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M J Wheeler

Publications and source records attributed to M J Wheeler.

At least 19 recordsLinked to original sources
PubMed2003

Genomic organization of the Papaver rhoeas self-incompatibility S(1) locus.

The self-incompatibility (SI) response in Papaver rhoeas depends upon the cognate interaction between a pollen-expressed receptor and a stigmatically expressed ligand. The genes encoding these components are situated within the S-locus. In order for SI to be maintained, the genes encoded by the S-locus must be co-inherited with no recombination between them. Several hypotheses, including sequence heterogeneity and chromosomal position, have been put forward to explain the maintenance of the S-locus in the SI systems of the Brassicaceae and the Solanaceae. A region of the Papaver rhoeas genome encompassing part of the self-incompatibility S(1) locus has been cloned and sequenced. The clone contains the gene encoding the stigmatic component of the response, but does not contain a putative pollen S-gene. The sequence surrounding the S(1) gene contains several diverse repetitive DNA elements. As such, the P. rhoeas S-locus bears similarities to the S-loci of other SI systems. An attempt to localize the P. rhoeas S-locus using fluorescence in situ hybridization (FISH) has also been made. The potential relevance of the findings to mechanisms of recombination suppression is discussed.

Amino Acid Sequence↗
PubMed1999

The effect of melatonin administration on pituitary hormone secretion in man.

OBJECTIVE: Evidence is accumulating that the nocturnal increase in melatonin may influence pituitary hormone secretion. The aim of this study was to determine the effect of exogenous melatonin, in concencetrations spanning the physiological range, on the release of pituitary hormones in man during daylight hours. DESIGN: A double blind, randomized, crossover study. SUBJECTS: Eight healthy male volunteers with a mean age of 21 +/- 0.5 years were studied on four occasions, observations being made after the adminstration of melatonin in doses of 0.05, 0.5 or 5.0 mg or placebo. They refrained from taking heavy exercise, alcohol and from smoking for 24 h prior to the study. MEASUREMENTS: Serum cortisol, growth hormone, prolactin and plasma oxytocin, vasopressin, sodium, osmolality and packed cell volume were measured in samples taken at 30 minutes intervals for 150 minutes after the administration of melatonin. RESULTS: Melatonin produced dose-dependent changes in circulating concentrations of oxytocin and vasopressin, the 0.5 mg dose being stimulatory, while 5.0 mg was inhibitory. These two doses stimulated growth hormone release, while there was no significant effect on prolactin or cortisol release. CONCLUSIONS: These results confirm that the nocturnal increase in melatonin could contribute to the patterns of oxytocin, vasopressin and growth hormone release seen over 24 h.

Adult↗
PubMed1999

The pituitary-adrenal axis in idiopathic retinal vasculitis.

AIMS: To determine whether patients with idiopathic retinal vasculitis have altered production of cortisol and dehydroepiandrosterone sulphate (DHEA-S), and whether differences in these variables occur between those who are sensitive (SS) and resistant (SR) to steroids. METHODS: 20 patients with retinal vasculitis (off treatment) and 10 control subjects were prospectively recruited. Morning cortisol and DHEA-S levels were measured, and cortisol secretion rates and short synacthen tests (SST) carried out in patients before treatment, when on prednisolone 20 mg/day, and in controls. RESULTS: There were no differences in any variables between patients and controls. For retinal vasculitis patients pretreatment, the SST was lower in SR patients (p=0.02). More of the SR patients had ischaemic retinal vasculitis ( p<0.001). CONCLUSIONS: Cortisol and DHEA-S are not involved in the pathogenesis of retinal vasculitis. SR in retinal vasculitis may be associated with a defective hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed1998

The dexamethasone suppression test in schizophrenia.

