Uptake of breast screening. Non-responders can be encouraged to attend.
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Breast Neoplasms↗
Biomedical subjects
J Stephenson
Publications and source records attributed to J Stephenson.
Evidence for 5-hydroxytryptamine1A receptor involvement in the control of prolactin secretion in man.
The effects of pindolol pretreatment (2 days) on prolactin and cortisol responses to a single dose of (+)-fenfluramine (30 mg po) were examined in nine healthy male volunteers. Pindolol pretreatment attenuated the (+)-fenfluramine-induced increase in prolactin concentrations but failed to affect the (+)-fenfluramine-induced cortisol increase. These data provide evidence in support of 5-HT1A receptor involvement in the regulation of prolactin secretion but question its importance in the regulation of cortisol secretion in man.
Adult↗
Possible co-existence of RAS activation and monosomy 7 in the leukaemic transformation of myelodysplastic syndromes.
The frequency of RAS activation was studied in 48 patients with acute myeloid leukaemia (AML) or with myelodysplastic syndromes (MDS), in order to address the question of whether patients possessing monosomy 7 or other alterations of chromosome 7 have a higher incidence of RAS activation than those lacking chromosome 7 abnormalities. Samples were screened for oncogenic point mutation by DNA amplification followed by oligonucleotide hybridization analysis at codons 12, 13 and 61 of N-RAS and codons 12 and 13 of K-RAS. Two additional samples were considered to have activated RAS due to additional karyotypic abnormalities t(5;12) or loss of both copies of chromosome 17 and hence, the neurofibromatosis (NF1) loci. The group of chronic myelomonocytic leukaemia (CMML) patients had activated RAS in 4/11 cases and inclusion of two CMMLt patients (with monosomy 7) brings this incidence to 5/13. No change in frequency of RAS activation was seen between groups containing de novo AML samples with or without chromosome 7 abnormalities (1/5 and 2/12, respectively). However, assessment of MDS samples in the process of, or subsequent to, leukaemic progression showed a difference between the two groups. The frequency of RAS activation in samples with monosomy 7 was 4/9 samples while none of the seven samples without chromosome 7 changes showed RAS activation. The co-existence of RAS activation and monosomy 7 in MDS indicates that these lesions can co-operate in the multistep process of leukemogenesis.
Base Sequence↗
Three-dimensional demarcation of perfusion zones corresponding to specific coronary arteries: application for automated interpretation of myocardial SPECT.
UNLABELLED: In this study, three-dimensional maps of specific coronary artery territories were derived and combined with normal distribution maps as a reference for automated characterization of defects, including location and size. METHODS: One hundred sixty-eight 99mTc-sestamibi myocardial perfusion SPECT scans from normal patients and patients with single-vessel disease were selected according to angiographic data. Five separate groups were established for men and women: normal, proximal left anterior descending (PLAD), distal left anterior descending (DLAD), right coronary artery (RCA) and left circumflex (LCx). All myocardial perfusion studies were aligned and sized to the same three-dimensional orientation using a previously developed automated image registration technique. Mean and variation three-dimensional templates were constructed from stress images in each group. Normal templates were demarcated with hypoperfusion regions obtained from disease templates. The defects were detected in the individual patient's images by a region-growing algorithm which identified abnormal voxels by comparison to the corresponding voxels in the mean and variation templates. RESULTS: Defects were quantified with respect to volume, location relative to the expected hypoperfusion zones and severity index. Abnormal regions could be marked directly on tomographic slices and visualized in various orientations. Single defects greater than 2% of the myocardium positioned within demarcated perfusion territories were detected in 105/119 abnormal patients and in 3/49 normal patients. CONCLUSION: Maps of myocardial perfusion zones created from images of angiographically selected patients provide a reference for automated localization of myocardial perfusion defects. A template-based region-growing is a robust technique for volumetric quantification and localization of abnormal regions.
Algorithms↗
Automated alignment and sizing of myocardial stress and rest scans to three-dimensional normal templates using an image registration algorithm.
