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Biomedical subjects

Jennifer Lee

Publications and source records attributed to Jennifer Lee.

At least 19 recordsLinked to original sources
PubMed2026

Cross-Ancestry and Phenome-Wide Associations of Cancer-Specific Polygenic Risk Scores.

PURPOSE: Genome-wide association studies have identified many common variants associated at low effect sizes with various cancers. Summing the effects of these variants into polygenic risk scores (PRS) can improve cancer risk prediction. However, cross-cancer and cross-phenotype pleiotropic associations of cancer-specific PRS are limited. METHODS: Using logistic regression models, we tested the association of 13 cancer-specific PRS with curated phenotypes representing the same 13 cancers and 340 cancer and cardiometabolic phecodes in 560,287 individuals (114,255 African ancestry [AFR] and 446,032 European ancestry [EUR]) from the Million Veteran Program. Models were stratified by ancestry and used age, principal components, and cancer-specific PRS per standard deviation as independent variables, and correction was applied for multiple comparisons. RESULTS: All 13 cancer-specific PRS were significantly associated with their respective cancers among EUR individuals with odds ratios per standard deviation of PRS (odds ratio [OR]) 1.05-1.70. Among AFR individuals, the effect sizes of the cancer PRS were lower, with OR 1.01-1.48, and cancer-specific PRS were significantly associated with their respective cancers for five of 13 cancers (bladder, breast in female patients, colorectal, prostate, and thyroid). In cancer-cancer pleiotropy studies, only the renal cancer-specific PRS was significantly associated with skin cancer (OR = 1.04, P = 4.5 × 10-06) among EUR individuals. PheWAS demonstrated five positive pleotropic associations with cardiometabolic conditions (thyroid cancer PRS with thyroid goiter, oral cancer PRS with diabetes phenotypes, and hypothyroidism) and two negative associations (oral and lung cancer PRS separately with coronary artery disease). CONCLUSION: Cancer PRS have stronger associations per cancer among EUR versus AFR individuals. In contrast to PRS of other chronic diseases, the majority of cancer-related PRS are highly specific and pleiotropic associations with other cancers and cardiometabolic traits are uncommon.

Female↗
PubMed2006

Mutational analysis of sigma70 region 4 needed for appropriation by the bacteriophage T4 transcription factors AsiA and MotA.

Transcriptional activation of bacteriophage T4 middle promoters requires sigma70-containing Escherichia coli RNA polymerase, the T4 activator MotA, and the T4 co-activator AsiA. T4 middle promoters contain the sigma70 -10 DNA element. However, these promoters lack the sigma70 -35 element, having instead a MotA box centered at -30, which is bound by MotA. Previous work has indicated that AsiA and MotA interact with region 4 of sigma70, the C-terminal portion that normally contacts -35 DNA and the beta-flap structure in core. AsiA binding prevents the sigma70/beta-flap and sigma70/-35 DNA interactions, inhibiting transcription from promoters that require a -35 element. To test the importance of residues within sigma70 region 4 for MotA and AsiA function, we investigated how sigma70 region 4 mutants interact with AsiA, MotA, and the beta-flap and function in transcription assays in vitro. We find that alanine substitutions at residues 584-588 (region 4.2) do not impair the interaction of region 4 with the beta-flap or MotA, but they eliminate the interaction with AsiA and prevent AsiA inhibition and MotA/AsiA activation. In contrast, alanine substitutions at 551-552, 554-555 (region 4.1) eliminate the region 4/beta-flap interaction, significantly impair the AsiA/sigma70 interaction, and eliminate AsiA inhibition. However, the 4.1 mutant sigma70 is still fully competent for activation if both MotA and AsiA are present. A previous NMR structure shows AsiA binding to sigma70 region 4, dramatically distorting regions 4.1 and 4.2 and indirectly changing the conformation of the MotA interaction site at the sigma70 C terminus. Our analyses provide biochemical relevance for the sigma70 residues identified in the structure, indicate that the interaction of AsiA with sigma70 region 4.2 is crucial for activation, and support the idea that AsiA binding facilitates an interaction between MotA and the far C terminus of sigma70.

