myelin-basic-protein and Peripheral-Nervous-System-Diseases

Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intraepidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials.

Topics: Axons; Biopsy; Humans; Microscopy, Immunoelectron; Myelin Basic Protein; Nerve Fibers; Nerve Tissue Proteins; Peripheral Nervous System Diseases; Skin; Ubiquitin Thiolesterase

Infantile Krabbe disease results in the accumulation of lipid-raft-associated galactosylsphingosine (psychosine), demyelination, neurodegeneration and premature death. Recently, axonopathy has been depicted as a contributing factor in the progression of neurodegeneration in the Twitcher mouse, a bona fide mouse model of Krabbe disease. Analysis of the temporal-expression profile of MBP (myelin basic protein) isoforms showed unexpected increases of the 14, 17 and 18.5 kDa isoforms in the sciatic nerve of 1-week-old Twitcher mice, suggesting an abnormal regulation of the myelination process during early postnatal life in this mutant. Our studies showed an elevated activation of the pro-apoptotic protease caspase 3 in sciatic nerves of 15- and 30-day-old Twitcher mice, in parallel with increasing demyelination. Interestingly, while active caspase 3 was clearly contained in peripheral axons at all ages, we found no evidence of caspase accumulation in the soma of corresponding mutant spinal cord motor neurons. Furthermore, active caspase 3 was found not only in unmyelinated axons, but also in myelinated axons of the mutant sciatic nerve. These results suggest that axonal caspase activation occurs before demyelination and following a dying-back pattern. Finally, we showed that psychosine was sufficient to activate caspase 3 in motor neuronal cells in vitro in the absence of myelinating glia. Taken together, these findings indicate that degenerating mechanisms actively and specifically mediate axonal dysfunction in Krabbe disease and support the idea that psychosine is a pathogenic sphingolipid sufficient to cause axonal defects independently of demyelination.

Topics: Animals; Animals, Newborn; Axons; Caspase 3; Cell Line, Transformed; Ceramides; Disease Models, Animal; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Leukodystrophy, Globoid Cell; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Motor Neurons; Myelin Basic Protein; Neural Conduction; Neurofilament Proteins; Peripheral Nervous System Diseases; Protein Isoforms; Psychosine; Sciatic Nerve; Spinal Cord

Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Multiple Sclerosis; Myelin Basic Protein; Peripheral Nervous System Diseases

Topics: Amino Acid Sequence; Amino Acids; Animals; Antigens; Chemical Phenomena; Chemistry; Demyelinating Diseases; Humans; Myelin Basic Protein; Neuritis; Peripheral Nervous System Diseases; Polyradiculoneuropathy; Sciatic Nerve

In the present study, we screened the sera of subjects chronically exposed to mixtures of pesticides (composed mainly of organophosphorus compounds (OPs) and others) and developed neurological symptoms for the presence of autoantibodies against cytoskeletal neural proteins. OPs have a well-characterized clinical profile resulting from acute cholinergic crisis. However, some of these compounds cause neuronal degeneration and demyelination known as organophosphorus compound-induced delayed neurotoxicity (OPIDN) and/or organophosphorus compound-induced chronic neurotoxicity (OPICN). Studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins against cytoskeletal neural proteins in patients with chemical-induced brain injury. In this study, we screened the serum of 50 pesticide-exposed subjects and 25 non-exposed controls, using Western blot analysis against the following proteins: neurofilament triplet proteins (NFPs), tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII), glial S100-B protein, and alpha-synuclein (SNCA). Serum reactivity was measured as arbitrary chemiluminescence units. As a group, exposed subjects had significantly higher levels of autoantibody reactivity in all cases examined. The folds of increase in of autoantibodies against neural proteins of the subjects compared to healthy humans in descending order were as follows: MBP, 7.67, MAG 5.89, CaMKII 5.50, GFAP 5.1, TAU 4.96, MAP2 4.83, SNCA 4.55, NFP 4.55, S-100B 2.43, and tubulin 1.78. This study has demonstrated the presence of serum autoantibodies to central nervous system-specific proteins in a group of farmers chronically exposed to pesticides who developed neurological signs and symptoms of neural injury. These autoantibodies can be used as future diagnostic/therapeutic target for OP-induced neurotoxicity.