BACKGROUND: Cortisol non-suppression following the dexamethasone suppression test (DST) has been found to a variable extent in schizophrenia. The aetiology is unclear but may be related to depression or negative symptoms. METHODS: The DST was administered to 64 patients with DSM-IV schizophrenia. All patients were screened for DSM-IV major depression and rated on the Hamilton Rating Scale for Depression (HRSD), Scale for Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: DSM-IV criteria for major depression was fulfilled by 36% of the patients and 42% of patients had a history of parasuicide. Four patients had undetectable levels of dexamethasone and were excluded from the endocrine analyses. Only one remaining patient had a cortisol level above the cut-off point (> 138 nmol/l), indicating escape from dexamethasone suppression. The post-dexamethasone cortisol level correlated significantly with HRSD and BPRS scores but not with the SANS. The SANS and HRSD scores were not correlated, but they were independently correlated with the BPRS score. CONCLUSIONS: In contrast to some other work, rates of dexamethasone non-suppression were very low; together with the high rates of depression, this suggests that depression in schizophrenia may have a different neuroendocrine profile from major depressive disorders. Failure to measure dexamethasone levels can be misleading.

Adult↗
PubMed1998

Melatonin administration and pituitary hormone secretion.

OBJECTIVE: The relationship between the pineal gland and pituitary function remains controversial, while the role of melatonin in the adaptation of the organism to the light-dark cycle of the environment is becoming increasingly recognized. The aim of this study was to investigate the effect of a manipulation of the melatonin rhythm on pituitary hormone secretion in man. DESIGN: Double-blind controlled clinical study. SUBJECTS: Ten adult healthy male volunteers, aged 21-33 years, were studied on two occasions: once after the administration of melatonin 5 mg orally for 4 days at 1700 hours and once after the administration of placebo, at similar times. On the day of each study the subjects undertook their normal duties but refrained from taking heavy exercise, from smoking and drinking alcohol. MEASUREMENTS: Serum cortisol, growth hormone, prolactin and plasma vasopressin, oxytocin, melatonin, sodium, potassium, osmolality and packed cell volume were measured over the following 24 hours. RESULTS: The cortisol peak was advanced and prolactin release increased after melatonin administration, while growth hormone was not affected. Vasopressin and oxytocin levels were found to increase during the night in the control study, but the period of the nocturnal increase in vasopressin concentrations was reduced after the administration of melatonin and the nocturnal increase of oxytocin was absent. CONCLUSION: Altering the melatonin rhythm may affect neuroendocrine function, influencing the nocturnal pattern of neurohypophysial hormone secretion, augmenting prolactin release and advancing the peak of cortisol release.

Administration, Oral↗
PubMed1998

Bright light exposure and pituitary hormone secretion.

OBJECTIVE: Exposure to bright light inhibits melatonin secretion in man. As the relationship between melatonin and pituitary function remains controversial, we investigated the effect of altering the melatonin rhythm by bright light during the early hours of darkness on pituitary hormone secretion in man. DESIGN: The investigation took the form of a randomized controlled clinical trial. SUBJECTS: Ten adult healthy male volunteers, who were non-smokers and aged 21-33 years, were studied on two occasions: once during exposure to bright light from 2000 h to 0200 h and once during exposure to normal room lighting over the same period. On each day of the study, the subjects were allowed to sleep after lights were switched off at 0200 h. Observations were also performed when subjects were exposed to normal room lighting from 2000 h to 2400 h, thereafter being allowed to sleep. On each study day the subjects undertook their normal duties but refrained from taking heavy exercise and drinking alcohol. MEASUREMENTS: Serum cortisol, GH and PRL, plasma vasopressin, oxytocin, melatonin, sodium, potassium and osmolality and packed cell volume were measured over 24 hours. RESULTS: Bright light delayed the nocturnal melatonin peak by 2 hours and resulted in a decrease in cortisol concentrations. Growth hormone levels decreased but subsequently there was a significantly greater nocturnal increase. The PRL peak was delayed and nocturnal vasopressin concentrations were lower in both the studies where subjects were exposed to a modified sleep schedule. CONCLUSION: Exposure to bright light during the early hours of darkness delays the nocturnal melatonin peak and alters cortisol, GH, PRL and nocturnal vasopressin secretion, while modification of the sleep pattern decreases vasopressin concentrations and alters its nocturnal peak.

Adult↗
PubMed1998

Neurohypophysial hormone and melatonin secretion over the natural and suppressed menstrual cycle in premenopausal women.

