Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

2008 ◽  
Author(s):  
Frans Cornelissen ◽  
Steve De Backer ◽  
Jan Lemeire ◽  
Berf Torfs ◽  
Rony Nuydens ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Nerve Fibers ◽  
Peripheral Neuropathies ◽  
Preclinical Research ◽  
Intra Epidermal Nerve Fibers

Rituximab, Fludarabine and Alkylating Agents in Peripheral Neuropathies Related to IgM Monoclonal Gammopathy with Autoantibody Activity against Myelin-Associated-Glycoprotein : a Retrospective Study of 15 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3883-3883 ◽  
Author(s):  
Lionel Karlin ◽  
Bertrand Arnulf ◽  
Lionel Galicier ◽  
Bouchra Asli ◽  
Marion Malphettes ◽  
...  
Keyword(s):  
Serum Level ◽  
Clinical Improvement ◽  
Alkylating Agents ◽  
Nerve Fibers ◽  
Antibody Activity ◽  
Peripheral Neuropathies ◽  
Disability Score ◽  
Myelin Associated Glycoprotein ◽  
Major Reduction ◽  
Grade Iii

Abstract Abstract 3883 Poster Board III-819 Treatment of peripheral neuropathies (PN) related to IgM monoclonal (MIgM) gammopathy with anti Myelin-Associated-Glycoprotein (MAG) antibodies remains unsatisfactory. Reducing the serum level of the MIgM is likely to be a reasonable goal because of its auto-antibody activity against antigens expressed on peripheral nerve and because of various data, including studies of MIgM and complement deposition along nerve fibers and transfer experiments in animals, which argue in favour of a causal link between the MIgM and the nerve lesions. Rituximab (R) in combination with Fludarabine (F) and/or alkylating agents is considered as a highly effective regimen for achieving excellent remission in Waldenström's macroglobulinemia. It has been poorly evaluated in MIgM anti-MAG antibody-related PN. We retrospectively studied a cohort of 15 patients (pts) who were treated with such association or with R alone. Median age at diagnosis was 64 years (range, 47-84). 13/15 pts had MIgM with kappa-light-chain. All pts had sensory symptoms including 9 with ataxia, and 3 presented with disabling motor involvement. Median INCAT (Inflammatory Neuropathy Course and Treatment) disability score was 4 (range, 2-12). Median MIgM level was 5.9 g/l (range: 1.8-28). In 2 pts, it was not detectable by serum electrophoresis (SEP) but only by serum immunofixation (SIF). No pt had evidence for an associated overt lymphoid proliferation. Anti-MAG antibodies were assessed by immuno-blot and ELISA techniques. Electrophysiologic evaluation showed a demyelinating, axonal or mixed neuropathy in 8, 2 and 5 pts, respectively. Nine pts had been previously treated (7 with alkylating agents alone and 2 with intravenous immunoglobulin infusions) and none had experienced any clinical or biological improvement. Median interval time between PN diagnosis and treatment with R +/- chemotherapy was 25.6 months (range, 1-159). Twelve pts received a combination of R + chemotherapy (7 R + F + Cyclophosphamide (C), 4 R + C or chlorambucil, 1 R + F) and 3 received R alone. Significant and durable clinical improvement (including INCAT disability score) occurred in 7 pts, all treated with R + chemotherapy. Among these responders, 5 had a major reduction (>90%) of the serum MIgM level (including 3 with disappearance of monoclonal component on SEP but not on SIF). On the opposite, neither clinical response nor INCAT disability score improvement was observed in any pt treated with R alone. Electromyography significantly improved in 3 of the 9 evaluable pts, all of whom with concomitant major reduction on the MIgM serum level while on R + chemotherapy. Seven pts experienced drug-induced cytopenias including 4 grade III-IV neutropenia and 1 grade III thrombopenia. Treatment-related infections occurred in 3 pts (2 herpes zoster, 1 cytomegalovirus retinitis). One pt developed parotid adenocarcinoma one year after completion of R+F+C therapy. One pt died from cardiac arrest during a surgical procedure for lithiasic cholecystitis. In conclusion, combination of R, F and alkylating agents in MIgM anti-MAG antibodies-related PN provides high rates of durable clinical improvement, even in first-line refractory pts. Response is most often correlated with significant reduction of the MIgM serum level but does not need its disappearance. R + chemotherapy toxicity is acceptable but adding F implies immunosuppressive consequences that should be carefully evaluated. Although this remains to be formally demonstrated, R + chemotherapy seems to be more effective than R alone. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Two Photon Fluorescence Microscopy of the Unstained Human Cochlea Reveals Organ of Corti Cytoarchitecture

