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Article ; Online: Dramatic Response After Switching MEK Inhibitors in a Patient With Refractory Mixed Histiocytosis.

Roeser, Anais / Jouenne, Fanelie / Vercellino, Laetitia / Calvani, Julien / Goldwirt, Lauriane / Lorillon, Gwenael / Tazi, Abdellatif

Journal of hematology

2022 Volume 11, Issue 5, Page(s) 185–189

Abstract: We report the case of a patient with progressive multisystem mixed histiocytosis associating Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) involving the bone marrow, whose lesions harbored ... ...

Abstract	We report the case of a patient with progressive multisystem mixed histiocytosis associating Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) involving the bone marrow, whose lesions harbored the
Language	English
Publishing date	2022-10-31
Publishing country	Canada
Document type	Case Reports
ZDB-ID	2662519-2
ISSN	1927-1220 ; 1927-1220
ISSN (online)	1927-1220
ISSN	1927-1220
DOI	10.14740/jh1030
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Article ; Online: Gender-specific elevation of plasma anthranilic acid in schizophrenia: Protection against glutamatergic hypofunction?

Steiner, Johann / Dobrowolny, Henrik / Guest, Paul C / Bernstein, Hans-Gert / Fuchs, Dietmar / Roeser, Julien / Summergrad, Paul / Oxenkrug, Gregory

Schizophrenia research

2022 Volume 243, Page(s) 483–485

MeSH term(s)	Humans ; Kynurenic Acid ; Schizophrenia ; ortho-Aminobenzoates
Chemical Substances	ortho-Aminobenzoates ; anthranilic acid (0YS975XI6W) ; Kynurenic Acid (H030S2S85J)
Language	English
Publishing date	2022-02-10
Publishing country	Netherlands
Document type	Letter
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2022.01.048
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Zs.A 2351: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cerebrospinal fluid monoamine levels in central disorders of hypersomnolence.

Barateau, Lucie / Jaussent, Isabelle / Roeser, Julien / Ciardiello, Claudio / Kilduff, Thomas S / Dauvilliers, Yves

Sleep

2021 Volume 44, Issue 7

Abstract: Study objectives: Whether the cause of daytime sleepiness in narcolepsy type 1 (NT1) is a direct consequence of the loss of orexin (ORX) neurons or whether low orexin reduces the efficacy of the monoaminergic systems to promote wakefulness is unclear. ... ...

Abstract	Study objectives: Whether the cause of daytime sleepiness in narcolepsy type 1 (NT1) is a direct consequence of the loss of orexin (ORX) neurons or whether low orexin reduces the efficacy of the monoaminergic systems to promote wakefulness is unclear. The neurobiology underlying sleepiness in other central hypersomnolence disorders, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), is currently unknown. Methods: Eleven biogenic amines including the monoaminergic neurotransmitters and their metabolites and five trace amines were measured in the cerebrospinal fluid (CSF) of 94 drug-free subjects evaluated at the French National Reference Center for Narcolepsy: 39 NT1(orexin-deficient) patients, 31 patients with objective sleepiness non orexin-deficient (NT2 and IH), and 24 patients without objective sleepiness. Results: Three trace amines were undetectable in the sample: tryptamine, octopamine, and 3-iodothyronamine. No significant differences were found among the three groups for quantified monoamines and their metabolites in crude and adjusted models; however, CSF 5-hydroxyindoleacetic acid (5-HIAA) levels tended to increase in NT1 compared to other patients after adjustment. Most of the biomarkers were not associated with ORX-A levels, clinical or neurophysiological parameters, but a few biomarkers (e.g. 3-methoxy-4-hydroxyphenylglycol and norepinephrine) correlated with daytime sleepiness and high rapid eye movement (REM) sleep propensity. Conclusions: We found no striking differences among CSF monoamines, their metabolites and trace amine levels, and few associations between them and key clinical or neurophysiological parameters in NT1, NT2/IH, and patients without objective sleepiness. Although mostly negative, these findings are a significant contribution to our understanding of the neurobiology of hypersomnolence in these disorders that remain mysterious and deserve further exploration.
MeSH term(s)	Amines ; Disorders of Excessive Somnolence ; Humans ; Idiopathic Hypersomnia ; Narcolepsy ; Orexins ; Wakefulness
Chemical Substances	Amines ; Orexins
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsab012
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Article: Plasma Anthranilic Acid and Leptin Levels Predict HAM-D Scores in Depressed Women.

