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Article: Noninvasive imaging of cell-mediated therapy for treatment of cancer.

Akins, Elizabeth J / Dubey, Purnima

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2008 Volume 49 Suppl 2, Page(s) 180S–95S

Abstract: Cell-mediated therapy (immunotherapy) for the treatment of cancer is an active area of investigation in animal models and clinical trials. Despite many advances, objective responses to immunotherapy are observed in a small number of cases, for certain ... ...

Abstract	Cell-mediated therapy (immunotherapy) for the treatment of cancer is an active area of investigation in animal models and clinical trials. Despite many advances, objective responses to immunotherapy are observed in a small number of cases, for certain tumor types. To better understand differences in outcomes, it is critical to develop assays for tracking effector cell localization and function in situ. The fairly recent use of molecular imaging techniques to track cell populations has presented researchers and clinicians with a powerful diagnostic tool for determining the efficacy of cell-mediated therapy for the treatment of cancer. This review highlights the application of whole-body noninvasive radioisotopic, magnetic, and optical imaging methods for monitoring effector cells in vivo. Issues that affect sensitivity of detection, such as methods of cell marking, efficiency of cell labeling, toxicity, and limits of detection of imaging modalities, are discussed.
MeSH term(s)	Adoptive Transfer ; Animals ; Antigen Presentation ; Cell Count ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Genes, Reporter ; Humans ; Immunotherapy/methods ; Immunotherapy, Active ; Luminescent Measurements/methods ; Lymphocytes/immunology ; Lymphocytes/pathology ; Magnetic Resonance Imaging ; Neoplasms/diagnosis ; Neoplasms/immunology ; Neoplasms/therapy ; Positron-Emission Tomography/methods ; Whole Body Imaging
Language	English
Publishing date	2008-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
DOI	10.2967/jnumed.107.045971
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Article: Mobilizing volunteers to sustain local suppression of a global marine invasion

Green, Stephanie J / Elizabeth B. Underwood / John L. Akins

Conservation letters. 2017 Nov., v. 10, no. 6

2017

Abstract: Species invasions often occur at geographic scales that preclude complete eradication, setting up longâterm battles for population control. To understand the extent to which exotic species removal by volunteers can contribute to local invasion ... ...

Abstract	Species invasions often occur at geographic scales that preclude complete eradication, setting up longâterm battles for population control. To understand the extent to which exotic species removal by volunteers can contribute to local invasion suppression and alleviate invasion effects, we studied the activities of volunteers culling invasive lionfish during annual âderbyâ events in the Atlantic. From 2012 to 2014, singleâday derbies reduced lionfish densities by 52% over 192 kmÂ² on average each year. Differences in recolonization and productivity between regions meant that annual events were sufficient to suppress the invasion below levels predicted to cause declines in native species in one region, but not the other. Population reduction was not related to catch per unit effort, confirming the importance of in situ monitoring to gauge control effectiveness. Culling by volunteers may be a useful tool in areas where exotic species are easily identified and safely captured, and culling can be promoted as an ongoing recreational activity. Strategically guiding volunteer effort toward sensitive or underserved habitats could aid practitioners in optimizing their use of limited resources for invasion management.
Keywords	habitats ; indigenous species ; introduced species ; monitoring
Language	English
Dates of publication	2017-11
Size	p. 726-735.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	LETTER
ISSN	1755-263X
DOI	10.1111/conl.12426
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Stress Regulation of Sustained Attention and the Cholinergic Attention System.

Eck, Samantha R / Xu, Song-Jun / Telenson, Alexander / Duggan, Michael R / Cole, Robert / Wicks, Brittany / Bergmann, Joy / Lefebo, Hanna / Shore, Marni / Shepard, Katherine A / Akins, Michael R / Parikh, Vinay / Heller, Elizabeth A / Bangasser, Debra A

Biological psychiatry

2020 Volume 88, Issue 7, Page(s) 566–575

Abstract: Background: Stress exacerbates symptoms of schizophrenia and attention-deficit/hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. We investigated whether ... ...

