Search PubMed⌕ Search

Biomedical subjects

D Hyndman

Publications and source records attributed to D Hyndman.

10 recordsLinked to original sources
PubMed2004

Stops walking when talking as a predictor of falls in people with stroke living in the community.

OBJECTIVE: To test "Stops walking when talking" (SWWT) as a predictor of falls among people with stroke living in the community. METHODS: People with stroke were identified through hospital records. Mobility, ADL (activities of daily living) ability, mental state, mood, and SWWT were assessed in a single session. Participants were followed prospectively for six months, using falls diaries and regular telephone calls. RESULTS: Sixty three participants (36 men, 27 women; mean (SD) age 68.4 (10.6)) were recruited. Four subjects had a brainstem lesion, 30 had right hemisphere, and 29 left hemisphere infarctions. Mean time since onset of stroke was 20 months (range 2-72). Twenty six subjects stopped walking when a conversation was started and 16 of them fell during the six month follow up period (11 experienced repeated falls). For all fallers (>or=1) the positive predictive value of SWWT was 62% (16/26), the negative predictive value 62% (23/37), specificity 70% (23/33) and sensitivity 53% (16/30). For repeat fallers (>or=2) the positive predictive value of SWWT was 42% (11/26), the negative predictive value 89% (33/37), specificity 69% (33/48) and sensitivity 73% (11/15). Those who stopped walking were significantly more disabled (p<0.001)-that is, they were more dependent in activities of daily living, had worse gross function as well as worse upper and lower limb function, and had depression (p = 0.012). CONCLUSIONS: The specificity of the SWWT test was lower but sensitivity was higher than previously reported. Although the SWWT test was easy to use, its clinical usefulness as a single indicator of fall risk in identifying those community dwelling people with stroke most at risk of falls and in need of therapeutic intervention is questionable.

Accidental Falls↗
PubMed2003

People with stroke living in the community: Attention deficits, balance, ADL ability and falls.

PURPOSE: To describe levels of attention deficits among people with stroke living in the community and explore relationships between attention, balance, function and falls. METHOD: Forty-eight mobile community-dwelling people with stroke (30 men, 18 women, mean age 68.4 +/- 11.2) were recruited to this cross-sectional investigation through General Practitioners. Twenty-six participants had a right, 21 a left hemisphere infarction and one had a brain stem lesion; mean time since stroke was 46 months (range five to 204). Participants' were interviewed about fall-events; attention, balance and function were assessed using standardised tests. RESULTS: Visual inattention was identified in five participants (10%), deficits of sustained attention in 15 (31%), auditory selective attention in nine (19%), visual selective attention in 17 (35%) and divided attention deficits in 21 participants (43%). Sustained and divided attention scores correlated with balance, ADL ability and fall-status (p < 0.01). The balance and function of subjects with normal attention were better than those with abnormal scores (p < 0.01). Analysis of variance revealed differences between repeat-fallers and non-fallers with no near-falls for divided attention, balance and ADL ability (p < 0.01). CONCLUSIONS: Attention deficits were common among this sample; sustained and divided attention deficits correlated with functional impairments and falls, highlighting that attention deficits might contribute to accident prone behaviour and falling.

Accidental Falls↗
PubMed2001

Crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding.

Pig aldehyde reductase containing the active site mutation tyrosine(50) to phenylalanine has been crystallized in the presence of the cofactor NADP(H) to a resolution of 2.2 A. This structure clearly shows loss of the tyrosine hydroxyl group and no other significant perturbations compared with previously determined structures. The mutant binds cofactor (both oxidized and reduced) more tightly than the wild-type enzyme but shows a complete lack of binding of the aldehyde reductase inhibitor barbitone, as determined by fluorescence titrations. Numerous attempts at preparing a ternary complex with a range of small aldehyde substrates were unsuccessful. This result, in addition to the inability of the mutant protein to bind the inhibitor, provides strong evidence for the proposal that the tyrosine hydroxyl group is essential for substrate binding in addition to catalysis.

Alcohol Oxidoreductases↗
PubMed2001

The crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding.

In order to understand more fully the structural features of aldo-keto reductases (AKRs) that determine their substrate specificities it would be desirable to obtain crystal structures of an AKR with a substrate at the active site. Unfortunately the reaction mechanism does not allow a binary complex between enzyme and substrate and to date ternary complexes of enzyme, NADP(H) and substrate or product have not been achieved. Previous crystal structures, in conjunction with numerous kinetic and theoretical analyses, have led to the general acceptance of the active site tyrosine as the general acid-base catalytic residue in the enzyme. This view is supported by the generation of an enzymatically inactive site-directed mutant (tyrosine-48 to phenylalanine) in human aldose reductase [AKR1B1]. However, crystallization of this mutant was unsuccessful. We have attempted to generate a trapped cofactor/substrate complex in pig aldehyde reductase [AKR1A2] using a tyrosine 50 to phenylalanine site-directed mutant. We have been successful in the generation of the first high resolution binary AKR-Y50F:NADP(H) crystal structure, but we were unable to generate any ternary complexes. The binary complex was refined to 2.2A and shows a clear lack of density due to the missing hydroxyl group. Other residues in the active site are not significantly perturbed when compared to other available reductase structures. The mutant binds cofactor (both oxidized and reduced) more tightly but shows a complete lack of binding of the aldehyde reductase inhibitor barbitone as determined by fluorescence titrations. Attempts at substrate addition to the active site, either by cocrystallization or by soaking, were all unsuccessful using pyridine-3-aldehyde, 4-carboxybenzaldehyde, succinic semialdehyde, methylglyoxal, and other substrates. The lack of ternary complex formation, combined with the significant differences in the binding of barbitone provides some experimental proof of the proposal that the hydroxyl group on the active site tyrosine is essential for substrate binding in addition to its major role in catalysis. We propose that the initial event in catalysis is the binding of the oxygen moiety of the carbonyl-group of the substrate through hydrogen bonding to the tyrosine hydroxyl group.

