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Article ; Online: Current state of the epilepsy drug and device pipeline.

Terman, Samuel W / Kirkpatrick, Laura / Akiyama, Lisa F / Baajour, Wadih / Atilgan, Deniz / Dorotan, Maria Kristina C / Choi, Hyoung Won / French, Jacqueline A

Epilepsia

2024 Volume 65, Issue 4, Page(s) 833–845

Abstract: The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well-tolerated treatments, but also precision treatments for rare epilepsies and seizure- ... ...

Abstract	The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well-tolerated treatments, but also precision treatments for rare epilepsies and seizure-monitoring devices. We summarize major recent and ongoing innovations in diagnostic and therapeutic products presented at the seventeenth Epilepsy Therapies & Diagnostics Development (ETDD) conference, which occurred May 31 to June 2, 2023, in Aventura, Florida. Therapeutics under development are targeting genetics, ion channels and other neurotransmitters, and many other potentially first-in-class interventions such as stem cells, glycogen metabolism, cholesterol, the gut microbiome, and novel modalities for delivering electrical neuromodulation.
MeSH term(s)	Humans ; Anticonvulsants/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/diagnosis ; Seizures/drug therapy
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17884
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Zs.A 517: 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 475: Show issues

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Article ; Online: Change in nomenclature for the immunologic synapse from Troxis Necrosis to trogocytosis.

French, Samuel W

Experimental and molecular pathology

2017 Volume 103, Issue 2, Page(s) 162

Abstract: ... Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was ...

Abstract	The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte. This process is performed by the immunologic synapse now called trogocytosis meaning "gnaw" (Martinez-Martin N et al., Immunity 2011, 35: 208-222 and Dustin ML, Cancer Immunol Res 2014, 2: 1023-1033). The repeated episodes of uptake of the hepatocyte bite by bite causes the hepatocyte to slowly disappear like the Cheshire cat. This immunological synapse process is also involved in drug hepatitis, Hashimoto's thyroiditis, type I diabetes, autoimmune adrenalitis, autoimmune gastritis and cancer therapy. Treatment of Alzheimer's disease is also now being studied with PD-L1 antibody as used in the treatment of cancer allowing recruitment of disease modifying leukocytes to the sites of brain pathology (Schwartz M. Science 2017, 357: 254-255). Acknowledgement: Supported by a Grant from NIAAAUO1-021898.
Language	English
Publishing date	2017-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2017.08.001
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Article ; Online: Successful treatment of severe immune checkpoint inhibitor associated autoimmune hepatitis with basiliximab: a case report.

Zarrabi, Maiah / Hamilton, Camille / French, Samuel W / Federman, Noah / Nowicki, Theodore S

Frontiers in immunology

2023 Volume 14, Page(s) 1156746

Abstract: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and its corresponding ligand PD-L1 are being increasingly used for a wide variety of cancers, including refractory sarcomas. Autoimmune hepatitis is a known side effect of ICIs, ...

Abstract	Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and its corresponding ligand PD-L1 are being increasingly used for a wide variety of cancers, including refractory sarcomas. Autoimmune hepatitis is a known side effect of ICIs, and is typically managed with broad, non-specific immunosuppression. Here, we report a case of severe autoimmune hepatitis occurring after anti-PD-1 therapy with nivolumab in a patient with osteosarcoma. Following prolonged unsuccessful treatment with intravenous immunoglobulin, steroids, everolimus, tacrolimus, mycophenolate, and anti-thymoglobulin, the patient was eventually treated with the anti-CD25 monoclonal antibody basiliximab. This resulted in prompt, sustained resolution of her hepatitis without significant side effects. Our case demonstrates that basiliximab may be an effective therapy for steroid-refractory severe ICI-associated hepatitis.
MeSH term(s)	Humans ; Female ; Immune Checkpoint Inhibitors/adverse effects ; Basiliximab ; Hepatitis, Autoimmune/diagnosis ; Hepatitis, Autoimmune/drug therapy ; Hepatitis, Autoimmune/etiology ; Nivolumab/adverse effects ; Antibodies, Monoclonal/adverse effects
Chemical Substances	Immune Checkpoint Inhibitors ; Basiliximab (9927MT646M) ; Nivolumab (31YO63LBSN) ; Antibodies, Monoclonal
Language	English
Publishing date	2023-05-30
Publishing country	Switzerland
Document type	Case Reports ; Research Support, N.I.H., Extramural ; Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1156746
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Article ; Online: Chronic alcohol binging injures the liver and other organs by reducing NAD⁺ levels required for sirtuin's deacetylase activity.

