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Biomedical subjects

S Todd

Publications and source records attributed to S Todd.

At least 55 records · Page 3Linked to original sources
PubMed1996

Structure-infectivity analysis of the human rhinovirus genomic RNA 3' non-coding region.

The specific recognition of genomic positive strand RNAS as templates for the synthesis of intermediate negative strands by the picornavirus replication machinery is presumably mediated by cis-acting sequences within the genomic RNA 3' non-coding region (NCR). A structure-infectivity analysis was conducted on the 44 nt human rhinovirus 14 (HRV14) 3' NCR to identify the primary sequence and/or secondary structure determinants required for viral replication. Using biochemical RNA secondary structure probing techniques, we have demonstrated the existence of a single stem-loop structure contained entirely within the 3' NCR, which appears to be phylogenetically conserved within the rhinovirus genus. We also report the in vivo analysis of a number of 3' NCR deletion mutations engineered into infectious cDNA clones which were designed to disrupt the stem-loop secondary structure to varying degrees. Large deletions (up to 37 nt) resulted in defective growth phenotypes, although they were not lethal. We propose that the absolute requirements for initiation of negative strand synthesis are less stringent than previously postulated, even though defined RNA secondary structure determinants may have evolved to facilitate and/or regulate the process of viral RNA replication.

Base Sequence↗
PubMed1996

Type II atrial flutter interruption with transesophageal pacing: use of propafenone and possible change of the substrate.

Type II atrial flutter (AFII) is an arrhythmia which usually cannot be interrupted by atrial pacing: the underlying mechanism is considered to be a leading circle without an excitable gap. We investigated whether the administration of propafenone, an antiarrhythmic drug, which primarily decreases conduction velocity, has a beneficial effect on AFII interruption using transesophageal pacing. Twelve patients with an AFII were randomized into 2 groups in which pacing was performed without treatment (group A) or two hours after the administration of 600 mg of oral propafenone (group B). Sinus rhythm was attained in 0 of 6 patients in group A and in 4 of 6 patients in group B (P < 0.05). The baseline mean cycle length was the same in both groups (175 +/- 7 (A) vs 168 +/- 8 ms (B); it lengthened significantly after the administration of propafenone (219 +/- 33 vs 168 +/- 8 ms; P < 0.05). Propafenone did not significantly lengthen the cycle in the two patients in whom interruption of the arrhythmia was impossible. Our data show that propafenone has a facilitating effect on atrial pacing only when it significantly prolongs the cycle length of the arrhythmia, possible expression of a conversion of AFII into type I, with an anatomical substrate and an excitable gap allowing arrhythmia capture and interruption. In the two patients in whom sinus rhythm was not restored, the absence of a direct dependence of the cycle length on the change in conduction velocity induced by propafenone may be explained by the persistence of a functionally determined circuit, resistant to atrial pacing.

Administration, Oral↗
PubMed1996

Speech perception and speech production skills of children with multichannel cochlear implants.

The acquisition of speech perception and speech production skills emerges over a protracted time course in congenitally deaf children with multichannel cochlear implants (CI). Only through comprehensive, longitudinal studies can the full impact of cochlear implantation be assessed. In this study, the performance of CI users was examined longitudinally on a battery of speech perception measures and compared with subjects with profound hearing loss who used conventional hearing aids (HA). The average performance of the multichannel cochlear implant users gradually increased over time and continued to improve even after 5 years of CI use. Speech intelligibility was assessed from recordings of the subjects' elicited speech and played to panels of listeners. Intelligibility was scored in terms of percentage of words correctly understood. The average scores for subjects who had used their CI for 4 years or more exceeded 40%.

Child, Preschool↗
PubMed1996

[Facilitating effect of propafenone pretreatment in the interruption of atrial flutter by transesophageal pacing].

