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Biomedical subjects

D L Evans

Publications and source records attributed to D L Evans.

At least 109 records · Page 6Linked to original sources
PubMed1995

Monoclonal antibody binding to a receptor on nonspecific cytotoxic cells (NCC) increases the expression of proto-oncogene kinases and protein kinase C.

Teleost nonspecific cytotoxic cells (NCC) initiate various cell triggering responses following receptor-target cell interactions. A putative receptor protein on NCC may alternatively initiate signalling processes following crosslinkage by homologous anti-receptor mab 5C6. In the present study, we demonstrated that binding to this receptor by mab 5C6 produced increased levels of expression of cytoplasmic src family proto-oncogene kinases lck, fyn and src. The phosphorylated isoforms of each kinase were approximately the same molecular weight (p60). Unlike their mammalian T-cell and natural killer (NK) cell counterparts, NCC p56lck did not autophosphorylate on tyrosine residues. This was determined by a lack of Western blot reactivity of teleost p56lck with anti-phosphotyrosine specific antibodies PT-66 or 4G10. Additional evidence for this lack of tyrosine phosphorylation was shown by experiments treating mab 5C6 activated NCC with sodium orthovanadate. This protein tyrosine phosphatase inhibitor did not affect levels of p56lck autophosphorylation. Mab 5C6 activated NCC were also examined to determine if levels of protein kinase C (PKC) expression were affected during triggering responses. Maximum increased PKC levels occurred 5-10 min following binding. The NCC receptor-activated PKC consisted of a 60,000 M(r) isoform and a 30,000 M(r) homologue equivalent to the mammalian PKC catalytic subunit. Not all kinases examined, however, were affected by mab 5C6 binding. Levels of expression of c-myc and cdc2p34 did not change following NCC activation. This is the first study of NK-like cells in cold-blooded vertebrates regarding the expression of these vital intermediary transducing kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Comparison of bronchoalveolar lavage findings and measurements of gas exchange during exercise in horses with poor racing performance.

Twenty-four Thoroughbred and twelve Standardbred racehorses aged between 2 and 6 years, presented for reported poor racing performance, underwent clinical exercise testing. During the last 10 s of exercise at each speed throughout an incremental speed exercise test on a treadmill inclined at a 10% slope, samples of arterial blood and expired gases were collected. Maximum oxygen uptake and the partial pressures of oxygen and carbon dioxide in arterial blood were determined. These values were compared between the two breeds of horses and also with reference to cytological findings of bronchoalveolar lavage samples, including neutrophil, erythrocyte and haemosiderophage percentage and the total nucleated cell concentration. The results revealed an inverse relationship (Spearman R = -0.45, p < 0.05) between the total nucleated cell count in bronchoalveolar lavage samples and arterial oxygen partial pressure during exercise at 11 m.s(-1). This result suggests that subclinical pulmonary disease may be a more important cause of poor racing performance than previously thought. Also of note was a positive correlation (Spearman R = 0.50, p < 0.05) between maximum oxygen uptake and the percentage of erythrocytes.

Journal Article↗
PubMed1995

Chronic vascular catheterisation of the koala and the rabbit.

Vascular access ports were surgically placed, first in rabbits maintained under laboratory conditions, and then in koalas maintained in a wildlife park. The ports remained patent for 9 months in rabbits and for up to 13 months in the koalas and were removed successfully. They allowed collection of blood samples without assistance or disturbance in koalas, and without stress as reflected by plasma cortisol concentration. The use of retention rings on the cannula tubing is recommended.

Animals↗
PubMed1995

Equine sweat composition: effects of adrenaline infusion, exercise and training.

Significant alterations in plasma electrolyte concentrations have been reported in horses following prolonged exercise, resulting from loss of hypertonic sweat. Sweat was collected from 10 horses undergoing a 10 week training programme; 5 at moderate intensity, to speeds of 10 m/s and 5 at low intensity, to speeds of 5 m/s. Sweat was collected from 2 sites in response to a submaximal exercise test (30 min at 50% VO2max and during an adrenaline infusion (dose mean +/- s.d.; 0.3 +/- 0.05 g/kg over 30 min). Sweat samples were analysed for sodium, chloride, potassium, protein, magnesium, calcium and urea concentrations. Sweat produced in response to exercise and adrenaline infusion was hypertonic and showed no significant differences in composition following training. However, the [NaCl] of sweat rose with increased duration of sweating. Sweat produced in response to adrenaline infusion was more dilute than that produced in response to exercise, which may be related to sympathetic outflow during exercise.

Animals↗
PubMed1995

Activity-wheel running attenuates suppression of natural killer cell activity after footshock.

