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Article ; Online: Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model.

Cohen-Nowak, Adam J / Cohen, Alexa J / Correia, Emily D / Portocarrero, Carla P / South, Andrew P / Nikbakht, Neda

2022 Volume 31, Issue 7, Page(s) 1083–1088

Abstract: Patients with epidermolysis bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and ... ...

Abstract	Patients with epidermolysis bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumour growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408 significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumour growth in mice without cutaneous or systemic toxicity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.
MeSH term(s)	Animals ; Carcinoma, Squamous Cell/metabolism ; Epidermolysis Bullosa/pathology ; Epidermolysis Bullosa Dystrophica ; Humans ; Inflammation ; Mice ; Severity of Illness Index ; Skin Neoplasms/metabolism ; Triterpenes/pharmacology ; Triterpenes/therapeutic use
Chemical Substances	Triterpenes ; omaveloxolone (G69Z98951Q)
Language	English
Publishing date	2022-03-31
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1130936-2
ISSN	1600-0625 ; 0906-6705
ISSN (online)	1600-0625
ISSN	0906-6705
DOI	10.1111/exd.14564
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.

Nevler, Avinoam / Brown, Samantha Z / Nauheim, David / Portocarrero, Carla / Rodeck, Ulrich / Bassig, Jonathan / Schultz, Christopher W / McCarthy, Grace A / Lavu, Harish / Yeo, Theresa P / Yeo, Charles J / Brody, Jonathan R

Journal of the American College of Surgeons

2020 Volume 230, Issue 4, Page(s) 659–667

Abstract: Background: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO: Study design: Two PDAC cell lines were exposed to normocapnic (5% CO!## ...

Abstract	Background: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO Study design: Two PDAC cell lines were exposed to normocapnic (5% CO Results: Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p < 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67). Conclusions: PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.
MeSH term(s)	Aged ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/etiology ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Cell Proliferation ; Chronic Disease ; Disease Progression ; Drug Resistance, Neoplasm ; Female ; Humans ; Hypercapnia/complications ; Hypercapnia/etiology ; Lung Diseases, Obstructive/complications ; Male ; Middle Aged ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/etiology ; Pancreatic Neoplasms/pathology ; Retrospective Studies
Language	English
Publishing date	2020-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1181115-8
ISSN	1879-1190 ; 1072-7515
ISSN (online)	1879-1190
ISSN	1072-7515
DOI	10.1016/j.jamcollsurg.2019.12.033
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Article ; Online: T-bet Is Required for the Rapid Clearance of Attenuated Rabies Virus from Central Nervous System Tissue.

Lebrun, Aurore / Portocarrero, Carla / Kean, Rhonda B / Barkhouse, Darryll A / Faber, Milosz / Hooper, D Craig

Journal of immunology (Baltimore, Md. : 1950)

2015 Volume 195, Issue 9, Page(s) 4358–4368

Abstract: Much of our understanding of CNS immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from ...

Abstract	Much of our understanding of CNS immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the CNS transaxonally, thereby bypassing the blood-brain barrier (BBB), and are cleared without neutrophil or monocyte infiltration. To better understand the role of CD4 T cell subsets in the clearance of the virus from CNS tissues, we examined the development of antiviral immunity in wild-type (WT) and T-bet knockout mice (T-bet(-/-)), which lack Th1 cells. Early control of RABV replication in the CNS tissues of WT mice is associated with the production of IFN-γ, with antiviral effects likely mediated through the enhanced expression of type I IFNs. Of interest, IFN-α and -γ are overexpressed in the infected T-bet(-/-) by comparison with WT CNS tissues, and the initial control of RABV infection is similar. Ultimately, attenuated RABV are cleared from the CNS tissues of WT mice by Ab locally produced by the activities of infiltrating T and B cells. Although T and B cell infiltration into the CNS of infected T-bet(-/-) mice is comparable, their activities are not, the consequence being delayed, low-level Ab production and prolonged RABV replication. More importantly, neither T-bet(-/-) mice immunized with an attenuated virus, nor WT mice with Th2 RABV-specific immunity induced by immunization with inactivated virus, are protected in the long term against challenge with a pathogenic RABV.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; Antibodies, Viral/metabolism ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; B-Lymphocytes/virology ; Blood-Brain Barrier/immunology ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/virology ; Central Nervous System/immunology ; Central Nervous System/metabolism ; Central Nervous System/virology ; Flow Cytometry ; Gene Expression/immunology ; Interferon-alpha/genetics ; Interferon-alpha/immunology ; Interferon-alpha/metabolism ; Interferon-beta/genetics ; Interferon-beta/immunology ; Interferon-beta/metabolism ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Fluorescence ; Rabies/immunology ; Rabies/metabolism ; Rabies/virology ; Rabies Vaccines/immunology ; Rabies Vaccines/metabolism ; Rabies virus/immunology ; Rabies virus/metabolism ; Rabies virus/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; T-Box Domain Proteins/deficiency ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/virology ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th1 Cells/virology ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Th2 Cells/virology ; Time Factors ; Vaccines, Attenuated/immunology ; Vaccines, Attenuated/metabolism
Chemical Substances	Antibodies, Viral ; Interferon-alpha ; Rabies Vaccines ; T-Box Domain Proteins ; T-box transcription factor TBX21 ; Vaccines, Attenuated ; Interferon-beta (77238-31-4) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2015-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1501274
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Article ; Online: Limited brain metabolism changes differentiate between the progression and clearance of rabies virus.

