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Article: Sepsis Causing Acquired Protein C and Protein S Deficiency.

Kannan, Arun / Chandra, Sweta / Lizcano, Jose / Murphy, Christie

JNMA; journal of the Nepal Medical Association

2014 Volume 52, Issue 193, Page(s) 729–731

Abstract: ... due to protein C deficiency acquired after initial exposure to warfarin. We present a rather unusual ... cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old ... as an acquired cause of protein C deficiency. ...

Abstract	Warfarin Induced Skin Necrosis is a well-known and dreaded complication in patients who is being started on warfarin without adequate bridging with other anticoagulants. The mechanism is thought to be due to protein C deficiency acquired after initial exposure to warfarin. We present a rather unusual cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old lady who has been on chronic warfarin therapy secondary to anti phospholipid syndrome was admitted to the hospital for acute ischemic cerebellar stroke. Warfarin was held due to acute thrombocytopenia. She was discharged after restarting the warfarin. She presented back with septic shock due to pneumonia. She was found to have multiple necrotic areas consistent with skin necrosis. Unfortunately, patient died due to multi organ failure despite goal directed therapy. This case demonstrates the importance of recognizing the sepsis as an acquired cause of protein C deficiency.
MeSH term(s)	Adult ; Anticoagulants/adverse effects ; Antiphospholipid Syndrome/drug therapy ; Cerebellar Diseases/complications ; Female ; Humans ; Necrosis/chemically induced ; Pneumonia/complications ; Protein C Deficiency/etiology ; Protein S Deficiency/etiology ; Shock, Septic/complications ; Skin/pathology ; Stroke/complications ; Warfarin/adverse effects
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2014-01
Publishing country	Nepal
Document type	Case Reports ; Journal Article
ZDB-ID	2209910-4
ISSN	1815-672X ; 0028-2715
ISSN (online)	1815-672X
ISSN	0028-2715
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Article ; Online: GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson’s disease

Lauren M. McIntyre / Francisco Huertas / Alison M. Morse / Rachel Kaletsky / Coleen T. Murphy / Vrinda Kalia / Gary W. Miller / Olexander Moskalenko / Ana Conesa / Danielle E. Mor

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 9

Abstract: Abstract Parkinson’s disease (PD) is a disabling neurodegenerative disorder in which multiple cell ... molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle ... the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new ...

Abstract	Abstract Parkinson’s disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

Salman Sohrabi / Danielle E. Mor / Rachel Kaletsky / William Keyes / Coleen T. Murphy

Communications Biology, Vol 4, Iss 1, Pp 1-

2021 Volume 9

Abstract: ... behavior in C. elegans, which is related to motor control symptoms in Parkinson’s disease. They apply ... for Parkinson’s disease. ...

Abstract	Salman Sohrabi et al. develop an automated, high-throughput assay to study spasm-like curling behavior in C. elegans, which is related to motor control symptoms in Parkinson’s disease. They apply this screening approach to identify four candidate drugs for potential late-in-life interventions for Parkinson’s disease.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Protein C and free protein S in children with sickle cell anemia.

Piccin, Andrea / Murphy, Ciarán / Eakins, Elva / Kinsella, Anthony / McMahon, Corrina / Smith, Owen P / Murphy, William G

Annals of hematology

2012 Volume 91, Issue 10, Page(s) 1669–1671

MeSH term(s)	Adolescent ; Anemia, Sickle Cell/blood ; Anemia, Sickle Cell/diagnosis ; Biomarkers/blood ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Protein C/metabolism ; Protein S/metabolism
Chemical Substances	Biomarkers ; Protein C ; Protein S
Language	English
Publishing date	2012-10
Publishing country	Germany
Document type	Letter
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-012-1447-9
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Article: Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia.

Piccin, Andrea / Murphy, Ciaran / Eakins, Elva / Kunde, Jan / Corvetta, Daisy / Di Pierro, Angela / Negri, Giovanni / Guido, Mazzoleni / Sainati, Laura / Mc Mahon, Corrina / Smith, Owen Patrick / Murphy, William

Journal of extracellular vesicles

2015 Volume 4, Page(s) 28414

Abstract: ... however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C ... PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large ... receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also ...

