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Biomedical subjects

E J Cooper

Publications and source records attributed to E J Cooper.

At least 19 recordsLinked to original sources

Oxygen tension and normalisation pressure modulate nifedipine-sensitive relaxation of human placental chorionic plate arteries.

Fetoplacental blood vessel constriction in response to reduced oxygenation has been demonstrated in placenta perfused in vitro. In pulmonary vessels, hypoxic vasoconstriction involves Ca2+ influx into smooth muscle through membrane ion channels including voltage-gated Ca2+ channels (VGCCs). We hypothesised that VGCCs are involved in agonist-induced constriction of fetoplacental resistance vessels and that their contribution is modulated by oxygen. Chorionic plate small arteries were studied using wire myography. Arteries were normalised at high (0.9 of L(13.3 kPa)) or low (0.9 of L(5.1 kPa)) stretch and experiments performed at 156, 38 or 15 mmHg oxygen. At low stretch, U46619 (thromboxane-mimetic) or KCl (smooth muscle depolarisation) constriction was greater at 38 than 156 or 15 mmHg oxygen. An L-type VGCC blocker nifedipine, inhibited KCl constriction by >85% but was less effective in U46619 constrictions (43-67%). At high stretch, nifedipine inhibition of KCl- and U46619-induced constriction was less at 15 than 38 or 156 mmHg oxygen. Oxygen did not affect constriction to U46619 or nifedipine-induced relaxation when vessels were normalised at high stretch. In conclusion, oxygen modulates chorionic plate arterial constriction at low stretch but regulation is lost at high stretch. U46619 constriction is underlain by VGCCs and nifedipine-insensitive processes; their relative contribution is influenced by oxygen.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

A comparison of bathwater and oral delivery of 8-methoxypsoralen in PUVA therapy for plaque psoriasis.

Bath-PUVA is an alternative to oral-PUVA for the treatment of psoriasis. This study compares the effectiveness of the two methods in two groups, each consisting of 17 patients with plaque psoriasis. Three patients who failed to improve with oral-PUVA were transferred to bath-PUVA and subsequently cleared. Another seven patients who returned with a further episode of psoriasis received the alternative treatment; this gave a group of 10 patients in whom a cross-over comparison was possible. In both comparisons bath-PUVA was as effective as, or more effective than, oral-PUVA and required, overall, less than 50% of the total UVA, although this saving was not as great as in previous reports. Bath-PUVA caused fewer immediate problems and was preferred by many patients. It is suitable for those taking other systemic medications and we recommend it as a valuable therapeutic option that should be available at all treatment centres.

Administration, Cutaneous↗

Amelanotic malignant melanoma following cryosurgery for atypical lentigo maligna.

Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.

Aged↗

Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices.

1. The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages ( approximately 10 and approximately 20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. 2. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a approximately 4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 microM). Similar effects were seen at high concentrations of THDOC (1-2 microM) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. 3. The effects of THDOC (1 microM) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. 4. At concentrations of THDOC likely to occur physiologically (50-100 nM), the decay time of IPSCs was also enhanced (25-50 %) in all cerebellar cell groups tested. In contrast, at 100 nM THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. 5. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the delta subunit of the GABAA receptor and possibly an increase in the alpha4 subunit.

Animals↗

Radioimmunoassay for salivary carbonic anhydrase in human parotid saliva.

A specific radioimmunoassay for human carbonic anhydrase (CA) VI has been developed and used to determine the concentrations of the enzyme in saliva. The assay detected as little as 200 pg of CA VI and the antibody used did not cross-react with CA II or other salivary proteins. The method showed an intra-assay variation of 8.5% and an inter-assay variation of 16.9%. The concentration in parotid saliva varied over a wide range (from 9.7 micrograms/ml to 121 micrograms/ml) with an average value of 47.0 +/- 39.2 (SD) micrograms/ml (n = 50). The mean secretion rate of CA VI from the combined parotid glands was 42.8 +/- 37.9 micrograms/min. CA VI represented about 3% of the total protein in parotid saliva.

