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Article: A Case of Metastatic CNS Melanoma of Unknown Primary Presenting with Seizures.

Nguyen, Viva / Aboulenain, Samar / Mohammed, Shawn / Perez Parra, Sahyli

2022 Volume 2022, Page(s) 3099750

Abstract: Seizures are a common occurrence. The goal of evaluating a seizure is to identify the etiology and to determine the likelihood of recurrence as well as guide management. We present a unique presentation of a 47-year-old female that presented with late ... ...

Abstract	Seizures are a common occurrence. The goal of evaluating a seizure is to identify the etiology and to determine the likelihood of recurrence as well as guide management. We present a unique presentation of a 47-year-old female that presented with late onset seizures admitted due to status epilepticus. Brain magnetic resonance indicated diffuse supratentorial hemorrhagic lesions. Neurological workup including brain vessel imaging, CT chest, abdomen, and pelvis as well as CSF and serological workup for vasculitis failed to demonstrate the cause of her brain lesions. Ultimately, a brain biopsy showed metastatic melanoma of unknown primary origin.
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Case Reports
ZDB-ID	2502642-2
ISSN	1687-9635 ; 1687-9627
ISSN (online)	1687-9635
ISSN	1687-9627
DOI	10.1155/2022/3099750
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Article ; Online: HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products

Eschbach, Jenna E / Puray-Chavez, Maritza / Mohammed, Shawn / Wang, Qiankun / Xia, Ming / Huang, Lin-Chen / Shan, Liang / Kutluay, Sebla B

mBio

2024 , Page(s) e0034824

Abstract: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune ... ...

Abstract	A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization Importance: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00348-24
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Article: A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.

Puray-Chavez, Maritza / LaPak, Kyle M / Jasuja, Ria / Pan, Jiehong / Xu, Jian / Eschbach, Jenna E / Mohammed, Shawn / Lawson, Dana Q / Wang, Qibo / Brody, Steven L / Major, Michael B / Goldfarb, Dennis / Kutluay, Sebla B

bioRxiv : the preprint server for biology

2024

Abstract: Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high ... ...

Abstract	Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2 replication at a post-entry step. Pharmacological inhibition of JAK1/2, depletion of the IFN-α receptor and cGAS-STING pathway effectors substantially increased SARS-CoV-2 replication in these cell models. While depletion of cGAS or STING was sufficient to reduce the preexisting levels of IFN-stimulated genes (ISGs), SARS-CoV-2 infection in STING knockout cells independently induced ISG expression. Remarkably, SARS-CoV-2-induced ISG expression in STING knockout cell as well as in primary human airway cultures was limited to uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway, but not viral sensing or IFN production, in productively infected cells. Of note, SARS-CoV-2-infected primary human airway cells also displayed markedly lower levels of STING expression, raising the possibility that SARS-CoV-2 can target STING expression or preferentially infect cells that express low levels of STING. Finally, ectopic ACE2 overexpression overcame the IFN-mediated blocks, suggesting the ability of SARS-CoV-2 to overcome these possibly saturable blocks to infection. Our study highlights that in addition to viral receptors, basal activation of the cGAS-STING pathway and innate immune defenses may contribute to defining SARS-CoV-2 cellular tropism.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.07.574522
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Article ; Online: A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models

Puray-Chavez, Maritza / LaPak, Kyle M. / Jasuja, Ria / Pan, Jiehong / Xu, Jian / Eschbach, Jenna E. / Mohammed, Shawn / Lawson, Dana Q. / Wang, Qibo / Brody, Steven L. / Major, Michael B. / Goldfarb, Dennis / Kutluay, Sebla B.

bioRxiv

Abstract	Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2 replication at a post-entry step. Pharmacological inhibition of JAK1/2, depletion of the IFN-alpha; receptor and cGAS-STING pathway effectors substantially increased SARS-CoV-2 replication in these cell models. While depletion of cGAS or STING was sufficient to reduce the preexisting levels of IFN-stimulated genes (ISGs), SARS-CoV-2 infection in STING knockout cells independently induced ISG expression. Remarkably, SARS-CoV-2-induced ISG expression in STING knockout cell as well as in primary human airway cultures was limited to uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway, but not viral sensing or IFN production, in productively infected cells. Of note, SARS-CoV-2-infected primary human airway cells also displayed markedly lower levels of STING expression, raising the possibility that SARS-CoV-2 can target STING expression or preferentially infect cells that express low levels of STING. Finally, ectopic ACE2 overexpression overcame the IFN-mediated blocks, suggesting the ability of SARS-CoV-2 to overcome these possibly saturable blocks to infection. Our study highlights that in addition to viral receptors, basal activation of the cGAS-STING pathway and innate immune defenses may contribute to defining SARS-CoV-2 cellular tropism.
Keywords	covid19
Language	English
Publishing date	2024-01-08
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.07.574522
Database	COVID19

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Article ; Online: Timing of elimination of hepatitis C virus in Canada's provinces.

