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Article ; Online: The p150N domain of chromatin assembly factor-1 regulates Ki-67 accumulation on the mitotic perichromosomal layer.

Matheson, Timothy D / Kaufman, Paul D

2016 Volume 28, Issue 1, Page(s) 21–29

Abstract: Chromatin assembly factor 1 (CAF-1) deposits histones during DNA synthesis. The p150 subunit of human CAF-1 contains an N-terminal domain (p150N) that is dispensable for histone deposition but promotes the localization of specific loci (nucleolar- ... ...

Abstract	Chromatin assembly factor 1 (CAF-1) deposits histones during DNA synthesis. The p150 subunit of human CAF-1 contains an N-terminal domain (p150N) that is dispensable for histone deposition but promotes the localization of specific loci (nucleolar-associated domains [NADs]) and proteins to the nucleolus during interphase. One of the p150N-regulated proteins is proliferation antigen Ki-67, whose depletion also decreases the nucleolar association of NADs. Ki-67 is also a fundamental component of the perichromosomal layer (PCL), a sheath of proteins surrounding condensed chromosomes during mitosis. We show here that a subset of p150 localizes to the PCL during mitosis and that p150N is required for normal levels of Ki-67 accumulation on the PCL. This activity requires the sumoylation-interacting motif within p150N, which is also required for the nucleolar localization of NADs and Ki-67 during interphase. In this manner, p150N coordinates both interphase and mitotic nuclear structures via Ki67.
MeSH term(s)	Cell Cycle/physiology ; Cell Nucleolus/metabolism ; Chromatin/metabolism ; Chromatin Assembly Factor-1/genetics ; Chromatin Assembly Factor-1/metabolism ; Chromosome Structures/metabolism ; Chromosomes/metabolism ; HeLa Cells ; Histones/genetics ; Histones/metabolism ; Humans ; Interphase/physiology ; Ki-67 Antigen/genetics ; Ki-67 Antigen/metabolism ; Mitosis/physiology ; Transcription Factors
Chemical Substances	CNOT8 protein, human ; Chromatin ; Chromatin Assembly Factor-1 ; Histones ; Ki-67 Antigen ; Transcription Factors
Language	English
Publishing date	2016-11-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E16-09-0659
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Article ; Online: Grabbing the genome by the NADs.

Matheson, Timothy D / Kaufman, Paul D

Chromosoma

2015 Volume 125, Issue 3, Page(s) 361–371

Abstract: The regions of the genome that interact frequently with the nucleolus have been termed nucleolar-associated domains (NADs). Deep sequencing and DNA-fluorescence in situ hybridization (FISH) experiments have revealed that these domains are enriched for ... ...

Abstract	The regions of the genome that interact frequently with the nucleolus have been termed nucleolar-associated domains (NADs). Deep sequencing and DNA-fluorescence in situ hybridization (FISH) experiments have revealed that these domains are enriched for repetitive elements, regions of the inactive X chromosome (Xi), and several RNA polymerase III-transcribed genes. NADs are often marked by chromatin modifications characteristic of heterochromatin, including H3K27me3, H3K9me3, and H4K20me3, and artificial targeting of genes to this area is correlated with reduced expression. It has therefore been hypothesized that NAD localization to the nucleolar periphery contributes to the establishment and/or maintenance of heterochromatic silencing. Recently published studies from several multicellular eukaryotes have begun to reveal the trans-acting factors involved in NAD localization, including the insulator protein CCCTC-binding factor (CTCF), chromatin assembly factor (CAF)-1 subunit p150, several nucleolar proteins, and two long non-coding RNAs (lncRNAs). The mechanisms by which these factors coordinate with one another in regulating NAD localization and/or silencing are still unknown. This review will summarize recently published studies, discuss where additional research is required, and speculate about the mechanistic and functional implications of genome organization around the nucleolus.
MeSH term(s)	Animals ; Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; Chromatin Assembly and Disassembly/physiology ; Chromosomes, Human, X/genetics ; Chromosomes, Human, X/metabolism ; Genome, Human/physiology ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Humans ; X Chromosome Inactivation/physiology
Chemical Substances	Heterochromatin
Language	English
Publishing date	2015-07-15
Publishing country	Austria
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	203083-4
ISSN	1432-0886 ; 0009-5915
ISSN (online)	1432-0886
ISSN	0009-5915
DOI	10.1007/s00412-015-0527-8
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Article: Grabbing the genome by the NADs