Abstract	Background: Stress exacerbates symptoms of schizophrenia and attention-deficit/hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. We investigated whether a 6-day variable stressor altered sustained attention and the cholinergic attention system in male and female rats. Methods: Sustained attention was tested with the sustained attention task. Successful performance on the sustained attention task relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nucleus basalis of Meynert (NBM). Thus, we evaluated whether variable stress (VS) altered the morphology of these neurons with a novel approach using a Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNA sequencing to identify VS-induced transcriptional changes in the NBM. Results: VS impaired attentional performance in the sustained attention task and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of male rats. Quantification of global transcriptional changes revealed that although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes. Conclusions: These studies suggest that VS impairs attention by inducing molecular and morphological changes in the NBM. Identifying mechanisms by which stress regulates attention may guide the development of novel treatments for psychiatric disorders with attention deficits.
MeSH term(s)	Acetylcholine ; Animals ; Basal Nucleus of Meynert/metabolism ; Choline O-Acetyltransferase/metabolism ; Cholinergic Agents ; Cholinergic Neurons ; Female ; Male ; Rats
Chemical Substances	Cholinergic Agents ; Choline O-Acetyltransferase (EC 2.3.1.6) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2020-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2020.04.013
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Article ; Online: In situ vaccination combined with androgen ablation and regulatory T-cell depletion reduces castration-resistant tumor burden in prostate-specific pten knockout mice.

Akins, Elizabeth J / Moore, Miranda L / Tang, Shuai / Willingham, Mark C / Tooze, Janet A / Dubey, Purnima

Cancer research

2010 Volume 70, Issue 9, Page(s) 3473–3482

Abstract: There is no effective treatment for prostate cancer arising after androgen ablation. Previous studies have analyzed the short-term effects of androgen ablation on the immune system and suggest an abatement of immune suppression by hormone removal. ... ...

Abstract	There is no effective treatment for prostate cancer arising after androgen ablation. Previous studies have analyzed the short-term effects of androgen ablation on the immune system and suggest an abatement of immune suppression by hormone removal. Because castration-resistant disease can arise years after treatment, it is crucial to determine the duration of immune potentiation by castration. Because immunotherapeutic efficacy is determined by the balance of immune cell subsets and their location within the tumor, we assessed the acute and chronic effect of androgen ablation on the localization of T-cell subsets within castration-resistant murine prostate cancer. We observed a transient increase in CD4+ and CD8+ T-cell numbers at the residual tumor after androgen ablation. More than 2 months later, regulatory T cells (Treg) were increasingly found within prostate epithelium, whereas CTLs, which were evenly distributed before androgen ablation, became sequestered within stroma. Anti-CD25 antibody administration along with castration enhanced CTL access to cancerous glands but did not increase effector function. Intraprostatic injection of LIGHT-expressing tumor cells increased the proportion of CD8+ T cells with functional capacity within the cancerous gland. In addition, Treg depletion within the tumor was enhanced. Together, these manipulations significantly reduced castration-resistant tumor burden. Thus, our results indicate that immune modulations, which prevent Treg accumulation and augment effector cell infiltration of prostatic epithelium, may be effective in reducing tumor burden or preventing tumor recurrence after androgen ablation therapy.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/immunology ; Adenocarcinoma/surgery ; Adenocarcinoma/therapy ; Androgens/deficiency ; Animals ; CD4-CD8 Ratio ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Orchiectomy ; PTEN Phosphohydrolase/deficiency ; PTEN Phosphohydrolase/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/surgery ; Prostatic Neoplasms/therapy ; Sarcoma/immunology ; Sarcoma/pathology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Tumor Necrosis Factor Ligand Superfamily Member 14/biosynthesis ; Tumor Necrosis Factor Ligand Superfamily Member 14/immunology
Chemical Substances	Androgens ; Cancer Vaccines ; Tnfsf14 protein, mouse ; Tumor Necrosis Factor Ligand Superfamily Member 14 ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67)
Language	English
Publishing date	2010-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-09-2490
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Article ; Online: Risk Factors Associated With 30-day Readmissions After Instrumented Spine Surgery in 14,939 Patients: 30-day readmissions after instrumented spine surgery.

Akins, Paul T / Harris, Jessica / Alvarez, Julie L / Chen, Yuexin / Paxton, Elizabeth W / Bernbeck, Johannes / Guppy, Kern H

Spine

2015 Volume 40, Issue 13, Page(s) 1022–1032

Abstract: Study design: A retrospective review of instrumented spine registry from an integrated US healthcare system.: Objective: Investigate the 30-day readmission rate and risk factors after instrumented spine surgery.: Summary of background data: ... ...