UNLABELLED: To optimize the interpretation of myocardial SPECT, we developed an automated method for alignment, sizing and quantification of images using three-dimensional reference templates. METHODS: Stress and rest reference templates were built using a hybrid three-dimensional image registration scheme based on principal-axes and simplex-minimization techniques. Normal patient studies were correlated to a common orientation, position and size. Aligned volumes were added to each other to create amalgamated templates. Separate templates were built for normal stress and rest SPECT 99mTc-sestamibi scans of 23 men and 15 women. The same algorithm was used to correlate abnormal test-patient studies with respective normal templates. The robustness of the fitting algorithm was evaluated by registering data with simulated defects and by repeated registrations after arbitrary misalignment of images. To quantify regional count distribution, 18 three-dimensional segments were outlined on the templates, and counts in the segment were evaluated for all test patients. RESULTS: Our technique provided accurate and reproducible alignment of the images and compensated for varying dimensions of the myocardium by adjusting scaling parameters. The algorithm successfully registered both normal and abnormal studies. The mean registration errors caused by simulated defects were 1.5 mm for position, 1.3 degrees for tilt and 5.3% for sizing (stress images), and 1.4 mm, 2.0 degrees and 3.7% (rest images); these errors were below the limits of visual assessment. CONCLUSION: Automated three-dimensional image fitting to normal templates can be used for reproducible quantification of myocardial SPECT, eliminating operator-dependence of the results.
Algorithms↗
Involvement of the 5-HT2 receptor in the 5-HT receptor-mediated stimulation of prolactin release.
The present study examined the involvement of 5-HT1C and 5-HT2 receptors in the regulation of prolactin release in the rat. Both the mixed 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the preferential 5-HT1C agonist, 2-chloro-6-(1-piperazinyl)pyrazine monohydrochloride (MK-212), elicited a significant increase in plasma prolactin concentration with DOI about 20 times more potent than MK-212. Treatment with DOI, but not with MK-212, induced head twitching in the rat, and this behavior was inhibited by both the mixed 5-HT2/5-HT1C receptor antagonist, ritanserin, and the selective 5-HT2 receptor antagonist, amperozide. DOI-induced prolactin release was also antagonized by ritanserin and amperozide, whereas only ritanserin affected MK-212-induced prolactin release. Furthermore, amperozide did not attenuate d-fenfluramine-elicited prolactin release, which is known to be antagonized by ritanserin. These data suggest that the pharmacological stimulation of prolactin release by DOI is mediated via the 5-HT2 receptor and that the 5-HT1C receptor may be of importance for the physiological regulation of prolactin release.
Amphetamines↗
Epidermal growth factor antagonizes vasopressin in vivo and in vitro.
Since EGF causes diuresis through a renal action and may antagonize the hydroosmotic effect of AVP in vitro we investigated the antagonistic action of EGF with AVP in vivo and the mechanism of the antagonism in vitro. Conscious ewes received i.m. injections of a selective AVP V2-receptor agonist (1-desamino, D-Arg8 vasopressin acetate, DDAVP) every 12 hours for days 5 to 16. All ewes received an i.v. isotonic saline infusion (100 ml/day) for days 1 to 8 and days 13 to 16, and i.v. EGF in 100 ml saline/day at doses of 0 (N = 8) or 10 (N = 8) micrograms/hr for days 9 to 12. DDAVP reduced both urine volume and water intake, and increased urine osmolality. In contrast, simultaneous infusion of EGF reversed the DDAVP-induced responses, resulting in a transient negative fluid balance, kaliuresis and a transient natriuresis (all P < 0.05). When EGF treatment ceased, the effects of DDAVP treatment alone gradually became apparent. From the in vitro studies, the AVP-related peptides displaced specific AVP V1- and V2-receptor antagonist radioligands from rat renal inner medullary membranes, whereas EGF had no effect. However, EGF antagonized AVP V2-stimulated cAMP production in a dose-dependent way (IC50 = 2 x 10(-7) M). Therefore, the diuretic effect of EGF is not via direct antagonism of the antidiuretic AVP V2-receptor but seems mediated by inhibition of the antidiuretic AVP V2-receptor second messenger system.
Animals↗
Deficiency of the human mitochondrial transcription factor h-mtTFA in infantile mitochondrial myopathy is associated with mtDNA depletion.
