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1. Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC

Author

Lenherr, Sara M, Clemens, J Quentin, Braffett, Barbara H, Cleary, Patricia A, Dunn, Rodney L, Hotaling, James M, Jacobson, Alan M, Kim, Catherine, Herman, William, Brown, Jeanette S, Wessells, Hunter, Sarma, Aruna V, Nathan, DM, Zinman, B, Crofford, O, Genuth, S, Brown-Friday, J, Crandall, J, Engel, H, Engel, S, Martinez, H, Phillips, M, Reid, M, Shamoon, H, Sheindlin, J, Gubitosi-Klug, R, Mayer, L, Pendegast, S, Zegarra, H, Miller, D, Singerman, L, Smith-Brewer, S, Novak, M, Quin, J, Genuth, Saul, Palmert, M, Brown, E, McConnell, J, Pugsley, P, Crawford, P, Dahms, W, Brillon, D, Lackaye, ME, Kiss, S, Chan, R, Orlin, A, Rubin, M, Reppucci, V, Lee, T, Heinemann, M, Chang, S, Levy, B, Jovanovic, L, Richardson, M, Bosco, B, Dwoskin, A, Hanna, R, Barron, S, Campbell, R, Bhan, A, Kruger, D, Jones, JK, Edwards, PA, Carey, JD, Angus, E, Thomas, A, Galprin, A, McLellan, M, Whitehouse, F, Bergenstal, R, Johnson, M, Gunyou, K, Thomas, L, Laechelt, J, Hollander, P, Spencer, M, Kendall, D, Cuddihy, R, Callahan, P, List, S, Gott, J, Rude, N, Olson, B, Franz, M, Castle, G, Birk, R, Nelson, J, Freking, D, Gill, L, Mestrezat, W, Etzwiler, D, Morgan, K, Aiello, LP, Golden, E, Arrigg, P, Asuquo, V, Beaser, R, Bestourous, L, and Cavallerano, J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Clinical Research, Urologic Diseases, Diabetes, Prevention, Reproductive health and childbirth, Renal and urogenital, Infection, Metabolic and endocrine, Adolescent, Adult, Blood Glucose, Body Mass Index, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Risk Factors, Surveys and Questionnaires, Urinary Incontinence, Urinary Tract Infections, Young Adult, DCCT/EDIC Research Group, diabetes mellitus, risk factors, urinary tract infections, Clinical Sciences, Urology & Nephrology, Clinical sciences
Abstract

PurposeWe examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus.Materials and methodsWomen enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model.ResultsA total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy.ConclusionsThe frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

Published
2016

2. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

Author

Chen, Zhuo, Miao, Feng, Paterson, Andrew D, Lachin, John M, Zhang, Lingxiao, Schones, Dustin E, Wu, Xiwei, Wang, Jinhui, Tompkins, Joshua D, Genuth, Saul, Braffett, Barbara H, Riggs, Arthur D, Natarajan, Rama, Nathan, DM, Zinman, B, Crofford, O, Genuth, S, Brown-Friday, J, Crandall, J, Engel, H, Engel, S, Martinez, H, Phillips, M, Reid, M, Shamoon, H, Sheindlin, J, Gubitosi-Klug, R, Mayer, L, Pendegast, S, Zegarra, H, Miller, D, Singerman, L, Smith-Brewer, S, Novak, M, Quin, J, Palmert, M, Brown, E, McConnell, J, Pugsley, P, Crawford, P, Dahms, W, Brillon, D, Lackaye, ME, Kiss, S, Chan, R, Orlin, A, Rubin, M, Reppucci, V, Lee, T, Heinemann, M, Chang, S, Levy, B, Jovanovic, L, Richardson, M, Bosco, B, Dwoskin, A, Hanna, R, Barron, S, Campbell, R, Bhan, A, Kruger, D, Jones, JK, Edwards, PA, Carey, JD, Angus, E, Thomas, A, Galprin, A, McLellan, M, Whitehouse, F, Bergenstal, R, Johnson, M, Gunyou, K, Thomas, L, Laechelt, J, Hollander, P, Spencer, M, Kendall, D, Cuddihy, R, Callahan, P, List, S, Gott, J, Rude, N, Olson, B, Franz, M, Castle, G, Birk, R, Nelson, J, Freking, D, Gill, L, Mestrezat, W, Etzwiler, D, Morgan, K, Aiello, LP, Golden, E, Arrigg, P, Asuquo, V, Beaser, R, and Bestourous, L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Diabetes, Human Genome, Nutrition, Autoimmune Disease, Prevention, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adolescent, Adult, Carrier Proteins, Cell Line, Tumor, Cohort Studies, DNA Methylation, Diabetes Mellitus, Type 1, Epigenomics, Female, Genetic Loci, Glycated Hemoglobin, Humans, Male, DCCT/EDIC Research Group, DNA methylation, TXNIP, diabetic complications, epigenetics, metabolic memory
Abstract

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.

Published
2016

3. A Qualitative Inquiry of Associations Between Family Environment and Suicidality for Transgender Youth Experiencing Homelessness.

Author

Morrow, Quin J. and McGuire, Jenifer K.

Subjects
*TRANSGENDER youth, *HOMELESSNESS, *HOME environment, *YOUNG adults, *SUICIDAL ideation, *ATTEMPTED suicide, *HOUSING stability
Abstract

Correlational research finds that transgender youth who have been homeless are more likely to have attempted suicide; however, there is not yet research explaining why this correlation might exist. To understand connections between housing insecurity and suicidality for transgender people the present study analyzed in-depth interviews with 30 transgender young people (ages 15–25) in the United States who had experienced homelessness. Interviews took place in LGBTQ community centers, and were analyzed for inductive themes using Qualitative Content Analysis. In contrast with theories suggesting that homelessness predicts increased suicidality because of the stressors of homelessness, this study found that gender-based parental rejection and other dysfunctional family dynamics interacted to create a hostile environment that contributed to both suicidality and homelessness for trans participants. In fact, suicide attempts occurred most often while participants still lived in disaffirming homes and usually ceased after participants left the unsafe home, suggesting that leaving a disaffirming family home, even if it results in homelessness, may decrease suicidality for some youth. Findings suggest that service providers working with transgender youth experiencing homelessness must consider familial gender disaffirmation, other familial stressors, and lack of access to shelter as equal threats to trans youth's wellbeing and design interventions accordingly. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC

