100 results on '"Beauchamp JR"'
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2. CT evaluation of soft tissue and muscle infection and inflammation: a systematic compartmental approach
- Author
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Beauchamp, Jr., Norman J., Scott, Jr., William W., Gottlieb, Lori M., and Fishman, Elliot K.
- Published
- 1995
- Full Text
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3. Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site
- Author
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Morgan, JE, Gross, JG, Pagel, CN, Beauchamp, JR, Fassati, A, Thrasher, AJ, Di Santo, JP, Fisher, IB, Xu, SW, Abraham, DJ, Partridge, TA, Morgan, JE, Gross, JG, Pagel, CN, Beauchamp, JR, Fassati, A, Thrasher, AJ, Di Santo, JP, Fisher, IB, Xu, SW, Abraham, DJ, and Partridge, TA
- Abstract
Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains. However, it is unclear whether it is due to secretion of proliferative factors or reduction of antiproliferative agents. To investigate this further, we have exploited the observation that the immortal myogenic C2 C12 cell line forms tumors far more rapidly in irradiated than in nonirradiated host muscle. We show that the effect of preirradiation on tumor formation is persistent and dose dependent. However, C2 C12 cells are not irreversibly compelled to form undifferentiated tumor cells by the irradiated muscle environment and are still capable of forming large amounts of muscle when reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we discovered that C2 C12 cells have a bimodal propensity to form tumors; some clones form no tumors even after extensive periods in irradiated graft sites, whereas others rapidly form extensive tumors. This illustrates the subtle interplay between the phenotype of implanted cells and the factors in the muscle environment.
- Published
- 2002
4. Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source
- Author
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Beauchamp, JR, Morgan, JE, Pagel, CN, Partridge, TA, Beauchamp, JR, Morgan, JE, Pagel, CN, and Partridge, TA
- Abstract
Myoblasts, the precursors of skeletal muscle fibers, can be induced to withdraw from the cell cycle and differentiate in vitro. Recent studies have also identified undifferentiated subpopulations that can self-renew and generate myogenic cells (Baroffio, A., M. Hamann, L. Bernheim, M.-L. Bochaton-Pillat, G. Gabbiani, and C.R. Bader. 1996. Differentiation. 60:47-57; Yoshida, N., S. Yoshida, K. Koishi, K. Masuda, and Y. Nabeshima. 1998. J. Cell Sci. 111:769-779). Cultured myoblasts can also differentiate and contribute to repair and new muscle formation in vivo, a capacity exploited in attempts to develop myoblast transplantation (MT) for genetic modification of adult muscle. Our studies of the dynamics of MT demonstrate that cultures of myoblasts contain distinct subpopulations defined by their behavior in vitro and divergent responses to grafting. By comparing a genomic and a semiconserved marker, we have followed the fate of myoblasts transplanted into muscles of dystrophic mice, finding that the majority of the grafted cells quickly die and only a minority are responsible for new muscle formation. This minority is behaviorally distinct, slowly dividing in tissue culture, but rapidly proliferative after grafting, suggesting a subpopulation with stem cell-like characteristics.
- Published
- 1999
5. PACS and unread images.
- Author
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Evers, Robert W., Yousem, David M., Deluca, Tom, Beauchamp Jr, Norman J., Smith, Sidney, and Beauchamp, Norman J Jr
- Published
- 2002
- Full Text
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6. Impact of pager notification on report verification times.
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Oguz, Kader Karli, Yousem, David M., Deluca, Tom, Herskovits, Edward H., Beauchamp Jr, Norman J., and Beauchamp, Norman J Jr
- Subjects
RADIOLOGY ,PAGERS (Beepers) ,RADIOLOGISTS ,ECONOMICS - Abstract
: Rationale and ObjectivesThe purpose of this study was to assess the impact on times of verification (TOVs) by a pager notification system (PNS) that informs physicians when reports are available for signature.: Materials and MethodsAn automated PNS was implemented in the authors'' department in November 2000. Monthly report verification times of each physician were collected for 3 months in the years before and after initiation of the PNS. Radiologists enrolled in the PNS and those who were not were assigned into two groups for analysis. Mean TOVs for the two sets of 3 months and for the two groups were calculated and differences recorded. Two-tailed t tests were used to assess for statistical differences between the groups.: ResultsTwenty-nine of 37 radiologists voluntarily enrolled in the PNS (group 1). Mean TOV was 26.75 hours (standard deviation [
SD] = 17.76 ) for these physicians before and 14.48 hours (SD = 11.86 ) after the PNS was employed (P < .01 ). For those physicians who did not enroll in the PNS, mean TOV was 11.53 hours (SD = 5.55 ) before and 9.77 hours (SD = 9.86 ) after the PNS was employed (P = .33 ). Both the absolute and percentage reductions in TOVs were significantly greater for those physicians enrolled in the PNS than for those who were not (P = .035 ). Twenty-three of 29 (79%) physicians who used the PNS showed a reduction in their report turnaround times.: ConclusionLinking the PNS with the radiology information system to notify physicians of unsigned reports was effective in reducing report verification times. [Copyright &y& Elsevier]- Published
- 2002
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7. NEUROIMAGING IN THE IDENTIFICATION OF LOW-GRADE AND NONNEOPLASTIC CNS LESIONS.
- Author
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Passe, Theodore J., Beauchamp Jr., Norman J., and Burger, Peter C.
- Published
- 1999
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8. A STUDY OF 'IT': HANDBOOK TREATMENT AND MAGAZINE USE.
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Beauchamp Jr., Emerson
- Subjects
PRONOUNS (Grammar) ,ENGLISH language education ,PERIODICALS - Abstract
Examines the handbook treatment and magazine use of the pronoun it. Categories of the pronoun; Number of times the pronoun was used in handbooks and magazines surveyed; Restriction on the use of the pronoun in some magazines.
- Published
- 1951
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9. Progression of Magnetic Resonance Imaging-Defined Brain Vascular Disease Predicts Vascular Events in Elderly.
- Author
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Longstreth Jr., W. T., Arnold, Alice M., Kuller, Lewis H., Bernick, Charles, Lefkowitz, David S., Beauchamp Jr., Norman J., and Manolio, Teri A.
