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PubMed2002

Molecular basis for the loss of CD28 expression in senescent T cells.

CD28(null) T cells are the most consistent biological indicator of the aging immune system in humans and are predictors of immunoincompetence in the elderly. The loss of CD28 is the result of an inoperative transcriptional initiator (INR), which consists of two nonoverlapping alpha and beta motifs that have distinct protein binding profiles but function as a unit. In CD28(null) T cells, there is a coordinate loss of alpha-/beta-bound complexes, hence the alphabeta-INR is inactive. In the present work therefore, studies were conducted to identify the components of such complexes that may account for the trans-activation of the alphabeta-INR. By affinity chromatography and tandem mass spectrometry, two proteins, namely, nucleolin and the A isoform of heterogeneous nuclear ribonucleoprotein-D0 (hnRNP-D0A), were identified to be among the key components of the site alpha complex. In DNA binding assays, specific antibodies indicated their antigenic presence in alpha-bound complexes. Transcription assays showed that they are both required in the trans-activation of alphabeta-INR-driven DNA templates. Because CD28 is T cell-restricted, and nucleolin and hnRNP-D0A are ubiquitous proteins, these results support the notion that cell-specific functions can be regulated by commonly expressed proteins. The present data also provide evidence for INR-regulated transcription that is independent of the known components of the basal transcription complex.

Base Sequence↗

PubMed1992

The psychophysiological investigation of multiple personality disorder: review and update.

In 1984 Putnam reviewed the literature on the psychophysiological investigation of multiple personality disorder (MPD). Since his review, a large number of studies have been conducted and reported in the literature and at professional conferences. Currently, psychophysiologic differences reported in the literature include changes in cerebral electrical activity, cerebral blood flow, galvanic skin response, skin temperature, event-related potentials, neuroendocrine profiles, thyroid function, response to medication, perception, visual functioning, visual evoked potentials, and in voice, posture, and motor behavior. We review the new research on the psychophysiological investigation of MPD from published, unpublished, and ongoing studies, and we attempt to place current findings into a conceptual framework. We have noted findings from unpublished and ongoing studies, and, perhaps unfortunately, they represent a large amount of the data presently available. We conclude with a critical analysis of current research methodology and suggestions for future research.

Brain Mapping↗

PubMed2000

Effect of CYP2E1 induction by ethanol on the immunotoxicity and genotoxicity of extended low-level benzene exposure.

Potential additive effects of ethanol consumption, a common life-style factor, and low-level benzene exposure, a ubiquitous environmental pollutant, were investigated. Ethanol is a potent inducer of the cytochrome P-450 2E1 (CYP2E1) enzyme, which bioactivates benzene to metabolites with known genotoxicity and immunotoxicity. A liquid diet containing 4.1% ethanol was used to induce hepatic CYP2E1 activity by 4-fold in female CD-1 mice. Groups of ethanol-treated or pair-fed control mice were exposed to benzene or filtered air in inhalation chambers for 7 h/d, 5 d/wk for 6 or 11 wk. The initial experiment focused on immunotoxicity endpoints based on literature reports that ethanol enhances high-dose benzene effects on spleen, thymus, and bone marrow cellularity and on peripheral red blood cell (RBC) and white blood cell (WBC) counts. No statistically significant alterations were found in spleen lymphocyte cellularity, subtype profile, or function (mitogen-induced proliferation, cytokine production, or natural killer cell lytic activity) after 6 wk of ethanol diet, 0.44 ppm benzene exposure, or both. This observed absence of immunomodulation by ethanol alone, a potential confounding factor, further validates our previously established murine model of sustained CYP2E1 induction by dietary ethanol. Subsequent experiments involved a 10-fold higher benzene level for a longer time of 11 wk and focused on genotoxic endpoints in known target tissues. Bone marrow and spleen cells were evaluated for DNA-protein cross-links, a sensitive transient index of genetic damage, and spleen lymphocytes were monitored for hprt-mutant frequency, a biomarker of cumulative genetic insult. No treatment-associated changes in either genotoxic endpoint were detected in animals exposed to 4.4 ppm benzene for 6 or 11 wk with or without coexposure to ethanol. Thus, our observations suggest an absence of genetic toxicity in CD-1 mice exposed to environmentally relevant levels of benzene with or without CYP2E1 induction.

Animals↗

PubMed1984

Raven IQ and language recovery following stroke.