Recent studies show that patients presenting with cytochrome oxidase (COX) deficiency in infancy may have reduced mitochondrial DNA (mtDNA) in muscle. The human mitochondrial transcription factor A (h-mtTFA) may be an important regulator of both transcription and replication of mtDNA. h-mtTFA levels were investigated in cell lines which were either free of mtDNA (rho 0) or temporarily depleted by treatment with dideoxycytidine (ddC), and in tissue from three patients with mtDNA depletion and cytochrome oxidase deficiency. h-mtTFA was compared with other mitochondrial proteins such as pyruvate dehydrogenase and porin by Western blotting. The ratio of mtDNA and h-mtTFA mRNA to reference nuclear probes was measured by dual labelling of dot blots. The ratio of mtDNA to nuclear DNA in skeletal muscle was low in muscle in the three patients and in other tissues in one. h-mtTFA was low in cells depleted either permanently or transiently of mtDNA, and this reduction in h-mtTFA roughly paralleled mtDNA levels. Similarly, treatment of rho 0 cell lines with ddC induced a reduction in mtDNA as well as h-mtTFA protein. The relationship between h-mtTFA and mtDNA levels suggests that they may be causally linked. MtDNA depletion was accompanied by an increase in the level of h-mtTFA RNA in the cell lines but low levels in the patient. This suggests that either h-mtTFA regulates mtDNA levels, or that h-mtTFA expression may be regulated by a feedback mechanism initiated by MtDNA Depletion.
Base Sequence↗
Effects of anti-emetics on water excretion in humans.
1. The anti-emetic drug metoclopramide has been shown to stimulate secretion of the antidiuretic hormone arginine vasopressin. Since metoclopramide is used to treat nausea, which is another potent stimulus to vasopressin secretion, the aim of this study was to determine whether metoclopramide might limit free water excretion and so cause hyponatraemia. 2. Metoclopramide 20 mg (0.2-0.3 mg/kg), prochlorperazine 12.5 mg (0.1-0.2 mg/kg) and placebo were administered intravenously in a double blind randomized crossover way at 2 week intervals and the effects on urine flow rate, plasma osmolality, thirst ratings and plasma sodium and atrial natriuretic peptide concentrations determined in water-loaded (10 mL/kg) healthy young men. 3. There were no differential effects on any variable of either drug versus placebo. 4. These results indicate that metoclopramide is unlikely to cause any significant water retention in a clinical setting or precipitate hyponatraemia.
Adult↗
Androgen manipulation and vasopressin binding in the rat brain and peripheral organs.
It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of this experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V1 antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V1 AVP receptor binding (as determined using the selective AVP V1 antagonist radioligand [125I](d(CH2)5,sarcosine7)AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. This study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors.
Androgens↗
Determining optimal work surface height for Surrey Memorial Hospital food service workers.
In anticipation of extensive kitchen renovations at Surrey Memorial Hospital, the median elbow height was determined for a group of 49 food service workers. From this measurement, an optimal range for work surface height of 824 mm to 874 mm was determined. This range is lower than that recommended by some ergonomics experts, and lower than the work surface height of much of the existing equipment in Patient Food Services. Work surface height should be considered when equipment is selected or modified as one possible measure to reduce the physical strain of food service work.
Body Height↗
Replication-incompetent adenoviruses as vectors for protective immunization against measles virus infection.
Despite the availability of an efficient live-attenuated measles virus vaccine about 1.5 million annual deaths from measles infections and their complications are recorded worldwide. Particularly in developing countries measles remains an unsolved problem and a new vaccine seems necessary. In our animal model of measles virus infection in rats we studied a candidate vaccine based on infectious replication incompetent (E1A-) adenovirus (RAd) where measles virus genes are expressed under the control of the cytomegalovirus immediate early promoter. The aim of the study was to characterize the cell mediated and humoral immunity after immunization with RAd and its protective effect. After challenge with a lethal dose of measles virus no signs of disease or histopathological changes were detected in RAd68-immunized rats. The elimination of measles virus was successful within a few days. The results demonstrate that defective recombinant adenovirus vectors can induce complete protection from experimental measles infection in rats.
Adenoviridae↗
Headaches in children: action or reassurance.
