Search PubMed⌕ Search

Biomedical subjects

P Evans

Publications and source records attributed to P Evans.

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

Structure-activity relationships of 4-(phenylethynyl)-6-phenyl-1,4-dihydropyridines as highly selective A3 adenosine receptor antagonists.

4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure-activity relationships at various positions of the dihydropyridine ring (the 3- and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed synthetically. Using the combined protection of the 1-ethoxymethyl and the 5-[2-(trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5-position allowing various substitutions. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A2A receptors. Structure-activity analysis at adenosine receptors indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position resulted in, at most, only moderate selectivity for A3 adenosine receptors. Ring substitution (e.g., 4-nitro) of the 4-phenylethylnyl group did not provide enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At the 3-position of the dihydropyridine ring, esters were much more selective for A3 receptors than closely related thioester, amide, and ketone derivatives. A cyclic 3-keto derivative was 5-fold more potent at A3 receptors than a related open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters and a series of substituted benzyl esters were prepared and tested. (Trifluoromethyl)-, nitro-, and other benzyl esters substituted with electron-withdrawing groups were specific for A3 receptors with nanomolar Ki values and selectivity as high as 37000-fold. A functionalized congener bearing an [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the synthesis of biologically active conjugates.

Adenosine↗
PubMed1997

The origin of lower extremity deep vein thrombi in acute venous thrombosis.

BACKGROUND: It has been taught that most deep venous thromboses (DVT) begin in the deep veins of the calf and propagate proximally. The duplex ultrasound scan, with its noninvasive characteristics and accuracy, has brought this premise into question. The purpose of this study was to determine the pattern and distribution of acute DVT as well as the different types of thrombi. METHODS: We performed a retrospective review of all duplex scans ordered for a diagnosis of acute lower extremite DVT at a 200-bed hospital over a 5-year period. RESULTS: There were 3,585 examinations performed on 2,654 patients. There were 461 patients (17.4%) with a venous thrombosis. Four types of venous thrombosis were identified: an isolated thrombosis in one venous segment (34%), a thrombosis extending over two or more contiguous segments (52%), multiple thromboses in noncontiguous segments (8%), and bilateral thrombi in different locations (6%). CONCLUSION: Calf vein thrombi represented 24% of all DVT. Thrombi in the major veins of the thigh and popliteal space without calf involvement were present in 49% of all DVT. The data in this paper indicate that most significant deep venous thromboses do not begin in the calf but instead arise in the proximal thigh or groin.

Acute Disease↗
PubMed1997

Maternal serum vascular endothelial growth factor during early pregnancy.

1. The objectives of the study were: (i) to investigate the serum concentrations of vascular endothelial growth factor (VEGF) in pregnant and non-pregnant women; and (ii) to study the relationship between the levels of maternal serum VEGF and the serum concentrations of human chorionic gonadotrophin (hCG) and progesterone during the first trimester. 2. Total immunoreactive VEGF was measured by competitive RIA using recombinant human VEGF165 and a polyclonal antiserum. Serum VEGF was measured in 60 non-pregnant women of childbearing age. These data were compared with serum VEGF measured in 363 women between 41 and 91 days of gestation. 3. The median serum VEGF concentration was 1.10 micrograms/l (interquartile range 0.91-1.30) in the nonpregnant women and 2.13 micrograms/l (interquartile range 1.62-2.77) in the pregnant women. Serum levels of VEGF were significantly higher among the pregnant cohort (P < 0.0001). Serum VEGF concentration was positively correlated with gestational age, increasing until ten completed weeks of pregnancy. Serum VEGF was negatively correlated with maternal height and weight, and positively correlated with serum hCG and serum progesterone (P < or = 0.0001 in all cases). Serum VEGF was lower in the pregnant women who smoked (P = 0.06). 4. Our data show a positive and highly significant correlation between maternal serum levels of VEGF and hormones reflecting placental function (hCG, progesterone). We speculate that VEGF production is increased by progesterone and hCG, and that VEGF has a positive influence on trophoblast development. VEGF may also be involved in the initiation of the maternal cardiovascular adaptation to pregnancy.

Adult↗
PubMed1996

Do human atherosclerotic lesions contain nitrotyrosine?

Nitrotyrosine has been widely used as a marker of peroxynitrite formation in normal and diseased tissues. However, studies of normal human aortic intima and atherosclerotic lesions at various stages of development failed to reveal its presence except in a very few specimens of both normal and diseased tissues. The techniques used to detect nitrotyrosine-HPLC with photodiode array detection and Western blotting- were able to identify nitrotyrosine after chemical nitration. Hence peroxynitrite may not be as important in the initiation of atherosclerosis as has commonly been proposed.

Antibody Specificity↗
PubMed1996

Urinary output of endogenous monoamine oxidase inhibitory activity is related to everyday stress.

The MAO A and B inhibitory components of urinary tribulin were investigated in normal individuals (11 males and 24 females, mean age +/- SD; 27.1 +/- 4.5 years) in relation to everyday stress. Volunteers collected a urine sample at the same time (late evening) on five days over a single week. On each occasion subjects also completed a mood adjective checklist which measured perceived stress levels over the day in question. For each subject all daily measures were aggregated. Mean individual urinary MAO A and B inhibitory activity was found to be positively correlated with stress scores both before (r = 0.38, p < 0.05 and r = 0.37, p < 0.05 respectively, n = 35) and after (r = 0.35, p < 0.05 and r = 0.33, p < 0.05 respectively, n = 35) correction for the effects of urinary volume. These results suggest that in normal healthy individuals high endogenous MAO inhibitory activity in the urine is indicative of a relatively enduring state of everyday stress.

