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Biomedical subjects

D L Evans

Publications and source records attributed to D L Evans.

At least 145 records · Page 8Linked to original sources
PubMed1993

Vitamin B12 deficiency and nervous system disease in HIV infection.

BACKGROUND: Vitamin B12 deficiency may result in a number of neurological and neuropsychiatric disorders. Patients with human immunodeficiency virus type 1 (HIV-1) infection may have a high rate of vitamin B12 deficiency and nervous system disease. Vitamin B12 deficiency may contribute to neurological disease in HIV-1-infected individuals. OBJECTIVE: To evaluate the possible contribution of vitamin B12 deficiency to neurological disease in HIV-1-infected individuals. MAIN OUTCOME MEASURES: Comparison of serum vitamin B12 levels with neurological, neuropsychological, and mood state abnormalities in 153 HIV-1-positive subjects and 57 high-risk seronegative controls. A subgroup of 67 subjects underwent additional extensive clinical neurophysiological, cerebrospinal fluid, and magnetic resonance imaging evaluations. RESULTS: No statistically significant relationships were noted between vitamin B12 levels and abnormalities on any of the measures examined. CONCLUSIONS: This study does not indicate an important role for vitamin B12 deficiency in the neurological disease of HIV-1 infection.

Adult↗
PubMed1993

Natural killer (NK) cells in domestic animals: phenotype, target cell specificity and cytokine regulation.

A comprehensive review of NK cells in animals of veterinary medical importance has not been previously published. However, these cells have a high level of immunological/medical relevance due to their role in tumour cell destruction and B-cell regulation, as well as their inhibitory activities against various parasites and bacteria. In the present review, NK cells from agriculturally important animals are characterized. Cell phenotype descriptions have shown that for each species, unique (i.e. non-cross-reactive with anti-human CD antibodies) and different monoclonals are required to identify NK cells. These cells lyse certain tumour and virus transformed target cells and, as might be expected from the diverse species compared in this review, analysis of the tissue distribution of NK cells gives highly varied results. NK cell morphology differs in these species from small agranular to large granular lymphocytes. The final area considered relates to studies on the effects of cytokines on NK function and to research identifying which cytokines (if any) are produced by NK cells during activation responses. The largest quantity of available data concerns functional and descriptive studies in these animals. However, it is appropriate to consider this research as a starting point on which to build comparative and molecular studies of the roles of NK cells in immunosurveillance and immunoregulation.

Animals↗
PubMed1993

Expression of an evolutionarily conserved function associated molecule on sheep, horse and cattle natural killer cells.

Natural killer (NK) cells are large granular lymphocytes that lyse a wide variety of transformed and virally-infected target cells without prior exposure to antigen, and without restriction by major histocompatibility complex antigens. Although NK cells have been identified in a variety of mammalian species, how NK cells recognize antigen and trigger lysis is unknown. Recently, monoclonal antibodies made against NK-like cells from teleost fish were shown to react with NK cells from humans and rats, and to inhibit their cytolytic activity. The role of this apparently evolutionarily conserved function-associated molecule (FAM) has been further investigated utilizing a variety of domesticated farm animal species. It was observed that the anti-FAM mAb reacted specifically with peripheral blood lymphocytes isolated from sheep, horses and cattle. Further, the anti-FAM mAb inhibited NK cell lytic activity in each of these species. Finally, the anti-FAM mAb was found to inhibit conjugate formation between NK and target cells, implying that the FAM was involved in antigen recognition by NK cells in each of these species. In conclusion, it appears that NK cell function is mediated by an evolutionarily conserved FAM in a wide variety of species.

Animals↗
PubMed1993

A novel target cell antigen involved in the NK-like lytic activity of antigen-specific cytotoxic T lymphocytes.

Monoclonal antibodies (mAbs) have been derived which identify a target cell antigen involved in human natural killer (NK) cell lysis. The effects of the mAbs on the NK-like cytotoxic activity exhibited by different populations of human cytolytic T cells were examined. The anti-target cell mAbs 1E7 and 18C2 inhibited the lysis of K562 target cells by endogenous NK cells, antigen-specific cytotoxic T lymphocytes (CTL) with NK-like activity, and non-major histocompatibility complex (MHC)-restricted T cells. Cytolysis of K562 target cells was not affected by treatment of the target cells with the anti-class I HLA mAb W6/32. Further, the anti-target cell mAbs had no effect on antigen-specific lysis by the CTL. The mAb W6/32, however, inhibited the antigen-specific killing. Experiments at the single-cell level revealed that the anti-target cell mAbs inhibited the formation of conjugates between the effector cells and K562 tumor cells but had no effect on CTL binding to the antigen-specific target cells. Thus, antigen-specific CTL exhibiting NK-like lytic function appeared to recognize a novel target cell antigen that is distinct from typical MHC antigens and is identical to the target-cell antigen recognized by true NK cells.

