Biomedical subjects

David J Moore

Publications and source records attributed to David J Moore.

At least 37 records · Page 2Linked to original sources

PubMed2005

FTIR spectroscopic studies of lipid dynamics in phytosphingosine ceramide models of the stratum corneum lipid matrix.

IR spectroscopic studies are reported for N-stearyl-D-erythro-phytosphingosine (Cer NP) and N-stearyl-2-hydroxy-D-erythro-phytosphingosine (Cer AP) in a hydrated model of the skin lipid barrier comprised of equimolar mixtures of each ceramide with cholesterol and d(35)-stearic acid. Examination of the methylene stretching, rocking and bending modes reveal some rotational freedom and hexagonal packing in both the ceramide and stearic acid chains. Analysis of the acid carbonyl stretch and the ceramide Amide I modes show both shift to higher frequencies, indicating weaker hydrogen bonding, in the mixed systems compared to the pure materials. For both systems, the fatty acid chain disordering temperatures are significantly increased from those of the pure acids. The observed behaviors of these phytosphingosine ceramide systems are fundamentally different from the previously reported analogous sphingosine ceramide systems. The implications of these observations for lipid organization in the stratum corneum are briefly discussed.

Ceramides↗

PubMed2005

Temperament and risky behaviors: a pathway to HIV?

BACKGROUND: Certain sexual behaviors and abuse of substances contribute to the risk of becoming HIV-infected. Because dispositional characteristics are likely to influence this process, we examined the association between temperament and HIV serostatus in subjects with heavy use of drugs and various sexual risk behaviors. METHODS: Two hundred and thirty individuals (81% of whom were HIV-infected) were assessed for underlying temperamental characteristics, substance use, and risky sexual behaviors. Toward this goal, a factor analysis was conducted on a new self-rated Temperament Autoquestionnaire (Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A)). MANOVA was used to examine overall associations between risky behaviors and temperament. Additionally, directed MANOVAs were conducted for each of six drugs of abuse (alcohol, marijuana, cocaine, opioids, other stimulants, and sedative hypnotics). RESULTS: Factor analysis confirmed the hypothesized temperament structure of five distinct factors: Cyclothymic, hyperthymic, anxious, irritable-explosive, and depressive. Heavy users of cocaine, other stimulants, and alcohol were more likely to have an irritable-explosive temperament. Interestingly, heavy users of opioids were more likely to show depressive and hyperthymic traits. The inclusion of HIV status as a predictor of temperament did not alter the results. Unlike a previous study, no direct significant relationships were found between risky sexual behaviors and specific temperaments. LIMITATIONS: Relatively small sample size for a factor analytic study, and cross-sectional design, which cannot determine a cause and effect relationship. CONCLUSIONS: We succeeded in studying and validating five distinct affective temperaments in a substance abuse population. Irritable-explosive, and to a lesser extent, depressive and hyperthymic traits, were associated with substance use, and may place individuals at risk for HIV infection via that mechanism. That current risky sexual practices were not directly linked to temperament may reflect modification in sexual behavior following the acquisition of HIV disease.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Feasibility of tracking phospholipid permeation into skin using infrared and Raman microscopic imaging.

The feasibility of monitoring the permeation of chain perdeuterated 1,2-dipalmitoylphosphatidylcholine (DPPC-d62) and 1-palmitoyl-d31, 2-oleoylphosphatidylcholine (P-d31OPC) vesicles into pigskin using infrared (IR) microscopic imaging and confocal Raman microscopy was demonstrated. The former technique permits the examination of the relative concentration of molecular species (e.g., endogenous and exogenous lipids and proteins) over spatial areas, approximately 1 mm, with a spatial resolution of approximately 10-12 microm. In contrast, Raman microscopy allows the confocal examination of tissue at depths up to 100 microm with a pixel size of about 2-3 microm3. Spectral signal/noise, however, is reduced from IR and significantly smaller areas are generally monitored. The permeation of the gel phase DPPC-d62 was limited to approximately 5-15 microm, whereas the liquid-crystalline phase P-d31OPC permeated to substantially greater depths (35-100 microm), at times ranging up to 24 h after application. The results are generally in accord with literature values. In addition, the state of the P-d31OPC (intact vesicles or molecularly dispersed with skin constituents) was evaluated from the spatial dependence of the deuteriopalmitate chain conformational order. Upon permeation, the chains became more ordered. The advantages and limitations of these imaging technologies are discussed.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Predictors of everyday functioning among older Mexican Americans vs. Anglo-Americans with schizophrenia.

