Publications by authors named "Andrew Bradford"

Article Synopsis
  • - E2F1 is a transcription factor that plays a dual role in cell growth, promoting both cell proliferation and tumor suppression, particularly when the tumor suppressor pRB is not functioning.
  • - The N-terminal region of E2F1 is crucial for activating tumor suppressor genes, as removing this region significantly reduces its ability to do so.
  • - GTF2H2, a general transcription factor, interacts with the N-terminal region of E2F1 and enhances its tumor suppressor gene activity, while its knockdown negatively impacts this function.
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Purpose: As primary care (PC) clinics seek to integrate behavioral health (BH) services into patient care, it is crucial to understand the experiences of the clinic team and the impact on workflow and well-being. This study was designed to identify perspectives and experiences of nurse practitioner-led PC teams as they implemented a behavioral health integration (BHI) model into their Federally Qualified Health Center PC practices.

Methods: We conducted in-depth qualitative interviews with staff members at three clinic sites that implemented BHI.

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Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The trans-activator protein Tax of HTLV-1 plays crucial roles in leukemogenesis by promoting proliferation of virus-infected cells through activation of growth-promoting genes. However, critical target genes are yet to be elucidated.

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators.

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Background: African American Women (AAW) are at high risk for stress-related cardiometabolic (CM) conditions including obesity, heart disease, and diabetes. Prior interventions lack attention to culturally-nuanced stress phenomena (Superwoman Schema [SWS], contextualized stress, and network stress), which are positively and significantly associated with unhealthy eating and sedentary behavior.

Purpose: The HARMONY Study is designed to test a culturally tailored mindfulness-based stress management intervention to address SWS, contextualized stress, and network stress as potential barriers to adherence to healthy exercise and eating goals.

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Obesity is associated with chronic low-level inflammation and is known to contribute to metabolic dysfunction and hypogonadotropic hypogonadism, which we have previously termed the 'Reprometabolic Syndrome.' To investigate potential factors involved in obesity-related reproductive endocrine dysfunction, we conducted a secondary analysis of inflammatory markers in a sample of normal weight women exposed to a one-month eucaloric high-fat diet (HFD), which, as reported earlier, induced the relative hypogonadotropic hypogonadism characteristic of Reprometabolic Syndrome. Eighteen healthy women with a BMI between 18.

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Adverse effects of obesity on reproduction are believed in part due to diet related factors leading to hyperlipidemia and hyperinsulinemia. It is unknown whether administration of a low fat eating plan, regardless of weight loss, will improve reproductive axis function in women with obesity. To develop an acceptable and feasible low fat eating plan for a diverse group of reproductive aged women with obesity.

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Importance: Weight loss before conception is recommended for women with overweight or obesity to improve fertility outcomes, but evidence supporting this recommendation is mixed.

Objective: To examine the effectiveness of weight loss interventions using lifestyle modification and/or medication in women with overweight or obesity on pregnancy, live birth, and miscarriage.

Data Sources: An electronic search of MEDLINE, Embase, Cochrane Library, including Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature was conducted through July 6, 2022, via Wiley.

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We examined the effects of 1 month of a eucaloric, high-fat (48% of calories) diet (HFD) on gonadotropin secretion in normal-weight women to interrogate the role of free fatty acids and insulin in mediating the relative hypogonadotropic hypogonadism of obesity. Eighteen eumenorrheic women (body mass index [BMI] 18-25 kg/m) were studied in the early follicular phase of the menstrual cycle before and after exposure to an HFD with frequent blood sampling for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), followed by an assessment of pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Mass spectrometry-based plasma metabolomic analysis was also performed.

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Article Synopsis
  • - The transcription factor E2F serves as a crucial link between the RB and p53 pathways, actively participating in tumor suppression by regulating cell proliferation through various growth-related genes.
  • - The tumor suppressor pRB controls E2F activity by binding to it, thereby preventing excessive cell growth, but is often mutated in cancers, leading to increased E2F activity and tumor progression.
  • - In response to dysregulation, E2F can activate the tumor suppressor p53, but in many cancers, p53 is also compromised, resulting in a breakdown of cellular safeguards against tumorigenesis.
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Objective: To establish conditions for effective hypothalamic suppression in women with normal and high body mass index (BMI) and test the hypothesis that intravenous (IV) administration of pulsatile recombinant follicle-stimulating hormone (rFSH) can overcome the clinically evident dysfunctional pituitary-ovarian axis in women with obesity.