Abstract	Study design: A retrospective review of instrumented spine registry from an integrated US healthcare system. Objective: Investigate the 30-day readmission rate and risk factors after instrumented spine surgery. Summary of background data: Published readmission rates range from 2% to over 20%. We were interested in learning which patients were at greatest risk, when did readmissions occur, and why. Method: 30-day readmission rates were determined for 14,939 patients after an index spine procedure between 1/2009 and 3/2013. Data were analyzed with descriptive statistics, univariate, and multivariate logistic regression analysis. Result: The average age of the cohort was 59 (SD = 13.4) and 52% were female. The 30-day readmission rate was 5.5% (821/14,939). The temporal pattern for readmission was: 17% (140) at week 1, 48% (394) at week 2, 72% (591) at week 3, and 100% (821) at week 4. The leading causes were wound complications (infection, hematoma, dehiscence, seroma), sepsis, pain management, pneumonia, and pulmonary emboli/deep venous thrombosis. In a multivariate model, readmission risk factors were: malignancy (OR 2.99, 95% CI: 1.56, 5.73), operative time more than 400 minutes (OR 2.59, 95% CI: 1.66, 4.02), operative time 300-399 minutes (OR 2.33, 95% CI: 1.54-3.52), hospital stay 6-10 days (OR 2.03, 95% CI: 1.31-3.14), hospital stay more than 10 days (OR 1.85, 95% CI: 1.1, -3.08), surgical complications (OR 1.67, 95% CI: 1.18, 2.36), operative time 200-299 (OR 1.52, 95% CI: 1.04, 2.22), depression (OR 1.48, 95% CI: 1.14, 1.93), rheumatoid arthritis (OR 1.45, 95% CI: 1.05, 2.01), deficiency anemia (OR 1.30, 95% CI: 1.05, 1.61), and hypothyroidism (OR 1.29, 95% CI: 1.01, 1.64). Conclusion: Surgical complications (dural tear, deep infections, superficial infections, epidural hematoma), malignancy, lengthy operative times, and lengthy initial hospitalizations are all risk factors for 30-day readmission. These findings should be considered during preoperative assessment and surgical planning. Level of evidence: 3.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Female ; Health Maintenance Organizations ; Humans ; Length of Stay ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Operative Time ; Orthopedic Procedures/adverse effects ; Orthopedic Procedures/instrumentation ; Patient Readmission ; Postoperative Complications/diagnosis ; Postoperative Complications/surgery ; Prosthesis Design ; Registries ; Reoperation ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Spine/physiopathology ; Spine/surgery ; Time Factors ; Treatment Outcome ; United States ; Young Adult
Language	English
Publishing date	2015-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	752024-4
ISSN	1528-1159 ; 0362-2436
ISSN (online)	1528-1159
ISSN	0362-2436
DOI	10.1097/BRS.0000000000000916
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Article: Is coral richness related to community resistance to and recovery from disturbance?

Zhang, Stacy Y / Speare, Kelly E / Long, Zachary T / McKeever, Kimberly A / Gyoerkoe, Megan / Ramus, Aaron P / Mohorn, Zach / Akins, Kelsey L / Hambridge, Sarah M / Graham, Nicholas A J / Nash, Kirsty L / Selig, Elizabeth R / Bruno, John F

PeerJ

2014 Volume 2, Page(s) e308

Abstract: More diverse communities are thought to be more stable-the diversity-stability hypothesis-due to increased resistance to and recovery from disturbances. For example, high diversity can make the presence of resilient or fast growing species and key ... ...

Abstract	More diverse communities are thought to be more stable-the diversity-stability hypothesis-due to increased resistance to and recovery from disturbances. For example, high diversity can make the presence of resilient or fast growing species and key facilitations among species more likely. How natural, geographic biodiversity patterns and changes in biodiversity due to human activities mediate community-level disturbance dynamics is largely unknown, especially in diverse systems. For example, few studies have explored the role of diversity in tropical marine communities, especially at large scales. We tested the diversity-stability hypothesis by asking whether coral richness is related to resistance to and recovery from disturbances including storms, predator outbreaks, and coral bleaching on tropical coral reefs. We synthesized the results of 41 field studies conducted on 82 reefs, documenting changes in coral cover due to disturbance, across a global gradient of coral richness. Our results indicate that coral reefs in more species-rich regions were marginally less resistant to disturbance and did not recover more quickly. Coral community resistance was also highly dependent on pre-disturbance coral cover, probably due in part to the sensitivity of fast-growing and often dominant plating acroporid corals to disturbance. Our results suggest that coral communities in biodiverse regions, such as the western Pacific, may not be more resistant and resilient to natural and anthropogenic disturbances. Further analyses controlling for disturbance intensity and other drivers of coral loss and recovery could improve our understanding of the influence of diversity on community stability in coral reef ecosystems.
Language	English
Publishing date	2014-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.308
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Article ; Online: Is coral richness related to community resistance to and recovery from disturbance?