Transesophageal atrial pacing is effective in the interruption of atrial flutter, and being simple and minimally invasive, is easily performed even on outpatients. The influence of antiarrhythmic drugs on this procedure is controversial. We investigated whether the administration of oral propafenone may facilitate the procedure. Thirty patients with type I atrial flutter were randomized into two groups in which transesophageal pacing was attempted, respectively, without treatment (Group A) and after oral administration of propafenone 600 mg (Group B). Transesophageal pacing was effective in interrupting atrial flutter in 53% (8/15) of patients in Group A and in 85% (13/15) of patients in Group B. A significant lengthening of the flutter cycle was observed in patients treated with propafenone (261 +/- 23 vs 217 +/- 25 ms, p < 0.01). Sinus rhythm resumed at a shorter paced cycle in patients of Group A (166 +/- 13 vs 187 +/- 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture was significantly lower in Group A (20.5 +/- 0.2 vs 23.3 +/- 1.2 mA, p < 0.01). In no patient the threshold for atrial capture was higher than the pain threshold. We did not observe abrupt enhancement of atrioventricular conduction. We can conclude that propafenone is effective and safe when used with transesophageal pacing in the termination of atrial flutter. The depressing effect of the drug on intraatrial conduction and the possible stabilizing effect on the reentry circuit appear to be outweighed by the positive effect of propafenone on the excitable gap of the circuit, facilitating its capture and account for the beneficial effect of the drug on arrhythmia termination.

Adult↗
PubMed1995

YAC contigs covering an 8-megabase region of 3p deleted in the small-cell lung cancer cell line U2020.

Somatic deletions of chromosome 3p occur at high frequencies in cancers of kidney, breast, cervix, head and neck, nasopharynx, and lung. The frequency of 3p deletion in lung cancer approaches 100% among small cell lesions and 70 to 80% in non-small cell lesions. This evidence strongly implies that one or more tumor suppressor genes of potentially widespread significance reside within the deleted region(s). Precise definition of the deleted target region(s) has been difficult due to the extensive area(s) lost and use of markers with low informativeness. However, improved definition remains essential to permit isolation of putative tumor suppressor genes from 3p. The identification of several small, homozygous 3p deletions in lung cancer cell lines has provided a critical resource that will assist this search. The U2020 cell line contains a small homozygous deletion that maps to a very proximal region of 3p and includes the marker D3S3. We previously identified a subset of DNA markers located within the deleted region and determined their relative order by pulsed-field gel mapping studies. In the present report, we describe the development of YAC contigs that span the majority of the deleted region and link up to flanking markers on both sides. The centromere proximal portion of the contig crosses the breakpoint from an X;3 translocation located within 3p12 providing both location and orientation to the map. PCR-based (CA)n microsatellite polymorphisms have been localized within and flanking the deletion region. These markers should greatly facilitate loss-of-heterozygosity studies of this region in human cancer. The contig provides a direct means for isolation of putative tumor suppressor genes from this segment of 3p.

Base Sequence↗
PubMed1995

An investigation of the relationship between antioxidant vitamin intake and coronary heart disease in men and women using discriminant analysis.

Smoking, high blood pressure and elevated blood cholesterol are the well-established 'classical' risk factors for coronary heart disease (CHD) in men and women. However, it is also well-known that there is a considerable degree of residual variation in CHD after these factors have been taken into account. Consideration of antioxidant vitamin status may help to reduce this unexplained variation. Here, discriminant analysis is applied to the baseline cross-sectional data from the Scottish Heart Health Study. The problem of possible behavioural changes after diagnosis for CHD is addressed by analysing diagnosed and undiagnosed CHD cases separately. Results show that the combined dietary intakes of the antioxidant vitamins C, E and carotene (assessed using a food frequency questionnaire) differentiate CHD prevalence as well as do the classical risk factors. For women, stepwise discriminant analysis shows that the effect of the antioxidant vitamins on CHD is removed by adjustment for the classical risk factors and age. For men, however, the antioxidant vitamins still contribute to the discriminant function. It is concluded that dietary antioxidant vitamins appear to have a significant effect on the prevalence of CHD, especially amongst men. The benefits and problems of using discriminant analysis in this practical context are discussed, including the assumptions that need to be tested.

Adult↗
PubMed1995

An investigation of the relationship between antioxidant vitamin intake and coronary heart disease in men and women using logistic regression analysis.

Antioxidant vitamin intake (C,E and carotene) is assessed from a food frequency questionnaire applied to 10,359 middle-aged men and women participating in the Scottish Heart Health Study. Logistic regression analysis is then used to quantify the relationship between antioxidant vitamin consumption and prevalent coronary heart disease (CHD), analysing diagnosed and undiagnosed cases separately. For men, there is a protective effect of all three antioxidants, before and after adjustment for a comprehensive set of confounding variables. For women the picture is less clear, only vitamin C is negatively associated with CHD, but the effect is removed by adjustment. The logistic regression model is also used to determine classification rules for deciding whether or not an individual has CHD. The classification error rates using the antioxidants are found to be very similar to those found using smoking, blood pressure and serum total cholesterol as classification variables. Significant interactions are found for the antioxidants with smoking, cholesterol and age. It is concluded that antioxidant vitamin intake protects against CHD for men. Logistic regression analysis is compared with discriminant analysis, and is found to have important advantages as an epidemiological tool.

