bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of Pregnancy‐Induced Hypertension in Twins by Early Administration of Low‐Dose Aspirin: A Preliminary Report
Authors: Caspi Eliahu , Raziel Arieh , Sherman Dan , Arieli Shlomo , Bukovski Ian , Weinraub Zvi 
Published: May 2013

PROBLEM: Effectiveness of early administered low‐dose aspirin in prevention of pregnancy‐induced hypertension (PIH) and fetal growth retardation in twin pregnancies was investigated in a randomized placebo controlled, double‐blind trial in 47 twin pregnancies.METHOD: Twenty‐four women received 100 mg of aspirin daily from mean gestational age of 17.7 wk, and 23 women ingested placebo from a mean gestational age of 18 wk until delivery. The placebo and aspirin group were similar in age, weight gain, zygosity, gravidity, parity, and obstetrical antecedents. Treatment lasted for a mean period of 16.8 wk and 18.3 wk in the placebo and aspirin groups, respectively. The mean gestational age at birth was 35.0 wk and 36.4 wk in the placebo and aspirin groups, respectively.RESULTS: PIH was noted in six women (26%) in the placebo group, but in only one woman (4%) in the aspirin treated patients (P<.05). The mean combined fetal weights of both twins, and the mean weight of the second twin at delivery were significantly higher in the aspirin treated mothers than in the placebo treated gravidas (mean difference of 781 g, P<.02 and mean difference of 488 g, P < .005, respectively). Intrauterine growth retardation (< 10th percentile) concerned 11 (24%) and six (13%) fetuses in the placebo and aspirin groups, respectively. No adverse effects of treatment to either the mothers or the infants were noted.CONCLUSION: Low‐dose aspirin reduces the incidence of PIH and has a beneficial effect on fetal growth in twin pregnancies. Additional clinical trials are needed in order to define and select subgroups of twins where aspirin treatment is recommended.
Antisperm Antibodies (ASAs) in Infertile Males: Subclass Distribution of IgA Antibodies and the Effect of an IgA1 Protease on Sperm‐Bound Antibodies
Authors: Kutteh William H. , Kilian Mogens , Ermel Leann D. , Byrd E. William , Mestecky Jiri 
Published: May 2013

PROBLEM: (1) To determine the IgA subclass distribution of antibodies in the serum and on the sperm of infertile male patients. (2) To determine the effect of an IgAl protease on the binding of IgA antisperm antibodies (ASA).METHOD: Fifteen infertile males with ASA in serum (10) or on sperm (5) were recruited for this study. Duration of infertility was at least one year. Monoclonal antibodies to human IgAl and IgA2 were conjugated to immunobeads. The distribution of IgAl and IgA2 subclass ASA was determined for positive serum and sperm samples. The effects of an IgAl protease (isolated from Neisseria meningitidis strain HF13) on sperm‐bound antibodies was evaluated by immunobead binding.RESULTS: In serum, the IgAl subclass ASA was predominate (91%) when compared with IgA2 (9%) subclass. Direct sperm‐bound antibodies displayed a distribution more characteristic of the secretory immune system with IgAl accounting for 63% and IgA2 accounting for 37% of the total IgA ASA. Enzyme treatment dramatically reduced the amount of serum IgA antibodies bound to sperm (P < 0.05). Similarly, a significant reduction in direct sperm‐bound antibodies was observed after enzymatic treatment with no loss in sperm motility.CONCLUSIONS: (1) Although IgAl direct sperm‐bound antibodies were dominant, when compared with serum there was a higher proportion of IgA2 subclass, which suggests a local production of IgA. (2) Specific IgAl protease treatment is capable of reducing the amount of immunobead‐detectable IgA on sperm. Hamster oocyte sperm‐penetration assays are ongoing to determine if this treatment might improve sperm penetration rates.
Octreotide Effect on Ovarian Morphology in Insulin‐Resistant PCOS Patients Following Six‐Month Decapeptyl Treatment
Authors: Goni Marie‐Helene , Markussis Viron , Tolis George 
Published: May 2013

