Miracle-dz/UniFAR-FTUs huggingface dataset:
SP1 and SP3 Mediate Progesterone-Dependent Induction of the 17beta Hydroxysteroid Dehydrogenase Type 2 Gene in Human Endometrium1

Abstract The opposing actions of estrogen and progesterone during the menstrual cycle regulate the cyclical and predictable endometrial proliferation and differentiation that is required for implantation. Progesterone indirectly stimulates the expression of 17beta hydroxysteroid dehydrogenase type 2 (HSD17B2), which catalyzes the conversion of biologically potent estradiol to weakly estrogenic estrone in the endometrial epithelium. We previously demonstrated upregulation of the HSD17B2 gene in human endometrial epithelial cells by factors secreted from endometrial stromal cells in response to progesterone. We investigated the underlying mechanism by which these stroma-derived, progesterone-induced paracrine factors stimulate HSD17B2 expression. Here, we show that transcription factors SP1 and SP3 interact with specific motifs in HSD17B2 promoter to upregulate enzyme expression in human endometrial epithelial cell lines. Conditioned medium (CM) from progestin-treated stromal cells increased levels of SP1 and SP3 in endometrial epithelial cells and induced HSD17B2 mRNA expression. Mithramycin A, an inhibitor of SP1-DNA interaction, reduced epithelial HSD17B2 promoter activity in a dose-dependent manner. Serial deletion and site-directed mutants of the HSD17B2 promoter demonstrated that two overlapping SP1 motifs (nt −82/−65) are essential for induction of promoter activity by CM or overexpression of SP1/SP3. CM markedly enhanced, whereas anti-SP1/SP3 antibodies inhibited, binding of nuclear proteins to this region of the HSD17B2 promoter. In vivo, we demonstrated a significant spatiotemporal association between epithelial SP1/SP3 and HSD17B2 levels in human endometrial biopsies. Taken together, these data suggest that HSD17B2 expression in endometrial epithelial cells, and, therefore, estrogen inactivation, is regulated by SP1 and SP3, which are downstream targets of progesterone-dependent paracrine signals originating from endometrial stromal cells.
Multigene DNA prime‐boost vaccines for SHIV89.6P

We assessed four prime‐boost vaccine regimens with a Gene Gun component for SHIV89.6P in Macaca nemestrina. A dosing experiment using β‐galactosidase plasmid showed that 30 or 45 shots per dose elicited higher titer antibody than smaller doses. For SHIV89.6P, we administered a six‐plasmid vaccine capable of producing non‐infectious virions in vivo in combination with either vaccinia recombinants or inactivated virus. DNA prime/vaccinia boost, or the reverse, elicited strong immune responses. The SHIV89.6P challenge virus was grown in M. nemestrina peripheral blood mononuclear cells and titered in vivo intrarectally. As has been observed for SHIV89.6P in M. mulatta, the infected M. nemestrina experienced rapid and severe loss of circulating CD4+ T cells. Vaccinated macaques were challenged three weeks after the last boost. DNA prime/vaccina boost or vaccina prime/DNA boost protected 11/12 animals from acute CD4+ T cell depletion and disease, while other regimens were not effective.
Effective obstetric paracervical block with reduced dose of bupivacaine: A prospective randomized double‐blind study comparing 25 mg (0.25 %) and 12.5 mg (0.125%) of bupivacaine

Background. To study whether paracervical block (PCB) with 12.5 mg (0.125 %) of bupivacaine is as effective as with 25 mg (0.25 %) and if there are differences in fetal heart rate (FMR) patterns between the doses.
Regulation of NGFI‐B/Nur77 gene expression in the rat ovary and in leydig tumor cells MA‐10