OBJECTIVE: Vasopressin, oxytocin and melatonin have been reported to be influenced by ovarian steroids. The neurohypophysial hormones have also been shown to display a diurnal pattern of secretion in men. We therefore studied the diurnal pattern of neurohypophysial hormone and melatonin secretion in premenopausal women and in women on oral contraceptives. DESIGN: Healthy normally cycling premenopausal women were studied over 24 hours during the midfollicular and midluteal phases of the menstrual cycle. Healthy premenopausal women on oral contraceptives were studied over 24 hours at similar times. SUBJECTS: Eight healthy normally cycling women and 7 healthy premenopausal women on oral contraceptives. MEASUREMENTS: Plasma vasopressin, oxytocin and melatonin were measured by radioimmunoassay. RESULTS: Vasopressin concentrations and its nocturnal peak were highest in the follicular phase of the natural menstrual cycle and attenuated in the women on oral contraceptives. Oxytocin concentrations did not vary between the two phases of the menstrual cycle, but increased on oestrogen administration. Overall melatonin secretion was augmented in the women on oral contraceptives. CONCLUSIONS: Vasopressin release and its nocturnal peak were greatest in the follicular phase of the menstrual cycle, while melatonin secretion was augmented in the women on oral contraception.

Adult↗
PubMed1998

The measurement of testosterone in hair.

Trace metals and drugs have been measured in hair for a number of years but there are no published papers on the measurement of steroids in human hair. We report here the measurement of testosterone in hair samples taken from men, women and prepubertal children. This was a preliminary investigation to see whether testosterone was detectable in hair and whether concentrations between men and women, and men and prepubertal children were different in line with concentrations of testosterone in the blood. Hair was digested in sodium hydroxide and the testosterone extracted before measurement by radioimmuno- assay. There was a clear difference between testosterone concentrations found in heir collected from men (12.9-77.7 pmol/g) and those found in hair from women (<0.9-10.8 pmol/g). There was no significant difference between the concentrations found in women and children. The authenticity of the testosterone measured was confirmed with GCMS.

Adult↗
PubMed1996

The effect of oophorectomy and hormone replacement on neurohypophyseal hormone secretion in women.

OBJECTIVE: There is evidence to suggest that the release of neurohypophyseal hormones may be influenced by the circulating concentrations of gonadal steroids. We therefore monitored this relationship in women undergoing prophylactic bilateral oophorectomy at the time of hysterectomy with subsequent hormone replacement therapy and compared it with that in women undergoing hysterectomy with conservation of ovaries. DESIGN: Patients were randomly allocated to receive either transdermal oestradiol patches, 0.05 mg/day, or subdermal implants containing either 50 mg oestradiol or 50 mg oestradiol with 100 mg testosterone. Blood samples for determination of plasma hormone concentrations, electrolytes and osmolality were obtained immediately before and after surgery and then at two-monthly intervals for 8 months and finally at 12 months. MEASUREMENTS: Free oestradiol, vasopressin and oxytocin were measured by radioimmunoassay. RESULTS: Vasopressin concentrations were found to fall after surgery in oophorectomized women, but not in those with ovaries. There were no changes in fluid balance to account for the reduced plasma vasopressin concentrations. During treatment oestradiol appeared to enhance and testosterone to suppress vasopressin release. Oophorectomy had no significant effect on plasma oxytocin concentrations, but in the groups receiving oestradiol implants concentrations fell significantly at 8 and 12 months compared with the value at 6 days. CONCLUSION: The observed changes in plasma vasopressin concentrations were consistent with the observations in experimental animals and provide evidence that vasopressin release in the human is influenced by gonadal steroids.

Adult↗
PubMed1996

Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia.

Six Welsh gelding ponies (weight 246 +/- 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.

Acepromazine↗
PubMed1996

Ciba Corning ACS:180 testosterone assay evaluated.

A fully automated direct assay of testosterone has been developed for the Ciba Corning ACS:180 immunoassay system. We have evaluated this method and compared specimen results with those from the Diagnostic Products Corp. (DPC) and Medgenix direct assays and an in-house extraction assay. Accuracy of the method was assessed by measuring GC-MS-targeted serum pools. Within-assay im- precision was <6% and between-assay imprecision <9% over the concentration range examined. High concentrations of lipid caused an increase in the measured testosterone but other potential interferents were without effect. Recovery was quantitative but was affected by sex-hormone-binding globulin. The method was positively biased with respect to the DPC and Medgenix assays but negatively biased with the extraction assay. Measurement of the GC-MS-targeted serum pools showed the assay to overestimate recovery by approximately 13%. The ACS:180 assay is particularly attractive as a routine assay because it is fully automated, obtains the first result in only 15 min, and shows good assay performance.