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Blood Pressure↗
Multiple binding sites for nicotine receptor antagonists in inhibiting [3H](-)-nicotine binding in rat cortex.
The displacement of [3H](-)-nicotine from its binding site in rat cerebral cortex by a number of antagonists was investigated. [3H](-)-Nicotine appeared to bind to a single site with a dissociation constant (KD) of 5.5 nM; pancuronium, gallamine and trimetaphan displaced [3H](-)-nicotine with inhibition constants (KI) of 57, 99 and 621 microM, respectively, whereas mecamylamine only displaced 50% of nicotine binding in concentration > 1 mM. For hexamethonium and (+)-tubocurarine the displacement of [3H](-)-nicotine binding appeared to involve two sites; the higher affinity site comprising 30% of the total binding for hexamethonium but 76% of the sites for (+)-tubocurarine. In the presence of mecamylamine (100 microM) the displacement of [3H](-)-nicotine binding by (+)-tubocurarine appeared to involve only a single site with an affinity similar to that for the high affinity site in the absence of mecamylamine whereas that for hexamethonium still involved two sites. It is suggested that (+)-tubocurarine may act at both the binding site for [3H](-)-nicotine per se and also at an allosteric site. The failure of mecamylamine to influence the binding of hexamethonium suggests that there may be more than one allosteric site or that hexamethonium may distinguish between subtypes of nicotine receptors in the cortex.
Animals↗
Methylation status within exon 3 of the c-myc gene as a prognostic marker in myeloma and leukaemia.
The third exon of the c-myc gene contains a CpG site which has been implicated as a regulatory region. When this site is methylated it has protein binding properties and binds a different set of proteins in normal and neoplastic cells. Recent work using myeloma cell lines indicates a correlation between hypomethylation at this site and enhanced expression of the myc protein. We investigated the methylation of this site in 10 cases of myeloma but found that there was no change from the high degree of methylation found in normal cells. Therefore, methylation status at this site is unlikely to serve as a prognosticator in myelomatosis. However, methylation changes at this site were observed in DNA from two cases of CMML, in which hypomethylation was observed and in three AML cases, which were completely methylated at this site.
Acute Disease↗
Familial MDS with 5q- abnormality.
Abnormalities of chromosome 5 and 7 are frequently found in primary MDS. Cases with familial monosomy 7 are well recognized, but there are no reports of familial MDS with deletion of 5q. We describe two sisters, aged 38 and 36 years, both of whom had MDS and interstitial deletion of 5q. The occurrence of this chromosomal abnormality reinforces the concept of tumour suppressor gene hypothesis in some cases with familial MDS.
Adult↗
Effects of an orally active vasopressin V1 receptor antagonist.
1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone (OPC-21268). 2. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, [125I]-[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 x 10(-8), 0.3 mol/L liver and 1.5 x 10(-8), 0.2 mol/L kidney. OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)-d(CH2)5[D-Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10(-4) mol/L). 3. After oral administration to rats, OPC-21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose-dependent manner. 4. These studies confirm that OPC-21268 is a potent non-peptide, orally effective V1 vasopressin receptor antagonist.
Administration, Oral↗
Living near a lead smelter: an environmental health risk assessment in Boolaroo and Argenton, New South Wales.
This paper outlines a risk assessment of a lead-contaminated residential site in Lake Macquarie, New South Wales, near the Pasminco Metals-Sulphide lead and zinc smelter. The assessment includes a hazard identification and a dose-response assessment based on recent research findings; an exposure assessment based on two interrelated indicators, soil/dust lead and blood lead; a risk characterisation; and finally, a discussion of environmental and behavioural options for the management of risk. The exposure assessment showed lead concentrations of 20 to 21,460 parts per million in soil survey samples, 23 to 35,870 parts per million in household dust, and a range of mean values for blood lead concentration of 11 micrograms/dl to 17 micrograms/dl, in four study groups. The proportions of children within these groups having blood lead concentrations of 10 micrograms/dl or greater, the current level of known health effect, ranged from 57 per cent to 85 per cent. The decision by the National Health and Medical Research Council in June 1993 to set a goal for blood lead of below 10 micrograms/dl has important implications for the definition and the management of the environmental health risk from 'living with lead' in the area assessed.
Child↗