NR4A1, also called NGFI‐B in the rat, Nur77 in the mouse and TR3 in humans, belongs to the orphan nuclear steroid hormone receptor superfamily and is one of the immediate‐early genes. In the endocrine organs, including the gonads, NGFI‐B/Nur77 gene expression is rapidly induced by pituitary hormones. NGFI‐B/Nur77 expression was found to be rapidly reduced by an estrogenic endocrine disrupter, diethylstilbestrol (DES) in theca interna cells of immature rat ovaries. DES treatment also triggered a rapid decrease of serum luteinizing hormone (LH) levels, suggesting that DES acts on the hypothalamo–pituitary axis to suppress LH secretion from the pituitary. The transcriptional regulation of NGFI‐B/Nur77 by LH/human chorionic gonadotropin (hCG) or 8‐bromoadenosine 3′–5′‐cyclic monophosphate (8 Br‐cAMP) was examined in mouse Leydig tumor cells MA‐10. Luciferase assays using NGFI‐B/Nur77 promoter constructs and electric mobility shift assays (EMSA) showed that NGFI‐B/Nur77 gene expression was mediated through three of the four activator protein‐1 (AP‐1)‐like sites, namely the −233 AP‐1, −213 AP‐1 and −69 AP‐1 sites adjacent to the transcription start site of the NGFI‐B/Nur77 promoter. We also demonstrated here that both the Jun family and cAMP‐responsive element binding (CREB) proteins bind to the −233 AP‐1 site, whereas the main binding protein to the −213 AP‐1 site was CREB, and Jun family protein to the −69 AP‐1 site, respectively. The rapid induction of NGFI‐B/Nur77 gene expression by LH/hCG in MA‐10 cells appears to be mediated by both CREB and Jun family proteins through the cAMP‐protein kinase A (PKA) pathway. Mol. Reprod. Dev. 75: 931–939, 2008. © 2007 Wiley‐Liss, Inc.
Use of Universal 16S rRNA Gene PCR as a Diagnostic Tool for Venous Access Port-Related Bloodstream Infections

ABSTRACT Amplification of the universal 16S rRNA gene using PCR has improved the diagnostic yield of microbiological samples. However, no data have been reported on the reliability of this technique with venous access ports (VAPs). We assessed the utility of 16S rRNA PCR for the prediction of VAP-related bloodstream infection (VAP-RBSI). During a 2-year period, we prospectively received all VAPs removed by interventional radiologists. PCR and conventional cultures were performed using samples from the different VAP sites. We compared the results of PCR with those of conventional culture for patients with confirmed VAP-RBSI. We collected 219 VAPs from 219 patients. Conventional VAP culture revealed 15 episodes of VAP-RBSI. PCR revealed a further 4 episodes in patients undergoing antibiotic therapy which would have gone undetected using conventional culture. Moreover, it had a negative predictive value of 97.8% for the prediction of VAP-RBSI when it was performed using biofilm from the internal surface of the port. In conclusion, universal 16S rRNA PCR performed with samples from the inside of VAPs proved to be a useful tool for the diagnosis of VAP-RBSI. It increased detection of VAP-RBSI episodes by 21.1% in patients undergoing antibiotic therapy whose episodes would have gone undetected using conventional culture. Therefore, we propose a new application of 16S rRNA PCR as a useful tool for the diagnosis of VAP-RBSI in patients receiving antibiotic therapy.
Recent advances in non‐invasive prenatal DNA diagnosis through analysis of maternal blood

Prenatal diagnosis of aneuploidy and single‐gene disorders is usually performed by collecting fetal samples through amniocentesis or chorionic villus sampling. However, these invasive procedures are associated with some degree of risk to the fetus and/or mother. Therefore, in recent years, considerable effort has been made to develop non‐invasive prenatal diagnostic procedures. One potential non‐invasive approach involves analysis of cell‐free fetal DNA in maternal plasma or serum. Another approach utilizes fetal cells within the maternal circulation as a source of fetal DNA. At the present time, fetal gender and fetal RhD blood type within RhD‐negative pregnant women can be reliably determined through analysis of maternal plasma. Furthermore, genetic alterations can be diagnosed in the maternal plasma when the mother does not have the alterations. However, the diagnosis of maternally inherited genetic disease and aneuploidy is limited using this approach. Non‐invasive prenatal diagnosis through examination of intact fetal cells circulating within maternal blood can be used to diagnose a full range of genetic disorders. Since only a limited number of fetal cells circulate within maternal blood, procedures to enrich the cells and enable single cell analysis with high sensitivity are required. Recently, separation methods, including a lectin‐based method and autoimage analyzing, have been developed, which have improved the sensitivity of genetic analysis. This progress has supported the possibility of non‐invasive prenatal diagnosis of genetic disorders. In the present article, we discuss recent advances in the field of non‐invasive prenatal diagnosis.
Mouse strain differences in autonomic responses to stress

