30 results on '"S Keenan"'
Search Results
2. Racial and ethnic differences in maternal self-reported sleep quality in pregnancy
- Author
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Caitlin MacGregor, Alexa A. Freedman, Lauren S. Keenan-Devlin, William A. Grobman, Hyagriv Simhan, Pathik D. Wadhwa, Claudia Buss, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2023
3. The association of group prenatal care and pregnancy outcomes among high stress pregnant individuals
- Author
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Lauren S. Keenan-Devlin, Lavisha Singh, Greg E. Miller, Linda M. Ernst, Jesica Britt, Britney P. Smart, Alexa A. Freedman, Amy Crockett, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2023
4. Thematic analysis of qualitative interviews looking at black birthing patient perspectives on police violence
- Author
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Britney P. Smart, Margaret Butler, Lauren S. Keenan-Devlin, Alexa A. Freedman, Thilini Fernando, Ashish Premkumar, Jasmin Flowers, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2023
5. Placental histology of term and preterm birth in a prospectively collected community sample
- Author
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Sunitha C. Suresh, Alexa A. Freedman, Lauren S. Keenan-Devlin, Greg E. Miller, Amy Crockett, Ann Borders, and Linda M. Ernst
- Subjects
Obstetrics and Gynecology - Published
- 2023
6. Association of maternal self-reported sleep quality with gestational diabetes
- Author
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Caitlin MacGregor, Alexa A. Freedman, Lauren S. Keenan-Devlin, William A. Grobman, Hyagriv Simhan, Pathik D. Wadhwa, Claudia Buss, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2023
7. Association between physical activity level and chronic inflammatory and vascular pathology in the placenta
- Author
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Sunitha C. Suresh, Alexa A. Freedman, Lauren S. Keenan-Devlin, Greg E. Miller, Amy Crockett, Ann Borders, and Linda M. Ernst
- Subjects
Obstetrics and Gynecology - Published
- 2023
8. The association of group prenatal care and inflammation among pregnant individuals reporting high stress
- Author
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Lauren S. Keenan-Devlin, Linda M. Ernst, Gregory Miller, Jesica Britt, Alexa A. Freedman, Britney P. Smart, Lavisha Singh, Amy Crockett, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2023
9. The impact of maternal ACEs on obstetric outcomes and psychosocial wellbeing during pregnancy
- Author
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Jesica Britt, Moonseong Heo, Lauren S. Keenan-Devlin, Ann Borders, Liwei Chen, and Amy Crockett
- Subjects
Obstetrics and Gynecology - Published
- 2023
10. Income loss and diet quality during the first COVID-19 lockdown in a UK and Australian sample: the role of distress as a potential mediator
- Author
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Gregory S. Keenan, William Samuel Royle, Lynne Marrow, and Lauren J. Owen
- Subjects
Nutrition and Dietetics ,General Psychology - Published
- 2022
11. Randomized Clinical Trial Comparing Group vs. Traditional Prenatal Care for Improving Equity in Birth Outcomes
- Author
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Amy H. Crockett, Liwei Chen, Emily Heberlein, Sarah Covington-Kolb, Jessica Britt, Xiaoqian Sun, Brian Witrick, Lu Zhang, Greg E. Miller, Ann Borders, Lauren S. Keenan-Devlin, and Moonseong Heo
- Subjects
Obstetrics and Gynecology - Published
- 2022
12. Association of maternal race/ethnicity and Education with breastfeeding practices
- Author
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Britney P. Smart, Lauren S. Keenan-Devlin, Margaret Butler, William A. Grobman, Pathik Wadhwa, and Ann Borders
- Subjects
Obstetrics and Gynecology - Published
- 2022
13. Comparing systemic inflammation in pregnancy for patients participating in group versus individual prenatal care
- Author
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Ann Borders, Lauren S. Keenan-Devlin, Britney P. Smart, Alexa A. Freedman, Lavisha Singh, Jessica Britt, Linda M. Ernst, Greg E. Miller, and Amy H. Crockett
- Subjects
Obstetrics and Gynecology - Published
- 2022
14. Lower limb joint kinetics in walking: The role of industry recommended footwear
