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Biomedical subjects

S J Taylor

Publications and source records attributed to S J Taylor.

At least 55 records · Page 3Linked to original sources

Validation of a lower limb model with in vivo femoral forces telemetered from two subjects.

A mathematical model of the human pelvis-leg system in the sagittal plane, with an anatomical model of the knee, was developed to calculate forces transmitted by the structural elements of the system. The model was used to study the influence of activity of hip flexors and extensors on the forces in the femur during isometric exercises and during level walking. Kinematic and kinetic data together with simultaneous electromyography (EMG) and in vivo axial forces transmitted along the prostheses from two patients implanted with instrumented massive proximal femoral prostheses were obtained. Comparison of the levels of the calculated axial forces in the model femur to the simultaneous telemetered forces showed good agreement for isometric tests. Interaction between the muscles and the bones during isometric tests was examined and bi-articular muscles were shown to play a major role in modulating forces in bones. The study supports the hypothesis that muscles balance the external limb moments, not only at joints but also along the limbs, decreasing the bending moments but increasing the axial compressive forces in bones. It is thus suggested that appropriate simulation of muscle force is necessary in in vitro laboratory experiments and in theoretical studies of load transmission in bones. The sagittal plane model underestimates the value of the maximum axial force in the femur during walking by about 30% but suggests that 70% was due to the action of the extensors or flexors. The results encourage further development of a three-dimensional model with anatomical models of the joints to include coronal and transverse planes for the study of adductors and abductors.

Evaluation Studies as Topic↗

The forces in the distal femur and the knee during walking and other activities measured by telemetry.

The forces and moments in the shaft of a distal femoral replacement were measured by telemetry for a subject during different activities, and calculations were then made of the forces at the knee. The axial force showed a small peak at heel-strike followed by two main peaks during stance. In level walking, the peak axial force was between 1,487 and 1,718 N (2.2-2.5 BW), the peak shear force was 269-368 N (0.4-0.54 BW) directed anteriorly on the tibia, the peak axial torque was 7 Nm internal, while the patellofemoral force was 466-571 N. The highest axial force was recorded for descending stairs (2.8 BW). Standing on one leg produced 2.4 BW, while lying supine and raising the leg produced 1.7 BW. The data produced may resemble that of a normal subject, and has application to basic joint mechanics, to joint reconstruction, and to total knee replacement design and evaluation.

Adult↗

Influence of processed corn grain in diets of dairy cows on digestion of nutrients and milk composition.

Five primiparous Holstein cows (55 d in milk) that were fitted with ruminal and duodenal cannulas were used in a 4 x 5 incomplete Latin square to determine the effects of blends of steam-flaked and dry-rolled corn on site and extent of nutrient digestion and milk yield and composition. Diets were fed as total mixed rations and consisted of 45% forage and 55% concentrate; each diet contained 27% corn grain. Dietary treatments were composed of blends of dry-rolled and steam-flaked corn in ratios of 100:0, 67:33, 33:67, and 0:100. Intake of dry matter; digestibilities of dry matter, organic matter, acid detergent fiber, cellulose, neutral detergent fiber, fatty acids, and N; and microbial efficiency were unaffected by diet. Ruminal, postruminal, and total tract digestion of starch increased linearly, and starch passage to the duodenum decreased linearly, as the proportion of dry-rolled corn in the diet decreased. Ruminal propionate and valerate increased linearly, and acetate, butyrate, isovalerate, and the acetate to propionate ratio decreased linearly, as proportions of dry-rolled corn in the diet decreased; however, no changes in total volatile fatty acid concentrations in ruminal fluid were observed. Ruminal fluid pH was similar across diets. A decrease in dry-rolled corn decreased ruminal ammonia N and plasma urea N linearly. Milk yield and composition, as well as milk N fractions, were similar across diets. Although changes in fatty acid composition of milk fat were small, linear decreases in percentages of trans-C16:1 and cis-9- and cis-10-C18:1, as well as a linear increase in the percentage of C18:2 occurred as the proportion of dry-rolled corn in the diet decreased. An increased proportion of dry-rolled corn in the diet decreased digestion of starch in the rumen, and patterns of volatile fatty acid concentrations shifted accordingly. However, no effects on lactational parameters were observed.