Schutsky, Keith / Portocarrero, Carla / Hooper, D Craig / Dietzschold, Bernhard / Faber, Milosz

PloS one

2014 Volume 9, Issue 4, Page(s) e87180

Abstract: Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue ... ...

Abstract	Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of carnitine and several acylcarnitines, suggesting that these compounds are neuroprotective. The most striking change seen in mock-treated RABV-infected mice was a dramatic increase in brain and serum corticosterone levels, with the later becoming elevated before clinical signs or loss of body weight occurred. We speculate that the rise in corticosterone is part of a strategy of RABV to block the induction of immune responses that would otherwise interfere with its spread. In support of this concept, we show that pharmacological intervention to inhibit corticosterone biosynthesis, in the absence of vaccine treatment, significantly reduces the pathogenicity of RABV. Our results suggest that widespread metabolic changes, including hypothalamic-pituitary-adrenal axis activation, contribute to the pathogenesis of RABV and that preventing these alterations early in infection with PET or pharmacological blockade helps protect brain homeostasis, thereby reducing disease mortality.
MeSH term(s)	3-Hydroxybutyric Acid/metabolism ; Adaptive Immunity ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Brain/metabolism ; Brain/virology ; Carnitine/analogs & derivatives ; Carnitine/metabolism ; Corticosterone/blood ; Disease Progression ; Energy Metabolism ; Female ; Gene Expression ; Host-Pathogen Interactions ; Hypothalamo-Hypophyseal System/metabolism ; Hypothalamo-Hypophyseal System/virology ; Mice ; Pituitary-Adrenal System/metabolism ; Pituitary-Adrenal System/virology ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Rabies/drug therapy ; Rabies/immunology ; Rabies/metabolism ; Rabies virus/immunology ; Viral Load ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Viral Vaccines/therapeutic use
Chemical Substances	Antiviral Agents ; Pyridines ; Viral Proteins ; Viral Vaccines ; acylcarnitine ; metapyrone (17286-92-9) ; Carnitine (S7UI8SM58A) ; 3-Hydroxybutyric Acid (TZP1275679) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2014-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0087180
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Article: Immunogenic properties of plant-derived recombinant smallpox vaccine candidate pB5.

Portocarrero, Carla / Markley, Karen / Koprowski, Hilary / Spitsin, Sergei / Golovkin, Maxim

Vaccine

2008 Volume 26, Issue 43, Page(s) 5535–5540

Abstract: The extracellular virion membrane protein B5 is a potent inducer of immune responses capable of protecting mice and primates against poxvirus infections. Here, we examined the antibody response induced in mice immunized intramuscularly (i.m.) or ... ...

