Expression of glucocorticoid and androgen receptors in bone marrow-derived hematopoietic and nonhematopoietic murine endometrial cells.

OBJECTIVE: To determine whether bone marrow (BM)-derived cells engrafting the murine endometrium express the glucocorticoid receptor (GR) and androgen receptor (AR). Recent data demonstrate that BM is a long-term source of multiple hematopoietic and nonhematopoietic endometrial cell types. Important roles for glucocorticoids and androgens in regulating endometrial functions, including decidualization and early embryo attachment/invasion, have very recently emerged. Whether endometrial cells of BM origin express glucocorticoid or ARs has not been previously studied. DESIGN: Animal study. SETTING: Basic science laboratory. ANIMAL(S): Wild-type C57BL/6J male mice expressing enhanced green fluorescent protein (GFP) and syngeneic wild-type C57BL/6J female mice aged 6-9 weeks. INTERVENTION(S): Murine bone marrow transplant. MAIN OUTCOME MEASURE(S): Bone marrow cells were harvested from adult wild-type C57BL/6 mice and subjected to flow cytometry to identify the percentage of hematopoietic and nonhematopoietic cells expressing GR or AR. Uterine tissue sections from lethally irradiated syngeneic adult female C57BL/6 mice that had been recipients of BM transplants from adult male transgenic donor mice ubiquitously expressing GFP were studied. Immunohistochemistry was performed in the uterine tissue sections of the recipient mice at 5, 9, and 12 months after transplant using specific anti-GR, anti-AR, anti-GFP, anti-CD45 (pan leukocyte marker), and anti-F4/80 (murine macrophage marker) primary antibodies. Confocal laser microscopy was used to localize and quantitate BM-derived (GFP+) cell types in the endometrial stromal and epithelial compartments and determine whether BM-derived cell types in the murine endometrium express GR or AR. RESULT(S): Hematopoietic cells comprised 93.6%-96.6% of all cells in the BM, of which 98.1% ± 0.2% expressed GR and 92.2% ± 4.4% expressed AR. Nonhematopoietic cells comprised 0.4%-1.3% of BM, of which 52.8% ± 5.9% expressed GR and 48.9% ± 3.4% expressed AR. After BM transplant, the proportion of cells originating from BM in the endometrial stromal compartment increased over time, reaching 13.5% ± 2.3% at 12 months after transplant. In the epithelial compartments, <1% of the cells were of BM origin at 12 months after transplant. Most (60%-72%) GR+ and/or AR+ BM-derived cells in the stroma were hematopoietic (CD45+) cells, of which 37%-51% were macrophages. Nonetheless, 28%-33% of GR+ cells, and 28%-40% of AR+ BM-derived cells, were nonhematopoietic (CD45-) stromal cells of BM origin. CONCLUSION(S): A substantial number of BM-derived cells express GR and AR, suggesting a role for these cells in both glucocorticoid-regulated and androgen-regulated endometrial functions, such as proliferation and/or decidualization.

Does Capsular Closure Affect Clinical Outcomes in Hip Arthroscopy? A Prospective Randomized Controlled Trial.

BACKGROUND: There is increasing concern of iatrogenic hip instability after capsulotomy during surgery. Greater emphasis is now being placed on capsular closure during surgery. There are no prospective studies that address whether capsular closure has any effect on outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate patient outcomes after interportal capsulotomy repair compared with no repair. We hypothesized that restoration of normal capsular anatomy with interportal repair will achieve clinical outcomes similar to those for no repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Adult patients with femoral acetabular impingement indicated for hip arthroscopy were randomized into either the capsular repair (CR) or the no repair (NR) groups. All patients underwent standard hip arthroscopy with labral repair with or without CAM/pincer lesion resection. Clinical outcomes were measured via the Hip Outcome Score-Activities of Daily Living (HOS-ADL) subscale, Hip Outcome Score-Sport Specific (HOS-SS) subscale, modified Harris Hip Score (mHHS), visual analog scale for pain, International Hip Outcome Tool, and Veterans RAND 12-Item Health Survey (VR-12). RESULTS: A total of 54 patients (56 hips) were included (26 men and 30 women) with a mean age of 33 years. The HOS-ADL score significantly improved at 2 years in both the NR group (from 68.1 ± 20.5 to 88.6 ± 20.0; P < .001) and the CR group (from 59.2 ± 18.8 to 91.7 ± 12.3; P < .001). The HOS-SS score also significantly improved in both the NR group (from 41.1 ± 25.8 to 84.1 ± 21.9; P < .001) and the CR group (from 32.7 ± 23.7 to 77.7 ± 23.0; P < .001). Improvement was noted for all secondary outcome measures; however, there was no significant difference between the groups at any time point. Between 1 and 2 years, the NR group showed significant worsening on the HOS-ADL (-1.21 ± 5.09 vs 4.28 ± 7.91; P = .044), mHHS (1.08 ± 10.04 vs 10.12 ± 11.76; P = .042), and VR-12 Physical (-2.15 ± 5.52 vs 4.49 ± 7.30; P = .014) subsets compared with the CR group. CONCLUSION: There was significant improvement in the VR-12 Physical subscale at 2 years postoperatively in the capsular CR group compared with the NR group. Capsular closure appears to have no detrimental effect on functional outcome scores after hip arthroscopy. We recommend restoration of native anatomy if possible when performing hip arthroscopy.

