ABSTRACT
Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues.
Subject(s)
Biological Assay , Immunoenzyme Techniques , Nerve Growth Factors/analysis , Neurons, Afferent/metabolism , Animals , Brain Chemistry , Cattle , Chick Embryo , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Humans , Mice , Myocardium/chemistry , Nerve Growth Factors/blood , Nerve Growth Factors/cerebrospinal fluid , Nerve Growth Factors/pharmacology , Rats , Rats, Wistar , Recombinant Proteins/blood , Recombinant Proteins/cerebrospinal fluid , Recombinant Proteins/metabolism , Sciatic Nerve/chemistry , Sensitivity and SpecificityABSTRACT
The POEMS syndrome is a synopsis of different symptoms such as polyneuropathy, organomegaly, endocrine disturbances, M-protein and skin changes. The leading symptoms are neuropathy and the skin symptoms. Additionally, a monoclonal light chain gammopathy is often found. The administration of immunosuppressive drugs yields a substantial improvement in some cases. We report here about a 72 year old lady who fell ill with a rapidly progressive neuropathy accompanied by hyperpigmentation and a morphea-like induration of the skin. A biopsy of the sural nerve showed a demyelinating axonal neuropathy and a focal vasculitis. Isoelectric focussing revealed oligoclonal bands in cerebrospinal fluid and serum. The cortisol serum level was very low and there were signs of a latent diabetes mellitus. These clinical features correspond to the POEMS syndrome. The prescription of initially 1 mg and later 0.5 mg prednisone improved the patient's condition dramatically.
Subject(s)
POEMS Syndrome/diagnosis , Aged , Biopsy , Electromagnetic Fields , Electromyography/drug effects , Female , Humans , Immunoglobulin E/analysis , Muscles/innervation , Neurologic Examination/drug effects , POEMS Syndrome/pathology , POEMS Syndrome/physiopathology , Peripheral Nerves/drug effects , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Prednisolone/administration & dosageABSTRACT
Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a variety of embryonic neurons in culture. The developmental expression of CNTF occurs clearly after the time period of the physiological cell death of CNTF-responsive neurons. This, together with the sites of expression, excludes CNTF as a target-derived neuronal survival factor, at least in rodents. However, CNTF also participates in the induction of type 2 astrocyte differentiation in vitro. Here we demonstrate that the time course of the expression of CNTF-mRNA and protein in the rat optic nerve (as evaluated by quantitative Northern blot analysis and biological activity, respectively) is compatible with such a glial differentiation function of CNTF in vivo. We also show that the type 2 astrocyte-inducing activity previously demonstrated in optic nerve extract can be precipitated by an antiserum against CNTF. Immunohistochemical analysis of astrocytes in vitro and in vivo demonstrates that the expression of CNTF is confined to a subpopulation of type 1 astrocytes. The olfactory bulb of adult rats has comparably high levels of CNTF to the optic nerve, and here again, CNTF-immunoreactivity is localized in a subpopulation of astrocytes. However, the postnatal expression of CNTF in the olfactory bulb occurs later than in the optic nerve. In other brain regions both CNTF-mRNA and protein levels are much lower.
Subject(s)
Astrocytes/chemistry , Brain/metabolism , Nerve Tissue Proteins/analysis , Optic Nerve/chemistry , RNA, Messenger/analysis , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Brain/embryology , Brain/growth & development , Cell Differentiation , Ciliary Neurotrophic Factor , Gene Expression/physiology , Kinetics , Microscopy, Fluorescence , Molecular Sequence Data , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Polymerase Chain Reaction , RNA, Messenger/genetics , RatsABSTRACT
A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF.