PROBLEM: Regulation of ovarian folliculogenesis involves bidirectional communication between the immune and endocrine systems. Somatostatin analogues have been reported to acutely suppress elevated androgens in polycystic ovary syndrome (PCOS). The aim of our study was to analyze the morphologic and hormonal‐metabolic response to octreotide therapy for one month in insulin‐resistant PCOS patients in whom luteinizing hormone (LH) effect had formerly been separated by a six‐month GnRH‐agonist (GnRH‐a) course.METHOD: Fifteen PCOS patients were studied two months after completing a six‐month GnRH‐a (decapeptyl 3.75 mg monthly injection) course. Seven of the patients (group A), who were insulin‐resistant and gave hyperinsulinemic response to a glucose challenge, received a 50‐μg subcutaneous injection of octreotide twice a day for one month. The nonhyperinsulinemic patients (group B) received placebo injections. Hormonal measurements, oral glucose tolerance test (OGTT), and transvaginal ovarian ultrasound were performed before and toward the end of the treatment period.RESULTS: After octreotide ovarian volume dropped significantly in group A (× ± SD) (19.2 + 5.1 versus 14.7 ± 5.5 cc, P = .02). LH levels increased (3.25 ± 1.22 versus 5.95 ± 4.34 mu/ml, P = .05) as did E2 levels (38.0 ± 11.4 versus 55.1 ± 12.7 pg/ml, P = .005). There was no change in follicle‐stimulating hormone, 17‐hydroxy‐progesterone, free testosterone, or androstenedione levels. Insulin secretion during OGTT dropped significantly (555 ± 294 versus 68 ± 29 μu/ml/hr, P = .002). Glucose tolerance was not affected. In contrast, the placebo‐treated group B patients showed an increase in ovarian volume (10.9 ± 3.5 versus 14.8 ± 3.3 cc, P = .001) while their gonadotropin and steroid profile relapsed, similarly to our patients receiving octreotide.CONCLUSIONS: Octreotide has an adjunctive beneficial effect to GnRH‐a on ovarian morphology although, at the dose used, there was no suppression of gonadotropin or ovarian steroid levels. The changes in ovarian morphology are probably mediated through suppression of insulin levels and/or other ovarian growth factors.
Separation of a 170‐K Delayed‐Implantation‐Associated Protein With Inhibitory Activity on Trophoblast Outgrowth and RNA Synthesis by Mouse Embryo
Authors: Katagiri Seiji , Yuen Basil Ho , Moon Young S. , Takahashi Yoshyuki , Kanagawa Hiroshi 
Published: May 2013

PROBLEM: To screen the uterine protein responsible for embryonic dormancy associated with delayed implantation.METHOD: Uterine protein extracts and sera from mice in which delayed implantation had been induced and those from pregnant mice were separated by three steps of chromatography and SDS‐PAGE by monitoring an inhibitory activity on trophoblast outgrowth. The presence of the separated protein in the uterine luminal fluid was assessed. Effect of the protein on cell proliferation and RNA synthesis by blastocysts were assessed.RESULTS: A 170‐K protein was found in the uterine tissue as well as uterine luminal fluid associated with delayed implantation. The 170‐K protein suppressed RNA synthesis by approximately 50% and cell proliferation in blastocysts.CONCLUSION: A 170‐K protein is secreted into the uterine lumen during delayed implantation period. The ability of 170‐K protein to suppress RNA synthesis and cell proliferation may play a role in regulation of embryonic dormancy associated with delayed implantation.
Lactation Stage‐Dependent Changes in Levels of Tumor Necrosis Factor/Cachectin in Milk
Authors: Rewinski M.J. , Yang T.J. 
Published: May 2013