OBJECTIVE: We assessed clinical, demographic, and cognitive predictors of everyday functioning in Mexican American and Anglo-American outpatients with schizophrenia. METHOD: Three groups of participants aged 40 years and over with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder were compared: 79 Anglo-Americans, 24 Mexican American patients who chose to be tested in English, and 33 Mexican American patients who preferred Spanish. The study was conducted from October 2001 to July 2004. RESULTS: On demographic, clinical, cognitive, and functional measures, Anglo-American participants were generally similar to Mexican American participants who opted for being tested in English. Mexican American participants who preferred Spanish were significantly different from the other 2 groups on several measures, including everyday functioning performance. To determine the predictors of everyday functioning, separate regression analyses were conducted for each of the 3 groups. Cognitive ability consistently accounted for the greatest proportion of variance in performance regardless of ethnicity, language preference, or education. Among the Mexican American participants, level of acculturation was the second strongest predictor of everyday functioning when the group was examined as a whole; however, acculturation was not a significant predictor when controlling for language preference. CONCLUSION: Cognitive performance and language preference (a proxy for acculturation) may play a particularly important role in predicting ability to perform everyday tasks. Further studies to better understand the potential impact of ethnicity, culture, education, and language on everyday functioning may help develop more specific and culture-sensitive intervention strategies for different ethnic groups.

Acculturation↗

PubMed2004

Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

Adult↗

PubMed2004

The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks.

CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells. Here, we have identified an unanticipated role for CK2. We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breakage. Moreover, we show that inhibiting XRCC1 phosphorylation by mutation of the CK2 phosphorylation sites or preventing CK2 activity using a highly specific inhibitor ablates the rapid repair of cellular DNA single-strand breaks by XRCC1. These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity.

Animals↗

PubMed2004

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons.

Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV-/METH+), HIV infected/methamphetamine nondependent (HIV+/METH-), and HIV negative/methamphetamine nondependent (HIV-/METH-). Study groups were comparable for age, education, and ethnicity, although the HIV-/METH- group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV- participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV-/METH+ (40%) and HIV+/METH- (38%) groups compared to the HIV-/METH- (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms.

Adult↗

PubMed2004

The impact of HIV-associated neuropsychological impairment on everyday functioning.

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons.

Activities of Daily Living↗

PubMed2004

Initial validation of a screening battery for the detection of HIV-associated cognitive impairment.

This study sought to develop and validate a screening battery for detecting HIV-related neuropsychological (NP) impairment. Six NP measures representing the ability areas most likely affected by HIV infection were paired in 14 combinations and their diagnostic accuracy rates compared. The measures were selected from a larger NP battery administered to 190 HIV-seropositive (HIV+) participants. Screening battery performance was classified as NP impaired if demographically corrected T-scores fell below 40 on both tests, or below 35 on one test. Using blind clinical ratings of NP test results from the larger battery as the "gold standard" for global NP status (impaired or unimpaired), we found that several test combinations demonstrated adequate diagnostic accuracy in detecting NP impairment. The most sensitive test combinations were the Hopkins Verbal Learning Test-Revised (HVLT-R; Total Recall) and the Grooved Pegboard Test nondominant hand (PND) pair and the HVLT-R and WAIS-III Digit Symbol (DS) subtest pair (sensitivity = 78% and 75%, respectively). Both test combinations (HVLT-R/PND, HVLT-R/DS) were more accurate than the HIV Dementia Scale (HDS) in classifying HIV+ participants as NP impaired or unimpaired. Results suggest that demographically corrected T-scores from pairs of common NP measures may serve as valid screening instruments to identify subjects with HIV-related neurocognitive impairment who could benefit from more extensive NP examination.

Adult↗

PubMed2004

A six-factor model of cognition in schizophrenia and related psychotic disorders: relationships with clinical symptoms and functional capacity.

