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249 results on '"Murdoch, William J."'

64. Maternal Undernutrition from Early- to Mid-Gestation Leads to Growth Retardation, Cardiac Ventricular Hypertrophy, and Increased Liver Weight in the Fetal Sheep

Author

Vonnahme, Kimberly A., primary, Hess, Bret W., additional, Hansen, Thomas R., additional, McCormick, Richard J., additional, Rule, Daniel C., additional, Moss, Gary E., additional, Murdoch, William J., additional, Nijland, Mark J., additional, Skinner, Donal C., additional, Nathanielsz, Peter W., additional, and Ford, Stephen P., additional

Published
2003
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68. pH-Responsive Nanoparticles for Cancer Drug Delivery.

Author

Walker, John, Jain, Kewal K., Youqing Shen, Huadong Tang, Radosz, Maciej, Van Kirk, Edward, and Murdoch, William J.

Abstract

Solid tumors have an acidic extracellular environment and an altered pH gradient across their cell compartments. Nanoparticles responsive to the pH gradients are promising for cancer drug delivery. Such pH-responsive nanoparticles consist of a corona and a core, one or both of which respond to the external pH to change their soluble/insoluble or charge states. Nanoparticles whose coronas become positively charged or become soluble to make their targeting groups available for binding at the tumor extracellular pH have been developed for promoting cellular targeting and internalization. Nanoparticles whose cores become soluble or change their structures to release the carried drugs at the tumor extracellular pH or lysosomal pH have been developed for fast drug release into the extracellular fluid or cytosol. Such pH-responsive nanoparticles have therapeutic advantages over the conventional pH-insensitive counterparts. [ABSTRACT FROM AUTHOR]

Published
2008
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93. Ovarian responses to undernutrition in pregnant ewes, USA.

Author

Murdoch, William J., Van Kirk, Edward A., Vonnahme, Kimberly A., and Ford, Stephen P.

Subjects
*OVARIAN atresia, *EWES, *REPRODUCTIVE health, *EMBRYOLOGY, *ENDOCRINOLOGY, *BIOLOGY, *REPRODUCTION
Abstract

In most mammals oogonia proliferate by mitosis and begin meiotic development during fetal life. Previous studies indicated that there is a delay in the progression to the first stage of meiotic arrest in germ cells of female fetuses of undernourished ewes. We report that underfeeding (50% NRC requirement beginning on Day 28 of pregnancy) provokes an increase in oxidative base lesions within DNA of mid-gestational (Day 78) fetal oogonia; this condition was associated with upregulation of the tumor suppressor/cell-cycle arrest modulator p53, antiapoptotic factor Bcl-2, and base-excision repair polymerase β. Fetal ovarian weights and germ cell concentrations were not altered by nutrient deprivation. Ovaries of ewes on control diets (100% NRC) contained more tertiary follicles than their restricted counterparts; however, peripheral venous estradiol-17β was not different between groups. There was no effect of treatment on p53 accumulation in maternal oocytes. Luteal structure-function was not perturbed by undernutrition. No fetal losses were attributed to the dietary restriction. It is proposed that DNA of interphase fetal oogonia is vulnerable to oxidative insults perpetrated by a nutritional stress to the dam, and that multiple/integrated adaptive molecular response mechanisms of cell-cycle inhibition (providing the time required for base repairs) and survival hence sustain the genomic integrity and population stability of the germline. [ABSTRACT FROM AUTHOR]

Published
2003
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94. <atl>Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells

Author

Murdoch, William J. and Van Kirk, Edward A.

Subjects
*OVARIAN cancer, *CARCINOMA, *DNA, *APOPTOSIS
Abstract

Ovarian surface epithelial cells have been implicated in the genesis of common ovarian cancers. The integrity of DNA of ovarian surface epithelial cells contiguous with the ovulatory stigma becomes compromised during the rupture process; most cells degenerate by apoptosis, however some, bearing sublethal lesions, persist along the margins of ovulated follicles. Clonal expansion of a genetically-damaged surface epithelial cell (i.e. with unrepaired DNA, but not committed to death) can presumably give rise to ovarian carcinoma. It was hypothesized that estradiol and progesterone regulate ovarian surface epithelial cell-cycle dynamics associated with folliculo-luteal transitions and ovulatory wound repair/remodeling. Progesterone up-regulated the tumor suppressor p53 and inhibited baseline and estradiol-stimulated proliferation of cultured sheep ovarian surface epithelial cells. Anti/mitotic responses to steroid hormones were transcriptionally- and receptor-dependent. Rates of apoptosis (DNA fragmentation) were unaffected by progesterone. High concentrations of estradiol, via a nongenomic (perhaps antioxidant) mechanism, suppressed basal and H2O2-induced apoptosis. We suggest that, progesterone serves to inhibit proliferation of ovarian surface epithelial cells throughout the luteal phase—providing the time (growth arrest) required to correct any metabolic disturbances to DNA that are perpetrated as an inevitable by-product of the ovulatory process. With luteolysis and dominance of an estrogenic preovulatory follicle the ovarian surface epithelium is then regenerated. Thus, it is conceivable that perturbations to the steroid hormonal milieu of ovarian cycles could be a predisposing factor for cancerous transformation of an ovarian surface epithelial cell. [Copyright &y& Elsevier]

Published
2002
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97. Tumour necrosis factor α up-regulates matrix metalloproteinase-2 activity in periovulatory ovine follicles: metamorphic and endocrine implications

Author

Gottsch, Michelle L., Kirk, Edward A. Van, and Murdoch, William J.