Adult↗
PubMed1996

Salivary monoamine oxidase A and B inhibitory activities correlate with stress.

MAO A and B inhibitory activities were determined, for the first time, in saliva samples. Saliva was collected on 4 occasions from 11 normal subjects (students) before and after delivering an important assessed oral presentation, a naturalistic stress inducing procedure. The first sample was collected 30 minutes before the presentation and 3 more within 40 minutes of finishing the presentation. At each collection a mood adjective checklist was completed. Mean MAO A inhibitory activity correlated with mean MAO B inhibitory activity (r = 0.872, p < 0.001, n = 11). Within subject analysis revealed a positive correlation between MAO A and B inhibitory activity and stress (r = 0.400, p < 0.01, n = 44 and r = 0.255, NS, n = 38 respectively). Mean MAO A and B inhibitory activity correlated with mean stress (r = 0.535, NS, n = 11 and r = 0.673, p < 0.05, n = 11 respectively). Peak MAO A and B inhibitory activities correlated with peak stress (r = 0.636, p < 0.05, n = 11 and r = 0.754, p < 0.01, n = 11, respectively). Salivary MAO A and B inhibitory activities were independent of salivary flow rate. We conclude that measurement of MAO A and B inhibitory activities in saliva is preferable to traditional urinary measures as sampling is less invasive and also supports a clear relationship to stress in normal individuals.

Female↗
PubMed1996

Fluorescent polymerase chain reaction of a panel of CA repeats on chromosome 6 in the indolent phase of follicular centre cell lymphoma.

Twenty-four cases of histologically defined follicle centre cell (FCC) lymphoma have been examined for allele imbalance at 19 microsatellite loci spanning the length of chromosome 6, including six markers within the major histocompatibility complex (MHC), using fluorescent polymerase chain reaction (PCR) to amplify microsatellites. Nineteen cases were observed in which imbalance of one or more markers on chromosome 6 had occurred (79%). The frequency of allele imbalance was significantly higher on 6p than 6q, and two regions of deletions, 6p24-25 and 6p21.3-23, were identified in which the loci showed a significantly high allele imbalance frequency.

Chromosomes, Human, Pair 6↗
PubMed1996

Microsatellite instability in follicle centre cell lymphoma.

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.

Chromosomes, Human, Pair 14↗
PubMed1996

Mobilization of Philadelphia-negative peripheral blood mononuclear cells in chronic myeloid leukaemia using hydroxyurea and G-CSF (filgrastim).

A relatively simple and non-toxic out-patient-based regimen for the mobilization of Philadelphia-negative (Ph-ve) mononuclear cells in chronic myeloid leukaemia (CML) was evaluated in 10 patients, nine in stable chronic phase and one in accelerated phase. They received oral hydroxyurea at a mean dose of 3.5 g/m2 daily for 7 d, followed by 300 micrograms of G-CSF daily until the last day of harvesting. In the nine chronic-phase patients the mean number of days from the end of hydroxyurea to the commencement of harvesting was 14.5 (range 10-18). The patient in accelerated phase recovered and was harvested after 6 d. The mean number of aphereses performed was 3.4. Adequate numbers of stem cells were obtained in 9/10 patients judged by our usual criteria. Side-effects were mild in comparison to published intravenous schedules. No patients lost their hair. Five (50%) patients required admission with neutropenic fever which responded to antibiotics in all cases. Four (40%) patients developed a transient rash and four (40%) experienced mild oral mucostis. This level of toxicity enabled half of the patients to be treated entirely on an out-patient basis. The harvest products were analysed for cells belonging to the leukaemic clone by conventional cytogenetics, FISH and PCR. All were PCR positive. The mean Ph positivities by cytogenetics and FISH were comparable at 18.1% and 15% respectively. Half the patients had > 98% normal metaphases. We conclude that this approach is comparable in efficacy to published intravenous regimens and significantly less toxic. It can be safely used at diagnosis before interferon therapy commences.

Administration, Oral↗
PubMed1996

Hook wire localization of inferior lesions in the breast.

Inferior lesions in the breast can be difficult to localize pre-operatively using the hook wire technique as the equipment does not readily allow an approach from below. Distorting the breast by rolling it against the cassette holder displaces an inferior lesion into a lateral position. The lesion can then be easily localized by the shortest needle path.

Breast Neoplasms↗
PubMed1996

Secretory immunoglobulin A and cardiovascular responses to acute psychological challenge.

Cardiovascular activity and secretory immunoglobulin A (sIgA) in saliva were recorded at rest, during a 30-min computer game task, and during subsequent recovery. Blood pressure (BP) rose and remained elevated during the task and returned to resting levels during recovery. This pressor response was produced by increased total peripheral resistance rather than increased cardiac output. SIgA secretion rate also increased during the task, although the effect proved significant only toward the end of the task. As such, the data provide preliminary indication that sIgA is sensitive to acute psychological challenge in the laboratory. Although correlational analyses revealed that sIgA reactions were stable, they were not significantly correlated with pressor reactions. The influence of task uncertainty was explored by comparing individuals who had previously played the computer game with those who had not. Task-induced increases in BP and sIgA were a feature of individuals new to the computer game. In contrast to these novice players, experienced players showed minimal increases in BP and no increases in sIgA.

Journal Article↗