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S C Miller

Publications and source records attributed to S C Miller.

At least 199 records · Page 11Linked to original sources
PubMed1986

Unexpected presence of estrogens in culture medium supplements: subsequent metabolism by the yeast Sacchromyces cerevisiae.

We have previously shown the presence of 17 beta-estradiol in extracts of commercially prepared Saccharomyces cerevisiae ss well as the production of estradiol by yeast grown in the laboratory. In our current study, yeast grown in a chemically defined medium synthesized estradiol in only small amounts, (less than 500 pg/liter). We have analyzed a variety of media commonly used for growing yeast and found that substantial estradiol production (greater than 5 ng/liter) was obtained when yeast were grown in medium supplemented with Bacto-peptone. The peptone was shown to contain significant amounts of estrone, and the results of the experiments establish a precursor-product relationship where estrone from the medium is metabolized to estradiol by S. cerevisiae. Studies with added [3H]estrone demonstrated rapid conversion into [3H]estradiol and a 3H-labeled nonpolar estrogen derivative. The commercially obtained yeast used previously had been grown in a molasses medium. We demonstrate here that the molasses medium contains substantial amounts of estrone and estradiol. We conclude that the conversion of estrone in a culture medium to estradiol in laboratory grown yeast and estrone and estradiol present in the commercially grown yeast medium account for the majority of estradiol found in yeast.

Chromatography, High Pressure Liquid↗
PubMed1985

Plasticity of the differentiated state.

Heterokaryons provide a model system in which to examine how tissue-specific phenotypes arise and are maintained. When muscle cells are fused with nonmuscle cells, muscle gene expression is activated in the nonmuscle cell type. Gene expression was studied either at a single cell level with monoclonal antibodies or in mass cultures at a biochemical and molecular level. In all of the nonmuscle cell types tested, including representatives of different embryonic lineages, phenotypes, and developmental stages, muscle gene expression was induced. Differences among cell types in the kinetics, frequency, and gene dosage requirements for gene expression provide clues to the underlying regulatory mechanisms. These results show that the expression of genes in the nuclei of differentiated cells is remarkably plastic and susceptible to modulation by the cytoplasm. The isolation of the genes encoding the tissue-specific trans-acting regulators responsible for muscle gene activation should now be possible.

Aged↗
PubMed1985

The rapid appearance of acid phosphatase activity at the developing ruffled border of parathyroid hormone activated medullary bone osteoclasts.

The localization of acid phosphatase (ACPase) activity in and near parathyroid hormone (PTH) activated osteoclasts was investigated using electron microscopic cytochemical methods. At 3 hours after oviposition in Japanese Quail hens, medullary bone osteoclasts were highly reactive for ACPase but lacked ruffled borders. There was no evidence of extracellular ACPase activity associated with these osteoclasts. At 20 minutes after PTH administration, osteoclasts had developing ruffled borders and ACPase activity was found in the matrix and extracellular space adjacent to most of these ruffled borders. ACPase activity was seldom observed beyond the resorption zone delineated by the osteoclast clear zones. These results provide direct cytochemical evidence that the ruffled border functions in the release and/or activation of ACPase. In addition, these results show that ACPase localization is rapidly responsive to exogenous PTH.

Acid Phosphatase↗
PubMed1985

Effects of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid and 1-hydroxyethylidene-1,1-bisphosphonic acid on calcium absorption, plasma calcium, longitudinal bone growth, and bone histology in the growing rat.

Phosphonate compounds are of considerable interest because of their effects on biological mineralization and mineral metabolism. The effects of graded doses given parenterally or orally of N,N,N',N'-ethylenediamine tetramethylene phosphonic acid (EDITEMPA) on calcium absorption, plasma calcium, endochondral bone elongation, and osseous tissue histology of rats were determined. In some experiments 1-hydroxyethylidene-1,1-bisphosphonic acid (HEBP) was included for comparison. Given sc for 7 days, EDITEMPA caused dose-related decreases in net weight gain, intestinal calcium absorption, and longitudinal bone growth. There were also increases in total plasma calcium concentrations and excess osteoid accumulation in bone. When EDITEMPA was given po for 7, 28, or 90 days, few changes in osseous tissues were observed and then only at the highest dose (333 mg/kg/day). An equivalent dose of HEBP caused substantial changes in osseous tissues and calcium parameters.

