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Biomedical subjects

D L Evans

Publications and source records attributed to D L Evans.

At least 91 records · Page 5Linked to original sources
PubMed1997

Cardiorespiratory responses to exercise in horses with different grades of idiopathic laryngeal hemiplegia.

The relationship between different grades of laryngeal function, as assessed by endoscopy at rest, and the measurements of indices of gas exchange and exercise capacity was assessed during a standardised treadmill exercise test in 149 horses. Horses with abnormalities other than idiopathic laryngeal hemiplegia (ILH) were excluded from the study and laryngeal function was graded according to an established system. There were no significant differences in age, weight, maximum oxygen uptake, maximum carbon dioxide production, maximum respiratory exchange ratio, maximum oxygen pulse and run time between the grades. Blood lactate concentration at 10 m/s was greater (P < 0.01) in horses with grade 5 laryngeal function than other grades. Minimum PaO2 (P < 0.001) and SaO2 (P < 0.01) were lower and maximum PaCO2 (P < 0.001), higher in horses with grades 4 and 5 laryngeal function than other grades. Horses with grade 4 function had a lower minimum CaO2 (P < 0.01) than horses with other grades. Minimum PAO2 decreased from grades 1 and 2 to grades 4 and 5 (P < 0.05). The minimum alveolar ventilation was lower (P < 0.05) in horses with grades 4 and 5 laryngeal function compared to other grades. The results of this study indicate that endoscopic assessment of laryngeal function at rest, using a simple grading system, provides an indication of dynamic changes in ventilation and the effects on blood gases during exercise. From the data, we suggest that horses that have some movement of the left arytenoid cartilage but are unable to achieve full abduction have similar ventilatory effects and blood gas responses during maximal exercise to those with complete paralysis. Some horses with grade 3 laryngeal function had blood gas results similar to those of horses with grades 4 and 5 laryngeal function, indicating that discrepancies may occur between the resting assessment and laryngeal function during strenuous exercise.

Animals↗
PubMed1997

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.

Adult↗
PubMed1997

Altered cell shape is linked to increased p34cdc2 gene expression in fibroblasts expressing a mutant E2F-1 transcription factor.

The E2F1 transcription factor or an amino terminal deletion mutant termed E2F1d87 was constitutively expressed in NIH3T3 fibroblasts. Cells expressing wild-type E2F1 display a morphology indistinguishable from that of normal fibroblasts. However, the E2F1d87-expressing cells exhibited a distinct rounding during culture in media containing 10% calf serum. The morphology change was most pronounced during S phase, which was considerably lengthened in the E2F1d87-expressing cells. Consistent with this rounded shape, the E2F1d87-expressing cells have significantly increased levels of both p34cdc2 mRNA and protein. Also observed was an increase in active p34cdc2 in immunoprecipitates from extracts of the E2F1d87 cell line, as assayed by histone H1 kinase assay. The upregulation of p34cdc2 expression occurs at the transcriptional level and requires ectopic E2F1d87 along with serum growth factor stimulation, since culture of these cells in low serum media results in a flattened shape and a drop in p34cdc2 expression compared to that of the control cells.

3T3 Cells↗
PubMed1997

Effects of training on the development of exercise-induced arterial hypoxemia in horses.

OBJECTIVES: To compare the development of exercise-induced arterial hypoxemia in horses before and after training, and to determine whether increases in maximum oxygen uptake (VO2max) following training results in a greater degree of exercise-induced arterial hypoxemia. ANIMALS: 13 three- to five-year-old. Standardbred geldings without clinical signs of respiratory or cardiovascular disorders. PROCEDURE: Horses were rested for 4 months prior to commencing a 16-week training program. Arterial blood was collected from the transverse facial artery during standardized exercise tests performed before and after 8 and 16 weeks of training. Variables measured during exercise tests included arterial blood gas tensions and VO2max. Training and testing was performed on a treadmill set at a 10% slope. RESULTS: Minimum arterial partial pressures of oxygen (PaO2) during exercise decreased from 83.3 +/- 1.5 mm of Hg before training to 77.8 +/- 1.0 mm of Hg after 16 weeks of training. Maximum arterial oxygen content increased from 239.2 +/- 3.1 to 257.9 +/- 3.8 ml/L, which resulted from an increase in hemoglobin concentration. The VO2max increased by 19% following training. Minimum values of PaO2 and arterial oxygen saturation were significantly correlated with VO2max when data from each stage of training were pooled. Calculated values for minimum alveolar oxygen tension decreased after 8 weeks of training, and alveolar ventilation increased at the end of training. Alveolar-arterial oxygen tension of difference increased by 4 mm of Hg following training. CONCLUSIONS: In trained horses, an increase in VO2max is associated with a decrease in minimum PaO2, during intense exercise and is mostly attributable to an increase in the alveolar-arterial oxygen tension difference. Therefore, interpretation of blood gas data from exercising horses should take into consideration VO2max.

