John Fanton
Oregon Health & Science University
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Featured researches published by John Fanton.
Nature Medicine | 1999
Laura Hewitson; Tanja Dominko; Diana Takahashi; Crista Martinovich; João Ramalho-Santos; Peter Sutovsky; John Fanton; Darla Jacob; Daymond Monteith; Martha Neuringer; David E. Battaglia; C Simerly; Gerald Schatten
Intracytoplasmic sperm injection has begun an era of considerable improvements in treating male infertility. Despite its success, questions remain about the dangers of transmitting traits responsible for male infertility, sex and autosomal chromosome aberrations and possible mental, physical and reproductive abnormalities. We report here the first births of rhesus monkeys produced by intracytoplasmic sperm injection at rates greater or equal to those reported by clinics. Essential assumptions about this process are flawed, as shown by results with the preclinical, nonhuman primate model and with clinically discarded specimens. Dynamic imaging demonstrated the variable position of the second meiotic spindle in relation to the first polar body; consequently, microinjection targeting is imprecise and potentially lethal. Intracytoplasmic sperm injection resulted in abnormal sperm decondensation, with the unusual retention of vesicle-associated membrane protein and the perinuclear theca, and the exclusion of the nuclear mitotic apparatus from the decondensing sperm nuclear apex. Male pronuclear remodeling in the injected oocytes was required before replication of either parental genome, indicating a unique G1-to-S transition checkpoint during zygotic interphase (the first cell cycle). These irregularities indicate that the intracytoplasmic sperm injection itself might lead to the observed increased chromosome anomalies.
Journal of Virology | 2001
Bijan Etemad-Moghadam; Daniela Rhone; Tavis Steenbeke; Ying Sun; Judith Manola; Rebecca Gelman; John Fanton; Paul Racz; Klara Tenner-Racz; Michael K. Axthelm; Norman L. Letvin; Joseph Sodroski
ABSTRACT The mechanism of the progressive loss of CD4+ T lymphocytes, which underlies the development of AIDS in human immunodeficiency virus (HIV-1)-infected individuals, is unknown. Animal models, such as the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae, can assist studies of HIV-1 pathogenesis. Serial in vivo passage of the nonpathogenic SHIV-89.6 generated a virus, SHIV-89.6P, that causes rapid depletion of CD4+ T lymphocytes and AIDS-like illness in monkeys. SHIV-KB9, a molecularly cloned virus derived from SHIV-89.6P, also caused CD4+ T-cell decline and AIDS in inoculated monkeys. It has been demonstrated that changes in the envelope glycoproteins of SHIV-89.6 and SHIV-KB9 determine the degree of CD4+ T-cell loss that accompanies a given level of virus replication in the host animals (G. B. Karlsson et. al., J. Exp. Med. 188:1159–1171, 1998). The envelope glycoproteins of the pathogenic SHIV mediated membrane fusion more efficiently than those of the parental, nonpathogenic virus. Here we show that the minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity is sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-lymphocyte depletion in monkeys. We also studied two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins by different mechanisms. Each of these changes attenuated the CD4+ T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4+ T lymphocytes in vivo.
Biology of Reproduction | 2000
L. Gabriel Sánchez-Partida; Gwendalyn M. Maginnis; Tanja Dominko; Crista Martinovich; Bryan McVay; John Fanton; Gerald Schatten
Abstract Artificial insemination (AI) and the cryopreservation of sperm with full reproductive capabilities are vital in the armamentarium of infertility clinics and reproductive laboratories. Notwithstanding the fantastic successes with AI and sperm cryopreservation in numerous species, including humans and cattle, these assisted reproductive technologies are less well developed in other species of importance for biomedical research, such as genetically modified mice and nonhuman primates. To that end, AI at high efficiency in the rhesus macaque (Macaca mullata) and the successful cryopreservation of rhesus sperm is presented here, as are the complexities of this primate model due to differences in reproductive tract anatomy and gamete physiology. Cryopreservation had no effect on the ability of sperm to fertilize oocytes in vitro or in vivo. Post-thaw progressive motility was not affected by cryopreservation; however, acrosome integrity was lower for cryopreserved (74.1%) than for fresh sperm (92.7%). Fertilization rates did not differ when fresh (58.1%; n = 32/55) or cryopreserved sperm (63.8%; n = 23/36) were used for in vitro fertilization. Similarly, pregnancy rates did not differ significantly after AI with fresh (57.1%; n = 8/14) or cryopreserved sperm (62.5%; n = 5/8). Seven live rhesus macaques were born following AI with fresh sperm, and three live offspring and two ongoing pregnancies were obtained when cryopreserved sperm were used. Cryopreservation of rhesus sperm as presented here would allow for the cost-effective storage of lineages of nonhuman primates with known genotypes. These results suggest that either national or international centers could be established as repositories to fill the global needs of sperm for nonhuman primate research and to provide the experimental foundation on which to explore and perfect the preservation of sperm from endangered nonhuman primates.
