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Biomedical subjects

S Robbins

Publications and source records attributed to S Robbins.

At least 19 recordsLinked to original sources

Loss of functional caveolae during senescence of human fibroblasts.

Primary human fibroblasts have a finite replicative lifespan in culture that culminates in a unique state of growth arrest, termed senescence that is accompanied by distinct morphological and biochemical alterations. Senescent cell responses to extracellular stimuli are believed to be altered at a point after receptors are bound by ligand, leading to improper integration of the signals which initiate DNA replication. In this study we demonstrate that one of the key organizing membrane microdomains for receptor signaling, caveolae, are absent in senescent cells. A comparison of young and senescent cells indicated that senescent cells contained a higher total amount of caveolins 1 and 2 but had significantly less of both proteins in the caveolar fraction. Additionally, caveolar fractions from senescent cells completely lacked the tyrosine-kinase activity associated with functional caveolae. Furthermore, old cells had little caveolar protein exposed to the outer plasma membrane as estimated by using an in vivo biotinylation assay and no detectable caveolin 1 on the cell surface when processed for immunofluoresence and confocal microscopy. Together, these data suggest that a fundamental loss of signal integration at the plasma membrane of senescent cells is due to the loss of signaling competent caveolae.

Caveolae↗

The effects of active immunization against gnRH on testicular development, feedlot performance, and carcass characteristics of beef bulls.

The objective was to determine the effects of a recombinant fusion protein anti-GnRH vaccine on testicular development, feedlot performance, and carcass quality of beef bulls. Crossbred beef bulls (n = 58, average weight 306 kg, 9 mo of age), were randomly allocated to two groups and received either an anti-GnRH vaccine (GnRH) or placebo (Control) by intramuscular injection on d 0, 56, and 112. There were group effects (P < 0.01; as a percentage of Control) on testicular weight (53%), daily sperm production (40%), and epididymal sperm reserves (16%). There were group x time interactions (P < 0.0001) for scrotal circumference and serum testosterone concentrations; at slaughter, bulls in the GnRH group had a smaller (P < 0.05) scrotal circumference (28.3 vs 33.9 cm) and lower (P < 0.05) serum testosterone concentrations (2.2 vs 8.6 ng/mL) than those in the Control group. Average daily gain, feed intake, and feed efficiency were not different between treatments during the backgrounding phase (d 0 to 84). During the finishing phase (d 98 to 182), ADG was greater (P < 0.05) for bulls in the Control group (1.69 vs 1.42 kg/d), as was carcass weight (6.9%; P < 0.01). However, GnRH bulls had numerically better feed efficiency (6.12 vs 7.08 kg DMI/kg gain; P < 0.23) and shear force values for ribeye that were 16% lower (P < 0.14) than Control bulls, warranting further investigation. Vaccinating bulls against GnRH suppressed testicular function, with growth and carcass characteristics similar to that expected with steers.

Animal Husbandry↗

Robotic selective sampling and total automation for anti-CMV screening.

The provision of anti-cytomegalovirus (CMV)-negative blood products causes the blood banking community considerable logistical problems. This is due firstly to the fact that only a select group of patients require anti-CMV-negative units, namely the immunocompromised. Secondly, the prevalence of CMV antibody in the blood donor population is high and, thirdly, the demand for anti-CMV-negative blood components continues to increase. To address this problem, a system of robotic selective sampling and total assay automation for anti-CMV screening has been developed. An in-house computer program generates a worklist from the donation database of samples requiring screening to meet clinical demand. Algorithms incorporated in the program ensure that the minimum number of samples possible are selected for provision of anti-CMV-negative products. This 'intelligent' selection of samples substantially reduces reagent cost. Robotic pipetting from the electronically derived worklist, masterplate to test plate robotic transfer and use of an automated assay processor maintains specific sample identification throughout. Results are read mechanically and transmitted directly to the main computer system. Robotic selective sampling and total assay automation produces an efficient, secure, auditable and completely traceable system for the provision of anti-CMV-negative units. The system produced a substantial reduction in labour costs with a 40% reduction in reagent usage. This system can be readily adapted for screening other markers on a selective basis.

Antibodies, Viral↗

Improving balance.