Administration, Oral↗
PubMed1985

Comparative study of mexiletine and quinidine in the treatment of ventricular ectopia.

Mexiletine is an antiarrhythmic agent, structurally similar to lidocaine, but useful orally as well as intravenously. The safety and efficacy of mexiletine was compared with quinidine in a double-blind, parallel, randomized study of patients with chronic ventricular ectopia of various causes. Mexiletine was statistically more effective (P less than .05) than quinidine, though the total number of patients studied was small. Like quinidine, side effects limited the usefulness of mexiletine in certain patients, but these side effects are quite distinct from those of quinidine and other type I antiarrhythmic drugs. Mexiletine should be a useful addition to the armamentarium of antiarrhythmic drugs when it is released for clinical use in the United States.

Administration, Oral↗
PubMed1985

Changes in dentin appositional rates during pregnancy and lactation in rats.

Dentin appositional rates were determined in pregnant and lactating rats and compared with those in non-pregnant, age-matched controls. Appositional rates were calculated from measurements of distance between fluorescent mineralized tissue markers. There were significant increases in dentin apposition during pregnancy, with the greatest increases seen in the first two weeks. Dentin appositional rates decreased significantly during mid-lactation. These results indicate that homeostatic changes during pregnancy and lactation affect mineralized tissue accretion.

Animals↗
PubMed1985

Activation of avian medullary bone osteoclasts by oxidized synthetic parathyroid hormone (1-34).

Synthetic bovine parathyroid hormone (1-34) [bPTH(1-34)] has been treated with hydrogen peroxide and assayed for the effect of such treatment on the ability of bPTH(1-34) to activate medullary bone osteoclasts during their quiescent period in the early phase of the ovulatory cycle in Japanese quail. In addition, the same batches of oxidized and unoxidized bPTH(1-34) were assayed for their hypercalcemic activity in Japanese quail and their capacity to stimulate renal adenylate cyclase activity in the same species. Three groups, each consisting of five 5-month-old egg-laying Japanese quail (Coturnix coturnix japonica), were used. Between 4 to 5 hr after oviposition the three groups were injected intraperitoneally with acid saline (control) solution, bPTH(1-34) at 40 micrograms/bird, or oxidized bPTH(1-34) at 40 micrograms/bird, respectively. Twenty minutes after injection, the femoral bones were removed, split, fixed, and appropriately processed for examination by electron microscopy. Both oxidized and unoxidized bPTH(1-34) stimulated the development of osteoclast ruffled borders within 20 min after injection of the hormone preparations. As anticipated from previously published work from this laboratory, oxidized bPTH(1-34) retained its hypercalcemic activity and lost its capacity to stimulate renal adenylate cyclase activity in the Japanese quail. These results support, but do not prove, the contention that bPTH(1-34) exhibits its responses in the Japanese quail through the mediation of more than one type of receptor.

Adenylyl Cyclases↗
PubMed1985

Distributions of cell populations within alpha-particle range of plutonium deposits in the rat and beagle testis.

Plutonium is not uniformly distributed in testicular tissues; thus some cell populations may receive larger or smaller radiation exposures than would be expected if the nuclide were uniformly distributed. The distributions of cell populations within alpha-particle range of Pu deposits in rat and beagle testes were determined. The data were collected from autoradiographs of testicular tissues containing 241Pu. A cell distribution factor (CDF) was determined for each cell population and is defined as the average number of each cell type within alpha-particle range of each observed Pu deposit relative to the number of each cell type that would be expected within alpha-particle range of each Pu deposit, if the deposits were distributed uniformly. In addition, the percentage of the spermatogonial stem cell population within alpha-particle range of Pu deposits was determined. In rats, the CDF for the spermatogonial stem cells is about 2.2. This value is similar to other enhancement and inhomogeneity factors reported for rodents in the literature. In beagles the CDFs to all cells in the seminiferous epithelium were less than the rats. In addition, the percentage of spermatogonial cells within alpha-particle range of Pu concentrations in the interstitial tissues was a factor of about 3 less in the dog than in the rat. The largest CDFs seen in both species were in the interstitial tissues, particularly for Leydig cells. Because the organization of testicular tissues in the beagle is quite different from rodents but more similar to human, the results from this study suggest that extrapolations from rodents to humans may tend to overestimate the potential for radiation exposure to spermatogonial stem cells as well as the fraction of the spermatogonial stem cell population at risk to exposure from internally deposited 239Pu.