- Author
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Jay Dicharry, Geoffrey S. Keenan, D. Casey Kerrigan, Jason R. Franz, and Ugo Della Croce
- Subjects
Adult ,Male ,musculoskeletal diseases ,Orthotic Devices ,medicine.medical_specialty ,Knee Joint ,Biophysics ,Walking ,Barefoot ,Cohort Studies ,Sports Equipment ,Young Adult ,Reference Values ,Humans ,Industry ,Medicine ,Orthopedics and Sports Medicine ,Range of Motion, Articular ,Ground reaction force ,Joint (geology) ,Foot ,business.industry ,Rehabilitation ,Biomechanics ,Equipment Design ,Gait ,Orthotic device ,Biomechanical Phenomena ,Shoes ,Lower Extremity ,Physical therapy ,Female ,Hip Joint ,Stress, Mechanical ,business ,Range of motion ,human activities ,Ankle Joint ,Muscle Contraction - Abstract
The effects of current athletic footwear on lower extremity biomechanics are unknown. The aim of this study was to examine the changes, if any, that occur in peak lower extremity net joint moments while walking in industry recommended athletic footwear. Sixty-eight healthy young adults underwent kinetic evaluation of lower extremity extrinsic joint moments while walking barefoot and while walking in current standard athletic footwear matched to the foot mechanics of each subject while controlling for speed. A secondary analysis was performed comparing peak knee joint extrinsic moments during barefoot walking to those while walking in three different standard footwear types: stability, motion control, and cushion. 3-D motion capture data were collected in synchrony with ground reaction force data collected from an instrumented treadmill. The shod condition was associated with a 9.7% increase in the first peak knee varus moment, and increases in the hip flexion and extension moments. These increases may be largely related to a 6.5% increase in stride length with shoes associated with increases in the ground reaction forces in all three axes. The changes from barefoot walking observed in the peak knee joint moments were similar when subjects walked in all three footwear types. It is unclear to what extent these increased joint moments may be clinically relevant, or potentially adverse. Nonetheless, these differences should be considered in the recommendation as well as the design of footwear in the future.
- Published
- 2011
15. Standards for Measures Used for Public Reporting of Efficiency in Health Care
- Author
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Sharon-Lise T. Normand, Jeremiah D. Schuur, John E. Brush, Frederick A. Masoudi, Andrew J. Epstein, Mary Norine Walsh, Vincent J. Bufalino, Michael E. Chernew, Sidney C. Smith, Paul A. Heidenreich, David B. Matchar, John S. Rumsfeld, Patricia S. Keenan, Harlan M. Krumholz, John A. Spertus, and Vivian Ho
- Subjects
Gerontology ,medicine.medical_specialty ,Medical education ,business.industry ,Public health ,media_common.quotation_subject ,MEDLINE ,Public health informatics ,Incentive ,Health care ,Medicine ,Quality (business) ,Outcomes research ,business ,Cardiology and Cardiovascular Medicine ,Health policy ,media_common - Abstract
The assessment of medical practice is evolving rapidly in the United States. An initial focus on structure and process performance measures assessing the quality of medical care is now being supplemented with efficiency measures to quantify the "value" of healthcare delivery. This statement, building on prior work that articulated standards for publicly reported outcomes measures, identifies preferred attributes for measures used to assess efficiency in the allocation of healthcare resources. The attributes identified in this document combined with the previously published standards are intended to serve as criteria for assessing the suitability of efficiency measures for public reporting. This statement identifies the following attributes to be considered for publicly reported efficiency measures: integration of the quality and cost; valid cost measurement and analysis; minimal incentive to provide poor quality care; and proper attribution of the measure. The attributes described in this statement are relevant to a wide range of efforts to profile the efficiency of various healthcare providers, including hospitals, healthcare systems, managed-care organizations, physicians, group practices, and others that deliver coordinated care.