Alanine↗
PubMed2006

Antibody-based surface plasmon resonance detection of intact viral pathogen.

Surface plasmon resonance (SPR) technique was used to directly detect an intact form of insect pathogen: the baculovirus, Autographa californica multiple nuclear polyhedrosis virus (AcMNPV). An SPR sensor chip with three bio-functional layers was used to detect the intact AcMNPV: amine-reactive crosslinker with a disulfide bond that chemisorbs to gold film, Protein A, and a mouse IgG monoclonal antibody raised against a surface protein of the target viral pathogen. A two-channel (reference & test) micro-fluidic SPR system is used for reliable measurement. Bio-specific response to the AcMNPV is compared with the response for tobacco mosaic virus (TMV) as control. Successive exposure of the sensor chip to both viruses verifies a specific response to AcMNPV. This serves as a prerequisite to the development of a new type of viral pathogen detection sensors.

Antibodies, Viral↗
PubMed2006

A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins.

Damaged DNA binding proteins (DDBs) play a critical role in the initial recognition of UV-damaged DNA and mediate recruitment of nucleotide excision repair factors. Previous studies identified DDB2 as a target of the CUL-4A ubiquitin ligase. However, the biochemical mechanism governing DDB proteolysis and its underlying physiological function in the removal of UV-induced DNA damage are largely unknown. Here, we report that the c-Abl nonreceptor tyrosine kinase negatively regulates the repair of UV-induced photolesions on genomic DNA. Biochemical studies revealed that c-Abl promotes CUL-4A-mediated DDB ubiquitination and degradation in a manner that does not require its tyrosine kinase activity both under normal growth conditions and following UV irradiation. Moreover, c-Abl activates DDB degradation in part by alleviating the inhibitory effect of CAND1/TIP120A on CUL-4A. These results revealed a kinase-independent function of c-Abl in a ubiquitin-proteolytic pathway that regulates the damage recognition step of nucleotide excision repair.

Animals↗
PubMed2006

Generation Challenge Programme (GCP): standards for crop data.

The Generation Challenge Programme (GCP) is an international research consortium striving to apply molecular biological advances to crop improvement for developing countries. Central to its activities is the creation of a next generation global crop information platform and network to share genetic resources, genomics, and crop improvement information. This system is being designed based on a comprehensive scientific domain object model and associated shared ontology. This model covers germplasm, genotype, phenotype, functional genomics, and geographical information data types needed in GCP research. This paper provides an overview of this modeling effort.

Crops, Agricultural↗
PubMed2006

The verbal numeric pain scale: effects of patient education on self-reports of pain.

BACKGROUND: Emergency department (ED) patients are frequently asked to provide a self-report of the level of pain experienced using a verbal numeric rating scale. OBJECTIVES: To determine the effects of patient education regarding the verbal numeric rating scale on self-reports of pain among ED patients. METHODS: In this prospective, interventional study, 310 eligible ED patients with pain, aged 18 years and older, were randomized to view either a novel educational video (n = 155) or a novel print brochure (n = 155) as an educational intervention, both developed to deliver educational information about the verbal numeric pain scale and its use. Participants initially rated their pain on a scale from 0 to 10 and then were administered the educational intervention. Following the educational intervention, participants completed a survey that included demographic information, postinterventional pain score, prior pain experience, and subjective rating of the helpfulness of the educational intervention. Fifty-five consecutive participants were enrolled as controls and received no educational intervention but gave a self-reported triage pain score and a second pain score at an equivalent time interval. Clinical significance was defined as a decrease in pain of 2 or more points following the education. RESULTS: Following the educational interventions, there were statistically significant, although not clinically significant, decreases in mean pain scores within each intervention group (video: mean change, 1 point [95% confidence interval [CI] = 0.7 to 1.2]; printed brochure: mean change, 0.6 points [95% CI = 0.4 to 0.8]). For participants in the control group (no intervention), there was no significant change (mean change, 0.2 points [95% CI = -0.2 to 0.5]). A clinically significant decrease in pain was seen in 28% of the video group, 23% of the brochure group, and 5% of controls. Most patients had no change (71% of the video group, 73% of the brochure group, and 89% of controls). Participants rated the helpfulness of the video educational intervention as 7.1 (95% CI = 6.7 to 7.5) and the print educational intervention as 6.7 (95% CI = 6.2 to 7.1) on a scale from 0 (least effective) to 10 (most helpful). CONCLUSIONS: Among ED participants with pain, both educational interventions (video and printed brochure) resulted in statistically and clinically significant decreased self-reported pain scores by 2 or more points in 26% of participants compared with 5% of controls. The educational interventions were rated as helpful by participants, with no appreciable difference between the two intervention groups.