Author

Nathan, D.M., Zinman, B., Crofford, O., Genuth, S., Brown-Friday, J., Crandall, J., Engel, H., Engel, S., Martinez, H., Phillips, M., Reid, M., Shamoon, H., Sheindlin, J., Gubitosi-Klug, R., Mayer, L., Pendegast, S., Zegarra, H., Miller, D., Singerman, L., Smith-Brewer, S., Novak, M., Quin, J., Genuth, Saul, Palmert, M., Brown, E., McConnell, J., Pugsley, P., Crawford, P., Dahms, W., Brillon, D., Lackaye, M.E., Kiss, S., Chan, R., Orlin, A., Rubin, M., Reppucci, V., Lee, T., Heinemann, M., Chang, S., Levy, B., Jovanovic, L., Richardson, M., Bosco, B., Dwoskin, A., Hanna, R., Barron, S., Campbell, R., Bhan, A., Kruger, D., Jones, J.K., Edwards, P.A., Carey, J.D., Angus, E., Thomas, A., Galprin, A., McLellan, M., Whitehouse, F., Bergenstal, R., Johnson, M., Gunyou, K., Thomas, L., Laechelt, J., Hollander, P., Spencer, M., Kendall, D., Cuddihy, R., Callahan, P., List, S., Gott, J., Rude, N., Olson, B., Franz, M., Castle, G., Birk, R., Nelson, J., Freking, D., Gill, L., Mestrezat, W., Etzwiler, D., Morgan, K., Aiello, L.P., Golden, E., Arrigg, P., Asuquo, V., Beaser, R., Bestourous, L., Cavallerano, J., Cavicchi, R., Ganda, O., Hamdy, O., Kirby, R., Murtha, T., Schlossman, D., Shah, S., Sharuk, G., Silva, P., Silver, P., Stockman, M., Sun, J., Weimann, E., Wolpert, H., Aiello, L.M., Jacobson, A., Rand, L., Rosenzwieg, J., Larkin, M.E., Christofi, M., Folino, K., Godine, J., Lou, P., Stevens, C., Anderson, E., Bode, H., Brink, S., Cornish, C., Cros, D., Delahanty, L., deManbey, A., Haggan, C., Lynch, J., McKitrick, C., Norman, D., Moore, D., Ong, M., Taylor, C., Zimbler, D., Crowell, S., Fritz, S., Hansen, K., Gauthier-Kelly, C., Service, F.J., Ziegler, G., Colligan, R., Schmidt, L., French, B., Woodwick, R., Rizza, R., Schwenk, W.F., Haymond, M., Pach, J., Mortenson, J., Zimmerman, B., Lucas, A., Luttrell, L., Lopes-Virella, M., Caulder, S., Pittman, C., Patel, N., Lee, K., Nutaitis, M., Fernandes, J., Hermayer, K., Kwon, S., Blevins, A., Parker, J., Colwell, J., Lee, D., Soule, J., Lindsey, P., Bracey, M., Farr, A., Elsing, S., Thompson, T., Selby, J., Lyons, T., Yacoub-Wasef, S., Szpiech, M., Wood, D., Mayfield, R., Molitch, M., Adelman, D., Colson, S., Jampol, L., Lyon, A., Gill, M., Strugula, Z., Kaminski, L., Mirza, R., Simjanoski, E., Ryan, D., Johnson, C., Wallia, A., Ajroud-Driss, S., Astelford, P., Leloudes, N., Degillio, A., Schaefer, B., Mudaliar, S., Lorenzi, G., Goldbaum, M., Jones, K., Prince, M., Swenson, M., Grant, I., Reed, R., Lyon, R., Kolterman, O., Giotta, M., Clark, T., Friedenberg, G., Sivitz, W.I., Vittetoe, B., Kramer, J., Bayless, M., Zeitler, R., Schrott, H., Olson, N., Snetselaar, L., Hoffman, R., MacIndoe, J., Weingeist, T., Fountain, C., Mendley, S., Johnsonbaugh, S., Patronas, M., Carney, M., Salemi, P., Liss, R., Hebdon, M., Counts, D., Donner, T., Gordon, J., Hemady, R., Kowarski, A., Ostrowski, D., Steidl, S., Jones, B., Herman, W.H., Martin, C.L., Pop-Busui, R., Greene, D.A., Stevens, M.J., Burkhart, N., Sandford, T., Floyd, J., Bantle, J., Wimmergren, N., Terry, J., Koozekanani, D., Montezuma, S., Rogness, B., Mech, M., Strand, T., Olson, J., McKenzie, L., Kwong, C., Goetz, F., Warhol, R., Hainsworth, D., Goldstein, D., Hitt, S., Giangiacomo, J., Schade, D.S., Canady, J.L., Burge, M.R., Das, A., Avery, R.B., Ketai, L.H., Chapin, J.E., Schluter, M.L., Rich, J., Johannes, C., Hornbeck, D., Schutta, M., Bourne, P.A., Brucker, A., Braunstein, S., Schwartz, S., Maschak-Carey, B.J., Baker, L., Orchard, T., Cimino, L., Songer, T., Doft, B., Olson, S., Becker, D., Rubinstein, D., Bergren, R.L., Fruit, J., Hyre, R., Palmer, C., Silvers, N., Lobes, L., Rath, P. Paczan, Conrad, P.W., Yalamanchi, S., J.Wesche, Bratkowksi, M., Arslanian, S., Rinkoff, J., Warnicki, J., Curtin, D., Steinberg, D., Vagstad, G., Harris, R., Steranchak, L., Arch, J., Kelly, K., Ostrosaka, P., Guiliani, M., Good, M., Williams, T., Olsen, K., Campbell, A., Shipe, C., Conwit, R., Finegold, D., Zaucha, M., Drash, A., Morrison, A., Malone, J.I., Bernal, M.L., Pavan, P.R., Grove, N., Tanaka, E.A., McMillan, D., Vaccaro-Kish, J., Babbione, L., Solc, H., DeClue, T.J., Dagogo-Jack, S., Wigley, C., Ricks, H., Kitabchi, A., Chaum, E., Murphy, M.B., Moser, S., Meyer, D., Iannacone, A., Yoser, S., Bryer-Ash, M., Schussler, S., Lambeth, H., Raskin, P., Strowig, S., Basco, M., Cercone, S., Barnie, A., Devenyi, R., Mandelcorn, M., Brent, M., Rogers, S., Gordon, A., Bakshi, N., Perkins, B., Tuason, L., Perdikaris, F., Ehrlich, R., Daneman, D., Perlman, K., Ferguson, S., Palmer, J., Fahlstrom, R., de Boer, I.H., Kinyoun, J., Van Ottingham, L., Catton, S., Ginsberg, J., McDonald, C., Harth, J., Driscoll, M., Sheidow, T., Mahon, J., Canny, C., Nicolle, D., Colby, P., Dupre, J., Hramiak, I., Rodger, N.W., Jenner, M., Smith, T., Brown, W., May, M., Hagan, J. Lipps, Agarwal, A., Adkins, T., Lorenz, R., Feman, S., Survant, L., White, N.H., Levandoski, L., Grand, G., Thomas, M., Joseph, D., Blinder, K., Shah, G., Burgess, D., Boniuk, I., Santiago, J., Tamborlane, W., Gatcomb, P., Stoessel, K., Ramos, P., Fong, K., Ossorio, P., Ahern, J., Beck, C., Gaston, P., Trail, R., Lachin, J., Cleary, P., Backlund, J., Bebu, I., Braffett, B., Diminick, L., Gao, X., Hsu, W., Klumpp, K., Larsen, M., McGee, P., Sun, W., Villavicencio, S., Anderson, K., Dews, L., Younes, Naji, Rutledge, B., Chan, K., Rosenberg, D., Petty, B., Determan, A., Kenny, D., Williams, C., Cowie, C., Siebert, C., Steffes, M., Arends, V., Bucksa, J., Nowicki, M., Chavers, B., O’Leary, D., Polak, J., Harrington, A., Funk, L., Crow, R., Gloeb, B., Thomas, S., O’Donnell, C., Soliman, E.Z., Zhang, Z.M., Li, Y., Campbell, C., Keasler, L., Hensley, S., Hu, J., Barr, M., Taylor, T., Prineas, R., Feldman, E.L., Albers, J.W., Low, P., Sommer, C., Nickander, K., Speigelberg, T., Pfiefer, M., Schumer, M., Moran, M., Farquhar, J., Ryan, C., Sandstrom, D., Geckle, M., Cupelli, E., Thoma, F., Burzuk, B., Woodfill, T., Danis, R., Blodi, B., Lawrence, D., Wabers, H., Gangaputra, S., Neill, S., Burger, M., Dingledine, J., Gama, V., Sussman, R., Davis, M., Hubbard, L., Budoff, M., Darabian, S., Rezaeian, P., Wong, N., Fox, M., Oudiz, R., Kim, L., Detrano, R., Cruickshanks, K., Dalton, D., Bainbridge, K., Lima, J., Bluemke, D., Turkbey, E., van der Geest, R.J., Liu, C., Malayeri, A., Jain, A., Miao, C., Chahal, H., Jarboe, R., Monnier, V., Sell, D., Strauch, C., Hazen, S., Pratt, A., Tang, W., Brunzell, J., Purnell, J., Natarajan, R., Miao, F., Zhang, L., Chen, Z., Paterson, A., Boright, A., Bull, S., Sun, L., Scherer, S., Lyons, T.J., Jenkins, A., Klein, R., Virella, G., Jaffa, A., Carter, R., Stoner, J., Garvey, W.T., Lackland, D., Brabham, M., McGee, D., Zheng, D., Mayfield, R.K., Maynard, J., Wessells, H., Sarma, A., Dunn, R., Holt, S., Hotaling, J., Kim, C., Clemens, Q., Brown, J., McVary, K., Lenherr, Sara M., Clemens, J. Quentin, Braffett, Barbara H., Cleary, Patricia A., Dunn, Rodney L., Hotaling, James M., Jacobson, Alan M., Kim, Catherine, Herman, William, Brown, Jeanette S., Wessells, Hunter, and Sarma, Aruna V.

