Biomedical subjects

J A Lucas

Publications and source records attributed to J A Lucas.

At least 19 recordsLinked to original sources

PubMed2006

Impact of changes in the target P450 CYP51 enzyme associated with altered triazole-sensitivity in fungal pathogens of cereal crops.

Control of diseases caused by fungi in both medicine and agriculture is heavily dependent on the use of triazoles. As a consequence, resistance to triazoles is a threat to both human health and the sustainability of agricultural production systems. In human pathogens, particularly Candida albicans, mutations encoding alterations in the target cytochrome P450 sterol 14alpha-demethylase (CYP51; where CYP is cytochrome P450) enzyme are the primary determinants of triazole resistance. In fungal pathogens of cereals, CYP51A1 modifications, some at positions known to contribute to a resistant phenotype in human pathogens, have also been identified in isolates with altered triazole-sensitivity. However, unlike medicine where resistance to triazoles is a major clinical problem, failures of triazoles to control crop diseases in the field are rare with mean population sensitivities generally remaining low, perhaps due to differences in the selection pressures imposed on human and cereal pathogen populations. Nonetheless, the biological potential for resistance exists, and the question remains as to whether widespread triazole resistance can develop in an important cereal pathogen.

Cytochrome P-450 Enzyme System↗

PubMed2004

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.

Aged↗

PubMed2001

Cloning of the CYP51 gene from the eyespot pathogen Tapesia yallundae indicates that resistance to the DMI fungicide prochloraz is not related to sequence changes in the gene encoding the target site enzyme.

Resistance to sterol 14 alpha-demethylase inhibitor (DMI) fungicides has been correlated with mutations in the CYP51 gene encoding the target enzyme eburicol 14 alpha-demethylase. CYP51 was isolated from the eyespot pathogen Tapesia yallundae revealing a predicted 526-amino acid product exhibiting homology to other fungal CYP51s. CYP51 was sequenced from four field isolates sensitive or resistant to the DMI fungicide prochloraz and partially sequenced from two further isolates and eight progeny from a cross between prochloraz-sensitive and -resistant parents. Two alleles of the gene were detected termed CYP51-1 and CYP51-2. No correlation was found between sequence change and fungicide sensitivity. Therefore prochloraz resistance involved a mechanism other than mutation in the target site gene.

Amino Acid Sequence↗

PubMed2001

Hippocampal atrophy correlates with clinical features of Alzheimer disease in African Americans.

CONTEXT: Imaging measurements may aid in the characterization and diagnosis of patients with Alzheimer disease (AD). Most research studies, however, have been performed on predominantly white study groups despite the fact that there may be biological differences in AD between African American and white patients. OBJECTIVE: To measure hippocampal volume in African American patients with AD and to correlate these measurements with the presence of AD and neuropsychological test performance. DESIGN: Survey study. SETTING: Academic center. PARTICIPANTS: Fifty-four healthy African American subjects and 32 African American patients with AD were studied. Hippocampal volumes were measured in all subjects from magnetic resonance images using established methods. MAIN OUTCOME MEASURE: Correlations were assessed between hippocampal volume and demographic variables, clinical group membership, and neuropsychological performance. RESULTS: The hippocampi of patients were atrophic with respect to those of healthy subjects (P<.01). Significant direct correlations were present between hippocampal volumes and performance on several different neuropsychological tests (r>0.5 and P<.01 for every test evaluated) when patients and healthy subjects were combined. CONCLUSIONS: Hippocampal atrophy is a feature of AD in African Americans as it is in white subjects. The neuropsychological-hippocampal volume correlations indicate that hippocampal volume measurements do represent a measure of the structural substrate of functional impairment in AD.

Black or African American↗

PubMed2001

Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy.