Alpha Particles↗
PubMed1984

Characterization of an estrogen-binding protein in the yeast Saccharomyces cerevisiae.

This paper further characterizes the estrogen-binding protein we have described in the cytosol of the yeast Saccharomyces cerevisiae. [3H]Estradiol was used as the radioprobe, and specific binding of cytosol fractions was measured by chromatography on Sephadex minicolumns. Other 3H-steroids did not exhibit specific binding. [3H]Estradiol binding was destroyed by treatment with trypsin, but not RNase, DNase, or phospholipase; N-ethylmaleimide substantially decreased the binding. The yeast did not metabolize estradiol added to the medium, and extraction and chromatography of the bound moiety showed it to be unmetabolized estradiol. Scatchard analysis of cytosol from both a and alpha mating types as well as the a/alpha diploid cell revealed similar binding properties: an apparent dissociation constant or Kd(25 degrees) for [3H]estradiol of 1.6-1.8 nM and a maximal binding capacity or Nmax of approximately 2000-2800 fmol/mg of cytosol protein. Gel exclusion chromatography on Sephacryl S-200 and high performance liquid chromatography suggested a Stokes radius of approximately 30 A. Sucrose gradient centrifugation showed a sedimentation coefficient of approximately 5 S, and the complex did not exhibit ionic dependent aggregation. The estrogen binder in S. cerevisiae differed in its steroidal specificities from classical mammalian estrogen receptors in rat uterus. 17 beta-Estradiol was the best competitor, 17 alpha-estradiol had about 5% the activity, and diethylstilbestrol exhibited negligible binding affinity as did tamoxifen, nafoxidine, and the zearalenones. In summary, a high affinity, stereospecific, steroid-selective binding protein has been demonstrated in the cytosol of the simple yeast S. cerevisiae. We speculate that this molecule may represent a primitive hormone receptor system, possibly for an estrogen-like message molecule.

Cytosol↗
PubMed1984

Life history of cells mediating natural resistance to tumor cells and bone-marrow transplants: the respective roles of cell lineage commitment and host environment in determining strain characteristics of natural resistance to foreign marrow grafts.

A class of cells present in the blood and lymphoid tissues of mammals produces rapid cytolysis of tumor cells on first contact. Abundant evidence suggests that such natural killer (NK) cells play a role in tumor immunosurveillance in vivo. A similarly prompt and spontaneous activity can cause the rejection of foreign marrow transplants. These phenomena are known collectively as natural resistance. The cells mediating natural resistance are lymphoid in morphology, but are neither T nor B lymphocytes. Kinetically, NK cells and cells mediating natural resistance to foreign marrow grafts are themselves nondividing but are rapidly renewed from radiosensitive proliferating precursors in the bone marrow. They appear to have no long-lived (memory) component. Newly formed NK cells have a short residence time in the spleen. Other general properties of the natural-resistance cell lineage, including strain variation, ontogeny, and cell phenotype, are reviewed in this article. The present study aimed to examine the respective roles of cell lineage commitment and of the host environment in determining strain characteristics of natural resistance to foreign marrow grafts. Chimeras produced by inoculating mice of a strain that normally has little or no natural resistance with bone marrow from adult mice of a highly resistant strain develop resistance to a third-party marrow allograft. Such chimeras do not develop the full rejection capacity of the high-resistance strain, however; and chimeras created by inoculating marrow from infant mice develop less resistance than those reconstituted by bone marrow from adult mice. The results demonstrate that the ability to reject foreign marrow grafts develops as an intrinsic property of the natural-resistance cell lineage. The host environment may provide an additional influence, however, particularly in the initial development of natural resistance in early postnatal life.

Animals↗
PubMed1984

Morphological and ultrastructural aspects of the activation of avian medullary bone osteoclasts by parathyroid hormone.