Feld, Jordan J / Klein, Marina B / Rahal, Yasmine / Lee, Samuel S / Mohammed, Shawn / King, Alexandra / Smyth, Daniel / Gonzalez, Yuri Sanchez / Nugent, Arlene / Janjua, Naveed Z

Canadian liver journal

2022 Volume 5, Issue 4, Page(s) 493–506

Abstract: BACKGROUND: ...

Abstract	BACKGROUND:
Language	English
Publishing date	2022-11-07
Publishing country	Canada
Document type	Journal Article
ISSN	2561-4444
ISSN (online)	2561-4444
DOI	10.3138/canlivj-2022-0003
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Article ; Online: Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans.

Hughes, Kiley / Shah, Ashka / Bai, Xiaofei / Adams, Jessica / Bauer, Rosemary / Jackson, Janelle / Harris, Emily / Ficca, Alyson / Freebairn, Ploy / Mohammed, Shawn / Fernández, Eliana M / Bainbridge, Chance / Brocco, Marcela / Stein, Wolfgang / Vidal-Gadea, Andrés G

G3 (Bethesda, Md.)

2022 Volume 12, Issue 3

Abstract: Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique ... ...

Abstract	Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have 12 isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive green fluorescent protein (GFP) expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Eating ; Ion Channels/metabolism ; Mechanoreceptors/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism
Chemical Substances	Caenorhabditis elegans Proteins ; Ion Channels ; Protein Isoforms
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkab429
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Article ; Online: Capsid Lattice Destabilization Leads to Premature Loss of the Viral Genome and Integrase Enzyme during HIV-1 Infection.

Eschbach, Jenna E / Elliott, Jennifer L / Li, Wen / Zadrozny, Kaneil K / Davis, Keanu / Mohammed, Shawn J / Lawson, Dana Q / Pornillos, Owen / Engelman, Alan N / Kutluay, Sebla B

Journal of virology

2020 Volume 95, Issue 2

Abstract: The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral ribonucleoprotein complex (vRNP) consisting of a dimeric viral genome and associated proteins, together constituting the viral core. Upon entry ... ...

Abstract	The human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein forms a conical lattice around the viral ribonucleoprotein complex (vRNP) consisting of a dimeric viral genome and associated proteins, together constituting the viral core. Upon entry into target cells, the viral core undergoes a process termed uncoating, during which CA molecules are shed from the lattice. Although the timing and degree of uncoating are important for reverse transcription and integration, the molecular basis of this phenomenon remains unclear. Using complementary approaches, we assessed the impact of core destabilization on the intrinsic stability of the CA lattice
MeSH term(s)	Animals ; Capsid/metabolism ; Capsid Proteins/genetics ; Capsid Proteins/metabolism ; Cell Line ; Cricetinae ; Genome, Viral ; HIV Integrase/metabolism ; HIV-1/physiology ; Humans ; Mutation ; RNA, Viral/metabolism ; Reverse Transcription ; Viral Core Proteins/metabolism ; Virion/genetics ; Virion/metabolism ; Virus Uncoating
Chemical Substances	Capsid Proteins ; RNA, Viral ; Viral Core Proteins ; HIV Integrase (EC 2.7.7.-)
Language	English
Publishing date	2020-12-22
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.00984-20
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Article: Induced sputum in cystic fibrosis: within-week reproducibility of inflammatory markers.

Smountas, Argyrios A / Lands, Larry C / Mohammed, Shawn R / Grey, Vijaylaxmi

Clinical biochemistry

2004 Volume 37, Issue 11, Page(s) 1031–1036

Abstract: Unlabelled: Analysis of induced sputum has provided significant insight into the inflammatory response in chronic respiratory diseases such as asthma. The thick, tenacious nature of cystic fibrosis (CF) sputum presents certain challenges to such ... ...

Abstract	Unlabelled: Analysis of induced sputum has provided significant insight into the inflammatory response in chronic respiratory diseases such as asthma. The thick, tenacious nature of cystic fibrosis (CF) sputum presents certain challenges to such evaluation. We describe the development of a methodology to assess CF sputum, and the within-week reproducibility (to limit the possibility of any change in clinical status) of cellular and inflammatory markers. Methods: Seventeen young adults [9 males, 8 females, mean age 24 (5), median (quartile range) years, percentage of predicted FEV(1) = 64.0 (18.0%)] with CF underwent sputum inductions on the Monday and Thursday of the same week. Patients were pretreated with 400 microg salbutamol and subsequently inhaled 5% saline via a breath enhanced nebulizer. Every 3-min nebulization was interrupted to allow for expectoration of sputum into a polypropylene pot. Sputum samples were dispersed with a solution of dithiothreitol (DTT) and deoxyribonuclease to allow for analysis of total cell count (TCC) and percentage neutrophils (%Neut). Measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and neutrophil elastase was performed on samples dispersed with DTT alone. Results: There were no significant differences between the measurements taken in the same week. Values for Day 1 versus Day 2 were as follows: TCC 20.8 (6.4) vs. 17.6 (2.5) x 10(6) cells/ml; %Neut: 94.1 (0.0) vs. 95.4 (0.5) %; TNF-alpha 7.5 (26.0) vs. 21.0 (44.0) pg/ml; IL-8 610.0 (422.0) vs. 524.0 (587.0) ng/ml and neutrophil elastase 110.0 (19.75) vs. 49.75 (60.75) microM. High intraclass correlation coefficients (ICC) for TCC, %Neut, TNF-alpha IL-8 and neutrophil elastase were found (ICC = 0.76, 0.82, 0.93, 0.82, 0.74, respectively). Conclusions: The method developed here for the analysis of CF sputum shows good reproducibility and can be used to evaluate therapeutic interventions in patients with cystic fibrosis.
MeSH term(s)	Adult ; Biomarkers/analysis ; Cystic Fibrosis/enzymology ; Cystic Fibrosis/immunology ; Cystic Fibrosis/pathology ; Female ; Humans ; Inflammation/metabolism ; Male ; Reproducibility of Results ; Sputum/cytology ; Sputum/enzymology ; Sputum/immunology
Chemical Substances	Biomarkers
Language	English
Publishing date	2004-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	0009-9120
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2004.07.008
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Article: Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein.

