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Background: Active surveillance (AS) represents a treatment option for renal masses in patients who are not surgical candidates either because of existing comorbidities or patient choice. Among renal masses undergoing AS, some grow rapidly and require treatment or progress to metastatic disease. Patient and tumour characteristics related to this more aggressive behaviour have been poorly studied., Objective: To report the analysis of a multi-institutional cohort of patients undergoing AS for small renal masses., Design, Setting, and Participants: This prospective study included 82 patients with 84 renal masses who underwent AS in three Canadian institutions between July 2001 and June 2009., Intervention: All patients underwent AS for renal masses presumed to be renal cell carcinoma (RCC) as based on diagnostic imaging., Measurements: Age, sex, symptoms at presentation, maximum diameter at diagnosis (cm), tumour location (central/peripheral), degree of endophytic component (1-100%), and tumour consistency (solid/cystic) were used to develop a predictive model of the tumour growth rate using binary recursive partitioning analysis with a repeated measures outcome., Results and Limitations: With a median follow-up of 36 mo (range: 6-96), the mean annual renal mass growth rate for the entire cohort was 0.25 cm/yr (standard deviation [SD]: 0.49 cm/yr). Only one patient (1.2%) developed metastatic RCC. Amongst all variables, maximum diameter at diagnosis was the only predictor of tumour growth rate, and two distinct growth rates were identified. Masses that are ≥2.45 cm in largest diameter at diagnosis grow faster than smaller masses. This series was limited by its moderate sample size, although it is the largest published prospective series to date., Conclusions: We confirm that most renal masses grow slowly and carry a low metastatic potential. Tumour size is a predictor of tumour growth rate, with renal masses <2.45 cm growing more slowly than masses >2.45 cm., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Partial nucleotide sequences of the haemagglutinin (H) gene of 18 measles viruses isolated in the Gambia during 1994 and 1995 show a high degree of homology (> 98.5%) when compared with each other. These sequences form a cluster distinct from measles viruses isolated from other geographic regions and from the sequences of vaccine strains and two isolates from the Gambia from earlier years. Despite the low level of genetic heterogeneity observed, a common feature of the Gambian isolates is the presence of three nucleotide changes (at positions 7963, 8649 and 8653) not observed in isolates from other locations.

The nucleotide sequences of the genome of the RSS-2 wild type strain of respiratory syncytial (RS) virus, which is known to induce upper respiratory tract infection in adults, and that of the attenuated ts1C candidate vaccine derived from it by three cycles of mutagenesis and selection of temperature-sensitive (ts) mutants, have been determined. Comparison of the sequences has located the genetic changes which contribute to the reduced pathogenicity in adults of the candidate vaccine. Thirty-seven nucleotide changes distinguish the wild type and ts1C, 13 of which confer amino acid substitutions; no mutations are present in extragenic regions. Partial nucleotide sequencing of the genomes of the first stage ts mutant (ts1A) and the second stage ts mutant (ts1B), which were intermediates in the derivation of the third stage mutant ts1C, established that five mutations resulting in amino acid substitutions had been induced in the first cycle of mutagenesis, one in the second cycle, and seven in the third cycle. The unique mutation differentiating ts1B from ts1A substitutes an alanine for a threonine at residue 736 in the polymerase (L) protein. The occurrence of a mutation in ts1C inducing substitution of a phenylalanine for a serine residue at an adjacent site (731) suggests that mutations in this region of the polymerase can have significant attenuating effects. The data suggest also that a mutation in the F gene may contribute to the attenuated phenotype.

The NS1 and NS2 proteins of human respiratory syncytial virus (RSV) were expressed using baculovirus. Antisera to these expressed proteins and to synthetic peptides were raised in rabbits and used to characterise the proteins. Multiple forms of both NS1 and NS2 proteins were detected in RSV infected cells by both immunoblotting and radioimmunoprecipitation when non-reducing, but not reducing, conditions were used. In pulse-labelling experiments the monomeric form of NS1 was stable, while that of NS2 was unstable with a half life of about 30 min. The NS1 protein associated with the matrix (M) protein and could be co-precipitated by a monoclonal antibody to M protein. The NS2 protein did not show any detectable association with RSV structural proteins. These results indicate that the NS1 and NS2 proteins have distinct roles in the viral life cycle.

The nucleocapsid protein (N) gene of two subgroup A and one subgroup B strains of avian pneumovirus has been cloned and sequenced. The gene of all three isolates comprised 1197 nucleotides (nt), which formed a single major open reading frame, potentially encoding a protein of 391 amino acid residues. The N gene of the two subgroup A isolates differed by only 1 nt but differed by 282 (24%) nt and 35 (11%) amino acids from the B isolate. The predicted protein was identical in length to that of human, bovine and ovine respiratory syncytial viruses, the amino acid identity being approximately 41% overall but with some regions of identity > 90%.