Steiner, Johann / Dobrowolny, Henrik / Guest, Paul C / Bernstein, Hans-Gert / Fuchs, Dietmar / Roeser, Julien / Summergrad, Paul / Oxenkrug, Gregory F

International journal of tryptophan research : IJTR

2021 Volume 14, Page(s) 11786469211016474

Abstract: Objectives: Major depressive disorder (MDD) is associated with dysregulations of leptin and tryptophan-kynurenine (Trp-Kyn) (TKP) pathways. Leptin, a pro-inflammatory cytokine, activates Trp conversion into Kyn. However, leptin association with down- ... ...

Abstract	Objectives: Major depressive disorder (MDD) is associated with dysregulations of leptin and tryptophan-kynurenine (Trp-Kyn) (TKP) pathways. Leptin, a pro-inflammatory cytokine, activates Trp conversion into Kyn. However, leptin association with down-stream Kyn metabolites in MDD is unknown. Methods: Fasting plasma samples from 29 acutely ill drug-naïve (n = 16) or currently non-medicated (⩾6 weeks; n = 13) MDD patients were analyzed for leptin, Trp, Kyn, its down-stream metabolites (anthranilic [AA], kynurenic [KYNA], xanthurenic [XA] acids and 3-hydroxykynurenine [3HK]), C-reactive protein (CRP), neopterin, body mass index (BMI), and insulin resistance (HOMA-IR). Depression severity was assessed by HAM-D-21. Results: In female (n = 14) (but not in male) patients HAM-D-21 scores correlated with plasma levels of AA (but not other Kyn metabolites) (rho = -0.644, Conclusions: Present findings of gender specific AA/Leptin correlations with HAM-D are important considering that AA and leptin are transported from plasma into brain, and that AA formation is catalyzed by
Language	English
Publishing date	2021-05-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2517435-6
ISSN	1178-6469
ISSN	1178-6469
DOI	10.1177/11786469211016474
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Article: Quinolinic acid, a kynurenine/tryptophan pathway metabolite, associates with impaired cognitive test performance in systemic lupus erythematosus.

Anderson, Erik W / Fishbein, Joanna / Hong, Joseph / Roeser, Julien / Furie, Richard A / Aranow, Cynthia / Volpe, Bruce T / Diamond, Betty / Mackay, Meggan

Lupus science & medicine

2021 Volume 8, Issue 1

Abstract: Objectives: Interferon-alpha, an important contributor to SLE pathogenesis, induces the enzyme indoleamine 2,3-dioxygenase in the kynurenine/tryptophan (KYN/TRP) pathway. This leads to a potentially neurotoxic imbalance in the KYN/TRP pathway ... ...