The role of mesenchymal-epithelial transition in endometrial function.

BACKGROUND: The human uterine endometrium undergoes significant remodeling and regeneration on a rapid and repeated basis, after parturition, menstruation, and in some cases, injury. The ability of the adult endometrium to undergo cyclic regeneration and differentiation/decidualization is essential for successful human reproduction. Multiple key physiologic functions of the endometrium require the cells of this tissue to transition between mesenchymal and epithelial phenotypes, processes known as mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT). Although MET/EMT processes have been widely characterized in embryonic development and in the context of malignancy, mounting evidence demonstrates the importance of MET/EMT in allowing the endometrium the phenotypic and functional flexibility necessary for successful decidualization, regeneration/re-epithelialization and embryo implantation. OBJECTIVE AND RATIONALE: The objective of this review is to provide a comprehensive summary of the observations concerning MET and EMT and their regulation in physiologic uterine functions, specifically in the context of endometrial regeneration, decidualization and embryo implantation. SEARCH METHODS: Using variations of the search terms 'mesenchymal-epithelial transition', 'mesenchymal-epithelial transformation', 'epithelial-mesenchymal transition', 'epithelial-mesenchymal transformation', 'uterus', 'endometrial regeneration', 'endometrial decidualization', 'embryo implantation', a search of the published literature between 1970 and 2018 was conducted using the PubMed database. In addition, we searched the reference lists of all publications included in this review for additional relevant original studies. OUTCOMES: Multiple studies demonstrate that endometrial stromal cells contribute to the regeneration of both the stromal and epithelial cell compartments of the uterus, implicating a role for MET in mechanisms responsible for endometrial regeneration and re-epithelialization. During decidualization, endometrial stromal cells undergo morphologic and functional changes consistent with MET in order to accommodate embryo implantation. Under the influence of estradiol, progesterone and multiple other factors, endometrial stromal fibroblasts acquire epithelioid characteristics, such as expanded cytoplasm and rough endoplasmic reticulum required for greater secretory capacity, rounded nuclei, increased expression of junctional proteins which allow for increased cell-cell communication, and a reorganized actin cytoskeleton. During embryo implantation, in response to both maternal and embryonic-derived signals, the maternal luminal epithelium as well as the decidualized stromal cells acquire the mesenchymal characteristics of increased migration/motility, thus undergoing EMT in order to accommodate the invading trophoblast. WIDER IMPLICATIONS: Overall, the findings support important roles for MET/EMT in multiple endometrial functions required for successful reproduction. The endometrium may be considered a unique wound healing model, given its ability to repeatedly undergo repair without scarring or loss of function. Future studies to elucidate how MET/EMT mechanisms may contribute to scar-free endometrial repair will have considerable potential to advance studies of wound healing mechanisms in other tissues.

Association of Cervical Microglandular Hyperplasia With Exogenous Progestin Exposure.

OBJECTIVES: Although microglandular hyperplasia is a benign endocervical lesion, it may raise concern of malignancy in an inexperienced pathologist, because clinicians may not be familiar with it on a report. It has been reported to occur in association with progestational stimulation, but this has not been well studied. The aim of the study was to evaluate this potential association. MATERIALS AND METHODS: This was an observational case control study of patients seen from January 01, 1991 to November 01, 2014 at the University Hospital, Newark, New Jersey. Cases of microglandular hyperplasia and controls were identified from the files of the Department of Pathology. Controls were cases of endocervical curettages for whom no microglandular hyperplasia was detected. Medical records were reviewed for evidence of exogenous progestin exposure within the previous 6 months. RESULTS: Eighty-nine cases of microglandular hyperplasia and 97 controls were identified. Of the cases of microglandular hyperplasia, 26 (29.2%) of 89 cases had exposure to progestational medication, significantly greater than that of controls (10/97, 10.3%; p = .0014). CONCLUSIONS: Our data show that a significantly higher percentage of women with microglandular hyperplasia had progestin exposure than women who do not exhibit this benign lesion. Clinicians and pathologists should be aware of this association, as well as the benign nature of the lesion.