Published
2016
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6. A Qualitative Inquiry of Associations Between Family Environment and Suicidality for Transgender Youth Experiencing Homelessness

Author

Quin J. Morrow and Jenifer K. McGuire

Subjects
Sociology and Political Science, Developmental and Educational Psychology
Abstract

Correlational research finds that transgender youth who have been homeless are more likely to have attempted suicide; however, there is not yet research explaining why this correlation might exist. To understand connections between housing insecurity and suicidality for transgender people the present study analyzed in-depth interviews with 30 transgender young people (ages 15–25) in the United States who had experienced homelessness. Interviews took place in LGBTQ community centers, and were analyzed for inductive themes using Qualitative Content Analysis. In contrast with theories suggesting that homelessness predicts increased suicidality because of the stressors of homelessness, this study found that gender-based parental rejection and other dysfunctional family dynamics interacted to create a hostile environment that contributed to both suicidality and homelessness for trans participants. In fact, suicide attempts occurred most often while participants still lived in disaffirming homes and usually ceased after participants left the unsafe home, suggesting that leaving a disaffirming family home, even if it results in homelessness, may decrease suicidality for some youth. Findings suggest that service providers working with transgender youth experiencing homelessness must consider familial gender disaffirmation, other familial stressors, and lack of access to shelter as equal threats to trans youth’s wellbeing and design interventions accordingly.

Published
2023
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7. Management of eating disorders for people with higher weight: clinical practice guideline

Author

Ralph, AF, Brennan, L, Byrne, S, Caldwell, B, Farmer, J, Hart, LM, Heruc, GA, Maguire, S, Piya, MK, Quin, J, Trobe, SK, Wallis, A, Williams-Tchen, AJ, Hay, P, Ralph, AF, Brennan, L, Byrne, S, Caldwell, B, Farmer, J, Hart, LM, Heruc, GA, Maguire, S, Piya, MK, Quin, J, Trobe, SK, Wallis, A, Williams-Tchen, AJ, and Hay, P

Abstract

INTRODUCTION: The prevalence of eating disorders is high in people with higher weight. However, despite this, eating disorders experienced by people with higher weight have been consistently under-recognised and under-treated, and there is little to guide clinicians in the management of eating disorders in this population. AIM: The aim of this guideline is to synthesise the current best practice approaches to the management of eating disorders in people with higher weight and make evidence-based clinical practice recommendations. METHODS: The National Eating Disorders Collaboration Steering Committee auspiced a Development Group for a Clinical Practice Guideline for the treatment of eating disorders for people with higher weight. The Development Group followed the 'Guidelines for Guidelines' process outlined by the National Health and Medical Research Council and aim to meet their Standards to be: 1. relevant and useful for decision making; 2. transparent; 3. overseen by a guideline development group; 4. identifying and managing conflicts of interest; 5. focused on health and related outcomes; 6. evidence informed; 7. making actionable recommendations; 8. up-to-date; and, 9. accessible. The development group included people with clinical and/or academic expertise and/or lived experience. The guideline has undergone extensive peer review and consultation over an 18-month period involving reviews by key stakeholders, including experts and organisations with clinical academic and/or lived experience. RECOMMENDATIONS: Twenty-one clinical recommendations are made and graded according to the National Health and Medical Research Council evidence levels. Strong recommendations were supported for psychological treatment as a first-line treatment approach adults (with bulimia nervosa or binge-eating disorder), adolescents and children. Clinical considerations such as weight stigma, interprofessional collaborative practice and cultural considerations are also discussed. CONCLU

Published
2022

8. Utrecht Gender Dysphoria Scale - Gender Spectrum (UGDS-GS): Construct validity among transgender, nonbinary, and LGBQ samples