- Published
- 2008
- Full Text
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16. Measuring interoceptive awareness in external eaters: a test of Schachter's ‘externality’ theory
- Author
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Peter J. Rogers, Gregory S. Keenan, and Jeffrey M. Brunstrom
- Subjects
Nutrition and Dietetics ,Psychology ,Social psychology ,General Psychology ,Externality ,Cognitive psychology ,Test (assessment) - Published
- 2016
17. Androgen regulation of growth hormone binding protein
- Author
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Gerhard Baumann, Gail E. Richards, Moisés Mercado, Gary D. Eakman, John S. Dallas, and Bruce S. Keenan
- Subjects
Male ,Delayed puberty ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biology ,Short stature ,Endocrinology ,Growth hormone-binding protein ,Internal medicine ,medicine ,Humans ,Testosterone ,Insulin-Like Growth Factor I ,Child ,Puberty, Delayed ,Growth factor ,Dihydrotestosterone ,Androgen ,Androgens ,medicine.symptom ,Carrier Proteins ,medicine.drug ,Hormone - Abstract
Male puberty is associated with elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I), as well as accelerated linear growth. These effects can be reproduced by administration of testosterone (T). To further elucidate the mechanisms underlying pubertal growth, we treated 14 boys with delayed puberty and short stature with either T (n = 7) or 5alpha-dihydrotestosterone (DHT) (n = 7) and compared the effect on plasma concentrations of GH, IGF-I, and GH binding protein (GHBP). Before treatment and after either three or four doses of T enanthate or DHT heptanoate, mean 12-hour GH concentration (8 AM to 8 PM) and plasma IGF-I, T, DHT, and GHBP levels were measured, and height velocity (HV) was measured over this interval. T treatment resulted in an increase of mean GH from 3.3 to 12.0 microg/L (P < .005) and of IGF-I from 22.3 to 45.4 nmol/L (P < .01). During treatment, HV was 11.0 +/- 1.1 cm/yr, consistent with normal pubertal growth, and plasma T was 22.5 +/- 5.3 nmol/L. GHBP decreased in this group from 937 to 521 pmol/L (P < .025). DHT treatment resulted in a small decrease of mean GH from 4.3 to 2.9 microg/L (P < .025) and of IGF-I from 29.4 to 27.2 nmol/L (nonsignificant [NS]). During treatment, HV was 9.3 +/- 1.1, not significantly different from the HV obtained with T treatment, and plasma DHT was 24.2 nmol/L at 1 week and 29.2 at 2 weeks postinjection. Likewise, there was a decrease in GHBP from 928 to 698 pmol/L (P < .025). The decline in GHBP with T treatment was apparently due to an androgen receptor-dependent mechanism, since the same effect was seen during treatment with the nonaromatizable androgen, DHT. This effect is opposite to the normal chronological trend upward for GHBP, which occurs from infancy into midpuberty. Factors determining the upward trend are not known, but are evidently independent of the plasma concentration of sex hormones and GH. The increase in IGF-I in response to T treatment despite a moderate decline in GHBP (and possibly GH receptor) levels is most likely due to the large increase in GH, which may override a modest decrease in GHBP/GH receptor.
- Published
- 1996
18. Contamination of nearshore subtidal sediments of Saudi Arabia from the Gulf War oil spill
- Author
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Theodor C. Sauer, Jacqueline Michel, Richard S. Keenan, Sunil Narumalani, Miles O. Hayes, and John R. Jensen
- Subjects
Oceanography ,Habitat ,Range (biology) ,Sediment ,Intertidal zone ,Sediment trap (geology) ,Satellite imagery ,Aquatic Science ,Contamination ,Pollution ,Soil contamination ,Geology - Abstract
Detailed sedimentological and dynamic-process studies of the shallow, subtidal habitats along on the Saudi Arabian coast were carried out 1 year after the Gulf War oil spill, as part of the NOAA ship Mt Mitchell cruise. Satellite imagery and space shuttle photography were used to characterize the subtidal habitats and select sampling sites. A total of 197 bottom-observation dives were carried out, and 170 bottom sediment and sediment trap samples were collected for chemical analysis. The results show no evidence of large-scale sinking of oil from the spill. Detailed chemical results showed that surficial subtidal sediments (0–5 cm) have been contaminated at levels ranging from
- Published
- 1993
19. High-density lipoprotein response to 5-α-dihydrotestosterone and testosterone in Macaca fascicularis: A hormone-responsive primate model for the study of atherosclerosis
- Author
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Jeffrey L. Probstfield, William Insull, Bruce S. Keenan, and Nancy G. Greger
- Subjects
Male ,medicine.medical_specialty ,Arteriosclerosis ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,chemistry.chemical_compound ,5 Alpha-Reductase Inhibitor ,5-alpha Reductase Inhibitors ,Endocrinology ,High-density lipoprotein ,Internal medicine ,biology.animal ,medicine ,Animals ,Testosterone ,Primate ,Orchiectomy ,biology ,Cholesterol, HDL ,Dihydrotestosterone ,Androgen ,Disease Models, Animal ,Macaca fascicularis ,Castration ,chemistry ,Azasteroids ,Lipoproteins, HDL ,Androstanes ,medicine.drug - Abstract