- Published
- 2011
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10. A National Neuroimaging Database: A call to action1.
- Author
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Yousem, David M., Bryan, R. Nick, Beauchamp Jr, Norman J., and Arnold, Alice M.
- Published
- 2004
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11. A decision guideline for emergency department utilization of noncontrast head computed tomography in HIV-infected patients
- Author
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Rothman, R. E., Keyl, P. M., Mcarthur, J. C., Beauchamp Jr, N. J., Danyluk, T., and Gabor Kelen
12. A review of the chronic toxicity, carcinogenicity, and possible mechanisms of action of inorganic acid mists in animals
- Author
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Swenberg, James A. and Beauchamp, Jr., Robert O.
- Subjects
SULFURIC acid ,CARCINOGENICITY - Abstract
Occupational exposure to inorganic acid mists containing sulfuric acid has been associated with increased laryngeal cancer. The primary objective of this review was to compile the literature regarding chronic toxicity and carcinogenicity of inorganic acid mists in laboratoryanimals. Several chronic toxicity studies had exposures of 1 year orlonger. Whereas numbers of animals were limited, no evidence of neoplastic or preneoplastic lesions was reported. Two studies evaluated the carcinogenicity of inorganic acid mists in rats; however, one was limited by a short duration of exposure and the other did not achievea maximum tolerated dose. A large lifetime study in hamsters evaluated the carcinogenicity of 100 mg/M
3 sulfuric acid mist, aswell as its ability to act as a promoter or co-carcinogen for benzo(a)pyrene. No evidence of carcinogenic potential was shown. Although an increase in papillomas was noted in the benzo(a)pyrene + H2 SO4 group, the co-carcinogenic or promoting potential was considered equivocal. Thus, no evidence from experimental animals strongly supports or refutes the induction of cancer by inorganic acid mists. A possible mechanism that could be associated with inorganicacid mist carcinogenicity relates to the genetic consequences of lowering the pH. Reduced pH can induce chromosomal aberrations, enhance depurination, and deamination of cytidine in DNA. This mechanism has not been evaluated in tissues of the respiratory tract. [ABSTRACT FROM AUTHOR]- Published
- 1997
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13. A critical review of the toxicology of glutaraldehyde
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Morgan, Kevin T., Beauchamp, Jr., Robert O., Clarke, David O., Fennell, Timothy R., Kari, Frank W., and St.Clair, Mary Beth G.
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TOXICOLOGY ,HEALTH ,HUMAN beings - Published
- 1992
14. Quantitative studies of the survival and proliferation of transplanted myoblasts
- Author
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Beauchamp, JR, Morgan, JE, and Partridge, TA
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- 1996
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15. Toxicity and analysis of carbon disulfide: an annotated bibliography
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Beauchamp, Jr, R
- Published
- 1974
16. Delta-Like 4 Activates Notch 3 to Regulate Self-Renewal in Skeletal Muscle Stem Cells.
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Low S, Barnes JL, Zammit PS, and Beauchamp JR
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- Animals, Cell Cycle genetics, Cell Cycle physiology, Cell Line, Cells, Cultured, Intracellular Signaling Peptides and Proteins genetics, Membrane Proteins genetics, Mice, Muscle Fibers, Skeletal metabolism, Myoblasts, Skeletal cytology, Receptor, Notch3 genetics, Satellite Cells, Skeletal Muscle cytology, Satellite Cells, Skeletal Muscle metabolism, Intracellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, Myoblasts, Skeletal metabolism, Receptor, Notch3 metabolism
- Abstract
Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a role for Notch3 (N3) in the self-renewal of muscle stem cells. We found that N3 is active in quiescent C2C12 reserve cells (RCs), and N3 over-expression and knockdown studies in C2C12 and primary satellite cells reveal a role in self-renewal. The Notch ligand Delta-like 4 (Dll4) is expressed by newly formed myotubes and interaction with this ligand is sufficient to maintain N3 activity in quiescent C2C12 RCs to prevent activation and progression into the cell cycle. Thus, our data suggest a model whereby during regeneration, expression of Dll4 by nascent muscle fibers triggers N3 signaling in associated muscle stem cells to recruit them to quiescence, thereby renewing the stem cell pool. Stem Cells 2018;36:458-466., (© 2017 AlphaMed Press.)
- Published
- 2018
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17. Basics of finance and accounting.
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Beauchamp NJ 3rd and Beauchamp NJ Jr
- Subjects
- United States, Accounting organization & administration, Financial Management organization & administration, Income, Practice Management, Medical organization & administration, Private Practice organization & administration, Radiology organization & administration
- Published
- 2014
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18. A guide to the external review of an academic radiology department.
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Collins J, Amis ES Jr, Beauchamp NJ Jr, Norbash AM, and Meltzer CC
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- United States, Academic Medical Centers organization & administration, Algorithms, Peer Review methods, Program Evaluation methods, Quality Assurance, Health Care organization & administration, Radiology Department, Hospital organization & administration
- Abstract
External reviews are used to evaluate a department on a routine basis or prior to reappointment or recruitment of a department chair. The Society of Chairs of Academic Radiology Departments (SCARD) developed a template that outlines important components of an external review report and a table that outlines the objective information that can be requested from the institution/department prior to the reviewer's site visit. The template is meant to facilitate a high-quality review and serve as a guide to a chair who is preparing for his/her first review, chairs who serve as external consultants, and institutional officials seeking review of a radiology department., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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19. Commentary: Masters of radiology panel discussion--how do we maintain control over imaging?
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Forman HP, Larson DB, Kazerooni EA, Norbash A, Javitt MC, and Beauchamp NJ Jr
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- Clinical Competence, Diagnostic Imaging economics, Diagnostic Imaging statistics & numerical data, Humans, Patient Safety, Quality Assurance, Health Care, Radiology economics, Referral and Consultation economics, Reimbursement Mechanisms economics, Diagnostic Imaging standards, Radiology organization & administration
- Published
- 2013
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20. Masters of radiology panel discussion--is imaging in decline?