Animals↗
PubMed1997

Prevalence of antithyroid antibodies in mood disorders.

We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non-psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent.

Adult↗
PubMed1997

Housing and exercise of dogs: effects on behavior, immune function, and cortisol concentration.

We examined the effect of supplemental exercise (either individually or with a conspecific) on the physical and psychological health of dogs by measuring immune, endocrine, and behavioral responses. Forty purpose-bred adult male beagles were assigned to one of four treatment conditions: exercised individually (EI), exercised with a conspecific (EC), nonexercised (NE), or cage control (CC). Each EI dog was removed from its cage, carried to an empty room, and allowed to exercise alone for 20 min/d 3 days a weeks for 12 weeks. Two EC dogs were allowed to exercise together following a similar schedule. To control for potential handling effects, NE dogs were removed from their cages, carried to the exercise room, but immediately returned to their cages, and CC dogs remained in their cages during scheduled exercise periods. Detailed behavioral observations, humoral immune responses to the antigen keyhole-limpet hemocyanin, peripheral blood mononuclear cell subsets, plasma cortisol concentration, body weight, and total and differential white blood cell (WBC) counts were routinely monitored. Results indicated few significant treatment effects on physiologic or behavioral measures. Specifically, EC dogs had lower percentages of B lymphocytes, and EC and EI dogs barked more than did NE or CC dogs. However, some physiologic and behavioral measures changed as a function of time regardless of treatment condition. Most notably, for all dogs over time, WBC counts, plasma cortisol values, and behavioral measures reflecting inactivity decreased, while measures reflecting high activity and abnormal behaviors increased. We concluded that neither exercise treatment substantially altered the physical health of research dogs, and perhaps more importantly, failed to prevent the development of abnormal behavior.

Animal Husbandry↗
PubMed1996

Isolation of two novel cDNAs whose products associate with the amino terminus of the E2F1 transcription factor.

The amino terminus of the E2F1 transcription factor is a protein-protein interaction domain since it associates with cyclin A/cdk2. Here, the two-hybrid yeast screen was used to clone genes whose products associate with the amino terminus of E2F1. The amino-terminal 121 amino acids of E2F1 were fused to the Lex A binding domain while a partial length cDNA library from the embryo of a 12 day old mouse was fused to the VP16 activation domain. Following coexpression of these fusions in yeast, two novel genes were cloned that code for proteins that associate with E2F1. In an in vitro assay, these E2F1 Binding Proteins (EBP1 and EBP2) associate with residues 1-121 of E2F1 or with the full-length protein; however, they do not associate with its carboxy terminus (residues 88-437). When EBP1 or EBP2 were expressed in COS cells along with E2F1 and the target promoter DNA polymerase alpha, repression of transcription was observed. However, no repression of DNA polymerase alpha was seen if the cells expressed a nonassociating mutant E2F1 (residues 88-437), along with EBP1 or EBP2. Finally, expression of the EBP2 gene is up-regulated in growing NIH3T3 fibroblasts, relative to serum-starved cells. However, this up-regulation of EBP2 expression is not seen in fibroblasts constitutively expressing E2F1.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Activation of nonspecific cytotoxic cells with a multiple antigenic peptide: specificity and requirements for receptor crosslinkage.