Adult↗

Comparative response of the immature and mature ovine fetus to corticotrophin-releasing hormone (CRH).

The aim of this study was to address the possibility that the low concentrations of adrenocorticotrophin (ACTH) seen in the ovine fetus between 90 and 120 days of gestation could be attributed to an alteration in the sensitivity or responsiveness of the fetal pituitary to corticotrophin-releasing hormone (CRH), a key regulator of ACTH secretion. Chronically cannulated ovine fetuses at Days 104-108 (n = 11, representing fetuses from this 90-120-day period) and Days 138-142 (n = 6) of pregnancy received graded doses of ovine CRH (0.8, 1.6, 3.8 and 7.6 micrograms h-1 for 60 min each, given consecutively and in ascending order) or isotonic saline (n = 4 at both age groups studied). Arterial blood samples were taken concurrently for analysis of plasma immunoreactive CRH, ACTH and cortisol throughout the infusion to assess the pituitary-adrenal response. Regression lines describing the relationship between log.PCRH and log.PACTH were calculated for both age group studied. A significant (P < 0.001) rightward shift in the log.PCRH/log.PACTH regression line for the Day 104-108 group was found, suggesting that the ovine fetus at this age is less sensitive or responsive to exogenous oCRH than the mature Day 138-142 fetus. This decreased responsiveness could explain the low concentrations of endogenous ACTH seen during the 90-120-day period.

Adrenocorticotropic Hormone↗

Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. I. Work-load and referral patterns.

From 1987 to 1989 a campaign to promote the early detection of cutaneous malignant melanoma was conducted in the areas of seven health authorities in England and Scotland (total population 3.6 million). Data were collected on 17,155 patients attending pigmented lesion clinics (PLCs) in each study area during the campaign. After a dramatic rise in PLC referral rates in the first month of the campaign the average monthly referral rate among the target population in the study period settled to an average of 13 per 10(5), a twofold increase compared with the pre-campaign period. Over 85% of patients at all PLCs were seen within 4 weeks of referral from their general practitioners. The melanoma to non-melanoma detection ratio was (1:33). The organization of future early detection initiatives needs careful review and planning, in order to improve their effectiveness in all sections of the population, and to enable health services to cope with the increased work-load.

Adult↗

Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. II. Characteristics and incidence of melanoma.

The effect on the detection and characteristics of melanoma, resulting from the Cancer Research Campaign's health education programme to promote the early detection of melanoma in the general population, was studied from 1987 to 1989. The seven study areas in England and Scotland yield a target population of 3.6 million. Data were collected from local clinic-based registers, pathology laboratories, and the cancer registries. The average annual incidence rates of melanoma were seven and 12 per 10(5) in males and females, respectively, age-standardized to England and Wales, 1988. These rates are similar to the national figures for Scotland, where there is a national melanoma register, but higher than those reported by the English and Welsh cancer registries. The incidence was significantly higher in females than males (P < 0.001), and increased with age. Fifty-three per cent and 65% of cases in males and females, respectively, were thin (Breslow thickness < or = 1.5 mm), similar to the national figures from Scotland. No significant decrease in the incidence of late-stage tumours was found in either sex as a result of the campaign. Because of difficulties with ascertainment of cases in England, the main evaluation will focus on future trends in mortality rates for melanoma.

Adult↗

Cutaneous malignant melanoma. Publicity, screening clinics and survival--the Edinburgh experience 1982-90.

The incidence of cutaneous malignant melanoma has increased considerably in south-east Scotland over recent years. In 1987 the Cancer Research Campaign launched a project to aid the early detection, diagnosis and treatment of malignant melanoma. Edinburgh, chosen as one of seven centres in the U.K. to participate in the study, was provided with funding for a direct access pigmented lesion clinic from 1987 to 1989. The changes in the pattern of cutaneous malignant melanoma before, during and after the publicity campaign have been examined; between 1982 and 1990. The incidence of malignant melanoma doubled from 5.7 to 11.4/100,000 per annum. The percentage of thin tumours (Breslow thickness < or = 1.5 mm) increased steadily and significantly (from 43% in 1982 to 68% in 1990), but the number of thick tumours (Breslow thickness > 3.0 mm) remained constant over the same period (22 +/- 3.8). The influence of publicity was assessed using a questionnaire. Those who were influenced by publicity were significantly younger and had more thin tumours (Breslow < or = 1.5 mm) than those who were uninfluenced by publicity. Five-year survival has significantly increased from 70% in the 1982-84 cohort to 84% in the 1987-89 cohort. The effect of the publicity campaign has been beneficial, but the impact on mortality cannot yet be assessed.