Ammonia↗

Ash content of detergent fibers in feeds, digesta, and feces and its relevance in fiber digestibility calculations.

The influence of insoluble ash in diet, digesta, and fecal samples was evaluated. Ash-free values of neutral detergent fiber (NDF) and acid detergent fiber (ADF) for feed, digesta, and fecal samples were compared with uncorrected values of NDF and ADF in two digestibility experiments. Six feed samples were selected at random along with four duodenal and two fecal samples; the latter two were a part of two digestion studies. The silica composition of feed samples was low with the exception of oat hay and rice straw. Ash-free values of NDF and ADF for digesta and fecal samples were lower than uncorrected values of NDF and ADF, and silica accounted for the majority of the differences. The use of ash-free values of NDF and ADF in both digestibility experiments with dairy cows resulted in more realistic digestibility estimates and reduced the amount of variability associated with the calculation of the digestibility of NDF and ADF in the rumen and total digestive tract. The source of the insoluble ash was not identified but could have come from individual feedstuffs or the consumption of sand. Sample contamination by silica and other ash components may influence NDF and ADF composition if the fiber residues are not ashed prior to calculation of NDF and ADF.

Animal Feed↗

Heteronuclear NMR studies of the combined Src homology domains 2 and 3 of pp60 c-Src: effects of phosphopeptide binding.

The results of heteronuclear NMR studies on the combined Src homology domains 2 and 3 (SH3-SH2) of pp60 c-Src are presented. Resonance assignments were obtained using heteronuclear triple-resonance experiments in conjunction with 15N-separated nuclear Overhauser effect spectroscopy (NOESY) data. A modified three-dimensional 13CO-15N-1H spectral correlation experiment [(HACA)CO(CA)-NH] with improved sensitivity is presented that provided additional sequential information and resolved several ambiguities. Chemical shifts and sequential- and medium-range NOE cross peaks indicate that the structures of both the SH3 and SH2 portions of the polypeptide are very similar to those of the isolated SH3 and SH2 domains. Binding of a high-affinity phosphopeptide, EPQpYEEIPIYL, induces large chemical shift changes at several locations in the SH2 domain. Comparison with known results for peptide binding to SH2 domains shows that the residues displaying the largest effects are all involved in peptide binding or undergo significant conformational changes upon binding. However, subtle changes of both 1H and 15N chemical shifts are observed for residues within the SH3 domain and the connecting linker region, indicating possible cross-domain communication.

Amino Acid Sequence↗

Specificity and determinants of Sam68 RNA binding. Implications for the biological function of K homology domains.

Sam68, a specific target of the Src tyrosine kinase in mitosis, possesses features common to RNA-binding proteins, including a K homology (KH) domain. To elucidate its biological function, we first set out to identify RNA species that bound to Sam68 with high affinity using in vitro selection. From a degenerate 40-mer pool, 15 RNA sequences were selected that bound to Sam68 with Kd values of 12-140 nM. The highest affinity RNA sequences (Kd approximately 12-40 nM) contained a UAAA motif; mutation to UACA abolished binding to Sam68. Binding of the highest affinity ligand, G8-5, was assessed to explore the role of different regions of Sam68 in RNA binding. The KH domain alone did not bind G8-5, but a fragment containing the KH domain and a region of homology within the Sam68 subgroup of KH-containing proteins was sufficient for G8-5 binding. Deletion of the KH domain or mutation of KH domain residues analogous to loss-of-function mutations in the human Fragile X syndrome gene product and the Caenorhabditis elegans tumor suppressor protein Gld-1 abolished G8-5 binding. Our results establish that a KH domain-containing protein can bind RNA with specificity and high affinity and suggest that specific RNA binding is integral to the functions of some regulatory proteins in growth and development.

