Search PubMed⌕ Search

Biomedical subjects

D P Evans

Publications and source records attributed to D P Evans.

At least 19 recordsLinked to original sources
PubMed2001

CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans.

Galectin-1 induces death of immature thymocytes and activated T cells. Galectin-1 binds to T cell-surface glycoproteins CD45, CD43, and CD7, although the precise roles of each receptor in cell death are unknown. We have determined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45(+) BW5147 T cells lacking the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) were resistant to galectin-1 death. The inhibitory effect of CD45 in C2GnT(-) cells appeared to require the CD45 cytoplasmic domain, because Rev1.1 cells expressing only CD45 transmembrane and extracellular domains were susceptible to galectin-1 death. Moreover, treatment with the phosphotyrosine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate(V) enhanced galectin-1 susceptibility of CD45(+) T cell lines, but had no effect on the death of CD45(-) T cells, indicating that the CD45 inhibitory effect involved the phosphatase domain. Expression of the C2GnT in CD45(+) T cell lines rendered the cells susceptible to galectin-1, while expression of the C2GnT in CD45(-) cells had no effect on galectin-1 susceptibility. When CD45(+) T cells bound to galectin-1 on murine thymic stromal cells, only C2GnT(+) T cells underwent death. On C2GnT(+) cells, CD45 and galectin-1 co-localized in patches on membrane blebs while no segregation of CD45 was seen on C2GnT(-) T cells, suggesting that oligosaccharide-mediated clustering of CD45 facilitated galectin-1-induced cell death.

Animals↗
PubMed1991

Effects of calcium buffering on the synthesis of the 26-kDa heat-shock protein family.

We have reported on the effect of heat in C127 cells having various basal levels of the Ca(2+)-binding proteins calmodulin (CaM) or parvalbumin [Evans, Simonette, Rasmussen, Means, and Tomasovic, J. Cell. Physiol. 142, 615-627 (1990)]. These studies suggested that induction of the synthesis of 26-kDa heat-shock protein (hsp-26) depended on increased intracellular free Ca2+ [Ca2+]i and that induction was abrogated by increased Ca(2+)-binding capacity. To evaluate further the role of [Ca2+]i in mediating the response to hyperthermia and the potential for Ca(2+)-buffering to affect these processes, we loaded C127 parental cells with the Ca2+ chelators BAPTA or quin-2 (5 microM for 60 min) and then immediately heated the cells (30 min at 43 degrees C) and labeled them (3 h at 37 degrees C) with [3H]leucine. Measurements of [Ca2+]i with quin-2 and fura-2 showed that an increase in [Ca2+]i occurred with this heat dose, but that the quin-2 buffered that increase. Two-dimensional gels showed that cells loaded with BAPTA and quin-2 had a reduced rate of synthesis of the most basic (nonphosphorylated) hsp-26a isoform. The apparent synthesis of the more acidic isoforms (hsp-26b, hsp-26c) was less affected, but labeling studies with 32P showed this reflected continued accumulation of these phosphorylated isoforms, especially the most highly phosphorylated hsp-26c. Although it reduced hsp-26a synthesis, the temporary buffering of [Ca2+]i did not alter the subsequent expression of heat killing or the extent of thermotolerance significantly, possibly because phosphorylated hsp-26 was still generated. These data support the hypothesis that perturbations of [Ca2+]i directly modulate induction of hsp-26a synthesis.

Acclimatization↗
PubMed1990

Altered synthesis of the 26-kDa heat stress protein family and thermotolerance in cell lines with elevated levels of calcium-binding proteins.

Using a bovine papilloma virus-based vector, mouse mammary adenocarcinoma cells have been transformed to express elevated amounts of functional calmodulin (CaM) (Rasmussen and Means, 1987) and another Ca2(+)-binding protein, parvalbumin (PV) (Rasmussen and Means, 1989) that is not normally synthesized in these cells. Parental cells (C127) and cells transformed by the vector alone (BPV-1), the vector containing a CaM gene (CM-1), or the vector containing parvalbumin (PV-1) were used to study the effect of increased synthesis of Ca2(+)-binding proteins on heat-stress protein (HSP) synthesis and cell survival following heating at 43 degrees C. The induction, stability, and repression of the synthesis of most HSPs after 43 degrees C heating was not significantly affected by increased amounts of Ca2(+)-binding proteins, but the rate of synthesis of all three isoforms of the 26-kDa HSP (HSP26) was greatly reduced. C127 cells, which have about one half as much CaM as do BPV-1 cells, synthesized the most HSP26. CM-1 cells, which have more than fourfold higher levels of CaM than do BPV-1 cells, had a rate of synthesis of HSP26 approaching that of unheated cells. BPV-1 cells, with a two-fold increase in CaM, were intermediate in HSP26 synthesis. This effect on HSP26 synthesis may be largely related to the Ca2(+)-binding capacity of CaM rather than to a specific CaM-regulated function, since PV-1 cells also showed reduced rates of HSP26 synthesis. Survival experiments showed that reduced HSP26 synthesis in cells with increased amounts of Ca2(+)-binding proteins did not significantly alter intrinsic resistance to continuous 43 degrees C heating. Thermotolerance was not reduced and appeared to develop more rapidly in CM-1 and PV-1 cells. These results suggest that (1) the signal for HSP26 synthesis can be largely abrogated by elevated Ca2+ binding protein levels, and (2) if these HSPs are involved in thermotolerance development, that function may be associated with intracellular Ca2+ homeostasis.