Female↗

Immunomodulation at the initiation of phototherapy and photochemotherapy.

The numbers and function of circulating lymphocyte subsets are within normal ranges in patients with psoriasis and are not affected by 4 weeks of ultraviolet (UV) therapy, except for a suppression in natural killer (NK) cell activity. However, it is possible that immunomodulation might occur at the initiation of phototherapy with a return to control values on more prolonged UV exposure. Thus, in this study the responses of 15 patients with chronic plaque psoriasis undergoing broad-band UVB therapy, 10 narrow-band (311-313 nm) UVB therapy and 10 PUVA therapy were compared. In each case, samples were taken immediately before starting treatment and 1 week later. Broad-band UVB and PUVA therapy had no effect on NK activity, but a significant reduction was found in the group receiving narrow-band UVB. In vitro lymphoproliferative responses to mitogens and to herpes simplex virus antigens did not alter with therapy, except there was a significant increase in mitogen responses (at optimal mitogen concentrations only) in the narrow-band UVB group. Generally no alterations in overall percentages of circulating mononuclear cells were found in any group. Samples were taken from the epidermis of the forearm and back of the patients receiving narrow-band UVB for the quantification of urocanic acid (UCA) isomers. The total UCA concentration remained unchanged after 1 week of therapy, while the percentage of cis-UCA increased significantly at both sites in the majority of patients. However, this rise did not correlate with the decrease in NK cell activity and the two parameters may not be related causally.

Adult↗

Prolonged regional vasoconstriction produced by NG-nitro-L-arginine in conscious sheep.

Nitric oxide (NO) is a potent endothelium-derived vasodilator whose synthesis can be blocked both in vitro and in vivo by structural analogues of its precursor, L-arginine (L-ARG). We examined the dose-response profile of one such analogue, NG-nitro-L-arginine (NOLA) in conscious sheep (n = 4) and used continuous monitoring techniques to study long-term changes in mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) and the relative responsiveness of the coronary, mesenteric, renal, and hindlimb vascular beds to NOLA [10 mg/kg, intravenous (i.v.) bolus] in 5 sheep. NOLA (3 and 10 mg/kg) increased MAP at 1 h from 73 +/- 4 to 86 +/- 3 mm Hg (p < 0.05) and 73 +/- 1 to 106 +/- 8 mm Hg (p < 0.05), respectively. CO and HR decreased significantly after 10 mg/kg NOLA. Plasma endothelin (ET) level was unchanged after all doses of NOLA. Continuous monitoring of MAP, CO, and blood flow for 24 h before and after NOLA injection showed that MAP increased rapidly owing to a decrease in total peripheral conductance (TPC), with short-term reflex decreases in HR and prolonged decreases in CO and stroke volume (SV). Coronary and iliac conductances changed comparatively little. Renal conductance decreased by 43% at 80 min, but was not different from control after 6 h. The greatest and most sustained decrease in conductance, by a maximum of 55% of control levels at 110 min, occurred in the mesenteric bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of [3H]MK-801 binding in the turtle retina: an autoradiographical study.