Adaptor Proteins, Signal Transducing↗

Size at birth and blood pressure: cross sectional study in 8-11 year old children.

OBJECTIVE: To identify which patterns of fetal growth, represented by different measurements of size at birth, are associated with increased blood pressure in children aged 8-11 years. DESIGN AND SETTING: School based, cross sectional survey conducted in 10 towns in England and Wales in 1994. SUBJECTS: 3010 singleton children (response rate 75%) with physical measurements and information on birth weight from parental questionnaires. Hospital birth records were examined for 1573. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure at age 8-11 years. RESULTS: In the whole group birth weight was inversely related to systolic pressure (regression coefficient -1.48 mm Hg/kg; 95% confidence interval -2.20 to -0.76) after adjustment for current body size. There was no significant association between birth weight and diastolic pressure. The association with systolic pressure was much stronger in girls (-2.54 mm Hg/kg; -3.60 to -1.48) than in boys (-0.64 mm Hg/kg; -1.58 to 0.30), with a significant difference between the sexes (P = 0.006). Among the other neonatal measures, head circumference and placental weight were inversely associated with subsequent blood pressure in girls, and placental ratio (placental weight:birth weight) was positively associated with blood pressure in boys. Neither ponderal index at birth nor length:head circumference ratio was related to blood pressure in either sex. CONCLUSIONS: In these contemporary children the association between birth weight and blood pressure was apparent only in girls. There was no evidence that measures of size at birth, which may be related to nutrition at critical periods of pregnancy (thinness at birth or shortness in relation to head circumference), are related to blood pressure in the offspring.

Birth Weight↗

Childhood size is more strongly related than size at birth to glucose and insulin levels in 10-11-year-old children.

In adults low birthweight and thinness at birth are associated with increased risk of glucose intolerance and non-insulin-dependent diabetes mellitus. We have examined the relations between size at birth (birthweight, thinness at birth) and levels of plasma glucose and serum insulin in children, and compared them with the effects of childhood size. We performed a school-based survey of 10-11-year-old British children (response rate 64%) with measurements made after an overnight fast. One group of children (n = 591) was studied fasting while the other (n = 547) was studied 30 min after a standard oral glucose load (1.75 g/kg). Serum insulin was measured by a highly specific ELISA method. Birthweight was assessed by maternal recall and thinness at birth using birth records. Neither fasting nor post-load glucose levels showed any consistent relationship with birthweight or ponderal index at birth. After adjustment for childhood height and ponderal index, both fasting and post-load insulin levels fell with increasing birthweight. For each kg increase in birthweight, fasting insulin fell by 16.9% (95% confidence limits 7.1-25.8%, p = 0.001) and post-load insulin by 11.6% (95% confidence limits 3.5-19.1%, p = 0.007). However, the proportional change in insulin level for a 1 SD increase in childhood ponderal index was much greater than that for birthweight (27.2% and -8.8%, respectively, for fasting insulin). We conclude that low birthweight is not related to glucose intolerance at 10-11 years, but may be related to the early development of insulin resistance. However, in contemporary children obesity is a stronger determinant of insulin level and insulin resistance than size at birth.

Adult↗

Relations between compressive axial forces in an instrumented massive femoral implant, ground reaction forces, and integrated electromyographs from vastus lateralis during various 'osteogenic' exercises.