Topics: Adult; Aged; Autoantibodies; Biomarkers; Cytoskeletal Proteins; Female; Glial Fibrillary Acidic Protein; Humans; Male; Middle Aged; Myelin Basic Protein; Neurofilament Proteins; Neurotoxicity Syndromes; Organophosphorus Compounds; Peripheral Nervous System Diseases; Pesticides

Topics: Animals; Dose-Response Relationship, Drug; Embryo, Mammalian; Ganglia, Spinal; Glycine; Glyphosate; Herbicides; In Vitro Techniques; Intermediate Filaments; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Myelin Sheath; Neurites; Nitric Oxide; Organ Culture Techniques; Peripheral Nervous System Diseases; Propylamines; S100 Proteins; Schwann Cells; Tumor Necrosis Factor-alpha

Topics: Autoantibodies; Congresses as Topic; Consensus; Humans; Immunoglobulin M; Myelin Basic Protein; Netherlands; Peripheral Nervous System Diseases

A 59-year-old man had been admitted to another hospital because of diplopia and thirst at the beginning of March and was diagnosed with diabetic ketoacidosis. He was referred to our hospital because he had limb weakness, dysarthria, and bilateral sensory impairment of the upper limbs, which worsened rapidly from the middle of March, although plasma glucose had been well controlled after the initiation of insulin therapy in the previous hospital. Contrast spinal MRI in our hospital revealed hyperintense lesions at the level of C4 to C5 and T10. The level of myelin basic protein was high (1,260 pg/ml) in the cerebrospinal fluid and serum anti-neurofascin antibody was negative. Nerve conduction study showed typical findings of demyelination at least 2 regions. Although anti-neurofascin antibody was negative, he was diagnosed with combined central and peripheral demyelination (CCPD) based on these clinical findings. After the repeated methylprednisolone pulse therapy for five times, the hyperintense lesions of the spinal cord disappeared gradually. He was bedridden at the beginning of his hospitalization but could ambulate with a cane on discharge 2 months after the admission. Then we received the result of anti-galactocerebroside antibody test as positive. This case suggested that high-dose steroid pulse therapy is safe and may be effective for anti-galactocerebroside antibody-positive CCPD.

Topics: Autoantibodies; Biomarkers; Cell Adhesion Molecules; Central Nervous System Diseases; Demyelinating Diseases; Galactosylceramides; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Myelin Basic Protein; Nerve Growth Factors; Peripheral Nervous System Diseases; Pulse Therapy, Drug; Treatment Outcome

Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect of TNF-α signaling suppression and the potential of TNF-α in the treatment of DPN, a recombinant human TNF-α receptor-antibody fusion protein (rhTNFR:Fc) was used. We focused on the pathophysiology of the sciatic nerve and examined the expression of myelin basic protein (MBP) under DPN status with or without TNF-α inhibition.. The DPN rat model was generated by intraperitoneal injection of streptozotocin and by feeding with a high-fat, high-sugar diet. The nerve conduction velocity (NCV) in sciatic nerve of rat was monitored over a period of four weeks. The histopathological changes in nerve tissue were examined through traditional tissue histology and ultrastructure transmission electron microscopy (TEM). The expression of MBP was examined through western blot analysis.. The DPN induced rats showed significant signs of nerve damage including lower NCV, demyelination of nerve fibers, disorganization of lamellar and axonal structures, and decreased expression of MBP in the nerve tissue. The inhibition of TNF-α in the DPN rats resulted in a significant recovery from those symptoms compared to the DPN rats.. Our study demonstrates that TNF-α plays a key role in the pathogenesis of DPN and its inhibition by rhTNFR:Fc can prove to be a useful therapeutic strategy for the treatment of and/or prevention from DPN symptoms.