A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-alpha-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 +/- 1.8 mg/dL SE to 66.6 +/- 2.2, P less than .005; monkey B, 62.9 +/- 1.6 to 80.2 +/- 1.7, P less than .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 +/- 5.0, P less than .01; monkey B, 43.5 +/- 0.5, P less than .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 +/- 1.5, P less than .005; monkey B, 44.5 +/- 3.5, P less than .001). T and the 5-alpha-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 +/- 1.9, NS; monkey B, 57.3 +/- 0.3, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
20. The effect of surprise on flavour-nutrient learning
- Author
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Rory Cutler, Greg S Keenan, Vanessa M B Herbert, Jeffrey M. Brunstrom, Danielle Ferriday, and Xavier Allirot
- Subjects
Meal ,Nutrition and Dietetics ,media_common.quotation_subject ,digestive, oral, and skin physiology ,Flavour ,Affect (psychology) ,Expected satiety ,Developmental psychology ,Associative learning ,Surprise ,Energy density ,Upward shift ,Psychology ,Social psychology ,General Psychology ,media_common - Abstract
Through exposure, flavours can come to predict energy composition and signal whether a food is likely to be filling and/or pleasant. While this ‘flavour-nutrient learning’ appears to be relatively robust in animals, research in humans has delivered mixed results. In this study we consider whether ‘being surprised’ by a food promotes human flavour-nutrient learning. In an initial session, participants (N = 92) provided a measure of the expected satiation of a novel high or low energy-dense breakfast (matched for sensory characteristics). Participants then consumed the meal and hunger and fullness was recorded over three hours. A measure of surprise was derived from the mismatch between expected satiation and actual satiety. One week later, participants completed each measure once again. Energy density did not affect changes in expected satiation. However, clear effects of surprise were evident – those who found the foods to be more filling than anticipated showed an upward shift in expected satiety (week 2 compared with baseline). They also selected smaller ‘ideal’ portion sizes. The reverse was the case in participants who were less full than expected. Albeit less clear, we also found evidence that surprise affected a measure of food reward. Being less full than initially expected was associated with decreased reward. These findings are interpreted as broadly consistent with predictions based on the Rescorla–Wagner model of associative learning.
- Published
- 2013
21. Microalbuminuria could improve risk prediction of stroke in patients with transient ischaemic attacks and minor strokes
- Author
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Angela C. Shore, S Keenan, H Eastwood, J Stewart, William David Strain, and Salim Elyas
- Subjects
education.field_of_study ,medicine.medical_specialty ,Framingham Risk Score ,business.industry ,Proportional hazards model ,Population ,General Medicine ,Transient ischaemic attacks ,medicine.disease ,Surgery ,Blood pressure ,Internal medicine ,Medicine ,Microalbuminuria ,cardiovascular diseases ,Risk factor ,business ,education ,Stroke - Abstract
Background Transient ischaemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes; they precede 23% of strokes within 90 days. Identification of patients at high risk of developing further strokes is essential to allow early intervention and avoid the catastrophic outcome of strokes. Elevated urinary albumin excretion rate (AER) is a risk factor and predicts cardiovascular disease, stroke, and mortality. Elevated AER can be detected with a point-of-care bedside test. Methods Patient demographics and the ABCD2 score were obtained for 150 consecutive patients with TIA who presented to the daily stroke clinic and the stroke unit. The ABCD2 score composite for age, blood pressure, clinical features, duration, and diabetes is the risk score presently used for stratifying patients with TIA. All patients had their albumin:creatinine ratio (ACR) measured from a urine sample obtained during their visit to the clinic or the stroke unit at Royal Devon & Exeter Hospital. Patients were followed up for any events, cardiovascular events, stroke, or death at day 7, 30, and 90. Findings Nine patients had recurrent strokes or TIAs by day 7 and 13 by day 9. Patients who had a recurrent stroke or TIA at day 7 and day 90 had a significantly higher ACR than those who did not have an event (4·00 mg/mmol [95% CI 1·89–8·40] vs 1·89 [95% CI 1·58–2·25]; p=0·03 and 3·73 [95% CI 2·12–6·56] vs 1·85 [95% CI 1·55–2·22]; p=0·02, respectively). After adjustment for sex and ABCD2 score, the 90-day predictive role of ACR persisted for those with versus those without subsequent events (adjusted ACR 3·48 mg/mmol [95% CI 1·96–6·19] vs 1·87 [95% CI 1·56–2·24], p=0·04). Stratification of the population at an ACR of 3.0 mg/mmol identified 39 patients at higher risk. Cox proportional hazards of progressing to stroke by day 90 if ACR was more than 3·0 mg/mmol was 3·2 (95% CI 1·07–9·45, p Interpretation Increased urinary albumin excretion, as detected by urinary ACR, is significantly elevated in patients who present with TIA or minor strokes and go on to have further strokes. The use of clinic urinary ACR test could improve the risk prediction of currently available stroke risk scores such as the ABCD2 score. Funding National Institute for Health Research and Stroke Research Network.