Abstract	Objectives: Interferon-alpha, an important contributor to SLE pathogenesis, induces the enzyme indoleamine 2,3-dioxygenase in the kynurenine/tryptophan (KYN/TRP) pathway. This leads to a potentially neurotoxic imbalance in the KYN/TRP pathway metabolites, quinolinic acid (QA), an N-methyl D-aspartate glutamatergic receptor (NMDAR) agonist, and kynurenic acid (KA), an NMDAR antagonist. We determined whether QA/KA ratios associate with cognitive dysfunction (CD) and depression in SLE. Methods: This cross-sectional study included 74 subjects with SLE and 74 healthy control (HC) subjects; all without history of neuropsychiatric disorders. Serum metabolite levels (KYN, TRP, QA, KA) were measured concurrently with assessments of cognition (Automated Neuropsychological Assessment Metrics (ANAM), 2×2 array), mood and pain, and compared between SLE and HC. Multivariable modelling in SLE was used to evaluate associations of metabolites with cognitive performance and depression. Results: Serum KYN/TRP and QA/KA ratios were elevated in SLE versus HC (p<0.0001). SLE performed worse than HC on four of five ANAM tests (all p≤0.02) and the 2×2 array (p<0.01), and had higher depression scores (p<0.01). In SLE, elevated QA/KA ratios correlated with poor performance on Match to Sample (MTS), a working memory and visuospatial processing task (p<0.05). Subjects with SLE with elevated QA/KA ratios also had slightly higher odds of depression, but this did not reach significance (p=0.09). Multivariable modelling in SLE confirmed an association between QA/KA ratios and poor MTS performance when considering potentially confounding factors (p<0.05). Conclusions: Elevated serum KYN/TRP and QA/KA ratios confirm KYN/TRP pathway activation in SLE. The novel association between increased QA/KA ratios and poor cognitive performance supports further study of this pathway as a potential biomarker or therapeutic target for SLE-mediated CD.
MeSH term(s)	Cognitive Dysfunction/diagnosis ; Cross-Sectional Studies ; Humans ; Kynurenine ; Lupus Erythematosus, Systemic ; Neuropsychological Tests ; Quinolinic Acid ; Tryptophan
Chemical Substances	Kynurenine (343-65-7) ; Tryptophan (8DUH1N11BX) ; Quinolinic Acid (F6F0HK1URN)
Language	English
Publishing date	2021-10-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2021-000559
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Article ; Online: Peripheral Tryptophan - Kynurenine Metabolism Associated with Metabolic Syndrome is Different in Parkinson's and Alzheimer's Diseases.

Oxenkrug, Gregory / van der Hart, Marieke / Roeser, Julien / Summergrad, Paul

Endocrinology, diabetes and metabolism journal

2017 Volume 1, Issue 4

Abstract: Insulin resistance (IR), obesity and other components of metabolic syndrome [MetS] are highly associated with Alzheimer's (AD) and Parkinson's (PD) diseases. Dysregulation of kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism was suggested as ... ...

Abstract	Insulin resistance (IR), obesity and other components of metabolic syndrome [MetS] are highly associated with Alzheimer's (AD) and Parkinson's (PD) diseases. Dysregulation of kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism was suggested as major contributor to pathogenesis of AD and PD and MetS. KP, the major source of NAD
Language	English
Publishing date	2017-11-19
Publishing country	Sweden
Document type	Journal Article
ISSN	2002-7354
ISSN (online)	2002-7354
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Article ; Online: Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease.

Roeser, Anais / Bravetti, Marine / Dong, Lida / Azoulay, Levi-Dan / Charlotte, Frederic / Miyara, Makoto / Ghillani-Dalbin, Pascale / Emile, Jean-Francois / El Kouari, Fadwa / Ouni, Hamza / Lacorte, Jean-Marc / Brocheriou, Isabelle / Amoura, Zahir / Cohen-Aubart, Fleur / Haroche, Julien

Haematologica

2023 Volume 108, Issue 2, Page(s) 513–521

Abstract: Erdheim-Chester disease (ECD) is a rare histiocytosis, considered to be an inflammatory myeloid neoplasm. Tropism for specific involvements of the disease remains unexplained. Vascular endothelial growth factor-A (VEGF) is implicated in cancer ... ...