Matheson, Timothy D / Paul D. Kaufman

Chromosoma. 2016 June, v. 125, no. 3

2016

Abstract	The regions of the genome that interact frequently with the nucleolus have been termed nucleolar-associated domains (NADs). Deep sequencing and DNA-fluorescence in situ hybridization (FISH) experiments have revealed that these domains are enriched for repetitive elements, regions of the inactive X chromosome (Xi), and several RNA polymerase III-transcribed genes. NADs are often marked by chromatin modifications characteristic of heterochromatin, including H3K27me3, H3K9me3, and H4K20me3, and artificial targeting of genes to this area is correlated with reduced expression. It has therefore been hypothesized that NAD localization to the nucleolar periphery contributes to the establishment and/or maintenance of heterochromatic silencing. Recently published studies from several multicellular eukaryotes have begun to reveal the trans-acting factors involved in NAD localization, including the insulator protein CCCTC-binding factor (CTCF), chromatin assembly factor (CAF)-1 subunit p150, several nucleolar proteins, and two long non-coding RNAs (lncRNAs). The mechanisms by which these factors coordinate with one another in regulating NAD localization and/or silencing are still unknown. This review will summarize recently published studies, discuss where additional research is required, and speculate about the mechanistic and functional implications of genome organization around the nucleolus.
Keywords	DNA-directed RNA polymerase ; NAD (coenzyme) ; X chromosome ; cell nucleolus ; eukaryotic cells ; fluorescence in situ hybridization ; genes ; heterochromatin ; high-throughput nucleotide sequencing ; non-coding RNA ; transactivators
Language	English
Dates of publication	2016-06
Size	p. 361-371.
Publishing place	Springer Berlin Heidelberg
Document type	Article
Note	Review
ZDB-ID	203083-4
ISSN	1432-0886 ; 0009-5915
ISSN (online)	1432-0886
ISSN	0009-5915
DOI	10.1007/s00412-015-0527-8
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Article ; Online: Ki-67 Contributes to Normal Cell Cycle Progression and Inactive X Heterochromatin in p21 Checkpoint-Proficient Human Cells.

Sun, Xiaoming / Bizhanova, Aizhan / Matheson, Timothy D / Yu, Jun / Zhu, Lihua Julie / Kaufman, Paul D

Molecular and cellular biology

2017 Volume 37, Issue 17

Abstract: The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and ... ...

Abstract	The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by codepletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of the cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive X (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S-phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.
MeSH term(s)	Cell Cycle/physiology ; Cell Division/physiology ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Replication/physiology ; Heterochromatin/metabolism ; Humans ; Ki-67 Antigen/metabolism
Chemical Substances	CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; Heterochromatin ; Ki-67 Antigen
Language	English
Publishing date	2017-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00569-16
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Article ; Online: Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

Jennings, Lindsey K / Lander, Laura / Lawdahl, Tricia / McClure, Erin A / Moreland, Angela / McCauley, Jenna L / Haynes, Louise / Matheson, Timothy / Jones, Richard / Robey, Thomas E / Kawasaki, Sarah / Moschella, Phillip / Raheemullah, Amer / Miller, Suzette / Gregovich, Gina / Waltman, Deborah / Brady, Kathleen T / Barth, Kelly S

Addiction science & clinical practice

2024 Volume 19, Issue 1, Page(s) 26

Abstract: Introduction: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer ... ...