The relationship between IQ and language recovery in aphasic patients was investigated using Raven's Coloured Progressive Matrices, Functional Communication Profile, and Schuell scores. The study involved 148 stroke patients who were part of a controlled trial of speech therapy. Although initial IQ correlated with severity of aphasia, no evidence was found for a relationship between IQ and subsequent language recovery. Nevertheless, initial IQ level was found to relate to some measures of physical status and to death soon after testing.

Aged↗

PubMed2004

Nutritional and technological evaluation of an enzymatically methionine-enriched soy protein for infant enteral formulas.

Enzymatically modified soy proteins have the amino acid profile and functional properties required for dietary support. The objective of this study was to evaluate the nutritional and technological properties of an enzymatically modified soy protein ultrafiltered fraction with bound methionine (F(1-10)E) to be used as a protein ingredient for infant enteral formulas. F(1-10)E was chemically characterized and biologically evaluated. Thirty-six weaning Wistar rats were fed during 3 weeks with a 4% casein-containing diet. Rats were divided into three groups and recovered for 3 weeks with 18% protein-containing diets based on: (1) F(1-10)E, (2) casein or (3) soy isolate+methionine. Nutritional indicators were weight gain, protein efficiency ratio, plasma proteins, apparent digestibility and protein in the carcass. Additionally, F(1-10)E was added as a protein ingredient of an enteral formula, and its sensory and rheological properties were compared with a hydrolyzed-whey protein commercial formula. F(1-10)E contained 68% protein and 5% sulphur amino acids, with 60% of peptides </=6 kDa. Casein-based and F(1-10)E-based diets were comparable (P>0.05) in weight gain (108 g and 118 g, respectively), protein efficiency ratio (2.7), apparent digestibility (93% and 95%), plasma proteins (5.7 mg/100 ml) and carcass protein (61%), and better than soy isolate-based+methionine diet (P<0.05). Viscosity of the commercial formula and our formula was similar during a 24-h period. Sensory acceptability was 8 for our formula and 3.5 for the commercial one, on a scale of 1-10 (P<0.05). Due to its nutritional, sensorial and rheological properties, F(1-10)E could be used as a protein source in infant enteral formulas.

Amino Acids↗

PubMed2005

Participation and activity performance of students with cerebral palsy within the school environment.

PURPOSE: The aims of this study were to investigate the levels of participation and activity performance of students with cerebral palsy within the inclusive school context, to explore the relationships between these two aspects of function and to identify predictors of participation among the various school activities. METHOD: Two hundred and forty-eight elementary school students were divided into three groups: 100 fully included (FI) students with CP, 100 matched by class and gender typical students (TS) and 48 students with CP in self-contained classes (SC). The School Function Assessment (SFA) was used as the main measurement for assessing the levels of participation and functional performance profiles. RESULTS: Significant differences (P<0.0001) in levels of participation were evident across the three study groups using MANOVA and ANOVAs analyses, where the TS level was the highest and the SC was the lowest. Comparison of the mean score of the physical and the cognitive/behavioural tasks performance revealed similar results among the three groups. Positive Pearson correlations were obtained between participation and both motor and cognitive/behavioural activity performance in the FI and the SC groups. Regression models for the FI and the SC groups were found significant (P<0.0001) and explained above 69% of the participation variance with physical activity performance as the most predictive variable. CONCLUSIONS: Significant differences exist between participation and activity performance of typical students and students with CP included in regular schools. Moreover, activity performance limitations were found to impact on school participation. These findings stress the continuing need to provide rehabilitative intervention towards removing existing barriers within the inclusive environment.

Activities of Daily Living↗

PubMed2006

Personal assistance, adaptations and participation in students with cerebral palsy mainstreamed in elementary schools.

PURPOSE: The aims of this study were to examine differences in level of participation of students with CP in full inclusion (FI group) as compared to self-contained classes (SC group), differences in the task supports provided for these two groups, the interrelationships between assistance and adaptation provided and the differential impact of physical task supports vs. cognitive/behavioural task supports on participation. METHOD: 148 elementary school students were divided into two groups: 100 fully included (FI) students with CP, and 48 students with CP in self-contained classes (SC). The School Function Assessment (SFA) was used as the main measurement for assessing the levels of participation and functional performance profiles. RESULTS: Statistically significant differences (p < 0.0001) were found between the two groups on all scales (physical and cognitive/behavioural assistance and adaptations). Supports provided to the SC group were significantly greater than to the FI group and physical task supports provided to both groups were significantly greater than cognitive/behavioural supports. Pearson correlations and Smallest Space Analyses (SSA) revealed significant (p < 0.01) moderate to strong correlations (0.57 > r < 0.77) between all four task supports, and between provided task supports and participation (0.66 > r < 0.82). CONCLUSIONS: This study's focus enhances our understanding of the impact of task supports to the various factors contributing to the dimensions of the ICF, as well as their interrelationship with participation. Devises and cognitive and behavioural adaptations are required in a wider manner in addition or alternative to physical assistance by adults if we are to increase the chance of students with severe CP to become participatory for academic and social tasks required in school.

