The application of control limits analysis to the myometric assessment of motor performance in neuropathy patients

Measurement of muscle strength by myometry is used to monitor the natural course and treatment response of motor system diseases, both in individual patients and clinical trials. However, the practical usefulness of myometric data is reliant upon a statistical method for analysing serial strength measurements which distinguishes disease-related changes from random fluctuations in patient performance and operator/device dependent measurement errors. In this study we have applied control limits analysis to this problem. Using hand-held dynamometry, sets of baseline strength measurements were collected on two separate occasions during a period of clinical stability from up to four muscle groups in 22 patients with peripheral neuropathies. From these sets of data, 76 control limits were calculated and then used to describe the inter-measurement variation in muscle strength in individual muscles. The range of control limits was wide, varying from <10% of baseline (in 36% of muscles tested) to >50% (in 4% of muscles tested), with 88% of muscles falling within 30% of baseline. Follow-up data were also collected from all patients, including those undergoing treatment. Control limits analysis is a powerful and simple method for assessing the significance of motor performance changes in individual muscles in patients undergoing serial monitoring and can be easily applied to both single patients and clinical trials

Nuclear factor 1 activates the feline leukemia virus long terminal repeat but is posttranscriptionally down-regulated in leukemia cell lines

A recombinant feline leukemia virus (FeLV) proviral clone (T17T-22) with a long terminal repeat (LTR) which differs from prototype FeLV by a point mutation within a conserved nuclear factor 1 (NF1)-binding motif in the LTR enhancer domain was found to be poorly expressed after DNA transfection. The NF1 point mutation reduced in vitro protein binding as assessed by gel shift analysis and reduced promoter activity significantly (2- to 10-fold). However, the degree of promoter impairment due to the NF1 site mutation varied according to cell type and was least severe in a feline leukemia cell line (T3) which had low levels of nuclear NF1 DNA-binding activity. Low NF1 DNA-binding activity was observed in three FeLV-induced leukemia cell lines (T3, T17, and FL74) and in murine F9 embryonal carcinoma cells. While similar levels of NF1 gene mRNA transcripts were detected in all cell lines, Western immunoblot analysis of F9, T17, and FL74 but not T3 nuclear extracts revealed very low levels of nuclear NF1 protein. These results indicate that NF1 activity is down-regulated in FeLV-induced leukemia cells by diverse posttranscriptional mechanisms. We suggest that NF1 down-regulation may be an important characteristic of target cells susceptible to FeLV transformation in vivo and may provide the selective pressure which favors duplication of the LTR core enhancer sequence in T-cell leukemogenic FeLV variants

Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after <i>Campylobacter</i> infection

We investigated the possible mechanisms of paralysis and recovery in a patient with the acute motor axonal neuropathy (AMAN) pattern of the Guillain-Barré syndrome. The AMAN pattern of GBS is characterized clinically by acute paralysis without sensory involvement and electrodiagnostically by low compound motor action potential amplitudes, suggesting axonal damage, without evidence of demyelination. Many AMAN patients have serologic or culture evidence of recent Campylobacter jejuni infection. Pathologically, the most severe cases are characterized by wallerian-like degeneration of motor axons affecting the ventral roots as well as peripheral nerves, but some fatal cases have only minor changes in the roots and peripheral nerves, and some paralyzed patients with the characteristic electrodiagnostic findings of AMAN recover rapidly. The mechanism of paralysis and recovery in such cases has been uncertain. A 64-year-old woman with culture-proven Campylobacter upsaliensis diarrhea developed typical features of AMAN. She improved quickly following plasmapheresis. Her serum contained IgG anti-GM1 antibodies. The lipopolysaccharide of the organism bound peanut agglutinin. This binding was blocked by cholera toxin, suggesting that the organism contained the Gal(beta1-3)GalNAc epitope of GM1 in its lipopolysaccharide. Motor-point biopsy showed denervated neuromuscular junctions and reduced fiber numbers in intramuscular nerves. In contrast, the sural nerve biopsy was normal and skin biopsy showed normal dermal and epidermal innervation. In AMAN the paralysis may reflect degeneration of motor nerve terminals and intramuscular axons. In addition, the anti-GM1 antibodies, which can bind at nodes of Ranvier, might produce failure of conduction. These processes are potentially reversible and likely to underlie the capacity for rapid recovery that characterizes some cases of AMAN