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Forman HP, Larson DB, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, and Beauchamp NJ Jr
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- Diagnostic Imaging trends, Humans, Diagnostic Imaging statistics & numerical data, Radiology trends
- Published
- 2013
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21. Masters of radiology panel discussion: hyperefficient radiology--can we maintain the pace?
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Forman HP, Larson DB, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, Beauchamp NJ Jr, and Mendelson EB
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- Humans, Relative Value Scales, Technology, Efficiency, Professional Practice trends, Radiology trends, Workload
- Published
- 2012
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22. Masters of radiology panel discussion: The future of the radiology job market.
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Forman HP, Larson DB, Kaye AD, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, Beauchamp NJ Jr, and Mendelson EB
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- Forecasting, Humans, United States, Employment trends, Radiology trends
- Published
- 2012
- Full Text
- View/download PDF
23. Masters of radiology panel discussion: maintaining maintenance of certification in the field of radiology.
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Forman HP, Larson DB, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, Beauchamp NJ Jr, and Mendelson EB
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- Humans, United States, Certification, Clinical Competence, Radiology education, Radiology standards
- Published
- 2012
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- View/download PDF
24. Masters of radiology panel discussion: women in radiology--how can we encourage more women to join the field and become leaders?
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Forman HP, Larson DB, Kaye AD, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, and Beauchamp NJ Jr
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- Female, Humans, Career Choice, Leadership, Physicians, Women, Radiology
- Published
- 2012
- Full Text
- View/download PDF
25. What is the role of the radiologist in holding down health care cost growth?
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Forman HP, Beauchamp NJ Jr, Kaye A, Larson DB, and Norbash A
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- Humans, Leadership, Politics, Cost Control, Diagnostic Imaging economics, Health Care Costs, Physician's Role
- Published
- 2011
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26. Masters of radiology panel discussion: encouraging and fostering mentorship--how we can ensure that no faculty member is left behind and that leaders do not fail.
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Forman HP, Larson DB, Norbash A, Javitt MC, Beauchamp NJ Jr, Monsees B, and Messinger N
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- United States, Workforce, Career Mobility, Faculty, Medical, Leadership, Mentors, Motivation, Radiology education
- Published
- 2011
- Full Text
- View/download PDF
27. Masters of radiology panel discussion: the commoditization of radiology.
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Forman HP, Larson DB, Kaye AD, Kazerooni EA, Norbash A, Crowe JK, Javitt MC, and Beauchamp NJ Jr
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- Humans, Commodification, Economic Competition, Radiology economics, Radiology trends
- Published
- 2011
- Full Text
- View/download PDF
28. Scenario planning.
- Author
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Enzmann DR, Beauchamp NJ Jr, and Norbash A
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- United States, Forecasting, Models, Organizational, Organizational Objectives, Radiology organization & administration
- Abstract
In facing future developments in health care, scenario planning offers a complementary approach to traditional strategic planning. Whereas traditional strategic planning typically consists of predicting the future at a single point on a chosen time horizon and mapping the preferred plans to address such a future, scenario planning creates stories about multiple likely potential futures on a given time horizon and maps the preferred plans to address the multiple described potential futures. Each scenario is purposefully different and specifically not a consensus worst-case, average, or best-case forecast; nor is scenario planning a process in probabilistic prediction. Scenario planning focuses on high-impact, uncertain driving forces that in the authors' example affect the field of radiology. Uncertainty is the key concept as these forces are mapped onto axes of uncertainty, the poles of which have opposed effects on radiology. One chosen axis was "market focus," with poles of centralized health care (government control) vs a decentralized private market. Another axis was "radiology's business model," with one pole being a unified, single specialty vs a splintered, disaggregated subspecialty. The third axis was "technology and science," with one pole representing technology enabling to radiology vs technology threatening to radiology. Selected poles of these axes were then combined to create 3 scenarios. One scenario, termed "entrepreneurialism," consisted of a decentralized private market, a disaggregated business model, and threatening technology and science. A second scenario, termed "socialized medicine," had a centralized market focus, a unified specialty business model, and enabling technology and science. A third scenario, termed "freefall," had a centralized market focus, a disaggregated business model, and threatening technology and science. These scenarios provide a range of futures that ultimately allow the identification of defined "signposts" that can suggest which basic features among the "possible futures" are playing out. Scenario planning provides for the implementation of appropriate constructed strategic responses. Scenarios allow for a pre-prepared game plan available for ready use as the future unfolds. They allow a deliberative response rather than a hastily constructed, urgent response., (Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
29. Masters of radiology panel discussion: Models for health care performance in radiology--how do we measure our productivity and ourselves?
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Forman HP, Norbash A, Beauchamp NJ Jr, Thrall JH, Larson DB, Kazerooni EA, Hricak H, Monsees B, Javitt MC, and Crowe JK
- Subjects
- Biomedical Research organization & administration, Certification, Humans, Organizational Objectives, Patient Satisfaction, Radiology education, Radiology Department, Hospital economics, Efficiency, Radiology Department, Hospital organization & administration, Workload
- Published
- 2011
- Full Text
- View/download PDF
30. Masters of radiology panel discussion: who is accountable for the appropriateness of studies--the radiologist, the referring physician, or both?
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Forman HP, Beauchamp NJ Jr, Kazerooni EA, Larson DB, Javitt MC, and Norbash A
- Subjects
- Humans, Liability, Legal, Radiography standards, Radiology standards, Referral and Consultation
- Published
- 2010
- Full Text
- View/download PDF
31. Masters of radiology panel discussion: radiology extenders--challenges and opportunities to balance the demands of our changing work environment.
- Author
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Forman HP, Javitt MC, Monsees B, Larson DB, Norbash A, Kaye A, Beauchamp NJ Jr, and Messinger N
- Subjects
- Attitude of Health Personnel, Efficiency, Organizational, Humans, Professional Autonomy, Radiology, Interventional, United States, Workforce, Nurse Practitioners, Physician Assistants, Radiology, Technology, Radiologic, Workload
- Published
- 2010
- Full Text
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32. Masters of radiology panel discussion: role of communication in today's radiologic practices.