PROBLEM: Determination of lactation stage‐dependent changes in levels of tumor neurosis factor (TNF) in milk.METHOD: Bioassay and immunoblocking assay were used to identify and assay tumor necrosis factor (TNF; mostly TNFα) in bovine milk at different stages of lactation.RESULTS: TNFα levels in milk started to increase steadily after the onset of drying‐off (weaning/involution), peaked at 4 to 6 wk prior to parturition and precipitously decreased to undetectable levels at parturition (colostrum). Thereafter, TNFα reappeared and maintained midlevel concentration in the mature (normal) milk throughout the rest of the lactation cycle. Analysis of cells in mammary secretions by flow cytometry revealed that elevated TNFα levels coincided with an increase in macrophages in the secretion from the dry period.CONCLUSIONS: These lactation stage‐dependent changes in TNFα levels reflect differential effects that TNFα have on involution and prepartum remodeling of the mammary gland of the dam and on gastrointestinal development and immunoregulatory function of the suckling.
Anti‐Sperm Antibodies in Female Mice: Responses Following Intrauterine Immunization
Authors: Stern Judy E. , Nelson Tina S. , Gibson Sarah H. , Colby Ester 
Published: May 2013

PROBLEM: The goal of this study was to measure anti‐sperm antibodies in serum following intraluminal uterine immunization and to compare this with the formation of antibodies following intraperitoneal (i.p.) or anal immunization.METHOD: Mice were immunized with human sperm, and antibody was measured using an indirect immunobead assay.RESULTS: High levels of anti‐sperm antibodies could be measured following intrauterine immunization and i.p. immunization. Anal immunization resulted in lower levels of antibody formation. Antibody formation after intrauterine immunization was less consistent following transcervical insertion than following needle insertion of sperm.CONCLUSION: The data suggest that intrauterine immunization can result in anti‐sperm antibody formation under some conditions.
Association of Sperm Antibodies With Other Autoantibodies in Infertile Men
Authors: Paschke R. , Bertelsbeck D. Schulze , Tsalimalma K. , Nieschlag E. 
Published: May 2013

PROBLEM: In many autoimmune diseases there is an increased incidence of other autoantibodies. However, the incidence of other autoantibodies in patients with seminal sperm antibodies is unknown. The most widely used tests to detect seminal and serum sperm antibodies are the mixed antiglobulin reaction (MAR) and the Tray agglutination test (TAT).METHOD: We therefore determined the incidence of antinuclear, antimitochondrial, thyroid peroxidase, and thyroglobulin antibodies, and rheumatoid factor in 147 patients investigated with MAR and 157 patients investigated with TAT.RESULTS: TAT positive patients had a significantly elevated incidence of antinuclear antibodies (χ2 test, P < 0.005) and thyroglobulin antibodies (χ2 test, P < 0.001). Thyroglobulin antibodies were increased in patients with MAR IgG > 40% and also significantly (χ2 test, P < 0.05) increased in MAR IgA positive patients. Furthermore, thyroid peroxidase antibodies were only found in TAT positive patients.CONCLUSIONS: The consistently increased incidence of thyroid autoantibodies in infertile patients with sperm antibodies may indicate an increased risk for the development of autoimmune thyroid disease. This finding therefore suggests screening of patients with immunologic infertility for autoimmune thyroid disease and a further evaluation of the prognostic and pathophysiologic significance of thyroid autoantibodies in immunologic infertility.
Anti‐ZP3 Antibodies Binding to the Human Zona Pellucida: Effect of Oocyte‐Storage Conditions
Authors: Hinsch Klaus‐Dieter , Hinsch Elvira , Pfisterer Susanne , Schill Wolf‐Bernhard , Gibbons William E. , Hodgen Gary D. , Oehninger Sergio 
Published: May 2013