Stacy Y. Zhang / Kelly E. Speare / Zachary T. Long / Kimberly A. McKeever / Megan Gyoerkoe / Aaron P. Ramus / Zach Mohorn / Kelsey L. Akins / Sarah M. Hambridge / Nicholas A.J. Graham / Kirsty L. Nash / Elizabeth R. Selig / John F. Bruno

PeerJ, Vol 2, p e

2014 Volume 308

Abstract: More diverse communities are thought to be more stable—the diversity–stability hypothesis—due to increased resistance to and recovery from disturbances. For example, high diversity can make the presence of resilient or fast growing species and key ... ...

Abstract	More diverse communities are thought to be more stable—the diversity–stability hypothesis—due to increased resistance to and recovery from disturbances. For example, high diversity can make the presence of resilient or fast growing species and key facilitations among species more likely. How natural, geographic biodiversity patterns and changes in biodiversity due to human activities mediate community-level disturbance dynamics is largely unknown, especially in diverse systems. For example, few studies have explored the role of diversity in tropical marine communities, especially at large scales. We tested the diversity–stability hypothesis by asking whether coral richness is related to resistance to and recovery from disturbances including storms, predator outbreaks, and coral bleaching on tropical coral reefs. We synthesized the results of 41 field studies conducted on 82 reefs, documenting changes in coral cover due to disturbance, across a global gradient of coral richness. Our results indicate that coral reefs in more species-rich regions were marginally less resistant to disturbance and did not recover more quickly. Coral community resistance was also highly dependent on pre-disturbance coral cover, probably due in part to the sensitivity of fast-growing and often dominant plating acroporid corals to disturbance. Our results suggest that coral communities in biodiverse regions, such as the western Pacific, may not be more resistant and resilient to natural and anthropogenic disturbances. Further analyses controlling for disturbance intensity and other drivers of coral loss and recovery could improve our understanding of the influence of diversity on community stability in coral reef ecosystems.
Keywords	Biodiveristy ; Resilience ; Stability ; Coral reef ; Disturbance ; Recovery ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	590
Language	English
Publishing date	2014-03-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Single and multiple congenic strains for hydrocephalus in the H-Tx rat.

Jones, Hazel C / Chen, Gin-Fu / Yehia, Baligh R / Carter, Barbara J / Akins, Elizabeth J / Wolpin, Logan C

Mammalian genome : official journal of the International Mammalian Genome Society

2005 Volume 16, Issue 4, Page(s) 251–261

Abstract: The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance. Previously, quantitative trait locus mapping using a backcross with Fischer F344 rats demonstrated genetic loci significantly linked to hydrocephalus on Chromosomes 10, 11, ... ...

Abstract	The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance. Previously, quantitative trait locus mapping using a backcross with Fischer F344 rats demonstrated genetic loci significantly linked to hydrocephalus on Chromosomes 10, 11, and 17. Hydrocephalus was preferentially associated with heterozygous alleles on Chrs 10 and 11 and with homozygous alleles on Chr 17. This study aimed to determine the phenotypic contribution of each locus by constructing single and multiple congenic strains. Single congenic rats were constructed using Fischer F344 as the recipient strain and a marker-assisted protocol. The homozygous strains were maintained for eight generations and the brains examined for dilated ventricles indicative for hydrocephalus. No congenic rats had severe (overt) hydrocephalus. A few pups and a significant number of adults had mild disease. The incidence was significantly higher in the C10 and C17 congenic strains than in the nonhydrocephalic F344 strain. Breeding to F344 to make F.H-Tx C10 or C11 rats heterozygous for the hydrocephalus locus failed to produce progeny with severe disease. Both bicongenic and tricongenic rats of different genotype combinations were constructed by crossing congenic rats. None had severe disease but the frequency of mild hydrocephalus in adults was similar to congenic rats and significantly higher than in the F344 strain. Rats with severe hydrocephalus were recovered in low numbers when single congenic or bicongenic rats were crossed with the parental H-Tx strain. It is concluded that the genetic and epigenetic factors contributing to severe hydrocephalus in the H-Tx strain are more complex than originally anticipated.
MeSH term(s)	Animals ; Brain/pathology ; Chromosome Mapping ; Chromosomes, Mammalian/genetics ; Crosses, Genetic ; Disease Models, Animal ; Electrophoresis, Agar Gel ; Genetic Markers/genetics ; Hydrocephalus/genetics ; Hydrocephalus/pathology ; Phenotype ; Rats ; Rats, Inbred Strains ; Species Specificity
Chemical Substances	Genetic Markers
Language	English
Publishing date	2005-04
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1058547-3
ISSN	1432-1777 ; 0938-8990
ISSN (online)	1432-1777
ISSN	0938-8990
DOI	10.1007/s00335-004-2390-4
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