- Author
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Forman HP, Javitt MC, Monsees B, Crowe JK, Beauchamp NJ Jr, Larson DB, Kaye A, Kazerooni EA, Norbash A, Messinger N, Hricak H, and Thrall JH
- Subjects
- Attitude of Health Personnel, Automation, Documentation, Humans, Communication, Radiology, Radiology Information Systems
- Published
- 2010
- Full Text
- View/download PDF
33. Skeletal muscle stem cells express anti-apoptotic ErbB receptors during activation from quiescence.
- Author
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Golding JP, Calderbank E, Partridge TA, and Beauchamp JR
- Subjects
- Animals, Apoptosis drug effects, Benzothiazoles pharmacology, Cell Survival, Humans, Ligands, MAP Kinase Kinase Kinases antagonists & inhibitors, Mice, Mice, Inbred C57BL, Muscle Cells enzymology, Protein Kinase Inhibitors pharmacology, Quinazolines, Receptor Protein-Tyrosine Kinases analysis, Receptor, ErbB-2 analysis, Receptor, ErbB-2 antagonists & inhibitors, Satellite Cells, Skeletal Muscle drug effects, Satellite Cells, Skeletal Muscle physiology, Signal Transduction drug effects, Stem Cells drug effects, Stem Cells enzymology, Tyrphostins pharmacology, Muscle Cells cytology, Receptor Protein-Tyrosine Kinases metabolism, Receptor, ErbB-2 metabolism, Satellite Cells, Skeletal Muscle enzymology
- Abstract
To be effective for tissue repair, satellite cells (the stem cells of adult muscle) must survive the initial activation from quiescence. Using an in vitro model of satellite cell activation, we show that erbB1, erbB2 and erbB3, members of the EGF receptor tyrosine kinase family, appear on satellite cells within 6 h of activation. We show that signalling via erbB2 provides an anti-apoptotic survival mechanism for satellite cells during the first 24 h, as they progress to a proliferative state. Inhibition of erbB2 signalling with AG825 reduced satellite cell numbers, concomitant with elevated caspase-8 activation and TUNEL labelling of apoptotic satellite cells. In serum-free conditions, satellite cell apoptosis could be largely prevented by a mixture of erbB1, erbB3 and erbB4 ligand growth factors, but not by neuregulin alone (erbB3/erbB4 ligand). Furthermore, using inhibitors specific to discrete intracellular signalling pathways, we identify MEK as a pro-apoptotic mediator, and the erbB-regulated factor STAT3 as an anti-apoptotic mediator during satellite cell activation. These results implicate erbB2 signalling in the preservation of a full compliment of satellite cells as they activate in the context of a damaged muscle.
- Published
- 2007
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34. Rapid and automatic calculation of the midsagittal plane in magnetic resonance diffusion and perfusion images.
- Author
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Nowinski WL, Prakash B, Volkau I, Ananthasubramaniam A, and Beauchamp NJ Jr
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- Humans, Information Storage and Retrieval methods, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Artificial Intelligence, Brain blood supply, Brain pathology, Cerebrovascular Circulation, Diffusion Magnetic Resonance Imaging methods, Image Enhancement methods, Image Interpretation, Computer-Assisted methods, Imaging, Three-Dimensional methods, Pattern Recognition, Automated methods
- Abstract
Rationale and Objectives: A near real-time and fully automatic method for calculation of the midsagittal plane (MSP) for magnetic resonance (MR) diffusion and perfusion images is introduced., Materials and Methods: The method is based on the Kullback-Leibler's (KL) measure quantifying the difference between two intensity distributions. The MSP is a sagittal plane with the highest KL measure. The method was validated quantitatively for 61 diffusion-weighted imaging (DWI), cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), peak height (PKHT), and time to peak (TPP) data sets of 11 stroke patients based on the ground truth provided by two raters., Results: Average angular errors are less than 1 degrees for DWI and less than 2 degrees for CBF and CBV. Average distance errors measured in the worst case (on the brain's bounding box) are less than 2.5 mm for DWI and less than 5 mm for CBF and CBV. This algorithmic accuracy is at the level of interrater variability. Results obtained for the other perfusions maps (MTT, PKHT, TTP) were inferior; therefore, processing of CBF or CBV is preferred for accurate and robust calculation of the MSP from perfusion maps. Calculation of the MSP takes about half a second on a standard computer., Conclusions: The proposed method is near real-time and fully automatic, and neither user interaction nor parameter setting is needed. It does not require preprocessing of data. The method potentially is useful in rapid and automated processing of MR stroke diffusion and perfusion images.
- Published
- 2006
- Full Text
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35. Pax7 and myogenic progression in skeletal muscle satellite cells.
- Author
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Zammit PS, Relaix F, Nagata Y, Ruiz AP, Collins CA, Partridge TA, and Beauchamp JR
- Subjects
- Animals, Cell Differentiation physiology, Cell Fusion, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Mice, MyoD Protein genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Satellite Cells, Skeletal Muscle cytology, Muscle, Skeletal cytology, MyoD Protein metabolism, PAX7 Transcription Factor metabolism, Satellite Cells, Skeletal Muscle physiology, Transcription, Genetic
- Abstract
Skeletal muscle growth and regeneration are attributed to satellite cells - muscle stem cells resident beneath the basal lamina that surrounds each myofibre. Quiescent satellite cells express the transcription factor Pax7 and when activated, coexpress Pax7 with MyoD. Most then proliferate, downregulate Pax7 and differentiate. By contrast, others maintain Pax7 but lose MyoD and return to a state resembling quiescence. Here we show that Pax7 is able to drive transcription in quiescent and activated satellite cells, and continues to do so in those cells that subsequently cease proliferation and withdraw from immediate differentiation. We found that constitutive expression of Pax7 in satellite-cell-derived myoblasts did not affect MyoD expression or proliferation. Although maintained expression of Pax7 delayed the onset of myogenin expression it did not prevent, and was compatible with, myogenic differentiation. Constitutive Pax7 expression in a Pax7-null C2C12 subclone increased the proportion of cells expressing MyoD, showing that Pax7 can act genetically upstream of MyoD. However these Pax7-null cells were unable to differentiate into normal myotubes in the presence of Pax7. Therefore Pax7 may be involved in maintaining proliferation and preventing precocious differentiation, but does not promote quiescence.