Abstract	The extracellular virion membrane protein B5 is a potent inducer of immune responses capable of protecting mice and primates against poxvirus infections. Here, we examined the antibody response induced in mice immunized intramuscularly (i.m.) or intranasally (i.n.) with plant-derived B5 (pB5) accompanied or not with plant total soluble protein (TSP) at various concentrations. Increasing amounts of TSP inhibited the pB5-specific response in both i.m.- and i.n.-immunized mice, with more dramatic effects in the latter. pB5 administered to mucosal surfaces induced specific IgG and IgA responses, whereas i.m. immunization produced high serum IgG titers and no IgA. A 6-fold increase in pB5 dosage administered i.n. led to an antibody response comparable to that obtained by i.m. injection. Our study addresses the quality/quantity issues of the pB5 subunit preparation and demonstrates the feasibility of mucosal administration of plant-derived smallpox subunit vaccine in obtaining a potent immune response. Overall, this work points to the practicability of needle-free mucosal administration of such vaccines in light of purity, dosage and adjuvant formulation.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Administration, Intranasal ; Animals ; Antibodies, Viral/analysis ; Antibodies, Viral/biosynthesis ; Blotting, Western ; Bronchoalveolar Lavage Fluid/cytology ; Cholera Toxin/pharmacology ; Enzyme-Linked Immunosorbent Assay ; Feces/chemistry ; Female ; Immunization ; Immunoglobulin A/analysis ; Immunoglobulin A/biosynthesis ; Immunoglobulin G/analysis ; Immunoglobulin G/biosynthesis ; Mice ; Mice, Inbred BALB C ; Smallpox Vaccine/biosynthesis ; Smallpox Vaccine/immunology ; Smallpox Vaccine/isolation & purification ; Nicotiana/metabolism ; Viral Matrix Proteins/biosynthesis ; Viral Matrix Proteins/immunology ; Viral Matrix Proteins/isolation & purification
Chemical Substances	Adjuvants, Immunologic ; Antibodies, Viral ; B5 protein, vaccinia virus ; Immunoglobulin A ; Immunoglobulin G ; Smallpox Vaccine ; Viral Matrix Proteins ; Cholera Toxin (9012-63-9)
Language	English
Publishing date	2008-08-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2008.07.063
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Zs.A 1930: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 458: Show issues

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Article ; Online: Postexposure treatment with the live-attenuated rabies virus (RV) vaccine TriGAS triggers the clearance of wild-type RV from the Central Nervous System (CNS) through the rapid induction of genes relevant to adaptive immunity in CNS tissues.

Li, Jianwei / Ertel, Adam / Portocarrero, Carla / Barkhouse, Darryll A / Dietzschold, Bernhard / Hooper, D Craig / Faber, Milosz

Journal of virology

2012 Volume 86, Issue 6, Page(s) 3200–3210

Abstract: Postexposure treatment (PET) of wild-type rabies virus (RV)-infected mice with a live-attenuated triple-glycoprotein RV variant (TriGAS) promotes survival but does not prevent the pathogenic RV from invading and replicating in the brain. Successful PET ... ...

Abstract	Postexposure treatment (PET) of wild-type rabies virus (RV)-infected mice with a live-attenuated triple-glycoprotein RV variant (TriGAS) promotes survival but does not prevent the pathogenic RV from invading and replicating in the brain. Successful PET is associated with the induction of a robust virus-neutralizing antibody response and clearance of the wild-type RV from brain tissues. Comparison of the transcriptomes of normal mouse brain with those of wild-type-RV-infected mice that had received either mock or TriGAS PET treatment revealed that many of the host genes activated in the mock-treated mice represent type I interferon (IFN) response genes. This indicates that RV infection induces an early type I IFN response that is unable to control the infection. In contrast, most of the activated genes in the brain of the RV-infected, TriGAS-treated mouse play a role in adaptive immunity, including the regulation of T cell activation, T cell differentiation, and the regulation of lymphocyte and mononuclear cell proliferation. These findings were confirmed by quantitative PCR (qPCR) array studies, which showed that 3 genes in particular, encoding chemokine ligand 3 (Ccl3), natural killer cell activator 2 (interleukin 12B [IL-12B]), and granzyme A (GzmA), were activated earlier and to a greater extent in the brains of RV-infected mice treated with TriGAS than in the brains of mock-treated mice. The activation of these genes, known to play key roles in the regulation of lymphocyte and mononuclear cell proliferation, is likely an important part of the mechanism by which TriGAS mediates its PET activity.
MeSH term(s)	Adaptive Immunity ; Animals ; Antibodies, Viral/immunology ; Central Nervous System/immunology ; Central Nervous System/virology ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Post-Exposure Prophylaxis ; Rabies/drug therapy ; Rabies/genetics ; Rabies/immunology ; Rabies/prevention & control ; Rabies Vaccines/immunology ; Rabies Vaccines/therapeutic use ; Rabies virus/immunology ; Up-Regulation ; Vaccines, Attenuated/immunology ; Vaccines, Attenuated/therapeutic use
Chemical Substances	Antibodies, Viral ; Rabies Vaccines ; Vaccines, Attenuated
Keywords	covid19
Language	English
Publishing date	2012-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.06699-11
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Zs.A 609: Show issues

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Article: Effect of long-term oral administration of green tea extract on weight gain and glucose tolerance in Zucker diabetic (ZDF) rats.