Abstract	Erdheim-Chester disease (ECD) is a rare histiocytosis, considered to be an inflammatory myeloid neoplasm. Tropism for specific involvements of the disease remains unexplained. Vascular endothelial growth factor-A (VEGF) is implicated in cancer pathophysiology and mutations of the RAS oncogene have been shown to induce upregulation of VEGF gene expression. We therefore hypothesized that VEGF might play a particular role in ECD pathophysiology. We conducted a retrospective, single-center study to assess serum VEGF (sVEGF) concentrations and determine whether they were associated with the characteristics of ECD patients, and to determine whether VEGF was expressed by histiocytes. We evaluated 247 ECD patients, 53.4% of whom had sVEGF levels above the normal range (>500 pg/mL). Patients with high sVEGF levels more frequently had cardiac and vascular involvement (58.3% vs. 41.4%, P=0.008 and 70.5% vs. 48.3%, P=0.0004, respectively). In treatment-naïve patients (n=135), the association of C-reactive protein >5 mg/L and sVEGF >500 pg/mL was strongly associated with vascular involvement (odds ratio=5.54 [95% confidence interval: 2.39-13.62], P<0.001), and independently associated with cardiac involvement (odds ratio=3.18 [95% confidence interval: 1.34-7.83], P=0.010) after adjustment for the presence of the BRAF V600E mutation. Changes in sVEGF concentration on treatment were associated with a response of cardiac involvement on consecutive cardiac magnetic resonance images. All histological samples analyzed (n=24) displayed histiocytes with intracytoplasmic expression of VEGF, which was moderate to high in more than 90% of cases. Our study suggests a role for VEGF in cardiac and vascular involvement in ECD.
MeSH term(s)	Humans ; Vascular Endothelial Growth Factor A/genetics ; Retrospective Studies ; Erdheim-Chester Disease/diagnosis ; Erdheim-Chester Disease/drug therapy ; Erdheim-Chester Disease/genetics ; Vascular Endothelial Growth Factors ; Neoplasms
Chemical Substances	Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
Language	English
Publishing date	2023-02-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.280755
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Article: Associations between circulating interferon and kynurenine/tryptophan pathway metabolites: support for a novel potential mechanism for cognitive dysfunction in SLE.

Anderson, Erik W / Jin, Ying / Shih, Andrew / Arazi, Arnon / Goodwin, Sara / Roeser, Julien / Furie, Richard A / Aranow, Cynthia / Volpe, Bruce / Diamond, Betty / Mackay, Meggan

Lupus science & medicine

2022 Volume 9, Issue 1

Abstract: Objective: Quinolinic acid (QA), a kynurenine (KYN)/tryptophan (TRP) pathway metabolite, is an N-methyl-D-aspartate receptor agonist that can produce excitotoxic neuron damage. Type I and II interferons (IFNs) stimulate the KYN/TRP pathway, producing ... ...

Abstract	Objective: Quinolinic acid (QA), a kynurenine (KYN)/tryptophan (TRP) pathway metabolite, is an N-methyl-D-aspartate receptor agonist that can produce excitotoxic neuron damage. Type I and II interferons (IFNs) stimulate the KYN/TRP pathway, producing elevated QA/kynurenic acid (KA), a potential neurotoxic imbalance that may contribute to SLE-mediated cognitive dysfunction. We determined whether peripheral blood interferon-stimulated gene (ISG) expression associates with elevated serum KYN:TRP and QA:KA ratios in SLE. Methods: ISG expression (whole-blood RNA sequencing) and serum metabolite ratios (high-performance liquid chromatography) were measured in 72 subjects with SLE and 73 healthy controls (HCs). ISG were identified from published gene sets and individual IFN scores were derived to analyse associations with metabolite ratios, clinical parameters and neuropsychological assessments. SLE analyses were grouped by level of ISG expression ('IFN high', 'IFN low' and 'IFN similar to HC') and level of monocyte-associated gene expression (using CIBERSORTx). Results: Serum KYN:TRP and QA:KA ratios were higher in SLE than in HC (p<0.01). 933 genes were differentially expressed ≥2-fold in SLE versus HC (p<0.05). 70 of the top 100 most highly variant genes were ISG. Approximately half of overexpressed genes that correlated with KYN:TRP and QA:KA ratios (p<0.05) were ISG. In 36 IFN-high subjects with SLE, IFN scores correlated with KYN:TRP ratios (p<0.01), but not with QA:KA ratios. Of these 36 subjects, 23 had high monocyte-associated gene expression, and in this subgroup, the IFN scores correlated with both KY:NTRP and QA:KA ratios (p<0.05). Conclusions: High ISG expression correlated with elevated KYN:TRP ratios in subjects with SLE, suggesting IFN-mediated KYN/TRP pathway activation, and with QA:KA ratios in a subset with high monocyte-associated gene expression, suggesting that KYN/TRP pathway activation may be particularly important in monocytes. These results need validation, which may aid in determining which patient subset may benefit from therapeutics directed at the IFN or KYN/TRP pathways to ameliorate a potentially neurotoxic QA/KA imbalance.
MeSH term(s)	Humans ; Kynurenine/metabolism ; Tryptophan/metabolism ; Interferons ; Lupus Erythematosus, Systemic/complications ; Kynurenic Acid/metabolism ; Quinolinic Acid/metabolism ; Cognitive Dysfunction/etiology
Chemical Substances	Kynurenine (343-65-7) ; Tryptophan (8DUH1N11BX) ; Interferons (9008-11-1) ; Kynurenic Acid (H030S2S85J) ; Quinolinic Acid (F6F0HK1URN)
Language	English
Publishing date	2022-11-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2022-000808
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Article: Peripheral kynurenine-3-monooxygenase deficiency as a potential risk factor for metabolic syndrome in schizophrenia patients.