- Published
- 2006
- Full Text
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36. Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.
- Author
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Mukamal KJ, Chung H, Jenny NS, Kuller LH, Longstreth WT Jr, Mittleman MA, Burke GL, Cushman M, Beauchamp NJ Jr, and Siscovick DS
- Subjects
- Aged, Apolipoproteins E genetics, Brain Infarction pathology, Cohort Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Hypertension genetics, Inflammation, Ischemia pathology, Lipids chemistry, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction, Prospective Studies, Risk, Risk Factors, Substance-Related Disorders complications, Thrombosis, Time Factors, Alcohol Drinking adverse effects, Brain Ischemia epidemiology, Brain Ischemia etiology, Stroke epidemiology, Stroke etiology, Vascular Diseases etiology
- Abstract
Background and Purpose: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype., Methods: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly., Results: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors., Conclusions: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.
- Published
- 2005
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37. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.
- Author
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Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, Manolio TA, Lefkowitz D, Jungreis C, Hirsch CH, O'Leary DH, and Furberg CD
- Subjects
- Aged, Cardiovascular Diseases complications, Cognition Disorders diagnosis, Female, Humans, Incidence, Leukoaraiosis pathology, Longitudinal Studies, Male, Risk Factors, Stroke epidemiology, Brain pathology, Leukoaraiosis diagnosis, Leukoaraiosis epidemiology, Magnetic Resonance Imaging
- Abstract
Background and Purpose: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging., Methods: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade., Results: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk., Conclusions: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.
- Published
- 2005
- Full Text
- View/download PDF
38. Mouse myotomes pairs exhibit left-right asymmetric expression of MLC3F and alpha-skeletal actin.
- Author
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Golding JP, Partridge TA, Beauchamp JR, King T, Brown NA, Gassmann M, and Zammit PS
- Subjects
- Animals, Female, Gene Expression Regulation, Developmental, Homeodomain Proteins genetics, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Muscle, Skeletal physiology, Nuclear Proteins genetics, Pregnancy, Situs Inversus genetics, Transcription Factors, Homeobox Protein PITX2, Actins genetics, Embryonic Development physiology, Muscle, Skeletal embryology, Myosin Light Chains genetics, Situs Inversus physiopathology
- Abstract
Most muscle originates from the myotomal compartment of the somites, paired structures flanking the neural tube. Whereas vertebrate embryos show molecular and morphological asymmetry about the left-right body axis, somitic myogenesis is thought to occur symmetrically. Here, we provide the first evidence that myotome pairs are transiently left-right asymmetric, with higher expression of alpha-skeletal actin and myosin light chain 3F (MLC3F) on the left side between embryonic day 9.5-10.25. In iv mutants with situs inversus, the asymmetric expression of alpha-skeletal actin and MLC3F was inverted, showing that this process is regulated by global left-right axis cues, initiated before gastrulation. However, although left-sided identity is later maintained by Pitx2 genes, we found that Pitx2c null embryos have normal left-biased expression of alpha-skeletal actin and MLC3F. Myotome asymmetry, therefore, is downstream of the iv mutation but upstream of, or unrelated to, the Pitx2c pathway., (Copyright (c) 2004 Wiley-Liss, Inc.)
- Published
- 2004
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39. Heparin-binding EGF-like growth factor shows transient left-right asymmetrical expression in mouse myotome pairs.
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Golding JP, Tsoni S, Dixon M, Yee KT, Partridge TA, Beauchamp JR, Gassmann M, and Zammit PS
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- Animals, Branchial Region metabolism, Epidermal Growth Factor genetics, Heparin-binding EGF-like Growth Factor, Intercellular Signaling Peptides and Proteins, Limb Buds, Mice genetics, Mice metabolism, Mice, Inbred C57BL, Somites metabolism, Epidermal Growth Factor metabolism, Mice embryology
- Abstract
Heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen and chemoattractant for diverse cell types including, keratinocytes, fibroblasts and vascular smooth muscle cells. In adult mice, skeletal muscle and endothelial cells prominently express HB-EGF, although analysis of embryonic expression has been limited to studies of heart and kidney development. Here we survey HB-EGF mRNA expression in E7.5-E15 mouse embryos and show that HB-EGF is expressed in branchial arches, limb buds and, transiently, in mature somites between E9.25 and E11. This somitic expression is restricted to the myotomal compartment. Intriguingly, within myotome pairs, the expression of HB-EGF is stronger on the left side of the body, whilst cognate receptors, ErbB1 and ErbB4, are symmetrically expressed in left and right somite pairs. In iv/iv mutant embryos, with inverted left-right body axis, the expression of HB-EGF was also inverted, now being stronger in myotomes on the right side of the body. Thus, the expression of HB-EGF in myotome pairs is regulated by global cues that define the left-right body axis.
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- 2004
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40. Myf5 expression in satellite cells and spindles in adult muscle is controlled by separate genetic elements.
