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Biomedical subjects

B J Andrews

Publications and source records attributed to B J Andrews.

At least 19 recordsLinked to original sources
PubMed1992

Interaction of the yeast Swi4 and Swi6 cell cycle regulatory proteins in vitro.

In budding yeast, two transcription factors, Swi4 and Swi6, control the expression of important cell cycle regulatory proteins (the G1 cyclins, Cln1 and Cln2, and the cyclin-like Hcs26) as well as the HO gene, whose product initiates mating-type switching. Both Swi4 and Swi6 are components of a protein complex that forms at a repeated sequence element, SCB (SWI4, -6-dependent cell cycle box), found in the upstream regulatory sequences of target genes. We show, by using proteins synthesized in vitro, a direct association between Swi4 and Swi6. The cdc10-Swi6 or ankyrin motifs present in both Swi4 and Swi6 are dispensable for their association, which is mediated instead by a region near the C terminus of each protein. Furthermore, we show that interaction with Swi6 is not necessary for specific recognition of the SCB sequence by the Swi4 protein; we propose that Swi4 is responsible for binding to the SCB sequence while Swi6, through its association with Swi4, regulates activity of the complex.

Cell Cycle↗
PubMed1992

Reduction of seating pressure using FES in patients with spinal cord injury. A preliminary report.

The aim of this study was to investigate the use of functional electrical stimulation (FES) as a means of pressure sore prevention in seated spinal cord injured (SCI) subjects. Nine SCI subjects took part in tests in which electrical stimulation was applied to the quadriceps with the lower legs restrained. Ischial pressures were measured during periods of quiet sitting and FES application. A strain gauged lever arm was used to measure the knee moment during quadriceps stimulation. The average pressure drop at the right and left buttocks was 44 mmHg and 27 mmHg respectively. In general the greatest reductions occurred in subjects with larger knee moments; however, there was no direct relationship between the pressure reduction obtained and the quadriceps strength. This form of FES may be useful as a prophylactic aid in the management of pressure sores in SCI subjects.

Adult↗
PubMed1991

Dishabituation of the flexion reflex in spinal cord-injured man and its application in the restoration of gait.

The flexion withdrawal reflex, evoked by surface electrical stimulation, has been used to provide hip flexion for the restoration of gait in paraplegics. A major limitation to its use has been the decrease in the magnitude of the response to repeated stimulation (habituation). In this study it was found that by using high intensity stimulation the response could be dishabituated. It was demonstrated that sufficient hip flexion for functional electrical stimulation-assisted gait was maintained using high intensity pulses in a one-step-ahead controller.

Adult↗
PubMed1991

Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription.

SWI4 of budding yeast codes for a component of a transcription factor (cell cycle box factor, or CCBF) necessary for G1-specific expression of HO. We show that SWI4 is essential for haploid cell viability at high temperature and in a/alpha cells at all temperatures: SWI4-deficient cells arrest as large unbudded cells. Eight high copy number plasmids were identified that allow swi4- strains to grow under nonpermissive conditions. Two carry G1 cyclin genes, CLN1 and CLN2; another carries HCS26, coding for a putative cyclin, a/alpha swi4- mutants exhibit 3- to 20-fold reductions in the levels of CLN1, CLN2, and HCS26 transcripts. The requirement of SWI4 for transcription appears to be direct: each gene contains sites similar to the CCBF-binding site; CCBF binds to the upstream region of HCS26. We propose that SWI4 participates in a positive feedback loop by which CLN1, CLN2, and possibly HCS26 promote their own transcription in G1.

Amino Acid Sequence↗
PubMed1991

Immunoprecipitation studies with biotinylated Entamoeba histolytica antigens.