Adaptation, Physiological↗

PubMedDate not supplied

Individual variation in morphological, physiological, and biochemical features associated with calling in spring peepers (Pseudacris crucifer).

In an eastern North American tree frog, the spring peeper (Pseudacris crucifer), calling rate has been correlated with reproductive success in the field. To determine the sources of individual variation in calling rate in this species, I analyzed males calling at rates greater than and less than the chorus average throughout one breeding season. Compared to low-rate callers, high-rate callers were relatively larger, heavier, older, and in better body condition, and their muscles used in calling had higher activities of the enzymes citrate synthase and beta-hydroxyacyl-CoA dehydrogenase. This muscle profile is functionally matched by cardiovascular correlates, as indicated by the larger ventricles and higher blood hemoglobin concentrations in high-calling rate males. These cardiovascular features are much less developed in females and may result from the fact that females do not engage in vigorous calling behavior. In P. crucifier, a male's calling rate may function as an indicator of the presence of a suite of functionally interrelated traits responsible for the maintenance of this sexually selected display behavior.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2005

Genomic profiling of neutrophil transcripts in Asian Qigong practitioners: a pilot study in gene regulation by mind-body interaction.

BACKGROUND AND OBJECTIVES: The great similarity of the genomes of humans and other species stimulated us to search for genes regulated by elements associated with human uniqueness, such as the mind-body interaction. DNA microarray technology offers the advantage of analyzing thousands of genes simultaneously, with the potential to determine healthy phenotypic changes in gene expression. The aim of this study was to determine the genomic profile and function of neutrophils in Falun Gong (FLG, an ancient Chinese Qigong) practitioners, with healthy subjects as controls. SUBJECTS AND DESIGN: Six (6) Asian FLG practitioners and 6 Asian normal healthy controls were recruited for our study. The practitioners have practiced FLG for at least 1 year (range, 1-5 years). The practice includes daily reading of FLG books and daily practice of exercises lasting 1-2 hours. Selected normal healthy controls did not perform Qigong, yoga, t'ai chi, or any other type of mind-body practice, and had not followed any conventional physical exercise program for at least 1 year. Neutrophils were isolated from fresh blood and assayed for gene expression, using microarrays and RNase protection assay (RPA), as well as for function (phagocytosis) and survival (apoptosis). RESULTS: The changes in gene expression of FLG practitioners in contrast to normal healthy controls were characterized by enhanced immunity, downregulation of cellular metabolism, and alteration of apoptotic genes in favor of a rapid resolution of inflammation. The lifespan of normal neutrophils was prolonged, while the inflammatory neutrophils displayed accelerated cell death in FLG practitioners as determined by enzyme-linked immunosorbent assay. Correlating with enhanced immunity reflected by microarray data, neutrophil phagocytosis was significantly increased in Qigong practitioners. Some of the altered genes observed by microarray were confirmed by RPA. CONCLUSION: Qigong practice may regulate immunity, metabolic rate, and cell death, possibly at the transcriptional level. Our pilot study provides the first evidence that Qigong practice may exert transcriptional regulation at a genomic level. New approaches are needed to study how genes are regulated by elements associated with human uniqueness, such as consciousness, cognition, and spirituality.

Adult↗

PubMed2004

Reference systems for kinase drug discovery: chemical genetic approaches to cell-based assays.

Protein kinases play key roles in a number of diseases, including cancer, inflammation, and diabetes. Disregulation of kinase-based signal transduction networks results in aberrant cell differentiation, activation, proliferation, and invasion. The growing importance of kinases as a major class of drug targets across multiple large clinical indications, together with the large number of kinases in the genome (~518), has generated a critical need for technologies that enable the identification of potent and selective kinase inhibitors with good drug-like properties. In this review, we describe methods used for developing cell-based assays for kinase inhibitors, discuss advantages and disadvantages of each approach, and describe new chemical genetic methods as reference systems for establishing cell-based assays and their use for functional selectivity profiling of kinase inhibitors.

Amino Acid Sequence↗

PubMed2006

Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain.