Adult↗
PubMed2006

Religious identity among Christian Korean-American adolescents.

This exploratory study examined religious identity among Christian Korean-American adolescents. Marcia's 1966 model of identity formation, which conceptualizes identity along dimensions of exploration and commitment, provided the framework for the current study. 49 participants, between the ages of 14 and 19 years, completed the Duke Religion Index, the religion items from the Extended Objective Measure of Ego Identity Status, the Pan-denominational Measure of Personal Devotion and Personal Conservatism, and six questions assessing perceived parental involvement. Analysis indicated that high scores on Organizational and Intrinsic Religiosity were positively correlated with the commitment statuses of Achievement and Foreclosure and negatively correlated with the noncommitment statuses of Moratorium and Diffusion. Also high scores on perceived parental involvement were positively correlated with the nonexploration status of Foreclosure and negatively correlated with the exploration status of Moratorium. Overall, the study provided a general portrait and initial examination of the formation of religious identity in a sample of Christian Korean-American adolescents.

Adolescent↗
PubMed2005

The use of complementary and alternative medicine among california adults with and without cancer.

This article examines the extent and correlates of complementary and alternative medicine (CAM) use among a population-based sample of California adults that is highly diverse in terms of sociodemographic characteristics and health status. As a follow-up to a state-wide health survey of 55,428 people, 9187 respondents were interviewed by phone regarding their use of 11 different types of CAM providers, special diets, dietary supplements, mind-body interventions, self-prayer and support groups. The sample included all participants in the initial survey who reported a diagnosis of cancer, all the non-white respondents, as well as a random sample of all the white respondents. The relation of CAM use to the respondents' demographic characteristics and health status is assessed. CAM use among Californians is generally high, and the demographic factors associated with high rates of CAM use are the same in California as have been found in other studies. Those reporting a diagnosis of cancer and those who report other chronic health problems indicate a similar level of visits to CAM providers. However, those with cancer are less likely to report using special diets, and more likely to report using support groups and prayer. Health status, gender, ethnicity and education have an independent impact upon CAM use among those who are healthy as well as those who report suffering from chronic health problems, although the precise relation varies by the type of CAM used.

Journal Article↗
PubMed2004

Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway.

Homeostasis under hypoxic conditions is maintained through a coordinated transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway and requires coactivation by the CBP and p300 transcriptional coactivators. Through a target-based high-throughput screen, we identified chetomin as a disrupter of HIF binding to p300. At a molecular level, chetomin disrupts the structure of the CH1 domain of p300 and precludes its interaction with HIF, thereby attenuating hypoxia-inducible transcription. Systemic administration of chetomin inhibited hypoxia-inducible transcription within tumors and inhibited tumor growth. These results demonstrate a therapeutic window for pharmacological attenuation of HIF activity and further establish the feasibility of disrupting a signal transduction pathway by targeting the function of a transcriptional coactivator with a small molecule.