Endocrine | 2002
Timothy M. Hazzard; Richard M. Rohan; Theodore A. Molskness; John Fanton; Robert J. D'Amato; Richard L. Stouffer
Ovulation and conversion of the follicle into the corpus luteum involve remarkable changes in vascular permeability and neovascularization of the luteinizing granulosa layer. To evaluate the importance of these vascular events in follicle rupture and luteal development, sequential experiments were designed in which vehicle or angiogenic inhibitors (TNP-470 or angiostatin) were injected directly into the preovulatory follicle of rhesus monkeys during spontaneous mentstrual cycles. After control injections, 13 of 14 animals exhibited serum levels of progesterone (P) during the subsequent luteal phase that were comparable to untreated animals in our colony. Following low-dose (400 pg/mL) TNP-470, serum P levels increased normally until d 8 of the luteal phase, but then declined prematurely by d 9 (p < 0.05 compared to controls) and remained below controls until menses. Following high-dose (2 µg/mL) TNP-470, serum P levels were diminished in the early luteal phase (d 3–5; p<0.05 compared to controls), but reached typical levels at mid luteal phase, only to decline prematurely by d 9 (p<0.05) and remain low until menses. Control ovaries displayed indices of follicle rupture (protruding stigmata) and luteinization. TNP-470-treated ovaries exhibited signs of distension (torn surface epithelium/tunica albuginea) and luteinization; however, a well-formed stigmata was not observed. A “trapped” oocyte was not observed in serial sections of developing corpora lutea from control or TNP-470-treated animals. However, the early corpus luteum of TNP-470-injected ovaries contained pockets of excessive numbers of blood cells that were absent in controls. Angiostatin did not alter serum P levels or ovarian morphology compared to controls. These data suggest that acute exposure to the antiangiogenic agent TNP-470 impairs the development and functional capacity of the primate corpus luteum in a dose-dependent manner. The results are consistent with a critical role for angiogenesis in cyclic ovarian function in primates.
Nature | 2004
David M. Lee; Richard R. Yeoman; David Battaglia; Richard L. Stouffer; M. B. Zelinski-Wooten; John Fanton; Don P. Wolf
Journal of Experimental Medicine | 1999
Scott W. Wong; Eric P. Bergquam; Ryan M. Swanson; Felix W. Lee; Stanley M. Shiigi; Nancy Avery; John Fanton; Michael K. Axthelm
Journal of Experimental Medicine | 1998
Gunilla B. Karlsson; Matilda Halloran; Dominik Schenten; Juliette Lee; Paul Racz; Klara Tenner-Racz; Judith Manola; Rebecca Gelman; Bijan Etemad-Moghadam; Elizabeth Desjardins; Richard T. Wyatt; Norma P. Gerard; Luisa Marcon; David H. Margolin; John Fanton; Michael K. Axthelm; Norman L. Letvin; Joseph Sodroski
Journal of Virology | 1999
Mark J. Cayabyab; Gunilla B. Karlsson; Bijan Etemad-Moghadam; Wolfgang Hofmann; Tavis Steenbeke; Matilda Halloran; John Fanton; Michael K. Axthelm; Norman L. Letvin; Joseph Sodroski
Fertility and Sterility | 2003
David M. Lee; Richard R. Yeoman; David Battaglia; Richard L. Stouffer; John Fanton; Don P. Wolf
Obstetrical & Gynecological Survey | 1999
Laura Hewitson; Tanja Dominko; Diana Takahashi; Crista Martinovich; João Ramalho-Santos; Peter Sutovsky; John Fanton; Darla Jacob; Daymond Monteith; Martha Neuringer; David E. Battaglia; C Simerly; Gerald Schatten