Oxenkrug, Gregory / van der Hart, Marieke / Roeser, Julien / Summergrad, Paul

Integrative clinical medicine

2017 Volume 1, Issue 1

Abstract: Increased predisposition of schizophrenia patients (SP) to development of obesity and insulin resistance suggested common signaling pathway between metabolic syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase (KMO), enzyme ... ...

Abstract	Increased predisposition of schizophrenia patients (SP) to development of obesity and insulin resistance suggested common signaling pathway between metabolic syndrome (MetS) and schizophrenia. Deficiency of kynurenine-3-monooxygenase (KMO), enzyme catalyzing formation of 3-hydroxykynurenine (3-HK) from kynurenine (Kyn), a tryptophan (Trp) metabolite, might contribute to development of MetS as suggested by non-expression of KMO genes in human fat tissue and elevated serum concentrations of Kyn and its metabolites, kynurenic (KYNA) and anthranilic (ANA) acids, in diabetic patients and Zucker fatty rats (ZFR). Markers of KMO deficiency: decreased 3-HK and elevated Kyn, KYNA and ANA, were observed in brains and spinal fluids of SP, and in brains and serum of experimental animals with genetically- or pharmacologically-induced KMO deficiency. However, elevated concentrations of ANA and decreased 3-HK were reported in serum of SP without concurrent increase of Kyn and KYNA. Present study aimed to re-assess serum Kyn metabolites (HPLC-MS) in a sub-group of SP with elevated KYNA. We found increased Kyn concentrations (by 30%) and Kyn:Trp ratio (by 20%) in serum of SP with elevated KYNA concentrations (by 40%). Obtained results and our previous data suggest that peripheral KMO deficiency might be manifested by, at least, two different patterns: elevated ANA with decreased 3-HK; and elevated KYNA and KYN. The latter pattern was previously described in type 2 diabetes patients and might underline increased predisposition of SP to development of MetS. Assessment of peripheral KMO deficiency might identify SP predisposed to MetS. Attenuation of the consequences of peripheral KMO deficiency might be a new target for prevention/treatment of obesity and diabetes in SP.
Language	English
Publishing date	2017-05-10
Publishing country	England
Document type	Journal Article
ISSN	2515-0219
ISSN	2515-0219
DOI	10.15761/ICM.1000105
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Article ; Online: Plasma xanthurenic acid in a context of insulin resistance and obesity in schizophrenia.

Oxenkrug, Gregory / Bernstein, Hans-Gert / Guest, Paul C / van der Hart, Marieke / Roeser, Julien / Summergrad, Paul / Steiner, Johann

Schizophrenia research

2019 Volume 211, Page(s) 98–99

MeSH term(s)	Case-Control Studies ; Humans ; Insulin Resistance ; Kynurenic Acid/blood ; Kynurenine/analogs & derivatives ; Kynurenine/blood ; Obesity/blood ; Schizophrenia/blood ; Xanthurenates/blood
Chemical Substances	Xanthurenates ; 3-hydroxykynurenine (27723548JL) ; Kynurenine (343-65-7) ; xanthurenic acid (58LAB1BG8J) ; Kynurenic Acid (H030S2S85J)
Language	English
Publishing date	2019-08-02
Publishing country	Netherlands
Document type	Letter ; Research Support, N.I.H., Extramural
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2019.07.038
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