Animals↗
PubMed2004

Instructional influences on analogue functional analysis outcomes.

Analogue assessments were conducted with a common contingency (escape from tasks) that varied only by three different instructions describing the contingency. In one condition, the contingency was described as "taking a break," in another condition it was described as "time-out," and no description of the contingency was provided in a third condition. The participant was a typically developing 5-year-old child with a diagnosis of attention deficit hyperactivity disorder. Rates of inappropriate behavior varied substantially across the three conditions as an apparent effect of the prior instructions. Some implications for conducting functional analyses with verbal children are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression.

INTRODUCTION: In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. METHOD: Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function. RESULTS: The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor-Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity. CONCLUSION: We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment.

Acute-Phase Reaction↗
PubMed2003

Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma.

Smad7 and Smad6 are inhibitory Smads that block transforming growth factor-beta (TGF-beta) superfamily signal transduction. Smad7 is overexpressed in chemically induced mouse epidermal tumors, where oncogenic activation of c-ras is a frequent event. To test the role of Smad7 overexpression in tumor progression, we used retroviruses to transduce Smad7 or Smad6 and v-ras(Ha) into primary mouse keratinocytes. By itself, Smad7 transiently enhanced keratinocyte proliferation, blocked normal differentiation, and induced keratin 8, a marker of malignant conversion, but did not cause tumor formation. Smad7 extended the in vitro life span, suppressed senescence, and increased transformation frequency 3-fold of primary keratinocytes coexpressing v-ras(Ha). Smad7/v-ras(Ha) coinfected keratinocytes rapidly progressed to squamous cell carcinomas in vivo, whereas pBabe/v-ras(Ha)- or Smad6/v-ras(Ha)-transduced keratinocytes formed only benign papillomas. Smad7/v-ras(Ha) tumors had elevated proliferation and defective nuclear localizaton of Smad2, Smad3, and Smad5, whereas only Smad5 was altered in Smad6/v-ras(Ha) tumors. Smad7 overexpression in vitro induced epidermal growth factor (EGF)-like growth factors TGF-alpha, heparin binding-EGF, amphiregulin, and EGF receptor tyrosine phosphorylation as well as the EGF-CFC growth factor cripto-1. TGF-alpha and cripto-1 were also overexpressed in Smad7/v-ras(Ha) tumors. These results suggest that Smad7 overexpression accelerates tumor progression through inhibition of TGF-beta superfamily signaling and up-regulation of the EGF-like superfamily of growth factors. This is the first demonstration that Smad7 overexpression can cause malignant conversion in a multistage cancer model and suggests that it may have an important role in the pathogenesis of human cancer.

Animals↗
PubMed2003

Advanced glycation end-product (AGE)-damaged IgG and IgM autoantibodies to IgG-AGE in patients with early synovitis.

Advanced glycation end-product (AGE)-damaged IgG occurs as a result of hyperglycemia and/or oxidative stress. Autoantibodies to IgG-AGE were previously demonstrated in patients with severe, longstanding rheumatoid arthritis (RA). We investigated whether IgG-AGE and anti-IgG-AGE antibodies were present early in the course of RA and other inflammatory arthropathies. We prospectively followed a cohort of 238 patients with inflammatory arthritis of duration less than 1 year. Patients were evaluated clinically and serologically, and radiographs were obtained at initial and 1-year visits. Sera were assayed for IgG-AGE and anti-IgG-AGE antibodies by enzyme-linked immunosorbent assay (ELISA). Rheumatoid factor (RF) was determined by nephelometry and ELISA. Of all patients, 29% had RF-positive RA, 15% had RF-negative RA, 18% had spondyloarthropathy, and 38% had undifferentiated arthritis. IgG-AGE was present in 19% of patients, and was similar in amount and frequency in all groups. Patients with elevated IgG-AGE levels had significantly higher levels of the inflammatory markers C-reactive protein and erythrocyte sedimentation rate, but there was no correlation with blood glucose levels. Overall, 27% of the patients had IgM anti-IgG-AGE antibodies. These antibodies were highly significantly associated with RFs (P < 0.0001) and with swollen joint count (P < 0.01). In early onset arthritis, IgG damaged by AGE was detected in all patient groups. The ability to make IgM anti-IgG-AGE antibodies, however, was restricted to a subset of RF-positive RA patients with more active disease. The persistence of the anti-IgG-AGE response was more specific to RA, and was transient in the patients with spondyloarthropathy and with undifferentiated arthritis who were initially found to be positive for anti-IgG-AGE antibodies.