The biotinylation of protein antigens for use in immunoprecipitation studies with parasite antigens is described. This technique was standardized to produce maximal labelling without compromising either the viability of the parasite or the antigenicity of labelled proteins. Live axenic Entamoeba histolytica trophozoites were optimally labelled by incubation of 10(7) parasites in 1 ml phosphate-buffered saline for 20 min at 37 degrees C with a final concentration of 10 mM N-hydroxy succinimido-biotin (NHS-B). Examination of antigens recognized by immunoglobulin from convalescent amoebic liver abscess patients and precipitated by protein A-Sepharose showed a general increase in immune response to amoebic antigens with time following treatment. Mass ratio mol. wts of immunoprecipitated antigens concur with those presented by other authors using alternate technology, in addition to recognizing antigens previously not identified by human sera. We therefore recommend biotinylation as a viable alternative to radiolabelling techniques for the study of parasite antigens and the humoral immune responses raised against them.

Animals↗
PubMed1990

Control of functional electrical stimulation with extended physiological proprioception.

The use of functional electrical stimulation (FES) of muscle for paraplegic locomotion, or grasp augmentation in tetraplegia, is limited by the variability in muscle response to stimulation as a result of several external and internal factors. Previous approaches to this problem have used position-servo controllers, which have been shown to function satisfactorily in the laboratory. However, such systems will fail should obstacles be encountered or should the stimulation hardware develop a fault. To prevent such potentially dangerous failures some form of sensory feedback is required. This paper describes the first application of a technique known as extended physiological proprioception (EPP) to the control of FES to compensate for muscle response variability and provide proprioceptive feedback via the appropriate sensory pathways. In the experimental system described, a paraplegic subject controlled the extension of his paralysed knee by shoulder protraction. A Bowden cable linked the two joints, and a dynamometer in this cable was used to derive the control signal for a computer-controlled stimulator which delivered surface stimulation to the quadriceps muscle group. Modelling and parameter identification were performed by analysis of the step response, and the controller was designed from consideration of the root locus. The advantages of the system, in terms of improved proprioceptive feedback and reduced limb-positioning error were assessed in a test of joint positioning accuracy with vision occluded. The EPP system showed improvements over both open and closed-loop position-servo controllers.

Artificial Limbs↗
PubMed1989

The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription.

Transcription of the HO gene of Saccharomyces cerevisiae, which encodes a site-specific endonuclease that initiates cell-type switching (reviewed in refs. 1,2), is restricted to a short window of the cell cycle in late G1 (refs 3,4). A repeated element in the upstream region of HO (the cell-cycle box, CCB) and two regulatory proteins, SWI4 and SWI6, are required for cell-cycle-dependent expression of HO. Biochemical experiments have identified a factor, CCBF (cell-cycle box factor), that binds to the CCB elements and that presumably plays a key part in cell-cycle regulation of HO. The SWI4 and SWI6 genes are required for formation of the CCBF-DNA complex. Here we report the nucleotide sequence of the SWI4 gene and show that it contains two copies of the conserved SWI6-cdc10 motif observed in SWI6 of budding yeast, the Schizosaccharomyces pombe cdc10 gene required for progression through G19, the Drosophila Notch gene, and in the Caenorhabditis elegans lin-12 and glp-1 genes. We demonstrate by using antibodies to the SWI4 protein in gel-shift assays that the protein is present in the CCBF-DNA complex.

Amino Acid Sequence↗
PubMed1989

Identification of a DNA binding factor involved in cell-cycle control of the yeast HO gene.

Transcription of the HO gene is controlled by at least eleven trans-acting regulators, which are responsible for limiting expression to mother cells and to one period in the cell cycle. A subset of these regulators and a repeated element (the cell-cycle box, CCB) are required for expression of HO during late G1. We describe gel retardation and footprinting experiments that identify a factor, CCBF (cell-cycle box factor), that binds to multiple cell-cycle box elements. We show that the SWI4 and SWI6 genes are required for formation of the CCBF-promoter complex in vitro, either as components of CCBF or as modulators of CCBF activity. The other SWI genes (SWI1, 2, 3, and 5) are not required. We also show that SWI4 and SWI6 are the only SWI genes required for expression in vivo from the CCB sequences. These observations indicate that the CCBF is responsible for cell-cycle regulation of HO and lead to the view that two of the SWI genes, SWI4 and SWI6, are specifically involved in this regulatory event.

Base Sequence↗
PubMed1989

Automatic detection of gait events: a case study using inductive learning techniques.