Measles virus (MV) was isolated from throat swab samples collected during the spring/summer 1993 in the Coventry area. Viral RNA was reverse transcribed and cDNA prepared using oligo- T primer. Using MV-specific primers the area encoding the external region of the haemagglutinin glycoprotein was amplified using nested PCR and cycle sequenced. Comparisons were made with the Edmonston strain and current MMR vaccine strain. It was found that a high degree of homology existed between all strains examined, but that a majority of clinical samples shared a premature termination signal that potentially shortened the haemagglutinin protein by 35 amino acids. The single clinical sample that lacked this early termination signal appeared to be closely related to the MMR strain and may result form a vaccine-related illness. Truncation of the haemagglutinin protein may have allowed MV to escape the immune response induced by vaccination with the current MMR vaccine.

The phosphoprotein (P) gene of two subgroup A strains of avian pneumovirus comprised 855 nucleotides containing only one substantial open reading frame encoding a protein of 278 amino acids, with a predicted M(r) of 30,323. In vitro translation of P mRNA in a wheat germ system resulted in the synthesis of two polypeptides of M(r) 35,000. Comparison of the deduced P protein sequence with that of the known mammalian pneumoviruses revealed overall amino acid identities ranging from 31 to 34.5%, suggesting a distant relationship. However, there was a much higher identity (63.2-68.4%) in a region of 57 residues, which included a heptad repeat sequence.

The immunogenicity and pathogenicity of a strain of respiratory syncytial (RS) virus modified by sequential induction of three temperature-sensitive (ts) mutations have been evaluated by intranasal administration to 22 adult volunteers. This modified virus, a triple ts mutant designated ts1C, was derived from a double mutant ts1B evaluated in a previous trial. The original isolate (strain RSS-2) and all its derivatives were propagated throughout in human diploid cells in a specially assigned laboratory. The triple mutant ts1C is unable to multiply in MRC-5 cells at 37 degrees C and above. Following nasal administration of ts1C, immune responses were observed in volunteers with low pre-existing neutralizing antibody titres. The ability of mutant ts1C to induce upper respiratory tract disease in adults was greatly diminished in comparison with the non-ts wild-type virus, but not markedly more so than a previously tested double ts mutant (ts1B) which replicates at 37 degrees C. Mutant ts1C, however, may have greater potential as a live vaccine in view of its inherently greater genetic stability.

Primary lateral sclerosis (PLS) bears close resemblance to cases of amyotrophic lateral sclerosis (ALS) presenting with spasticity, but histopathological studies have shown significant difference between the two conditions. When the lower motor neurons in cases of ALS and PLS are compared with the equivalent cells of control subjects, morphometric studies indicate significantly decreased size and increased convexity (rounding) of the cell bodies only in ALS. In both disorders there is loss or shrinkage of the largest cortical motor neurons (Betz cells) in the primary motor cortex, though this change is not conspicuous in all cases of ALS. Morphometry reveals in both diseases a general reduction in the sizes of pyramidal cells in the precentral gyrus, indicating that smaller neurons are involved. The cortical motor neurons shrink more in PLS than in ALS. It is concluded that there is clear difference between ALS and PLS. In PLS, quantitative histopathological data show that the neuronal degeneration is confined to long descending pathways, notably the corticospinal system, with no concomitant involvement of lower motor neurons. In ALS, lower motor neuron degeneration occurs in all cases, whereas involvement of the motor cortex is variable.

Respiratory syncytial virus strains (subgroup A) isolated from around the world during the period 1988-1991 were analysed to determine their relatedness. Analysis was by restriction mapping and nucleotide sequencing following amplification of selected regions of the virus genome by polymerase chain reaction (PCR). Twenty-three viruses of subgroup A isolated from cities in temperate regions of the Northern and Southern hemispheres and the tropics during the period 1988-1991 fell into distinct groupings closely related to four of the six lineages defined in analysis of recurrent epidemics within the same city (Birmingham, UK) during the same period. These observations confirm that multiple lineages of RS virus co-circulate locally, and show that very similar viruses are present simultaneously in widely separated countries.

We have cloned eight intergenic regions from the Pneumovirus pneumonia virus of mice that link the nine small and medium sized genes previously described (Chambers et al., 1990). The nucleotide sequences of the clones confirm the locations of these genes and their mRNA transcripts in the viral genome. The intergenic regions vary in size from 2-56 nucleotides and show only faint homology to each other or to their analogues in respiratory syncytial virus. Sequence alignments suggest that the location of the transcriptional start site for the mRNA encoding the major nucleocapsid protein of pneumonia virus of mice and respiratory syncytial virus may have altered during virus evolution by gain or loss of a transcriptional start signal.

The virulence and immunogenicity of a wild-type respiratory syncytial (RS) virus together with four temperature sensitive (ts) mutants derived from this isolate were tested by intranasal inoculation into adult volunteers. Resistance to challenge correlated with neutralizing antibody titres in nasal secretions and to a lesser extent in serum. All ts mutants were reduced in virulence. Mutant ts1B caused mild or asymptomatic infections yet induced antibody responses comparable with wild-type RS virus. Ts1B might be developed further to produce a live-virus vaccine.