ACTH precursors: biological significance and clinical relevance.
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Biomedical subjects
Publications and source records attributed to A White.
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This study was undertaken to develop a functional model of otitis media with effusion (OME) in the pig (Sus scrofa), with the purpose of investigating the origin of lymphocytes populating the middle ear during the course of an inflammatory process. The relevance of the model to the human condition of OME is to a large extent dependent on the anatomical and physiological similarities between the middle ear cavity and the pharyngeal lymphoid tissue of the pig and man. Anatomical specimens were collected from 7 young Large White pigs to determine the gross anatomy of the middle ear cavity and the histological characteristics of the middle ear mucosa. It was found that the anatomy of the 3 parts of the middle ear cavity in man and in the pig is broadly similar, although some minor differences were observed. The porcine eustachian tube was seen to be cartilaginous throughout its length in contrast to the part osseous, part cartilaginous structure found in man; the porcine ossicles were slightly different in shape to those of man and the air cell system was situated inferior to the tympanic cavity in the pig as opposed to posteriorly in man. This paper describes the structure and morphology of the pig middle ear cavity and compares and contrasts it with that of man. The minor differences observed are of anatomical importance but do not diminish the usefulness of the pig middle ear cleft as a potential model for human middle ear disorders.
A 54-year-old woman had a 3 year history of a recurrent bilateral axillary rash during the summer months. Both axillae showed hyperkeratotic, fissured and cobblestone plaques. Skin biopsy showed the histology previously defined as axillary granular parakeratosis. This finding may indeed represent an unusual contact reaction to anti-perspirants interfering with epidermal keratinization.
The effects of exercise stress on erythrocyte beta-adrenergic receptor characteristics and plasma concentrations of adrenaline, noradrenaline and thyroid hormones were studied in Thoroughbred racehorses during rest and after exercise. Five minutes after a maximal speed race of 1200 +/- 200 m (mean +/- s.d.), both plasma adrenaline and noradrenaline concentrations increased with respect to basal values (from 2.48 +/- 0.15 to 3.83 +/- 0.27 and from 2.13 +/- 0.11 to 3.53 +/- 0.27 nmol/l respectively). The increment of adrenaline was greater in high performance (HP) as compared to low performance (LP) horses (76.9 vs. 43.5%), in accordance with the contribution of the adrenal medulla in the sympathoadrenal response to exercise. Triiodothyronine (T3), but not thyroxine (T4) levels increased 5 min after exercise (from 55.6 +/- 2.9 to 81 +/- 3.7 ng/dl and from 0.67 +/- 0.04 to 0.70 +/- 0.05 micrograms/dl respectively). No differences were observed in basal values of thyroid hormones or in the percentage of T3 increment, when comparing HP vs. LP horses. Erythrocyte membranes obtained 5 min after racing showed decreased concentrations of beta-adrenergic receptors (beta-AR) and dissociation constant as compared to basal values (50.1 +/- 7.0 vs. 95.7 +/- 12.0 fmol/mg protein and 0.97 +/- 0.24 vs. 2.04 +/- 0.3 nmol/l respectively). This temporal pattern suggest that the observed changes in beta-AR characteristics could be mediated by catecholamines, but not by thyroid hormones, in this model. This down regulation of beta-AR may act as a protecting mechanism preventing the erythrocytes from the decrease in membrane fluidity known to be provoked by adrenergic agonists. The accomplished study showed that, in the Thoroughbred horse, there is a homeostatic response to race stress, characterised by a sudden increase in plasma catecholamines and T3 and a parallel decrease in beta-AR concentration on the erythrocyte membrane. In this way the racing horse could rapidly adjust its metabolism to the exercise stress, but at the same time override one possible undesirable side-effect caused by these hormonal changes. Further studies will be required to establish performance-related differences occurring in endocrine changes.
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Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.
The -514T allele of hepatic lipase is associated with increased high density lipoprotein-cholesterol levels in men, but not in women. This observation suggests that the -514C to T polymorphism may diminish the response of hepatic lipase to androgens. To test this hypothesis, five -514T and five -514C homozygous men were treated with the anabolic steroid stanozolol for 6 days. The mean increase in hepatic lipase activity was similar in the two groups (45+/-10 vs. 51+/-10 mmol x hr(-1) x l(-1), P = 0.5). To evaluate the association between the -514 polymorphism and hepatic lipase activity at different physiological androgen concentrations, hepatic lipase genotypes and activities were measured in 44 men and 40 premenopausal women. The effect of the -514T allele on hepatic lipase activity was significant and quantitatively similar in both sexes. These data indicate that the -514 polymorphism does not influence the response of hepatic lipase activity to androgens, and that the effects of this polymorphism on hepatic lipase activity are independent of androgen action.