Design: Prospective interventional study.

Setting: Academic medical center.

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The TFDP1 gene codes for the heterodimeric partner DP1 of the transcription factor E2F. E2F, principal target of the tumor suppressor pRB, plays central roles in cell proliferation by activating a group of growth-related genes. E2F also mediates tumor suppression by activating tumor suppressor genes such as ARF, an upstream activator of the tumor suppressor p53, when deregulated from pRB upon oncogenic changes.

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Article Synopsis
  • The transcription factor E2F is central to cell growth and tumor suppression, but its activity is often heightened in cancer due to the inactivation of the tumor suppressor pRB.
  • Current cancer treatment trials aim to inhibit E2F activity to slow down cancer cell proliferation, but these methods can also affect normal cells since they rely on the same growth pathways.
  • Deregulated E2F activity, exclusive to cancer cells, activates tumor suppressor genes and is not dependent on growth-stimulating partners, revealing its potential as a targeted cancer therapy.
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Introduction: Obesity is characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism, reducing fertility and increasing risk of pregnancy complications and birth defects. We termed this phenotype 'Reprometabolic Syndrome' and showed that it can be recapitulated by acute infusions of lipid/insulin into healthy, normal weight, eumenorrheic women. Herein, we examined the broader impact of hyperlipidemia and euglycemic hyperinsulinemia on anterior pituitary trophic hormones and their targets.

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Introduction: Studies using lipid infusions to raise fatty acid levels require heparin to release lipoprotein lipase (LPL), thus calling into question the appropriate control infusion for this type of study: saline alone or saline plus heparin. We aimed to evaluate whether the addition of heparin alone, in doses needed to release LPL, would alter circulating free fatty acids (FFAs) and/or affect gonadotropins.

Materials And Methods: This was a secondary analysis using combined data from eumenorrheic normal-weight women subjected to "control" conditions in 1 of 2 separate studies.

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The role of β-catenin/TCF transcriptional activity in endometrial cancer (EC) recurrence is not well understood. We assessed the impact of Wnt/β-catenin inhibition in EC models. In an analysis of the Cancer Genome Atlas, we confirmed that CTNNB1 mutations are enriched in recurrent low-risk EC and showed that aberrant Wnt/β-catenin pathway activation is associated with recurrence.

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Objective: To study the reprometabolic syndrome in normal-weight, eumenorrheic women by infusing a combination of insulin and lipid. Women with obesity have been shown to have reduced gonadotropins and impaired luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (GnRH).

Design: Randomized crossover.

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Context: Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin.

Objective: To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction.

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Transgender and non-binary people are more likely to face barriers to healthcare than their cisgender counterparts. The majority of work in this area centers on the experiences of transgender people in northern cities and urban enclaves, yet over 500,000 transgender people live in the U.S.

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In obese ovulatory women, serum luteinizing Hormone (LH) and follicle stimulating hormone (FSH) are lowered compared with normal weight women. This relative hypogonadotropic hypogonadism represents a potential etiology for overall decreased fertility in obesity. The objective was to determine if administration of an aromatase inhibitor (AI) to ovulating obese women would normalize LH and FSH by interrupting estradiol negative feedback.

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Background And Objectives: This article is the second of a 2-part series examining results regarding self-reported learning and practice change from the American Board of Pediatrics 2017 pilot of an alternative to the proctored, continuing certification examination, termed the Maintenance of Certification Assessment for Pediatrics (MOCA-Peds). Because of its design, MOCA-Peds has several learning advantages compared with the proctored examination.

Methods: Quantitative and qualitative analyses with 5081 eligible pediatricians who registered to participate in the 2017 pilot; 81.

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It is well known the dimerization state of receptor tyrosine kinases (RTKs), in conjunction with binding partners such as the growth factor receptor bound protein 7 (Grb7) protein, plays an important role in cell signaling regulation. Previously, we proposed, downstream of RTKs, that the phosphorylation state of Grb7SH2 domain tyrosine residues could control Grb7 dimerization, and dimerization may be an important regulatory step in Grb7 binding to RTKs. In this manner, additional dimerization-dependent regulation could occur downstream of the membrane-bound kinase in RTK-mediated signaling pathways.

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Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment.

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