French, Samuel W

Experimental and molecular pathology

2016 Volume 100, Issue 2, Page(s) 303–306

Abstract: NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins ...

Abstract	NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking.
MeSH term(s)	Acetylation ; Alcohol Dehydrogenase/metabolism ; Binge Drinking/metabolism ; Binge Drinking/physiopathology ; Cell Cycle Checkpoints/physiology ; Humans ; Liver/metabolism ; Mitochondria/metabolism ; NAD/metabolism ; Signal Transduction/physiology ; Sirtuins/metabolism
Chemical Substances	NAD (0U46U6E8UK) ; Alcohol Dehydrogenase (EC 1.1.1.1) ; Sirtuins (EC 3.5.1.-)
Language	English
Publishing date	2016-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2016.02.004
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Zs.A 183: Show issues

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Article ; Online: An unexpected diagnosis of histiocytic sarcoma.

Byers, Joshua T / French, Samuel W

Experimental and molecular pathology

2018 Volume 106, Page(s) 60–62

MeSH term(s)	Ascites/etiology ; Biomarkers, Tumor ; Diagnostic Errors ; Fatal Outcome ; Gastrointestinal Hemorrhage/etiology ; Hepatitis C, Chronic/complications ; Histiocytes/pathology ; Histiocytic Sarcoma/complications ; Histiocytic Sarcoma/diagnosis ; Histiocytic Sarcoma/metabolism ; Histiocytic Sarcoma/pathology ; Humans ; Male ; Middle Aged ; Peritoneal Neoplasms/chemistry ; Peritoneal Neoplasms/complications ; Peritoneal Neoplasms/diagnosis ; Peritoneal Neoplasms/pathology ; Peritonitis/diagnosis
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2018-11-28
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2018.11.012
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Zs.A 183: Show issues

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Article ; Online: Single-shot optical projection tomography for high-speed volumetric imaging of dynamic biological samples.

Darling, Connor / Davis, Samuel P X / Kumar, Sunil / French, Paul M W / McGinty, James

Journal of biophotonics

2022 Volume 16, Issue 2, Page(s) e202200232

Abstract: A single-shot adaptation of Optical Projection Tomography (OPT) for high-speed volumetric snapshot imaging of dynamic mesoscopic biological samples is presented. Conventional OPT has been applied to in vivo imaging of animal models such as D. rerio, but ... ...

Abstract	A single-shot adaptation of Optical Projection Tomography (OPT) for high-speed volumetric snapshot imaging of dynamic mesoscopic biological samples is presented. Conventional OPT has been applied to in vivo imaging of animal models such as D. rerio, but the sequential acquisition of projection images typically requires samples to be immobilized during the acquisition. A proof-of-principle system capable of single-shot tomography of a ~1 mm
MeSH term(s)	Animals ; Imaging, Three-Dimensional/methods ; Zebrafish ; Tomography, Optical/methods ; Embryo, Mammalian
Language	English
Publishing date	2022-09-29
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2390063-5
ISSN	1864-0648 ; 1864-063X
ISSN (online)	1864-0648
ISSN	1864-063X
DOI	10.1002/jbio.202200232
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Article ; Online: Piecemeal necrosis is due to the immunologic synapse formation and internalization of intact TCR-MHC II complexes by CD4 T cells.

French, Samuel W / Lu, Jiajie G

Experimental and molecular pathology

2018 Volume 105, Issue 1, Page(s) 150–152

Abstract: The nature of the immunologic synapse in autoimmune hepatitis is defined. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the plasma membrane. This complex is ... ...

Abstract	The nature of the immunologic synapse in autoimmune hepatitis is defined. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the plasma membrane. This complex is quickly removed from the liver cell and taken into the T cell cytoplasm to be digested by the lysosome. The liver cell is gradually diminished to the point of its total removal by the lymphocytes binding to it.
MeSH term(s)	CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/ultrastructure ; Hepatitis, Autoimmune/immunology ; Hepatitis, Autoimmune/pathology ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunological Synapses/immunology ; Necrosis ; Receptors, Antigen, T-Cell/immunology
Chemical Substances	Histocompatibility Antigens Class II ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2018-07-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2018.07.004
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Challenges and directions in epilepsy diagnostics and therapeutics: Proceedings of the 17th Epilepsy Therapies and Diagnostics Development conference.