In humans, anxiety disorders are often accompanied by an overactive autonomic nervous system, reflected in increased body temperature (BT) and heart rate (HR). In rodents, comparable effects are found after exposure to stress. These autonomic parameters can give important information on stress and anxiety responses in mice. In the present experiments, stress reactivity of three frequently used mouse strains [129 Sv/Ev, Swiss Webster (SW) and C57 BL/6] was assessed using their autonomic stress responses. BT, HR and activity were telemetrically measured. Undisturbed circadian rhythms already showed clear differences between the mouse strains. Hereafter, autonomic responses to stressors with increasing intensity were measured. Strain differences were found in magnitude and duration of the stress responses, especially after high‐intensity stressors. Generally, C57BL/6 mice showed the largest autonomic response, SW the lowest and the 129Sv/Ev the intermediate response. Interestingly, the observed ranking in autonomic stress response does not match the behavioral stress responsivity of these strains. Finally, sensitivity to the anxiolytic diazepam (0, 1, 2, 4 and 8 mg/kg) was tested using the stress‐induced hyperthermia paradigm. Pharmacological sensitivity to diazepam differed between the strains with the 129Sv/Ev being most sensitive. These studies show that simultaneous measurement of behavioral and autonomic parameters under stressful conditions contributes considerably to a better interpretation of anxiety and stress levels in mice.
Does Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Contribute to Impairment of Fibrinolysis in Patients with Preeclampsia and/or Intrauterine Fetal Growth Retardation?

Summary Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a relatively recently described glycoprotein (MM 55 KDa) that can be converted into its active form by the thrombin/thrombomodulin complex and potentially inhibits fibrinolysis. Since it represents a link between coagulation and fibrinolysis, TAFI can be expected to play a part in various clinical conditions associated with a thrombotic tendency. Preeclampsia (PE) and intrauterine fetal growth retardation (IUFGR) are fairly common complications of pregnancy that are characterized by hemostatic abnormalities. TAFI antigen and its influence on hemostasis was investigated in 46 women with PE and/or IUFGR and in 16 normal pregnancies. We found a significant decrease of TAFI antigen in the patient group. Using the recently described method Overall Hemostatic Potential (OHP) in plasma, we measured clot lysis time (CLT) and overall fibrinolytic potential (OFP). We found that CLT is prolonged and OFP decreased in patients with PE and/or IUFGR. Since OFP did not increase after addition of the specific inhibitor of TAFI (potato tuber carboxypeptidase inhibitor), it seems that TAFI does not contribute to the impairment of fibrinolysis in these patients. Since serum albumin was decreased together with presence of proteinuria and aminotransferases were increased in the patients, it seems that one explanation for the decrease in TAFI could be reduced hepatic synthesis and an increased loss in urine. It can be speculated that this mechanism can prevent more serious thrombotic complications in patients with PE and/or IUFGR.
Childhood exposure to violence and lifelong health: Clinical intervention science and stress-biology research join forces

Abstract Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child's body, alterations that may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people.
Primary cultures of fully differentiated and pure human intestinal epithelial cells.

The epithelium of the small intestinal mucosa is a highly dynamic system particularly well suited for analyzing key biological phenomena such as cell differentiation and migration, cell-matrix interactions, and apoptosis. However, in vitro models of fully differentiated normal human enterocytes are still lacking. The objective of the present study was to investigate the possibility of generating such differentiated intestinal cell cultures from the fetal small intestine. For this purpose, various dissociation methods were tested in order to obtain pure, viable, and functional enterocytes. One of these methods, based on the procedure to recover epithelial cells grown on Matrigel and involving the use of Matrisperse, a nonenzymatic dissociating solution, was found to allow the isolation of the integral epithelial lining from the mesenchyme. In culture, these epithelial fractions plated on collagen I spread rapidly and reached confluence after 3-4 days. When tested after 5-7 days, these primary cultures of differentiated enterocytes (PCDE) remained well preserved. Both goblet and absorptive cells exhibit all the main characteristics of intact villus intestinal cells as assessed by electron microscopy. Indirect immunofluorescence and Western blot analyses confirmed the purity of PCDE. The functional status of these cells was demonstrated by the presence of uniformly distributed tight junction, zonula adherens, and desmosomal components at the region of cell to cell contact as well as expression of various brush border enzymes, namely sucrase-isomaltase and lactase, and goblet cell mucins. As expected, cell proliferation was found to be negligible as assessed by DNA synthesis. Taken together, these data show that primary cultures of pure and viable differentiated enterocytes can be generated from the human fetal small intestine.
Chiropractic referral: the views of a group of conventional medical practitioners with an interest in unconventional therapies.

