Many studies have documented an association between chronic low back pain (LBP) and deficits in back muscle strength and endurance. The sub-optimal performance is believed to be the result of alterations in the size and structure of the muscle, although the long-standing issue of whether the observed changes precede or are a consequence of the pain remains unresolved. If consequent to the problem, and predominantly related to disuse of the muscles, then it may be expected that a relationship between muscle structure and symptom duration would exist. Lumbar paraspinal muscle samples were obtained from 59 chronic LBP patients using the percutaneous biopsy technique. The samples were subject to routine histochemical analysis for the examination of muscle fibre type characteristics and cytochemical architectural changes. In 55 of the patients, the gross cross-sectional areas of magnetic resonance images of the trunk muscles were also measured. Multivariate analysis showed that symptom duration was the strongest predictor of the individual proportions of the fast-fatigable type IIX fibres; with age and gender included in the model, nearly 30% of the variance in fibre type distribution could be accounted for. Duration of pain had no influence on fibre size. Gross muscle cross-sectional area correlated directly with lean body mass and inversely with age, but showed no relationship with symptom duration. Pathological changes in the internal fibre structure were more frequently encountered in older patients, and were independent of symptom duration. The results suggest that, over the long term, fibre type transformations rather than alterations in fibre size are the predominant changes to be found in the muscles of chronic LBP patients. The direction of change supports the results of many previous studies that have demonstrated corresponding differences in the fatigability of the muscles. There is a strong case for the early implementation of active measures to attempt to offset the development of these changes in back pain patients.

We present in this paper the nucleotidic sequence of the FUR4 gene encoding the uracil permease in the yeast Saccharomyces cerevisiae. The deduced amino acid sequence of the permease has 633 residues; it consists of many hydrophobic stretches, only the N-terminal and C-terminal ends of the protein (about 100 and 50 amino acids respectively) being mostly hydrophilic. No N-terminal hydrophobic signal peptide is present, although it is shown in this work that the biosynthesis of the uracil permease goes through the secretion/glycosylation pathway. Using the results of three different methods, allowing the prediction of transmembrane a helices in proteic sequences, we drew a model of folding of the permease in the membrane.In yeast many specific permeases have been characterized both by genetic and physiological analysis [I, 21. The lunetic properties of this kind of protein, analysed in microorganisms (where the lactose permease of Escherichia coli deserves special mention [3,4]) and in mammalian cells, led to the formulation of phenomenological models of functioning where the concept of a 'carrier' was developed, but the mechanisms of transport at molecular level are poorly understood. This requires a knowledge of structure and organization of the carrier protein. Unfortunately in microorganisms where the genetic approach is feasible, the biochemical and structural analysis of such proteins lags much behind the physiological and genetic analysis owing to both their low concentration in the plasma membrane and their physicochemical properties.Molecular cloning of the gene, allowing genetic amplification and DNA sequencing, is one way to gain insight into the protein circumventing the isolation of the protein as a first stage. Indeed molecular cloning of the lactose permease of E. coli allowed both determination of the primary structure by DNA sequencing and, thanks to overexpression of the cloned gene, purification of the lactose permease. Also the DNAs coding for the human glucose transporter [5] and murine erythrocyte anion-exchange protein [6] were sequenced leading to the complete elucidation of the primary structure of the proteins. In Saccharomyes cerevisiae the DNA sequences of two amino acid permeases were recently published [7-91. In our laboratory two permeases specific for pyrimidine uptake, namely the uracil permease and the purine-cytosine permease, have been previously described [lo, 111. The genes coding for these permeases were cloned [12, 131 and the nucleotide sequence of these genes determined. This paper presents the sequence of the uracil permease translated from the unique reading frame found for the gene. Features of the primary structure of the protein are shown. Use was made of proteinstructure prediction programs and this led to the proposal of a working model of the protein structure, which will be discussed. MATERIALS AND METHODS Strains and mediaYeast strains are isogenic derivatives of the wild-type strain FLIOO (F. Lacroute), except for GRF18 (a gift from G. R. Fink, M. I. T., Cambr...

The synovial fluids (SF) of patients with rheumatoid arthritis (RA) were investigated for their effects on thymocytes of C3H/HeJ mice. Of the 20 SF tested, 17 (85%) showed an augmentation of the phytohaemagglutinin (PHA) induced thymocyte stimulation. Out of 16 SF of patients with osteoarthrosis, such an activity was detected in only one (6.25%). Further characterisation of the amplification factor revealed that (1) the SF of RA patients augmented both the PHA and the Concanavalin A response of the thymocytes (2) in the absence of mitogens, SF-treated thymocytes showed an increased uptake of 3H-thymidine, (3) the SF did not propagate the growth of an interleukin 2 dependent ovalbumin specific T cell clone, but (4) the SF were found to be required for optimal interleukin 2 release by spleen cells stimulated with suboptimal doses of lectin. Based on these biological effects the factor in the SF of RA patients is suggested to represent an interleukin 1 (IL-1). IL-1 produced in cultures by activated macrophages has been shown to stimulate T and B cell functions and to induce the production of collagenase and prostaglandins by cultured synovial cells. Both properties of IL-1 could be relevant in the pathogenesis of RA.

Parkin-deficient animals exhibit mitochondrial degeneration and increased oxidative stress vulnerability, and both mice and flies lacking DJ-1 are hypersensitive to environmental toxins associated with Parkinson's disease (PD). We used recombinant adeno-associated virus (AAV) gene transfer to study the influence of DJ-1 and Parkin on the dopaminergic system of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, a model for sporadic PD. After MPTP lesioning, significantly more dopamine neurons survived in the virus-injected substantia nigra of the AAV-DJ-1 and AAV-Parkin mice when compared with AAV-enhanced green fluorescent protein injected controls. Protection at the neuronal level was supported by increased amphetamine-induced contralateral turning behavior. Normal mice expressing DJ-1 showed apomorphine-induced ipsilateral turning, suggesting a hyporesponsiveness of striatal dopamine D1 receptors in the DJ-1-expressing hemisphere. MPTP drastically reduced dopamine to 19% of normal levels and neither DJ-1 nor Parkin protected against MPTP-induced catecholamine loss under these conditions. Our results show that Parkin and DJ-1 inhibit dopamine neuron death and enhance amphetamine-induced dopaminergic function in a mouse model of idiopathic PD. However, DJ-1 overexpression also reduced postsynaptic dopamine receptor responses in normal mice. These results warrant further exploration of DJ-1 and Parkin gene therapy for PD, although a better understanding of their effects on behavior and dopamine neurotransmission is required before these proteins can be safely used.