Biomedical subjects

J H Segars

Publications and source records attributed to J H Segars.

11 recordsLinked to original sources

PubMed1992

Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2RIIBP in undifferentiated embryonal carcinoma cells.

H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex (MHC) class I genes. The binding occurs through the GG(T/A)CA motif present also in many other genes. The role of H-2RIIBP in developmental regulation of MHC class I genes has been studied in undifferentiated N-Tera2 embryonal carcinoma cells by transient cotransfection of an expressible H-2RIIBP plasmid and a chloramphenicol acetyltransferase reporter gene linked to the MHC class I promoter. Transfection of the expression plasmid led to production of H-2RIIBP transcripts and enhanced MHC class I promoter activity in cells that were treated with retinoic acid but not yet differentiated. Retinoic acid concentrations required for transactivation overlapped with those capable of inducing morphological differentiation and expression of endogenous MHC class I genes in these cells. This enhancement was mediated by region II, as a heterologous thymidine kinase promoter driven by region II also served as a target for H-2RIIBP transactivation. Deletion of the bulk of the DNA-binding domain or the ligand-binding domain of H-2RIIBP, but not of the N-terminal domain, abolished transactivation, indicating that the former two domains are critical for the enhancement. Moreover, H-2RIIBP transactivation exhibited a strict cell-type restriction. As observed in other cell lines, N-Tera2 cells that had undergone differentiation failed to elicit transactivation, suggesting that H-2RIIBP acts in concert with a cofactor expressed in undifferentiated N-Tera2 cells that requires retinoic acid for its function. These results suggest that H-2RIIBP can function as a developmentally specific transcription factor for MHC class I genes.

Base Sequence↗

PubMed1992

H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.

H-2RIIBP (RXR beta) is a member of the nuclear hormone receptor superfamily that activates transcription of MHC class I genes in response to retinoic acid (RA). Using chemical cross-linking, co-immunoprecipitation, gel mobility shift and streptavidin-biotin DNA precipitation assays, we show that H-2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3R alpha and RAR alpha). H-2RIIBP heterodimer formation required a conserved sub-domain of its C-terminal region, occurred independently of target DNA and was much more efficient than either T3R alpha/RAR alpha heterodimer or H-2RIIBP homodimer formation. Heterodimers displayed enhanced binding to target DNA elements and contacted DNA in a manner distinct from that of homodimers. A functional role for heterodimers in vivo was demonstrated by synergistic enhancement of MHC class I transcription following co-transfection of H-2RIIBP with T3R alpha or RAR alpha. We provide biochemical evidence that H-2RIIBP formed heterodimers with several naturally occurring nuclear proteins. The results suggest that H-2RIIBP, by virtue of its ability to heterodimerize, enhances combinatorial diversity and versatility in gene regulation mediated by nuclear hormone receptors.

Amino Acid Sequence↗

PubMed1992

H-2RIIBP expressed from a baculovirus vector binds to multiple hormone response elements.

H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex class I genes. Based on its homology with Drosophila XR2C/CF1, H-2RIIBP may play a role in development. By using a baculovirus expression system, a large amount of recombinant H-2RIIBP was produced. The recombinant protein accumulated in the nucleus of insect cells. A series of monoclonal antibodies reacting with the recombinant H-2RIIBP was then generated. A DNA-protein immunoprecipitation assay was developed with these antibodies, enabling the DNA-binding specificity of H-2RIIBP to be distinguished from that of an endogenous region II binding factor expressed in uninfected insect cells. We show that H-2RIIBP binds to estrogen response elements with an affinity comparable to that for the region II enhancer. H-2RIIBP also bound to some, but not all, thyroid hormone response elements and retinoic acid response elements, albeit at a lower affinity. Binding to these elements was demonstrated without exogenous addition of a ligand. The H-2RIIBP binding specificity determined by this assay was in agreement with the specificity assessed by Southwestern and gel mobility shift assays. Furthermore, methylation interference assays indicated that H-2RIIBP recognizes the conserved hormone response motif GG(T/A)CA. Taken together, these data demonstrate that H-2RIIBP is capable of binding to hormone response elements of a variety of genes. They suggest that H-2RIIBP may exert a pleiotropic function.

Amino Acid Sequence↗

PubMed1991

Selective fallopian tube canalization.

Infertility is an increasingly common problem. Occlusion of the fallopian tubes is one of the principal causes, and until recently surgery was the only available treatment. The success rate of surgery is often low, particularly with occlusion of the proximal tube. Selective fallopian tube canalization under fluoroscopic guidance has been successful in alleviating proximal tubal obstruction. This procedure may be performed in the outpatient setting and is a safe, cost-effective alternative to surgery.

Adult↗

PubMed1990

The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET).

The use of gonadotropin releasing hormone agonists (Gn-RHa) has been shown to improve the response in patients classified as "poor responders" undergoing ovarian stimulation for in vitro fertilization/embryo transfer (IVF/ET). This study sought to determine whether GnRHa therapy would benefit patients undergoing IVF/ET who had been classified as "good responders" in prior attempts. Twenty-three patients who had completed a prior IVF/ET attempt but who failed to conceive underwent ovarian stimulation using a combination of GnRHa and human menopausal gonadotropin (hMG). Each patient's prior stimulation served as her control and consisted of clomiphene citrate (CC)/hMG in 18 patients and follicle stimulating hormone (FSH) and/or hMG in 5 patients. The numbers of oocytes retrieved, oocytes fertilized, embryos cleaved, and embryos transferred were all significantly greater in cycles treated with GnRHa/hMG compared to control cycles. The clinical pregnancy rate was 39% and the ongoing pregnancy rate was 26% during the cycle when GnRHa pretreatment was utilized. These data suggest that GnRHa therapy is of benefit even to those patients previously classified as "good responders" undergoing ovarian stimulation for IVF/ET.