Our objective was to examine whether rapid eye movement (REM) sleep behavior disorder occurs in disproportionally greater frequency in multiple system atrophy (MSA), Parkinson's disease (PD), and dementia with Lewy bodies (DLB), collectively known as the synucleinopathies, compared to other nonsynucleinopathy neurodegenerative disorders. In study 1, we reviewed the clinical records of 398 consecutive patients evaluated at Mayo Clinic Rochester for parkinsonism and/or cognitive impairment. The frequency of suspected and polysomnogram (PSG)-confirmed REM sleep behavior disorder (RBD) among subjects with the synucleinopathies MSA, PD, or DLB was compared to the frequency among subjects with the nonsynucleinopathies Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), mild cognitive impairment (MCI), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). In study 2, we reviewed the clinical records of 360 consecutive patients evaluated at Mayo Clinic Jacksonville for parkinsonism and/or cognitive impairment. The frequency of probable RBD among patients with PD and DLB was compared to the frequency among patients with AD and MCI. In study 3, we reviewed the brain biopsy or postmortem autopsy diagnoses of 23 Mayo Clinic Rochester patients who had been clinically examined for possible RBD and a neurodegenerative disorder. In study 1, patients with MSA, PD, or DLB were more likely to have probable and PSG-confirmed RBD compared to subjects with the nonsynucleinopathies (probable RBD 77/120=64% vs. 7/278=3%, p < 0.01; PSG-confirmed RBD 47/120=39% vs. 1/278=0%, p < 0.01). In study 2, patients with PD and DLB were more likely to have probable RBD compared to those with AD and MCI (56% vs. 2%, p < 0.01). In study 3, of the 23 autopsied patients who had been questioned about possible RBD, 10 were clinically diagnosed with RBD. The neuropathologic diagnoses in these 10 included Lewy body disease in nine, and MSA in one. Of the other 13 cases, 12 did not have a history suggesting RBD, and the one case who did had normal electromyographic atonia during REM sleep on PSG and autopsy findings of PSP. Only one of these 13 had a synucleinopathy. The positive predictive values for RBD indicating a synucleinopathy for studies 1-3 were 91.7%, 94.3%, and 100.0%, respectively. Clinically suspected and PSG-proven RBD occurs with disproportionally greater frequency in MSA, PD, and DLB compared to other neurodegenerative disorders. In the setting of degenerative dementia and/or parkinsonism, we hypothesize that RBD is a manifestation of an evolving synucleinopathy.

Adult↗

PubMed2001

Quantitative and qualitative outcome measures after thalamic deep brain stimulation to treat disabling tremors.

OBJECTIVE: We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed. METHODS: Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed. RESULTS: Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < 0.001), lower-limb (P < 0.01), and midline (P < 0.001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < 0.01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < 0.001) and postural (P < 0.01) tremors and ipsilateral postural tremor (P < 0.05). Activities of daily living improved after unilateral surgery (P < 0.001) and additionally after bilateral surgery (P < 0.05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants. CONCLUSION: Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible.

Activities of Daily Living↗

PubMed2001

Extensive metabolic and neuropsychological abnormalities associated with discrete infarction of the genu of the internal capsule.

OBJECTIVE: The clinical presentation of capsular genu infarct varies. Prominent faciolingual weakness and subcortical dementia are the rule, but symptoms depend on the precise location and extension of the lesion beyond the genu. The aim was to characterise the radiographic, electroencephalographic, and neuropsychometric abnormalities in a woman who had a history of recurrent transient memory loss. METHOD: Case report. RESULTS: Magnetic resonance imaging showed an infarct in the genu of the left internal capsule. Positron emission tomography scan demonstrated decreased metabolic activity in the ipsilateral temporal, occipitotemporal, and contralateral cerebellar hemispheres. Electroencephalography showed intermittent rhythmic delta activity in the left frontotemporal region, and findings on neuropsychometric evaluation were consistent with cognitive impairment. Follow up evaluation 7 months after the stroke showed improvement in some areas of the cognitive domain, but residual neuropsychometric and neurophysiological abnormalities persisted. CONCLUSION: This case illustrates that cerebral and cerebellar diaschisis may contribute to the symptomatic presentation and recovery from capsular genu infarct, although its precise role remains elusive.

Aged↗

PubMed2000

A profound deficiency in thymic progenitor cells in mice lacking Jak3.

