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Madeleine E. Cunningham Gavin R. Meehan Sophie Robinson Denggao Yao Rhona McGonigal Hugh J. Willison 《Journal of the peripheral nervous system : JPNS》2020,25(2):143-151
In mouse models of acute motor axonal neuropathy, anti‐ganglioside antibodies (AGAbs) bind to motor axons, notably the distal nerve, and activate the complement cascade. While complement activation is well studied in this model, the role of inflammatory cells is unknown. Herein we aimed to investigate the contribution of phagocytic cells including macrophages, neutrophils and perisynaptic Schwann cells (pSCs) to distal nerve pathology. To observe this, we first created a subacute injury model of sufficient duration to allow inflammatory cell recruitment. Mice were injected intraperitoneally with an anti‐GD1b monoclonal antibody that binds strongly to mouse motor nerve axons. Subsequently, mice received normal human serum as a source of complement. Dosing was titrated to allow humane survival of mice over a period of 3 days, yet still induce the characteristic neurological impairment. Behaviour and pathology were assessed in vivo using whole‐body plethysmography and post‐sacrifice by immunofluorescence and flow cytometry. ex vivo nerve‐muscle preparations were used to investigate the acute phagocytic role of pSCs following distal nerve injury. Following complement activation at distal intramuscular nerve sites in the diaphragm macrophage localisation or numbers are not altered, nor do they shift to a pro‐ or anti‐inflammatory phenotype. Similarly, neutrophils are not significantly recruited. Instead, ex vivo nerve‐muscle preparations exposed to AGAb plus complement reveal that pSCs rapidly become phagocytic and engulf axonal debris. These data suggest that pSCs, rather than inflammatory cells, are the major cellular vehicle for axonal debris clearance following distal nerve injury, in contrast to larger nerve bundles where macrophage‐mediated clearance predominates. 相似文献
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Blepharophimosis,short humeri,developmental delay and hirschsprung disease: Expanding the phenotypic spectrum of MED12 mutations 下载免费PDF全文
Bertrand Isidor Tiphaine Lefebvre Claudine Le Vaillant Gaëlle Caillaud Laurence Faivre Frédéric Jossic Madeleine Joubert Norbert Winer Cédric Le Caignec Guntram Borck Anna Pelet Jeanne Amiel Annick Toutain Nathalie Ronce Martine Raynaud Alain Verloes Albert David 《American journal of medical genetics. Part A》2014,164(7):1821-1825
106.
Jonathan L. Curry Michael T. Tetzlaff Priyadharsini Nagarajan Carol Drucker Adi Diab Sharon R. Hymes Madeleine Duvic Wen‐Jen Hwu Jennifer A. Wargo Carlos A. Torres‐Cabala Ronald P. Rapini Victor G. Prieto 《Journal of cutaneous pathology》2017,44(2):158-176
Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti‐CTCLA‐4 antibody or anti‐PD‐1/PD‐L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti‐PD‐1 and of 556 patients receiving anti‐PD‐L1, DT of any type and grade were reported in 1474 (~39%) and 95 (~17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti‐PD‐1/PD‐L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care 相似文献
107.
Varea Costello Madeleine Sowash Aahana Gaur Michael Cardis Helena Pasieka Glenn Wortmann Sheena Ramdeen 《Emerging infectious diseases》2022,28(5):1002
A case of monkeypox was diagnosed in a returning traveler from Nigeria to Maryland, USA. Prompt infection control measures led to no secondary cases in 40 exposed healthcare workers. Given the global health implications, public health systems should be aware of effective strategies to mitigate the potential spread of monkeypox. 相似文献
108.
Jonathan L. Curry Victor G. Prieto Dan M. Jones Franscisco Vega Madeleine Duvic A. Hafeez Diwan 《Journal of cutaneous pathology》2011,38(3):295-297
Immunodeficiency‐related lymphoproliferative disorders (IR‐LPD) may occur in the setting of immunosuppressive therapy with methotrexate and TNF‐α antagonists. As far as we are aware, this is the first report of an Epstein‐Barr virus‐associated B‐cell lymphoproliferative disorder, secondary to methotrexate therapy in a patient with mycosis fungoides/Sézary syndrome. Curry JL, Prieto VG, Jones DM, Vega F, Duvic M, Diwan AH. Transient iatrogenic immunodeficiency‐related B‐cell lymphoproliferative disorder of the skin in a patient with mycosis fungoides/Sézary syndrome. 相似文献
109.
A progressive reduction in muscle fiber conduction velocity is typically observed during fatiguing muscle contraction. Although
the exact causes of the conduction velocity decrease have not yet been fully established, increasing evidence suggests that
changes in extracellular potassium concentration may be largely responsible. In this study, a mathematical model was developed
to examine the effect of extracellular potassium concentration on the muscle fiber action potential and conduction velocity.
The model was used to simulate changes in extracellular potassium concentration at a range of temperatures and extracellular
potassium accumulation during repetitive stimulation of the muscle fiber at 37 °C. The action potential broadened, and its
amplitude and conduction velocity decreased as extracellular potassium concentration increased. The potassium-induced changes
in action potential shape and conduction velocity were eliminated when the inward rectifier channels were removed from the
model. The results support the hypothesis that accumulation of extracellular potassium ions may be a major contributor to
the reduction in muscle fiber conduction velocity and loss of membrane excitability during fatiguing contractions. They additionally
suggest that inward rectifier currents play a critical role in potassium-induced membrane depolarization, leading to increased
sodium inactivation and resulting in the observed reduction in conduction velocity and membrane excitability. 相似文献
110.
Madeleine Okome-Nkoumou Vincent Guiyedi Magloire Ondounda Nora Efire Philippe Clevenbergh Mireille Dibo Arnaud Dzeing-Ella 《The American journal of tropical medicine and hygiene》2014,90(2):211-215
Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis. 相似文献