Adolescent↗
PubMed1993

Identification of a vimentin-like function associated molecule (FAM) on rat NK cells: evidence for receptor function.

Monoclonal antibody (MoAb) 5C6 specifically binds to fish, rat and human NK cells and inhibits cytotoxicity. The molecule recognized by this MoAb is a 50-53-kDa membrane protein on rat leukaemic NK (CRC) cells. In the present study, we have obtained a partial internal amino acid sequence from a purified 42-kDa fragment of the CRC-function associated molecule (FAM). Three tryptic peptide fragments were sequenced and each showed homology to intermediate filament vimentin sequences as deduced from (GenBank) mouse cDNA sequences. Amino acid composition analysis indicated that similar to cytoskeletal vimentin, the FAM contained a high percentage of non-polar amino acids. To further assess the similarities between this protein and vimentin, two commercially available anti-vimentin MoAbs and one anti-vimentin polyclonal antibody were tested for binding and inhibition of NK cytotoxicity. All anti-vimentin MoAbs inhibited killing by rat NWNA cells of appropriate targets. Anti-vimentin MoAb 13.2 bound to 41% of NWNA cells compared with approximately 58% binding for MoAb 5C6. Capping and sequential binding experiments showed that MoAb 5C6 effectively removed, from CRC-cell membranes, the protein recognized by MoAb V9. Sequential addition of these two MoAbs (MoAb 13.2 followed by MoAb V9) to CRC cells did not produce competitive binding. Biochemical and Western blot analysis of the vimentin-like protein obtained from CRC cells indicated that this protein has a molecular weight of 48-50 kDa, with an isoelectric point of pH 6.1-6.3. This protein is cross-reactive by Western blot analysis with anti-vimentin and anti-intermediate filament (IFA) antigen MoAbs but not with anti-desmin or anti-actin MoAbs. The molecular weight heterogeneity (43 versus 48-50 kDa) of the CRC protein was also examined. Western blot analysis of the CRC extract after different in vitro incubation times at 37 degrees C and 4 degrees C demonstrated that the 50-53-kDa 'native' protein degraded to a 42-kDa protein by 24 and 48 h respectively. This degradation was inhibitable by 10 mM EGTA. Evidence is presented which indicates that a vimentin-like protein on transformed rat NK cells may be an antigen binding receptor which initiates target cell lysis.

Amino Acid Sequence↗
PubMed1993

Nutrient intake of horses in thoroughbred and standardbred stables.

Twenty-five Thoroughbred (TB) and 25 Standardbred (SB) stables were visited to determine their feeding practices. The ingredients of the main feed of the day for a mature gelding of average size in full training were weighted at each stable. Nutrient content of diets was calculated using published data for the individual ingredients. Results are expressed as mean +/- sd. The estimated body weight of TB horses was 493 +/- 34 kg and 437 +/- 32 kg for SB horses. There was considerable variation in diet composition and nutrient intake between stables. The TB trainers fed 11.0 +/- 2.4 kg and SB trainers 11.8 +/- 2.5 kg per day. The concentrate component of the diet weighed 7.8 +/- 1.6 and 7.7 +/- 2.3 kg for TB and SB stables, respectively, and the roughage component for TB horses 3.3 +/- 1.4 and SB horses 4.1 +/- 1.4 kg per day. The digestible energy intake of horses at TB stables was 129 +/- 29 MJ per day and at SB stables 132 +/- 31 MJ per day. Crude protein intake of TB horses was 1452 +/- 363 g and SB horses 1442 +/- 338 g per day. There were differences in some feeding practices at TB and SB stables. Standardbred trainers fed more roughage than TB trainers. Standardbred trainers fed chaffed lucerne (alfalfa) and cereal hays as the major roughage, whereas TB trainers fed more hay. The major hay type fed by TB trainers was lucerne, whereas many SB trainers preferred clover hay. Both trainers fed oats as the major grain, but TB trainers fed slightly more maize (corn) than SB trainers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1993

Effects of sodium bicarbonate on cardiorespiratory measurements and exercise capacity in thoroughbred horses.

