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Biomedical subjects

R Winston

Publications and source records attributed to R Winston.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of Wilms' tumor suppressor gene (WT1) in human endometrium: regulation through decidual differentiation.

The Wilms' tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract and functions as a tissue-specific developmental regulator. In addition to its gene-regulatory function through DNA binding properties, WT-1 also regulates transcription by formation of protein-protein complexes. These properties place WT-1 as a major regulator of cell growth and differentiation. In view of these observations, we studied WT1 mRNA and protein in human endometrial extracts and in endometrial stromal cells (ESCs) differentiating into decidual cells in vitro, by RT-PCR and Western blotting, respectively. WT1 protein expression was also studied in situ in the proliferative and the secretory phase of the menstrual cycle in the early pregnant state. Analysis by PCR of total RNA prepared from human ESCs demonstrated the presence of WT1 mRNA and four WT1 mRNA splice variants. Western blot analysis of nuclear protein extracts from ESCs yielded one immunoreactive protein of the expected size (approximately 52-54 kDa) recognized by the WT1 antibody. Immunohistochemical staining showed that WT1 protein is localized only to nuclei of human endometrial stromal cells. It remains constant in the proliferative and the secretory phase of the menstrual cycle and is increased remarkably during decidualization in early pregnancy. ESCs decidualized in vitro were investigated for WT-1 expression, which confirmed that decidualizing stimuli (E2, medroxy-progesterone-acetate, and relaxin for 12 d or cAMP and progesterone for 1-4 d) induced WT-1 mRNA (P < 0.05) and increased protein levels (P < 0.05). These data indicate that in humans the WT1 gene is expressed in ESCs and its mRNA and protein levels remain constant in the proliferative and the secretory phase of the menstrual cycle and that WT1 mRNA and protein expression increases significantly in ESCs when these cells differentiate into decidual cells.

Cells, Cultured↗
PubMed2000

A prospective, randomized controlled trial comparing the efficacy of recombinant follicle-stimulating hormone in three different in vitro fertilization protocols.

OBJECTIVE: To compare the following IVF protocols: a short protocol and long protocols starting on day 2 or day 21. All protocols used recombinant FSH (rFSH) for ovarian stimulation. DESIGN: Prospective, randomized study. SETTING: An assisted reproduction unit at a university center. PATIENT(S): Patients undergoing IVF (n = 150) were treated according to one of the three treatment protocols allocated by a random method. INTERVENTION(S): All patients used buserelin acetate and rFSH. Patients began the long protocol on day 2 (group 1) or day 21 (group 2) of the cycle. Patients in group 3 began the short protocol on day 2 of the cycle. MAIN OUTCOME MEASURE(S): Ovarian response, implantation rates, and pregnancy rates (PRs). RESULT(S): Patients treated with the short protocol (group 3) were stimulated in a shorter time, required less rFSH, and achieved higher E(2) levels. The numbers of follicles, oocytes, and embryos were similar in all three groups. The implantation rates were similar in groups 1 and 2 (11.8% and 13.3%, respectively), and both were higher than in group 3 (4.1%). Clinical PRs per oocytes retrieved were 19.6%, 18.6%, and 8.3% in groups 1, 2, and 3, respectively. CONCLUSION(S): The implantation rate was significantly higher with the long protocols than with the short protocol, with a tendency for a higher PR as well.

Adult↗
PubMed2000

Comparison of pure tone and transient otoacoustic emissions screening in a grade school population.

HYPOTHESIS: Otoacoustic emissions provide an alternative to traditional pure tone hearing screening in a diverse grade school population. BACKGROUND: Mandated pure tone hearing screening programs for grade school children have several significant limitations. Otoacoustic emissions have been shown to be a reliable screening test in newborns, but there are no data on screening a diverse grade school population. METHODS: Five hundred eighty-three grade school children in four separate school populations were screened for hearing loss using the standard pure tone four-frequency protocol and transient evoked otoacoustic emissions. Students failing either test received a comprehensive audiogram by an audiologist that served as the "gold standard." Sensitivity and specificity of both tests were compared. RESULTS: The sensitivity and specificity of pure tone screening was 87% and 80%, respectively, compared with 65% and 91% for transient evoked otoacoustic emissions. CONCLUSION: Pure tone screening was a statistically significant better screening test for detecting hearing loss in this population of grade school children.

Arizona↗
PubMed2000

Dynamic assays of inhibin B and oestradiol following buserelin acetate administration as predictors of ovarian response in IVF.