The activation of physiologically inactive medullary bone osteoclasts by parathyroid hormone (PTH) was examined using light and electron microscopy and histomorphometric methods. Medullary bone osteoclasts are functionally inactive during the avian egg-laying cycle when an egg shell is not being calcified in the shell gland. Japanese quail hens were given 0.5 IU/g PTH and the medullary bone osteoclasts were examined up to 90 min later. Administration of PTH results in rapid changes in osteoclast morphology and ultrastructure. Within 10 min ectoplasmic regions containing condensed-appearing material are evident in areas of the cell adjacent to bone surfaces. In tannic acid-fixed specimens, these ectoplasmic regions contain bundles of filaments extending perpendicularly from the osteoclast plasma membrane into the cytoplasm. It is in these areas that ruffled border development is initiated. Even at 10 min after PTH administration, mineral crystals are seen between the developing cell surface invaginations and folds. By 15 min after PTH administration, ruffled borders have appeared next to bone surfaces. The rapid development of ruffled borders on medullary bone osteoclasts after PTH is confirmed by electron microscope histomorphometry. By 30 min after PTH administration, ruffled borders are well developed and large endocytic vacuoles are beginning to appear in the osteoclast cytoplasm. Light microscope histomorphometric measurements indicate that osteoclasts are also increasing in size and spreading along bone surfaces with time after PTH administration. This study provides a morphologic and ultrastructural description of osteoclast activation by PTH. The results indicate that osteoclasts may effect rapid changes in bone resorption and mineral metabolism due to exogenous PTH in hens.

Animals↗
PubMed1984

Identification and characterization of mononuclear phagocytes isolated from rat testicular interstitial tissues.

Rat testicular interstitial tissues contain numerous mononuclear phagocyte-like cells. Dispersed testicular tissues are allowed to settle onto a glass substrate and the strongly adherent cells are identified as the same cells that have been described in vivo, based on the retention of an in vivo marker (plutonium). These putative testicular intersitial tissue macrophages (TIMs) have adhesion and cell surface features characteristic of mononuclear phagocytes, as determined by scanning electron microscopy. Immediately after isolation from testicular tissues, TIMs show a strong staining reaction for nonspecific esterase. These cells have Fc and complement receptors and some express Ia cell-surface antigens. About two thirds of the TIMs phagocytose sheep red blood cells and most of the cells are capable of nonspecific phagocytosis of polystyrene beads. This study demonstrates that the phagocytic cells found in testicular interstitial tissues have morphological, histochemical, phagocytic, and immunological properties characteristic of functionally active mononuclear phagocytes. These results suggest that these resident mononuclear phagocytes may play a role in immune-related functions in the testis.

Animals↗
PubMed1984

Changes in endochondral bone elongation rates during pregnancy and lactation in rats.

The rates of endochondral bone elongation during pregnancy and lactation in rats have been studied. The rate of growth at the distal femoral epiphyseal growth plate was measured using fluorescent bone markers. Endochondral growth rates were substantially increased in pregnant animals when compared with age-matched, nonmated controls. There were also increases in growth plate thickness, hypertrophic cell lacunar height, and the calculated rate of cell production during pregnancy. At parturition, this growth trend was reversed and during lactation there were significant decreases in endochondral growth rates. There were also corresponding decreases in growth plate thickness, hypertrophic cell lacunar height, and the calculated rate of cartilage cell production. These results indicate that significant changes occur in maternal endochondral growth rates during the reproductive cycle in rats.

Animals↗
PubMed1984

Fetal thymic pre-T cells neither demonstrate nor develop natural killer cell activity.

The postulate made by some investigators that functional NK cells are of pre-T lineage remains highly controversial. The present study tested this possibility by adoptive transfer of fetal thymocytes, rich in pre-T cells, into aged syngeneic mice which show thymic involution and low or no splenic NK activity. Splenic NK activity of aged CBA/J mice at 1 or 3 days after intravenous injection of fetal thymocytes was measured with a 4-hr chromium-release assay. Another group received saline only and a third group received either thymocytes as above or saline, and were subsequently injected with the interferon inducer, poly(I:C), 12 hr prior to removal of their spleens for the NK assay. The results revealed that reconstitution with fetal thymocytes did not restore NK activity in aged mice at 1 or 3 days after thymocyte inoculation. Poly(I:C) treatment caused an elevation of NK activity in both thymocyte-injected and control mice. The spleens of aged hosts given young adult splenocytes, on the other hand, had significantly elevated NK activity over controls. Collectively, the results demonstrate that while the adult spleen contains functional NK cells, the fetal thymus, rich in pre-T cells, does not contain functional NK cells or NK precursors as detected by maturation into functional NK cells within 3 days in the aged secondary hosts.

Aging↗