Abstract	Introduction: Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients. Method: A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. Results: Total MP AV was lower in crisis (1.26×10(6) ml(-1); 0.56-2.44×10(6)) and steady state (1.35×10(6) ml(-1); 0.71-3.0×10(6)) compared to transfusion (4.33×10(6) ml(-1); 1.6-9.2×10(6), p<0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml(-1); interquartile range 0.43-0.62) compared with all other groups: HbAA (0.72 IU ml(-1); 0.66-0.82, p<0.001); HU (0.67 IU ml(-1); 0.58-0.77, p<0.001); steady state (0.63 IU ml(-1); 0.54-0.70, p<0.05) and transfusion (0.60 IU ml(-1); 0.54-0.70, p<0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml(-1); 0.54-0.70) compared with HbAA (0.72 IU ml(-1); 0.66-0.80, p<0.01). PS levels were significantly higher in HbAA (0.85 IU ml(-1); 0.72-0.97) compared with crisis (0.49 IU ml(-1); 0.42-0.64, p<0.001), HU (0.65 IU ml(-1); 0.56-0.74, p<0.01) and transfusion (0.59 IU ml(-1); 0.47-0.71, p<0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml(-1); 0.42-0.64 vs. 0.68 IU ml(-1); 0.58-0.79, p<0.05). There was high correlation (R>0.9, p<0.05) between total numbers of AV-positive MP (MP AV) and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p<0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p<0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p<0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p<0.05) and steady state (0.0%, p<0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p<0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L(-1) (0.31-0.49) versus steady state: 0.27 nmol L(-1) (0.25-0.32; p<0.01) and control: 0.28 nmol L(-1) (0.27-0.31; p<0.01). CT-proET-1 levels were reduced in patients on HU therapy: 43.6 pmol L(-1) (12.6-49.6) versus control: 55.1 pmol L(-1) (45.2-63.9; p<0.05). NO levels were significantly lower in chest crisis (19.3 mmol L(-1) plasma; 10.7-19.9) compared with HU (22.2 mmol L(-1) plasma; 18.3-28.4; p<0.05), and HbSC (30.6 mmol L(-1) plasma; 20.8-39.5; p<0.05) and approach significance when compared with steady state (22.5mmol L(-1) plasma; 16.9-28.2; p=0.07). Conclusion: Protein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET-1 were elevated suggesting a role for therapy inhibiting ET-1 in chest crisis.
Language	English
Publishing date	2015-11-23
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	2683797-3
ISSN	2001-3078
ISSN	2001-3078
DOI	10.3402/jev.v4.28414
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Article ; Online: Staphylococcus aureus manganese transport protein C is a highly conserved cell surface protein that elicits protective immunity against S. aureus and Staphylococcus epidermidis.

Anderson, Annaliesa S / Scully, Ingrid L / Timofeyeva, Yekaterina / Murphy, Ellen / McNeil, Lisa K / Mininni, Terri / Nuñez, Lorna / Carriere, Marjolaine / Singer, Christine / Dilts, Deborah A / Jansen, Kathrin U

The Journal of infectious diseases

2012 Volume 205, Issue 11, Page(s) 1688–1696

Abstract: ... no vaccines available. We evaluated whether manganese transport protein C (MntC), which is conserved ... across the staphylococcal species group, could confer protection against S. aureus and ... Staphylococcus epidermidis. In vivo analysis of S. aureus MntC expression revealed that expression occurs very early during ...

Abstract	Staphylococcus aureus and other staphylococci cause severe human disease, and there are currently no vaccines available. We evaluated whether manganese transport protein C (MntC), which is conserved across the staphylococcal species group, could confer protection against S. aureus and Staphylococcus epidermidis. In vivo analysis of S. aureus MntC expression revealed that expression occurs very early during the infectious cycle. Active immunization with MntC was effective at reducing the bacterial load associated with S. aureus and S. epidermidis infection in an acute murine bacteremia model. Anti-MntC monoclonal antibodies have been identified that can bind S. aureus and S. epidermidis cells and are protective in an infant rat passive protection model and induce neutrophil respiratory burst activity. This is the first description of a protein that has the potential to provide protection across the staphylococcal species group.
MeSH term(s)	Animals ; Antibodies, Bacterial/blood ; Antibodies, Bacterial/immunology ; Bacteremia/immunology ; Bacteremia/prevention & control ; Bacteremia/therapy ; Bacterial Load ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Carrier Proteins/genetics ; Carrier Proteins/immunology ; Disease Models, Animal ; Female ; Immunization, Passive ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Mice ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Staphylococcal Infections/immunology ; Staphylococcal Infections/prevention & control ; Staphylococcal Infections/therapy ; Staphylococcal Vaccines/administration & dosage ; Staphylococcal Vaccines/genetics ; Staphylococcal Vaccines/immunology ; Staphylococcus aureus/immunology ; Staphylococcus epidermidis/immunology ; Treatment Outcome
Chemical Substances	Antibodies, Bacterial ; Bacterial Proteins ; Carrier Proteins ; Membrane Proteins ; Staphylococcal Vaccines
Language	English
Publishing date	2012-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jis272
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Article ; Online: Metal-free reductive cleavage of C-N and S-N bonds by photoactivated electron transfer from a neutral organic donor.