The study was designed to examine whether dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were correlated with the ovarian response to stimulation in IVF. A total of 37 patients undergoing IVF treatment was studied when the long protocol was started in the early follicular phase. Blood samples were taken twice: on day 2 of the menstrual cycle, before the first s.c. administration of buserelin acetate 0.5 mg and on day 3, 24 h later. Inhibin B and oestradiol concentrations were compared with the ovarian response to stimulation. The ovarian response was defined in two ways: 'number of oocytes/total recombinant (r) follicle stimulating hormone (FSH) dose'; and 'square-root (number of follicles/total rFSH dose)'. The following measurements were highly correlated with the ovarian response to stimulation: increase in oestradiol (day 3-day 2 oestradiol concentration) [correlation coefficient (r) = 0.68, P: < 0.0001] and sum of inhibin B (day 2 + day 3 inhibin B concentrations) (r = 0.6, P: < 0.0001). Age and basal concentrations of FSH and inhibin B were inferior to the above measurements in terms of correlation with the ovarian response. In conclusion, dynamic measurements of inhibin B and oestradiol following single administration of buserelin acetate were highly correlated with the ovarian response to stimulation for IVF treatment.

Adult↗
PubMed1999

The human uniqueness of HIV: innate immunity and the viral Tat protein.

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period of post-infection latency, the titers of those natural antibodies decline and other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with HIV Tat protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparently induced Tat-reactive antibodies do arise. Evidence of a temporal relationship between the decline of the Tat reactive natural antibodies and progression of HIV pathogenesis, including demise of CD4+T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tat-related pathogenicity may be limited by the immune system recognition of the natural antibody-reactive sequences of Tat as "self" with consequent induction of tolerance and restriction of production of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resistance to tolerance-based diminishment of the protective natural antibodies. Although not yet defined, that characteristic may be shared by the occasionally observed HIV+ humans known as LTNP (longterm-non-progressors).

Animals↗
PubMed1997

Innate natural antibodies. Primary roles indicated by specific epitopes.

Two members of a unique class of natural antibodies have been identified in all of a large cohort of sera from clinically normal humans of broad age distribution. By means of a series of 10-12 mer peptides the epitope for each of those antibodies was characterized with regard to amino acid identity and conformation. Similar epitope specificity was revealed for the IgM isotopes of cord blood and early post natal sera and for IgM and IgG of adult sera, suggesting that the class of natural antibodies represented by the two identified in this study includes those genomically coded for at their effector level of maturation in the B cells of the neonate. Assay of series of specimens from each of four clinically normal adults revealed that those two natural antibodies are present at relatively constant titer, unique to each individual, over four to five and a half year periods. Those observations imply that the primary function of that class of natural antibodies may be related to maintenance of homeostasis and the molecular identity of each of the two epitopes suggests a role, for each, as monitor or control in intracellular traffic. The previous identification of those epitopes in a conserved protein of HIV also provides support for the proposition that a secondary function of natural antibodies, arising from fortuitous coincidence of the identity of the epitopes, may be that of early defense against infectious invaders.

Adult↗
PubMed1997

An innate natural antibody is reactive with a cryptic sequence of lactoferrin exposed on sperm head surface.

Lactoferrin (LF), an 80-kDa glycoprotein of ubiquitous occurrence in body fluids, is multifunctional and capable of assuming different configurations to serve those functions. The capacity of LF to undergo endocytosis and the recent demonstration of LF binding to sequence specific DNA indicate that a function or capability of LF, in addition to iron chelation, bacteriostasis, and receptor-specific lymphocyte binding, may be that of gene activation or silencing. The data of this report present a human physiological system, that of sperm entry into the oocyte in performance of fertilization in which, since LF is a component of the sperm protein coat, that capability could be expressed. However, the configuration of LF in that locus is one in which a revealed cryptic sequence provides the specific binding site for a natural antibody present in the fertilization milieu. The presence of that antibody suggests that a system of control of the potential interaction of LF with the intra-ooplasmic DNA, that of gametes or pronuclei, is operative. The configuration of LF on the sperm surface and designation of the reactive site for the natural antibody were enabled by a monoclonal antibody secreted by a hybridoma derived from a human cord blood B cell. Thus, in addition to information concerning the molecular flexibility of LF, these observations support the proposition that the repertoire of natural antibodies provides an innate homeostatic system, with each antibody serving a specific role.

Antigen-Antibody Reactions↗