Nonspecific cytotoxic cells (NCC) of teleost fish recognize a conserved antigenic determinant found on the protozoan Tetrahymena pyriformis and on many different tumor target cells. This determinant is located on a 46-kDa Tetrahymena protein referred to as natural killer target antigen (NKTag). The NKTag cognate sequence recognized by NCC is composed of seven to nine amino acids. In the present study, synthetic peptides of the cognate NKTag determinant were prepared as multiple antigenic peptides (MAP). Immobilized MAP activated NCC lysis of IM-9 target cells in the absence of antigen presenting cells or exogenous added cytokines. NCC binding to immobilized MAP produced two- to fivefold increased lysis of IM-9, U937, and HL-60 target cells compared to scrambled control MAP (composed of the same amino acids only in random sequence). NCC receptor crosslinkage was required for activation. Immobilized monomeric homologous cognate peptide did not activate increased NCC lysis of IM-9 target cells; however, NCC preincubated with soluble homologous monomer inhibited MAP activation of lysis. Ligand activation of NCC was antigen specific. Binding of the immobilized ligand with anti-MAP mab 22A12 prior to addition of NCC blocked activation. Mab 22A12 also inhibited NCC lysis of IM-9 target cells. A possible mechanism of NCC activation was determined. Binding of NCC to immobilized MAP produced significantly increased membrane expression of a putative receptor as defined by mab 5C6 binding. These studies demonstrate that activation of NCC by a target cell antigenic determinant depends on crosslinkage of an NCC "receptor" by polymeric repetitive sequences, a soluble or fixed monomer cannot activate but can inhibit activation, and MAP binding initiates increased expression of a putative NCC receptor protein.

Amino Acid Sequence↗
PubMed1996

Influence of cognitive reserve on neuropsychological functioning in asymptomatic human immunodeficiency virus-1 infection.

OBJECTIVE: To evaluate the influence of cognitive reserve or brain reserve capacity on neuropsychological performance in early human immunodeficiency virus (HIV)-1 infection. DESIGN: Cross-sectional group comparison study, based on neuropsychological performance, of HIV-1 seropositive and HIV-1 seronegative participants. SUBJECTS: Seventy-five medically asymptomatic HIV-1-seropositive homosexual or bisexual men and 50 HIV-1-seronegative homosexual or bisexual male controls. Subjects were grouped by HIV-1 status (seropositive vs seronegative) and by cognitive reserve scores (low reserve vs high reserve). MEASURES: Cognitive reserve scores were based on a combination of years of education, a measure of occupational attainment, and an estimate of premorbid intelligence. Performance on a battery of neuropsychological tests was summarized by empirically derived factor scores and clinical summary ratings. RESULTS: The HIV-1-seropositive subjects with low cognitive reserve scores exhibited significantly greater deficits on measures of attention and information processing speed, verbal learning and memory, executive functioning, and visuospatial performance than did the HIV-1-seropositive subjects with high cognitive reserve scores. In contrast, there were no significant group differences on these measures between both groups of HIV-1-seronegative subjects. CONCLUSIONS: Early neuropsychological impairments in HIV-1 infection are most evident in individuals with lower cognitive reserve. As has been found in other neurologic disorders, such as Alzheimer's disease, individuals with greater cognitive reserve may be less sensitive to the initial clinical effects of the underlying neuropathologic process.

Adolescent↗
PubMed1996

Mapping of the epitope recognized by non-specific cytotoxic cells: determination of the fine specificity using synthetic peptides.

NCC recognize a conserved target cell antigen (NKTag) expressed on protozoan parasites and on transformed tumour cells. In the present study, synthetic peptides corresponding to N-terminal, C-terminal and internal NKTag(deduced) amino acid sequences were tested for binding and inhibition of NCC lysis of sensitive target cells. A 20-mer peptide equivalent to amino acids (aa) nos. 55-74 specifically inhibited NCC lysis of human EBV transformed target cells (IM-9). Inhibitory effects were nonreversible and concentration dependent, and 30 min pre-incubation produced optimum inhibition. The inhibitory 20-mer peptide was truncated into 17, 14, 10, 9 and 6-mer peptides and tested for inhibition of cytotoxicity. All produced almost complete inhibition except the 6-mer which had no activity. The NKTag sequence required for NCC binding (minimally) consisted of seven amino acids [aa nos 68-74 (ARG-ASN-LEU-THR-PHE-ILE-LEU-)]. The specificity of inhibition and the distribution of target cells expressing NKTag was determined. A 14-mer peptide composed of aa nos 61-74 inhibited lysis of HL-60, IM-9, DAUDI, YAC-1, U937 and NC-37 target cells. Flanking peptides (aa nos 35-54 and 75-94) were negative. Biotinylated aa nos 61-74 bound to NCC effector cells. The recognition requirements for aa sequence versus aa content were determined. Randomization of the aa in the cognate 9-mer obliterated the inhibitory effects. The 17-mer (cognate) synthetic peptide inhibited conjugate formation between NCC and IM-9 targets. These data demonstrate that NCC recognize a conserved antigen determinant on susceptible target cells consisting of a minimum of 7-9 amino acids in the N-terminal region of NKTag.