Physical fitness, serum relaxin and duration of gestation.

BACKGROUND: Women are recommended to perform regular exercise during pregnancy but the impact of physical fitness on duration of gestation and miscarriage is inconsistent. In addition, a dose-response relation between the amount of weekly exercise and increased risk of miscarriage in early pregnancy has been observed. Previous studies have mostly used an epidemiologic method. Larger studies using careful measurement of physical fitness are needed. Besides physical fitness, maternal circulating concentrations of the hormone relaxin have been associated with decreased duration of gestation. METHODS: A prospective cohort including 20 women with miscarriage and 460 women with spontaneous onset of labour, recruited from maternal health care centres in central Sweden, were examined in early pregnancy regarding estimated absolute peak oxygen uptake (VO2 peak, est.) by cycle ergometer test, and maternal circulating serum relaxin concentrations. RESULTS: Women with miscarriage displayed the highest level of absolute VO2 peak, est. (2.61 l/min) and the lowest serum relaxin concentrations (640 ng/l). Among women with spontaneous onset of labour, the mean absolute VO2 peak, est. increased successively from the lowest estimated oxygen uptake of 2.31 l/min among those with preterm birth (n = 28), to an oxygen uptake of 2.49 l/min among women with postterm birth (n = 31). An opposite trend was shown regarding serum relaxin concentrations from women with miscarriage to those with postterm birth. Serum relaxin concentrations, but not absolute VO2 peak, est. was significantly and independently associated with duration of gestation in women with miscarriages, and absolute VO2 peak, est., age and multiple pregnancy were independently associated with duration of gestation in women with spontaneous onset of labour. CONCLUSIONS: Physical fitness appears to be a protective factor of established pregnancies and not significantly involved in the risk of early miscarriage. Additional studies are needed to more clearly define the role of relaxin in miscarriage.

Web-Based Education Prior to Knee Arthroscopy Enhances Informed Consent and Patient Knowledge Recall: A Prospective, Randomized Controlled Study.

BACKGROUND: Preoperative patient education is an important part of the informed consent process, and a perceived lack of information can lower patient satisfaction. We sought to evaluate the effect of a web-based multimedia patient education tool on the perioperative experience of patients undergoing first-time knee arthroscopy for a meniscal tear. METHODS: Adult patients undergoing knee arthroscopy for the first time for a primary diagnosis of a meniscal tear were consecutively enrolled into the study from January 2014 through June 2014. Patients were equally randomized to a control group, who received standard preoperative counseling, or the intervention group, who completed a twenty-minute web-based multimedia tutorial in addition to standard counseling. The web-based tutorial covered relevant anatomy, pathology, and general perioperative instructions, and it was completed prior to the preoperative visit. Patients completed surveys that evaluated their preparedness for surgery and knowledge recall at the preoperative visit, on the day of surgery, and after the first postoperative visit. RESULTS: Sixty-four patients were enrolled, and fifty-five patients (86%; twenty-nine in the control group and twenty-six in the intervention group) with complete data sets were included in the analysis. Preoperatively, the intervention group felt significantly more informed about the surgery and more clearly understood the risks and benefits of, and alternatives to, the surgery (all p < 0.001). Postoperatively, the intervention group reported being significantly more satisfied with the perioperative education that they had received and felt more informed about their surgery and rehabilitation (p ≤ 0.05). Patients in the intervention group were significantly more likely to correctly answer questions regarding their surgical details at the first postoperative visit (p ≤ 0.03). CONCLUSIONS: Patients who completed the web-based tutorial had improved preoperative knowledge and preparedness as well as enhanced postoperative knowledge recall regarding their surgical procedure. The tutorial received high user satisfaction scores with low user burden scores and was an effective tool for enhancing the patients' perioperative experience.

Myometrial artery calcifications and aging.

