SUMMARY One hundred and one adults (19 to 74 years of age) with cerebral palsy were interviewed and examined. There were 52 subjects with dyskinesia, 28 with spastic quadriparesis, 11 with spastic diplegia, and 10 with spastic hemiplegia. Neuromuscular dysfunction was mild in two cases, moderate in 72 and severe in 27. 76 per cent of the subjects had multiple musculoskeletal problems. In 63 per cent, these occurred under 50 years of age, suggesting that abnormal biomechanical forces and immobility had led to excessive physical stress and strain, overuse syndromes, and possibly early joint degeneration. A number of the patients had urinary complaints due to difficulties with toilet accessibility and possible neurogenic bladder. General health care seemed satisfactory for acute illnesses, but preventive health care was almost totally lacking. Treatment for the musuculoskeletal system and availability of adaptive devices were less adequte than for children with cerebral palsy. RÉSUMÉ État médical et fonctionnel des IMC/IMOC adulies Cent un adultes avec IMC/IMOC, âgés de 19 à 74 ans, ont été interrogés et examinés. 52 d'entre eux presentaient une dyskinésie, 28 une quadriparésie spastique, 11 une diplégie spastique et 10 une hemiplégie spastique. La dysfonction neuromusculaire était légère dans deux cas, modérée dans 72 cas et sévère dans 27 cas. II y avait des problèmes musculo‐squelettiques multiples chez 76 pour cent des sujets. Dans 63 pour cent des cas, ils étaient apparus avant l'âge de cinquante ans suggérant que des forces biomêcaniques anormales et l'immobilité avaient provoque stress et contraintes, syndrome de fatigue, et peut‐être une dégénérescenee articulaire précoce. Quelques‐uns des sujets se plaignaient de difficultés urinaires en rapport avec une mauvaise accessibilitéà la toilette et peut‐être avec une vessie neurologique. La prise en charge médicale générale semblail satisfaisante pour les affections aiguës mais les soins préventifs étaient presque totalement absents. Le traitement du systgme musculo‐squelettique et la disponibilité d'appareillages de tous types étaient moins bons que chez les enfants IMC/IMOC. ZUSAMMENFASSUNG Medizinischer und funktioneller Status bei Erwachsenen mil Cerebralparese 101 Erwachsene mit Cerebralparese (CP) im Alter von 19 bis 74 Jahren wurden befragt und untersucht. 52 hatten eine Dyskinesie, 28 eine spastische Tetraparese, 11 eine spastische Diplegie und 10 eine spastische Hemiplegie. Die neuromuskuläre Dysfunktion war bei zwei Patienten gering, bei 72 mittelschwer und bei 27 schwer. 76 Prozent der Patienten hatten multiple Muskel‐Skelett‐Probleme. Bei 63 Prozent traten diese vor dem 50. Lebensjahr auf, was vermuten läst, daß abnorme biomechanische Kräfte und Immobilität zu übermäigem körperlichen Streß und zu Anstrengungen, Überheanspruchungssyndromen und möglicherwcise zu früher Gelenkdegeneration geführt haben. Einige Patienten hatten Beschwerden beim Wasserlassen, die durch schlechte Erreichbarkeit von Toiletten und möglicher weise durch eine neurogene Blase be...

Transfer RNA is one of the most richly modified biological molecules. Biosynthetic pathways that introduce these modifications are underexplored, largely because their absence does not lead to obvious phenotypes under normal growth conditions. Queuosine (Q) is a hypermodified base found in the wobble positions of tRNA Asp, Asn, His, and Tyr from bacteria to mankind. Using liquid chromatography MS methods, we have screened 1,755 single gene knockouts of Escherichia coli and have identified the key final step in the biosynthesis of Q. The protein is homologous to B 12 -dependent iron-sulfur proteins involved in halorespiration. The recombinant Bacillus subtilis epoxyqueuosine (oQ) reductase catalyzes the conversion of oQ to Q in a synthetic substrate, as well as undermodified RNA isolated from an oQ reductase knockout strain. The activity requires inclusion of a reductant and a redox mediator. Finally, exogenously supplied cobalamin stimulates the activity. This work provides the framework for studies of the biosynthesis of other modified RNA components, where lack of accessible phenotype or obvious gene clustering has impeded discovery. Moreover, discovery of the elusive oQ reductase protein completes the biosynthetic pathway of Q.biochemistry | queuosine | reductive dehalogenation N early 100 modifications have been identified in RNA, many of which are found in tRNA and are common to eukaryotes, bacteria, and archaea (1). Most of these modifications are likely not essential under normal laboratory conditions, making discovery of biosynthetic pathways by phenotypic methods impossible. Queuosine (Q), a hypermodified RNA base containing a 7-deazapurine core, is among the more complex RNA modifications described to date. Q replaces the guanine in the wobble positions of the subset of tRNA molecules with a 5′-GUN-3′ sequence in their anticodon loops (His, Asp, Asn, and Tyr). Conservation of Q in RNA of organisms in nearly all kingdoms of life (2) suggests that the modification may be of cardinal importance. A physiological role for Q has eluded discovery partly because of gaps in understanding of the biosynthetic pathway. De novo biosynthesis of Q occurs in bacteria whereas eukaryotes acquire the free base, queuine, from dietary sources (3-5). The bacterial pathway for biosynthesis of Q has been elucidated up to the penultimate intermediate, epoxyqueuosine (oQ) (6, 7). However, the enzyme that catalyzes the final step in the pathway, conversion of oQ to Q, had yet to be identified. Because no selectable phenotypes have been demonstrated for the modification, discovery of the final step in the pathway required a different approach that melded modern analytical methods and emerging tools in bacterial genetics. This methodology has led to successful identification of the final step and can be generalized to other RNA modifications where lack of phenotype has hindered discovery of the biosynthetic pathway.Structural parallels between the 7-deazapurine core of queuosine and 7-deazapurine-containing antibiotic toyocamycin ...

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