- Author
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Zammit PS, Carvajal JJ, Golding JP, Morgan JE, Summerbell D, Zolnerciks J, Partridge TA, Rigby PW, and Beauchamp JR
- Subjects
- Animals, Chromosomes, Artificial, Bacterial genetics, Culture Techniques, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Mechanoreceptors growth & development, Mechanoreceptors metabolism, Mice, Mice, Transgenic, Muscle Denervation, Muscle Spindles growth & development, Muscle Spindles metabolism, Muscle, Skeletal cytology, Myogenic Regulatory Factor 5, Satellite Cells, Skeletal Muscle metabolism, DNA-Binding Proteins genetics, Muscle Proteins genetics, Muscle, Skeletal growth & development, Muscle, Skeletal metabolism, Trans-Activators genetics
- Abstract
The myogenic regulatory factor Myf5 is integral to the initiation and control of skeletal muscle formation. In adult muscle, Myf5 is expressed in satellite cells, stem cells of mature muscle, but not in the myonuclei that sustain the myofibre. Using the Myf5(nlacZ/+) mouse, we now show that Myf5 is also constitutively expressed in muscle spindles-stretch-sensitive mechanoreceptors, while muscle denervation induces extensive reactivation of the Myf5 gene in myonuclei. To identify the elements involved in the regulation of Myf5 in adult muscle, we analysed reporter gene expression in a transgenic bacterial artificial chromosome (BAC) deletion series of the Mrf4/Myf5 locus. A BAC carrying 140 kb upstream of the Myf5 transcription start site was sufficient to drive all aspects of Myf5 expression in adult muscle. In contrast, BACs carrying 88 and 59 kb upstream were unable to drive consistent expression in satellite cells, although expression in muscle spindles and reactivation of the locus in myonuclei were retained. Therefore, as during development, multiple enhancers are required to generate the full expression pattern of Myf5 in the adult. Together, these observations show that elements controlling adult Myf5 expression are genetically separable and possibly distinct from those that control Myf5 during development. These studies are a first step towards identifying cognate transcription factors involved in muscle stem cell regulation.
- Published
- 2004
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41. Role of interleukin-1beta in acute inflammation and graft death after cell transplantation to the heart.
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Suzuki K, Murtuza B, Beauchamp JR, Brand NJ, Barton PJ, Varela-Carver A, Fukushima S, Coppen SR, Partridge TA, and Yacoub MH
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- Animals, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, Biomarkers, Cell Differentiation, Cell Division, Cell Line, Transformed transplantation, Cell Survival drug effects, Cell Transplantation adverse effects, Female, Graft Survival drug effects, Histone Demethylases, Immunoglobulin G pharmacology, Immunoglobulin G therapeutic use, Interleukin-1 antagonists & inhibitors, Interleukin-1 biosynthesis, Interleukin-1 genetics, Male, Mice, Myoblasts pathology, Myocarditis drug therapy, Myocarditis prevention & control, Myocardium metabolism, Peroxidase analysis, Proteins analysis, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-1 physiology, Myoblasts transplantation, Myocarditis etiology
- Abstract
Background: Poor survival of grafted cells is a major factor hindering the therapeutic effect of cell transplantation; however, the causes of cell death remain unclear. We hypothesized that interleukin-1beta (IL-1beta) might play a role in the acute inflammatory response and graft death after cell transplantation and that inhibition of IL-1beta might improve graft survival., Methods and Results: 14C-labeled male skeletal muscle precursor cells were implanted into female mouse hearts by direct intramuscular injection. The amount of 14C-label provides an estimate of the surviving cell number, whereas the amount of male-specific Smcy gene measured by polymerase chain reaction indicates the total (surviving+proliferated) number of donor-derived cells. At 10 minutes after implantation, 44.8+/-2.4% of the grafted cells survived and this steadily decreased to 14.6+/-1.1% by 24 hours, and to 7.9+/-0.6% by 72 hours (n=6 in each point). Proliferation of the surviving cells, which began after 24 hours, resulted in an increase in the total cell number from 15.5+/-0.8% at 24 hours to 24.4+/-1.6% at 72 hours. Acute inflammation was prominent at 24 hours and was reduced by 72 hours, in parallel with IL-1beta expression. Administration of anti-IL-1beta antibody improved graft survival at both 24 (25.6+/-1.6%) and 72 hours (14.8+/-1.1%) and resulted in a 2-fold increase in the total cell number at 72 hours (45.8+/-2.4%). The effects of IL-1beta inhibition corresponded with a reduced inflammatory response., Conclusions: IL-1beta is involved in acute inflammation and graft death after direct intramyocardial cell transplantation. Targeted inhibition of IL-1beta may be a useful strategy to improve graft survival.
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- 2004
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42. Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?
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Zammit PS, Golding JP, Nagata Y, Hudon V, Partridge TA, and Beauchamp JR
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- Animals, Down-Regulation, Genes, Reporter, Homeodomain Proteins metabolism, Mice, Mice, Transgenic, MyoD Protein metabolism, PAX7 Transcription Factor, Cell Differentiation physiology, Satellite Cells, Skeletal Muscle physiology
- Abstract
Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7-ve progeny destined for differentiation. Some of the Pax7+ve/MyoD-ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool.
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- 2004
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43. White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke.
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Kuller LH, Longstreth WT Jr, Arnold AM, Bernick C, Bryan RN, and Beauchamp NJ Jr
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- Aged, Female, Humans, Male, Radiography, Risk Factors, Brain pathology, Leukoaraiosis pathology, Magnetic Resonance Imaging, Stroke diagnostic imaging, Stroke epidemiology
- Abstract
Background and Purpose: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors., Methods: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.
- Published
- 2004
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44. A national neuroimaging database: a call to action.
- Author
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Yousem DM, Bryan RN, Beauchamp NJ Jr, and Arnold AM
- Subjects
- Humans, United States, Cerebrovascular Disorders, Databases, Factual, Magnetic Resonance Imaging
- Published
- 2004
45. Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart.
