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Book ; Online ; E-Book: Principles and practice of clinical research

Gallin, John I. / Ognibene, Frederick P. / Johnson, Laura L.

2018

Title variant	Clinical research
Author's details	edited by John I. Galli, Frederick P. Ognibene, Laura Lee Johnson
Keywords	Research / methods ; Research \|x methods / methods ; Medicine/Research ; Medicine/Research/Methodology
Language	English
Size	1 Online-Ressource (xvii, 806 Seiten)
Edition	Fourth edition
Publisher	Academic Press
Publishing place	London
Publishing country	Great Britain
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019509995
ISBN	9780128499047 ; 9780128499054 ; 0128499044 ; 0128499052
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Nystagmus in the B6(CG)Tyr(c-2J)/J Albino Mouse: A Functional and RNA-Seq Analysis.

Johnson, Laura L / Abrahante, Juan E / McLoon, Linda K

Investigative ophthalmology & visual science

2024 Volume 65, Issue 1, Page(s) 26

Abstract: Purpose: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. ... ...

Abstract	Purpose: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. Albino mice have nystagmus; however, a pigmented mouse with a tyr mutation making it phenotypically albino, the B6(CG)-Tyr(c-2J)/J (B6 albino), had not been tested. We tested optokinetic response (OKR) in B6 albino and control mice. RNA-Seq was performed on extraocular muscles (EOM), tibialis anterior (TA) muscle, abducens (CN6), and oculomotor (CN3) neurons to uncover molecular differences that may contribute to nystagmus. Methods: OKR was measured using an ISCAN system. RNA was isolated from four tissues to identify differentially expressed genes and validated with qPCR and immunohistochemistry. Ingenuity pathway analyses identified top biological pathways. Results: All B6 albino mice tested had nystagmus. Differential RNA expression analysis showed 383 genes differentially expressed in EOM, 70 in CN3, 20 in CN6, and 639 in the TA. Two genes were differentially expressed in all four tissues: wdfy1 and nnt. Differences were validated by qPCR and immunostaining. Conclusions: The tyr mutation in B6 albino mice, genotypically pigmented and phenotypically albino, is sufficient to result in spontaneous nystagmus. The two genes with decreased expression in the B6 albino tissues examined, wdfy1 and nnt, have been implicated in mitochondrial dysfunction and stem cell maintenance in other systems. Their function in extraocular muscle is unknown. These studies suggest that this mouse model of nystagmus may allow molecular identification of candidate nystagmus-related genes.
MeSH term(s)	Animals ; Mice ; RNA-Seq ; Nystagmus, Pathologic/genetics ; Nystagmus, Optokinetic ; Oculomotor Muscles ; RNA/genetics
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.1.26
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Article ; Online: Parasites, Infections, and Inoculation in Synthetic Minimal Cells.

Cash, Brock / Gaut, Nathaniel J / Deich, Christopher / Johnson, Laura L / Engelhart, Aaron E / Adamala, Katarzyna P

ACS omega

2023 Volume 8, Issue 7, Page(s) 7045–7056

Abstract: Synthetic minimal cells provide a controllable and engineerable model for biological processes. While much simpler than any live natural cell, synthetic cells offer a chassis for investigating the chemical foundations of key biological processes. Herein, ...

Abstract	Synthetic minimal cells provide a controllable and engineerable model for biological processes. While much simpler than any live natural cell, synthetic cells offer a chassis for investigating the chemical foundations of key biological processes. Herein, we show a synthetic cell system with host cells, interacting with parasites and undergoing infections of varying severity. We demonstrate how the host can be engineered to resist infection, we investigate the metabolic cost of carrying resistance, and we show an inoculation that immunizes the host against pathogens. Our work expands the synthetic cell engineering toolbox by demonstrating host-pathogen interactions and mechanisms for acquiring immunity. This brings synthetic cell systems one step closer to providing a comprehensive model of complex, natural life.
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.2c07911
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Article ; Online: Nystagmus Associated With the Absence of MYOD Expression Across the Lifespan in Extraocular and Limb Muscles.

Johnson, Laura L / Hebert, Sadie / Kueppers, Rachel B / McLoon, Linda K

Investigative ophthalmology & visual science

2023 Volume 64, Issue 12, Page(s) 24

Abstract: Purpose: The extraocular muscles (EOMs) undergo significant levels of continuous myonuclear turnover and myofiber remodeling throughout life, in contrast to limb skeletal muscles. Activation of the myogenic pathway in muscle precursor cells is ... ...