We studied whether voluntary running in an activity wheel moderates splenic natural killer (NK) cell cytotoxicity after footshock. Young (50-day) male Fischer 344 rats were randomly assigned to 1) sedentary (n = 16) or 2) activity-wheel (n = 16) groups that each received controllable or uncontrollable footshock on 2 consecutive days or 3) a sedentary home-cage control group (n = 8). Spleens and trunk blood were collected 30 min after the second footshock session. Cytotoxicity was determined by a standard 4-h 51Cr release assay. Percentages of OX6+ (B), OX8+ [T suppressor/cytotoxic (Ts/c)], W3/25+ (T helper), Thy-1.1 (Pan T cell marker), and 5C6+ (NK) cells were determined by flow cytometry. Plasma adrenocorticotropic hormone, corticosterone, and prolactin concentrations were measured by radioimmunoassay as modulators of NK activity. Percentage of specific lysis after footshock was approximately 52% of control values for sedentary animals compared with approximately 96% of control values for activity-wheel animals. The groups did not differ in percentages of NK or Ts/c cells. We conclude that voluntary activity-wheel running protects against the suppression of splenic NK activity induced by footshock. This protective effect of wheel running is not explained by an elevation in baseline NK activity; increased percentages of splenic NK or Ts/c cells; or plasma levels of adrenocorticotropic hormone, corticosterone, and prolactin.

Adrenocorticotropic Hormone↗
PubMed1995

Maximal accumulated oxygen deficit in thoroughbred horses.

Thoroughbred horses have a high aerobic capacity, approximately twice that of elite human athletes. Whereas the aerobic capacity of horses can be accurately measured, there have been no measurements of anaerobic capacity. The aim of this study was to determine whether maximal accumulated O2 deficit (MAOD) could be measured in horses and used as an estimate of anaerobic capacity, as in human athletes. Six fit Thoroughbred horses were used with the exercise protocol utilizing a treadmill set at a 10% incline. O2 uptake VO2 was measured via an open-flow system for seven submaximal speeds (3-9 m/s), and maximal VO2 (135 +/- 3 ml.kg-1.min-1) was determined. The horses performed three tests at 105 and 125% and six tests at 115% of maximal VO2. The MAOD test was performed with the treadmill accelerated rapidly from 1.5 m/s (mean acceleration time 8 s) to the calculated speed (11-14 m/s). VO2 was measured every 10 or 15 s, and the test ended when the horse no longer kept pace with the treadmill. The mean run times were 165, 98, and 57 s for intensities of 105, 115, and 125% maximal VO2. The mean MAOD values were 31 +/- 2, 30 +/- 1, and 32 +/- 2 (SE) ml O2 eq/kg for the three intensities (P > 0.05). The proportion of energy derived from aerobic and anaerobic sources was calculated from the difference between calculated O2 demand and the VO2 curve. There was no correlation between MAOD and maximal VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of treadmill incline and speed on metabolic rate during exercise in thoroughbred horses.

We examined the effect of treadmill speed and incline on O2 uptake (VO2), CO2 production, heart rate (HR), plasma lactate concentration, economy of locomotion, stride frequency, and stride length. A further aim was to examine the relationships between HR and VO2 and lactate and VO2 and whether these relationships vary with alterations in treadmill incline. The experiment was a latin square design, using five horses and five treadmill inclines (0, 2.5, 5.0, 7.5, and 10.0%). Fit Thoroughbred horses exercised for 4 min at 3 m/s at 0% slope, after which the treadmill was set to the allocated incline. Speeds tested ranged from 1 to 13 m/s. The relationships of VO2 and CO2 production with speed were curvilinear at 0 and 2.5% and linear at 5, 7.5, and 10% inclines. There was a linear relationship of HR and speed with a significant effect of incline. The plasma lactate concentration increased exponentially with speed, and there was a significant effect of incline. Stride length increased linearly and stride frequency increased in a curvilinear manner with speed but there was no effect of incline. There were linear relationships of HR with VO2 and HR with VO2 when expressed as percentage of maximum VO2 and maximum HR that were not affected by incline. The O2 cost of exercise on a 10% incline was approximately 2.5 times that for exercise on the flat. The strong relationship between the percentages of maximum HR and maximum VO2 indicates that over a wide range of exercise intensities the relative VO2 can be accurately predicted from measurements of HR.

Animals↗
PubMed1995

Somatic symptoms and HIV infection: relationship to depressive symptoms and indicators of HIV disease.