- Published
- 2013
22. Exploring flavour–nutrient learning using a novel paired-discrimination task
- Author
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Gregory S. Keenan, R. Cutler, Jeffrey M. Brunstrom, and X. Allirot
- Subjects
Meal ,Nutrition and Dietetics ,Test food ,digestive, oral, and skin physiology ,Flavour ,Novel food ,Task (project management) ,Test (assessment) ,Statistics ,Energy density ,Session (computer science) ,Psychology ,Social psychology ,General Psychology - Abstract
Flavours can acquire the capacity to signal nutrient composition and to influence meal size. In humans, attempts to demonstrate this ‘flavour–nutrient learning’ have achieved mixed results. The present studies were designed to explore whether humans have the capacity to discriminate between high (study 1: 113 kcal/100 g; study 2: 98 kcal/100 g) and low energy-dense (study 1: 66 kcal/100 g; study 2: 57.4 kcal/100 g) versions of a novel test food. Two studies were conducted. In each study, participants attended the laboratory on consecutive days. In each session, they consumed a version of the novel food and abstained from eating for 3 h afterwards. In Study 1, purple and orange versions of the test foods were formulated (the pairing between colour and energy density was counterbalanced across participants). In Study 2, both versions of the test food were pink. Importantly, the high and low energy-dense test foods were matched for their sensory characteristics and their portion sizes (g). Allocation of the test foods was counterbalanced across the first and second session. Three hours after the second session, participants returned to the laboratory and were required to identify the order in which they consumed each version. Chi-squared analysis revealed that the number of correct discriminations was not significantly different from the number of incorrect discriminations in both studies (p = 0.763). We attribute this to a general inability to encode and compare appetite across test days.
- Published
- 2012
23. Poster 141: Osteosarcoma of the Mid Femur Presenting as Lumbago in a Young Adult Recovering From Hallux Surgery: A Case Report
- Author
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Geoffrey S. Keenan
- Subjects
medicine.medical_specialty ,Rehabilitation ,business.industry ,medicine.medical_treatment ,Physical Therapy, Sports Therapy and Rehabilitation ,medicine.disease ,Surgery ,Back pain ,Medicine ,Osteosarcoma ,Femur ,medicine.symptom ,Young adult ,business - Published
- 2008
24. Pseudovaginal Perineoscrotal Hypospadias: Genetic Heterogeneity
- Author
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Bruce S. Keenan
- Subjects
Pseudovaginal perineoscrotal hypospadias ,Genetic heterogeneity ,business.industry ,Urology ,Androgenic steroids ,Ambiguous external genitalia ,medicine ,Biochemical diagnosis ,urologic and male genital diseases ,Bioinformatics ,medicine.disease ,business - Abstract
Defects in either the production or the action of androgenic steroids have been demonstrated to cause pseudovaginal perineoscrotal hypospadias, a syndrome of male hermaphoditism. The ability to make a rapid, specific biochemical diagnosis in an infant with this syndrome, and thus to predict the infant's response to androgens, could be a valuable aid in the assignment of sex to an infant with ambiguous external genitalia.