We examined the effects of sodium bicarbonate in 6 Thoroughbred horses during submaximal and maximal treadmill exercise. Cardiorespiratory function was assessed together with the effect on exercise capacity by determining the run time to fatigue at maximal intensities. To discriminate between sodium bicarbonate's alkalinising effects and the fluid shifts that could result from the high osmotic load, we administered an equimolar solution of sodium chloride as a control. The horses were given sodium bicarbonate (1 g/kg bwt) or an equivalent number of moles of sodium chloride by nasogastric tube. Arterial blood samples were collected before exercise and 5 h after treatment, resulting in mean standard bicarbonate values of 39.6 mmol/l in horses treated with sodium bicarbonate compared with 24.2 mmol/l in horses that received saline. The horses were exercised on a treadmill at 40, 60 and 80% of their VO2max for 4, 2 and 2 mins respectively. The horses were walked for 3 mins and accelerated rapidly to a speed approximately equivalent to 110% VO2max and run until fatigued. The horses ran for 170 +/- 20 secs (mean +/- sem) after administration of sodium bicarbonate compared with 128 +/- 13 secs after receiving sodium chloride (P < 0.02). At rest and throughout submaximal and maximal exercise, the bicarbonate-treated horses had significantly lower arterial oxygen tensions and higher arterial carbon dioxide tensions. There were no differences in cardiac output, heart rate, oxygen uptake or carbon dioxide production between the saline and bicarbonate treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Correlation of racing performance with blood lactate and heart rate after exercise in thoroughbred horses.

At 2 and 5 mins after an 800-m gallop, venous blood was collected from 26 Thoroughbred racehorses for measurement of blood lactate concentration, packed cell volume (PCV) and haemoglobin concentration. In addition, 14 racehorses were given a strenuous submaximal treadmill exercise test. Heart rates during and after exercise at 10 m/sec on a treadmill inclined at 5 degrees were recorded. Blood samples at 2 and 5 mins after exercise were used to measure PCV, blood and plasma lactate and ammonia concentrations. Results of each exercise test were compared with the retrospective performance of horses in races, using Timeform ratings. The results of the field tests were also compared with the performance of each horse in a race 2 days later. There were no significant correlations between any of the measurements taken after the field test and either subsequent race performance or Timeform rating. Heart rate 4 mins after treadmill exercise was significantly correlated with Timeform rating (r = -0.565, P < 0.05). Blood and plasma lactate concentrations 2 and 5 mins after treadmill exercise were all significantly correlated with Timeform. The highest correlations were with blood lactate concentrations 2 and 5 mins after exercise (r = -0.68, P < 0.01). There were no significant correlations between Timeform and heart rate during exercise at 10 m/sec, heart rates at 1, 3 and 5 mins after exercise, PCV and plasma ammonia at 2 and 5 mins, or the differences between lactate concentration in plasma or blood at 2 and 5 mins after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Personality disorder in patients infected with HIV: a controlled study with implications for clinical care.

OBJECTIVE: Previous studies of psychiatric illness in populations infected with or at risk for HIV have not included systematic evaluation for personality disorders. The authors present the first controlled study of 1) personality disorders in HIV-positive and HIV-negative homosexual men and 2) the impact of personality disorder on coping, social support, and mood in asymptomatic HIV-positive homosexual men. METHOD: The authors studied 58 asymptomatic HIV-positive and 53 HIV-negative homosexual men living outside the high-prevalence epicenters of the AIDS epidemic. Personality disorder was assessed with a clinician-administered interview, the Structured Clinical Interview for DSM-III-R. RESULTS: There was a significantly higher prevalence of personality disorder in the HIV-positive (33%) than in the HIV-negative (15%) subjects. In the HIV-positive subjects, those with a personality disorder (compared to those without a personality disorder) showed 1) significantly greater mood disturbance, with higher scores on the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Profile of Mood States Total Mood Dysfunction, and the Beck Hopelessness Scale, 2) greater use of denial and helplessness when coping with the threat of AIDS, and 3) greater social conflict. CONCLUSIONS: These findings suggest that personality disorder is common in the HIV-positive population. Compared with HIV-infected patients without a personality disorder, patients with a personality disorder may experience greater dysphoria and be more likely to cope with the threat of AIDS in a dysfunctional way. Recognition of the impact of personality disorder on coping with HIV infection is important for comprehensive, sensitive, and effective clinical care.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Psychosocial predictors of high-risk sexual behavior among HIV-negative homosexual men.