Amino Acid Sequence↗
PubMed1996

Accuracy of Accusport for measurement of lactate concentrations in equine blood and plasma.

The aim of this study was to investigate correlations between lactate concentrations in equine whole blood and plasma measured with Accusport1 and Yellow Springs Instruments (YSI2) (2300) methods. The effect of packed cell volume (PCV) on the accuracy of Accusport was also investigated. Blood samples were collected from Thoroughbred horses at 5-10 min intervals after a treadmill exercise test. Blood was added to NaEDTA (for PCV measurement) and to 2 tubes containing lithium heparin anticoagulant (for lactate assays). At concentrations greater than 10 mmol/l, Accusport1 greatly underestimated the blood lactate concentration. Accusport1 also underestimated blood lactate concentration when PCV were greater than 53%. Accusport1 accurately measured plasma lactate concentration in the range 0.8-20 mmol/l.

Animals↗
PubMed1996

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses.

Thirteen standardbred horses were trained as follows: phase 1 (endurance training, 7 wk), phase 2 (high-intensity training, 9 wk), phase 3 (overload training, 18 wk), and phase 4 (detraining, 12 wk). In phase 3, the horses were divided into two groups: overload training (OLT) and control (C). The OLT group exercised at greater intensities, frequencies, and durations than group C. Overtraining occurred after 31 wk of training and was defined as a significant decrease in treadmill run time in response to a standardized exercise test. In the OLT group, there was a significant decrease in body weight (P < 0.05). From pretraining values of 117 +/- 2 (SE) ml.kg-1.min-1, maximal O2 uptake (VO2max) increased by 15% at the end of phase 1, and when signs of overtraining were first seen in the OLT group, VO2max was 29% higher (151 +/- 2 ml.kg-1.min-1 in both C and OLT groups) than pretraining values. There was no significant reduction in VO2max until after 6 wk detraining when VO2max was 137 +/- 2 ml.kg-1.min-1. By 12 wk detraining, mean VO2max was 134 +/- 2 ml.kg-1.min-1, still 15% above pretraining values. When overtraining developed, VO2max was not different between C and OLT groups, but maximal values for CO2 production (147 vs. 159 ml.kg-1.min-1) and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLT group. Overtraining was not associated with a decrease in VO2max and, after prolonged training, decreases in VO2max occurred slowly during detraining.

Animals↗
PubMed1995

Rat brain binding sites for pramipexole, a clinically useful D3-preferring dopamine agonist.

Pramipexole (PPX) is currently being evaluated for treatment of schizophrenia and Parkinson's disease. In studies with cloned subtypes of the dopamine (DA) D2 receptor subfamily, PPX has higher affinity for the D3 compared to the D2 and D4 subtypes; unlike 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), it does not bind to sigma sites. Receptor binding autoradiography with [3H]PPX (5 nM, 62 Ci/mmol) was used to evaluate the distribution of PPX binding sites within the rat brain. Consistent with its preference for D3-binding sites, the highest concentrations of [3H]PPX binding sites were found in the islets of Calleja (ICj), previously reported to contain D3 but not D2 or D4 mRNA. [3H]PPX binding was also high in other mesolimbic areas such as the nucleus accumbens (N. accum), olfactory tubercle, and amygdala. [3H]PPX binding was also high in caudate (Cd), although slightly less than in mesolimbic areas. Less [3H]PPX binding sites were found in ventral tegmental area (VTA) and substantia nigra, areas rich in cell bodies for DA neurons. Thus, although PPX most potently stimulates DA autoreceptors, PPX binding sites have their highest concentrations in projection areas containing both DA terminal and postsynaptic receptors. Because of PPX's preferential affinity for the D3 receptor subtype and its resultant high mesolimbic binding, it could have a unique therapeutic profile for treatment of psychiatric and/or neurological diseases.

Animals↗
PubMed1995

Expression of a deletion mutant of the E2F1 transcription factor in fibroblasts lengthens S phase and increases sensitivity to S phase-specific toxins.