PROBLEM: The zona pellucida protein 3 (ZP3) is a zona pellucida (ZP) glycoprotein crucially involved in fertilization. ZP3 plays a major role in sperm binding and induction of the acrosome reaction. In different species, ZP3 proteins differ in their primary structure as derived from cDNA clones. The hemizona assay (HZA) is a bioassay that evaluates binding of human sperm to human ZP and is highly predictive of fertilization outcome under in vitro conditions.METHOD: In these studies, we used antisera generated against synthetic ZP3 peptides to compare antibody binding patterns to ZP with sperm‐ZP binding capacity under different HZA conditions.RESULTS: Analysis of antibody binding to hemizonae derived from metaphase II human oocytes that were used either after refrigeration at 4°C or stored in a hyperosmotic salt solution revealed a strong reaction with human ZP3. However, treatment of human oocytes using a protocol to freeze embryos with the addition of 1,2 propanediol drastically reduced binding of ZP3 antibodies to the hemizonae. Nevertheless, no significant difference of sperm binding occurred under HZA conditions when oocytes were refrigerated, salt‐stored, or frozen with 1,2 propanediol.CONCLUSIONS: Our results indicate that the ZP3 protein backbone might be altered by 1,2 propanediol‐treatment while the glycoprotein‐receptor remains intact. We conclude that antisera against ZP3 peptides can be used as markers for the ZP3 protein backbone in human oocytes and might be useful tools for the evaluation of ZP3 protein integrity.
Myometrial Expression of mRNA Encoding Epidermal Growth Factor Receptor (EGFR) Throughout the Menstrual Cycle
Authors: Heiner James S. , Cai L. , Ding H. , Rutgers J.K.L. 
Published: May 2013

PROBLEM: To investigate the quantitative changes in expression of EGFR mRNA in the myometrium throughout the menstrual cycle.METHOD: Myometrium was collected at hysterectomy from 27 women with a history of regular cycles. Total RNA (20 μg) was isolated and analyzed by Northern blot using a human EGF‐R specific 32P‐labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units (DSU). Endometrial specimens from the same uteri were simultaneously evaluated for histologic dating of menstrual cycle day. EGFR gene expression in endometrium was previously reported. Statistical significance of the differences in myometrial gene expression between menstrual phases was evaluated by student's t test.RESULTS: EGFR mRNA was expressed in all myometrial tissues tested. Levels were higher in the late proliferative phase than in all other phases (P < .05). Women over 40 years old had lower proliferative phase expression than younger women.CONCLUSION: This data suggests that myometrial EGFR mRNA expression varies in association with the histologic phases of the normal menstrual cycle, and may be affected by aging, even when cycles occur at regular intervals.
Gestational Age Correlates With Immunosuppressive Properties of Hydatidiform Mole Pregnancies
Authors: Bennett William A. , Long Cecil A. , Mcgehee Ramon P. , Cowan Bryan D. 
Published: May 2013

PROBLEM: Soluble trophoblast extracts (HME) from some human hydatidiform mole pregnancies suppress IL‐2‐dependent T‐cell proliferation, while others express no immunosuppressive bioactivity. This study was designed to determine if suppression by HME was correlated with gestational age, uterine size, or hCG secretion.METHOD: Soluble extracts were prepared from nine hydatidiform mole trophoblast samples and screened for immunosuppressive activity using a murine cytotoxic T‐cell proliferation assay (CTLL‐2). Gestational ages were determined from last menstrual cycle and uterine size was estimated at the time of surgery. Serum samples were collected prior to uterine evacuation and were assayed for human chorionic gonadotropin (hCG).RESULTS: Four of nine HME samples significantly (P < 0.05) suppressed CTLL2 proliferation, while five exhibited no suppressive activity. A strong positive correlation (r = 0.639) was noted for the relationship between gestational age of the molar pregnancies and interleukin‐2(IL‐2)‐stimulated CTLL2 proliferation (expressed as % of control) in the presence of HME (500 μg/mL). This indicates that HME suppression of CTLL2 proliferation is highest in early gestation and then declines with increasing gestational age. A similar correlation was observed between estimated uterine size at surgery and CTLL2 proliferation with added HME, although the association was not as strong (r = 0.359). No association was noted between hCG levels and CTLL2 proliferative responses (r = −0.091).CONCLUSIONS: The results of this study suggest that production of immunosuppressive factors by hydatidiform mole trophoblast is developmentally regulated, and decreases with advancing gestation.
Nuclear Regulation of HLA Class I Genes in Human Trophoblasts
Authors: Chiang Mimi H. , Main Elliott K. 
Published: May 2013