Janle, Elsa M / Portocarrero, Carla / Zhu, Yongxin / Zhou, Qin

Journal of herbal pharmacotherapy

2005 Volume 5, Issue 3, Page(s) 55–65

Abstract: There have been some claims that green tea reduces weight and lowers blood glucose in diabetes. Intraperitoneal injections of green tea catechins in diabetic rats have shown beneficial effects. To determine if oral administration of green tea would ... ...

Abstract	There have been some claims that green tea reduces weight and lowers blood glucose in diabetes. Intraperitoneal injections of green tea catechins in diabetic rats have shown beneficial effects. To determine if oral administration of green tea would prevent development of diabetes, young Zucker diabetic rats were dosed with green tea extract containing 50-125 mg/kg of Epigallocatechin gallate (EGCG) starting at 7 weeks of age, before the appearance of excessive weight gain and glucose elevation. While there was a trend toward lower weight gain and average daily glucose, there was no statistically significant difference.
MeSH term(s)	Administration, Oral ; Analysis of Variance ; Animals ; Body Weight/drug effects ; Catechin/administration & dosage ; Catechin/analogs & derivatives ; Catechin/pharmacokinetics ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/prevention & control ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Eating/drug effects ; Glucose/metabolism ; Glucose Intolerance/drug therapy ; Hypoglycemic Agents/therapeutic use ; Male ; Plant Extracts/administration & dosage ; Rats ; Rats, Zucker ; Tea
Chemical Substances	Hypoglycemic Agents ; Plant Extracts ; Tea ; Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2005
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2035818-0
ISSN	1522-9106 ; 1522-8940
ISSN (online)	1522-9106
ISSN	1522-8940
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Zs.A 5852: Show issues

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Article ; Online: Akt is required for Stat5 activation and mammary differentiation.

Chen, Chien-Chung / Boxer, Robert B / Stairs, Douglas B / Portocarrero, Carla P / Horton, Rachel H / Alvarez, James V / Birnbaum, Morris J / Chodosh, Lewis A

Breast cancer research : BCR

2010 Volume 12, Issue 5, Page(s) R72

Abstract: Introduction: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been ... ...

Abstract	Introduction: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but not Akt2, exhibit a pronounced metabolic defect during late pregnancy and lactation that results from a failure to upregulate Glut1 as well as several lipid synthetic enzymes. Despite this metabolic defect, however, both Akt1-deficient and Akt2-deficient mice exhibit normal mammary epithelial differentiation and Stat5 activation. Methods: In light of the overlapping functions of Akt family members, we considered the possibility that Akt may play an essential role in regulating mammary epithelial development that is not evident in Akt1-deficient mice due to compensation by other Akt isoforms. To address this possibility, we interbred mice bearing targeted deletions in Akt1 and Akt2 and determined the effect on mammary differentiation during pregnancy and lactation. Results: Deletion of one allele of Akt2 in Akt1-deficient mice resulted in a severe defect in Stat5 activation during late pregnancy that was accompanied by a global failure of terminal mammary epithelial cell differentiation, as manifested by the near-complete loss in production of the three principal components of milk: lactose, lipid, and milk proteins. This defect was due, in part, to a failure of pregnant Akt1(-/-);Akt2(+/-) mice to upregulate the positive regulator of Prlr-Jak-Stat5 signaling, Id2, or to downregulate the negative regulators of Prlr-Jak-Stat5 signaling, caveolin-1 and Socs2. Conclusions: Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Cell Survival ; Female ; Janus Kinases/metabolism ; Lactation ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/metabolism ; Mice ; Mice, Knockout ; Milk Proteins/biosynthesis ; Organ Culture Techniques ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; STAT5 Transcription Factor/metabolism ; Signal Transduction
Chemical Substances	Milk Proteins ; STAT5 Transcription Factor ; Janus Kinases (EC 2.7.10.2) ; Akt1 protein, mouse (EC 2.7.11.1) ; Akt2 protein, mouse (EC 2.7.11.1) ; Akt3 protein, mouse (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2010-09-17
Publishing country	England
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	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/bcr2640
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Zs.A 5494: Show issues

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Article: Early blood-brain barrier permeability in cerebella of PLSJL mice immunized with myelin basic protein.