Adult↗

PubMed1990

Selective fallopian tube cannulation: initial experience in an infertile population.

We have studied a group of 19 patients presenting with proximal tubal occlusion. Seventy-three percent (22/30) of tubes attempted were successfully cannulated. Sixty-two percent (5/8) of tubes remained patent in limited follow-up at 3 to 6 months. We conclude that selective fallopian tube cannulation may provide an alternative to microsurgical tubal anastomosis in selected patients.

Catheterization↗

PubMed1990

Endometrial inadequacy after treatment with human menopausal gonadotropin/human chorionic gonadotropin.

The incidence of abnormal endometrial histology in patients undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) treatment during cycles of in vitro fertilization (IVF) or gamete intrafallopian transfer has been reported to be 52% to 91%. The incidence of endometrial inadequacy, as judged by a single late luteal endometrial biopsy, has not been studied in hMG/hCG non-IVF cycles. In the current study, 30 patients (30 cycles) undergoing hMG/hCG treatment were evaluated by an endometrial biopsy. The incidence of endometrial inadequacy was found to be 27%. No preovulatory predictors for endometrial inadequacy could be identified. Therefore, luteal support for patients undergoing non-IVF hMG/hCG cycles should be considered.

Adult↗

PubMed1990

Effects of contrast agents on the fallopian tube in a rabbit model.

The authors evaluated the effect of different iodinated contrast agents on the fallopian tube and adnexal tissue in 15 rabbits. Ethiodized oil, an oil-soluble agent, was used in five rabbits. The following water-soluble agents were used: iothalamate meglumine 30% (n = 3), iothalamate meglumine 60% (n = 3), and ioxilan (n = 4). The agents were injected through catheters placed in the fallopian tubes. Fallopian tubes and peritoneal cavities were histologically evaluated. The contralateral tube served as a control. Ioxilan and iothalamate meglumine 30% produced no pathologic response in the tube or peritoneal cavity. Iothalamate meglumine 60% was associated with mild inflammatory infiltrate, mucosal edema, giant cell reaction, and periovarian adhesions that were bilateral but more pronounced on the injected side. Use of ethiodized oil resulted in papillary fibrous adhesions on the ovarian surface, and fat granulomas were seen in the periovarian tissues. The safety of oil-based contrast agents for use in hysterosalpingography is therefore questioned. No significant differences were found among the water-soluble contrast agents.

Adnexa Uteri↗

PubMed1990

A laparoscopic method for excision of large retroperitoneal paraovarian cysts.

Large retroperitoneal paraovarian cysts often present in reproductive-age women as an adnexal mass, with the appearance of a simple cyst on ultrasound. This report describes a laparoscopic method for removal of large paraovarian retroperitoneal cysts. Use of this technique permits successful removal of these cysts while avoiding laparotomy.

Adolescent↗

PubMed1989

The human blastocyst produces a soluble factor(s) that interferes with lymphocyte proliferation.

Animal studies have reported that the blastocyst produces immunosuppressive factors that are critical to successful implantation. The production of such factor(s) by the human blastocyst has not yet been described. To test that hypothesis, the spent media of 67 human embryos developed in vitro was evaluated using either the allogeneic one-way mixed lymphocyte response (MLR) or the concanavalin A (Con-A) stimulated lymphocyte response (SLR). Conditioned embryo media was obtained at in vitro fertilization (IVF) in aliquots of (A) the first 24 hours in vitro, (B) the second 24 hours in vitro, and (C) from 24 hours until development of the blastocyst stage. Control media consisted of Ham's F-10 medium (Gibco, Grand Island, NY) with identical maternal serum concentration to test media. Conditioned media (either A, B, or C) or control media was added to 200-microL wells containing lymphocytes in either the MLR or SLR. A significant suppressive effect of 25% to 60% was observed in seven of nine samples of blastocyst-conditioned media (P less than 0.05). No significant suppressive effect was found in the earlier embryo media (A or B) in either the MLR or the SLR. These data suggest that the human blastocyst produces a factor(s) that interferes with lymphocyte proliferation.

Blastocyst↗

PubMed1989

Peritoneal reaction resulting from iodinated contrast material: comparative study.

A consensus does not exist as to the optimal contrast agent for hysterosalpingography. This study was undertaken to evaluate the early and delayed inflammatory responses of the peritoneal surfaces to various types of iodinated contrast media. Guinea pigs received intraperitoneal injections of lactated Ringer solution, iothalamate meglumine, diatrizoate sodium, ioxilan, or ethiodized oil. The inflammatory response of the peritoneal surfaces was assessed at 1,7, and 30 days. Five animals were studied at each time point for each agent. No animals that received Ringer lactate or iothalamate meglumine had inflammation at any time. Ioxilan produced inflammation in two of five animals at 7 days and no inflammation at 1 or 30 days. Ethiodized oil produced no inflammation at 1 day; however, three animals had inflammation at 7 days, and all five had inflammation at 30 days. The 30-day group showed striking inflammatory response with granulomatous features. The authors recommend the continued use of meglumine-based water-soluble ionic contrast material for hysterosalpingography.

Animals↗