A new imaging device, termed a "cryomacroscope", was used to observe macrofractures in the cryoprotectant cocktails DP6 and VS55. Details of the design and construction of the cryomacroscope were presented in Part I of this report, which focused on describing the apparatus and observations of crystallization. Part I and the current paper (Part II) describe events that occur as 1 mℓ of cryoprotectant contained in a glass vial is cooled from room temperature down to cryogenic temperatures (∼ -135°C). The presence of cracking, as well as patterns in their position and orientation, are found to be dependent on the cooling rate and on the specific cryoprotectant cocktail. Cracks, if present, disappear upon rewarming, although they appear to be sites for later preferential crystallization. Computations which predict temperatures and mechanical stresses are used to explain observations of cracking. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

Journal Article↗
PubMed2004

Promotion of iridium-catalyzed methanol carbonylation: mechanistic studies of the cativa process.

The iridium/iodide-catalyzed carbonylation of methanol to acetic acid is promoted by carbonyl complexes of W, Re, Ru, and Os and simple iodides of Zn, Cd, Hg, Ga, and In. Iodide salts (LiI and Bu(4)NI) are catalyst poisons. In situ IR spectroscopy shows that the catalyst resting state (at H(2)O levels > or = 5% w/w) is fac,cis-[Ir(CO)(2)I(3)Me](-), 2. The stoichiometric carbonylation of 2 into [Ir(CO)(2)I(3)(COMe)](-), 6, is accelerated by substoichiometric amounts of neutral promoter species (e.g., [Ru(CO)(3)I(2)](2), [Ru(CO)(2)I(2)](n), InI(3), GaI(3), and ZnI(2)). The rate increase is approximately proportional to promoter concentration for promoter:Ir ratios of 0-0.2. By contrast anionic Ru complexes (e.g., [Ru(CO)(3)I(3)](-), [Ru(CO)(2)I(4)](2)(-)) do not promote carbonylation of 2 and Bu(4)NI is an inhibitor. Mechanistic studies indicate that the promoters accelerate carbonylation of 2 by abstracting an iodide ligand from the Ir center, allowing coordination of CO to give [Ir(CO)(3)I(2)Me], 4, identified by high-pressure IR and NMR spectroscopy. Migratory CO insertion is ca. 700 times faster for 4 than for 2 (85 degrees C, PhCl), representing a lowering of Delta G(++) by 20 kJ mol(-1). Ab initio calculations support a more facile methyl migration in 4, the principal factor being decreased pi-back-donation to the carbonyl ligands compared to 2. The fac,cis isomer of [Ir(CO)(2)I(3)(COMe)](-), 6a (as its Ph(4)As(+) salt), was characterized by X-ray crystallography. A catalytic mechanism is proposed in which the promoter [M(CO)(m)I(n)] (M = Ru, In; m = 3, 0; n = 2, 3) binds I(-) to form [M(CO)(m)I(n+1)](-)H(3)O(+) and catalyzes the reaction HI(aq) + MeOAc --> MeI + HOAc. This moderates the concentration of HI(aq) and so facilitates catalytic turnover via neutral 4.

Journal Article↗
PubMed2004

Interstitial fluid analysis for assessment of organ function.

Evaluation methods are required for non-heart-beating donor (NHBD) kidneys to ensure the success of transplantation. In this study, the microdialysis technique was employed for the ex-vivo assessment of hypothermically preserved NHBD kidney function. Microdialysis probes were placed in the renal cortex of 2 h warm ischaemic porcine kidneys to monitor interstitial pyruvate dynamics during hypothermic machine perfusion with perfusate containing 29.4 mM fructose-1,6-diphosphate (FDP). The presence of exogenous FDP in the perfusate induced no changes in the renal flow rate and vascular resistance, renal artery effluent biochemistry, or pyruvate concentration relative to untreated control kidneys. Significant increases in pyruvate production (P < 0.05), however, were observed after 12 h of perfusion in the interstitial fluid of FDP-treated kidneys relative to control kidneys. After 24 h of perfusion, interstitial fluid concentrations of pyruvate were 149.1 +/- 58.4 vs. 55.6 +/- 17.9 micro M (P < 0.05) in the FDP and control group, respectively. The microdialysis probe collected the interstitial fluid directly from the cellular sites of metabolic and synthetic activity, where perfusate dilution was minimal. Consequently, the biochemical changes induced by the organ metabolic activity were detected only at the interstitial level, in the microdialysates. Interstitial fluid pyruvate may be a good indicator of kidney function. The addition of FDP to the perfusion solution during ischaemic kidney preservation resulted in enhanced pyruvate production in the extracellular space, indirectly reflecting an increase in anaerobic ATP production. The pyruvate will be transformed during organ reperfusion into acetyl Co-A enzyme allowing an immediate start of aerobic metabolism. This in turn can increase the amount of ATP available to the cells and may help prevent reperfusion injury upon transplantation.

Animals↗
PubMed2003

Comprehensive analysis of gene expression in rat and human hepatoma cells exposed to the peroxisome proliferator WY14,643.