Cross Reactions↗
PubMed1995

Total intravenous anaesthesia in ponies using detomidine, ketamine and guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects.

Pharmacokinetics and some pharmacological effects of anaesthesia induced by a combination of detomidine, ketamine and guaiphenesin were investigated in eight ponies. Cardiopulmonary function was studied and plasma met-enkephalin, dynorphin, beta-endorphin, arginine vasopressin, adrenocorticotrophin, cortisol, 11-deoxycortisol and catecholamine concentrations were measured. The combination produced slight cardiorespiratory depression, hyperglycaemia and a reduction in haematocrit. There were no changes in plasma opioids, pituitary peptides or catecholamines. Plasma cortisol concentration decreased and plasma 11-deoxycortisol increased indicating a suppression of steroidogenesis. Steady state ketamine and guaiphenesin concentrations were attained during the infusion period, and ketamine concentrations likely to provide adequate analgesia for surgical operations were achieved (more than 2.2 micrograms ml-1). Steady state detomidine concentration was not attained. The ponies took on average 68 minutes to recover to standing and the recovery was uneventful.

Anesthesia, Intravenous↗
PubMed1995

Raised serum 11-deoxycortisol in men with persistent acne vulgaris.

OBJECTIVE: Acne vulgaris is androgen dependent but the hormonal mechanisms are unclear. Although there have been many studies of serum hormones in women with acne there are few studies in men and the results are conflicting. We have therefore carried out a further study in men. DESIGN AND PATIENTS: Fifty men with acne vulgaris were age-matched against 50 normal men. MEASUREMENTS: Serum levels of dehydroepiandrosterone sulphate (DHEAS), 17 alpha-hydroxyprogesterone, 11-deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay and LH, FSH and oestradiol by automated ELISA. RESULTS: The acne patients had higher levels of androstenedione, median 7.35 nmol/l, (interquartile range 2-7) vs 6.05 (2.3), P = 0.004; testosterone, 21.7 nmol/l (7.5) vs 17.55 (7.7), P = 0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P = 0.007, but also had higher levels of 11-deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P = 0.022. The LH, FSH, 17 alpha-hydroxyprogesterone, DHEAS, oestradiol and SHBG levels were not significantly different. Examination of the Spearman rank correlation coefficient matrices for the serum levels of 17 alpha-hydroxyprogesterone, androstenedione and 11-deoxycortisol showed that the strongest correlation was between androstenedione and 11-deoxycortisol. CONCLUSION: Although there was overlap between the results of the acne patients and controls the acne patients tended to have higher levels of androstenedione, testosterone, free androgen index and 11-deoxycortisol. The higher levels of 11-deoxycortisol are suggestive of 11 beta-hydroyxlase dysfunction which could be due to a primary adrenal defect or a consequence of raised androgens. Also, a pathway between androstenedione and 11-deoxycortisol has been described in sheep and, although unsubstantiated in man, requires consideration.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Raised serum androgens and increased responsiveness to luteinizing hormone in men with acne vulgaris.

We have investigated the hormone profiles and the relationship between serum testosterone and luteinizing hormone in men with long-standing acne vulgaris. In the controls, age correlated with the free androgen index and with serum dehydroepiandrosterone-sulphate, so for the purposes of comparison 33 men with acne vulgaris were age-matched against 33 controls. Compared with controls, the acne patients had higher medians of serum androstenedione, testosterone and free androgen index. In both groups there was a significant correlation between testosterone and luteinizing hormone levels. For a given level of luteinizing hormone the patients with acne tended to have higher levels of serum testosterone than normal controls. These results indicate that in this group of men with long-standing acne there was either increased responsiveness of the target organ to luteinizing hormone or there was an increased amount of androgen-secreting tissue.

Acne Vulgaris↗