2021 ◽  
Vol 15 ◽  
Author(s):  
Janani S. Iyer ◽  
Richard Seist ◽  
In Seok Moon ◽  
Konstantina M. Stankovic
Keyword(s):  
Fluorescence Microscopy ◽  
Auditory Nerve ◽  
Imaging Technique ◽  
Organ Of Corti ◽  
Nerve Fibers ◽  
Sensory Cells ◽  
Two Photon ◽  
Human Cochlea ◽  
Two Photon Fluorescence ◽  
Photon Fluorescence

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, and it typically originates from the cochlea. Methods to visualize intracochlear cells in living people are currently lacking, limiting not only diagnostics but also therapies for SNHL. Two-photon fluorescence microscopy (TPFM) is a high-resolution optical imaging technique. Here we demonstrate that TPFM enables visualization of sensory cells and auditory nerve fibers in an unstained, non-decalcified adult human cochlea.

scholarly journals Keratinocytes produce IL-17c to protect peripheral nervous systems during human HSV-2 reactivation

2017 ◽  
Vol 214 (8) ◽  
pp. 2315-2329 ◽  
Author(s):  
Tao Peng ◽  
R. Savanh Chanthaphavong ◽  
Sijie Sun ◽  
James A. Trigilio ◽  
Khamsone Phasouk ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Ex Vivo ◽  
Neurite Growth ◽  
Nerve Fibers ◽  
Primary Neurons ◽  
Peripheral Neuropathies ◽  
Specific Receptor ◽  
Skin Biopsies ◽  
Simplex Virus ◽  
Initial Target

Despite frequent herpes simplex virus (HSV) reactivation, peripheral nerve destruction and sensory anesthesia are rare. We discovered that skin biopsies obtained during asymptomatic human HSV-2 reactivation exhibit a higher density of nerve fibers relative to biopsies during virological and clinical quiescence. We evaluated the effects of HSV infection on keratinocytes, the initial target of HSV replication, to better understand this observation. Keratinocytes produced IL-17c during HSV-2 reactivation, and IL-17RE, an IL-17c–specific receptor, was expressed on nerve fibers in human skin and sensory neurons in dorsal root ganglia. In ex vivo experiments, exogenous human IL-17c provided directional guidance and promoted neurite growth and branching in microfluidic devices. Exogenous murine IL-17c pretreatment reduced apoptosis in HSV-2–infected primary neurons. These results suggest that IL-17c is a neurotrophic cytokine that protects peripheral nerve systems during HSV reactivation. This mechanism could explain the lack of nerve damage from recurrent HSV infection and may provide insight to understanding and treating sensory peripheral neuropathies.

scholarly journals Hepatocyte innervation in primates.