To better understand how the E2F1 transcription factor contributes to the process of cell proliferation, NIH-3T3 cell lines were generated that constitutively express either the wild-type E2F1 protein or an amino terminal deletion mutant, termed E2F1d87. Proliferating E2F1d87-expressing cells exhibit a significant lengthening of S phase relative to control and E2F1 cell lines and are hypersensitive to the cytotoxic effects of the S phase-specific antitumor drug camptothecin. This sensitivity is associated with an increase in drug-induced p53 and WAF1 levels. The E2F1 and E2F1d87 cell lines are both able to initiate, but not complete, S phase under conditions of serum starvation. However, quantitation of DNA synthesis, during culture in serum-deprived media, indicates that the E2F1d87 cell line synthesizes more DNA/cell as compared to the E2F1 cell line. Consistent with this relative increase in DNA synthesis, the E2F1d87 cell line undergoes camptothecin-induced apoptosis when cultured under conditions of serum starvation, while the control and E2F1 cell lines are unaffected by drug treatment under the same conditions. Thus, the sensitivity of the E2F1d87 cell line to camptothecin is not dependent on cell proliferation. The data presented here suggest that cell cycle parameters can be manipulated in order to enhance sensitivity of a cell to the toxic effects of specific chemotherapeutic agents.

3T3 Cells↗
PubMed1995

Molecular evolution and secondary structural conservation in the B-cell lymphoma leukemia 2 (bcl-2) family of proto-oncogene products.

The nature of the bcl-2 family of proto-oncogenes was analyzed by sequence alignment, secondary structure prediction, and phylogenetic techniques. Phylogenies were inferred from both the nucleic acid and amino acid sequences of the human, murine, rat, and chicken sequences for BCL-2 and BCL-X, human MCL1, murine A1, the nematode Caenorhabditis elegans and Caenorhabditis briggsiae ced-9 proteins, and the sequences BHRF1 from Epstein-Barr and LMW5-HL from African swine fever viruses. Both sequence alignment and secondary structure prediction techniques supported the conservation of both the overall secondary structure and the carboxy-terminal transmembrane domain in all members of the family. All the treeing methods employed (distance matrix, maximum likelihood, and parsimony) supported a tree in which the proapoptotic proteins BCL-2 and BCL-X represent the most recent additions to the group. All the trees also indicated that the viral proteins BHRF1 and LMW-HL arose from a common ancestor, an ancestor they shared in common with the pro-apoptotic control protein BAX, indicating that this function of BAX evolved only recently. The most ancient branches are represented by the nematode ced-9 protein and by the control genes MCL1 and A1, which in the treeing methods employed represent separate lineages within the most ancient grouping. These results demonstrate the evolution of a highly conserved family of developmental control genes from nematode to man--genes that encode proteins essential for normal development but which are highly conserved in terms of predicted structure and possible cellular localization. The evolutionary analysis also indicates that the family may be even larger than originally predicted and that other members are waiting to be discovered.

Amino Acid Sequence↗
PubMed1995

Reforming Georgia's mental health system.

Legislation passed in 1993 makes sweeping administrative structural changes in Georgia's mental health system. Underlying these changes is the core value that consumers and families should be empowered to participate in the design, contracting, and evaluation of services. The key structural component is the creation of regional boards, comprised of at least 50% consumers and family members, which have the capacity to plan and contract for services and to evaluate the outcomes of those services. This paper describes Georgia's mental health system before these changes, the development of the initiative for reform, the process and problems associated with the passage of the legislation, and the current status of the implementation of the legislation.

Community Mental Health Services↗
PubMed1995

Growth of Chinese hamster ovary (CHO) cells expressing the 5-HT2 serotonin receptor in suspension culture: an efficient method for large-scale acquisition of membrane protein for drug evaluation.

Chinese hamster ovary (CHO) cells expressing the rat 5-HT2 serotonin receptor were grown and evaluated in suspension culture to provide an efficient method of producing membrane-bound receptors for drug discovery. Expression of the 5-HT2 receptor in cells grown in batch suspension culture fluctuated as a function of culture age. Both receptor expression and receptor G-protein coupling were the highest early (1.9 pmol/mg membrane protein) but declined rapidly as the culture increased in age. However, addition of fresh serum-containing medium to stationary-phase cells reversed the decline and, after 24 h of growth, resulted in maximal receptor density and G-protein coupling. This serum response was found to be reproducible and lead to the establishment of a semi-continuous batch culture system in which cells were maintained in a growth state that supported high levels of membrane-incorporated and G protein-coupled receptors. In this system, 50% of the culture volume could be removed at 24-h intervals for membrane preparation and the lost volume replenished with fresh medium, resulting in a continuous supply of high-quality membrane preparations.

Animals↗