Author

Katherine G. Spencer, Jenifer K. McGuire, Peggy T. Cohen-Kettenis, G. Nic Rider, Jessica N. Fish, Jory M. Catalpa, Dianne Berg, Thomas D. Steensma, and Quin J Morrow

Subjects
Gender dysphoria, Health (social science), Gender identity, Health Policy, Medicine (miscellaneous), Construct validity, Genderqueer, medicine.disease, Spectrum (topology), Article, Gender Studies, Scale (social sciences), Transgender, medicine, Measurement invariance, Psychology, Clinical psychology
Abstract

Background: Researchers combined both versions of the original Utrecht Gender Dysphoria Scale (UGDS) to create a single gender spectrum version (UGDS-GS) which measures dissatisfaction with gender identity and expression over time as well as comfort with affirmed gender identity. Aim: This study examined the construct validity of the newly revised, UGDS-GS. Method: Tests of measurement invariance were conducted in stages to assess measurement invariance of the UGDS-GS across three groups: cisgender, binary transgender, and nonbinary/genderqueer. Results: Findings indicate that the UGDS-GS functions acceptably in all three gender groups (configural and metric invariance). Also, across binary transgender and nonbinary/genderqueer groups, the measure functions very similarly with all four types of invariance. Item level findings highlight the specificity of the measure to distinguish experiences of binary transgender and nonbinary/genderqueer persons differently from cisgender LGBQ individuals. Conclusions: The UGDS-GS demonstrates a large degree of invariance across binary transgender, nonbinary/genderqueer, and cisgender LGBQ subgroups; and therefore, findings indicate this revision to be a substantial improvement. This 18-item self-report, Likert-type scale measure is a) inclusive of all gender identities and expressions (e.g., transfeminine spectrum, transmasculine spectrum, genderqueer, nonbinary, cisgender); b) appropriate for use longitudinally from adolescence to adulthood; and c) administered at any point in the social or medical transition process, if applicable, or in community-based research focused on gender dysphoria that examines cisgender and transgender persons.

Published
2020
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12. Utrecht Gender Dysphoria Scale--Gender Spectrum

Author

McGuire, Jenifer K., primary, Berg, Dianne, additional, Catalpa, Jory M., additional, Morrow, Quin J., additional, Fish, Jessica N., additional, Rider, G. Nic, additional, Steensma, Thomas, additional, Cohen-Kettenis, Peggy T., additional, and Spencer, Katherine, additional

Published
2020
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19. Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