Topics: Animals; Axons; Blotting, Western; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Humans; Immunohistochemistry; Male; Microscopy, Electron, Transmission; Motor Neurons; Myelin Basic Protein; Nerve Fibers; Neural Conduction; Peripheral Nervous System Diseases; Rats; Rats, Wistar; Receptors, Tumor Necrosis Factor, Type I; Recombinant Fusion Proteins; Sciatic Nerve; Sensory Receptor Cells; Tumor Necrosis Factor-alpha

The transcription factor Sox10 functions during multiple consecutive stages of Schwann-cell development in the peripheral nervous system (PNS). Although Sox10 continues to be expressed in mature Schwann cells of the adult peripheral nerve, it is currently unclear whether it is still functional. Here, we used a genetic strategy to selectively delete Sox10 in glia of adult mice in a tamoxifen-dependent manner. The tamoxifen-treated mice developed a severe peripheral neuropathy that was associated with dramatic alterations in peripheral nerve structure and function. Demyelination and axonal degeneration were as much evident as signs of neuroinflammation. Compound action potentials exhibited pathophysiological alterations. Sox10-deleted Schwann cells persisted in the peripheral nerve, but did not exhibit a mature, myelinating phenotype arguing that Sox10 is rather required for differentiation and maintenance of the differentiated state than for survival. Our report is the first evidence that Sox10 is still essentially required for Schwann-cell function in the adult PNS and establishes a useful model in which to study human peripheral neuropathies.

Topics: Action Potentials; Animals; CD3 Complex; Cell Death; Cell Proliferation; Estrogen Antagonists; Gene Expression Regulation; Homeostasis; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Electron, Transmission; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Neural Conduction; Peripheral Nervous System Diseases; Platelet Endothelial Cell Adhesion Molecule-1; Schwann Cells; Sciatic Nerve; SOXE Transcription Factors; Tamoxifen; Time Factors

In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126-/- mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.

Topics: Animals; Cochlear Nerve; Early Growth Response Protein 2; Immunohistochemistry; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Myelin Basic Protein; Myelin P0 Protein; Octamer Transcription Factor-6; Peripheral Nerves; Peripheral Nervous System Diseases; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; Schwann Cells

Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis, we induced 60-70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two pmp22 alleles (pmp22(+/-)). Induction time for the CB was significantly shorter in pmp22(+/-) mice than that in pmp22(+/+) mice. This shortened induction was also found in myelin-associated glycoprotein knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin. Pmp22(+/-) nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [(3)H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.

Topics: Action Potentials; Age Factors; Animals; Biophysics; Disease Models, Animal; Electric Stimulation; Gene Expression Regulation; Kv1.2 Potassium Channel; Luminescent Proteins; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Muscle, Skeletal; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Nerve Block; Nerve Fibers; Neural Conduction; Peripheral Nerves; Peripheral Nervous System Diseases; Protein Binding; Reaction Time; Saxitoxin; Sodium Channels; Tritium

Peripheral neurotoxicity is a frequent complication limiting docetaxel chemotherapy in patients with cancer. We developed an experimental model that closely mimics the course of neuropathy in patients, aiming to investigate both the mechanisms of neurotoxicity at biochemical, functional and morphological levels and the potential neuroprotective role of neuroactive steroids. We demonstrated that treatment with dihydroprogesterone (DHP) or progesterone (P) counteracts docetaxel-induced neuropathy, preventing nerve conduction and thermal threshold changes, and degeneration of skin nerves in the foodpad. Neuroactive steroids also counteract the changes in gene expression of several myelin proteins and calcitonin gene-related peptide induced by docetaxel in sciatic nerve and lumbar spinal cord, respectively. Most nerve abnormalities observed during the treatment with docetaxel spontaneously recovered after drug withdrawal, similarly to what occurs in patients. However, results of midterm follow-up experiments indicated that animals cotreated with DHP or P have a faster recovery of the neuropathy compared with docetaxel-treated rats. Our study confirmed that neuroactive steroids exert a protective effect on peripheral nerves at different levels, suggesting that they might represent a new therapeutic frontier for patients with chemotherapy-induced neuropathy.