OBJECTIVE: This study examined the relationship of the somatic symptoms fatigue and insomnia with indicators of both psychiatric disturbance and HIV disease severity. METHOD: Study participants were 98 asymptomatic HIV-infected and 71 uninfected homosexual men; 82 HIV-infected and 64 uninfected men had 6-month follow-up examinations. Scales from the self-reported Profile of Mood States measured fatigue and dysphoric mood. Major depression diagnosis was determined by the Structured Clinical Interview for DSM-III-R. Selected items from the Hamilton depression and anxiety scales measured insomnia and other symptoms of depression. Performance on a battery of standardized tests determined neuropsychological function ratings. RESULTS: At study entry, complaints of fatigue and insomnia were associated with dysphoric mood, major depression, and other non-HIV-related symptoms of major depression but not with CD4 cell counts or neuropsychological functioning. Increases in levels of fatigue and insomnia over the 6-month follow-up period were associated with increases in non-HIV-related symptoms of depression and in severity of dysphoric mood. Increases in fatigue were also associated with decrements in motor functioning. Otherwise, fatigue or insomnia were not associated with HIV disease progression. CONCLUSIONS: These findings suggest that complaints of fatigue and insomnia in otherwise asymptomatic HIV-infected patients are likely to be related to psychological disturbances and possibly major depression, which can be treated. HIV-infected patients who complain of fatigue or insomnia should routinely be assessed for major depression.

Adult↗
PubMed1995

Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection.

OBJECTIVE: Previous research has documented a possible relation of stress and depression to cell-mediated immunity. The authors examined how stressful events and depression may affect key parameters of cellular immunity in subjects with and without HIV infection. METHOD: Data were collected on 99 asymptomatic HIV-positive and 65 HIV-negative homosexual men as part of an ongoing, longitudinal study. Criticisms of previous studies of psychoimmunity were addressed by 1) using a comprehensive, semistructured interview to measure the objective context of stressful events, 2) double labeling of lymphocytes with monoclonal antibodies to measure subsets of cytotoxic/suppressor T lymphocytes and natural killer (NK) cells, and 3) controlling for circadian effects and methodological factors. RESULTS: In the HIV-positive men, severe stress was significantly associated with reductions in NK cell populations and a subset of T cells thought to represent cytotoxic T effector cells, particularly the CD8+ T cells expressing the CD57 antigen. In the HIV-negative men, no clear and consistent relation between stress and immune system measures was found. Depression was not correlated with any variables in either of the groups, perhaps due to the low levels of depressive symptoms. CONCLUSIONS: The findings suggest that stress is associated with reductions in killer lymphocytes (decreased NK cell and cytotoxic T lymphocyte phenotypes). The data provide evidence that stress may alter cell populations that provide cytotoxic defense against infection in HIV-positive men and indicate that the clinical significance of stress-related changes in cytotoxic T lymphocytes and NK cells in HIV infection warrants further study.

Adaptation, Psychological↗
PubMed1995

Secondary mania: diagnosis and treatment.

Increasing evidence indicates that subtypes of bipolar disorder differ not only in symptomatology and associated clinical features, but by differences in age at onset, illness course, and response to treatment. Secondary manic states differ from typical bipolar states and are often especially difficult to treat. Although the correction of the underlying organic factors (toxic, metabolic, or infectious) may effectively reverse the manic presentation, many organic factors are not reversible (trauma, stroke, and aging), and the presence of these etiologic factors can complicate traditional antimanic treatments. Lithium may be effective for treating patients with secondary mania, but data from published studies show that in this population the associated adverse effects often limit its usefulness. Anticonvulsants appear to offer an effective alternative. Divalproex sodium, in particular, has been shown to be an effective and well-tolerated treatment in open trials in the elderly and other patient groups with secondary mania. Controlled clinical trials are necessary to confirm the efficacy and tolerability of mood-stabilizing anticonvulsants in the treatment of secondary mania.

Age of Onset↗
PubMed1994

Differential sensitivity to the induction of apoptosis by cisplatin in proliferating and quiescent immature rat thymocytes is independent of the levels of drug accumulation and DNA adduct formation.

Immature rat thymocytes readily undergo apoptosis following exposure to many different stimuli, including agents which cause DNA damage, such as the topoisomerase II inhibitor etoposide and irradiation. We have shown previously that cells isolated from the immature rat thymus are resistant to the induction of apoptosis by the DNA-damaging agent cis-diamminedichloroplatinum(II) (cisplatin) (D. L. Evans and C. Dive, Cancer Res., 53:2133-2139, 1993). More than 85% of these thymocytes are quiescent. Here, we demonstrate that following purification of the minority subpopulation of thymocytes that are proliferating, a 2-h exposure to 50 microM cisplatin resulted in rapid apoptosis with 66% apoptotic cells by 12 h. In contrast, purified, nonproliferating thymocytes treated with cisplatin exhibited control levels of apoptosis at 12 h. Both proliferating and nonproliferating thymocytes rapidly underwent apoptosis following continuous exposure to methylprednisolone (10 microM) and etoposide (10 microM). The discrepancy in the levels of apoptosis seen in proliferating and quiescent thymocytes in response to cisplatin could not be attributed to changes in total cellular levels of cisplatin or to the number of DNA-platinum adducts which were determined, respectively, by atomic absorption spectrometry and competitive enzyme-linked immunoadsorbent assay. These results imply that in contrast to engagement of thymocyte apoptosis by methylprednisolone and etoposide, where apoptosis was proliferation independent, cisplatin-induced apoptosis depends on the presence of cells in S and G2-M phases of the cell cycle. Moreover, comparison of etoposide and cisplatin responses in thymocytes suggests that DNA damage per se may not be sufficient to induce apoptosis and that the type of DNA damage is important in this regard.