Humans and mice with genetic deficiencies that lead to loss of signaling through common gamma-chain (gammac)-containing cytokine receptors have severe defects in B and T lymphocytes. In humans, these deficiencies lead to a complete absence of T cells, whereas in mice, small thymuses give rise to normal numbers of peripheral T cells. We have examined the first wave of developing T cells in Jak3-/-, IL-7-/-, and IL-7Ralpha-/- fetal mice, and have found a near absence of thymic progenitor cells. This deficiency is highlighted by the complete inability of Jak3-/- progenitor cells to reconstitute T cell development in the presence of competing wild-type cells. These data clearly demonstrate a strong common basis for the T cell deficiencies in mice and humans lacking gammac/Jak3 signaling pathways.

Animals↗

PubMed2000

Neuropsychological functioning in a patient with essential tremor with and without bilateral VIM stimulation.

The effects of deep brain stimulation on motor functions, cognitive abilities, and mood were assessed in an 80-year-old, right-handed male with a chronic history of essential tremor. Electrodes were implanted bilaterally in the ventral intermediate nucleus of the thalamus during a single operation. Upon evaluation at 3 months postsurgery, bilateral stimulation was associated with a clinically significant reduction in tremor ratings and improvement in manual dexterity. At that time, a battery of neuropsychological measures was administered with and without bilateral stimulation. The patient demonstrated comparable performances on measures of visuospatial perception, attention, mental tracking, verbal learning, and verbal recognition memory in both the "on" and "off" conditions. Without stimulation, the patient demonstrated declines of greater than 1 SD on measures of verbal fluency and verbal recall compared to when the stimulators were active. Responses to mood rating scales also indicated greater subjective distress without stimulation. Results are discussed in the context of previous studies of the effects of thalamic stimulation on neurocognitive functioning.

Aged↗

PubMed2000

Genetic control of resistance to the sterol 14alpha-demethylase inhibitor fungicide prochloraz in the cereal eyespot pathogen Tapesia yallundae.

Sexual crosses were used to determine the genetic basis of resistance to the sterol 14 alpha-demethylase inhibitor fungicide prochloraz in the cereal eyespot pathogen Tapesia yallundae. Three different crosses between sensitive parental strains (22-432 and 22-433 [the concentration required to inhibit growth by 50% (IG(50)) for each was </=0.03 mg/liter]) and field isolates from France and New Zealand with differing levels of resistance (PR11 [IG(50) = 0.5 mg/liter], PR1 [IG(50) = 1.0 mg/liter], and 11-3-18 [IG(50) = 2.4 mg/liter]) yielded progeny showing a bimodal distribution, with an even number of sensitive and resistant progeny. This indicated the segregation of a single major gene for resistance in each cross, which was confirmed by the use of backcrosses, crosses between F(1) progeny, and control crosses between sensitive parents. However, there was also evidence of additional quantitative genetic components responsible for the increased IG(50)s of the more resistant isolates. A further cross was made between isolate PR11 and an F(1) progeny arising from isolate 11-3-18, and this also yielded progeny which were entirely prochloraz resistant. This suggested that resistance genes were allelic in these two isolates, with resistance conferred by a gene at the same locus (or closely linked loci), despite the fact that the isolates (PR11 and 11-3-18) originated from different continents.

Ascomycota↗

PubMed2000

Predictors of neuropsychological outcome in patients following microelectrode-guided pallidotomy for Parkinson's disease.