Despite general awareness that human immunodeficiency virus (HIV) is transmitted sexually, people continue to engage in high-risk behavior. As part of a larger HIV project, the Coping in Health and Illness Project (CHIP), we studied the association of psychosocial factors with sexual risk taking behaviors in 53 HIV-negative gay men residing in a HIV non-epicenter. Risk behavior was measured on a 3-point scale, taking into account condom use, number of sexual partners, and type of sexual activity. Independent variables included mood, coping, history of substance dependence, social support, and acceptance of sexual orientation. Sixty percent of the subjects practiced lower-risk, 17.3% practiced moderate-risk, and 23.1% practiced high-risk behavior. We found that risk behavior was positively correlated with optimism (Life Orientation Test) (OR = 2.7; 95% CI = 1.3-5.5), anger (POMS) (OR = 2.6; 95% CI = 1.2-5.7), and negatively related to emotional control (Courtauld) (OR = 0.5; 95% CI = 0.3-1.0), and gay self-acceptance (OR = 0.35; 95% CI = 0.2-0.8). Further study is needed to determine if sexual risk-taking behavior in HIV-negative gay men will be reduced by enhancing gay self-esteem, increased understanding and adaptive use of anger, and modifying overly optimistic attitudes to increase realism.

Adaptation, Psychological↗
PubMed1993

The effect of roughage source on exercise performance and metabolism in thoroughbred horses.

The effects of roughage source on metabolism and exercise capacity were investigated using 6, previously conditioned, mature thoroughbred horses in a cross-over experiment. The horses were assigned to either non-alfalfa or alfalfa roughage diets which were isocaloric. The diets were fed for 2 weeks, after which the horses were exercise tested and then fed the alternate diet. Horses were exercised on a high-speed treadmill using a rapid incremental test. Arterial blood samples were collected for blood gas analysis and acid base measurements and venous blood samples for lactate and red blood cell potassium analysis. Mixed expired gas samples were collected for measurement of oxygen uptake, carbon dioxide production and respiratory exchange ratio. Heart rate was measured by telemetry ECG and respiratory frequency by observation. When the 2 diets were compared there were no significant differences in treadmill exercise capacity nor in any of the metabolic or cardiorespiratory measurements made before, during or after the exercise period. We concluded that roughage source has no effect on cardiorespiratory and metabolic function during or after exercise, and does not affect endurance performance during a treadmill exercise test.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Heparin binding site, conformational change, and activation of antithrombin.

Alignment of the heparin-activated serpins indicates the presence of two binding sites for heparin: a small high-affinity site on the D-helix corresponding in size to the minimal pentasaccharide heparin, and a longer contiguous low-affinity site extending to the reactive center pole of the molecule. Studies of the complexing of antithrombin and its variants with heparin fractions and with reactive center loop peptides including intermolecular loop-sheet polymers all support a 3-fold mechanism for the heparin activation of antithrombin. Binding to the pentasaccharide site induces a conformational change as measured by circular dichroism. Accompanying this, the reactive center becomes more accessible to proteolytic cleavage and there is a 100-fold increase in the kass for factor Xa but only a 10-fold increase for thrombin, to 6.4 x 10(4) M-1 s-1. To obtain a 100-fold increase in the kass for thrombin requires in addition a 4:1 molar ratio of disaccharide to neutralize the charge on the extended low-affinity site. Full activation requires longer heparin chains in order to stabilize the ternary complex between antithrombin and thrombin. Thus, addition of low-affinity but high molecular weight heparin in conjunction with pentasaccharide gives an overall kass of 2.7 x 10(6) M-1 s-1, close to that of maximal heparin activation.

Allosteric Regulation↗
PubMed1992

The mechanism of Z alpha 1-antitrypsin accumulation in the liver.

Most northern Europeans have only the normal M form of the plasma protease inhibitor alpha 1-antitrypsin, but some 4% are heterozygotes for the Z deficiency variant. For reasons that have not been well-understood, the Z mutation results in a blockage in the final stage of processing of antitrypsin in the liver such that in the Z homozygote only 15% of the protein is secreted into the plasma. The 85% of the alpha 1-antitrypsin that is not secreted accumulates in the endoplasmic reticulum of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. These inclusions are associated with hepatocellular damage, and 10% of newborn Z homozygotes develop liver disease which often leads to a fatal childhood cirrhosis. Here we demonstrate the molecular pathology underlying this accumulation and describe how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive centre loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. Z antitrypsin polymerized in vitro has identical properties and ultrastructure to the inclusions isolated from hepatocytes of a Z homozygote. The concentration and temperature dependence of this loop-sheet polymerization has implications for the management of the liver disease of the newborn Z homozygote.

Circular Dichroism↗
PubMed1992

Detection of function-associated molecules on rat NK cells and their role in target cell lysis.