OBJECTIVE: To test the hypothesis that shoes made with a sole material that retains compressed thickness between steps (low resiliency) provide balance better than and comfort equal to shoes composed of high resiliency sole material. SETTING: Older subjects were recruited from a medical clinic population, and younger subjects came from a recreational sports population. DESIGN: A randomized-order, cross-over, controlled comparison design. PARTICIPANTS: Groups comprised random samples of 30 older (mean age 66 years, SD+/-3.0), and 30 younger (mean age 34 years, SD+/-6.0) healthy men who met age selection criteria. MEASUREMENTS: Stability was inferred by sway measures: sway velocity (cm x s(-1)), X-Y area (cm2), and radial area (cm2). Comfort was measured by direct scaling and magnitude estimation using an 11-point ratio scale. RESULTS: Stability inferred by sway velocity was 311% (P < .001) and 31% (P < .001) poorer for younger and older groups, respectively, for high and low resiliency interfaces. Sway velocity with low resiliency interface was lower than bare platform, the lowest ever recorded under equivalent conditions (P < .001). All interfaces were equally comfortable. CONCLUSIONS: Stability rises with low resiliency interfaces and declines with high resiliency interfaces: sway velocity in older people wearing hard-soled footwear incorporating low resiliency technology would be 20% lower than in younger people wearing most current athletic and walking shoes. Inasmuch as existing theory can not account for improved balance with interfaces, we propose that when humans are supported by rigid support surfaces, elastic biologic tissues store energy from postural adjustments and locomotion, which is returned as a reaction force causing overshoot. This amplifies frontal plane foot movement and attenuates foot position awareness, causing less precise postural adjustments and instability. Low resiliency interfaces dissipate energy and thereby moderate overshoot. Low resiliency interface technology is capable of improving stability, which portends improved health for unstable older people in particular.

Adult↗

Factors associated with ankle injuries. Preventive measures.

A sense of foot position in humans is precise when barefoot, but is distorted by athletic footwear, which accounts for the high frequency of ankle sprains in shod athletes. It is unclear whether taping and rigid and semi-rigid devices protect against ankle sprains, as all of the studies suggesting this are flawed by inadequate controls. If these devices do protect the ankle, it is not through added support but rather through a partial correction of the deceased foot position awareness caused by footwear. Since taping and rigid and semi-rigid devices interfere with normal movement, there is concern that these might actually increase the frequency of injury at the ankle and/or at different locations. In this respect, taping is less of a concern because it interferes least with normal movement. The best solution for reducing ankle sprains in shod athletes is the use of more advanced footwear to retain maximal tactile sensitivity, thereby maintaining an awareness of foot position comparable to that of the barefoot state or perhaps even improving on it.

Ankle Injuries↗

Osteoclastic activation is the principal mechanism leading to secondary osteoporosis in rheumatoid arthritis.

OBJECTIVE: To use clinical measures and biochemical markers of bone turnover to investigate mechanisms of generalized bone loss in early rheumatoid arthritis (RA). METHODS: We studied 232 patients with RA of less than 2 years' duration and 72 healthy controls using serial dual x-ray absorptiometry scanning of lumbar spine and hips. Patients attended the clinic for clinical and laboratory assessment with storage of serum, urine, and plasma at each visit. Change in bone mineral density (BMD) was calculated for patients and controls and compared with baseline and mean serial values of bone markers over the same intervals. Serum was assayed for procollagen I carboxyterminal propeptide (PICP) and skeletal alkaline phosphatase (sALP); urine for pyridinoline and deoxypyridinoline corrected for creatinine; and plasma for interleukin 1 (IL-1) and IL-6. RESULTS: Patients lost bone significantly faster than controls at all sites (p < 0.01 for all). At first visit patients had significantly lower PICP levels than controls (p < 0.05) and sALP correlated with initial BMD in both patients (p < 0.01, r > 0.35, all sites) and controls (p < 0.0001, r > 0.50, all sites). We rescanned 167 patients at one year and 121 patients at 2 years. Mean urinary pyridinoline and deoxypyridinoline levels correlated strongly with BMD change at all sites, were increased in patients with active disease (p < 0.005), and correlated closely with mean C-reactive protein (CRP) (p < 0.005, r > 0.41 for both). CONCLUSION: This study suggests that osteoclastic activation, rather than suppression of bone formation, is the dominant process leading to bone loss in early RA. Although urinary pyridinoline and deoxypyridinoline were excellent markers of BMD change, CRP was found to be best overall. This provides a rational approach for selecting and treating patients with RA to reduce their established longterm risk of osteoporotic fracture.

Absorptiometry, Photon↗

Studies on the mutagenicity of mild gasification products of coal and their subfractions by the Salmonella/microsomal assay.