Aldehyde Reductase↗
PubMed2000

Crystal structure of CHO reductase, a member of the aldo-keto reductase superfamily.

Chinese hamster ovary (CHO) reductase is an enzyme belonging to the aldo-keto reductase (AKR) superfamily that is induced by the aldehyde-containing protease inhibitor ALLN (Inoue, Sharma, Schimke, et al., J Biol Chem 1993;268: 5894). It shows 70% sequence identity to human aldose reductase (Hyndman, Takenoshita, Vera, et al., J Biol Chem 1997;272:13286), which is a target for drug design because of its implication in diabetic complications. We have determined the crystal structure of CHO reductase complexed with nicotinamide adenine dinucleotide phosphate (NADP)+ to 2.4 A resolution. Similar to aldose reductase and other AKRs, CHO reductase is an alpha/beta TIM barrel enzyme with cofactor bound in an extended conformation. All key residues involved in cofactor binding are conserved with respect to other AKR members. CHO reductase shows a high degree of sequence identity (91%) with another AKR member, FR-1 (mouse fibroblast growth factor-regulated protein), especially around the variable C-terminal end of the protein and has a similar substrate binding pocket that is larger than that of aldose reductase. However, there are distinct differences that can account for differences in substrate specificity. Trp111, which lies horizontal to the substrate pocket in all other AKR members is perpendicular in CHO reductase and is accompanied by movement of Leu300. This coupled with movement of loops A, B, and C away from the active site region accounts for the ability of CHO reductase to bind larger substrates. The position of Trp219 is significantly altered with respect to aldose reductase and appears to release Cys298 from steric constraints. These studies show that AKRs such as CHO reductase are excellent models for examining the effects of subtle changes in amino acid sequence and alignment on binding and catalysis.

Alcohol Oxidoreductases↗
PubMed1996

Software to determine optimal oligonucleotide sequences based on hybridization simulation data.

In the design of oligonucleotide sequences for targeting DNA or RNA sequences, it can be difficult to identify sequences that will hybridize only to the intended target. The term "sequence-specific" or "sequence-nonspecific" is often used to describe the interactions of an oligonucleotide with a mixture of DNA or RNA. Our new computer program, HYBsimulator (formerly OligoProbe DesignStation), creates a set of candidate oligonucleotides from a target gene. For each of the candidate oligonucleotides, a large sequence database is searched for sequences that will hybridize to the oligonucleotide. This is referred to as computer hybridization simulation (CHS). Using the nearest-neighbor model, the HYBsimulator takes into account mismatches in hybridization and calculates the melting temperature (Tm) or free energy for hybridization to all sequences in a database. The specificity of each oligonucleotide is then quantified by the number of genes that may hybridize and the predicted Tms or free energies of hybridization to those genes. The CHS data are used to select oligonucleotides based on their specificity with respect to a database.

Base Sequence↗
PubMed1991

Composition of the subsistence foods of the Wopkaimin people of Papua New Guinea.

Forty-four samples of food, representing 35 species of animals and plants consumed by the Wopkaimin people of highland Papua New Guinea, were analyzed for their nutrient composition, many for the first time. Moisture, protein, fat and minerals (Na, K, Mg, Ca, Fe, Zn, Cu) were assayed directly. Energy and total carbohydrate content were calculated. The animal foods were high in protein, Fe and Zn. Ca was very high (greater than 1000mg/100g) in birds, frogs and fish containing soft edible bones. Leafy vegetables were relatively high in protein, iron and calcium. The five samples of taro (Colocasia esculenta) showed wide variation in composition. The results provide further information on the nutritional value of Papua New Guinean foods.

Food Analysis↗
PubMedDate not supplied

Interference between balance, gait and cognitive task performance among people with stroke living in the community.

PURPOSE: To explore differences in cognitive-motor interference between people with stroke and controls when performing functional tasks and to compare dual task performance of stroke fallers and non-fallers. METHOD: Thirty-six people with stroke (mean age 66.5, SD 11.8, mean time since onset 16 months, range 7 - 56) and 24 controls (mean age 62.3, SD 11.61) performed balance and gait tasks in isolation and in conjunction with a cognitive task (remembering a seven item-shopping list). Three-dimensional movement analysis was used to assess anterior posterior (AP) and lateral (ML) sway; 5 m walk time, stride length and velocity. RESULTS: In the single task condition, people with stroke had greater AP sway, reduced velocity and stride length and a longer 5 m walk time than controls (p < 0.01). In the dual task condition, sway reduced and gait slowed in both groups (p < 0.01 for AP sway, stride length, velocity, walk time); only the increase in walk time was greater in people with stroke than in the controls (F = 4.2, p = 0.046). Cognitive performance was maintained during the balance trials but deteriorated during the dual task gait trials in people with stroke (p = 0.017). Similar trends were noted for fallers and non-fallers with stroke: Only group effects for stride length and velocity reached significance (p < 0.05) and only the reduction in stride length was significantly greater among fallers than non-fallers (F = 12.3, p = 0.001). CONCLUSIONS: People with stroke and controls employed similar strategies during the simultaneous performance of simple functional and silent cognitive tasks and maintained postural stability. Increased walk time and decreased cognitive recall were greater for people with stroke and reduced stride length distinguished fallers from non-fallers.

Accidental Falls↗