OBJECT: The authors studied neuropsychological performance following microelectrode-guided posteroventral pallidotomy in patients with Parkinson's disease (PD) and evaluated correlations with presurgical and surgical factors. METHODS: Neuropsychological changes 3 months (43 patients) and 12 months (27 patients) after microelectrode-guided pallidotomy for PD are reported in a series of 44 consecutive patients with the disease, who improved neurologically, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the "off' (p<0.001) and best "on" (p<0.001) states. Findings of the vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised (p<0.01), Letter Fluency (p<0.001), Verbal Fluency for semantic categories (p<0.001), and the Wisconsin Card Sorting Test (p<0.01) showed a significant decline in neuropsychological performance in patients 3 months after undergoing left-sided pallidotomy. Impairment in the language domain (semantic fluency) persisted at the 12-month follow-up examination (p<0.01). Visual memory improved after right-sided pallidotomies (p<0.01 after 3 months), with a nonsignificant trend toward persistent improvement 1 year postsurgery (p<0.02 after 12 months). Preoperative semantic fluency was influenced by patient age (p<0.001) and by the width of the third ventricle (p<0.05), as measured by magnetic resonance imaging. A regression model revealed that semantic fluency 3 months postoperatively was significantly affected by the baseline score (p<0.001), side of surgery (p<0.001), handedness (p<0.01), and patient age (p<0.05). However, postoperative lesion volume, lesion location, number of tracks, number of lesions, distance from anatomical landmarks, or UPDRS score did not significantly contribute to neuropsychological outcome. CONCLUSIONS: Neuropsychological changes in a cohort of patients with PD who underwent pallidotomy and experienced excellent clinical benefits and minimum postoperative complications, emphasize the importance of neuropsychological examinations and further investigation of predictive factors.

Aged↗

PubMed2000

Determinants of health-promoting behavior among women ages 65 and above living in the community.

This study utilized Pender's Health Promotion Model to investigate through canonical correlation analysis the role that select cognitive-perceptual factors (health self-determinism, learned helplessness, self-esteem, and perceived health) and modifying factors (age, race, marital status, education, and income) play in understanding participation of community-living older adult women (age > or = 65) in the health-promoting behaviors of health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, and stress management. These were measured by the Health-Promoting Lifestyle Profile II in a convenience sample of 107 community-living older adult women (mean age 76.7 years). Gender-specific benefits and barriers to participating in health-promoting behaviors were also explored using open-ended questions. Two significant canonical variates were demonstrated. These indicated that age, marital status, race, education, and self-esteem and the two health-related factors of perceived health and health self-determinism made statistically significant contributions to the health-promoting behaviors of physical activity, nutrition, spiritual growth, and interpersonal relations. Benefits identified included better psychological well-being, coping with the general issues of aging, social interaction, improved function, and management of existing health problems. Internal barriers focused on perceived physical difficulties with all types of health-promoting behaviors; external barriers included aspects of the activity itself, lack of support from others and structural barriers. Study results suggest that older adult women (age > or = 65) participate in health-promoting behaviors for both health enhancement and health management reasons and that barriers may be a more important determinant of older women's health-promoting lifestyle behaviors than previously described in the model.

Aged↗

PubMed1999

Single-turnover analysis of mutant human apurinic/apyrimidinic endonuclease.

Apurinic/apyrimidinic endonuclease (AP endo) is a key enzyme in the repair of oxidatively damaged DNA. Using single-turnover conditions, we recently described substrate binding parameters for wild type human AP endo. In this study, we utilized four enzyme mutants, D283A, D308A, D283A/D308A, and H309N, and assayed them under steady state and single-turnover conditions. The turnover number of the single aspartate mutants was decreased 10-30-fold in comparison to that of the wild type. The decrease in the turnover number was accompanied by a 17- and 50-fold decrease in the forward rate constant (kon) for substrate binding by D308A and D283A, respectively. The dissociation rate constant for substrate (koff) was unchanged for the D308A mutant but was 10 times faster for the D283A mutant than for the wild type. The apparent Km values for both of the single aspartate mutants were about equal to their respective KD values. To account for the kinetic behavior of the D308A mutant, it was necessary to insert a conformational change into the kinetic scheme. In contrast to the single aspartate mutants, the turnover number for the double mutant was 500-fold lower than that of the wild type, its apparent Km was 2.5-fold higher, and binding to substrate was weak. Mutation of His309 caused the greatest decrease in activity, resulting in a turnover number that was more than 30000-fold lower than that of the wild type and an apparent Km that was 13-fold higher, supporting the notion that His309 is intimately involved in catalysis. Molecular dynamics simulation techniques suggested that conversion of either aspartate to alanine resulted in major shifts in the spatial localization of key amino acids. Despite the fact that the two aspartates flank His309, the movement they engendered was distinct, consistent with the differences in catalytic behavior. We suggest that the conformation of the active site is largely maintained by the two aspartates, which enable efficient binding and cleavage of abasic site-containing DNA.