Topics: 20-alpha-Dihydroprogesterone; Analysis of Variance; Animals; Body Weight; Disease Models, Animal; Docetaxel; Gene Expression Regulation; Male; Myelin Basic Protein; Myelin P0 Protein; Myelin Proteins; Nerve Fibers; Neural Conduction; Neuroprotective Agents; Pain Threshold; Peripheral Nervous System Diseases; Progesterone; Rats; Rats, Inbred F344; Sciatic Nerve; Taxoids

Immunohistochemistry was used to examine the expression of prostaglandin E(2) receptors EP1 and EP4 in sciatic nerves from the rat chronic constriction injury (CCI) model of neuropathic pain. At 21 days post-surgery the CCI rats had developed mechanical hyperalgesia on the operated side, and quantitative image analysis showed a highly significant doubling of the area occupied by EP1- and EP4-positive pixels in sections from CCI nerves when compared to sham-operated controls. Co-localisation studies with the marker ED1 revealed that 73% of the EP1-positive cells and 54% of the EP4-positive cells in the injured nerves represented infiltrating macrophages. Cells negative for ED1 and positive for either EP1 or EP4 were characterised as Schwann cells from their morphology and expression of myelin basic protein and S100 antigens. Similar EP1- and EP4-positive Schwann cell profiles were observed in sections of uninjured control nerves. Low levels of EP receptor expression were found in neurofilament-immunostained axons, but no consistent differences were observed in the levels of axonal EP staining between CCI and control tissue. These data provide further evidence of the importance of prostaglandins in the pathogenesis of neuropathic pain, and suggest that not only infiltrating macrophages but also Schwann cells may be involved in the modulation of these mediators in response to nerve injury.

Topics: Animals; Axons; Chemotaxis, Leukocyte; Chronic Disease; Disease Models, Animal; Immunohistochemistry; Inflammation; Ligation; Macrophages; Male; Myelin Basic Protein; Neuralgia; Peripheral Nervous System Diseases; Prostaglandins; Rats; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Prostaglandin E, EP4 Subtype; S100 Proteins; Schwann Cells; Sciatic Neuropathy; Up-Regulation

Clusterin is a protein involved in multiple biological events, including neuronal cytoprotection, membrane recycling and regulation of complement-mediated membrane attack after injury. We investigated the effect of recombinant human clusterin in preclinical models of peripheral neuropathies. Daily treatment with clusterin accelerated the recovery of nerve motor evoked potential parameters after sciatic nerve injury. Prophylactic or therapeutic treatment of experimental autoimmune neuritis rats with clusterin also accelerated the rate of recovery from the disease, associated with remyelination of demyelinated nerve fibers. These data demonstrate that clusterin is capable of ameliorating clinical, neurophysiological and pathological signs in models of peripheral neuropathies.

Topics: Animals; Clusterin; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Hippocampus; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Myelin Sheath; Nerve Growth Factors; Nerve Regeneration; Neurons; Organ Culture Techniques; Peripheral Nerves; Peripheral Nervous System Diseases; Recombinant Proteins; Sciatic Neuropathy; Treatment Outcome

Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.

Topics: Animals; Animals, Newborn; Cell Differentiation; Cells, Cultured; Cerebellum; Coculture Techniques; Demyelinating Diseases; Embryo, Mammalian; Ganglia, Spinal; Humans; Immunohistochemistry; Mice; Mice, Neurologic Mutants; Microscopy, Electron; Multipotent Stem Cells; Myelin Basic Protein; Nerve Tissue Proteins; Neurons; Peripheral Nervous System Diseases; Rats; Schwann Cells; Skin; Stem Cell Transplantation

We show that normal peripheral nerve myelination depends on strict dosage of the most abundantly expressed myelin gene, myelin protein zero (Mpz). Transgenic mice containing extra copies of Mpz manifested a dose-dependent, dysmyelinating neuropathy, ranging from transient perinatal hypomyelination to arrested myelination and impaired sorting of axons by Schwann cells. Myelination was restored by breeding the transgene into the Mpz-null background, demonstrating that dysmyelination does not result from a structural alteration or Schwann cell-extrinsic effect of the transgenic P(0) glycoprotein. Mpz mRNA overexpression ranged from 30-700%, whereas an increased level of P(0) protein was detected only in nerves of low copy-number animals. Breeding experiments placed the threshold for dysmyelination between 30 and 80% Mpz overexpression. These data reveal new points in nerve development at which Schwann cells are susceptible to increased gene dosage, and suggest a novel basis for hereditary neuropathy.

