Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

Sequential electrodiagnostic evaluation of diabetic neuropathy after combined pancreatic and renal transplantation

To asses the long-term evolution of diabetic polyneuropathy after a combined kidney-pancreas transplant, an electrophysiological study was performed in 20 diabetic patients before transplant, and 1 (n=18), 2 (n=16), 3 (n=10) and 4 years (n=5) at a later date. Motor and sensory scores were calculated for conduction velocity and amplitude to determine the physiopathological process. During evolution the scores were not found to be decreasing. Motor and sensory velocity scores were significantly improved (p<0.05) 1=" and=" 2=" years=" after=" the=" graft,=" when=" score=" values=" tended=" to=" stabilize.=" motor=" and=" sensory=" amplitude=" scores,=" which=" are=" more=" sensitive=" for=" axonal=" loss=" assessment=" were=" slightly=" but=" not=" significantly=">     

Idiopathic ocular neuromyotonia: a neurovascular compression syndrome?

Ocular neuromyotonia in the muscles innervated by the right oculomotor nerve was diagnosed in a patient without a history of radiation therapy. Electromyography of the levator palpebrae showed continuous motor unit activity. Brain MRI disclosed a close contact between the right third cranial nerve and a basilar artery dolichoectasia. The patient partly benefited from carbamazepine therapy. This unique finding suggests that neurovascular compression syndrome could be an hitherto unrecognised cause of ocular neuromyotonia.     

Effect of d-amphetamine repeated administration on rat antioxidant defences

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-β-d-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs. Received: 19 October 1998 / Accepted: 11 January 1999     

Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles.

Dissolution, translocation, and disposition have been shown to play a key role in the fate and effects of inhaled particles and fibers. Concepts that have been applied in the micron size range may be usefully applied to the nanoscale range, but new challenges are presented based on the small size and possible change in the dissolution:translocation relationship. The size of the component molecule itself may be on the nanoscale. Solute concentration, surface area, surface morphology, surface energy, dissolution layer properties, adsorbing species, and aggregation are relevant parameters in considering dissolution at the nanoscale. With regard to the etiopathology caused by these types of particulates, the metrics of dose (particle number, surface area, mass or shape) is not yet well defined. Analytical procedures for assessing dissolution and translocation include chemical assay and particle characterization. Leaching of substituents from particle surfaces may also be important. Compartmentalization within the respiratory tract may add another dimension of complexity. Dissolution may be a critical step for some nanoscale materials in determining fate in the environment and within the body. This review, combining aspects of particle toxicology, material science, and analytical chemistry, is intended to provide a useful basis for developing relevant dissolution assay(s) for nanoscale particles.