INTRODUCTION: Duloxetine hydrochloride is a dual reuptake inhibitor of both serotonin and norepinephrine. In the present open-label study, the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks was evaluated and compared to routine care in the therapy of patients diagnosed with diabetic peripheral neuropathic pain (DPNP). METHODS: Patients who completed a 13-week, double-blind, duloxetine and placebo acute therapy period were rerandomly assigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N=161) or routine care (N=76) for an additional 52 weeks. Routine care consisted primarily of gabapentin, amitriptyline, and venlafaxine. The study included male or female outpatients 18 years of age or older with a diagnosis of DPNP caused by type 1 or type 2 diabetes. RESULTS: A higher percentage of routine care-treated patients experienced 1 or more serious adverse events. No statistically significant therapy-group difference was observed in the overall incidence of treatment-emergent adverse events (TEAEs). The TEAEs reported by 10% or more of duloxetine 60 mg BID-treated patients were nausea, and by the routine care-treated patients were peripheral edema, pain in the extremity, somnolence, and dizziness. Duloxetine did not appear to adversely affect glycemic control, lipid profiles, nerve function, or the course of DPNP. There were no statistically significant therapy-group differences observed in the 36-item Short-Form Health Survey subscales or in the EuroQol 5-Dimension Questionnaire. CONCLUSIONS: In this study, duloxetine was safe and well tolerated compared to routine care in the long-term management of patients with DPNP.

Amines↗

PubMed1999

Rationale, design, and baseline results of the Pravastatin-to-Simvastatin Conversion Lipid Optimization Program (PSCOP).

A program designed to increase the percentage of patients at a Department of Veterans Affairs health system who meet their cholesterol goals as recommended by the National Cholesterol Education Program (NCEP) is described, and baseline results are reported. Patients with an active prescription for pravastatin between February 4 and June 4, 1997, were identified for conversion to simvastatin by means of the Pravastatin-to-Simvastatin Conversion Lipid-Optimization Program; 1361 patients were eligible for conversion. Each patient was mailed a survey for determining risk factors for coronary heart disease (CHD) and NCEP-recommended low-density lipoprotein (LDL) cholesterol goal and was asked to provide a fasting blood sample for determination of lipid profile, liver function, and serum creatine phosphokinase concentration. The patients were asked to make a follow-up laboratory visit six to seven weeks after they had started taking simvastatin. The percentage change from baseline and the percentage of patients who meet their LDL cholesterol goal before and after the conversion will be determined. A total of 1115 patients were converted to simvastatin. Only 35.4% of patients taking pravastatin to prevent a second CHD-related event met or exceeded their LDL cholesterol goal. Only 36.2% of patients with two or more CHD risk factors who were taking pravastatin for primary prevention met or exceeded their LDL cholesterol goal. In a veterans population, less than half of patients receiving a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor had LDL cholesterol concentrations that met goals recommended by the NCEP.

Aged↗

PubMed2004

The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice.

In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.

Animals↗

PubMed1993

Identification and measurement of productive behaviors in senile dementia of the Alzheimer type.

Caregivers of 106 individuals with senile dementia of the Alzheimer type (SDAT) were administered the Functional Behavior Profile (FBP) as part of a caregiver assessment battery. Three factors--task performance, problem solving, and social interaction--accounted for 70.6% of the variance. Analysis yielded a reliable and valid assessment that documents the observable productive behaviors of a person with SDAT. Significant differences across the stages of the disease were observed. The FBP can serve as a guide for individualized caregiving strategies by helping the caregiver focus on the presence of productive behaviors useful in managing the impaired person.

Aged↗

PubMed2026

The evolution of Ca2+-ATPases across plants with profiles in Rhododendron and the function of key members in alleviating high calcium stress.

Ca2+-ATPase (CAP) is a key Ca2+ efflux protein in plants. Our previous research suggests that CAPs may play a crucial role in the adaptation of rhododendrons to high calcium environments. However, the evolution, variation, characteristic expression, and subfunctionalization of this gene family in Rhododendron remain unknown. Through the analysis of pan-genomes and pan-transcriptomes, we elucidated the systematic evolution of CAPs in plants, as well as their characteristic expression patterns in Rhododendron. During the evolutionary process from lower to higher plants, CAPs can be divided into six clades and exhibit structural conservation. CAPs have emerged and differentiated in lower plants such as algae, and they have undergone significant amplification in Eudicots plants like rhododendrons. Three Rhododendron species (Rhododendron bailiense, R. delavayi, and R. irroratum) located in the karst province of Guizhou in Southwest China exhibit the highest copies of CAPs, suggesting a strong association between CAP copy number variation and habitat, particularly in high calcium environments. Through multiple transcriptome analyses, we revealed that CAPs are induced under various environmental/developmental conditions (e.g. karst environments, high altitude, early flower development, hormones, etc.). Co-expression network analysis highlighted key members of calcineurin B-like protein (CBL) and CBL-interacting protein kinases (CIPK) that are associated with the high expression of CAPs. Experimental validation demonstrated that CAPb1 and CAPd1 significantly alleviate high calcium stress, and the CAPb1-CIPK1-CBL1 and CAPd1-CIPK2-CBL1 modules can further enhance the alleviation. These findings provide new insights into the evolution, characteristic expression, and function of CAPs, as well as new perspectives on the high calcium adaptability of rhododendrons.