OBJECTIVE: This study aims to determine whether myometrial artery calcifications increase with age and whether uterine sections are an appropriate model for studying vascular aging. METHODS: An observational study of 172 women (aged 45 y or older) who underwent hysterectomy for benign indications at the University Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women with a history of malignancy, undocumented last menstrual period, or unavailable uterine tissue slides were excluded. H&E-stained uterine sections were evaluated for myometrial artery calcifications (defined as the presence of acellular densely basophilic material within the media of vessels) by a single pathologist in a blinded manner. RESULTS: Between July 1, 2009 and June 1, 2012, hysterectomies were performed on 441 women, 172 of whom met inclusion criteria. Seventeen women (9.9%) had myometrial artery calcifications detectable on H&E-stained tissue sections. None of 84 women aged 45 to 49 years, 2 of 51 women (3.9%) aged 50 to 59 years (aged 56 and 58 y), 10 of 27 women (37%) aged 60 to 69 years, and 5 of 10 women (50%) aged 70 to 81 years had myometrial artery calcifications. The prevalence of myometrial artery calcifications significantly increased with advancing age (P = 0.022). CONCLUSIONS: Myometrial artery calcifications increase with advancing age. Histological sections of uterine tissue from hysterectomy specimens seem to be a useful model for evaluating vascular aging markers.

Effect of single embryo transfer on the risk of preterm birth associated with in vitro fertilization.

PURPOSE: To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF). METHODS: This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period. RESULTS: The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate (20-37 weeks gestation) following eSET was 17.6 % (269/1527). This is significantly greater than the preterm birth rate for all patients undergoing IVF over the same time period (12 %, P < 0.001). CONCLUSIONS: Elective single embryo transfer does not reduce the risk of preterm delivery associated with in vitro fertilization (IVF).

Does a diagnosis of atrophic vaginitis on Papanicolaou test signify the presence of inflammation?

OBJECTIVE: Vaginal atrophy in menopause shows increased parabasal cells on cytology. This may be accompanied by abundant neutrophils. A shift in maturation index in the absence of significant inflammation is more accurately termed "atrophic pattern." This study aims to determine whether a diagnosis of "atrophic vaginitis" or atrophic pattern on Papanicolaou test is a reliable indicator of what is present on the slide. METHODS: A retrospective review of Papanicolaou test slides from University Hospital Newark was performed. Cases that had been diagnosed as either atrophic vaginitis (n = 100) or atrophic pattern (n = 100) were selected. Exclusion criteria included any additional diagnosis of neoplasia. Slides were re-reviewed and scored based on abundance of neutrophils: 0 to 5, 6 to 10, or more than 10 neutrophils per high-power field (×40), with 10 fields per slide reviewed. Data were analyzed by χ analysis. RESULTS: Among 200 cases with atrophic vaginitis or atrophic pattern, the proportion of those diagnosed with atrophic vaginitis to those diagnosed with atrophic pattern increased across three neutrophil categories (P < 0.0001). CONCLUSIONS: A diagnosis of atrophic vaginitis on Papanicolaou test is reliably associated with increased numbers of neutrophils. A diagnosis of atrophic pattern is indicative of low numbers of neutrophils. As the Papanicolaou test diagnosis of atrophic vaginitis does not correlate with clinical symptoms, a single diagnostic term that does not suggest a disease process would more reliably communicate cytology findings to clinicians.

Cervical conization for cervical intraepithelial neoplasia (CIN) 2 and 3 in HIV-positive women: a case-control study.

OBJECTIVE: The purposes of the study were to investigate the outcomes of cervical conization for cervical intraepithelial neoplasia (CIN) 2 and 3 in HIV-positive women and age-matched HIV-negative controls and to determine whether positive margin, positive endocervical curettage, CD4 count, or viral load was associated with the persistence of CIN 2,3 or residual CIN 2,3 on the specimen from repeat excision procedure or hysterectomy. MATERIALS AND METHODS: HIV-positive women and HIV-negative controls with CIN 2,3 on cervical conization were enrolled in the study. Patients who underwent repeat conization or hysterectomy were identified, and the specimens were evaluated for residual CIN 2,3. CD4 count and viral load within 8 weeks of procedure were analyzed. RESULTS: A total of 44 patients and 44 age-matched controls were identified. Persistent CIN 2,3 was diagnosed in 28 HIV-positive (63.6%) and 14 HIV-negative patients (31.8%; odds ratio [OR] = 4.7, 95% confidence interval [CI] = 1.9-11.5, p < .001). In HIV-positive women, a positive margin was associated with a higher persistence rate after cervical conization (OR = 5.3, 95% CI = 1.17-24.14, p = .03). In HIV-negative patients, positive endocervical curettage was associated with a higher persistence rate after conization (OR = 12, 95% CI = 2.24-64.23, p = .004). Of HIV-positive women, 75% had residual CIN 2,3 on the specimen from repeat procedure compared to 45.2% of controls (OR = 3.6, 95% CI = 1.3-10.6, p = .018). CD4 count or viral load was not associated with the rate of residual disease or persistence rate after cervical conization, but the lowest OR that the sample size allowed to assess with 90% power was 5.02. CONCLUSIONS: HIV-positive women have a higher rate of residual disease and higher persistence rate after conization for CIN 2,3 than age-matched HIV-negative controls.

