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Biomedical subjects

C Phelps

Publications and source records attributed to C Phelps.

29 records · Page 2Linked to original sources

Bipolar illness preceded by anorexia nervosa in identical twins.

Concordant bipolar illness in a set of identical twins, preceded in one twin by anorexia nervosa, is described. The literature on monozygotic twins discordant for anorexia nervosa and on the relationship between anorexia nervosa and affective illness is briefly reviewed. It is concluded that familial affective disorders can predispose adolescent females to develop anorexia nervosa.

Adolescent↗

Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.

Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.

Animals↗

The binding of ethyl isocyanide to ferroperoxidase.

The equilibrium and kinetics of ethyl isocyanide binding to ferroperoxidase were studied. At pH9.1 the results of both studies are consistent with a single-process model with an affinity constant of 95m(-1) and combination and dissociation constants of 2.2x10(3)m(-1).s(-1) and 23s(-1) respectively. Ethyl isocyanide is not bound significantly at pH values lower than 6.0, and in this behaviour and the pH-dependence of the affinity constant, similarities exist between isocyanide and cyanide binding. The enthalpy of the process measured by equilibrium methods is -59kJ/mol (-14kcal/mol). At pH values below 9, the ethyl isocyanide adduct changes in a slow time-dependent manner, giving rise to a new species. These changes are reversible on increasing the pH. The results are discussed in relation to other known information about ligand binding to ferroperoxidase and to myoglobin.

Cyanides↗

The binding of cyanide to ferroperoxidase.

1. The equilibrium and kinetics of cyanide binding to ferroperoxidase were investigated. At pH9.1 the equilibrium and kinetic measurements agree closely and disclose a single process with an affinity constant of 1.1x10(3)m(-1) and combination and dissociation velocity constants of 29m(-1).s(-1) and 2.5x10(-2)s(-1) respectively. 2. At pH values below 8 the affinity constant falls until at pH6.0 the ferroperoxidase.cyanide complex is no longer formed. This is shown to be associated with the formation of ferriperoxidase.cyanide complex in the mixture even in the presence of excess of sodium dithionite. 3. Rapid-pH-jump experiments show a fast pseudo-first-order interconversion between ferroperoxidase.cyanide complex at pH9.1 and ferriperoxidase.cyanide complex at pH6.0. 4. The kinetics of binding of cyanide to dithionite-reduced peroxidase at pH6.0 are complicated and radically different from those observed at pH9.1. 5. Above pH8 the change of affinity constant with pH is consistent with the undissociated species, HCN, being bound by the ferroperoxidase. The enthalpy for this process measured both by equilibrium and kinetic methods is about -8kcal/mol. 6. The binding of cyanide to reconstituted peroxidases, proto, meso and deutero, was investigated. 7. The results are discussed in relation to known data on cyanide binding to other haemoproteins.

Binding Sites↗

The hydrogen ion equilibria of horseradish peroxidase and apoperoxidase.

1. The reversible proton dissociation equilibria of peroxidase, apoperoxidase and haem-recombined apoperoxidase have been explored in 150mm-potassium chloride at 20 degrees C at pH3-11.5. 2. Complementary heat measurements have been made of the classes of titratable groups to determine their intrinsic DeltaH dissociation. 3. These curves are interpreted as showing that there are two histidine residues capable of titration in peroxidase whereas there are three such in apoperoxidase. 4. Concomitant spectroscopic investigations indicate profound differences in the tyrosine ionizations in the two proteins. In peroxidase one group only of the five residues ionizes up to pH11.5. In apoperoxidase four residues are titratable. 5. Spectroscopic titration in 6m-guanidinium chloride and 150mm-potassium chloride reveal one tyrosine residue fewer in peroxidase than in apoperoxidase. 6. These findings are discussed in terms of the ;side chain' groups responsible for binding the haem group in peroxidase. A proximal imidazole group seems probable as is also the involvement of a distally placed tyrosine. 7. The differences between apo- and holo-peroxidase are stressed, particularly in respect of abnormal carboxyl group titration in the former.

Amino Acids↗

The combination of carbon monoxide-haem with apoperoxidase.

1. Static titrations reveal an exact stoicheiometry between various haem derivatives and apoperoxidase prepared from one isoenzyme of the horseradish enzyme. 2. Carbon monoxide-protohaem reacts rapidly with apoperoxidase and the kinetics can be accounted for by a mechanism already applied to the reaction of carbon monoxide-haem derivatives with apomyoglobin and apohaemoglobin. 3. According to this mechanism a complex is formed first whose combination and dissociation velocity constants are 5x10(8)m(-1)sec.(-1) and 10(3)sec.(-1) at pH9.1 and 20 degrees . The complex is converted into carbon monoxide-haemoprotein in a first-order process with a rate constant of 235sec.(-1) for peroxidase and 364sec.(-1) for myoglobin at pH9.1 and 20 degrees . 4. The effects of pH and temperature were examined. The activation energy for the process of complex-isomerization is about 13kcal./mole. 5. The similarity in the kinetics of the reactions of carbon monoxide-haem with apoperoxidase and with apomyoglobin suggests structural similarities at the haem-binding sites of the two proteins.

Binding Sites↗

Alterations by estrogen and hypothyroidism in the effects of septal lesions on lordosis behavior of male rats.

Earlier experiments indicated that chronic exposure to estradiol benzoate (EB) following septal lesions can increase the subsequent levels of female sexual behavior in male rats tested several months later following priming doses of EB. However, the present study demonstrates that a single injection of a large dose of EB (50 microng) two days after septal destruction did not modify subsequent responsiveness to EB priming in male rats relative to sham operated controls. Yet male rats given 10 daily injections of 5.0 microng EB/day immediately following a septal lesion were more responsive to EB than oil treated controls when tested later for lordosis behavior. Therefore, the capacity for EB to alter the behavioral effects of septal lesions on lordosis behavior in male rats is related to both chronic administration and a period of susceptibility to some action of EB during the immediate post-lesion period. In two additional experiments, chronic hypothyroidism induced by propylthiouracil or thyroidectomy was also found to modify the effects of septal lesions on female sexual behavior of male rats. These latter results indicate that EB is not unique in its capacity to alter the behavioral effects of septal lesions in male rats, and are consistent with the view that both EB and hypothyroidism may interact with some dynamic process associated with recovery from brain lesions.

Animals↗

A nurse-managed special care unit.

The authors describe the first year of operation of a nurse-managed intensive care unit (ICU). Concerned with the problems, costs, and inadequacies of caring for long-term patients in traditional ICUs, nurse administrators designed a special care unit that incorporates a physical design facilitating family involvement and rehabilitative care, registered nurse case management, and a shared governance management philosophy. Compared with traditional ICUs, the effectiveness of the special care unit is tested in terms of patient and nurse outcomes. Implications of this innovation for health-care delivery systems and the nursing profession are discussed.

Aged↗