Confirmatory factor analysis was used to examine a proposed factor structure of a comprehensive neuropsychological battery used to study patients with schizophrenia and related psychotic disorders (n = 209). An a priori six-factor model and five nested models were evaluated successively, using maximum likelihood confirmatory factor analysis. In all multifactor models, the factors were significantly intercorrelated. A six-factor model with two pairs of correlated errors fit the neuropsychological data significantly better than competing models with fewer factors. The six factors included verbal crystallized, attention/working memory, verbal episodic memory, speed of information processing, visual episodic memory, and reasoning/problem solving. Severity of negative symptoms was significantly associated with worse performance on attention/working memory and verbal crystallized factors, but positive symptoms, depression, and a summary measure of psychopathology were not significantly related to neuropsychological performance. Impairment on a performance-based measure of functional capacity was significantly related to all neuropsychological factors. A simultaneous confirmatory factor analysis using the original sample and a group of healthy subjects (n = 131) demonstrated that the six-factor model of cognition was generalizable and applied equally well to both groups.

Adolescent↗

PubMed2004

Bipolar disorder in middle-aged and elderly adults: is age of onset important?

The literature is mixed about whether age of onset is a useful variable in explaining the heterogeneity of late-life bipolar disorder. The aim of this study was to examine the relationship of age of onset with clinical, family history, and neuropsychological functioning in middle-aged and older patients with bipolar disorder. A total of 87 outpatients with bipolar disorder with a mean age of 59 (range, 42-89) were included in this study. Age of onset was analyzed as a continuous variable and was split at age 40 years into early-onset and late-onset groups. Participants were administered measures of psychopathology, cognitive functioning, and medication usage. Few meaningful differences emerged between early-onset and late-onset groups, except that overall psychopathology was significantly lower in the late-onset group. Age of onset did not relate to differences in family history, depressive symptoms, cognitive functioning, or medication use whether used as a categorical or continuous variable. Thus, the validity of late-onset bipolar disorder as a distinct syndrome was not corroborated by this study. Interpretation of these findings is limited by the sample size, cross-sectional design, and a lack of brain imaging data. Further research on the clinical features and neurobiological aspects of late-life bipolar disorder is needed.

Adult↗

PubMed2004

Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing.

Cleanser technology has come a long way from merely cleansing to providing mildness and moisturizing benefits as well. It is known that harsh surfactants in cleansers can cause damage to skin proteins and lipids, leading to after-wash tightness, dryness, barrier damage, irritation, and even itch. In order for cleansers to provide skin-care benefits, they first must minimize surfactant damage to skin proteins and lipids. Secondly, they must deposit and deliver beneficial agents such as occlusives, skin lipids, and humectants under wash conditions to improve skin hydration, as well as mechanical and visual properties. While all surfactants tend to interact to some degree with lipids, their interaction with proteins can vary significantly, depending upon the nature of their functional head group. In vitro, ex vivo, and in vivo studies have shown that surfactants that cause significant skin irritation interact strongly with skin proteins. Based on this understanding, several surfactants and surfactant mixtures have been identified as "less irritating" mild surfactants because of their diminished interactions with skin proteins. Surfactants that interact minimally with both skin lipids and proteins are especially mild. Another factor that can aggravate surfactant-induced dryness and irritation is the pH of the cleanser. The present authors' recent studies demonstrate that high pH (pH 10) solutions, even in the absence of surfactants, can increase stratum corneum (SC) swelling and alter lipid rigidity, thereby suggesting that cleansers with neutral or acidic pH, close to SC-normal pH 5.5, may be potentially less damaging to the skin. Mildness enhancers and moisturizing agents such as lipids, occlusives, and humectants minimize damaging interactions between surfactants, and skin proteins and lipids, and thereby, reduce skin damage. In addition, these agents play an ameliorative role, replenishing the skin lipids lost during the wash period. The present review discusses the benefits of such agents and their respective roles in improving the overall health of the skin barrier.

Detergents↗

PubMed2004

The need to decide if all estrogens are intrinsically similar.

We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17-beta-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens. Key words: diethylstilbestrol, estrogen, gene expression, genistein, microarray, phytoestrogen, toxicogenomics, uterus.

Animals↗

PubMed2004

Phenotypic anchoring of gene expression changes during estrogen-induced uterine growth.