PROBLEM: Human trophoblast expression of class I human leukocyte antigen (HLA) genes is unique in that there is no classical gene expression, but nonclassical HLA‐G is expressed and only by cytotrophoblast cells. This differential expression of classical versus nonclassical class I genes suggests tissue specific regulation. Recently, a negative regulatory element (NRE), 180 bp 5′ to transcription initiation was identified in a murine embryonal carcinoma cell line that markedly inhibited class I gene expression (Flanagan et al., Proc Natl Acad Sci USA 1991; 83:3145–3149).METHOD: Here we analyzed the human HLA‐A2 gene for a putative NRE sequence and determined whether such a sequence is capable of binding to factors present in a variety of class I‐null cell lines.RESULTS: Sequence analysis revealed that the NRE for human HLA‐A2 is identical to that for mouse H‐2Ld. Using gel shift assays with nuclear extracts (NE) from a variety of cell types, we demonstrated specific binding to the HLA‐A2 NRE sequence. The choriocarcinoma cell lines JEG and BeWo and the F9 cells (all negative for classical gene expression) contained this DNA binding factor(s). This binding factor was not present in NE from lymphocytes or a variety of other cell lines that were positive for classical gene expression.CONCLUSION: Human trophoblasts appear to have a tissue specific nuclear binding factor that may down regulate classical class I expression upon binding to the NRE sequence. The HLA‐G gene does not have this NRE region thus enabling its expression by these cells.
Characterization of Lymphocyte Subpopulations and T Cell Activation In Endometriosis
Authors: Witz Craig A. , Montoya Iris A. , Dey Tammy D. , Schenken Robert S. 
Published: May 2013

PROBLEM: Numerous studies have characterized the lymphocyte subpopulations in normal eutopic endometrium and suggested a role for the cytokine secretory products of these lymphocytes in regulating endometrial cell proliferation and differentiation. Recent studies have shown that ectopic endometrium contains a greater concentration of scattered stromal lymphocytes than does eutopic endometrium. However, the lymphocyte subpopulations and their activation status have not been characterized in ectopic endometrium.METHODS: We performed immunohistochemical studies on serial sections of proliferative and secretory phase eutopic endometrium and ectopic endometrium obtained during the proliferative phase using monoclonal antibodies to CD4 (T helper‐inducer cells), CD8 (T cytolytic‐suppressor cells), CD22 (B‐cells), CD56 (natural killer cells), and VLA‐1 (T‐cell activation marker).RESULTS: Ectopic endometrium contained significantly more scattered stromal CD4, CD8, and activated T cells than did proliferative and secretory eutopic endometrium. There were more activated T‐cells in proliferative than in secretory eutopic endometrium. Ectopic endometrium contained significantly fewer NK cells than proliferative and secretory endometrium.CONCLUSIONS: These results demonstrate that (1) the increased lymphocyte population in ectopic endometrium is due to increased numbers of CD4 and CD8 cells, and (2) a greater number of activated T cells are present in ectopic endometrium as compared to eutopic endometrium. Increased concentration of stromal T cells and enhanced VLA‐1 expression in ectopic endometrium suggest that cytokine products of the activated T‐cells may be involved in regulating cellular processes of endometriosis tissue.
Interferon‐Gamma (IFN‐γ) and Interleukin‐6 (IL‐6) in Peritoneal Fluid and Macrophage‐Conditioned Media of Women With Endometriosis
Authors: Keenan Jeffrey A. , Chen Thomas T. , Chadwell Nancy L. , Torry Donald S. , Caudle Michael R. 
Published: May 2013

PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN‐γ) and interleukin‐6 (IL‐6), and peritoneal macrophage production of IL‐6, in women with and without endometriosis.METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN‐γ and IL‐6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA.RESULTS: IL‐6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL‐6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL‐6 or IFN‐γ.CONCLUSIONS: Peritoneal macrophage IL‐6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN‐γ does not appear to be responsible for the activation of macrophages in women with endometriosis.