Terman, Samuel W / Kirkpatrick, Laura / Kerr, Wesley T / Akiyama, Lisa F / Baajour, Wadih / Atilgan, Deniz / Dorotan, Maria Kristina C / Choi, Hyoung Won / French, Jacqueline A

Epilepsia

2024 Volume 65, Issue 4, Page(s) 846–860

Abstract: Substantial efforts are underway toward optimizing the diagnosis, monitoring, and treatment of seizures and epilepsy. We describe preclinical programs in place for screening investigational therapeutic candidates in animal models, with particular ... ...

Abstract	Substantial efforts are underway toward optimizing the diagnosis, monitoring, and treatment of seizures and epilepsy. We describe preclinical programs in place for screening investigational therapeutic candidates in animal models, with particular attention to identifying and eliminating drugs that might paradoxically aggravate seizure burden. After preclinical development, we discuss challenges and solutions in the design and regulatory logistics of clinical trial execution, and efforts to develop disease biomarkers and interventions that may be not only seizure-suppressing, but also disease-modifying. As disease-modifying treatments are designed, there is clear recognition that, although seizures represent one critical therapeutic target, targeting nonseizure outcomes like cognitive development or functional outcomes requires changes to traditional designs. This reflects our increasing understanding that epilepsy is a disease with profound impact on quality of life for the patient and caregivers due to both seizures themselves and other nonseizure factors. This review examines selected key challenges and future directions in epilepsy diagnostics and therapeutics, from drug discovery to translational application.
MeSH term(s)	Animals ; Humans ; Anticonvulsants/therapeutic use ; Quality of Life ; Epilepsy/diagnosis ; Epilepsy/drug therapy ; Seizures/drug therapy ; Disease Models, Animal
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17875
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Zs.A 517: 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 475: Show issues

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Article: The Role of FAT10 in Alcoholic Hepatitis Pathogenesis.

Jia, Yue / Ji, Ping / French, Samuel W

Biomedicines

2020 Volume 8, Issue 7

Abstract: FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFNγ and TNFα in all cell types and tissues. Increased FAT10 expression may induce increasing mitotic non-disjunction and chromosome instability, leading to tumorigenesis. In this ... ...

Abstract	FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFNγ and TNFα in all cell types and tissues. Increased FAT10 expression may induce increasing mitotic non-disjunction and chromosome instability, leading to tumorigenesis. In this review, we summarized others' and our work on FAT10 expression in liver biopsy samples from patients with alcoholic hepatitis (AH). FAT10 is essential to maintain the function of liver cell protein quality control and Mallory-Denk body (MDB) formation. FAT10 overexpression in AH leads to balloon degeneration and MDB aggregation formation, all of which is prevented in fat10-/- mice. FAT10 causes the proteins' accumulation, overexpression, and forming MDBs through modulating 26s proteasome's proteases. The pathway that increases FAT10 expression includes TNFα/IFNγ and the interferon sequence response element (ISRE), followed by NFκB and STAT3, which were all up-regulated in AH. FAT10 was only reported in human and mouse specimens but plays critical role for the development of alcoholic hepatitis. Flavanone derivatives of milk thistle inhibit TNFα/IFNγ, NFκB, and STAT3, then inhibit the expression of FAT10. NFκB is the key nodal hub of the IFNα/TNFα-response genes. Studies on Silibinin and other milk thistle derivatives to treat AH confirms that overexpressed FAT10 is the major key molecule in these networks.
Language	English
Publishing date	2020-07-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines8070189
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Article ; Online: Is the diagnosis of acute luminal appendicitis clinically meaningful?

Byers, Joshua T / French, Samuel W

Experimental and molecular pathology

2017 Volume 103, Issue 2, Page(s) 135–136

MeSH term(s)	Acute Disease ; Appendicitis/diagnosis ; Appendicitis/surgery ; Appendix/pathology ; Appendix/surgery ; Epithelium/pathology ; Female ; Humans ; Male ; Pelvic Inflammatory Disease/diagnosis ; Pelvic Inflammatory Disease/therapy
Language	English
Publishing date	2017-08-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2017.08.004
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