Adult↗
PubMed1995

RNA-protein interactions directed by the 3' end of human rhinovirus genomic RNA.

The replication of a picornavirus genomic RNA is a template-specific process involving the recognition of viral RNAs as target replication templates for the membrane-bound viral replication initiation complex. The virus-encoded RNA-dependent RNA polymerase, 3Dpol, is a major component of the replication complex; however, when supplied with a primed template, 3Dpol is capable of copying polyadenylated RNAs which are not of viral origin. Therefore, there must be some other molecular mechanism to direct the specific assembly of the replication initiation complex at the 3' end of viral genomic RNAs, presumably involving cis-acting binding determinants within the 3' noncoding region (3' NCR). This report describes the use of an in vitro UV cross-linking assay to identify proteins which interact with the 3' NCR of human rhinovirus 14 RNA. A cellular protein(s) was identified in cytoplasmic extracts from human rhinovirus 14-infected cells which had a marked binding preference for RNAs containing the rhinovirus 3' NCR sequence. This protein(s) showed reduced cross-linking efficiency for a 3' NCR with an engineered deletion. Virus recovered from RNA transfections with in vitro transcribed RNA containing the same 3' NCR deletion demonstrated a defective replication phenotype in vivo. Cross-linking experiments with RNAs containing the poliovirus 3' NCR and cytoplasmic extracts from poliovirus-infected cells produced an RNA-protein complex with indistinguishable electrophoretic properties, suggesting that the appearance of the cellular protein(s) may be a common phenomenon of picornavirus infection. We suggest that the observed cellular protein(s) is sequestered or modified as a result of rhinovirus or poliovirus infection and is utilized in viral RNA replication, perhaps by binding to the 3' NCR as a prerequisite for replication complex assembly at the 3' end of the viral genomic RNA.

Base Sequence↗
PubMed1995

Data capture workstations, scanned forms, and pen-based systems for clinician use.

Data capture is the most difficult aspect of creating an automated medical record. The U.S. Department of Veterans Affairs (V.A.) is developing, testing and evaluating the benefits of a number of data capture technologies, including physician's workstations, scanned forms, and pen-based system as an aid to medical data capture in the outpatient clinic environment. The software being used for physician data entry, which supports a variety of data capture devices, will be demonstrated.

Computer Peripherals↗
PubMed1994

Physical and genetic mapping of human chromosome 3 loci containing microsatellite repeats.

One hundred and six microsatellite repeat-containing loci, including 59 CA-containing repeats from the CEPH/Genethon collection, were regionally assigned on human chromosome 3 using a somatic cell hybrid mapping panel, diving the chromosome into 14 intervals. The others were dinucleotide and tetranucleotide repeat-containing loci newly developed for human chromosome 3, of which 26 were also localized by means of genetic linkage analysis against selected CEPH microsatellites. The regional assignment of these two marker sets in a common mapping panel facilitates their integration. Incorporation of these highly polymorphic loci into the developing physical and genetic maps should provide useful information for studies of various diseases involving chromosome 3.

Base Sequence↗
PubMed1994

Assessing the impact of the All-Wales Mental Handicap Strategy: a survey of four districts.

The All-Wales Mental Handicap Strategy (AWS) pledged government leadership and additional resources for the task of developing community based residential, domiciliary, respite, daycare and professional services for people with mental handicaps and their families throughout Wales. Ultimately, the authors of the AWS sought to affect for the better the extent to which people with mental handicaps experience typical community life. A large random sample of people with mental handicaps in four diverse districts was used to track changes in services received, professional input, involvement in individual planning, the number of community activities pursued, and the size and range of individuals' social networks across the middle 4 years of the AWS. The balance between private housing and service residence remained unchanged although, with the ageing of the cohort, there was a decrease in the proportion living with parents and an increase in those living independently or in another family situation. There was an increase in the availability of residential services in the form of ordinary housing and an associated contraction in large congregate care facilities. However, not all moves were towards more ordinary living. Some people moved from large statutory sector specialist facilities to other atypical forms of residence, as did some people from family homes. Family support services in the form of family aides and short-term care increased significantly, but indicators still suggest that an expansion of these services is merited. Day services diversified slightly, but without affecting the major role of the traditional centre. There was a decrease in the numbers receiving a fulltime service. Only a third of the sample received regular individual plan reviews of the services they received and the developmental goals set in their name. In general, individuals were involved in a greater number of community activities that brought them into contact with other citizens. However, such an increase has not led to significant changes in the size or composition of people's friendship networks. Overall, the changes in service provision and family and user experience have been in line with the direction set by the AWS. However, the degree of change still required before the new pattern of services envisaged by the AWS is substantially in existence, or the experience of people with mental handicaps conforms with the guiding principles which underpin it, is considerably greater than that achieved after 7 of its initial 10 years.

