T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Imaging of posttraumatic brachial plexus injury

After reviewing a series of 220 patients operated upon between 1975 and 1985 for traumatic brachial plexus injuries, the authors present the results of 103 myelographies, 48 computed tomographies (CT scans) combined with standard myelography, and 25 series of images obtained by magnetic resonance imaging (MRI). To evaluate precisely the type and level of injury, the accuracy of these three techniques was compared with clinical and operative findings. The accuracy of myelography was considered good in 84% of the cases, but 4% were evaluated as false positive results and 12% as false negative or doubtful results. The combined CT scan and myelography reduced the number of doubtful results and accuracy reached 94.25%, but they did not visualize the roots distal to the spinal foramina. MRI correlated well with CT scan images and, in addition, offered visualization of distal radicular injuries. MRI seems a promising diagnostic procedure and should also help to situate nerve grafts and check their viability.     

Cystic fibrosis mortality trends in France.

BACKGROUND: In 1992 France set up a national cystic fibrosis observatory (Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. METHODS: The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. RESULTS: In 2001-2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994-1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. CONCLUSIONS: These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.     

Atherosclerosis--multi-organ involvement the rule rather than the exception

Atherosclerosis is a systemic disorder and significant lesions often occur in organ systems other than the symptomatic area. Three groups of patients, those admitted to hospital with either coronary artery disease, carotid artery stenosis or peripheral vascular disease, were examined for concomitant atherosclerotic lesions. Non-invasive tests, namely duplex scanning of the carotid arteries, arm ergometer exercise testing, and segmental pressure of the limbs, were used during evaluation. A clear association between ischaemic heart disease, carotid artery stenosis and femoropopliteal disease was found. Women appear to be more prone to multi-organ involvement than men; their higher average age on admission to hospital is a possible explanation for this in some cases, but not all.     

Probing the coupling of Ca2+ and rigor activation of rabbit psoas myofibrillar ATPase with ethylene glycol

We have exploited solvent perturbation to probe the coupling of Ca²⁺ and rigor activation of the ATPase of myofibrils from rabbit psoas. Three techniques were used: overall myofibrillar ATPases by the rapid-flow quench method; kinetics of the interaction of ATP with myofibrils by fluorescence stopped-flow; and myofibrillar shortening by optical microscopy. Because of its extensive use with muscle systems, ranging from myosin subfragment-1 to muscle fibres, we chose 40% ethylene glycol as the relaxing agent. At 4°C, the glycol had little effect on the myofibrillar ATPase at low [Ca²⁺], but at high [Ca²⁺] the activity was reduced 50-fold, close to the level found under relaxing conditions, and there was no shortening. However, the ATPase of chemically cross-linked myofibrils (permanently activated even without Ca²⁺) was reduced only 3–4-fold. The lesser reduction of the ATPase of permanently activated myofibrils was also observed in single turnover experiments in which activation occurs by a few heads in the rigor state activating the remaining heads. The addition of ADP, which also promotes strong head-thin filament interactions, also activated the ATPase but only in the presence of Ca²⁺. Further experiments revealed that in 40% ethylene glycol, Ca²⁺ does initiate shortening but only with the aid of strong interactions and at temperatures above 15°C. This confirms that in the organized and intact myofibril, Ca²⁺ and rigor activation are coupled, as proposed previously for regulated actomyosin subfragment-1. This revised version was published online in September 2006 with corrections to the Cover Date.     

Identification of lingual motor control circuits using two strains of pseudorabies virus

First-order interneurons that project to hypoglossal motoneurons are distributed within reticular formation subdivisions in the pons and medulla in areas thought to control licking, swallowing, chewing, and respiration. Movement of the tongue in each of these functions is achieved by the coordinated action of both intrinsic and extrinsic lingual muscles. Interneuron populations that project to these different lingual motoneuronal pools appear to be largely overlapping in the reticular formation. Because of the functional coupling between intrinsic and extrinsic muscles during most tongue movements, one might predict that individual pre-hypoglossal interneurons project to multiple motoneuronal pools. To test this hypothesis, one strain of pseudorabies virus was injected into the styloglossus muscle (an extrinsic lingual muscle) and a second strain of pseudorabies virus was injected into the intrinsic lingual muscles of the anterior tongue in the same preparation. Rats were perfused with fixative 84-96 h later, and dual-labeling immunohistochemistry was performed to reveal populations of single- and double-labeled brainstem neurons. Motoneurons innervating the different lingual muscles were spatially segregated within the hypoglossal motor nucleus, and no double-labeled motoneurons were observed. In contrast, pre-hypoglossal neurons projecting to each lingual motoneuron pool were highly overlapping in the reticular formation, and many were double-labeled. These observations suggest that coactivation of lingual muscles can be achieved, at least in part, through divergent projections of first-order interneurons to anatomically and functionally distinct pools of lingual motoneurons in the hypoglossal nucleus.     

Coding the sweet taste in the nucleus of the solitary tract: differential roles for anterior tongue and nasoincisor duct gustatory receptors in the rat

1. A variety of chemicals that humans describe as sweet drive neurons in the nucleus of the solitary tract (NST) of the rat more vigorously when applied to the taste receptors associated with the nasoincisor ducts (NID) than when applied to taste receptors on the anterior tongue (AT). 2. The differential effects of sweet stimuli applied to the AT and NID also are evident in the set of across-neuron correlations produced by these stimuli. The psychophysical similarity among the sweet stimuli is better accounted for by responses to stimulation of the NID than by responses to stimulation of the AT (mean correlation between pairs of sweet stimuli = +0.70 for the NID, +0.44 for the AT). 3. Disaccharides or polysaccharides of glucose, i.e., maltose (0.3 M) and Polycose (0.1 M), are poor stimuli on the NID, evoking responses only 17.8 and 26.7% as great as the response elicited by sucrose (0.3 M), an optimal stimulus for this receptor subpopulation. This suggests that Polycose and maltose interact with receptor sites distinct from those with an affinity for sweet stimuli. Polycose and maltose also are ineffective stimuli on the AT, evoking responses only 11.8 and 4.9% as large as the response evoked by an optimal stimulus for this receptor subpopulation, a mixture of electrolytes (0.3 M NaCl, 0.03 M HCl, and 0.01 M quinine HCl). 4. The relative effectiveness of the sweet sugars in driving NST neurons (sucrose greater than fructose greater than glucose) correlates with their order of effectiveness in generating preference behavior in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)