Adult↗
PubMed2003

Surveillance cultures to monitor quality of gastrointestinal endoscope reprocessing.

OBJECTIVES: High-level disinfection of GI endoscopes can be reliably obtained under controlled conditions with approved reprocessing methods. However, there are scant data regarding the effectiveness of these methods in clinical practice and no published methods of verification. The purpose of this study is to review retrospectively the results of environmental cultures of flexible endoscopes and to analyze the pattern of results. METHODS: Cultures of selected GI endoscopes listed as ready to use were obtained by adding 5-15 ml of trypticase soy broth or saline or 30-50 ml of sterile water to the biopsy channel of an endoscope. This wash was collected in a sterile container, plated onto blood and MacConkey agar, incubated at 37 degrees C, and examined for growth at 24 and 48 h. Personnel trained in accordance with approved procedures performed endoscope reprocessing. RESULTS: A total of 312 surveillance cultures were performed between 1990 and 1999. Initially, three of 17 water bottles were found to be contaminated with Pseudomonas species. The bottles were sterilized daily; only sterile water was used and subsequent cultures were negative. Between 1992 and 1994, 15/129 (11.6%) cultures were positive; 14 (93%) were from duodenoscopes. From 1995 to 1997, 18/124 (14.5%) cultures were positive, but only six (33%) were from duodenoscopes. However, 10 (55.6%) positive cultures were obtained from therapeutic upper endoscopes, attributed to faulty mechanical cleaning by nonnursing personnel after emergent procedures. The reprocessing procedure was altered, with improvement. One duodenoscope was persistently culture positive and was found to have a damaged biopsy channel. There were no recognized iatrogenic infections associated with endoscopic procedures. Organisms cultured were commonly gram-negative rods. CONCLUSIONS: The use of environmental endoscope culturing is a rapid, simple, inexpensive method to monitor effectiveness of standard reprocessing procedures. Disinfection is less effective with poor mechanical cleansing, and high-titer positivity is a marker for poor cleaning technique. Standard upper and lower scopes are commonly culture negative. Duodenoscopes, because of their inherent complexity, and other scopes used in emergent conditions require particular attention. Surveillance culture results can be used to identify patterns of poor technique, to reinforce proper procedure, and to modify clinical practice. No associated clinical illness was apparent during this study.

Bacteria↗
PubMed2003

A survey of New Yorkers after the Sept. 11, 2001, terrorist attacks.

OBJECTIVE: This study examined the prevalence of psychiatric symptoms among residents/workers in Manhattan 3-6 months after the Sept. 11, 2001, terrorist attacks. METHOD: A total of 1,009 adults (516 men and 493 women) were interviewed in person throughout Manhattan. All answered questions about themselves before and after September 11 that included their emotional status. RESULTS: A total of 56.3% had at least one severe or two or more mild to moderate symptoms. Women reported significantly more symptoms than men. Loss of employment, residence, or family/friends correlated with greater and more severe symptoms. The most distressing experiences appeared to be painful memories and reminders; dissociation was rare. Only 26.7% of individuals with severe symptoms were obtaining treatment. CONCLUSIONS: Over half of the individuals had some emotional sequelae 3-6 months after September 11, but the percent was decreasing. Only a small portion of those with severe responses was seeking treatment.

Adaptation, Psychological↗