Topics: Animals; Blotting, Western; Demyelinating Diseases; Gene Dosage; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Myelin Basic Protein; Myelin P0 Protein; Myelin Proteins; Organ Specificity; Peripheral Nervous System Diseases; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Schwann Cells; Sciatic Nerve

An expanded follow-up assessment of the autoantibody response to neuronal and astroglial autoantigens (NF68; NF160; NF200; MBP; GFAP) as early markers of neurotoxicity was performed in male workers exposed to lead (Pb) of a battery factory (n=50) and a matched reference group (R) of workers at a food packing plant (n=39). Mean age, years of exposure and blood lead (PbB ug/dl) (+/-SD) for lead and R, respectively, were: Age:39 +/- 6; 41 +/- 7; Yrs. Exposed: 14 +/- 6:0; PbB: 32 +/- 11: 16 +/- 5 percent with detectable titers to nervous system proteins in the Pb and R populations, respectively, were: Anti-NF68: 59; 17; Anti-NF160: 28; 15; Anti-NF200: 25; 0; Anti-GFAP: 90; 20; Anti-MBP: 16; 4. Autoantibodies to nervous system proteins predominated in workers occupationally exposed to Pb compared to R. Anti-NF68 and GFAP titers were the most frequently encountered. Anti-NF68 titers were significantly correlated with years of exposure (r = 0.538, p < 0.0001) and with PbB (r=0.325, p < 0.05). Furthermore, the number of detectable autoantibody types correlated with clinical scores of sensorimotor deficits (r = 0.459, p < 0.0001). This study suggests that autoantibodies provide a promising biomarker of neurotoxicity while providing information on subcellular targets. It also raises concerns of toxicant-induced autoimmune neuropathy.

Topics: Adult; Air Pollutants, Occupational; Autoantibodies; Biomarkers; Case-Control Studies; Egypt; Environmental Monitoring; Epidemiological Monitoring; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunoglobulin G; Immunoglobulin M; Inhalation Exposure; Lead Poisoning; Male; Middle Aged; Myelin Basic Protein; Occupational Diseases; Occupational Exposure; Peripheral Nervous System Diseases; Sensitivity and Specificity; Surveys and Questionnaires; Threshold Limit Values; Urban Health

A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.

Topics: Adolescent; Adult; Biopsy; Charcot-Marie-Tooth Disease; Child; Female; Gene Dosage; Genetic Predisposition to Disease; Genotype; Humans; Immunohistochemistry; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin Proteins; Nerve Compression Syndromes; Paralysis; Peripheral Nervous System Diseases; Sural Nerve

Topics: Autoantibodies; Biopsy; Epitopes; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunoglobulin M; Microscopy, Confocal; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Paraproteinemias; Peripheral Nerves; Peripheral Nervous System Diseases; Polyneuropathies; S100 Proteins; Sural Nerve

To study whether nervous tissue trauma provokes myelin antigen autoreactive T and B cell responses in humans we examined consecutive blood samples from 7 patients with polyneuropathy undergoing diagnostic sural nerve biopsy and 8 control patients undergoing other types of minor surgery. The antigen-specific T cells were assessed by enumerating cells secreting interferon-gamma (IFN-gamma) in response to the myelin components P0, P2, myelin basic protein (MBP) and myelin associated glycoprotein (MAG), and to 4 selected MBP peptides. B cell mediated immunity was assessed by counting numbers of cells secreting antibodies directed against the myelin proteins. On day 7 after biopsy, there were 3-10-fold increased numbers of T and B cells reactive with P0, P2, MBP and MAG in blood of polyneuropathy patients compared to controls, while levels of cells recognizing purified protein derivate or responding to phytohemagglutinin (PHA) did not differ significantly. Comparison of prebiopsy levels on day 0 with post-biopsy levels on day 7 in the polyneuropathy patients revealed a significant increase in T cells recognizing P0, P2 and MAG, and in B cells secreting IgG antibodies against P0 and P2. On day 14 after nerve biopsy these differences were no longer seen. We suggest that in patients with polyneuropathy, sural nerve biopsy with the ensuing wallerian degeneration and myelin breakdown causes transiently increased levels of circulating myelin autoreactive T and B cells. It remains to be determined if this has a physiological role in nerve trauma responses and/or affects the clinicopathological course of the peripheral neuropathy.