A subject, who had undergone surgery to replace one hip joint and the proximal half of the femur with an instrumented titanium implant, performed brief exercises whilst simultaneous measurements were made of compressive axial force in the implant using short-range wireless telemetry, ground reactions using a Kistler force plate, and electromyographic activity of the vastus lateralis (VL) and erector spinae (ES) muscles using surface electrodes. Recordings were made barefoot and wearing 'trainers'. The exercises (slow jumping in counter movement style, fast continuous jumping, and jogging on the spot) have been found effective in controlled interventions for increasing bone mineral density in women. The implant forces were 250-400% BW. The values were about twice the magnitude of the ground reaction forces and significantly correlated with them for both peak force and its rate of rise but their relative magnitudes varied depending on mode of activity (jumping or jogging). Implant forces were significantly related to the muscle activity; in multiple regression analysis implant forces during take off from slow jumps VL contributed significantly in addition to the ground reaction (98% total explained variance). There was more activity in VL during jumping than jogging for the same implant force which may explain why jumping appears to be more osteogenic than jogging for the femur. For the same ground reaction, wearing trainers increased both the magnitude of the compressive loading of the femur and its rate of rise.

Analysis of Variance↗

Telemetry of forces from proximal femoral replacements and relevance to fixation.

Two proximal femoral replacements were instrumented to enable axial forces to be determined at two sites within the prosthesis: in the main shaft and near the tip of the intramedullary stem. The goal was to measure the changes in force distribution over time, as indicated by the ratio of the two forces. Inductive coupling between a coil worn around the leg and a small implanted coil was used, both to supply power to electronic circuits sealed into a welded cavity in the prosthesis and to telemeter data from the prosthesis. Data from both subjects were recorded over the first two years following surgery. For the first subject, there was an increase in mean shaft force excursions (peak force minus resting force) during level walking from 0.53 x BW after 1 week 2.77 x BW after 23 months. The corresponding mean tip force excursions were 0.13 x BW and 1.74 x BW, respectively. The ratio of mean tip force excursions to shaft force excursions steadily increased over the same period from 25 to 63%. Similar increases over time in the tip/shaft ratio were found during treadmill walking, stair climbing and stair descending. Data from the second subject were obtained for the shaft forces only, and were consistent with those from the first subject. The progressive transfer of axial load from the proximal to the distal part of the IM stem recorded telemetrically, together with radiographic observations, suggested that bone remodelling had taken place together with a less stable interface around the proximal part of the stem. This process evidently began soon after implantation.

Bicycling↗

Phosphorylation of the Src substrate Sam68 by Cdc2 during mitosis.

Sam68 (Src-associated in mitosis) is an SH3 (Src-homology 3), SH2 (Src-homology 2), and RNA binding protein which associates with and is tyrosine phosphorylated by wild-type and activated forms of c-Src in a mitosis-specific manner. We now show that Sam68 immunoprecipitated from either HeLa S3 or NIH3T3 cells is phosphorylated on threonine residues exclusively during mitosis as well as on serine residues during both interphase and mitosis. Recombinant Sam68, expressed as a glutathione S-transferase (GST) fusion protein, was phosphorylated on threonine and serine residues after incubation with mitotic lysates several-fold more extensively than after incubation with unsynchronized lysates. Cdc2 was identified as the kinase responsible for the mitotic threonine phosphorylation by (1) immunodepletion of the mitotic Sam68 kinase from cell lysates with anti-Cdc2 antibodies, (2) inhibition of Sam68 phosphorylation in vitro and in vivo by the cyclin-dependent kinase inhibitor olomoucine and (3) phosphorylation of Sam68 by purified Cdc2. These data demonstrate that Sam68 is a direct target of Cdc2 and may therefore mediate some of its biological effects during mitosis.

3T3 Cells↗

Applying bandwidth feedback scheduling to a golf shot.

Bandwidth knowledge of results (KR) involves the presentation of precise error KR only on those trials in which a preset criterion of accuracy is not met. When the criterion is met, only a general statement referring to this success is given. It has been shown that bandwidth KR increases movement consistency relative to 100% relative frequency KR (Lee & Carnahan, 1990). While this and other KR schedules have been successful in promoting motor learning, there has been no attempt to generalize this finding to a motor task requiring whole-body coordination. This study examined whether, by using information feedback suited to a complex task (Kernodle & Carlton, 1992), the findings relating to bandwidth feedback would transfer to such a task. Participants practiced a golf chipping task with either KR or error correcting transitional information, under 0, 5, or 10% bandwidth conditions. Participants in the 10% bandwidth condition who had received transitional information performed more consistently in retention than all other participants. This result provides support for the generalization of bandwidth feedback principles to complex tasks.