Journal Article↗

PubMed2002

Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload.

BACKGROUND: To test the hypothesis that human sperm DNA could sustain iron-induced oxidative damage and reduce its fertilizing ability, we studied patients with homozygous beta-thalassaemia major (HbTh) as a model of iron overload. METHODS: Sperm from six thalassaemic patients and five age-matched controls were assessed by the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. Semen parameters, endocrine markers of testicular function, iron profiles and the presence of organ dysfunction were also determined. RESULTS: All patients with HbTh were iron overloaded (median ferritin: 2251 microg/l) and had evidence of spontaneous spermatogenesis. Thalassaemic patients had more sperm DNA damage than the controls (P < 0.01). The sperm DNA damage by SCSA and TUNEL were positively correlated (P < 0.05). Sperm motility and TUNEL results were negatively correlated (P < 0.05), while the age of onset of chelation and sperm DNA damage were positively associated with both SCSA (R(2) = 0.80, P = 0.016) and TUNEL data (R(2) = 0.67, P < 0.044). No other biochemical or clinical data were associated with sperm DNA damage. CONCLUSIONS: The increase in sperm DNA damage and the negative correlation between sperm motility and DNA damage suggest that iron overload in HbTh predisposes sperm to oxidative injury. This finding has important implications in assisted reproductive procedures such as ICSI where there is increased risk of transmitting defective DNA to the offspring.

Adult↗

PubMed1989

A comparison of measures of health status in rheumatoid arthritis.

One hundred and five patients with rheumatoid arthritis were assessed on two occasions separated by 15 months, by means of the ARA functional scale, the Mallya and Mace index, the Health Assessment Questionnaire (HAQ) and the Functional Limitations Profile (FLP). Thirty three per cent of patients were assessed as clinically changed in terms of the ARA scale. On both occasions cross-sectional correlations were strongest between the health status measures (HAQ and FLP) and grip strength and the Ritchie articular index. The sensitivity and specificity of the two health status measures in relation to clinical change were calculated and overall the HAQ and FLP achieved similarly modest levels of sensitivity and specificity. The greater amount of precision and information provided by the FLP has to be weighed against the simpler measurement assumptions and shorter time required to administer the HAQ.

Arthritis, Rheumatoid↗

PubMed2003

Estrogen regulation of aquaporins in the mouse uterus: potential roles in uterine water movement.

Estrogen stimulates water imbibition in the uterine endometrium. This water then crosses the epithelial cells into the lumen, leading to a decrease in viscosity of uterine luminal fluid. To gain insight into the mechanisms underlying this estrogen-stimulated water transport, we have explored the expression profile and functionality of water channels termed aquaporins (AQPs) in the ovariectomized mouse uterus treated with ovarian steroid hormones. Using immunocytochemical analysis and immunoprecipitation techniques, we have found that AQP-1, -3, and -8 were constitutively expressed. AQP-1 expression was restricted to the myometrium and may be slightly regulated by ovarian steroid hormones. AQP-3 was expressed at low levels in the epithelial cells and myometrium, whereas AQP-8 was found in both the stromal cells and myometrium. AQP-2 was absent in vehicle controls but strongly up-regulated by estrogen in the epithelial cells and myometrium of the uterus. This localization implicates all four isotypes in movement of water during uterine imbibition and, based on their localization to the luminal epithelial cells, AQP-2 and -3 in facilitating water movement into the lumen of the uterus. The analysis of the plasma membrane permeability of luminal epithelial cells by two separate cell swelling assays confirmed a highly increased water permeability of these cells in response to estrogen treatment. This finding suggests that estrogen decreases the luminal fluid viscosity, in part, by enhancing the water permeability of the epithelial layer, most likely by increasing the expression of AQP-2 and/or the availability of AQP-3. Together these results provide novel information concerning the mechanism by which estrogen controls water imbibition and luminal fluid viscosity in the mouse uterus.

Algorithms↗