Peroxisome proliferators (PPs) are an important class of chemicals that act as hepatic tumor promoters in laboratory rodents. The key target for PPs is the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPARalpha) and these chemicals cause cancer by altering the expression of a subset of genes involved in cell growth regulation. The purpose of the present study was to utilize high-density gene expression arrays to examine the genes regulated by the potent PP Wy14,643 (50 microM, 6 h) in both rat (FaO) and human (HepG2) hepatoma cells. Treatment of FaO cells, but not HepG2, revealed the expected fatty acid catabolism genes. However, a larger than expected number of protein kinases, phosphatases, and signaling molecules were also affected exclusively in the FaO cells, including MAPK-phosphatase 1 (MKP-1), Janus-activated kinases 1 and 2 (JAK1 and 2), and glycogen synthetase kinase alpha and beta (GSKalpha and beta). The mRNA accumulation of these genes as well as the protein level for GSK3alpha, JAK1, and JAK2 and MKP-1 activity was corroborated. Due to the importance of MKP-1 in cell signaling, this induction was examined further and was found to be controlled, at least in part, at the level of the gene's promoter. Interestingly, overexpression of MKP-1 in turn affected the constitutive activity of PPARalpha. Taken together, the gene expression arrays revealed an important subset of PP-regulated genes to be kinases and phosphatases. These enzymes not only would affect growth factor signaling and cell cycle control but also could represent feedback control mechanisms and modulate the activity of PPARalpha.

Animals↗
PubMed2003

Effects of alcoholism and gender on brain metabolism.

OBJECTIVE: Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism. METHOD: Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group. RESULTS: In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference). CONCLUSIONS: Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.

Adult↗
PubMed2002

Multi-residue method for rapid screening and confirmation of pesticides in crude extracts of fruits and vegetables using isocratic liquid chromatography with electrospray tandem mass spectrometry.

A LC-MS-MS method capable of the quantitative determination of a range of pesticide residues present in crude extracts from a variety of fruit and vegetables has been developed. Isocratic LC conditions have been used in conjunction with electrospray ionisation tandem mass spectrometry to detect and identify up to 38 pesticides presented as various mixtures in different matrices. The utility of the method is demonstrated by the analysis of crude extracts, with no sample clean up, from grape, kiwi fruit, strawberry, spinach, lemon, peach and nectarine. Mean recoveries ranging from 63 to 96% with relative standard deviations < 20% were obtained for 30 of the 38 pesticides following analysis of organic produce fortified at concentrations between 0.01 and 0.8 mg/kg. Detected residues were quantified from interpolation against calibration data generated using matrix-matched standards that covered analyte concentration ranges between 0.005 and 0.8 microg/ml. Conditions suitable for the qualitative and quantitative confirmation of residues detected in samples are specified.

Chromatography, High Pressure Liquid↗
PubMed2002

Spectroscopic characterisation of indium(III) chloride and mixed ligand complexes.

Acidic solutions of InCl3 plus InBr3 contain mixed halide complexes and solvent extraction yields the four-coordinate anions InCl(n)Br(4 - n)-, whose v(In-Cl) and v(In-Br) modes are reported. Two solid products of InCl3 with 15-crown-5 have been identified; crystallisation from aqueous HCI gave a molecular adduct containing InCl3(H2O)2, whereas the ionic complex [InCl2(15-crown-5)][InCl4] was produced under anhydrous conditions. The vibrational spectra are assigned.

Biophysical Phenomena↗
PubMed2002

Acid-base buffering in organ preservation solutions as a function of temperature: new parameters for comparing buffer capacity and efficiency.

Control of acidity and preventing intracellular acidosis are recognized as critical properties of an effective organ preservation solution. Buffer capacity and efficiency are therefore important for comparing the relative merits of preservation fluids for optimum hypothermic storage, but these parameters are not available for the variety of organ preservation solutions of interest in transplantation today. Moreover, buffer capacity is dependent upon both concentration and pH such that buffer capacity is not easily predicted for a complex solution containing multiple buffer species. Using standard electrometric methods to measure acid dissociation constants, this study was undertaken to determine the maximum and relative buffer capacities of a variety of new and commonly used hypothermic preservation solutions as a function of temperature. The reference data provided by these measurements show that comparative buffer capacity and efficiency vary widely between the commonly used solutions. Moreover, the fluids containing zwitterionic sulfonic acid buffers such as Hepes possess superior buffering for alpha-stat pH regulation in the region of physiological importance.

Acid-Base Equilibrium↗
PubMed2002

Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: procedure and application to the preclinical evaluation of chemopreventive agents.

Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds.

Animals↗
PubMedDate not supplied

Vitreous preservation of articular cartilage grafts.

Articular cartilage has proved refractory to satisfactory cryopreservation using conventional freezing methods. Therefore, an ice-free cryopreservation method by vitrification was tested. Osteochondral plugs from New Zealand White rabbits were preserved using either a freezing method or an ice-free vitrification method of cryopreservation. Preserved and fresh control plugs were implanted in the tibial plateau of allogeneic recipients. A modified O'Driscoll grading scale, based on gross pathology, histopathology, and histochemistry, was used to evaluate the explants.The histology of fresh and vitrified explants was essentially the same, while the frozen cryopreserved explants were devoid of chondrocytes and only fibroblastlike cells were observed. The O'Driscoll grading indicated that both fresh and vitrified plugs performed significantly better than frozen plugs (p < or =.05). The results demonstrate the feasibility of vitrification as a storage method for cartilaginous tissues.

Animals↗