Grey, Vijaylaxmi / Mohammed, Shawn R / Smountas, Argyrios A / Bahlool, Rasha / Lands, Larry C

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2003 Volume 2, Issue 4, Page(s) 195–198

Abstract: Background: The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the ... ...

Abstract	Background: The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the lung. This increased demand for glutathione (GSH) in cystic fibrosis may be limiting if nutritional status is compromised. We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein. Methods: Twenty-one patients who were in stable condition were randomly assigned to take a whey protein isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were compared with nutritional status and lung parameters. Results: At baseline there were no significant differences in age, height, weight, percent ideal body weight or percent body fat. Lymphocyte GSH was similar in the two groups. After supplementation, we observed a 46.6% increase from baseline (P < 0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. Conclusion: The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress in the lung in cystic fibrosis.
MeSH term(s)	Adolescent ; Adult ; Cystic Fibrosis/diagnosis ; Cystic Fibrosis/therapy ; Dietary Supplements ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Glutathione/drug effects ; Glutathione/metabolism ; Humans ; Male ; Milk Proteins/therapeutic use ; Probability ; Reference Values ; Respiratory Function Tests ; Severity of Illness Index ; Treatment Outcome ; Whey Proteins
Chemical Substances	Milk Proteins ; Whey Proteins ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2003-12
Publishing country	Netherlands
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2084724-5
ISSN	1569-1993
ISSN	1569-1993
DOI	10.1016/S1569-1993(03)00097-3
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Zs.A 6028: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Role of heme oxygenases in sepsis-induced diaphragmatic contractile dysfunction and oxidative stress.

Barreiro, Esther / Comtois, Alain S / Mohammed, Shawn / Lands, Larry C / Hussain, Sabah N A

American journal of physiology. Lung cellular and molecular physiology

2002 Volume 283, Issue 2, Page(s) L476–84

Abstract: Heme oxygenases (HOs), essential enzymes for heme metabolism, play an important role in the defense against oxidative stress. In this study, we evaluated the expression and functional significance of HO-1 and HO-2 in the ventilatory muscles of normal ... ...

Abstract	Heme oxygenases (HOs), essential enzymes for heme metabolism, play an important role in the defense against oxidative stress. In this study, we evaluated the expression and functional significance of HO-1 and HO-2 in the ventilatory muscles of normal rats and rats injected with bacterial lipopolysaccharide (LPS). Both HO-1 and HO-2 proteins were detected inside ventilatory and limb muscle fibers of normal rats. Diaphragmatic HO-1 and HO-2 expressions rose significantly within 1 and 12 h of LPS injection, respectively. Inhibition of the activity of inducible nitric oxide synthase (iNOS) in rats and absence of this isoform in iNOS(-/-) mice did alter sepsis-induced regulation of muscle HOs. Systemic inhibition of HO activity with chromium mesoporphyrin IX enhanced muscle protein oxidation and hydroxynonenal formation in both normal and septic rats. Moreover, in vitro diaphragmatic force generation declined substantially in response to HO inhibition both in normal and septic rats. We conclude that both HO-1 and HO-2 proteins play an important role in the regulation of muscle contractility and in the defense against sepsis-induced oxidative stress.
MeSH term(s)	Animals ; Diaphragm/physiopathology ; Escherichia coli Infections/physiopathology ; Heme Oxygenase (Decyclizing)/metabolism ; Heme Oxygenase (Decyclizing)/physiology ; Heme Oxygenase-1 ; Male ; Membrane Proteins ; Mice ; Mice, Knockout/genetics ; Muscle Contraction ; Muscle, Skeletal/enzymology ; Nitric Oxide Synthase/genetics ; Nitric Oxide Synthase/physiology ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution
Chemical Substances	Membrane Proteins ; Nitric Oxide Synthase (EC 1.14.13.39) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39) ; Nos2 protein, rat (EC 1.14.13.39) ; Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Hmox1 protein, mouse (EC 1.14.14.18) ; heme oxygenase-2 (EC 1.14.14.18)
Language	English
Publishing date	2002-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00495.2001
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