Topics: Adolescent; Aged; Autoantibodies; Autoimmunity; B-Lymphocytes; Biopsy; Female; Humans; Immunoglobulin G; Interferon-gamma; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin P2 Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Peptide Fragments; Peripheral Nervous System Diseases; Sural Nerve; T-Lymphocytes; Time Factors; Wallerian Degeneration

We studied 61 patients with complications of Semple-type postexposure rabies immunization. Thirty-six had neurologic signs, and 25 had only fever, headache, or myalgia. Thirty-two patients had CNS complications, and 4 had an acute peripheral neuropathy. Disease was acute and monophasic in 33, but 3 patients had progressive disease, including 1 patient with a relapsing-remitting course. No clinical features, including CSF content of myelin basic protein, were prognostic indicators. In three of six patients with encephalomyelitis, lymphocytes showed a proliferative response to myelin.

Topics: Central Nervous System Diseases; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Humans; Lymphocyte Activation; Myelin Basic Protein; Peripheral Nervous System Diseases; Rabies Vaccines

In 27 potential neuropathies an enzyme-linked immunosorbent assay, using P2 preparations from either bovine or equine myelin, detected all cases of cauda equina neuritis in which there was caudal involvement. The test was of limited value in differentiating neuropathies involving only cranial or other peripheral nerves.

Topics: Animals; Cauda Equina; Chromatography, High Pressure Liquid; Diagnosis, Differential; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Horse Diseases; Horses; Male; Myelin Basic Protein; Myelin P2 Protein; Neuritis; Peripheral Nervous System Diseases

The presence of myelin basic protein (MBP)-like material in cerebrospinal fluid (CSF) usually reflects breakdown of central nervous system myelin. Immunoreactive MBP levels were measured in 70 CSF specimens from 66 patients with a variety of peripheral neuropathies. Immunoreactive MBP was present in CSF in 70% (16 of 23) of patients with biopsy-proved chronic demyelinating polyneuropathies, whereas in neuropathies producing primarily axonal damage it was present in only 22% (5 of 23). In Guillain-Barré syndrome, 45% (9 of 20) of patients had immunoreactive MBP in the CSF. We conclude that MBP-like material is present in the CSF of most patients with longstanding demyelinating polyradiculoneuropathies and probably reflects detection of peripheral nervous system P1 protein.

Topics: Demyelinating Diseases; Humans; Myelin Basic Protein; Peripheral Nervous System Diseases; Polyradiculoneuropathy

Topics: Humans; Myelin Basic Protein; Peripheral Nervous System Diseases

Tumors from two patients with carcinomatous neuropathy were studied with an immunohistochemical method using anti-myelin basic protein (anti-MBP) sera. In both cases, immunoreactive MBP was clearly demonstrated in some of the tumor cells, which were widely distributed either singly or, more often, in clusters. The staining intensity varied from cell to cell. An autoimmune mechanism to nervous elements has been suggested in the pathogenesis of carcinomatous neuropathy. MBP is known to be a highly specific and potent antigen that can induce allergic neuritis in animals. In one patient the progressively worsening neurologic condition rapidly improved after gastrectomy removed the carcinoma. It is possible that immunoreactive MBP in tumor cells may function as an "antigen" in the development of carcinomatous neuropathy.

Topics: ACTH Syndrome, Ectopic; Adenocarcinoma; Aged; Autoimmune Diseases; Humans; Lung Neoplasms; Male; Myelin Basic Protein; Neoplasm Proteins; Peripheral Nervous System Diseases; Stomach Neoplasms

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS.