O'Sullivan, Steven / Doni, Eswararao / Tuttle, Tell / Murphy, John A

Angewandte Chemie (International ed. in English)

2013 Volume 53, Issue 2, Page(s) 474–478

Abstract: ... from dialkylamines at room temperature. It also cleaves a) ArCNR and b) ArNC bonds. This study also highlights ... the assistance given to these cleavage reactions by the groups attached to N in (a) and to C in (b), by lowering ...

Abstract	A photoactivated neutral organic super electron donor cleaves challenging arenesulfonamides derived from dialkylamines at room temperature. It also cleaves a) ArCNR and b) ArNC bonds. This study also highlights the assistance given to these cleavage reactions by the groups attached to N in (a) and to C in (b), by lowering LUMO energies and by stabilizing the products of fragmentation.
Language	English
Publishing date	2013-12-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.201306543
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Article: Response to C.S. Sims.

Murphy, J A

Health physics

1997 Volume 73, Issue 6, Page(s) 958

MeSH term(s)	Contract Services ; Government Agencies ; Humans ; Licensure ; Occupational Health ; Radiation Monitoring/legislation & jurisprudence ; Radioactive Hazard Release/prevention & control ; United States
Language	English
Publishing date	1997-12
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	2406-5
ISSN	1538-5159 ; 0017-9078
ISSN (online)	1538-5159
ISSN	0017-9078
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Article ; Online: Complexes of Gilman reagents with C-S and C-N double bonds: sigma or pi bonding?

Bertz, Steven H / Moazami, Yasamin / Murphy, Michael D / Ogle, Craig A / Richter, Joshua D / Thomas, Andy A

Journal of the American Chemical Society

2010 Volume 132, Issue 28, Page(s) 9549–9551

Abstract: ... at -100 degrees C inside the probe of an NMR spectrometer to give high yields of complexes. Typical ... interesting, since it involved a transient intermediate that was identified as a complex with a C-N double ... bond. Methyl isothiocyanate gave a stable C-N double-bond complex. ...

Abstract	Upon rapid injection, a variety of thiocarbonyl compounds react with the Gilman reagent Me(2)CuLi at -100 degrees C inside the probe of an NMR spectrometer to give high yields of complexes. Typical examples of substrates include carbon disulfide, methyl dithioacetate, methyl dithiobenzoate, thiobenzophenone, ethylene trithiocarbonate, and phenyl isothiocyanate. Evidence suggesting the formal oxidation state of copper in these complexes to be Cu(III) is presented. The last example was particularly interesting, since it involved a transient intermediate that was identified as a complex with a C-N double bond. Methyl isothiocyanate gave a stable C-N double-bond complex.
Language	English
Publishing date	2010-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja103068h
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Article: Metabolism of R,S-[2-(14)C]abscisic acid by non-stressed and water-stressed detached leaves of wheat (Triticum aestivum L.).

Murphy, G J

Planta

2013 Volume 160, Issue 3, Page(s) 250–255

Abstract: Metabolism of R,S-[2-(14)C]abscisic acid (ABA) was studied in detached leaves of six wheat ...

Abstract	Metabolism of R,S-[2-(14)C]abscisic acid (ABA) was studied in detached leaves of six wheat (Triticum aestivum) cultivars, using non-stressed leaves or leaves water stressed by desiccation to 90% of their original fresh weight. The rate constant of ABA metabolism was similar in nonstressed leaves of all cultivars. Water stress resulted in significantly lower rate constants in two cultivars which accumulated high levels of ABA when stressed, the constants decreasing by a factor of about 1.5. Rate constants for the remainder of the cultivars were not significantly different from those for the non-stressed controls. It was calculated that if decreased metabolism was the mechanism for the accumulation of ABA following water stress the rate constants of metabolism would have to be reduced by a factor of between 25 and 70. The results therefore support the hypothesis that enhanced synthesis rather than reduced degradation is the main process by which ABA levels are elevated following experimentally induced water stress. There were differences between the six cultivars in the products of ABA metabolism. Over the time period studied, oxidation to phaseic acid and dihydrophaseic acid as well as to other unidentified metabolites appeared to be the predominant pathway of ABA metabolism, rather than conjugation to ABA glucose ester and other more polar compounds.
Language	English
Publishing date	2013-11-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	208909-9
ISSN	1432-2048 ; 0032-0935 ; 1866-2749
ISSN (online)	1432-2048
ISSN	0032-0935 ; 1866-2749
DOI	10.1007/BF00402862
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