Anti-effector cell mAb 5C6.10.4 (5C6) inhibits cytotoxic activity of fish nonspecific cytotoxic cells (NCC). We now show that 5C6 also inhibits mammalian NK cell activity using fresh and cultured (CRC) leukemic rat NK cells. The inhibitory activity of 5C6 was caused by blocking of conjugate formation between NK cells and YAC-1 targets. Binding studies done by flow cytometry (FCM) showed that mAb 5C6 specifically bound to 8% of unfractionated rat spleen cells. Enrichment by nylon-wool fractionation produced 27.2% specific binding, along with a 3.4-fold enrichment in cytotoxic activity. Tissue distribution studies revealed that the highest number of cells recognized by mAb 5C6 were found in NWNA spleen cells (28.7%), followed by liver (18.9%) and peripheral blood (13.9). Two-color FCM showed that although all 3.2.3 mAb-positive cells were also stained with mAb 5C6, a small percentage of 3.2.3. negative noncytotoxic NWNA spleen T cells were 5C6 positive. Redirected lysis experiments demonstrated that anti-effector mAb-producing myeloma cells could be killed by CRC and NWNA spleen cells. In addition, mAb 5C6 produced specific inhibition of redirected lysis of each myeloma target. Experiments were also conducted to determine the signaling capability of the FAM complex. Binding of the anti-FAM mAbs to NWNA rat spleen cells caused a rapid increase in cytosolic free calcium of approximately 472 nM. Western blot analysis of CRC cell lysates showed that the molecules recognized by anti-FAM mAbs have molecular weights of 38 and 42 kDa. These studies indicate that the anti-effector mAbs recognize a functionally relevant molecule on rat NK cells that is involved in the first steps of cytolysis, i.e., antigen recognition, and which also triggers the activation of signal-transducing events in these cells.

Animals↗
PubMed1992

Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds.

The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij] quinolin-2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1- ij]quinazolin-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and compared with those of other tricyclic ligands known to have high affinity at these receptors.

Aminoquinolines↗
PubMed1992

Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry.

Necrosis and apoptosis are two distinct modes of cell death which differ in morphology, mechanism and incidence. Membrane disruptants, respiratory poisons and hypoxia cause ATP depletion, metabolic collapse, cell swelling and rupture leading to inflammation. These are typical features of necrosis. Apoptosis plays a crucial role in embryogenesis and development and is also prevalent in tumours. It is characterised by cell shrinkage, chromatin condensation and systematic DNA cleavage. Apoptotic cells are rapidly engulfed by phagocytes, thus preventing inflammatory reaction to degradative cell contents. In vivo, apoptosis is almost impossible to quantify due to problems of heterogeneity and the short half-life of an apoptotic cell. In vitro, mechanistic studies are further complicated by a late phase of apoptosis where the cell membrane becomes permeable to vital dyes and which occurs in the absence of phagocytes. Here we describe a novel and rapid multiparameter flow cytometric assay which discriminates and quantifies viable, apoptotic and necrotic cells via measurement of forward and side light scatter (proportional to cell diameter and internal granularity, respectively) and the DNA-binding fluorophores Hoechst 33342 and propidium. It is anticipated that mechanistic studies of apoptosis in a variety of cell types will greatly benefit from this mode of analysis.

Animals↗
PubMed1992

Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression.

The effects of major depression on peripheral blood natural killer cell phenotypes and natural killer cell activity were studied by comparing depressed and normal control subjects. Depressed subjects exhibited (1) significant reductions in Leu-11 (CD16) natural killer effector cells and natural killer cell activity and (2) a dissociation of the normal positive correlation between the percentage of Leu-11 cells and natural killer cell activity. These findings suggest that alterations in the availability and the killing capacity of circulating Leu-11 natural killer cells appear to be responsible for depression-related reductions in natural killer cell activity. Moreover, men with major depression showed marked reductions in Leu-11 cells, natural killer cell activity, and Leu-7 (HNK-1) lymphocytes compared with normal control men. By contrast, depressed women did not differ significantly from normal control women on any of these three immune function measures. Severity of depression as assessed by Hamilton Rating Scale for Depression scores was not associated with natural killer cell activity or Leu-7 lymphocyte levels in either men or women with major depression. Hamilton Rating Scale for Depression severity ratings were, however, strongly inversely correlated with Leu-11 lymphocyte counts among men, but not women, with major depression. These data begin to elucidate the immunological mechanisms by which natural killer cell activity is altered in depression and suggest that some measures of immunity may be differentially affected in male and female subjects with the syndrome of major depression.

Adolescent↗