Diagnosing idiopathic dystonia: must it take so long?

Idiopathic dystonia is a chronic, disabling movement disorder. This study attempted to verify anecdotal evidence that sufferers experience delay in achieving a correct diagnosis. A survey of 133 patients revealed that diagnosis after first seeking help required a mean of 3.8 years. Diagnostic latency varied considerably, with 22 per cent of respondents reporting a diagnostic latency of more than five years, while a further 22 per cent reported a latency of one month or less, with a sample median of 1.5 years. Respondents consulted a mean of 8.3 practitioners, including a mean of 2.1 general practitioners and 1.6 neurologists. Results were consistent with reports of lengthy diagnostic delays and inappropriate referrals. Greater awareness of dystonia and referral of suspected cases to a neurologist interested in movement disorders are recommended.

Nucleotide sequence and analysis of the plant-inducible locus pinF from Agrobacterium tumefaciens.

Several loci on the tumor-inducing plasmid from Agrobacterium tumefaciens were transcriptionally activated in the presence of wounded plant tissue or extracts. The inducible virulence loci were required for efficient tumor formation. In contrast, the plant-inducible locus pinF was not observed to be absolutely essential for virulence. Mutants in pinF showed an attenuated virulence on a variety of dicotyledonous hosts, and this attenuation became more pronounced with decreasing numbers of bacterial cells in the inoculum. The DNA sequence of a 5.5-kilobase region which included the pinF locus from the octopine-type tumor-inducing plasmid A6 was determined. Four open reading frames consistent with the observed transcription of pinF were observed. Two of the open reading frames, pinF1 and pinF2, coded for polypeptides with relative molecular weights of 47,519 (pinF1) and 46,740 (pinF2). A comparison of the amino acid sequences of pinF1 and pinF2 indicated that they were similar to each other and to known polypeptide sequences for cytochrome P-450 enzymes.

Studies on spin labeled ribonucleic acids encapsulated by viral proteins.

Spin labeled poly rA (sl-poly rA) was encapsulated by the coat proteins of two plant viruses having different morphologies: TMV, a rigid rod and CCMV, an icosahedral sphere. Electron microscopy showed that the resultant particles were morphologically similar to the parent virus from which the coat protein was obtained. Encapsulation produced progressive immobilization of the spin label. The motion of the spin label attached to TMV-sl-poly rA appears anisotropic with a correlation time about the long axis of approximately 5 x 10(-6) sec. Exogenous nuclease had no effect on the epr spectrum of this nucleo-protein complex. The epr spectrum of CCMV-sl-poly rA was isotropic with a correlation time less than 5 x 10(-7). CCMV-sl-poly rA was partially degraded by T2 ribonuclease. Theoretical calculations of correlation times for the motion of the nucleo-protein particles were similar to the experimentally derived values suggesting that the nucleo-protein particles are tightly packed with little potential for internal motion.

Mapping of putative transforming sequences of EBV DNA.

The linkage of restriction enzyme fragments of DNA of the B95-8 strain of Epstein-Barr virus has been determined. Two approaches are being employed to define which EBV DNA sequences are needed to initiate and maintain the transformation of lymphocytes to lymphoblasts capable of long-term growth in culture. The first approach is to determine the differences between the DNA of strains of EBV which possess transforming capacity and the DNA of the HR-1 strain which cannot transform. The data indicate that EBV (HR-1) DNA lacks approximately 2--3 x 10(6) daltons of DNA contained largely in the HsuI B and EcoRI (J-K) and A fragments of EBV (B95-8) DNA and in the EcoRI A and HsuI B fragment of the W91 strain. The DNA common to HsuI B and EcoRI A fragments lies between 27 and 42 x 10(6) daltons from the HsuI A end of the molecule. This finding is compatible with the hypothesis that the inability of the HR-1 strain to transform is due to the absence of DNA needed for transformation. The second approach is to identify and map the DNA encoding polyadenylated viral RNA in cultures of restringently infected cells which contain the EBNA antigen and show no evidence of abortive or productive infection. Previous data indicated that viral RNA species encoded by 5% of the viral DNA are adenylated and identified in the polyribosomes of restringently infected cells. The data indicate that these RNAs are encoded primarily by the HsuI A (and to a lesser extent, B) fragment of EBV (B95-8) DNA. This would place the DNA encoding the viral RNA processed in restrigently infected cells adjacent to and possibly overlapping the small DNA segment deleted from the DNA of the non-transforming HR-1 strain.