Abstract	Purpose: The extraocular muscles (EOMs) undergo significant levels of continuous myonuclear turnover and myofiber remodeling throughout life, in contrast to limb skeletal muscles. Activation of the myogenic pathway in muscle precursor cells is controlled by myogenic transcription factors, such as MYOD. Limb muscles from MyoD-/- mice develop normally but have a regeneration defect, and these mice develop nystagmus. We examined MyoD-/- mice to determine if they have an aging phenotype. Methods: Eye movements of aging MyoD-/- mice and littermate controls (wild type) were examined using optokinetic nystagmus (OKN). We assessed limb muscle function, changes to myofiber number, mean cross-sectional area, and abundance of the PAX7 and PITX2 populations of myogenic precursor cells. Results: Aging did not significantly affect limb muscle function despite decreased mean cross-sectional areas at 18+ months. Aging wild type mice had normal OKN responses; all aging MyoD-/- mice had nystagmus. With OKN stimulus present, the MyoD-/- mice at all ages had shorter slow phase durations compared to wild type age matched controls. In the dark, the MyoD-/- mice had a shorter slow phase duration with age. This correlated with significantly decreased fiber numbers and cross-sectional areas. The EOM in MyoD-/- mice had increased numbers of PAX7-positive satellite cells and significantly decreased PITX2-positive myonuclei. Conclusions: The absence of MYOD expression in aging mice causes a decrease in on-going myofiber remodeling, EOM fiber size, and number, and is associated with the development of spontaneous nystagmus. These results suggest that muscle-specific mutations can result in nystagmus, with increasing aging-related changes in the MyoD-/- EOM.
MeSH term(s)	Animals ; Mice ; Longevity ; Nystagmus, Pathologic ; Aging ; Nystagmus, Optokinetic ; Muscle, Skeletal
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.12.24
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Article ; Online: Development of Nystagmus With the Absence of MYOD Expression in the Extraocular Muscles.

Johnson, Laura L / Kueppers, Rachel B / Shen, Erin Y / Rudell, Jolene C / McLoon, Linda K

Investigative ophthalmology & visual science

2021 Volume 62, Issue 13, Page(s) 3

Abstract: Purpose: Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life ... ...

Abstract	Purpose: Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life compared with limb skeletal muscles, we hypothesized that the absence of MYOD would result in their abnormal structure and function. To assess structural and functional changes in the extraocular muscles in MyoD-/- mice, fiber size and number and optokinetic nystagmus reflex (OKN) responses were examined. Methods: OKN was measured in MyoD-/- mice and littermate wild-type controls at 3, 6, and 12 months. The extraocular muscles were examined histologically for changes in mean myofiber cross-sectional area, total myofiber number, and nuclei immunostained for PAX7 and PITX2, markers of myogenic precursor cells. Results: The MyoD-/- mice developed nystagmus, with both jerk and pendular waveforms, in the absence and in the presence of moving visual stimulation. At 12 months, there were significant losses in mean myofiber cross-sectional area and in total number of orbital layer fibers in all rectus muscles, as well as in global layer fibers in the superior and inferior rectus muscles. Haploinsufficient mice showed abnormal OKN responses. PITX2-positive cell entry into myofibers of the MyoD-/- mice was significantly reduced. Conclusions: This study is the first demonstration of the development of nystagmus in the constitutive absence of expression of the muscle-specific transcription factor MYOD. We hypothesize that myofiber loss over time may alter anterograde and/or retrograde communication between the motor nerves and extraocular muscles that are critical for maintaining normalcy of extraocular muscle function.
MeSH term(s)	Animals ; Disease Models, Animal ; Follow-Up Studies ; Gene Expression Regulation ; Mice ; MyoD Protein/biosynthesis ; MyoD Protein/genetics ; Nystagmus, Pathologic/diagnosis ; Nystagmus, Pathologic/genetics ; Nystagmus, Pathologic/metabolism ; Oculomotor Muscles/diagnostic imaging ; Oculomotor Muscles/metabolism
Chemical Substances	MyoD Protein ; MyoD1 myogenic differentiation protein
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.62.13.3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Accommodation of missing data in supportive and palliative care clinical trials.

Kurland, Brenda F / Johnson, Laura L / Diehr, Paula H

Current opinion in supportive and palliative care

2012 Volume 6, Issue 4, Page(s) 465–470

Abstract: Purpose of review: Clinical trials to evaluate the supportive and palliative care treatments have some different missing data concerns than the other clinical trials. This study reviews the literature on missing data as it may apply to these trials.: ... ...

Abstract	Purpose of review: Clinical trials to evaluate the supportive and palliative care treatments have some different missing data concerns than the other clinical trials. This study reviews the literature on missing data as it may apply to these trials. Recent findings: Prevention of missing data through study design and conduct is a recent area of focus. Missing data can be minimized by simplifying trial participation for patients, their caregivers, and trialists. Run-in periods with active drug or collecting data from observer (proxy) respondents may complicate a trial but may be used to address some specific concerns. Many analyses can accommodate data missing because of nonresponse by multiple imputation, using carefully chosen imputation models. Analysis of trials evaluating end-of-life care should distinguish between missing data and truncation because of death. Summary: Likely patterns for missing data should be discussed when planning a clinical trial, as modifications to trial design can minimize missing data while still addressing study aims. Many statistical analysis methods are available to accommodate missing data, but robustness of study conclusions to assumptions about mechanisms underlying the missingness should be evaluated by sensitivity analyses.
MeSH term(s)	Clinical Trials as Topic/statistics & numerical data ; Data Collection/methods ; Data Interpretation, Statistical ; Humans ; Palliative Care ; Research Design ; Survival Analysis
Language	English
Publishing date	2012-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2633726-5
ISSN	1751-4266 ; 1751-4258
ISSN (online)	1751-4266
ISSN	1751-4258
DOI	10.1097/SPC.0b013e328358441d
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Article: Longitudinal Data with Follow-up Truncated by Death: Match the Analysis Method to Research Aims.