OBJECTIVE To identify, from a list of conditions prepared by leaders in the Australian chiropractic profession, disorders that medical practitioners regard as suitable for referral for chiropractic care. DESIGN A descriptive study in which eight hundred and twenty (820) medical practitioners with an interest in "unconventional" interventions were invited to respond to a mailed questionnaire. PARTICIPANTS Medical practitioners with a demonstrable interest in at least one form of nonconventional therapy were surveyed. Seven hundred and ninety-six medical practitioners who subscribe to a professional organization committed to "alternative" nutritional approaches in health care were sent mail. Twenty-four practitioners known to be sympathetic to chiropractic were also included. The response rate was 28%. RESULTS Medical respondents who refer to chiropractors more frequently consider a larger number of conditions suitable for chiropractic care than those who never refer. Referral of patients with visceral disorders enjoys relatively little support, especially among practitioners who never actually use chiropractic referral as an intervention option. Analysis of perceptions regarding chiropractic referral of patients with headaches suggests that the perceived etiology of the symptom is a consideration in making referral decisions. CONCLUSION Chiropractic referral for musculoskeletal care enjoys substantial support, whereas referral for chiropractic intervention in visceral conditions continues to be largely opposed by those members of the medical profession participating in this study.
Physiognomic Cues to Age and the Activation of Stereotypes of the Elderly in Interaction

This article reports the results of a study on the relationship between physiognomic cues to age and the activation of positive versus negative stereotypes of elderly individuals in interaction. Predictions were based upon a model of the role of elderly stereotypes in interaction. One group of undergraduates sorted photographs of elderly adults into four age categories, fifty-five to sixty-four, sixty-five to seventy-four, seventy-five and older, and other. Those photographs that were placed in the same age category by two-thirds or more of the students were used as a pool for the second phase of the study. This process produced a set of twenty-four photographs, eight (4 male and 4 female) from each of the three elderly age groups. A second group of students paired these photographs with sets of traits describing ten stereotypes of elderly persons, some positive and some negative. Results indicated that, as predicted by the stereotype-communication model, participants associated the positive stereotypes of elderly individuals with young-old physiognomic characteristics, whereas they associated the negative ones with old-old physiognomy. The results also suggested that gender may be a component of some stereotypes, and that some physiognomic characteristics may be considered prototypical of particular stereotypes. These results illustrate the importance of passive nonverbal elements of the communication situation in the activation of stereotypes of elderly individuals in interaction.
The PPARγ Pro12Ala Polymorphism Is Not Associated with Body Mass Index or Waist Circumference among Hispanics from Colorado

Background/Aims: First to determine if body mass index (BMI) or waist circumference (WC) differ by possession of the Ala allele of the peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala polymorphism, and second, to determine if dietary fat intake and physical activity moderate these potential relationships among Hispanic Americans from Colorado. Methods: We studied 216 Hispanic pedigrees (1,850 nuclear families) from the San Luis Valley and Denver (mean age 50 years). The families were genotyped for the Pro12Ala polymorphism of the PPARγ gene. BMI, WC and diabetes status were measured in the clinic, and, for diabetics, self-reported BMI at diabetes diagnosis was used. Data were analyzed using the Family-Based Association Test (FBAT). We conducted overall and stratified analyses by tertiles of monounsaturated, polyunsaturated (PUFA) and saturated (SFA) fat intake, the PUFA:SFA ratio, and physical activity. We also used generalized estimating equations (GEE) to further explore the FBAT findings. Results: The average BMI and WC were ∼29 kg/m2 and 101 cm, respectively. The frequency of the Ala allele was 13.5%. We did not find the Ala allele to be associated with BMI or WC overall (p = 0.58 and 0.23, respectively). We did find the Ala allele to be associated with increased BMI in those with high dietary PUFA and PUFA:SFA ratio (p = 0.007 and 0.01, respectively); however, these findings were not confirmed using the GEE models. Conclusions: One previous study has reported the Ala allele to be associated with higher BMI among Hispanics; however, we did not find this association. Further, we could not conclude that dietary fat intake or physical activity altered any association between BMI or WC and the Ala allele.
Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse

