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28. CADMIUM MOBILIZATION BY NITROGEN DONOR CHELATING AGENTS.

Author

Jones, Mark M., Xu, Cunyong, Singh, Pramod K., and Walker, Ernest M.

Abstract

The relative abilities of a series of acyclic polyamine chelating agents containing only nitrogen donors (N-donors) to induce the urinary excretion of cadmium has been examined in the rat. The compounds examined include triethylenetetramine dihydrochloride (TRIEN), tris(2-aminoethyl)amine trihydrochloride (TREN), tetraethylenepentamine pentahydrochloride (TETRAEN), and pentaethylenehexamine hexahydrochloride (PENTAEN). Sodium N-methyl-D-glucamine-N-carbodithioate (NaG) was used as a positive control compound. The polyamines induced a significant increase in the urinary excretion of cadmium in rats that had been loaded with cadmium at least 4 d prior to the polyamine treatments. A comparison of these with similar data on macrocylic nitrogen donor systems, which form much more stable complexes with cadmium but are also ineffective in enhancing the excretion of cadmium from such aged deposits, suggests that the factors responsible for the relative inefficiency of these compounds may involve either a difficulty in penetrating cellular membranes or a slow rate of reaction with biologically bound cadmium. The occurrence of oliguria and anuria following the administration of the several of the polyamines indicates that their use is accompanied by significant renal damage in cadmium-exposed rats. [ABSTRACT FROM AUTHOR]

Published
1996
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32. Management of sickle hemoglobinopathies in pregnant patients

Author

Miller, Joseph M., Horger, Edgar O., Key, Thomas C., and Walker, Ernest M.

Abstract

During the past decade, pregnancy outcome has improved among patients with sickle hemoglobinopathies. The role of prophylactic exchange transfusion in this improvement is uncertain. This study reviews the experience in 64 pregnancies managed at the Medical University Hospital over a 7 year period. Prophylactic exchange transfusion was not associated with improved pregnancy outcome and was associated with significant antibody formation. Exchange transfusion may best be reserved as a treatment modality when infection, crisis, or symptomatic anemia occurs in patients with a sickle hemoglobinopathy.

Published
1981
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33. Effects of prolonged exposure to dietary DDT and PCB on rat liver morphology

Author

Jonsson, Haldor T., Walker, Ernest M., Greene, William B., Hughson, Michael D., and Hennigar, Gordon R.

Abstract

Livers from mature female rats exposed for up to 36 weeks to dietary levels of Aroclor® 1242 (75 or 150 ppm) and/or commercial grade DDT (75 or 150 ppm) were compared to those from animals receiving basal diets. In earlier studies, reproductive effects of the test substances were assessed. Moreover, the markedly abnormal gross appearance of the livers led to examination of the hepatic effects of PCB and DDT in more detail, at both the light microscope (LM) and electron microscope (EM) levels.

Published
1981
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34. Automated erythrocytopheresis for sickle cell anemia during pregnancy

Author

Key, Thomas C., Horger, Edgar O., Walker, Ernest M., and Mitchum, Ernestine N.

Abstract

Automated erythrocytopheresis allows for selective removal of erythrocytes from whole blood by means of extracorporeal centrifugation and separation. Remaining cellular and liquid fractions are returned to the patient, along with donor erythrocytes. Supertransfusion with the use of plasmapheresis and simultaneous direct transfusion of erythrocytes increases the hematocrit while maintaining stable intravascular volume. This technique was used in the prophylactic exchange transfusion in eight pregnant women with sickle hemoglobinopathies. Two patients required repeat procedures 7 arid 13 weeks later for hemoglobin A concentration or hematocrit less than 25%, The results from the first five pregnancies are detailed. All pregnancies were carried to term, with the delivery of healthy infants. There was no fetal or neonatal morbidity, and the only maternal morbidity was a case of puerperal endometritis. Erythrocytopheresis has been established as a flexible and useful means of managing gravid patients with sickle hemoglobinopathies.

Published
1980
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35. Antitumor Action of Dichloro (4,5–dimethyl–o–phenylenediamine–N,N') platinum (II)1

Author

Gale, Glen R., Atkins, Loretta M., Walker, Ernest M., Smith, Alayne B., and Meischen, Sandra J.