Frozen sections (15 microns) of the turtle (Pseudemys scripta elegans) retina were incubated in 1.6 nM [3H]MK-801. Autoradiograms were generated using dry autoradiographical techniques. A band of [3H]MK-801 labelling was observed in the outer plexiform layer and cells were occasionally labelled in the inner nuclear and ganglion cell layers. This pattern of labelling was enhanced by preincubation in 1.0 mM glycine but not affected by pre-incubation in 3.0 mM N-methyl-D-aspartate (NMDA). We did not observe labelling associated with somata of bipolar cells and photoreceptors, or in the inner plexiform layer. The distribution of label suggests that [3H]MK-801 was bound to horizontal cells and occasional ganglion and/or amacrine cells. We have previously reported that exposure of L-type horizontal cells to MK-801 irreversibly altered the intracellular response of the cell to exogenous NMDA. The present finding strongly suggests that these physiological effects of MK-801 were due to specific binding of MK-801 to the NMDA receptor complex on the horizontal cell membrane.

Animals↗

Hemodynamic and renal effects of atrial natriuretic factor (99-126) in volume expanded sheep.

The renal and hemodynamic effects of atrial natriuretic factor 99-126 (ANF) were examined in hypervolemic sheep and the results compared to responses previously observed in normal isovolemic sheep. Infusion of 500 ml dextran over 60 min increased blood pressure by 6 +/- 2 mmHg, associated with increases in cardiac output and stroke volume. No change was seen in heart rate nor total peripheral resistance. Subsequent infusion of ANF at 100 micrograms/h for 60 min reduced blood pressure by 6 +/- 1 mmHg and decreased stroke volume and cardiac output. There was no change in heart rate. Total peripheral resistance decreased slightly, to a similar degree to that seen after control infusion of 500 ml dextran. Moderate increases in urine volume, sodium and chloride excretion were seen after infusion of dextran and subsequent infusion of ANF markedly enhanced these renal effects. The renal changes produced by ANF in volume expanded sheep were significantly greater than those observed in normal sheep. Although normal sheep are more sensitive to the hemodynamic than to the renal effects of ANF, after dextran pretreatment there was enhancement of the renal responses with little change in the effects on blood pressure.

Animals↗

Seminal transferrin, an index of Sertoli cell function: is it of clinical value?

To determine the clinical value of seminal transferrin measurements, transferrin concentrations in seminal plasma were determined by single radial immunodiffusion. Men with various disorders of spermatogenesis had significantly lower mean values than those with normal semen (170 micrograms/ejaculate, s.e.m. = 18.4), oligospermia (40.5 micrograms, s.e.m. = 7.2) or azoospermia due to primary seminiferous tubule failure (65.9 micrograms, s.e.m. = 29.1). In these subjects with patent genital tracts, seminal transferrin was directly correlated with sperm concentration and indirectly correlated with serum FSH levels. Seminal transferrin increased following gonadotrophin treatment of men with gonadotrophin deficiency from 19.6 micrograms (s.e.m. = 5.5) to 108.6 micrograms (s.e.m. = 31.7). Patients with genital tract obstructions also had low levels; vasal agenesis (21.8 micrograms, s.e.m. = 5.6), vasectomy (48.5 micrograms, s.e.m. = 21.0), epididymal obstruction (46.6 micrograms, s.e.m. = 7.1). These results confirm that most seminal transferrin comes from the testes and reflects Sertoli cell function. However, there is a very wide range of transferrin levels in normal semen and a number of normospermic samples have low values similar to those seen with abnormal Sertoli cell function or obstruction. Thus, measurement of seminal transferrin is of limited diagnostic value.

Genital Diseases, Male↗

Protein carboxyl methylase in asthenospermia.

Protein carboxyl methylase (PCM) activity was measured in human spermatozoa of 16 normal fertile men and 26 men with various forms of asthenospermia. PCM activities were in the range 14-635 pmol/min per 10(9) sperm. Six men with idiopathic asthenospermia had low PCM activity but the defect of sperm motility was not severe (sperm motility 25-50%). One man with zero sperm motility and sparse mitochondria in the midpiece spiral had high PCM activity. Two men, one with idiopathic asthenospermia and the other with asthenospermia following vasoepididymostomy, also had high PCM activities. PCM activity did not correlate with motility or motility index but there was a correlation between PCM activity and the proportion of immature forms in semen. Thus, the relationship between PCM activity and low motility of sperm is not simple and other cells also contribute to overall seminal PCM activity.

Epididymitis↗