Objectives: An abnormal CD4+ T cell subset related to inflammation exposure (inflammation-related cells, IRC) has been identified in rheumatoid arthritis (RA). Patients with inflammatory and non-inflammatory diseases were used to examine the relationship between inflammation and this T cell subset in vivo. Methods: Blood was collected from healthy controls and patients with RA (active disease or in clinical remission), Crohn’s disease and osteoarthritis. IRC and chemokine receptors were quantified by flow cytometry. Thymic activity and apoptotic factors were measured by real-time polymerase chain reaction. Circulating cytokines were measured by enzyme-linked immunosorbent assay. CXCR4 and SDF1 in synovial biopsies were measured using immunohistochemistry. Results: IRC were identified in patients with RA (p<0.0001) and Crohn’s disease (p = 0.005), but not in those with osteoarthritis. In RA in remission, IRC persisted (p<0.001). In remission, hyperproliferation of IRC was lost, chemokine receptor expression was significantly lowered (p<0.007), Bax expression dropped significantly (p<0.001) and was inversely correlated with IRC (rho = −0.755, p = 0.03). High IRC frequency in remission was associated with relapse within 18 months (OR = 6.4, p<0.001) and a regression model predicted 72% of relapse. Conclusions: These results suggest a model in which, despite the lack of systemic inflammation, IRC persist in remission, indicating that IRC are an acquired feature of RA. They have, however, lost their hyper-responsiveness, acquired a potential for survival, and no longer express chemokine receptors. IRC persistence in remission confirms their important role in chronic inflammation as circulating precursors of pathogenic cells. This was further demonstrated by much higher incidence of relapse in patients with high IRC frequency in remission.
Plasma levels of soluble glycoprotein VI (sGPVI) are associated with ischemic stroke

Platelet collagen receptor glycoprotein VI (pGPVI) is elevated in patients with acute coronary syndrome (ACS) and ischemic stroke. Recently, we developed a novel bead-based sandwich immunoassay to determine soluble GPVI (sGPVI), which has been validated in ACS patients. This study aimed to evaluate the plasma levels of sGPVI and pGPVI expression in patients with suspected stroke. We consecutively evaluated 176 patients, who were admitted to the stroke unit. Surface expression of pGPVI was determined by flow cytometry, sGPVI concentrations were determined using our sandwich immunoassay. Unlike patients with TIA, patients with stroke showed significantly decreased plasma levels of sGPVI compared to patients with non-ischemic (NI) events (TIA: mean [µg/L] ± standard deviation): 6.1 ± 2.1 vs. NI: 8 ± 4; p = 0.192; stroke: 5.9 ± 2.3 vs. NI; p = 0.013), whereas for pGPVI, patients with TIA and ischemic stroke revealed a significantly increased platelet surface expression compared to NI patients (TIA: mean fluorescence intensity [MFI] ± standard deviation): 20.9 ± 5.4 vs. NI: 17.6 ± 5.2; p = 0.021; stroke: 20.3 ± 6.2 vs. NI; p = 0.016). Using logistic regression analysis, both sGPVI (p = 0.002) and pGPVI (p = 0.012) are independently associated with ischemic stroke compared to other laboratory markers. To predict the individual risk for ischemic stroke using the plasma levels of sGPVI, receiver operating characteristic (ROC) analysis determined an optimal cutoff value of sGPVI at 6.5 µg/l, thus, patients with decreased plasma levels (<6.5 µg/l) have a 1.5-fold adjusted odds ratio (95%confidence interval, 1.4–2.7). Lower plasma levels of sGPVI are associated with the slightly elevated risk of stroke and may be a promising novel biomarker.