Mild gasification of coal is a technology being developed in the United States in order to upgrade lower rank coals and facilitate their use in coal-burning electric generation plants. Thirteen coal-derived mild gasification products from different coal sources and processing conditions have been examined for their potential biohazards. The mutagenicity of these samples was tested with the Ames Salmonella/microsomal assay. Two solvents, dimethyl sulfoxide (DMSO) and polyoxyethylene-sorbitan monooleate (Tween 80), were used to dissolve samples in a manner to facilitate their interaction with the test organisms. The results showed that 9 of the 13 samples displayed mutagenic activity in test strains TA98 and/or TA100 with or without metabolic activation, whether dissolved in Tween 80 or DMSO. Five mutagenic and two nonmutagenic samples were class-fractionated into basic, acidic, nonpolar, and polar neutral subfractions to examine their class-related mutagenic activities. Results of the testing of subfractions of the five mutagenic and one nonmutagenic samples showed mutagenic activity in at least the nonpolar neutral fraction. The subfractions of the another nonmutagenic sample did not display any mutagenic activity. Chemical characterization of the subfractions revealed the existence of aromatic hydrocarbons in certain subfractions, which may be responsible for the mutagenic activity of the coal-derived mild gasification products.

Animals↗

Balance and vertical impact in sports: role of shoe sole materials.

OBJECTIVE: Athletic shoes and mats are support surface interfaces composed of relatively soft compressible materials designed to protect against injuries occurring in sports through force of vertical impact. Impact remains high with their use because humans land harder with them. We hypothesize that this hard-landing strategy is an attempt by the user to improve stability, by compressing the material to a less destabilizing thinner-stiff variety. We tested this hypothesis by comparing impact and balance on materials consisting of ethyl-vinyl acetate (EVA) foams of varying stiffness, identical to that found in soles of athletic footwear. DESIGN: Randomized-order, crossover trial, controlled comparison, blinded. SETTING: Volunteers were selected from the general community. PARTICIPANTS: A random sample of 12 healthy men from the general population (mean age 30 years, SD +/- 6). Additional selection criteria were absence of disabilities influencing ability to walk, run, and balance, and no history of frequent falls. METHODS: Impact testing and stability measures were performed on the same test day. Ground reaction forces were measured for ten barefoot footfalls. The protocol required stepping forward from perch to surface 4.5 cm below. Stability testing was performed with one-legged standing consisting of placing left foot on top of right for 30 sec, barefoot, eyes open, and gaze straight, with arms to side. Subjects confronted four surface conditions presented in random order: a bare rigid platform, and the platform covered with one of three 2.5-cm-thick materials. RESULTS: Steady state vertical impact was a negative function of interface stiffness, with the softest interface producing the greatest vertical impact, and the stiffest interface the least vertical impact. Vertical impact and stability measures were also negatively related, with the strongest correlation obtained with the softest interface (r = -.87, p < .001). No relation between these variables was obtained for the rigid surface. CONCLUSION: Balance and vertical impact are closely related. This supports the hypothesis that landing hard on soft surfaces is an attempt to transform the interface into a form associated with improved stability. According to these findings, currently available sports shoes and mats are too soft and thick, and should be redesigned to protect the persons using them.

Adult↗

Foot position awareness in younger and older men: the influence of footwear sole properties.

OBJECTIVES: To test the hypotheses that foot position awareness is related positively to stability, positively to shoe sole hardness, and negatively to shoe sole thickness, and that foot position awareness declines with advancing years. SETTING: Older subjects were consecutive volunteers from a medical clinic; younger subjects were volunteers from the community. DESIGN: Randomized-order, cross-over, controlled comparison. PARTICIPANTS: Older subjects were a random sample of 13 healthy men, mean age 72.58 years, SD +/- 4.50. Younger subjects were a random sample of 13 male subjects from the general population, mean age 28.13 years, SD +/- 3.96. Additional selection criteria were absence of disabilities influencing ability to walk and no history of frequent falls. MEASUREMENTS: Balance failure frequency, defined as falls per 100 meters of beam walking; rearfoot angle in degrees, measured via an optical position measurement system; perceived maximum supination when walking, in degrees, estimated by subjects using a ratio scale; foot position error, in degrees, was defined as the rearfoot angle minus perceived maximum supination. RESULTS: Foot position error during walking: (1) increases with advancing years; footwear conditions absolute mean error for older sample of 15.48 degrees, SE +/- 1.56 degrees, and younger sample 5.44 degrees, SE +/- 1.03 degrees (P > .001); (2) is positively related to stability (r = .367, P < .001); (3) is positively related to midsole thickness (F(1,11) = 19.89, P < .001); (4) is negatively related to midsole hardness (F(2,22) = 29.80, P < .001); (5) correlates best with perceived maximum supination (r = .901, P < .001). CONCLUSION: Foot position awareness is related causally to stability; shoes with thin, hard soles provide better stability for men than those with thick, soft midsoles. Foot position awareness declines with advancing years.

Adult↗

Hazard of deceptive advertising of athletic footwear.