Animals↗
PubMed1990

Affinity isolation of heat-shock and other calmodulin-binding proteins following hyperthermia.

The interaction of calmodulin (CaM) with heat-shock and other binding proteins was studied in rat adenocarcinoma cells. Cells were equilibrium-labeled for 48 h prior to heating for 1 h at 43 degrees C, or pulse-labeled for 2 h at 37 degrees C after heating, to monitor the effect of heat on the affinity of CaM-binding proteins synthesized under these conditions. A CaM antagonist shown to sensitize to heat killing, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], was used in competition assays to help monitor any changes in affinity. We found that heating tended to reduce the CaM-binding of proteins synthesized before heating relative to their 37 degrees C controls and proteins synthesized after heating tended to have increased binding relative to their respective controls. Members of the heat-shock protein (hsp) 90-, 70-, and 26-kDa families were among the proteins that bound to CaM and were eluted by W-7. The peak elution fractions for the hsp's and other cellular proteins varied, but hsp-70 eluted in the early fractions. The hsp-70 family was also found to be among a number of W-7-binding proteins. We conclude that the assumption that CaM antagonists potentiate killing of heated cells solely by competing nonspecifically for CaM-binding protein sites on CaM does not explain the process completely. These antagonists could also act by competing for CaM-binding sites with specific proteins whose interaction with CaM is important for survival following heating, or by directly binding to other proteins whose function is important for survival and inhibiting their activity. We do not have sufficient data to discern the predominant mechanism among these possibilities, but we believe all are likely to occur in heated cells and speculate that inhibition of the functions of the hsp-70 family is important in several of these antagonist actions.

Adenocarcinoma↗
PubMed1986

Survival of rat mammary tumor cell clones and DNA strand damage following adriamycin treatment.

Tumor cell subpopulations have been shown to be heterogeneous in a number of phenotypic characteristics, including responses to cytotoxic drugs. This phenotypic heterogeneity has been used here to study mechanisms associated with Adriamycin (doxorubicin HCl)-induced cytotoxicity. Clonogenic survival and alkaline elution methods were employed to examine the response of two tumor cell subpopulations to Adriamycin. The cells were derived from a primary 13762NF rat mammary adenocarcinoma (clone MTC) and a lung metastasis in the same animal (clone MTLn3). The MTC cells were significantly more resistant to Adriamycin than were the MTLn3 cells; the dose effective in reducing cell survival by 50% was 10-fold higher. Protein-associated DNA strand breakage assayed by alkaline elution was dose-dependent in both clones, and MTC cells were again more resistant to break induction than were MTLn3. These results showed that clonal tumor subpopulations isolated from a primary tumor and its metastases possessed different intrinsic survival responses to Adriamycin treatment in vitro and that this survival response correlated with Adriamycin-induced production of protein-associated DNA single-strand breaks.

Animals↗
PubMed1985

European double-blind multicenter study comparing isoxicam and indomethacin in treatment of degenerative joint disease.

A three-month, double-blind, indomethacin-controlled, European multicenter study of isoxicam (Maxicam), a nonsteroidal anti-inflammatory drug, was conducted in 365 patients who had degenerative joint disease of the knee or hip. Patients were randomly assigned to receive one of two treatments: isoxicam, 133 mg per day (Week 1), 166 mg per day (Week 2), and 200 mg per day (Weeks 3 to 12); or indomethacin, 100 mg per day (Week 1), 125 mg per day (Week 2), and 150 mg per day (Weeks 3 to 12). Efficacy measurements included, for patients with knee or hip involvement, intensity of starting pain on motion, pain on walking, night pain, overall assessment by physician and patient, and global assessment at the end of treatment; maximal extension and flexion (knee); extent of pain-free abduction and maximal abduction (hip). The results of the efficacy measurements favor isoxicam over indomethacin, although the differences are not statistically significant. The isoxicam group had significantly fewer adverse reactions than the indomethacin group.