- Published
- 1980
25. Diurnal and longitudinal variations in human milk sodium and potassium: implication for nutrition and physiology
- Author
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Susan W. Buzek, Elaine Potts, Bruce S. Keenan, Buford L. Nichols, and Cutberto Garza
- Subjects
Adult ,medicine.medical_specialty ,Time Factors ,Adolescent ,Sodium ,Potassium ,Medicine (miscellaneous) ,chemistry.chemical_element ,Urine ,Excretion ,chemistry.chemical_compound ,Pregnancy ,Internal medicine ,medicine ,Humans ,Lactation ,Longitudinal Studies ,Circadian rhythm ,Aldosterone ,Nutrition and Dietetics ,Milk, Human ,Postpartum Period ,Diurnal temperature variation ,Circadian Rhythm ,Diet ,Endocrinology ,chemistry ,Female ,Postpartum period - Abstract
Human milk sodium ([Nal]) and potassium ([K)] concentrations were measured every 4 h for 24 h in 28 subjects 3.5 to 32 wk postpartum. A diurnal variation in milk Na was seen, which was reciprocal to K. Significant negative correlations between Na and K were seen in these periods: 3.5 to 6; 8 to 18, 20 to 32 wk postpartum (p less than 0.01 for each). The mean 24 h milk sodium concentrations (x(Na)) decreased between 3.5 and 18 wk postpartum (p less than 0.005 by paired t test). Changes in mean potassium (-XK) were not statistically significant. Diet apparently does not affect milk Na. Administration of a low Na diet: 10.8 +/- .9 (SD) mEq Na/day and 60 to 100 mEq K/day for 2 days did not change x(Na). But urinary Na decreased 7-fold as aldosterone increased 5-fold. No significant correlation was seen between 24 h Na excretion in urine and x(Na) in milk (n = 51). A significant positive correlation was seen between urinary K and -XK in milk (r = 0.36), p less than 0.001).
- Published
- 1982
26. Androgen receptor in human skin fibroblasts characterization of a specific 17β-hydroxy-5α-androstan-3-one-protein complex in cell sonicates and nuclei
- Author
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Bruce S. Keenan, Claude J. Migeon, Arthur J. Hadjian, and Walter J. Meyer
- Subjects
Male ,Clinical Biochemistry ,Receptors, Cell Surface ,Human skin ,Binding, Competitive ,Biochemistry ,Endocrinology ,Drug Stability ,medicine ,Humans ,Testosterone ,Binding site ,Receptor ,Molecular Biology ,Cells, Cultured ,Skin ,Cell Nucleus ,Pharmacology ,Testicular feminization ,Binding Sites ,Chemistry ,Androgen binding ,Organic Chemistry ,Temperature ,Proteins ,Dihydrotestosterone ,Fibroblasts ,Androgen receptor ,Kinetics ,Cell culture ,Chromatography, Gel ,Protein Binding ,Subcellular Fractions ,medicine.drug - Abstract
Cultured human skin fibroblasts were shown to contain an androgen binding activity (receptor) which was heat-labile and destroyed by trypsin. Specific binding was seen after incubations of these cells with 1,2-3-H-testosterone, 1,2-3-H17beta-hydroxy-5alpha-androstan-3-one (dihydrotestosterone, DHT) and 1,2-3-H-5alpha-androstane-3alpha, 17beta-diol. This receptor had a high affinity (Kd=0,2-1.6 nM) and a high degree of specificity for DHT. It was measured as a 3-H-DHT-protein complex by gel filtration chromatography using a method which distinguishes specific from nonspecific binding. Receptor activity was distributed about equally between nuclear and extranuclear components at all times studied and was present in both compartments when cell incubations were carried out at 4 degrees and 37 degrees. Saturation analysis indicated that there were 1250-18,600 binding sites per whole cell. By sucrose gradient centrifugation the receptor had a sedimentation coefficient (S20,w) of about 4. Cells grown for 8 days without serum in the medium maintained the same levels of 3-H-DHT binding. Within 15 hours puromycin (20 mug/ml) in serum-free medium caused a 40-60 percent decrease in binding for the same cell lines. Although the highest levels of 3-H-DHT binding were observed in fibroblasts from newborn foreskin, appreciable cytosol and nuclear binding were seen in cells from forearm, neck and abdominal skin. Receptor activity was stable during prolonged culture. Fibroblasts from several skin sites from patients with the androgen insensitivity syndrome (testicular feminization) had no detectable specific DHT binding. In this study it was demonstrated that skin fibroblasts can rapidly convert testosterone to its active form, DHT, bind DHT to a specific receptor protein and transport this complex to their nuclei. Therefore this may prove to be a convenient system for studying androgen action in vitro.