Abstract

Dichloro (4,5–dimethyl–o–phenyl–enediamine–N,N′)platinum (II) (DDPP) was synthesized by the reaction of 4,5–dimethyl–o–phenylenediamine with potassium tetrachlo–roplatinate. The resulting compound extended up to 176% the survival times of BALB/c mice bearing the Ehrlich ascites tumor and up to 74% the survival times of BDF1mice bearing the L1210 leukemia. In studies using Ehrlich ascites tumor cells in vitro, DDPP was found to be a potent inhibitor of synthesis of DNA, RNA, and protein; the concentrations which conferred 50% inhibition following 1.5 hr of incubation with the compound were 3 × 10-5to 5 × 10-5M. Inhibition of nucleic acid and protein synthesis in vitro, once established, was not ameliorated by washing the cells with fresh medium devoid of DDPP. Cellular DNA, RNA, and protein, each appropriately labeled with a radioisotopically labeled precursor, became more acid–soluble upon incubation of the cells in vitrowith DDPP. The rate of loss of viability of cells incubated in vitrowith DDPP, as assessed by the trypan blue exclusion method, was found to be considerably greater than the rate obtained upon incubation of cells with an equivalent concentration of cis–dichlorodiammineplatinum(II).

Published
1973
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36. Antitumor and Antimitogenic Properties of the Photochemical Reaction Product of Ammonium Hexachloroiridate(IV)1

Author

Gale, Glen R., Walker, Ernest M., Smith, Alayne B., and Stone, Anita E.

Abstract

The photochemical reaction product of ammonium hexachloroiridate(IV) retards the rate of development of the Ehrlich ascites carcinoma in BALB/c mice and, to a lesser degree, the development of the L1210 leukemia in BDF1mice. Of the various dos age regimens examined, a maximum of 140% increase of mean survival time was obtained with mice bearing the Ehrlich carcinoma, but only a 20% increase was demonstrated with mice bearing the L1210 leukemia. Blastogenic transformation of phytohemagglutinin-stimulated human lymphocytes in culture was also inhibited by the product, as evidenced by a reduced rate of incorporation of thymidine into cultured cells. No evidence was obtained that the product was a selective inhibitor of deoxyribonucleic acid synthesis; rates of ribonucleic acid and protein synthesis were inhibited to the same extent as the rate of deoxyribonucleic acid synthesis in both cultured human lymphocytes and Ehrlich ascites carcinoma cells in vitro.

Published
1971
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41. Antileukemic Properties of Organoplatinum Complexes2

Author

Meischen, Sandra J., primary, Gale, Glen R., additional, Lake, Lanny M., additional, Frangakis, Crist J., additional, Rosenblum, Michael G., additional, Walker, Ernest M., additional, Atkins, Loretta M., additional, and Smith, Alayne B., additional

Published
1976
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49. Aging influences multiple indices of oxidative stress in the heart of the Fischer 344/NNia x Brown Norway/BiNia rat.

Author

Asano S, Rice KM, Kakarla S, Katta A, Desai DH, Walker EM, Wehner P, and Blough ER

Subjects
Aldehydes metabolism, Analysis of Variance, Animals, Blood Pressure physiology, Female, Heart physiopathology, Heat-Shock Proteins metabolism, Immunoblotting, Immunohistochemistry, Male, Microscopy, Fluorescence, Mitogen-Activated Protein Kinases metabolism, Myocardium pathology, Phosphorylation, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Rats, Inbred BN, Rats, Inbred F344, Regression Analysis, Signal Transduction physiology, Superoxides metabolism, Tyrosine analogs & derivatives, Tyrosine metabolism, Aging physiology, Myocardium metabolism, Oxidative Stress, Reactive Oxygen Species metabolism
Abstract

We report the influence of aging on multiple markers of oxidative-nitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSd x Brown Norway/BiNia (F344/NXBN) rats. Compared to adult (6-month) hearts, indices of oxidative (superoxide anion [O2*-], 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were 34.1 +/- 28.1%, 186 +/- 28.1% and 94 +/- 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r > 0.669; r > 0.710 and P < 0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-kappaB) activities, signaling (mitogen-activated protein kinases along with Src), apoptotic (Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.

Published
2007
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