Abstract	Introduction: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. Methods: A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. Results: A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided "general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. Conclusions: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.
MeSH term(s)	United States ; Humans ; National Institute on Drug Abuse (U.S.) ; Emergency Service, Hospital ; Naloxone/therapeutic use ; Opioid-Related Disorders/drug therapy ; Nitrosamines
Chemical Substances	N-nitrosoiminodiacetic acid (25081-31-6) ; Naloxone (36B82AMQ7N) ; Nitrosamines
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2492632-2
ISSN	1940-0640 ; 1940-0640
ISSN (online)	1940-0640
ISSN	1940-0640
DOI	10.1186/s13722-024-00453-x
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Article ; Online: A qualitative study of self-evaluation of junior doctor performance: is perceived 'safeness' a more useful metric than confidence and competence?

Roland, Damian / Matheson, David / Coats, Timothy / Martin, Graham

BMJ open

2015 Volume 5, Issue 11, Page(s) e008521

Abstract: Objectives: The terms confidence and competence have been poorly defined and are often misused by junior doctors. Given safe practice relies on healthcare professionals being aware of their own skill sets improving self-assessment of confidence and ... ...

Abstract	Objectives: The terms confidence and competence have been poorly defined and are often misused by junior doctors. Given safe practice relies on healthcare professionals being aware of their own skill sets improving self-assessment of confidence and competence is important. The aim of this work was to explore junior doctors' understanding of how they perceive their own performance in respect of managing feverish children in an emergency department. Setting: A children's emergency department in a tertiary hospital in the East Midlands, UK. Participants: 22 Junior doctors volunteered to undertake focus groups via a meta-planning methodology over 2 years (14 participants in the first year and 8 in the second). Results: Although doctors were aware of the difference between confidence and competence they were not able to distinguish between them in practical terms. The feeling of being 'safe' emerged as a term in which there was a shared understanding compared to reported confidence and competence. Conclusions: A perception of 'safeness' is a concept that may aid self-evaluation and we present a matrix that might be used by supervisors and educators to examine this and its relationship with confidence and competence.
MeSH term(s)	Clinical Competence/standards ; Diagnostic Self Evaluation ; Education, Medical, Continuing ; Emergency Service, Hospital ; Focus Groups ; Humans ; Medical Staff, Hospital/psychology ; Qualitative Research ; Surveys and Questionnaires ; Tertiary Care Centers ; United Kingdom
Language	English
Publishing date	2015-11-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2015-008521
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Article ; Online: Ki-67 Contributes to Normal Cell Cycle Progression and Inactive X Heterochromatin in p21 Checkpoint-Proficient Human Cells

Sun, Xiaoming / Bizhanova, Aizhan / Matheson, Timothy D. / Yu, Jun / Zhu, Lihua Julie / Kaufman, Paul D.

Molecular and Cellular Biology. 2017 Sept. 1, v. 37, no. 17 p.e00569-16-

2017

Abstract	The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by codepletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of the cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive X (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S-phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.
Keywords	DNA replication ; females ; fibroblasts ; gene expression ; heterochromatin ; humans ; interphase ; neoplasms ; nuclear lamina ; transcription (genetics) ; cell cycle
Language	English
Dates of publication	2017-0901
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00569-16
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Development of a Multi-Target Contingency Management Intervention for HIV Positive Substance Users.

Stitzer, Maxine / Calsyn, Donald / Matheson, Timothy / Sorensen, James / Gooden, Lauren / Metsch, Lisa

Journal of substance abuse treatment

2017 Volume 72, Page(s) 66–71

Abstract: Contingency management (CM) interventions generally target a single behavior such as attendance or drug use. However, disease outcomes are mediated by complex chains of both healthy and interfering behaviors enacted over extended periods of time. This ... ...