- Published
- 1975
27. The effect of diet upon carbohydrate metabolism, insulin resistance, and blood pressure in congenital total lipoatrophic diabetes
- Author
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Alan J. Garber, John H. Holcombe, Arthur H. Rubenstein, Bruce S. Keenan, V.Elaine Potts, George W. Clayton, and Rebecca T. Kirkland
- Subjects
Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blood Pressure ,Carbohydrate metabolism ,Glucagon ,Plasma renin activity ,Endocrinology ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Renin ,medicine ,Humans ,Insulin ,Child ,Triglycerides ,Diabetes Mellitus, Lipoatrophic ,biology ,Sodium ,medicine.disease ,Insulin receptor ,Basal (medicine) ,biology.protein ,Carbohydrate Metabolism ,Female ,Insulin Resistance ,Energy Intake - Abstract
An 11-yr-old female with congenital total lipodystrophy had nonketotic hyperglycemia with resistance to both endogenous and exogenous insulin and systemic hypertension. Twenty-four hour patterns of secretion and mean concentrations of growth hormone, cortisol, Luteinizing Hormone (LH), and Follicle-Stimulating Hormone (FSH) were normal. Plasma glucagon was elevated during periods of hyperglycemia, but was normal during normoglycemia, even though insulin resistance was still evident. Insulin receptor density and affinity for insulin as determined in monocytes and erythrocytes were normal during hyperglycemia. Therapy with insulin and pimozide were not effective in controlling hyperglycemia. However, a diet restricted to 1800–2000 cal per day of average sodium content resulted in euglycemia and normal blood pressure without insulin therapy. Fasting serum glucose decreased from 393 to 65 mg/dl. In addition, triglycerides decreased from 304 to 115 mg/dl, glucagon from 421 to 126 pg/ml, and liver size returned to normal. There was a correlation between blood pressure and fasting glucose: systolic, r = 0.725, n = 54, p < 0.001; diastolic, r = 0.424, n = 54, p < 0.001. Plasma renin activity (PRA) and plasma aldosterone (PA) levels were mildly elevated in both the hypertensive and normotensive states. Plasma renin activity was 2.15 ± 0.73, (SD) ng/ml/hr supine and 5.32 ± 1.81 upright over an 11-day period when urinary sodium excretion was 96.0 ± 25.5 meq/day. When fasting glucose levels were 332–393 mg/dl, glucose turnover was 1967 μmole/min (normal, 696 ± 120, SD), net glucose decay during i.v. glucose tolerance (IVGTT) 15.6 g/50 min/1.73m2 (normal, 16.7 ± 3.7), and Kg was 0.52%/min (normal, 1.86 ± 0.51, SD). After intensive diet therapy, fasting glucose was 97 and glucose turnover was 810 μmole/min, net glucose decay was 15.18 and Kg was 0.92. When the subject was hyperglycemic, plasma alanine concentration was normal, as was alanine conversion to glucose. Basal unbound insulin levels were elevated during hyperglycemia and normal during euglycemia. Insulin release, which was negligible during the first IVGTT, had a more normal pattern during the second test. In this patient with lipoatrophy, insulin resistance did not appear to derive from known insulin antagonists. The data suggested that insulin resistance may derive from a reversible loss of coupling of a normal insulin receptor to metabolic pathways. This loss may be tissue specific, involving adipose tissue and liver but not muscle, and appears to occur at insulin levels that are increased but lower than would otherwise cause a loss of hormone responsiveness in normal and obese individuals. An unknown antagonist, if present, must be diet-dependent.