Author

Tang, W.H. Wilson, primary, McGee, Paula, additional, Lachin, John M., additional, Li, Daniel Y., additional, Hoogwerf, Byron, additional, Hazen, Stanley L., additional, Nathan, D.M., additional, Zinman, B., additional, Crofford, O., additional, Genuth, S., additional, Brown‐Friday, J., additional, Crandall, J., additional, Engel, H., additional, Engel, S., additional, Martinez, H., additional, Phillips, M., additional, Reid, M., additional, Shamoon, H., additional, Sheindlin, J., additional, Gubitosi‐Klug, R., additional, Mayer, L., additional, Pendegast, S., additional, Zegarra, H., additional, Miller, D., additional, Singerman, L., additional, Smith‐Brewer, S., additional, Novak, M., additional, Quin, J., additional, Genuth, Saul, additional, Palmert, M., additional, Brown, E., additional, McConnell, J., additional, Pugsley, P., additional, Crawford, P., additional, Dahms, W., additional, Gregory, N.S., additional, Lackaye, M.E., additional, Kiss, S., additional, Chan, R., additional, Orlin, A., additional, Rubin, M., additional, Brillon, D., additional, Reppucci, V., additional, Lee, T., additional, Heinemann, M., additional, Chang, S., additional, Levy, B., additional, Jovanovic, L., additional, Richardson, M., additional, Bosco, B., additional, Dwoskin, A., additional, Hanna, R., additional, Barron, S., additional, Campbell, R., additional, Bhan, A., additional, Kruger, D., additional, Jones, J.K., additional, Edwards, P.A., additional, Carey, J.D., additional, Angus, E., additional, Thomas, A., additional, Galprin, A., additional, McLellan, M., additional, Whitehouse, F., additional, Bergenstal, R., additional, Johnson, M., additional, Gunyou, K., additional, Thomas, L., additional, Laechelt, J., additional, Hollander, P., additional, Spencer, M., additional, Kendall, D., additional, Cuddihy, R., additional, Callahan, P., additional, List, S., additional, Gott, J., additional, Rude, N., additional, Olson, B., additional, Franz, M., additional, Castle, G., additional, Birk, R., additional, Nelson, J., additional, Freking, D., additional, Gill, L., additional, Mestrezat, W., additional, Etzwiler, D., additional, Morgan, K., additional, Aiello, L.P., additional, Golden, E., additional, Arrigg, P., additional, Asuquo, V., additional, Beaser, R., additional, Bestourous, L., additional, Cavallerano, J., additional, Cavicchi, R., additional, Ganda, O., additional, Hamdy, O., additional, Kirby, R., additional, Murtha, T., additional, Schlossman, D, additional, Shah, S., additional, Sharuk, G., additional, Silva, P., additional, Silver, P., additional, Stockman, M., additional, Sun, J., additional, Weimann, E., additional, Wolpert, H., additional, Aiello, L.M., additional, Jacobson, A., additional, Rand, L., additional, Rosenzwieg, J., additional, Larkin, M.E., additional, Christofi, M., additional, Folino, K., additional, Godine, J., additional, Lou, P., additional, Stevens, C., additional, Anderson, E., additional, Bode, H., additional, Brink, S., additional, Cornish, C., additional, Cros, D., additional, Delahanty, L., additional, eManbey, ., additional, Haggan, C., additional, Lynch, J., additional, McKitrick, C., additional, Norman, D., additional, Moore, D., additional, Ong, M., additional, Taylor, C., additional, Zimbler, D., additional, Crowell, S., additional, Fritz, S., additional, Hansen, K., additional, Gauthier‐Kelly, C., additional, Service, F.J., additional, Ziegler, G., additional, Barkmeier, A., additional, Schmidt, L., additional, French, B., additional, Woodwick, R., additional, Rizza, R., additional, Schwenk, W.F., additional, Haymond, M., additional, Pach, J., additional, Mortenson, J., additional, Zimmerman, B., additional, Lucas, A., additional, Colligan, R., additional, Luttrell, L., additional, Lopes‐Virella, M., additional, Caulder, S., additional, Pittman, C., additional, Patel, N., additional, Lee, K., additional, Nutaitis, M., additional, Fernandes, J., additional, Hermayer, K., additional, Kwon, S., additional, Blevins, A, additional, Parker, J., additional, Colwell, J., additional, Lee, D., additional, Soule, J., additional, Lindsey, P., additional, Bracey, M., additional, Farr, A., additional, Elsing, S., additional, Thompson, T., additional, Selby, J., additional, Lyons, T., additional, Yacoub‐Wasef, S., additional, Szpiech, M., additional, Wood, D., additional, Mayfield, R., additional, Molitch, M., additional, Adelman, D., additional, Colson, S., additional, Jampol, L., additional, Lyon, A., additional, Gill, M., additional, Strugula, Z., additional, Kaminski, L., additional, Mirza, R., additional, Simjanoski, E., additional, Ryan, D., additional, Johnson, C., additional, Wallia, A., additional, Ajroud‐Driss, S., additional, Astelford, P., additional, Leloudes, N., additional, Degillio, A., additional, Schaefer, B., additional, Mudaliar, S., additional, Lorenzi, G, additional, Goldbaum, M., additional, Jones, K., additional, Prince, M., additional, Swenson, M., additional, Grant, I., additional, Reed, R., additional, Lyon, R., additional, Kolterman, O., additional, Giotta, M., additional, Clark, T., additional, Friedenberg, G., additional, Sivitz, W.I., additional, Vittetoe, B., additional, Kramer, J., additional, Bayless, M., additional, Zeitler, R., additional, Schrott, H., additional, Olson, N., additional, Snetselaar, L., additional, Hoffman, R., additional, MacIndoe, J., additional, Weingeist, T., additional, Fountain, C., additional, Miller, R., additional, Johnsonbaugh, S., additional, Patronas, M., additional, Carney, M., additional, Mendley, S., additional, Salemi, P., additional, Liss, R., additional, Hebdon, M., additional, Counts, D., additional, Donner, T., additional, Gordon, J., additional, Hemady, R., additional, Kowarski, A., additional, Ostrowski, D., additional, Steidl, S., additional, Jones, B., additional, Herman, W.H., additional, Martin, C.L., additional, Pop‐Busui, R., additional, Greene, D.A., additional, Stevens, M.J., additional, Burkhart, N., additional, Sandford, T., additional, Floyd, J., additional, Bantle, J., additional, Flaherty, N., additional, Terry, J., additional, Koozekanani, D., additional, Montezuma, S., additional, Wimmergren, N., additional, Rogness, B., additional, Mech, M., additional, Strand, T., additional, Olson, J., additional, McKenzie, L., additional, Kwong, C., additional, Goetz, F., additional, Warhol, R., additional, Hainsworth, D., additional, Goldstein, D., additional, Hitt, S., additional, Giangiacomo, J., additional, Schade, D.S, additional, Canady, J.L., additional, Burge, M.R., additional, Das, A., additional, Avery, R.B., additional, Ketai, L.H., additional, Chapin, J.E., additional, Schluter, M.L., additional, Rich, J., additional, Johannes, C., additional, Hornbeck, D., additional, Schutta, M., additional, Bourne, P.A., additional, Brucker, A., additional, Braunstein, S., additional, Schwartz, S., additional, Maschak‐Carey, B.J., additional, Baker, L., additional, Orchard, T., additional, Cimino, L., additional, Songer, T., additional, Doft, B., additional, Olson, S., additional, Becker, D., additional, Rubinstein, D., additional, Bergren, R.L., additional, Fruit, J., additional, Hyre, R., additional, Palmer, C., additional, Silvers, N., additional, Lobes, L., additional, Rath, P. Paczan, additional, Conrad, P.W., additional, Yalamanchi, S., additional, Wesche, J., additional, Bratkowksi, M., additional, Arslanian, S., additional, Rinkoff, J., additional, Warnicki, J., additional, Curtin, D., additional, Steinberg, D., additional, Vagstad, G., additional, Harris, R., additional, Steranchak, L., additional, Arch, J., additional, Kelly, K., additional, Ostrosaka, P., additional, Guiliani, M., additional, Good, M., additional, Williams, T., additional, Olsen, K., additional, Campbell, A., additional, Shipe, C., additional, Conwit, R., additional, Finegold, D., additional, Zaucha, M., additional, Drash, A., additional, Morrison, A., additional, Malone, J.I., additional, Bernal, M.L., additional, Pavan, P.R., additional, Grove, N., additional, Tanaka, E.A., additional, McMillan, D., additional, Vaccaro‐Kish, J., additional, Babbione, L., additional, Solc, H., additional, DeClue, T.J., additional, Dagogo‐Jack, S., additional, Wigley, C., additional, Ricks, H., additional, Kitabchi, A., additional, Chaum, E., additional, Murphy, M.B., additional, Moser, S., additional, Meyer, D., additional, Iannacone, A., additional, Yoser, S., additional, Bryer‐Ash, M., additional, Schussler, S., additional, Lambeth, H., additional, Raskin, P., additional, Strowig, S., additional, Basco, M., additional, Cercone, S., additional, Barnie, A., additional, Devenyi, R., additional, Mandelcorn, M., additional, Brent, M., additional, Rogers, S., additional, Gordon, A., additional, Bakshi, N., additional, Perkins, B., additional, Tuason, L., additional, Perdikaris, F., additional, Ehrlich, R., additional, Daneman, D., additional, Perlman, K., additional, Ferguson, S, additional, Palmer, J., additional, Fahlstrom, R., additional, de Boer, I.H., additional, Kinyoun, J., additional, Van Ottingham, L., additional, Catton, S., additional, Ginsberg, J., additional, McDonald, C., additional, Harth, J., additional, Driscoll, M., additional, Sheidow, T., additional, Mahon, J., additional, Canny, C., additional, Nicolle, D., additional, Colby, P., additional, Dupre, J., additional, Hramiak, I., additional, Rodger, N.W., additional, Jenner, M., additional, Smith, T., additional, Brown, W., additional, May, M., additional, Lipps Hagan, J., additional, Agarwal, A., additional, Adkins, T., additional, Lorenz, R., additional, Feman, S., additional, Survant, L., additional, White, N.H., additional, Levandoski, L., additional, Grand, G., additional, Thomas, M., additional, Joseph, D., additional, Blinder, K., additional, Shah, G., additional, Burgess, D., additional, Boniuk, I., additional, Santiago, J., additional, Tamborlane, W., additional, Gatcomb, P., additional, Stoessel, K., additional, Ramos, P., additional, Fong, K., additional, Ossorio, P., additional, Ahern, J., additional, Meadema‐Mayer, L., additional, Beck, C., additional, Farrell, K., additional, Quin, J, additional, Gaston, P., additional, Trail, R., additional, Lachin, J., additional, Backlund, J., additional, Bebu, I., additional, Braffett, B., additional, Diminick, L., additional, Gao, X., additional, Hsu, W., additional, Klumpp, K., additional, Pan, H., additional, Trapani, V., additional, Cleary, P., additional, McGee, P., additional, Sun, W., additional, Villavicencio, S., additional, Anderson, K., additional, Dews, L., additional, Younes, Naji, additional, Rutledge, B., additional, Chan, K., additional, Rosenberg, D., additional, Petty, B., additional, Determan, A., additional, Kenny, D., additional, Williams, C., additional, Cowie, C., additional, Siebert, C., additional, Steffes, M., additional, Arends, V., additional, Bucksa, J., additional, Nowicki, M., additional, Chavers, B., additional, O'Leary, D., additional, Polak, J., additional, Harrington, A., additional, Funk, L., additional, Crow, R, additional, Gloeb, B., additional, Thomas, S., additional, O'Donnell, C., additional, Soliman, E.Z., additional, Zhang, Z.M., additional, Li, Y., additional, Campbell, C., additional, Keasler, L., additional, Hensley, S., additional, Hu, J., additional, Barr, M., additional, Taylor, T., additional, Prineas, R., additional, Feldman, E.L., additional, Albers, J.W., additional, Low, P., additional, Sommer, C., additional, Nickander, K., additional, Speigelberg, T., additional, Pfiefer, M., additional, Schumer, M., additional, Moran, M., additional, Farquhar, J., additional, Ryan, C., additional, Sandstrom, D., additional, Geckle, M., additional, Cupelli, E., additional, Thoma, F., additional, Burzuk, B., additional, Woodfill, T., additional, Danis, R., additional, Blodi, B., additional, Lawrence, D., additional, Wabers, H., additional, Gangaputra, S., additional, Neill, S., additional, Burger, M., additional, Dingledine, J., additional, Gama, V., additional, Sussman, R., additional, Davis, M., additional, Hubbard, L., additional, Budoff, M., additional, Darabian, S., additional, Rezaeian, P., additional, Wong, N., additional, Fox, M., additional, Oudiz, R., additional, Kim, L, additional, Detrano, R., additional, Cruickshanks, K., additional, Dalton, D., additional, Bainbridge, K., additional, Lima, J., additional, Bluemke, D., additional, Turkbey, E., additional, der Geest, ., additional, Liu, C., additional, Malayeri, A., additional, Jain, A., additional, Miao, C., additional, Chahal, H., additional, Jarboe, R., additional, Monnier, V., additional, Sell, D., additional, Strauch, C., additional, Hazen, S., additional, Pratt, A., additional, Tang, W., additional, Brunzell, J., additional, Purnell, J., additional, Natarajan, R., additional, Miao, F., additional, Zhang, L., additional, Chen, Z., additional, Paterson, A., additional, Boright, A., additional, Bull, S., additional, Sun, L., additional, Scherer, S., additional, Lyons, T.J., additional, Jenkins, A., additional, Klein, R., additional, Virella, G., additional, Jaffa, A., additional, Carter, R., additional, Stoner, J., additional, Garvey, W.T., additional, Lackland, D., additional, Brabham, M., additional, McGee, D., additional, Zheng, D., additional, Mayfield, R.K., additional, Maynard, J., additional, Wessells, H., additional, Sarma, A, additional, Dunn, R., additional, Holt, S., additional, Hotaling, J., additional, Kim, C., additional, Clemens, Q., additional, Brown, J., additional, and McVary, K., additional