Animals↗
PubMed1994

Pathways of signaling in nonspecific cytotoxic cells: effects of protein kinase and phosphatase inhibitors and evidence for membrane tyrosine phosphorylation.

The present study was done to examine the role of protein kinases (PK) and phosphatases in nonspecific cytotoxic cell (NCC) activation processes. Treatment of NCC with 30 or 60 microM H-7 prior to adding IM-9 target cells significantly inhibited cytotoxicity. A similar concentration and time-dependent inhibition response was observed following treatment with H-8. The calcium and cyclic nucleotide antagonist HA1004, however, produced a significant increase in cytotoxicity at 30 and 60 microM concentrations. Treatment with genistein produced almost 100% inhibition of NCC lysis of IM-9 targets at a 142 micrograms/ml concentration. Studies were also carried out to determine the effects of these cytotoxicity modulators on stimulus-induced responses. In all cases where the costimulus consisted of the calcium ionophore A23187, cytotoxicity was markedly increased. In experiments using subsaturating concentrations of mab 5C6 as the costimulus, genistein completely reversed (inhibited) the modulating effects of this mab. Additional evidence for protein phosphorylation was obtained by immunoprecipitation and Western blot analysis (using antiphosphotyrosine mab 4G10) of membranes from mab 5C6-stimulated NCC. The role of protein phosphorylation on cytotoxic activity was further analyzed by the use of phosphatase inhibitors. Preincubation of NCC with either sodium orthovanadate or sodium fluoride significantly increased cytotoxicity. Lithium chloride had little or no effect on the killing of IM-9 target cells. These data indicate that multiple second messenger pathways participate in NCC lytic responses, the most crucial of which appears to facilitate phosphorylation of tyrosine residues on membrane proteins.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Gait and respiration in standardbred horses when pacing and galloping.

The relationship between gait and the respiratory response to exercise was examined in five standardbred racehorses which exercised on a treadmill at a pace and a gallop. After an initial warm-up, respiratory rate and stride frequency were measured after one and two minutes of treadmill exercise at 80 per cent of maximal oxygen consumption (VO2max), after one minute at 100 per cent VO2max and after two minutes at 100 per cent VO2max (galloping horses only). Exercise at 100 per cent VO2max continued until the horses showed signs of fatigue. Arterial blood was collected during exercise and when they were fatigued for the measurement of oxygen and carbon dioxide tensions, haemoglobin saturation and pH. Venous blood temperature was also recorded. The mean (SE) time to signs of fatigue was significantly (P < 0.05) less in the pacing horses (7.2 [0.4] minutes) than in the galloping horses (8.0 [0.4] minutes). The mean (SE) resting PCO2 was 47.7 (1.9) torr. During the pacing and galloping exercises at 80 per cent and 100 per cent VO2max the PCO2 remained in the range of 41.1 to 66.8 torr, despite concurrent hyperthermia and acidosis. The PCO2 during exercise was not significantly dependent on gait or exercise intensity. The PO2 was significantly higher in pacing horses during exercise at 80 per cent VO2max (111 [7] vs 96 [6] torr). The mean (SE) arterial blood pH decreased from 7.428 (0.025) during pacing at 5 m sec-1 to 7.250 (0.042) when the horses were fatigued.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Blood lactate disappearance after maximal exercise in trained and detrained horses.

The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thoroughbred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (VO2max, ml kg-1 min-1), VLA4 (velocity at which blood lactate concentration was 4 mmol litre-1); LA8 (lactate concentration [mmol litre-1] during exercise at 8 m sec-1), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rtd). The trained horses had a significantly lower LA8 (2.1 +/- 0.1 vs 6.5 +/- 1 mmol litre-1, P < 0.01), higher VLA4 (9.8 +/- 0.2 vs 5.8 +/- 0.6 m sec-1, P < 0.01) and higher VO2max (156.3 +/- 3.8 vs 107.1 +/- 3.9 ml kg-1 min-1, P < 0.001). The value of Rtd and the time of peak lactate concentration were not significantly different.

Animals↗