- Published
- 1980
28. Production of antisera against contraceptive steroids
- Author
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W.R. Slaunwhite, S. Keenan, and N. Kundu
- Subjects
medicine.medical_specialty ,Clinical Biochemistry ,Dose-Response Relationship, Immunologic ,Booster dose ,Cross Reactions ,Biochemistry ,Endocrinology ,Estradiol Congeners ,Internal medicine ,Norgestrel ,medicine ,Animals ,Bovine serum albumin ,Molecular Biology ,Pharmacology ,Antiserum ,Progesterone Congeners ,biology ,Chemistry ,Organic Chemistry ,Antibody titer ,Contraceptives, Oral, Synthetic ,Mestranol ,Antibody production ,Antibody Formation ,biology.protein ,Rabbits ,Antibody ,Haptens ,Contraceptives, Oral ,medicine.drug - Abstract
A four step synthesis of 6-(0-carboxymethyl) oximinoethynylestradiol is reported. This compound, 6-(0-carboxymethyl) oximinomestranol, the 3-(0-carboxymethyl) oximes of norethindrone and norgestrel and the 3-hemisuccinate of ethynylestradiol were synthesized and conjugated with bovine serum albumin. Rabbits were immunized at 3 dose levels of haptene (20, 66 and 200 nmoles) and eight weeks later with a booster containing 66 nmoles of haptene. The antibody titer and association constant of responding rabbits was nearly independent of dose although most antibody production occurred after the booster injection. Antibodies to mestranol crossreacted more than 100 percent with ethynylestradiol and to a small extent with norethindrone and norgestrel.The methods of synthesis of the 6-(0-carboxymethyl) oxime derivative of 6-oxoethynylestradiol-17beta, the 3-succinyl derivative of ethiny estradiol-17beta and the 3-carboxymethyl oxime derivative of norethindrone and norgestrel as well as the synthesis of the corresponding bovine serum albumin (BSA) conjugates required for the specific antisera for mestranol, ethinyl estradiol, norethindrone, and norgestrel in rabbits are described. The synthesis of 6-(0-carboxymethyl) oxime derivative involves a 4-step synthesis and a chromatographic purification which is an improvement over past methods. Conjugation to BSA was by the carbodiimide method. Response of immunization was measured in terms of titer, association constant, and cross-reactivity as a function of time after immunization with 3 dose levels of each antigen. Titer response was independent of dose for the original injection. Ethiny estradiol-3-conjugates had very low titers.
- Published
- 1977
29. The Stoichiometry and Kinetics of the Inducible Cysteine Desulfhydrase from Salmonella typhimurium
- Author
-
Bruce S. Keenan, Nicholas M. Kredich, and Linda J. Foote
- Subjects
chemistry.chemical_classification ,Sulfide ,Thiazolidine ,Kinetics ,Substrate (chemistry) ,Cooperative binding ,Cell Biology ,Biochemistry ,chemistry.chemical_compound ,Enzyme ,chemistry ,Molecular Biology ,Stoichiometry ,Cysteine - Abstract
Studies using highly purified cysteine desulfhydrase from Salmonella typhimurium reveal that only a small fraction of the cysteine utilized by the enzyme appears as pyruvate. The isolation of 2-methyl-2, 4-thiazolidinedicarboxylic acid from reaction mixtures offers an explanation for this unusual stoichiometry. The relative amounts of pyruvate and thiazolidine produced during a reaction depend upon the cysteine concentration, pH, and the presence of a protein termed Fraction B, which prevents the formation of the thiazolidine. We propose that 2-aminoacrylate may be an intermediate in the formation of 2-methyl-2, 4-thiazolidinedicarboxylic acid. Substrate velocity curves for cysteine desulfhydrase reveal positive cooperativity with an n value of 1.9 and a Km, for l-cysteine of 0.17 to 0.21 mm. The product, sulfide, inhibits the reaction with a Ki of 0.010 mm. Sulfide inhibition is of the linear competitive type at high cysteine concentrations, but it becomes nonlinear and more pronounced at low cysteine concentrations.
- Published
- 1973
30. The Purification and Subunit Structure of Cysteine Desulfhydrase from Salmonella typhimurium
- Author
-
Bruce S. Keenan, Nicholas M. Kredich, and Linda J. Foote
- Subjects
chemistry.chemical_classification ,Chemistry ,Protein subunit ,Tryptophanase activity ,Tryptophan ,Cell Biology ,Random hexamer ,Biochemistry ,Amino acid ,chemistry.chemical_compound ,Enzyme ,Pyridoxal phosphate ,Sodium dodecyl sulfate ,Molecular Biology - Abstract
The inducible enzyme, cysteine desulfhydrase, was purified from Salmonella typhimurium to a state of near homogeneity. This enzyme has a very low tryptophanase activity, lacks cystathionase and tryptophan synthetase activities, and appears to be a specific cysteine desulfhydrase. The purified native enzyme has an s20,w of 10.4 and a molecular weight of 229,000 as determined by equilibrium sedimentation. Polyacrylamide electrophoresis in sodium dodecyl sulfate showed a single species of polypeptide chain with a molecular weight of 37,000 while the pyridoxal phosphate content was found to be 1 mole per 37,700 g of protein. These data, together with the results of amino acid analyses, tryptic peptide maps, and an NH2-terminal amino acid analysis, indicate that the native enzyme is a hexamer, containing 6 moles of pyridoxal phosphate, and composed of six identical polypeptide chains with NH2-terminal serines.
- Published
- 1972
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