A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene expression levels, uterine weights, and histologic parameters were analyzed 1, 2, 4, 8, 24, 48, and 72 hr after exposure to the reference physiologic estrogen 17 beta-estradiol (E2). A multistep analysis method, involving unsupervised hierarchical clustering followed by supervised gene ontology-driven clustering, was used to define the transcriptional program associated with E2-induced uterine growth and to identify groups of genes that may drive specific histologic changes in the uterus. This revealed that uterine growth and maturation are preceded and accompanied by a complex, multistage molecular program. The program begins with the induction of genes involved in transcriptional regulation and signal transduction and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation, and epithelial cell differentiation. Furthermore, we have identified genes with common molecular functions that may drive fluid uptake, coordinated cell division, and remodeling of luminal epithelial cells. These data define the mechanism by which an estrogen induces organ growth and tissue maturation, and demonstrate that comparison of temporal changes in gene expression and conventional toxicology end points can facilitate the phenotypic anchoring of toxicogenomic data.

Animals↗

PubMed2003

Prediction of incident neurocognitive impairment by plasma HIV RNA and CD4 levels early after HIV seroconversion.

BACKGROUND: Neuropsychological (NP) impairment is a relatively common sequela in human immunodeficiency virus (HIV)-infected individuals with advanced disease. Early antecedents of NP dysfunction, however, remain poorly understood. OBJECTIVE: To determine whether early markers of immunocompetence and viral replication in individuals who have undergone seroconversion would be of prognostic value in identifying subjects who would become cognitively impaired. METHODS: Seventy-four subjects with estimable seroconversion dates and normal cognition at baseline (a median of 1 year after seroconversion) received NP and laboratory evaluations, including reverse transcription-polymerase chain reaction measurements of plasma (N = 74) and cerebrospinal fluid (n = 47) levels of HIV RNA. Subjects were followed up longitudinally, and were considered to have reached the end point if they became cognitively impaired. RESULTS: Using Kaplan-Meier estimates, the subgroups with the most rapid progression to NP impairment were (1) subjects with early reductions in CD4 counts (<400 cells/microL at baseline; P =.007) and (2) those with elevated plasma HIV RNA values (>4.5 log10 copies/mL; P =.03) early after seroconversion. Using proportional hazards modeling, the highest-risk subjects had both CD4 counts less than 400 cells/microL and HIV RNA levels greater than 4.5 log10 copies/mL (risk ratio, 6.0; P =.01). In most subjects (7/9 [78%]), NP impairment developed before an acquired immunodeficiency syndrome-defining illness. CONCLUSIONS: Neurocognitive outcomes in HIV are strongly influenced by very early systemic virological and immunological events. Patients with high plasma levels of HIV RNA and low CD4 counts early after infection should be aggressively treated to prevent immunological decline and NP deterioration.

Adult↗

PubMed2003

Computerized reaction time battery versus a traditional neuropsychological battery: detecting HIV-related impairments.

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the "gold standard," impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments.

AIDS Dementia Complex↗

PubMed2003

The functional impact of HIV-associated neuropsychological impairment in Spanish-speaking adults: a pilot study.

Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide, and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluates English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures, and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessments included the following domains: Medication Management, Cooking, Finances, Shopping, and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p <.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers.

AIDS Dementia Complex↗

PubMed2003

Infrared microspectroscopic imaging maps the spatial distribution of exogenous molecules in skin.

Infrared (IR) microscopic imaging is used, in a series of proof-of-principle experiments to map the spatial distribution of two penetration enhancers, dimethylsulphoxide (DMSO) and propylene glycol, in skin. The current instrumentation utilizes a 64 x 64 array of IR detectors imaged at the focal plane of an IR microscope, each collecting a complete mid-infrared spectrum of the skin section on each pass of the interferometer. The spatial area sampled by each element in the array is approximately 6.3 x 6.3 microm. Any spectral parameter (e.g., arising from lipid or protein vibrational modes of the endogenous tissue or the exogenous component) may be quantitatively analyzed across the entire array of 4096 spectra, thereby generating an IR spectroscopic image of that particular parameter throughout the sample. The images directly reveal the spatial heterogeneity of the protein and lipid distributions. In transverse slices of skin, the depth dependencies of the spatial distribution of triglyceride and protein have been monitored, and compared to those of the exogenous penetration enhancers. Images of both DMSO and propylene glycol suggest that each penetrates the skin to a depth of at least 1 mm (under our experimental protocols), and reveals a spatial distribution that is essentially coincident with the protein constituents of the skin. These results demonstrate that IR microscopic imaging has great potential for mechanistic studies of topical, dermal, and transdermal delivery.

Animals↗