Administration, Oral↗
PubMed1980

A model of reflex tracheal constriction in the dog.

1 A tracheal pouch with its nerve and blood supply intact has been prepared in situ in dogs. 2 Mechanical stimulation of the upper airways in dogs anaesthetized with chloralose induced a consistent increase in pouch pressure which was abolished by bilateral vagal section. 3 The response of the pouch following mechanical stimulation of the airways was abolished by intravenous pentobarbitone, atropine, administered systemically or when present in the pouch, and tetracaine, applied to the stimulus area or when present in the pouch. 4 Salbutamol had no inhibitory effects on the response regardless of its route of administration. 5 These results suggest that the increase in pouch pressure following mechanical stimulation of the upper airways is mediated by a vagal reflex arc. 6 The technique may distinguish between drugs the site of action of which is at the afferent or efferent end of this reflex arc.

Airway Resistance↗
PubMed1980

A model of irritant-induced bronchoconstriction in the spontaneously breathing guinea-pig.

1 Inhalation of an aqueous aerosol of citric acid caused bronchoconstriction in anaesthetized guinea-pigs which was abolished by bilateral vagal section. 2 Conscious guinea-pigs developed slow, laboured breathing within 90 s of exposure to citric acid aerosol. The onset of this pattern of breathing was delayed by prior aerosol administration of atropine, ipratropium bromide, isoprenaline and tetracaine. 3 The data suggest that exposure of guinea-pigs to citric acid may be a useful model of reflex bronchoconstriction.

Animals↗
PubMed1980

Medicines of choice in low back pain.

The marketed formulations of 6 analgesic preparations were compared in the treatment of patients suffering from acute exacerbations of low back pain using a crossover trial of balanced incomplete block design. Sixty out-patients with symptoms resulting from a mechanical or degenerative condition were each prescribed 3 drugs which were administered consecutively for 1 week each. The medications (and daily dosages) were coded as A --aspirin (3600 mg), B --dextropropoxyphene plus paracetamol (260 mg plus 2600 mg), C --indomethacin (150 mg), D --mefenamic acid (1500 mg), E --paracetamol (4000 mg), and F --phenylbutazone (300 mg). Daily pain scores were significantly lower (p less than 0.05) during treatment D than during treatments E and B, and significantly lower (p less than 0.05) during treatment A than during treatment B. There were large and significant differences between treatments in the percentages of recommended doses acceptable to the patients and in the number of defaults from the prescribed regimens. The patients chose F and D significantly more (p less than 0.05) often than A. Overall, there were consistently superior performances by mefenamic acid and phenylbutazone with little to choose between the two.

Acetaminophen↗
PubMed1978

Lumbar spinal manipulation on trial. Part I--clinical assessment.

Thirty-two patients with chronic low back pain were treated three times at weekly intervals with rotational manipulation. Patients with femoral or sciatic root pain were included provided they did not exhibit root compression signs. Background therapy of codeine phosphate was administered throughout. There was a significant increase in spinal flexion measured clinically during the three-week period of manipulation followed by a significant decrease in the three-week period after manipulation. The first week of manipulative treatment was more painful than the corresponding week in the control group but in the second and third weeks there was less pain in the manipulated group. Pain scores were reduced to a significant degree within four weeks of starting treatment only in the group manipulated in the first treatment period. Patients benefitting subjectively from manipulation were more likely to be older and to have had symptoms for a shorter period than those not deriving benefit. The age of onset of symptoms was significantly later in the responders.

Adult↗
PubMed1978

Lumbar spinal manipulation on trial. Part II--radiological assessment.

In a trial of manipulation for chronic low back pain, radiographs of the lumbar spine and radiographic assessment of spinal motion were of no value in predicting or assessing the response of the patients to manipulation. Although radiography of the lumbar spine is a commonly requested investigation, it contributes little to the management of such patients except to exclude serious spinal pathology before any form of physical treatment is commenced.

Adult↗
PubMed1978

Studies on the role of histamine and 5-hydroxytryptamine in immunity against the nematode Trichostrongylus colubriformis. IV. Inhibition of the expulsion of worms transplanted into the duodenum of immune guinea pigs.

Significant numbers of fourth larval stage Trichostrongylus colubriformis from sheep donors are expelled from the small intestine of T. colubriformis-immune guinea pigs within 8 h of transplantation into this organ. This model system for the immune expulsion of gastrointestinal nematode parasites was used in the current experiments to examine the effect of drugs recently shown to modify the release of histamine. The experiments showed that worm expulsion was inhibited by the beta-adrenergic agonists salbutamol and isoprenaline, the phosphodiesterase inhibitors aminophylline and ICI 63,197, the antiallergic drug ICI 74,917 and the antihistamine mepyramine. The beta-blocker propranolol prevented inhibition of worm expulsion following salbutamol treatment and there was some evidence of synergistic action between salbutamol and ICI 63,197. The results support previous findings suggesting an important role for histamine release in the effector mechanism of the immune response of guinea pigs against the parasitic nematode T.colubriformis.