Adult↗

How are nations trying to prevent suicide? An analysis of national suicide prevention strategies.

Recent increases in suicide rates internationally have focused attention on suicide as an important area of public health concern. In this review, strategies developed by various countries to halt this trend are compared. Nine out of 15 countries respond to enquiry about the state of development of suicide prevention strategies and programmes. Comprehensive strategies have been or are being developed by Finland, Norway, Australia, New Zealand and Sweden. The organization of these strategies differs between countries. The interventions have similar targets and are presented in detail There are some similarities in strategy content but evident differences in organization. Further developments should not only be based on research, but also consider the diverse experiences of other countries, and they should incorporate appropriate structures for monitoring and evaluation.

Europe↗

Insulin-like growth factor I receptor signaling in transformation by src oncogenes.

R- cells, a line of mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I (IGF-I) receptor genes, are refractory to transformation by several viral and cellular oncogenes. Using colony formation in soft agar as a measure of full transformation, we report here that R- cells can be transformed by v-src, although they still cannot be transformed by the activated c-src527 (mutation at tyrosine 527 to phenylalanine), which readily transforms mouse embryo cells with a wild-type number of IGF-I receptors (W cells). Although v-src is a more potent inducer of tyrosine phosphorylation than c-src527, the extent of phosphorylation of either insulin receptor substrate 1 or Shc, two of the major substrates of the IGF-I receptor, does not seem sufficiently different to explain the qualitative difference in soft agar growth. v-src, however, is considerably more efficient than c-src527 in its ability to tyrosyl phosphorylate, in R- cells, the focal adhesion kinase, Stat1, and p130cas. These results indicate that v-src, but not c-src527, can bypass the requirement for a functional IGF-I receptor in the full transformation of mouse embryo fibroblasts and suggest that qualitative and quantitative differences between the two oncogenes can be used to identify some of the signals relevant to the mechanism(s) of transformation.

3T3 Cells↗

Functional MRI of pain- and attention-related activations in the human cingulate cortex.

The aims of the study were to use functional magnetic resonance imaging (fMRI) to 1) locate pain-related regions in the anterior cingulate cortex (ACC) of normal human subjects and 2) determine whether each subject's pain-related activation is congruent with ACC regions involved in attention-demanding cognitive processes. Ten normal subjects underwent fMRI with a 1.5-T standard commercial MRI scanner. A conventional gradient echo technique was used to obtain data from a single 4-mm sagittal slice of the left ACC, approximately 3.5 mm from midline. For each subject, interleaved sets of 6 images were obtained during a pain task, an attention-demanding task, and at rest, for a total of 36 images per task. Pain of different intensities was evoked via electrical stimulation of the right median nerve. The attention-demanding task consisted of silent word generation (verbal fluency). Additional experiments obtained data from the right ACC. A pixel-by-pixel statistical analysis of task versus rest images was used to determine task-related activated regions. The pain task resulted in a 1.6-4.0% increase in mean signal intensity within a small region of the ACC. The exact location of this activation varied from subject to subject, but was typically in the posterior part of area 24. The signal intensity changes within this region correlated with pain intensity reported by the subject. The attention-demanding tasks increased the mean signal intensity by 1.3-3.3% in a region anterior and/or superior to the pain-related activation in each subject. The activated region was typically larger than the pain-related activation. In some cases this activation was at or superior to the ACC border, near the supplementary motor area. These regions did not show any pain-intensity-related activation. In one subject both right and left ACC were imaged, revealing bilateral ACC activation during the attention task but only contralateral pain-related activation. These findings shed light on pain- and attention-related cognitive processes. The results provide evidence for a region in the posterior part of the ACC that is involved in pain and a more anterior region involved in other attention-demanding cognitive tasks.

Adult↗