Spitsin, Sergei / Portocarrero, Carla / Phares, Timothy W / Kean, Rhonda B / Brimer, Christine M / Koprowski, Hilary / Hooper, D Craig

Journal of neuroimmunology

2008 Volume 196, Issue 1-2, Page(s) 8–15

Abstract: The blood-brain barrier (BBB) is dramatically but transiently compromised in the cerebella of myelin basic protein immunized mice at least 1 week prior to the development of the paralytic phase of experimental allergic encephalomyelitis (EAE). Treatment ... ...

Abstract	The blood-brain barrier (BBB) is dramatically but transiently compromised in the cerebella of myelin basic protein immunized mice at least 1 week prior to the development of the paralytic phase of experimental allergic encephalomyelitis (EAE). Treatment of mice with the peroxynitrite-dependent radical scavenger uric acid (UA) during the first week after immunization blocks the early increase in cerebellar BBB permeability and the subsequent development of clinical signs of EAE. These results indicate that the early loss of BBB integrity in the cerebellum is likely to be a necessary step in the development of paralytic EAE.
MeSH term(s)	Animals ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/immunology ; Capillary Permeability/drug effects ; Capillary Permeability/immunology ; Cerebellum/metabolism ; Cerebellum/pathology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/chemically induced ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Encephalomyelitis, Autoimmune, Experimental/physiopathology ; Female ; Fluorescein ; Gene Expression Regulation/drug effects ; Intercellular Adhesion Molecule-1/genetics ; Intercellular Adhesion Molecule-1/metabolism ; Macrophage-1 Antigen/genetics ; Macrophage-1 Antigen/metabolism ; Mice ; Myelin Basic Protein/immunology ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Statistics, Nonparametric ; Time Factors
Chemical Substances	Antigens, CD ; Macrophage-1 Antigen ; Myelin Basic Protein ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2008-04-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2008.02.004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Plant-produced hepatitis B core protein chimera carrying anthrax protective antigen domain-4.

Bandurska, Katarzyna / Brodzik, Robert / Spitsin, Sergei / Kohl, Thomas / Portocarrero, Carla / Smirnov, Yuri / Pogrebnyak, Natalia / Sirko, Agnieszka / Koprowski, Hilary / Golovkin, Maxim

Hybridoma (2005)

2008 Volume 27, Issue 4, Page(s) 241–247

Abstract: The hepatitis B core antigen (HBcAg) can generate a strong immune response and is recognized as an effective carrier for foreign epitopes. The domain-4 epitope of the anthrax protective antigen (PA-D4) plays an essential role in generating protective ... ...

Abstract	The hepatitis B core antigen (HBcAg) can generate a strong immune response and is recognized as an effective carrier for foreign epitopes. The domain-4 epitope of the anthrax protective antigen (PA-D4) plays an essential role in generating protective immunity against virulent Bacillus anthracis. Here we report the successful production of a recombinant protein comprised of the antigenic PA-D4 integrated into the c/e1 loop of HBcAg in transgenic low-alkaloid Nicotiana tabacum. Sera of mice injected with the plant-derived purified HB/PA-D4 protein exhibited significant anti-PA- and anti-HBcAg-specific IgG titers; however, formation of virus-like particles (VLP) was not observed. These data support the feasibility of producing complex protein chimeras in plants.
MeSH term(s)	Animals ; Anthrax Vaccines/biosynthesis ; Anthrax Vaccines/immunology ; Anthrax Vaccines/isolation & purification ; Antigens, Bacterial/biosynthesis ; Antigens, Bacterial/chemistry ; Antigens, Bacterial/immunology ; Bacterial Toxins/biosynthesis ; Bacterial Toxins/chemistry ; Bacterial Toxins/immunology ; Female ; Hepatitis B Core Antigens/biosynthesis ; Hepatitis B Core Antigens/chemistry ; Hepatitis B Core Antigens/immunology ; Mice ; Mice, Inbred BALB C ; Models, Biological ; Plants, Genetically Modified/metabolism ; Plants, Genetically Modified/ultrastructure ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/immunology ; Recombinant Fusion Proteins/isolation & purification ; Nicotiana/genetics ; Nicotiana/metabolism ; Nicotiana/ultrastructure
Chemical Substances	Anthrax Vaccines ; Antigens, Bacterial ; Bacterial Toxins ; Hepatitis B Core Antigens ; Recombinant Fusion Proteins ; anthrax toxin
Language	English
Publishing date	2008-08-14
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	791095-2
ISSN	1557-8348 ; 1554-0014 ; 0272-457X
ISSN (online)	1557-8348
ISSN	1554-0014 ; 0272-457X
DOI	10.1089/hyb.2008.0008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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