- Author
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Suzuki K, Murtuza B, Beauchamp JR, Smolenski RT, Varela-Carver A, Fukushima S, Coppen SR, Partridge TA, and Yacoub MH
- Subjects
- Animals, Antioxidants pharmacology, Antioxidants therapeutic use, Cell Count instrumentation, Cell Death, Cell Line transplantation, Cytokines analysis, Female, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myoblasts, Skeletal pathology, Myocarditis etiology, Myocarditis pathology, Oxidative Stress, Peroxidase analysis, Reverse Transcriptase Polymerase Chain Reaction, Superoxide Dismutase pharmacology, Superoxide Dismutase therapeutic use, Graft Rejection pathology, Myoblasts, Skeletal transplantation, Myocardium pathology
- Abstract
Survival and proliferation of skeletal myoblasts within the cardiac environment are crucial to the therapeutic efficacy of myoblast transplantation to the heart. We have analyzed the early dynamics of myoblasts implanted into the myocardium and investigated the mechanisms underlying graft attrition. At 10 min after implantation of [14C]thymidine-labeled male myoblasts into female mice hearts, 14C measurement showed that 39.2 +/- 3.0% of the grafted cells survived, and this steadily decreased to 16.0 +/- 1.7% by 24 h and to 7.4 +/- 0.9% by 72 h. PCR of male-specific Smcy gene calculated that the total (surviving plus proliferated) number of donor-derived cells was 18.3 +/- 1.6 and 23.3 +/- 1.3% at 24 and 72 h, respectively, indicating that proliferation of the surviving cells began after 24 h. Acute inflammation became prominent by 24 h and was reduced by 72 h as indicated by myeloperoxidase activity and histological findings. Multiplex RT-PCR revealed corresponding changes in IL-1beta, TGF-beta, IL-6, and TNF-alpha expression. Treatment with CuZn-superoxide dismutase attenuated the initial rapid death and resulted in enhanced cell numbers afterward, giving a twofold increased total number at 72 h compared with the nontreatment. This effect was associated with reduced inflammatory response, suggesting a causative role for superoxide in the initial rapid graft death and subsequent inflammation. These data describe the early dynamics of myoblasts implanted into the myocardium and suggest that initial oxidative stress and following inflammatory response may be important mechanisms contributing to acute graft attrition, both of which could be potential therapeutic targets to improve the efficiency of cell transplantation to the heart.
- Published
- 2004
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46. Sleep-disordered breathing and white matter disease in the brainstem in older adults.
- Author
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Ding J, Nieto FJ, Beauchamp NJ Jr, Harris TB, Robbins JA, Hetmanski JB, Fried LP, and Redline S
- Subjects
- Aged, Arousal physiology, Cerebrovascular Disorders diagnosis, Cerebrovascular Disorders epidemiology, Electrooculography, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Polysomnography, Population Surveillance methods, Severity of Illness Index, Sleep Apnea Syndromes epidemiology, Sleep Stages physiology, Brain pathology, Brain Stem pathology, Sleep Apnea Syndromes diagnosis
- Abstract
Study Objectives: To examine whether sleep-disordered breathing is associated with white matter disease in the brainstem., Design: A population-based longitudinal study., Setting: Allegheny County, PA; Sacramento County, CA; and Washington County, MD., Patients or Participants: A total of 789 individuals, aged 68 years or older, drawn from the Sleep Heart Health Study., Interventions: N/A., Measurements and Results: The participants underwent home polysomnography in 1995-1998 and cerebral magnetic resonance imaging in both 1992-1993 and 1997-1998. The apnea-hypopnea index was not associated with white matter disease in the brainstem, with or without adjusting for age, sex, race, community, body mass index, smoking status, alcohol use, systolic blood pressure, and the use of antihypertensive medication. In contrast, the arousal index (number of arousals per hour of sleep) was inversely associated with brainstem white matter disease (odds ratio = 0.75 for a SD increase in the arousal index, 95% confidence interval: 0.62, 0.92)., Conclusions: The frequency of apneas and hypopneas was not associated with brainstem white matter disease in these older adults. A unique relationship with arousal frequency suggests that ischemic changes in the brainstem may be associated with arousals during sleep.
- Published
- 2004
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47. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium.
- Author
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Murtuza B, Suzuki K, Bou-Gharios G, Beauchamp JR, Smolenski RT, Partridge TA, and Yacoub MH
- Subjects
- Animals, Collagen biosynthesis, Collagen genetics, Extracellular Matrix metabolism, Interleukin 1 Receptor Antagonist Protein, Matrix Metalloproteinases biosynthesis, Matrix Metalloproteinases genetics, Mice, Myoblasts, Skeletal metabolism, Myocardial Infarction, Myocytes, Cardiac metabolism, Receptors, Interleukin-1 antagonists & inhibitors, Reverse Transcriptase Polymerase Chain Reaction, Sialoglycoproteins metabolism, Interleukin-1 antagonists & inhibitors, Myoblasts, Skeletal transplantation, Myocardium metabolism, Sialoglycoproteins genetics
- Abstract
After myocardial infarction (MI), adverse remodeling with left ventricular (LV) dilatation is a major determinant of poor outcome. Skeletal myoblast (SkM) implantation improves cardiac function post-MI, although the mechanism is unclear. IL-1 influences post-MI hypertrophy and collagen turnover and is implicated in SkM death after grafting. We hypothesized that SkM expressing secretory IL-1 receptor antagonist (sIL-1ra) at MI border zones would specifically attenuate adverse remodeling and exhibit improved graft cell number. Stable murine male SkM lines (5 x 10(5) cells), expressing or nonexpressing (cont) for sIL-1ra, were implanted into infarct border zones of female nude mice immediately after left coronary artery occlusion. LV ejection fraction (LVEF), end-diastolic diameter, and transmitral peak early/late (E/A) flow velocity ratio were determined by echocardiography. Cardiac myocyte hypertrophy and fibrosis were assessed by morphometry, picrosirius red staining, and hydroxyproline assay. At 3 weeks, cont-SkM-engrafted hearts showed reduced hypertrophy, improved LVEF (55.7 +/- 1.2% vs. MI-only: 40.3 +/- 2.9%), and preserved E/A ratios. sIL-1ra-SkM implantation enhanced these effects (LVEF, 67.0 +/- 2.3%) and significantly attenuated LV dilatation (LV end-diastolic diameter, 4.0 +/- 1.1 mm vs. cont-SkM, 4.5 +/- 1.2 mm vs. MI-only, 4.8 +/- 1.8 mm); this was associated with greater graft numbers, as shown by PCR for male-specific smcy gene. Enzyme zymography showed attenuated matrix metalloproteinase-2 and -9 up-regulation post-MI by either donor SkM type, although infarct-remote zone collagen was reduced only with sIL-1ra-SkM. These results suggest that SkM implantation improves cardiac function post-MI by modulation of adverse remodeling, and that this effect can be significantly enhanced by targeting IL-1 as a key upstream regulator of both adverse remodeling and graft cell death.
- Published
- 2004
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48. Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures.