Kurland, Brenda F / Johnson, Laura L / Egleston, Brian L / Diehr, Paula H

Statistical science : a review journal of the Institute of Mathematical Statistics

2009 Volume 24, Issue 2, Page(s) 211

Abstract: Diverse analysis approaches have been proposed to distinguish data missing due to death from nonresponse, and to summarize trajectories of longitudinal data truncated by death. We demonstrate how these analysis approaches arise from factorizations of the ...

Abstract	Diverse analysis approaches have been proposed to distinguish data missing due to death from nonresponse, and to summarize trajectories of longitudinal data truncated by death. We demonstrate how these analysis approaches arise from factorizations of the distribution of longitudinal data and survival information. Models are illustrated using cognitive functioning data for older adults. For unconditional models, deaths do not occur, deaths are independent of the longitudinal response, or the unconditional longitudinal response is averaged over the survival distribution. Unconditional models, such as random effects models fit to unbalanced data, may implicitly impute data beyond the time of death. Fully conditional models stratify the longitudinal response trajectory by time of death. Fully conditional models are effective for describing individual trajectories, in terms of either aging (age, or years from baseline) or dying (years from death). Causal models (principal stratification) as currently applied are fully conditional models, since group differences at one timepoint are described for a cohort that will survive past a later timepoint. Partly conditional models summarize the longitudinal response in the dynamic cohort of survivors. Partly conditional models are serial cross-sectional snapshots of the response, reflecting the average response in survivors at a given timepoint rather than individual trajectories. Joint models of survival and longitudinal response describe the evolving health status of the entire cohort. Researchers using longitudinal data should consider which method of accommodating deaths is consistent with research aims, and use analysis methods accordingly.
Language	English
Publishing date	2009-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2009740-2
ISSN	2168-8745 ; 0883-4237
ISSN (online)	2168-8745
ISSN	0883-4237
DOI	10.1214/09-STS293
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Article ; Online: Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study

Campbell William / Roth Mark / Johnson Laura L / Baer David / Mahabir Somdat / Clevidence Beverly / Taylor Philip R

Nutrition Journal, Vol 6, Iss 1, p

2007 Volume 3

Abstract: Abstract Background The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise ... ...

Abstract	Abstract Background The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. Methods This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. Results and discussion In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/m 2 ) had a 2-fold increase, and obese women (BMI > 30 kg/m 2 ) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m 2 ) women. When the models for the different measures of adiposity were assessed by multiple R 2 , models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. Conclusion Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.
Keywords	Nutrition. Foods and food supply ; TX341-641 ; Home economics ; TX1-1110 ; Technology ; T ; DOAJ:Nutrition and Food Sciences ; DOAJ:Agriculture and Food Sciences
Subject code	630
Language	English
Publishing date	2007-01-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study

Mahabir, Somdat / Baer, David / Johnson, Laura L / Roth, Mark / Campbell, William / Clevidence, Beverly / Taylor, Philip R

Nutrition journal. 2007, v. 6, no. 3

2007

Abstract: Background: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures ... ...

Abstract	Background: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. Methods: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. Results and discussion: In multivariate analysis, women who were overweight (BMI > 25 to < or = 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. Conclusion: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.
Keywords	women ; menopause ; nutrition research ; diet study techniques ; body mass index ; body fat ; body fat distribution ; leptin ; lifestyle ; smoking (habit) ; cross-sectional studies ; dual-energy X-ray absorptiometry ; adipose tissue ; adipocytes
Language	English
Size	7 p.
Document type	Article
DOI	10.1186/1475-2891-6-3
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study.

Mahabir, Somdat / Baer, David / Johnson, Laura L / Roth, Mark / Campbell, William / Clevidence, Beverly / Taylor, Philip R

Nutrition journal

2007 Volume 6, Page(s) 3

Abstract	Background: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. Methods: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. Results and discussion: In multivariate analysis, women who were overweight (BMI > 25 to < or = 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI < or =25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. Conclusion: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.
MeSH term(s)	Absorptiometry, Photon ; Aged ; Body Fat Distribution ; Body Mass Index ; Cross-Over Studies ; Female ; Humans ; Leptin/blood ; Middle Aged ; Obesity/blood ; Postmenopause/physiology ; Smoking
Chemical Substances	Leptin
Language	English
Publishing date	2007-01-17
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1475-2891
ISSN (online)	1475-2891
DOI	10.1186/1475-2891-6-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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