Experimental evidence for bone marrow as a source of nonhematopoietic endometrial stromal and epithelial compartment cells in a murine model.

Human endometrium has the remarkable ability to regenerate all cellular compartments with every menstrual cycle; the cellular source remains unknown. The objective of the present study was to determine whether the bone marrow (BM) is a source of multiple endometrial cell types using a murine BM transplant model. BM cells were harvested from transgenic donor mice that ubiquitously express green fluorescent protein (GFP) and were injected into lethally irradiated, syngeneic female recipient mice. Recipients with successful hematopoietic reconstitution were sacrificed at 3, 5, 9, and 12 mo posttransplant, after which hysterectomy was performed. Numbers of GFP-positive, CD45-positive, and CD45-negative cells in the endometrial stromal and epithelial compartments were determined. In the stromal compartment, BM-derived cells (BMDCs) were detectable as early as 3 mo posttransplant, and the BM remained a long-term contributor of nonhematopoietic endometrial cells. Nonhematopoietic endometrial cells comprised 47.3%-72.2% of total BMDCs in the stromal compartment at 12 mo posttransplant. In contrast, BMDCs were not detected in the glandular or luminal epithelial compartments until 12 mo posttransplant. These data demonstrate that the BM is a significant source of nonhematopoietic endometrial stromal compartment cells and contributes to a much lesser extent to the epithelial compartments. That BM is a source of nonhematopoietic cells in the endometrial stromal and epithelial compartments provides a potential mechanism by which monthly regeneration of the endometrium may occur.

Reproductive tract actions of relaxin in models of human pregnancy.

Elucidating the role(s) of relaxin in women has been greatly hampered by its species specificity. Suitable experimental models of relaxin action in women are limited. We established a non-human primate model of early human pregnancy to study the effects of relaxin in vivo and used three well characterized in vitro models of human endometrial function for study of mechanisms involved. Results from these studies clearly demonstrate that relaxin is an import ant factor in human endometrium which causes accommodation to and maintenance of early pregnancy and uses multiple physiological and biochemical mediators.

Endometrial stem cells and reproduction.

Abnormal endometrial function remains a significant cause of implantation failure, recurrent pregnancy loss, and other pathologies responsible for female infertility. The development of novel therapies to treat infertility due to endometrial dysfunction requires an understanding of the latest advancements in endometrial cell biology, such as the role of endometrial stem cells. The remarkable regenerative capacity of the human endometrium is absolutely essential for successful reproduction and likely requires a population of stem cells in the endometrium. The purpose of this review is to provide an introduction to some of the newest concepts in endometrial stem cell biology.

Collagen expression in the pregnant human cervix is decreased with labor.

OBJECTIVE: The current study tested the hypothesis that collagen content in the pregnant cervix decreases with labor, using morphologically preserved specimens, avoiding limitations of earlier studies. Collagen abundance remote from pregnancy was also evaluated. MATERIALS AND METHODS: Histologic sections of postpartum cervix obtained from 22 cases of total hysterectomy performed immediately after delivery: 13 cases performed after delivery with no labor and 9 cases in which labor had ensued before delivery. Cervices from 10 nonpregnant uteri served as additional controls. Sections were stained, and quantitative histomorphometric assessment of relative collagen abundance was performed using computer-assisted image analysis. Data were assessed for differences using rank sum tests. Relationships between cervical collagen abundance and age, parity, ethnicity, or mode of delivery were also assessed. RESULTS: Quantitative assessment of collagen abundance in trichrome-stained cervical sections revealed significantly decreased cervical collagen expression in sections from pregnant uteri. Mean percent collagen was 73.5% ± 3.5% (±SEM) in cervices from nonpregnant uteri (n = 10) and 21.5% ± 2.2% in cervices from pregnant uteri (n = 22, p < .0001). Cervical collagen content was significantly lower (p = .04) in cervices from cases in which labor had ensued before delivery (mean percent collagen = 16.1% ± 3.4%, n = 9) than in those in which delivery occurred with no labor (25.3% ± 2.3%, n = 13). No relationships between collagen expression and age, parity, ethnicity, or mode of delivery were observed. CONCLUSIONS: Collagen expression seems to be reduced in the postpartum cervix, particularly after labor has ensued.