Adolescent↗
PubMed1994

Transduction of a human RNA sequence by poliovirus.

Cells infected with poliovirus express a virally encoded polyprotein which undergoes self-mediated cleavage into structural and nonstructural viral proteins. Most of these cleavages are catalyzed by the 3C proteolytic domain of the polyprotein. Polyprotein synthesized in vitro from an RNA template containing a three-nucleotide insertion in 3C underwent proteolytic processing at all but one of the 3C-dependent cleavage sites. When transfected into HeLa cells, this RNA template displayed a lethal phenotype. We report here the isolation of two pseudorevertant progeny strains with restored protein-processing phenotypes, one of which appears to have arisen by transduction of a stretch of nucleotides from human 28S rRNA.

Amino Acid Sequence↗
PubMed1994

Attentional misguidance in visual search.

Previous research has shown that a task-irrelevant sudden onset of an object will capture an observer's visual attention or draw it to that object (e.g., Yantis & Jonides, 1984). However, further research has demonstrated the apparent inability of an object with a task-irrelevant but unique color or luminance to capture attention (Jonides & Yantis, 1988). In the experiments reported here, we reexplore the question of whether task-irrelevant properties other than sudden onset may capture attention. Our results suggest that uniquely colored or luminous objects, as well as salient though irrelevant boundaries, do not appear to capture attention. However, these irrelevant features do appear to serve as landmarks for a top-down search strategy which becomes increasingly likely with larger display set sizes. These findings are described in terms of stimulus-driven and goal-directed aspects of attentional control.

Adolescent↗
PubMed1994

Medical data capture and display: the importance of clinicians' workstation design.

The Department of Veterans Affairs is developing, testing and evaluating the benefits of physicians' workstations as an aid to medical data capture in an outpatient clinic setting. The physician's workstation uses a graphical user interface to aid the clinician in recording encounter data. Various input devices including keyboard, mouse, pen, voice, barcode reader, and tablet are available on the workstations, and user preferences will be examined. Access to general services such as electronic mail and reference databases is also available. The workstation provides a wide variety of patient specific data from the hospital information system, including image data. The single data collection process by the clinician will also provide data for the cost recovery process.

Computer Peripherals↗
PubMed1993

Dinucleotide repeat loci contribute highly informative genetic markers to the human chromosome 2 linkage map.

Microsatellite repeat loci can provide informative markers for genetic linkage. Currently, the human chromosome 2 genetic linkage map has very few highly polymorphic markers. Being such a large chromosome, it will require a large number of informative markers for the dense coverage desired to allow disease genes to be mapped quickly and accurately. Dinucleotide repeat loci from two anonymous chromosome 2 genomic DNA clones were sequenced so that oligonucleotide primers could be designed for amplifying each locus using the polymerase chain reaction (PCR). Five sets of PCR primers were also generated from nucleotide sequences in the GenBank Database of chromosome 2 genes containing dinucleotide repeats. In addition, one PCR primer pair was made that amplifies a restriction fragment length polymorphism on the TNP1 gene (Hoth and Engel, 1991). These markers were placed on the CEPH genetic linkage map by screening the CEPH reference DNA panel with each primer set, combining these data with those of other markers previously placed on the map, and analyzing the combined data set using CRI-MAP and LINKAGE. The microsatellite loci are highly informative markers and the TNP1 locus, as expected, is only moderately informative. A map was constructed with 38 ordered loci (odds > or = 1000:1) spanning 296 cM (male) and 476 cM (female) of chromosome 2 compared with 306 cM (male) and 529 cM (female) for a previous map of 20 markers.

Animals↗