Published
2018
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23. Lymphatics

Author

Tsuchiya, M., Asakura, H., Hibi, N., Watanabe, Y., Enomoto, Y., Forkert, P. G., Davidson, J. W., Hobbs, Barry B., Hay, John B., Atkins, J. L., O’Morchoe, C. C. C., Pinter, G. G., Quin, J. W., Shannon, A. D., Courtice, F. C., Ackerman, Norman B., Deysine, Maximo, Mader, Milan, Rosario, Eliseo, Aufses, Arthur H., Jr., Maher, William P., Grayson, John, editor, and Zingg, Walter, editor

Published
1976
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24. Significance of epicardial and intrathoracic adipose tissue volume among type 1 diabetes patients in the DCCT/EDIC: A pilot study

Author

Darabian, S, Backlund, JYC, Cleary, PA, Sheidaee, N, Bebu, I, Lachin, JM, Budoff, MJ, Nathan, DM, Zinman, B, Crofford, O, Genuth, S, Brown-Friday, J, Crandall, J, Engel, H, Engel, S, Martinez, H, Phillips, M, Reid, M, Shamoon, H, Sheindlin, J, Gubitosi-Klug, R, Mayer, L, Pendegast, S, Zegarra, H, Miller, D, Singerman, L, Smith-Brewer, S, Novak, M, Quin, J, Palmert, M, Brown, E, McConnell, J, Pugsley, P, Crawford, P, Dahms, W, Brillon, D, Lackaye, ME, Kiss, S, Chan, R, Orlin, A, Rubin, M, Reppucci, V, Lee, T, Heinemann, M, Chang, S, Levy, B, Jovanovic, L, Richardson, M, Bosco, B, Dwoskin, A, Hanna, R, Barron, S, Campbell, R, Bhan, A, Kruger, D, Jones, JK, Edwards, PA, Carey, JD, Angus, E, Thomas, A, Galprin, A, McLellan, M, Whitehouse, F, Bergenstal, R, Johnson, M, Gunyou, K, Thomas, L, Laechelt, J, Hollander, P, Spencer, M, Kendall, D, Cuddihy, R, Callahan, P, List, S, Gott, J, Rude, N, Olson, B, Franz, M, Castle, G, Birk, R, Nelson, J, Freking, D, Gill, L, Mestrezat, W, Etzwiler, D, Morgan, K, and Aiello, LP

Subjects
DCCT/EDIC Research Group
Abstract

© 2016 Darabian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: Type 1 diabetes (T1DM) patients are at increased risk of coronary artery disease (CAD). This pilot study sought to evaluate the relationship between epicardial adipose tissue (EAT) and intra-thoracic adipose tissue (IAT) volumes and cardio-metabolic risk factors in T1DM. Method: EAT/IAT volumes in 100 patients, underwent non-contrast cardiac computed tomography in the Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were measured by a certified reader. Fat was defined as pixels' density of -30 to -190 Hounsfield Unit. The associations were assessed using-Pearson partial correlation and linear regression models adjusted for gender and age with inverse probability sample weighting. Results: The weighted mean age was 43 years (range 32-57) and 53% were male. Adjusted for gender, Pearson correlation analysis showed a significant correlation between age and EAT/IAT volumes (both p

Published
2016
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25. Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling

Author

Quin, J, Chan, KT, Devlin, JR, Cameron, DP, Diesch, J, Cullinane, C, Ahern, J, Khot, A, Hein, N, George, AJ, Hannan, KM, Poortinga, G, Sheppard, KE, Khanna, KK, Johnstone, RW, Drygin, D, McArthur, GA, Pearson, RB, Sanij, E, Hannan, RD, Quin, J, Chan, KT, Devlin, JR, Cameron, DP, Diesch, J, Cullinane, C, Ahern, J, Khot, A, Hein, N, George, AJ, Hannan, KM, Poortinga, G, Sheppard, KE, Khanna, KK, Johnstone, RW, Drygin, D, McArthur, GA, Pearson, RB, Sanij, E, and Hannan, RD