Is the diagnosis of atypical glandular cells of undetermined significance associated with greater risk at an inner city hospital?

OBJECTIVE: To test the hypothesis that the high-risk patients at an inner city hospital with atypical glandular cells of undetermined significance (AGC) on their Pap smears have a higher rate of underlying significant pathology than that reported in published data. STUDY DESIGN: This was an Institutional Review Board-approved retrospective review of all AGC Pap smears performed at University Hospital, Newark, New Jersey, between January 1, 2001, and July 30, 2008. We defined significant pathology as cervical intraepithelial neoplasia 2 (CIN 2) or greater, endocervical adenocarcinoma in situ or greater, or simple hyperplasia or greater of the endometrium. RESULTS: Medical records of 126 patients were reviewed. Forty did not meet inclusion criteria; 86 patients were included in the analysis. Thirty of the 86 (34.9%) patients were found to have significant pathology. CONCLUSION: Patients with AGC Pap results at our inner city hospital have a high risk for underlying significant pathology.

Body mass index of patients with endometrial hyperplasia: comparison to patients with proliferative endometrium and abnormal bleeding.

OBJECTIVE: Endometrial hyperplasia is a known risk factor for the development of endometrial cancer, particularly atypical hyperplasia, with a subsequent risk of up to 30%. Of the known risk factors for endometrial hyperplasia, obesity is the most preventable, but there is a paucity of data addressing the association. We tested the hypothesis that patients with endometrial hyperplasia have a higher body mass index (BMI) than patients with abnormal bleeding who are found to have proliferative endometrium. STUDY DESIGN: This was an Institutional Review Board-approved retrospective study using University Hospital Department of Pathology records. All patients who had endometrial sampling performed between January 1, 2001, and July 30, 2008, were included. The experimental group consisted of patients with endometrial hyperplasia including simple, complex and atypical hyperplasia. The control group consisted of patients who underwent endometrial sampling for abnormal bleeding during the same time period and were diagnosed with proliferative endometrium. BMI was calculated based on documented height and weight within 30 days of endometrial sampling. RESULTS: Forty-two patients with hyperplasia and 103 patients with proliferative endometrium met inclusion criteria, including documented height and weight and nonexposure to hormones. The median BMI in the hyperplasia group was 38 kg/m2 (95% CI 34.8-42.4) and 30 kg/m2 (95% CI 29.9-33.3) in the proliferative group (p < 0.0001). CONCLUSION: These data suggest that higher BMI is associated with endometrial hyperplasia as compared to women with lower BMIs and abnormal bleeding.

Endometrial expression of relaxin and relaxin receptor in endometriosis.

Our studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis.

Circulating relaxin and cervical length in midpregnancy are independently associated with spontaneous preterm birth.

OBJECTIVE: We sought to examine associations among serum relaxin levels, cervical length, and spontaneous preterm birth (sPTB). STUDY DESIGN: We conducted a case-control study within a cohort of 1080 singleton pregnant women. In all, 38 women (3.5%) delivered spontaneously preterm (< 37 completed weeks of gestation). Relaxin was measured in serum in gestational weeks 12 and 19, cervical length only in week 19. Associations to sPTB were evaluated by logistic regression analysis and receiver operating characteristic curves. RESULTS: Cervical length and relaxin in week 19, but not week 12 were associated to sPTB. There were no correlations between cervical length and relaxin level in week 12 (controls: Spearman rho: -0.07, P = .45; cases: Spearman rho: -0.07, P = .72) or week 19 (controls: Spearman rho: -0.03, P = .77; cases: Spearman rho: 0.04, P = .84). CONCLUSION: There were no correlation between relaxin concentrations and the cervical length, indicating that relaxin is probably not the cause of preterm shortening of the cervix.

A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas.

Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5-fold, with an EC(50) of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG-05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum-starved U373 cells with substance P reduces apoptosis by 53 +/- 1% (p < 0.05), and treatment with NK1R antagonist L-733,060 increases apoptosis by 64 +/- 16% (p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L-733,060 causes cleavage of Caspase-3 and proteolysis of poly (ADP-ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R-mediated Akt phosphorylation revealed total involvement of non-receptor tyrosine kinase Src and phosphatidyl-3-kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen-activated protein/extracellular signal-related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis.