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Jennifer S Lee

Publications and source records attributed to Jennifer S Lee.

8 recordsLinked to original sources
PubMed2025

Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction.

Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving the treatment of diseases. We employed a cross-disciplinary approach to identify potential therapeutics for the prevention of metabolic-dysfunction-associated steatotic liver disease (MASLD) in at-risk individuals by using humans as a model organism. We identified 212 putative candidate genes associated with MASLD by using data from a large multi-ancestry genetic association study, of which 158 (74.5%) were previously unreported. From this set, we identified 57 genes that encode for druggable protein targets and for which the effects of increasing genetically predicted gene expression on MASLD risk align with the function of that drug on the protein target. We then used We then evaluated these potential targets for evidence of efficacy by using Mendelian randomization, pathway analysis, and protein structural modeling. Through these approaches, we present compelling evidence to suggest that the activation of FADS1 by icosapent ethyl, as well as S1PR2 by fingolimod, could be a promising therapeutic strategy for MASLD prevention.

Humans↗
PubMed2006

Reproductive risk factors for cutaneous melanoma in women: a case-control study.

Reproductive hormonal factors may have a potential role in cutaneous melanoma. This study estimated the risk of melanoma in women related to self-reported changes in nevi during pregnancy, while using oral contraceptives and/or hormone replacement therapy. Trained interviewers administered a questionnaire obtaining information about oral contraceptive use, hormone replacement therapy, reproductive history, sun exposure, occupation, and medical history from 318 Caucasian women newly diagnosed between 1991 and 1992 from two pigmented lesion clinics in San Francisco, California, and Philadelphia, Pennsylvania. A total of 395 frequency-matched control participants were recruited from hospital-affiliated outpatient clinics. Clinicians conducted skin examinations to assess the number and type of nevi, extent of freckling, solar damage, and skin type. For women aged less than 55 years, there was an association between a livebirth 5 years before diagnosis (odds ratio = 2.6, 95% confidence interval: 1.3, 5.3) and between number of births and melanoma risk (for > or = 3 births: odds ratio = 3.3, 95% confidence interval: 1.7, 6.5; ptrend < 0.001). Changes in nevi during recent pregnancies were a risk factor for melanoma, based upon small numbers (odds ratio = 2.9, 95% confidence interval: 1.1, 8.1). Oral contraceptive use and hormone replacement therapy were not associated with melanoma risk.

Adult↗
PubMed2006

Comparison of methods to measure low serum estradiol levels in postmenopausal women.

CONTEXT: Accurate measurement of low serum estradiol (E(2) < 30 pg/ml or < 110 pmol/liter) is needed to study relationships between endogenous E(2) and risks of diseases in older women. OBJECTIVE: The objective of this study was to determine whether an extraction-based (indirect) assay or a non-extraction-based (direct) assay correlates better with mass spectrometry and body mass index (BMI). DESIGN/SETTING: In a pilot study of 40 postmenopausal women, endogenous E(2) measurements from three indirect and four direct assay methods and gas chromatography-tandem mass spectrometry (GC-MS/MS) were compared. A confirmatory study compared an indirect and a direct assay, selected among those in the pilot study, to GC-MS/MS; this study was conducted in 374 postmenopausal women not taking hormone therapy from the Ultra Low-dose TRansdermal estrogen Assessment (ULTRA) trial. MAIN OUTCOMES: Pearson correlation coefficients among E(2) measurements by assay methods and BMI, and their confidence intervals, by bias-corrected bootstrap method, were used. RESULTS: In the pilot study, E(2) by three indirect assays correlated better (P < 0.03) with GC-MS/MS and with BMI than measurements by four direct assays. In the confirmatory study, the indirect assay correlated better (P < 0.01) with GC-MS/MS and BMI than the direct assay. Measurements by the indirect and direct assays were overestimated, but deviations in direct assay measurements were less precise. Mean E(2) by the indirect and direct assays were higher (by 14 and 68%, respectively) and less reproducible than by GC-MS/MS. CONCLUSION: Until mass spectrometry is practical for wide use, extraction-based indirect assays may be preferable for measuring low postmenopausal serum E(2).

Aged↗
PubMed2006

Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations.

BACKGROUND: First-degree relatives of patients with breast or ovarian cancer have increased risks for these cancers. Little is known about how their risks vary with the patient's cancer site, carrier status for predisposing genetic mutations, or age at cancer diagnosis. METHODS: We evaluated breast and ovarian cancer incidence in 2,935 female first-degree relatives of non-Hispanic White female patients with incident invasive cancers of the breast (n = 669) or ovary (n = 339) who were recruited from a population-based cancer registry in northern California. Breast cancer patients were tested for BRCA1 and BRCA2 mutations. Ovarian cancer patients were tested for BRCA1 mutations. We estimated standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) for breast and ovarian cancer among the relatives according to the patient's mutation status, cancer site, and age at cancer diagnosis. RESULTS: In families of patients who were negative or untested for BRCA1 or BRCA2 mutations, risks were elevated only for the patient's cancer site. The breast cancer SIR was 1.5 (95% CI, 1.2-1.8) for relatives of breast cancer patients, compared with 1.1 (95% CI, 0.8-1.6) for relatives of ovarian cancer patients (P = 0.12 for difference by patient's cancer site). The ovarian cancer SIR was 0.9 (95% CI, 0.5-1.4) for relatives of breast cancer patients, compared with 1.9 (95% CI, 1.0-4.0) for relatives of ovarian cancer patients (P = 0.04 for difference by site). In families of BRCA1-positive patients, relatives' risks also correlated with the patient's cancer site. The breast cancer SIR was 10.6 (95% CI, 5.2-21.6) for relatives of breast cancer patients, compared with 3.3 (95% CI, 1.4-7.3) for relatives of ovarian cancer patients (two-sided P = 0.02 for difference by site). The ovarian cancer SIR was 7.9 (95% CI, 1.2-53.0) for relatives of breast cancer patients, compared with 11.3 (3.6-35.9) for relatives of ovarian cancer patients (two-sided P = 0.37 for difference by site). Relatives' risks were independent of patients' ages at diagnosis, with one exception: In families ascertained through a breast cancer patient without BRCA mutations, breast cancer risks were higher if the patient had been diagnosed before age 40 years. CONCLUSION: In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patient's cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations.

Adult↗
PubMed2005

Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study.

OBJECTIVE: Antiestrogens reduce the risk of estrogen receptor-positive (ER+) but not ER-negative (ER-) breast cancer. Women at high risk of ER+ cancer would be the most likely to benefit from these treatments, but the best approach to predicting ER+ cancer is uncertain. METHODS: We prospectively assessed putative risk factors for breast cancer and archived serum at -190 degrees C from a community-based cohort of 7,676 women ages > or =65 years who had no history of breast cancer. Follow-up for breast cancer over 10.5 years was 99% complete. Using a case-cohort design, we measured baseline levels of estradiol and testosterone in 196 cases of invasive ER+ cancer and 378 randomly selected controls. RESULTS: Women whose testosterone level in highest two quintiles had a 4-fold increased risk of ER+ breast cancer (P < 0.0001). High estradiol concentration also indicated an increased risk but was not a significant predictor after adjustment for testosterone. Women with >16 years of education had a 2.1 times increased risk (P = 0.03) of ER+ cancer, but no other risk factors were significantly related to an increased risk of ER+ cancer. Women with a family history of breast cancer had a 2.9-fold increased risk of ER- cancer (P = 0.002) but no increased risk of ER+ cancer (relative hazard = 1.2, 0.8-1.8). CONCLUSIONS: High serum testosterone and advanced education predicted ER+ breast cancer. If confirmed, high testosterone level may be more accurate than family history of breast cancer and other conventional risk factors for identifying older women who are most likely to benefit from antiestrogen chemoprevention.

Aged↗
PubMed2002

Validation of electronic student encounter logs in an emergency medicine clerkship.

Handheld electronic patient encounter logs offer opportunities to understand and enhance medical students' clinical experiences. Before using the data, the reliability of log entries needs to be verified. We assessed the sensitivity and specificity of handheld patient encounter logs by comparing documented entries with reliable external data sources. During an Emergency Medicine clerkship, medical students voluntarily recorded their patients' diagnoses in an Electronic Student Encounter Log (E-SEL) on handheld computers. We used patient demographics to match anonymous log entries with medical charts. Most students recorded 60% or more of their patient encounters and on average 60% of their patients' medical problems in the log. The false positive rate was 26% for patient encounters and 19% for patient problems. In general, students recorded more diagnoses in more detail than was available in the patient's ED chart. Improvements in the log's interface and documentation incentives should enhance the log's accuracy and utility.

Clinical Clerkship↗
PubMedDate not supplied

Current GI endoscope disinfection and QA practices.

High-level disinfection (HLD) of GI endoscopes is readily achieved when published guidelines are observed. Contamination is linked to breakdowns in accepted procedure. However, there is no recognized method of verifying adequacy of endoscope reprocessing in routine practice and no data regarding current quality assurance (QA) practice. Prior reports have demonstrated a wide variation in routine clinical practice of GI endoscopy HLD. The goal of this study was to determine current practice at regional endoscopy centers with regard to endoscope cleaning and HLD, maintenance, and QA practice. An anonymous multiple-choice questionnaire was mailed to 367 SGNA members in Pennsylvania, Delaware, Virginia, Maryland, and District of Columbia and completed by 230 (63%). The majority of responders were hospital-based and 59% of the units performed over 3000 procedures per year. After use the endoscope was hand-carried or transported in a dry container (97%) to a separate cleaning room (85%) for HLD by technicians (40%). Wide variations existed in manual step procedures including use of disposable (50%) brushes and number of times channel brushed: once (21%), twice (35%), or three to five times (37%). Soaking duration in disinfectant (70% gluteraldehyde) was for <10 min (8%), 10-20 min (35%), 20-30 min (38%), 30-40 min (7%), and >40 min (3%). Sixty-seven percent had an active unit infection control (IC) service and 98% had a QA program. Monitoring of cleaning effectiveness was by visual inspection (50%) and culturing endoscopes (17%). Culture was done weekly (1%) and <biannually (6.5%) and performed by swabing the endoscope end (5%) or rinsing the biopsy channel (8%). If culture positive, most would remove the instrument from clinical use and reevaluate the protocol and personnel for technique lapses. Two respondents were aware of a procedure-related infection. Wide practice variations were noted in manual cleaning and in soaking time during automated HLD in this community. Fewer variations were noted in cleaning personnel and training, location and methods of cleaning, and presence of IC services and QA programs. Endoscope culturing was infrequently done and positive cultures were rare. While most units claim to have ongoing QA programs, few use objective criteria to monitor effective disinfection or lapses in technique. Iatrogenic infection is uncommonly recognized following GI endoscope procedures.

Disinfectants↗