Abstract

RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limiting step for cell growth and proliferation. Inhibition of Pol I by CX-5461 can selectively induce p53-mediated apoptosis of tumour cells in vivo. Currently, CX-5461 is in clinical trial for patients with advanced haematological malignancies (Peter Mac, Melbourne). Here we demonstrate that CX-5461 also induces p53-independent cell cycle checkpoints mediated by ATM/ATR signaling in the absence of DNA damage. Further, our data demonstrate that the combination of drugs targeting ATM/ATR signaling and CX-5461 leads to enhanced therapeutic benefit in treating p53-null tumours in vivo, which are normally refractory to each drug alone. Mechanistically, we show that CX-5461 induces an unusual chromatin structure in which transcriptionally competent relaxed rDNA repeats are devoid of transcribing Pol I leading to activation of ATM signaling within the nucleoli. Thus, we propose that acute inhibition of Pol transcription initiation by CX-5461 induces a novel nucleolar stress response that can be targeted to improve therapeutic efficacy.

Published
2016

27. New copper(II) complexes incorporating unsymmetrical tetradentate ligands with cis-N2O2 chromophores: synthesis, molecular structure, substituent effect and thermal stability

Author

Donald Van Derveer, Quin J. Meng, Rei X. Wang, Carl R. Jackson, Xiu R. Bu, and Xiao Z. You

Subjects
Ligand, Acetylacetone, Aryl, Substituent, chemistry.chemical_element, Photochemistry, Copper, Inorganic Chemistry, chemistry.chemical_compound, chemistry, Polymer chemistry, Materials Chemistry, Electronic effect, Moiety, Molecule, Physical and Theoretical Chemistry
Abstract

Five new tetradentate unsymmetrical ligands, ethylene-N-(acetylacetoneimine)-N′-(ortho-hydroxyl arylaldimine) (aryl = 3,5-dibromophenyl, 3-methylphenyl, 3,6-dimethylphenyl, 3,5-dichlorophenyl, 3,5-dibromoacetophenone), have been prepared and characterized for studies of the general structure of their copper(II) complexes and assessment of the substituent effects on central metal ions. Upon reaction with copper(II) ions, the ligands derived from aryls, where aryls are 3,5-dibromophenyl, 3-methylphenyl, 3,6-dimethylphenyl and 3,5-dibromoacetophenone, give the corresponding copper(II) complexes while the ligand derived from 3,5dichlorophenyl undergoes partial hydrolysis leading to the cleavage of an acetylacetone moiety. The general coordination configuration has been revealed by an X-ray crystallographic study of one of the complexes, ethylene-N-(acetylacetoneiminato)-N′-(o-hydroxy-3,5-dibromoacetophenoneiminato)copper(II), which exhibits an approximately square-planar geometry with a slight tetrahedron distortion. An ESR study of the copper(II) complexes in solution indicates electronic effects from substituents influence the reactivity of central metal ions. In addition, a key step in preparation of the unsymmetrical ligands has been dramatically improved to ensure synthetic reproducibility and eliminate the decomposition of an intermediate, 7-amino-4-methyl-5azo-3-heptene-2-one, AMAHO. Thermal stability of the complexes has been also evaluated to assess the compatibility of the two donating moieties.

Published
1997
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36. Derivatives of 5-[[1-4(4-carboxybenzyl)imidazolyl]methylidene]hydantoins as orally active angiotensin II receptor antagonists

Author

John C. Hodges, Sylvester Klutchko, Quin J rd, James M. Hamby, C. J. C. Connolly, Amy Mae Bunker, Jeremy J. Edmunds, Panek Rl, Ila Sircar, and R. T. Winters

Subjects
Carboxybenzyl, Angiotensin receptor, Angiotensin Receptor Antagonists, Angiotensin II receptor type 1, Stereochemistry, Substituent, Hydantoin, Angiotensin II, chemistry.chemical_compound, chemistry, Drug Discovery, Molecular Medicine, Tetrazole, hormones, hormone substitutes, and hormone antagonists
Abstract

A series of 5-[[1-(4'-carboxybenzyl)imidazolyl]methylidene]hydantoins have been prepared and evaluated as in vitro and in vivo angiotensin II (Ang II) antagonists. Variation of substituents on the hydantoin ring leads to potent and selective Ang II antagonists with nanomolar IC50 values at the AT1 receptor and negligible affinity for the AT2 receptor. Preferred substituents include an n-butyl at R1 and an alkyl or heteroarylmethyl substituent at R2. The selection of the R2 substituent was guided in part by the calculation of its log P since a significant correlation was observed between CLOGP and AT1 binding affinity. The biphenyl tetrazole pharmacophore, common to a number of AT1 antagonists, could be replaced by, for example, a 4-carbomethoxyphenyl substituent resulting in potent Ang II antagonists both in vitro and in vivo. A representative compound of this series is 57, which reduced the mean arterial blood pressure of renal hypertensive rats by 40% at 30 mg/kg po and by 25% at 10 mg/kg po. In addition this compound was efficacious in the salt-deplete normotensive monkey model maximally decreasing blood pressure 27% at 10 mg/kg po. In summary, these compounds belong to a novel class of Ang II antagonists that lack the biphenyl tetrazole moiety yet display appreciable and long lasting oral activity.

Published
1995
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37. Nonpeptide angiotensin II receptor antagonists. 2. Design, synthesis, and structure-activity relationships of 2-alkyl-4-(1H-pyrrol-l-yl)-1H-imidazole derivatives: profile of 2-propyl-1-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-4-[2-(trifluoroacetyl)-1H-pyrrol-1-yl]-1H-imidazole-5-carboxylic acid (CI-996)

Author

C. R. Kostlan, R. T. Winters, Jeremy J. Edmunds, John C. Hodges, S. J. Kesten, Quin J rd, Ila Sircar, Amy Mae Bunker, C. J. C. Connolly, and James M. Hamby

Subjects
chemistry.chemical_classification, Angiotensin II receptor type 1, Chemistry, Stereochemistry, Decarboxylation, Carboxylic acid, Substituent, Angiotensin II, Haloketone, chemistry.chemical_compound, Drug Discovery, Molecular Medicine, Imidazole, Pyrrole
Abstract