Topics: Acute Disease; Brain Diseases; Female; Humans; Male; Multiple Sclerosis; Myelin Basic Protein; Peripheral Nervous System Diseases; Recurrence; Remission, Spontaneous; Time Factors

Topics: Aged; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin M; Immunologic Techniques; Male; Microscopy, Electron; Myelin Basic Protein; Myelin Sheath; Paraproteinemias; Peripheral Nervous System Diseases; Spinal Nerves; Sural Nerve

We examined the in vivo demyelinating activity of serum from dogs with acute canine idiopathic polyneuropathy (ACIP), a Guillain-Barré syndrome (GBS)-like illness. Sera from 6 ACIP cases demyelinated rat sciatic nerves more intensely than 11 control sera. Serum activity increased after guinea pig serum (gps) was added, although gps alone had little effect. ACIP sera did not bind more to whole nerve cross sections or Schwann cells in vitro than control sera, and did not contain elevated antigalactocerebroside titers. We do not as yet know the pathogenic importance of the demyelinating factor in ACIP and control dog serum, or understand its relationship to the demyelinating constituent in serum from humans with GBS.

Topics: Animals; Demyelinating Diseases; Dog Diseases; Dogs; Guinea Pigs; Myelin Basic Protein; Myelin Sheath; Peripheral Nerves; Peripheral Nervous System Diseases; Rats; Schwann Cells; Sciatic Nerve

Patients admitted to the neurosurgical wards for the management of nervous system tumours, subarachnoid and intracerebral haemorrhage, head injury, spinal and peripheral nerve lesions, and other miscellaneous neurosurgical conditions, were studied by assay of serum immunoreactivity for myelin basic protein. Of 171 patients, 70% proved to have elevated myelin basic protein activity. In cerebral cases the extent of brain damage assessed by clinical methods appeared to correlate with the appearance of elevated serum myelin basic protein. In spinal and peripheral nerve cases no similar elevation of myelin basic protein was observed.

Topics: Adolescent; Adult; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Myelin Basic Protein; Nervous System Diseases; Peripheral Nervous System Diseases; Postoperative Complications; Prognosis; Radioimmunoassay; Spinal Cord Diseases

Topics: Antibodies; Humans; Leprosy; Myelin Basic Protein; Peripheral Nervous System Diseases

The macrophage migration inhibition factor (MIF) assay and a counterimmunodiffusion assay were utilized to measure immune responses to human myelin basic protein in 75 patients with multiple sclerosis (MS) and in 120 control subjects. Eight out of ten MS patients in acute exacerbation and one out of seventeen convalescent, but none of chronically ill MS patients gave positive results in the MIF test. Forty-six percent of the patients with negative MIF assays but only 22% of those with positive assays had positive antibody results. In the counterimmunodiffusion assay, myelin basic protein antibody was demonstrated in almost 2/3 of patients during convalescence but it was not present in those whose illness had been stable for 6 months or longer. While no correlation with the stage or duration of the illness was present in other disorders, in MS an inverse correlation with clinical activity and in vitro evidence of cellular sensitization to encephalitogenic basic protein was apparent.

Topics: Autoantibodies; Central Nervous System Diseases; Encephalitis; Humans; Immunity, Cellular; Macrophage Migration-Inhibitory Factors; Multiple Sclerosis; Myasthenia Gravis; Myelin Basic Protein; Peripheral Nervous System Diseases

A direct macrophage migration test is described, which proved to be useful for the detection of cellular hypersensitivity in man. We used a modification of the method described by Hughes & Paty (1972). In this method the MLR is abolished by 100 rad gamma-irradiation of the peritoneal exudate cells prior to pooling with human lymphocytes. Experiments with various intensity of irradiation, PPD, muscle antigen and encephalitogenic factor were performed to check this method. In a pilot study lymphocytes of patients with diseases of the central or peripheral nervous system or of muscle were tested. This proved that a hypersensitivity of Ef was present in various diseases of the CNS, while in muscle diseases positive tests were found using muscle antigen.

Topics: Antigens; Ascitic Fluid; Cell Migration Inhibition; Central Nervous System Diseases; Gamma Rays; Humans; Immunity, Cellular; Lymphocyte Culture Test, Mixed; Lymphocytes; Macrophages; Muscles; Muscular Diseases; Myelin Basic Protein; Peripheral Nervous System Diseases; Radiation Effects; Tuberculin; Tuberculin Test