Abstract

Abstract. The collagenous matrix of the wall of periovulatory follicles is degraded and remodelled during ovulatory ovarian rupture and luteinization. Matrix metalloproteinase-2 (MMP-2) belongs to a family of zinc endopeptidases that cleave extracellular proteins; its primary substrate is the type IV collagen of basement membranes. Tumour necrosis factor α (TNFα) is a putative mediator of collagenolysis and ovulation. The objective of this investigation was to ascertain the regulatory role of TNFa on MMP-2 activity relevant to the folliculo-luteal transition in ewes. Luteal regression and the preovulatory surge of gonadotropins were induced by administration of prostaglandin F 2 α and gonadotropin-releasing hormone (GnRH) on Days 14 and 15.5 (= 0 h) of the oestrous cycle, respectively. Ovulation occurs from the dominant follicle approximately 24 h after GnRH. An immunocapture-activity assay was used to measure MMP-2 in follicular extracts. Bioactive MMP-2 increased from 0 to 20 to 40 h after GnRH. Enzyme was immunolocalized at 40 h to the connective tissue framework that invades the parenchyma of the formative corpus luteum. Activity of MMP-2 was up-regulated by incubation (20 h) of 0-h follicular explants with TNFα; this response was suppressed by the transcriptional inhibitor actinomycin D. Activity of MMP-2 was reduced when preovulatory follicular tissues were incubated (12-h explants for 6 h) with TNFα antiserum. Ovulation was blocked by intrafollicular injection of TNFα antiserum. Unruptured follicles luteinized, but were deficient in collagenous/vascularized trabeculae, and produced less progesterone than their control luteal counterparts. It is suggested that TNFα, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum. Extra keywords: corpus luteum, luteinized unruptured follicle, progesterone, sheep, type IV collagen.

Published
2000

98. Production of Low Molecular Weight Chemoattractants for Leukocytes by Periovulatory Ovine Follicles1

Author

Murdoch, William J. and Mccormick, Richard J.

Abstract

Studies were performed to determine if periovulatory ovine follicles secrete chemoattractants for leukocytes, and if so, to begin to elucidate the chemical nature of such factors. Tissues were obtained at 0, 12, 24, and 36 h Ater initiation of the preovulatory surge of luteinizing hormone and placed in short-term incubation (ovulation occurs at approximately 24 h). Follicular-conditioned medium was tested for its ability to attract leukocytes by utilizing a linear under-agarose assay: chemotaxis was quantified as a function of the leading front of migration of cells. Neutrophils and eosinophils were attracted toward media conditioned with tissues of 24 and 36 h. Monocytes responded toward medium of tissues collected at 36 h. There was no evidence for chemoattraction of basophils or lymphocytes. Chemoattractant activity for granulocytes and monocytes was of low molecular weight origin (<3000) and water-soluble. High performance liquid chromatographic separation of this sample produced a distinct peak with recoverable activity. The isolated fraction was rich in glycine. Eosinophils also migrated toward an additional low molecular weight attractant that was extracted into ethyl acetate. Leukocytes attracted into periovulatory follicles might produce substances (eg., proteolytic enzymes and angiogenic factors) that play a role in the mechanisms of ovulation and luteinization.

Published
1989
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99. The effect of a progesterone-releasing intrauterine contraceptive device on uterine secretion of prostaglandin F2αand life-span of corpora lutea in the ewe

Author

Murdoch, William J., Lewis, Gregory S., Inskeep, E.Keith, and Tillson, Stephen A.

Abstract

Two studies were conducted to investigate the effect of a progesterone-releasing intrauterine contraceptive device (IUD) on uterine secretion of prostaglandin (PG) F2αassociated with IUD-induced luteolysis in sheep. In bilaterally ovulating ewes receiving an IUD on day 3 (estrus = day 0) intrauterine release of progesterone (90 μg per day) by the device did not prevent premature luteolysis or the increased concentration of PGF2αin uterine venous plasma on day 5 caused by conventional IUD's. In the second study a progesterone-releasing IUD (645 μg per day) inserted adjacent to the intact ovary at unilateral ovariectomy on day 14 inhibited early luteolysis in the subsequent estrous cycle and reduced the uterine secretion of PGF2αon day 5, without affecting concentrations of progesterone in the peripheral circulation at the intervening estrus. It is suggested that locally delivered intrauterine progesterone can inhibit IUD-induced luteolysis in the ewe by suppressing the uterine secretion of PGF2α.

Published
1978
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