Abstract	Contingency management (CM) interventions generally target a single behavior such as attendance or drug use. However, disease outcomes are mediated by complex chains of both healthy and interfering behaviors enacted over extended periods of time. This paper describes a novel multi-target contingency management (CM) program developed for use with HIV positive substance users enrolled in a CTN multi-site study (0049 Project HOPE). Participants were randomly assigned to usual care (referral to health care and SUD treatment) or 6-months strength-based patient navigation interventions with (PN+CM) or without (PN only) the CM program. Primary outcome of the trial was viral load suppression at 12-months post-randomization. Up to $1160 could be earned over 6 months under escalating schedules of reinforcement. Earnings were divided among eight CM targets; two PN-related (PN visits; paperwork completion; 26% of possible earnings), four health-related (HIV care visits, lab blood draw visits, medication check, viral load suppression; 47% of possible earnings) and two drug-use abatement (treatment entry; submission of drug negative UAs; 27% of earnings). The paper describes rationale for selection of targets, pay amounts and pay schedules. The CM program was compatible with and fully integrated into the PN intervention. The study design will allow comparison of behavioral and health outcomes for participants receiving PN with and without CM; results will inform future multi-target CM development.
Language	English
Publishing date	2017-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	605923-5
ISSN	1873-6483 ; 0740-5472
ISSN (online)	1873-6483
ISSN	0740-5472
DOI	10.1016/j.jsat.2016.08.018
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Article ; Online: A separable domain of the p150 subunit of human chromatin assembly factor-1 promotes protein and chromosome associations with nucleoli.

Smith, Corey L / Matheson, Timothy D / Trombly, Daniel J / Sun, Xiaoming / Campeau, Eric / Han, Xuemei / Yates, John R / Kaufman, Paul D

Molecular biology of the cell

2014 Volume 25, Issue 18, Page(s) 2866–2881

Abstract: Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular ... ...

Abstract	Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus.
MeSH term(s)	Cell Nucleolus/metabolism ; Chromatin Assembly Factor-1/physiology ; Chromosomes, Human/metabolism ; HeLa Cells ; Humans ; Ki-67 Antigen/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Transport ; Transcription Factors
Chemical Substances	CNOT8 protein, human ; Chromatin Assembly Factor-1 ; Ki-67 Antigen ; Transcription Factors
Language	English
Publishing date	2014-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E14-05-1029
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Article ; Online: United States regulatory requirements for skin and eye irritation testing.

Choksi, Neepa Y / Truax, James / Layton, Adrienne / Matheson, Joanna / Mattie, David / Varney, Timothy / Tao, Jenny / Yozzo, Krystle / McDougal, Andrew J / Merrill, Jill / Lowther, Donnie / Barroso, Joao / Linke, Brenda / Casey, Warren / Allen, David

Cutaneous and ocular toxicology

2018 Volume 38, Issue 2, Page(s) 141–155

Abstract: Purpose: Eye and skin irritation test data are required or considered by chemical regulation authorities in the United States to develop product hazard labelling and/or to assess risks for exposure to skin- and eye-irritating chemicals. The combination ... ...

Abstract	Purpose: Eye and skin irritation test data are required or considered by chemical regulation authorities in the United States to develop product hazard labelling and/or to assess risks for exposure to skin- and eye-irritating chemicals. The combination of animal welfare concerns and interest in implementing methods with greater human relevance has led to the development of non-animal skin- and eye-irritation test methods. To identify opportunities for regulatory uses of non-animal replacements for skin and eye irritation tests, the needs and uses for these types of test data at U.S. regulatory and research agencies must first be clarified. Methods: We surveyed regulatory and non-regulatory testing needs of U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) agencies for skin and eye irritation testing data. Information reviewed includes the type of skin and eye irritation data required by each agency and the associated decision context: hazard classification, potency classification, or risk assessment; the preferred tests; and whether alternative or non-animal tests are acceptable. Information on the specific information needed from non-animal test methods also was collected. Results: A common theme across U.S. agencies is the willingness to consider non-animal or alternative test methods. Sponsors are encouraged to consult with the relevant agency in designing their testing program to discuss the use and acceptance of alternative methods for local skin and eye irritation testing. Conclusions: To advance the implementation of alternative testing methods, a dialog on the confidence of these methods to protect public health and the environment must be undertaken at all levels.
MeSH term(s)	Animal Testing Alternatives/legislation & jurisprudence ; Animals ; Eye/drug effects ; Government Agencies ; Government Regulation ; Humans ; Skin/drug effects ; Toxicity Tests ; United States
Language	English
Publishing date	2018-12-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	605635-0
ISSN	1556-9535 ; 1556-9527 ; 0731-3829
ISSN (online)	1556-9535
ISSN	1556-9527 ; 0731-3829
DOI	10.1080/15569527.2018.1540494
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