- Author
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Reimann J, Brimah K, Schröder R, Wernig A, Beauchamp JR, and Partridge TA
- Subjects
- Biopsy, Cells, Cultured, Humans, Muscle Fibers, Skeletal cytology, Muscle Fibers, Skeletal metabolism, Muscle, Skeletal metabolism, Myofibrils metabolism, PAX7 Transcription Factor, Regeneration physiology, Satellite Cells, Skeletal Muscle metabolism, Cadherins metabolism, Cell Nucleus metabolism, Homeodomain Proteins metabolism, Muscle, Skeletal pathology, Satellite Cells, Skeletal Muscle cytology
- Abstract
Demonstration of the importance of the paired box transcription factor Pax7 for the murine myosatellite cell population, with persistent expression in mature skeletal muscle, prompted us to investigate the distribution of Pax7 protein in biopsy samples of normal and pathological human skeletal limb muscle. Immunostaining for M-cadherin, an adhesion molecule present at the interface between myofibre and satellite cell, and the characteristic position adjacent to the muscle fibre and beneath the fibre's basement membrane were used to identify satellite cells. Anti-Pax7 reactivity was found in the majority of satellite cells but a small population was Pax7 negative. Neither could we identify Pax7-positive nuclei in freshly regenerating myotubes or in presumed myoblasts in these biopsies. Similarly, in myogenic cell cultures derived from the explantation of human foetal muscle Pax7 expression was low or undetectable at the proliferative myoblast stage but it became prominent in an increasing proportion of mononucleate cells after the induction of differentiation. This expression was, however, restricted to mononucleate cells; it did not persist into the differentiation stage of newly formed multinucleate myotubes. Despite this, in the biopsy samples, we occasionally found Pax7-positive nuclei in muscle fibres that seemed to be undergoing degenerative changes. Most of these were found to be the nuclei of cells engaged in focal regenerative processes, but Pax7 re-expression by myonuclei "in distress" cannot be ruled out entirely.
- Published
- 2004
- Full Text
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49. Cavernous carotid artery calcification and white matter ischemia.
- Author
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Babiarz LS, Yousem DM, Wasserman BA, Wu C, Bilker W, and Beauchamp NJ Jr
- Subjects
- Adult, Aged, Aged, 80 and over, Calcinosis diagnosis, Calcinosis diagnostic imaging, Carotid Artery Diseases diagnosis, Carotid Artery Diseases diagnostic imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors, Tomography, X-Ray Computed, Brain Ischemia etiology, Calcinosis complications, Carotid Artery Diseases complications, Carotid Artery, Internal diagnostic imaging, Carotid Artery, Internal pathology
- Abstract
Background and Purpose: The relevance of cavernous carotid artery calcification on unenhanced CT scans of the brain has recently been investigated against the backdrop of the widespread implementation of coronary artery calcification scoring. We sought to determine whether the degree of cavernous carotid artery calcification correlated with scores of white matter hyperintensity seen on MR images. In so doing, we sought to establish a relative risk for future stroke on the grade of carotid calcification., Methods: Neuroradiologic findings in 187 patients who underwent CT and MR imaging examinations within 1 month of each other were retrospectively reviewed. The degree of circumferential calcification and thickness of calcification were graded for the cavernous carotid arteries on the basis of CT findings. Using the scale developed by the Cardiovascular Health Study, the white matter was graded for degree of disease on the basis of MR findings. Correlation tests and regression analyses were performed to determine the impact of age, race, and sex on results., Results: Although the cavernous carotid calcification scores and the MR imaging white matter scores showed good correlation (P <.001), the effect was mediated by age. With age factored in as a covariant, no correlation was shown between CT calcification scores and MR imaging white matter scores. Sex had no effect, but African American study participants had worse MR imaging white matter scores than did white participants., Conclusion: After adjusting for age, cavernous carotid calcification grades and MR imaging white matter scores do not show a significant correlation. The relative risk for future stroke cannot be predicted from cavernous carotid calcifications.
- Published
- 2003
50. Kinetics of myoblast proliferation show that resident satellite cells are competent to fully regenerate skeletal muscle fibers.
- Author
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Zammit PS, Heslop L, Hudon V, Rosenblatt JD, Tajbakhsh S, Buckingham ME, Beauchamp JR, and Partridge TA
- Subjects
- Animals, Cell Division, Cell Lineage, Cell Nucleus metabolism, Cells, Cultured, Kinetics, Mice, Mice, Mutant Strains, Muscle Proteins genetics, Muscle Proteins metabolism, MyoD Protein genetics, Myogenic Regulatory Factor 5, Satellite Cells, Skeletal Muscle metabolism, DNA-Binding Proteins, Muscle Fibers, Skeletal physiology, Muscle, Skeletal physiology, MyoD Protein metabolism, Regeneration, Satellite Cells, Skeletal Muscle cytology, Trans-Activators
- Abstract
The satellite cell compartment provides skeletal muscle with a remarkable capacity for regeneration. Here, we have used isolated myofibers to investigate the activation and proliferative potential of satellite cells. We have previously shown that satellite cells are heterogeneous: the majority express Myf5 and M-cadherin protein, presumably reflecting commitment to myogenesis, while a minority is negative for both. Although MyoD is rarely detected in quiescent satellite cells, over 98% of satellite cells contain MyoD within 24 h of stimulation. Significantly, MyoD is only observed in cells that are already expressing Myf5. In contrast, a minority population does not activate by the criteria of Myf5 or MyoD expression. Following the synchronous activation of the myogenic regulatory factor+ve satellite cells, their daughter myoblasts proliferate with a doubling time of approximately 17 h, irrespective of the fiber type (type I, IIa, or IIb) from which they originate. Although fast myofibers have fewer associated satellite cells than slow, and accordingly produce fewer myoblasts, each myofiber phenotype is associated with a complement of satellite cells that has sufficient proliferative potential to fully regenerate the parent myofiber within 4 days. This time course is similar to that observed in vivo following acute injury and indicates that cells other than satellite cells are not required for complete myofiber regeneration.
- Published
- 2002
- Full Text
- View/download PDF
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