Showing papers by "University of Massachusetts Medical School published in 1975"

The Effect of Estrogen and Progesterone on Uterine Prostaglandin Biosynthesis in the Ovariectomized Rat

Abstract: The role of 17a-estradiol and progesterone in the in vivo synthesis of prostaglandins by the ovariectomized rat uterus was investigated. Seven days after ovariectomy, rats were treated with progesterone (2 mg X 2 days) then given a single injection of estradiol. Prostaglandin E (PGE) and F (PGF) were determined by RIA in uterine tissue and uterine vein plasma (UVP) at 0, 0.5, 1, 2, 4, 8, 12 and 24 h after the administration of 1713-estradiol (10 Mg). PGF and PGE content (ng/uterus) remains constant from the time of estradiol administration to the latest time period studied. PGF and PGE concentrations (ng/100 mg uterine wt) show a gradual decline during the course of estrogen action which becomes significant only 12 and 24 h after estradiol administration and is correlated with the increase in uterine weight. Following progesterone administration, there is a significant increase in both uterine PGE content and concentration from ovariectomized levels. These results indicate that levels measured in UVP represent a true de novo synthesis of prostaglandins and could not be accounted for by the release of stored material into the uterine vein. PGF levels in UVP rose from control values of 2.42 ± 0.53 ng/ml to a maximum of 23.30 ± 4.96 ng/ml at 12 h and by 24 hhad returned to basal levels. A comparison with animals not treated with progesterone revealed low levels of PGF in UVP at all time periods studied (0.5-12 h). PGE levels in UVP after estradiol administration to progesterone-treated and untreated rats were similar, although at 12 h, levels in progesterone-treated rats were significantly greater than the untreated group. Determinations of estradiol in peripheral plasma by RIA revealed a sharp peak 1 h after administration followed by a rapid decline to control values by 12 h. Using the optimal conditions for prostaglandin biosynthesis as determined in the first part of this experiment (i.e.: 2 days of progesterone pretreatment and uterine cannulation 12 h after estradiol administration), the effect of estradiol doses between 0.001 and 100 g was investigated. Maximum UVP levels of PGE and PGF were obtained with doses greater than 1.0 Mg estradiol. The simultaneous administration of progesterone (2, 10 or 50 mg) with estradiol (10 Mg) significantly reduced PGF concentration in UVP, whereas only 50 mg progesterone was effective in significantly reducing PGE levels. Fifty mg of progesterone alone was without effect on PGE and PGF levels in UVP. It is concluded that estrogens are the predominant ovarian steroids involved in the regulation of uterine prostaglandin biosynthesis in the rat; however, important roles for progesterone in the expression of estradiol stimulated activity are indicated.

Prolonged antioestrogenic activity of ICI 46, 474 in the ovariectomized mouse.

Abstract: Prolonged antiestrogenic activity of ICI 46474 the trans-isomer of 1-(para-beta-dimethyl aminoethoxyphenyl)-12-diphenylbut-l-ene in the ovariectomized mouse was studied. The ability of the uterus and vagina to accumulate radio-labeled estradiol in vivo at various times after the administration of ICI 46474 was compared with the ability of the vagina to respond to estrogen. 3-mg ICI 46474 subcutaneously (sc) produced vaginal refractoriness to sc administered estradiol for up to 6 weeks. Maximum accumulation of (6 7-tritiated)estradiol-17beta was found in the uterus and vagina after 3-4 hours. 6 weeks after ICI 46474 administration radioactivity in the vagina was comparable to the controls and by 10 weeks uterine levels returned to control values. ICI 46474 caused an estrogenic effect upon the uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or bind estradiol.

New manual and automated method for determining activity of creatine kinase isoenzyme MB, by use of dithiothreitol: clinical applications.

Abstract: The method is based on the selective activating capacity of dithiothreitol on creatine kinase isoenzyme MB, after isoenzyme MM is activated by glutathione. Isolated isoenzymes MM and MB of human and canine origin were assayed individually and in mixtures of known activities. When glutathione was present in the assay medium the activity of each isoenzyme could be measured individually, but glutathione did not activate isoenzyme MB if it was present in a mixture with MM. Dithiothreitol, added to the serum before assay, activated the isoenzyme MB in the mixture. Values for MB activities obtained for isolated isoenzyme MB and for the isoenzyme mixture after dithiothreitol was added averaged 110 and 111 U/liter, respectively ( r = 0.998; y = 1.007 x + 0.298; n = 10). In the serum of 40 patients with documented acute transmural myocardial infarction, the mean proportion of isoenzyme MB activity measured in this way was 5.5% (coefficient of variation, 7.7%). Isoenzyme MB activities measured by use of dithiothreitol compared well with those obtained by conventional electrophoresis/spectrophotometry ( r = 0.998; y = 1.09 x -0.65) and spectrofluorometry ( r = 0.996; y = 1.10 x + 0.80). The assay of MB activity by the dithiothreitol method was automated, by use of an Abbott Bichromatic Analyser and a Calbiochem Super-Stat Pack Kit. In 60 isoenzyme MB determinations the manual and automated method correlated well ( r = 0.990; y = 1.0 x -1.36). The simplicity of isoenzyme MB determination by use of dithiothreitol and its ease of automation allow routine monitoring of the isoenzyme activity in patients with ischemic heart disease

The immune system of the nine-banded armadillo (Dasypus novemcinctus, Linn).