A novel series of nonpeptide angiotensin II (AII) receptor antagonists containing a 1H-pyrrol-1-yl moiety at the 4-position of the imidazole have been developed. The pyrrole group occupies the same lipophilic pocket at the receptor as the chloro group in DuP 753 (68) and EXP 3174 (69) and the pentafluoro group in DuP 532 (70), respectively. The impetus for its selection came from bioisosteric considerations based on hydrophobic and electronic substituent constants. An extensive study of the structure-activity relationships revealed several highly potent AII receptor antagonists. An acyl substitution at the 2-position of the pyrrole ring improved activity, most notably in the in vivo rat model. In addition, the 2-substituted pyrrole compounds improved chemical stability toward extremely facile decarboxylation reaction associated with unsubstituted pyrrole analogues, thus facilitating development of these agents. The IC50's of 18, 20, and 42 (< 1 nM) were better than the reference compounds 69 and 70, respectively. These compounds were selective AII antagonists that compete at the AT1 receptor and showed no affinity at the AT2 receptor at concentrations up to 10 microM. Upon intravenous administration in a normotensive rat model, compound 18 inhibited the AII-induced responses with ED50 of 6 micrograms/kg per min. In a renal hypertensive rat model, the antihypertensive potency of compound 18, at a dose of 10 mg/kg, was very similar to those 68 and 69, respectively. Compound 18 demonstrated a dose-related (3-30 mg/kg) decrease in blood pressure that was sustained for greater than 24 h. On the basis of its profile, compound 18, designated as CI-996, has been selected for in-depth studies. The design, synthesis, in vitro, and in vivo structure-activity relationships are described.

Published
1993
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38. Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype

Author

Neergaard Sj, Klutchko, C. J. Blankley, Quin J rd, C. J. C. Connolly, Sebastian A, Himmelsbach Rj, John C. Hodges, Chucholowski A, and Van Nieuwenhze Ms

Subjects
Pyridines, Tetrazoles, Losartan, Angiotensin Receptor Antagonists, Structure-Activity Relationship, Adrenal Glands, Drug Discovery, medicine, Animals, Structure–activity relationship, Binding site, Receptor, Binding Sites, Receptors, Angiotensin, Chemistry, Angiotensin II, Biphenyl Compounds, Imidazoles, Stereoisomerism, Biological activity, Rats, Biochemistry, Molecular Medicine, Rabbits, Angiotensin II Receptor Binding, medicine.drug
Abstract

Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace 125I-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.

Published
1991
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41. Book reviews

Author

Luce, A. A., Falkiner, N. M., Quin, J. S., O’Sullivan, M., Chambers, M., Irvine, G. M., Naughten, M., and Kinnear, N.

Published
1951
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43. UBF levels determine the number of active ribosomal RNA genes in mammals

Author

Sanij, E, Poortinga, G, Sharkey, K, Hung, S, Holloway, TP, Quin, J, Robb, E, Wong, LH, Thomas, WG, Stefanovsky, V, Moss, T, Rothblum, L, Hannan, KM, McArthur, GA, Pearson, RB, Hannan, RD, Sanij, E, Poortinga, G, Sharkey, K, Hung, S, Holloway, TP, Quin, J, Robb, E, Wong, LH, Thomas, WG, Stefanovsky, V, Moss, T, Rothblum, L, Hannan, KM, McArthur, GA, Pearson, RB, and Hannan, RD

Abstract

In mammals, the mechanisms regulating the number of active copies of the approximately 200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1-induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation.

Published
2008

48. Quantification of the Spatial Variability of the Ocean Surface Roughness and Momentum Flux

Author

UNIVERSITY OF SOUTH ALABAMA MOBILE, Chen, Quin J., UNIVERSITY OF SOUTH ALABAMA MOBILE, and Chen, Quin J.

Abstract

It is well known that physical processes occurring at the air-sea interface, such as air-sea mass, momentum, and energy exchanges, are controlled by the ocean surface roughness that has often been characterized in the literature as being homogeneous in space and time from a large-scale point of view. However, the ocean surface roughness is heterogeneous within a wavelength. The surface areas on wave crests are usually rougher than those on wave troughs. The mechanisms range from capillary ripples on wave crests to larger scale wave breaking. Ambient swell and non-uniform currents can also cause significant spatial variations of the surface roughness as short waves become steeper on the swell crest than those on the swell trough. This study parameterizes the spatial variability of the sea surface roughness and quantifies the resultant variations of momentum and energy exchanges between the atmosphere and the coastal ocean using a phase-resolving numerical wave model. These results have been presented at conferences and submitted to a journal for possible publication. This report is organized as follows. First, the author presents the new parameterization of the momentum flux transferred from the wind to surface gravity waves in the coastal zone. Next, he analyzes the effect of wave nonlinearity on the drag coefficient using Stokes' second-order wave theory. Then he shows how to implement the parameterized wind stress into the phase resolving Boussinesq wave model with enhanced dispersion properties. After that, tests of the extended Boussinesq model with the wind forcing against wave measurements in a shallow lake were carried out followed by an application of the model to the study of sea-swell interactions. The report ends with a summary of the findings. (5 figures, 28 refs.)

Published
2003

49. Combined analysis of Two-Year Follow-up from two open-label randomized trials comparing efficacy of three nucleoside reverse transcriptase inhibitor backbones for previously untreated HIV-1 nfection: OzCombo 1 and 2

Author

Amin, J., Moore, A., Carr, A., French, M.A., Law, M., Emery, S., Cooper, D.A., Kotsiou, G., Norrito, L., Dwyer, D., Packham, D., Fordham, M., Garsia, R., Baker, D., Doong, N.C., Quan, D., Beveridge, A., Genn, W., Quin, J., Mulholland, J., Sowden, D., Rawlinsen, M., Rebic, D., Street, A., De Graaf, B., Roney, J., Bryant, M., McCormack, C., Hoy, J.N., Shaw, D.V., Ferguson, W., Waddell, R., Papanaoum, K., French, M.R., Scull, N., Todhunter, L., Mallal, S., James, R., Foreman, E., Amin, J., Moore, A., Carr, A., French, M.A., Law, M., Emery, S., Cooper, D.A., Kotsiou, G., Norrito, L., Dwyer, D., Packham, D., Fordham, M., Garsia, R., Baker, D., Doong, N.C., Quan, D., Beveridge, A., Genn, W., Quin, J., Mulholland, J., Sowden, D., Rawlinsen, M., Rebic, D., Street, A., De Graaf, B., Roney, J., Bryant, M., McCormack, C., Hoy, J.N., Shaw, D.V., Ferguson, W., Waddell, R., Papanaoum, K., French, M.R., Scull, N., Todhunter, L., Mallal, S., James, R., and Foreman, E.

Abstract

Purpose: To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients. Method: Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken. Results: For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/wL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: m44 (p = .08) and m14 (p = .56) cells/wL and m0.1 (p = .40) and m0.1 (p = .6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p = .44) and 1.0 (p = .95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p = .07] and 7.6% [p = .02], respectively). Conclusion: For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.

Published
2003

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