1977 ◽  
Vol 74 (1) ◽  
pp. 299-313 ◽  
Author(s):  
W G Forssmann ◽  
S Ito
Keyword(s):  
Electron Microscopy ◽  
Fluorescence Microscopy ◽  
Close Association ◽  
Tree Shrew ◽  
Nerve Fibers ◽  
Adrenergic Nerves ◽  
Nerve Endings ◽  
Similar Distribution ◽  
Liver Lobule ◽  
Space Of Disse

The efferent innervation and some characteristics of nerve fibers of the liver lobule in the tree shrew, a primate, are described. Nerve endings on hepatocytes were encountered regularly and were determined to be efferent adrenergic nerves. Transmission electron microscopy revealed nerve endings and varicosities in close apposition to the hepatocytes adjacent to the connective tissue of the triads as well as within the liver lobule in the space of Disse. Fluorescence microscopy indicated the existence of adrenergic nerves with a similar distribution. Autoradiography of the avid uptake of exogenous [3H]norepinephrine indicated that all intralobular nerves are potentially norepinephrinergic (adrenergic). Chemical sympathectomy with 6-OH-dopamine resulted in the degeneration of all intralobular liver nerve fibers as revealed by fluorescence microscopy and electron microscopy. Substantial regeneration occurred after 60-90 days but was not completed by that time. Some nerves were also observed in close association with von Kupffer cells and endothelial cells. The functional significance of the efferent liver innervation is discussed.

scholarly journals Human IAPP is a driver of painful diabetic peripheral neuropathy

2021 ◽  
Author(s):  
Mohammed M. H. Asiri ◽  
Sabine Versteeg ◽  
Elisabeth M. Brakkee ◽  
J. Henk Coert ◽  
C. Erik Hack ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sensory Neurons ◽  
Nerve Fibers ◽  
Elevated Plasma ◽  
Β Cells ◽  
Islet Amyloid ◽  
Painful Diabetic Peripheral Neuropathy ◽  
Intra Epidermal Nerve Fibers

AbstractPeripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM), of which the pathogenesis is not fully understood. We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage islet β-cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth. Transgenic hIAPP Ob/Ob mice, an established animal model for T2DM, as well as hIAPP mice, which have elevated plasma hIAPP levels but no hyperglycaemia. Both transgenic mice developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intra-epidermal nerve fibers (IENF), suggesting hIAPP is a mediator of diabetic neuropathy. Intraplantar and intravenous hIAPP injection in WT mice induced long-lasting mechanical hypersensitivity and reduced IENF, whereas non-aggregating murine IAPP or mutated hIAPP (Pramlintide) did not have these effects, and were not toxic for cultured sensory neurons. In T2DM patients, significantly more hIAPP oligomers were found in the skin compared to non-T2DM controls. Thus, we provide evidence that hIAPP is toxic to sensory neurons, and mediates peripheral neuropathy in mice. The presence of hIAPP aggregates in skin of humans with T2DM supports the notion that human IAPP is a potential driver of T2DM neuropathy in man.

Some Biological Applications of High Voltage Electron Microscopy

1974 ◽  
Vol 32 ◽  
pp. 298-299
Author(s):  
Hans Ris
Keyword(s):  
High Voltage ◽  
Chromosome Structure ◽  
Nerve Fibers ◽  
Good Resolution ◽  
High Voltage Electron Microscopy ◽  
Voltage Electron ◽  
University Of Wisconsin ◽  
High Voltage Electron ◽  
One Year ◽  
The University

The High Voltage Electron Microscope Laboratory at the University of Wisconsin has been in operation a little over one year. I would like to give a progress report about our experience with this new technique. The achievement of good resolution with thick specimens has been mainly exploited so far. A cold stage which will allow us to look at frozen specimens and a hydration stage are now being installed in our microscope. This will soon make it possible to study undehydrated specimens, a particularly exciting application of the high voltage microscope.Some of the problems studied at the Madison facility are: Structure of kinetoplast and flagella in trypanosomes (J. Paulin, U. of Georgia); growth cones of nerve fibers (R. Hannah, U. of Georgia Medical School); spiny dendrites in cerebellum of mouse (Scott and Guillery, Anatomy, U. of Wis.); spindle of baker's yeast (Joan Peterson, Madison) spindle of Haemanthus (A. Bajer, U. of Oregon, Eugene) chromosome structure (Hans Ris, U. of Wisconsin, Madison). Dr. Paulin and Dr. Hanna are reporting their work separately at this meeting and I shall therefore not discuss it here.

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