Alanine↗

PubMed1999

Testing normal older people three or four times at 1- to 2-year intervals: defining normal variance.

Normative data were presented that defined the upper and lower standards for deciding if cognitive abilities show reliable change over 2 or more testing occasions when retesting occurs at 1- to 2-year intervals. The Mayo Cognitive Factor Scores (MCFS; G. E. Smith et al., 1994) were analyzed because they permit the quantitation of overall functioning in 5 clinically important cognitive domains: established verbal knowledge, nonverbal reasoning, attention and concentration, new learning, and delayed memory. To the authors' knowledge, this is the first report of both group-level and individual-level data analyses derived from a respectably sized sample of normal persons who have been tested 3 or more times at clinically common test-retest intervals.

Aged↗

PubMed1998

A neuropsychological study of panic disorder: negative findings.

BACKGROUND: Gray (1982) proposed that the septo-hippocampal system, which plays an important role in learning and memory, may partially mediate anxiety. Thus, patients with anxiety disorders may manifest neurocognitive performance deficits. We hypothesized that patients with panic disorder would demonstrate learning and memory deficits relative to normal comparison subjects. METHOD: Comprehensive neuropsychological batteries were administered to 69 panic disorder subjects and 19 normal volunteers. RESULTS: There were no significant group differences in any neuropsychological performance domain including learning, memory, attention, visuospatial functioning, and psychomotor speed. Multiple regression conducted to evaluate the contribution of clinical symptoms to neuropsychological impairment within the panic disorder sample revealed that anxiety severity did not affect neuropsychological test performance. LIMITATIONS: Most patients had mild or moderate, rather than severe, panic disorder. CONCLUSION: Neuropsychological dysfunction was not associated with panic disorder.

Adolescent↗

PubMed1998

Analysis of visuospatial errors in patients with Alzheimer's disease or Parkinson's disease.

Ska and colleagues (1990) reported that patients with possible or probable Alzheimer's Disease (AD) make characteristic errors on a measure of line orientation judgment. We examined errors of line orientation judgment in a sample of 31 patients with probable AD, 28 patients with idiopathic Parkinson's disease (PD), and 24 normal elderly controls (NC). Results indicated that, in comparison to NC participants, some error types were made more frequently by patients with PD and patients with AD. No error type, however, was specific to AD alone. in contrast, PD patients were more likely than AD or NC participants to make a specific error in oblique line judgment. This finding is discussed in the context of visuospatial analysis and selective attention in patients with PD.

Aged↗

PubMed1998

Mayo's older Americans normative studies: category fluency norms.

Age-adjusted normative data are presented for persons over age 55 years on a common measure of category fluency. Further adjustment for education is also provided. These data were obtained as part of a series of projects known collectively as Mayo's Older Americans Normative Studies (MOANS). The normative information provided here should prove useful for characterizing performance on the individual measure of category fluency. In addition, these data should promote greater accuracy in comparing category fluency scores with performance on any other measures with MOANS norms, including tests of letter fluency. Limitations and unique features of MOANS normative data are also discussed.

Aged↗

PubMed1998

Normative data for the Mattis Dementia Rating Scale.

Age-adjusted normative data are presented for persons over age 55 on the Mattis Dementia Rating Scale. Additional adjustment for the effect of education on test performance is also provided. These data were collected as part of Mayo's Older Americans Normative Studies (MOANS) in a continuing effort to develop age-appropriate norms for older persons on commonly used neuropsychological tests. The normative data presented here should prove more useful in characterizing the presence and severity of general cognitive dysfunction than currently available norms. Limitations and unique features of MOANS normative data are also discussed.

Aged↗