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It is widely recognised that impaired social relations are characteristic of school-aged children with behavioural disorders, and predict a poor long-term outcome (Parker & Asher, 1987). However, little is known about the early antecedents of social impairment in behaviourally disturbed children. The aim of the present study was to explore three areas of potential dysfunction in younger children: theory of mind, emotion understanding, and executive function. Forty preschoolers, rated by their parents on the Strengths and Difficulties Questionnaire (Goodman, 1994) as "hard to manage" (H2M) were compared with a control group on a set of: (1) theory of mind tasks (including an emotion prediction task involving either a nice or a nasty surprise); (2) emotion understanding stories (that required affective perspective-taking skills as well as situational understanding); and (3) simple executive function tasks (adapted for preschoolers, and tapping inhibitory control, attentional set-shifting, and working memory). Small but significant group differences were found in all three cognitive domains. In particular, hard-to-manage preschoolers showed poor understanding of emotion and executive control, poor prediction or recall of a false belief, and better understanding of the belief-dependency of emotion in the context of a trick than a treat. Moreover, executive function was associated with performance on the theory of mind tasks for the hard-to-manage group alone, suggesting both direct and indirect links between executive dysfunction and disruptive behaviour.
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A micro-scale method for separation and measurement of dityrosine in human cerebrospinal fluid (CSF) is described utilizing liquid-liquid extraction and ion-paired, reversed-phase high-performance liquid chromatography with fluorimetric detection. A mobile phase containing 1-heptanesulfonic acid linearly increased in methanol from 0 to 100% over 30 min allows the resolution of dityrosine from other fluorescent compounds with excitation at 285 nm and emission at 410 nm. As little as 0.15 ml CSF sample can be utilized with a detection limit of 60 pg dityrosine on the column. This method facilitates the use of CSF dityrosine as a measure of free radical mediated protein damage in the central nervous system.
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This study compared rates of performance of cardiac procedures in relation to gender, race, and geographic location in patients hospitalized for myocardial infarction. The Atherosclerosis Risk in Communities (ARIC) study provides population data and standardized data collection methods. Hospital records of eligible people aged 35 to 74 years were abstracted in communities of 4 states in the United States: North Carolina, Mississippi, Maryland, and Minnesota. Between January 1987 and December 1991, 5,462 "definite" hospitalized patients with myocardial infarctions were identified. Women treated in nonteaching hospitals were less likely than men to have coronary angiography (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5 to 1.0), coronary artery bypass graft surgery (CABG) (OR 0.6, 95% CI 0.4 to 0.8), and thrombolytic therapy (OR 0.8, 95% CI 0.6 to 1.0), after controlling for age, race, severity of myocardial infarction, co-morbidity, and geographic area. Findings were similar in teaching hospitals. Blacks in the biracial communities were significantly less likely than whites to have coronary angiography, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, and thrombolytic therapy. After controlling for age, race, severity of myocardial infarction and co-morbidity, no consistent geographic differences were observed, except for Forsyth whites having the highest and Washington County the lowest odds for coronary angiography. Appropriate outcome measures would serve to evaluate the effect, if any, of the differences described on the ARIC population.
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Recent structural studies provide a fresh look at the catalytic mechanism of polysaccharide hydrolysis by retaining beta-glycosyl hydrolases. Highlights include insights into saccharide ring distortion, both upon binding and during the course of catalysis, and evidence for the regulation of the pKa of key catalytic residues.
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We present a patient with severe Cushing's syndrome secondary to an invasive pituitary tumour. Cortisol secretion fluctuated between severe hypercortisolaemia associated with features of Cushing's syndrome to recurrent symptomatic hypocortisolaemia. Normal ACTH precursors to ACTH ratio during the various stages of cortisol secretion indicated that periodic decreased prohormone processing did not contribute to the unique presentation in the patient. Thus, the the extreme fluctuations of plasma cortisol levels are most probably due to unexplained erratic changes of ACTH secretion.