Abstract: The armadillo is rapidly emerging as an animal for biomedical research. A morphological study of the immune system of the armadillo was undertaken to try to demonstrate a possible defect in the morphogenesis of the lymphoid organs that could account for their susceptibility to leprosy. Blood from 20 domesticated adult armadillos revealed lymphocytes predominated among circulating leukocytes in the majority of animals, whereas in wild animals neutrophils predominated. Necropsies revealed well-developed thymus glands and the thymus-dependent areas in lymph nodes and spleens contained abundant lymphoid cells. Hence, we conclude that the susceptibility of the armadillo to leprosy cannot be explained on a morphological basis.

Problems in the Measurement of Urinary TRH

Abstract: Many studies of TRH physiology have been based on the radioimmunoassay of TRH in urine. In view of the inability of serum to deactivate urine TRH and the interference of urea with the TRH assay, measurement of urine TRH by radioimmunoassay may not be a true reflection of the actual concentration of TRH.

Inhibition of oestradiol binding to mouse uterine and vaginal oestrogen receptors by triphenylethylenes.

Abstract: This study was undertaken to determine the ability of ICI 46474 the trans-isomer of 1(p-beta-dimethylaminoethoxyphenyl)-12-diphenylbut-1-ene and of H774 to inhibit binding of (tritiated)-estradiol to the 8S estrogen receptor derived from ovariectomized mouse uterus and vagina tissues. Charles River CD strain mice were ovariectomized primed with 1 mcg of estradiol-17beta and used 2 weeks later. Animals were killed and uteri and vaginae dissected and immediately frozen. For use tissues were powdered and homogenized in 20 volumes of buffer. The subsequent techniques used are described. Results showed the presence of an 8S estradiol-binding macromolecule in both uterus and vagina tissues of the mouse. Since ICI 46474 and H774 inhibit the binding of estradiol to the mouse uterine and vaginal estrogen receptors part of their mechanism of action as antiestrogens and antifertility agents may be by direct antagonism of the 1st step of estrogen action in target tissues by binding estrogen receptor. This interaction with estrogen receptor also suggests how these compounds initiate estrogenic responses.

Studies on cyclic AMP metabolism in human epidermoid carcinoma (HEp-2) cells.

Abstract: Cultured human epidermoid carcinoma (HEp-2) cells were found to contain a highly responsive, catecholamine-sensitive adenyl cyclase activity in cellfree preparations. By contrast, cyclic AMP levels in intact HEp-2 cells were at best only marginally increased by catecholamines under a variety of conditions. The lack of an intact cell response could not be accounted for by escape of cyclic AMP to the medium, excessive phosphodiesterase activity, inactivation of the catecholamine, or by unusual kinetics of the system. However, in the presence of 1-methyl,3-isobutylxanthine (MIX), a potent phosphodiesterase inhibitor, a moderate catecholamine response was observed in the intact cells. A significant elevation of cyclic AMP levels in the presence of MIX was observed at 0.3 μ M epinephrine, and maximal levels occurred at 10 μ M . Norepinephrine was much less effective than either epinephrine or isopropylnorepinephrine at 10 μ M concentrations. In addition, intact cells slowly but steadily released cyclic AMP into the incubation medium over the course of 60-min incubations in the presence of MIX and epinephrine; maximum intracellular levels were reached by 5 min.

Initial clinical experiences with a Fresnel zone-plate imager.

Abstract: First clinical studies with a Fresnel zone-plate radioisotope imager demonstrate high resolution, sharp tomography, and freedom from scatter. Improved radionuclide imaging is demonstrated, at least for small organs like the thyroid. Certain limitations are present that indicate a need for additional development before application to routine clinical practice.

Effects of prolactin and LH on the activity of delta5-3beta hydroxy-steroid dehydrogenase, dihydro-orotic dehydrogenase, b-hydroxybutyrate dehydrogenase and glucose-6-phosphate dehydrogenase in the testis of the dwarf mice.

Abstract: The activity of delta5-3beta Hydroxysteroid hydro-genase, dihydro orotic dehydrogenase, B-Hydroxybutyrate dehydrogenase and glucose-6-phosphate dehydrogenase was studied in the testes of hereditary dwarf mice treated with Prolactin or LH. Two months old dw/dw dwarf mice were injected twice daily, for 14 days, either with 100 mug ovine Prolactin, or 5 mug ovine LH twice a day. Prolactin treatment increased the activity of all the enzymes assessed. Treatment with LH stimulated the activity of all the enzymes as compared to the saline treated animals but less than the Prolactin treated ones. The data bearing that the increased activity of several oxidising enzymes in the testes of hereditary dwarf mice is increased with Prolactin, is consistent with the suggested effect of this hormone on testicular steroidogenesis.

Organ culture of osteopetrotic (ia) rat bone: evidence that the defect is cellular.

Abstract: Calvarial bone from osteopetrotic (ia) rats and normal littermates has been cultured in a chemically defined medium supplemented with homologous serum to test for the presence of inhibitors or the absence of promoters of bone resorption in mutant serum. In addition, the response of mutant and normal bone to parathyroid extract and hydrocortisone was tested in vitro. The results indicate that mutant and normal serum do not differ with respect to their ability to support bone resorption and that ia bone responds to hydrocortisone but not parathyroid extract in organ culture. These data indicate that the skeletal defect in ia rats is not humoral but cellular.

Organization and Function of a Hospital Biomedical Engineering Internship Program

Abstract: This paper describes the development of an internship program between St. Vincent Hospital (SVH), a large community teaching hospital, and Worcester Polytechnic Institute (WPI), a school of engineering. The primary objective of the internship program is the education of the student through problem solving in the hospital environment under close faculty-physician supervision. WPI receives an expanded educational base, and SVH receives a diversified base of technical assistance. During the last three years of operation 70 students, 12 faculty, and 15 hospital project advisors have worked together on 29 different student projects. The organization and operation of the internship program are presented, and the essential features leading to its success are analyzed.