Albuterol↗
PubMed1977

Human eosinophils, acidic tetrapeptides (ECF-A) and histamine. Interactions in vitro and in vivo.

The ECF-A acidic tetrapeptides Val-Gly-Ser-Glu, Ala-Gly-Ser-Glu and the analogue Val-Gly-Asp-Glu were selectively chemotactic for human eosinophils over a narrow dose range although eosinophils from different individuals varied in their dose-response pattern. Histamine abrogated the chemotactic properties of the individual tetrapeptides. When Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu were combined in various concentrations the resultant chemotaxis was either negligible or no greater than that produced when each peptide was tested separately. Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu both promoted eosinophil accumulation when applied to the abraded skin of man or i.d. to the marmoset. Biopsies of marmoset skin revealed that peptide-induced eosinophilia was not associated with mast-cell degranulation. Histamine, which was chemotactic in vitro, did not lead to appreciable eosinophil accumulation in vivo, and combinations of histamine and the acidic tetrapeptides evoked little or no cutaneous eosinophil infiltration either in man or the marmoset. These studies suggest that there is a complex interaction between histamine and the ECF-A tetrapeptides; however, the tetrapeptides alone can promote the recruitment and localization of eosinophils by a mechanism apparently independent of mast-cell degranulation.

Animals↗
PubMed1976

The mechansim of tachyphylaxis to ICI 74,917 and disodium cromoglycate.

Pre-incubation in vitro of sensitised peritoneal mast cells for 10 min with either ICI 74,917 (10-5 M) abolished the ability of either drug to inhibit histamine release when subsequently presented to the cells at the same time as antigen. In the case of disodium cromoglycate, tachyphylaxis was abolished by washing the cells after pre-incubation with the drug. The failure to abolish tachyphylaxis to ICI 74,917 was due to the high pre-incubation concentration employed, as at lower concentrations (10-8 M) tachyphylaxis to ICI 74917 was readily abolished by washing. Tachyphylaxis to these anti-allergic agents may be related to a physical blocking of drug receptor sites on or in mast cells.

Animals↗
PubMed1975

Inhibition of immediate hypersensitivity reactions in laboratory animals by a phenanthroline salt (ICI 74,917).

1. The activity of a new anti-allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea-pig. 2. Following intravenous administration, I.C.I. 74,917 inhibits in a dose-dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat-labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate. 3. To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect. 4. Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE-like antibody, is reduced in the presence of I.C.I. 74,917. 5. Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5-hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat-stable homocytotropic or heterologous (guinea-pig) antibodies. 6. Although not a bronchodilator in the guinea-pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen-induced bronchospasm was demonstrated in the Konzett-Rossler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea-pig. 7. I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea-pigs or to a guinea-pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide. 8. These results indicate that in the rat, mouse and guinea-pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.

Anaphylaxis↗
PubMed1975

Inhibition of immediate hypersensitivity reactions in the rat by ICI 74,917 and disodium cromoglycate.

ICI 74,917, a potent inhibitor of IgE-mediated passive cutaneous anaphylaxis (PCA) in the rat, exhibited tachyphylaxis in that pre-dosing sensitised rats with a high dose of compound reduced the inhibitory effect on rat PCA of a second dose given at challenge. This phenomenon was most apparent when the pre-dose-challenge dose interval was 15--60 min. Similar findings were obtained using antigen-induced histamine release in vitro from rat peritoneal cells. In these respects, ICI 74,917 was similar to disodium cromoglycate (DSCG) although DSCG appeared less effective in inducing tachyphylaxis than ICI 74,917. There was no evidence in vivo or in vitro that a high dose of either DSCG or ICI 74,917 enhanced the activity of a second low dose of either drug given at challenge.

Animals↗
PubMed1975

Prophylaxis and treatment of experimental anaphylaxis in cattle by sodium meclofenamate.

Sodium meclofenamate was compared to saline for efficacy in preventing and treating experimentally induced, acute, systemic anaphylaxis in cattle. Respiratroy changes were shown to be reduced to the greatest extent. Lacrimation and collapse were not affected. The timing and routes of administration giving maximum efficacy were those which gave maximum plasma levels of the drug closest to the time of exposure of the animal to the specific antigen.

Administration, Oral↗