One of the problems which occurs in the development of a control system for functional electrical stimulation of the lower limbs is to detect accurately specific events within the gait cycle. We present a method for the classification of phases of the gait cycle using the artificial intelligence technique of inductive learning. Both the terminology of inductive learning and the algorithm used for the analyses are fully explained. Given a set of examples of sensor data from the gait events that are to be detected, the inductive learning algorithm is able to produce a decision tree (or set of rules) which classify the data using a minimum number of sensors. The nature of the redundancy of the sensor set is examined by progressively removing combinations of sensors and noting the effect on both the size of the decision trees produced and their classification accuracy on 'unseen' testing data. Since the algorithm is able to calculate which sensors are more important (informative), comparisons with the intuitive appreciation of sensor importance of five researchers in the fields were made, revealing that those sensors which appear intuitively most informative may, in fact, provide the least information. Comparison results with the standard statistical classification technique of linear discriminant analysis are also presented, showing the relative simplicity of the inductively derived rules together with their good classification accuracy. In addition to the control of FES, such techniques are also applicable to automatic gait analysis and the construction of expert systems for diagnosis of gait pathologies.

Algorithms↗
PubMed1988

Hybrid FES orthosis incorporating closed loop control and sensory feedback.

A hybrid functional electrical stimulation (FES) orthosis is described, comprising a rigid ankle-foot brace, a multi-channel FES stimulator with surface electrodes, body mounted sensors, a 'rule-based' controller and an electro-cutaneous display for supplementary sensory feedback. The mechanical brace provides stability, without FES activation of muscles, for standing postures normally adopted by patients. This avoids inducing muscle fatigue during prolonged upright activity. However, stability is conditional upon the position of the ground reaction vector (GRV) relative to the knee joint. The finite state FES controller reacts automatically to destabilizing shifts of the GRV by stimulating appropriate anti-gravity musculature to brace the leg. The FES system also features a control mode to initiate and terminate flexion of the leg during forward progression. A simple mode of supplementary sensory feedback was used during the laboratory standing tests to assist the patient in maintaining a set posture. Preliminary results of laboratory tests for two spinal cord injured subjects are presented.

Adult↗
PubMed1988

Reduction of muscle fatigue in man by cyclical stimulation.

In order to develop a control system for electrical stimulation of paralysed muscle and improve muscle resistance to fatigue, it is useful to investigate the possibilities of simulating the control systems of the normal body. One way is the periodic shifting of stimulation from one muscle to another. This technique is called sequential stimulation and allows sufficient rest time for each muscle to reduce fatigue and consequently prolong muscle strength. It can also be seen to improve the muscle recovery time. In the following study, the muscles rectus femoris, vastus lateralis and vastus medialis were used to keep the knee locked and extended during stimulation. Several experiments were carried out using a three-channel computer controlled stimulator. The results for three-phase sequential stimulation (33% duty cycle per muscle) were most effective and significantly improved the muscle fatigue characteristics.

Electric Stimulation↗
PubMed1988

Characterization of Schistosoma mansoni monoclonal antibodies which block in-vitro killing: failure to demonstrate blockage of immunity in vivo.

We have characterized various anti-schistosomular surface MoAbs previously shown to partially block in-vitro killing of schistosomula by human sera and eosinophils (Dunne et al. 1987). Immunodiffusion analysis showed that four IgM and one IgG3 MoAbs recognized periodate sensitive epitopes on the same molecular species present in schistosomular antigen but their patterns of reactivity with soluble egg antigen demonstrated that at least three distinct epitopes were involved. SDS-PAGE analysis showed the IgMs to react with 125I-labelled surface antigens of Mr 35,000-38,000 and Mr 20,000, and the IgG3 to react with an Mr 38,000 antigen. In spite of their effect in vitro, transfer of the IgM MoAbs at the time of challenge of mice vaccinated with irradiated cercariae or of mice injected with an unrelated (anti-Mr 16,000) protective MoAb failed to produce in-vivo blocking. Similarly, injection of Schistosoma mansoni eggs, prior infection with worms of one sex, or passive transfer of serum from single-sex infected mice failed to influence the resistance conferred by vaccination with irradiated cercariae.

Animals↗