OBJECTIVES: Athletic footwear are associated with frequent injury that are thought to result from repetitive impact. No scientific data suggest they protect well. Expensive athletic shoes are deceptively advertised to safeguard well through "cushioning impact", yet account for 123% greater injury frequency than the cheapest ones. This study tested the hypothesis that deceptive advertising creates a false sense of security with users of expensive athletic shoes, inducing attenuation of impact moderating behaviour, increased impact, and injury. METHODS: Fifteen young healthy male volunteers confronted four surfaces: a bare force moment platform, and three with this platform covered by identical shoe sole material made to appear different and advertised divergently. Advertising messages suggested superior impact absorption and protection (deceptive message), poor impact absorption and high injury risk (warning message), and unknown impact absorption and safety (neutral message). Ground reaction forces were recorded for 10 barefoot footfalls, according to a protocol requiring stepping forward from perch to a surface 4.5 cm below. RESULTS: Impact varied as a function of advertising message (p < 0.001). Deceptive message equalled neutral message in eliciting higher impact than the warning message and the bare platform. Differences grew with repetitions (p < 0.001). CONCLUSIONS: These data provide a plausible mechanism explaining higher injury frequency in users of expensive athletic shoes. This is the first report to suggest: (1) deceptive advertising of protective devices may represent a public health hazard and may have to be eliminated presumably through regulation; (2) a tendency in humans to be less cautious when using new devices of unknown benefit because of overly positive attitudes associated with new technology and novel devices.

Adult↗

Semirigid instrumentation in the management of lumbar spinal conditions combined with circumferential fusion. A multicenter study.

STUDY DESIGN: Patients with the diagnosis of degenerative disc conditions or spondylolisthesis undergoing circumferential fusion with posterior pedicle screw fixation using a semirigid rod were reviewed. OBJECTIVES: To determine the effectiveness of this approach in achieving a spinal fusion and satisfactory clinical outcome, and to determine the complications associated with the procedure. SUMMARY OF BACKGROUND DATA: The use of instrumentation to stabilize the lumbar motion segments and thereby enhance the fusion rate has been proposed in a number of studies. Semirigid fixation was believed to be effective in achieving these objectives without concern for stress-shielding, which was suggested by some authors using rigid fixation systems. METHODS: Patients who required spinal fusion with anterior and posterior approaches because of specific lumbar pathology or previous surgeries were selected. The surgery consisted of an anterior interbody fusion using allograft, followed by a posterolateral fusion and pedicle screw fixation. Fusion was determined by continuity of trabecular bridging, and outcomes were determined by pain reduction and return to previous levels of activity. Fusion was considered solid if the two posterolateral areas were fused (Zones one and two), if the anterior interbody area was fused (Zone three), or if all three zones were fused. Complications were documented during and after surgery. RESULTS: Sixty-two percent of patients had previous surgery with 25% of these patients having a diagnosis of pseudarthrosis. Fifty-five percent of patients had two or more levels fused, and 43% were heavy smokers. Ninety-seven percent of patients had successful fusions. Pain was significantly reduced on a pain analogue scale from 7.1 to 2.1 in the back and from 5.8 to 1.5 in the leg (p < 0.006 and 0.0001, respectively). Fifty-nine percent of patients returned to their previous level of activity, and 18% returned to lighter work or job retraining, for a total of 77% returning to the same or lighter levels of activity. Complications included metal failure, 4.9%; neurologic deficit, 1.2%; deep infection, 1.2%; deep venous thrombosis, 4.9%; and vascular injury, 2.4%. Fatal pulmonary embolus occurred in one patient. CONCLUSION: This technique produces a satisfactory fusion rate (97%) and a good clinical outcome based on pain reduction and return to a satisfactory level of activity (77%). It is associated with few, but significant, complications that compare well with other reported series in a difficult group of patients. This procedure should be reserved for patients who are considered to be at high risk for not achieving spinal fusion.

Adolescent↗

Pharmacological attempts to improve the bioavailability of oral etoposide.

Etoposide demonstrates incomplete and variable bioavailability after oral dosing, which may be due to its concentration and pH-dependent stability in artificial gastric and intestinal fluids. The use of agents that may influence etoposide stability and, thereby, bioavailability, was investigated in a number of clinical studies. Drugs that influence the rate of gastric emptying, while modulating the time of drug absorption, did not significantly alter the etoposide area under the concentration-time curve (AUC) or bioavailability. Specifically, metoclopramide had little effect on the etoposide absorption profile and did not significantly alter the AUC (AUC with etoposide alone, 68.4 +/- 20.3 micrograms ml-1 h, versus 74.3 +/- 25.9 micrograms ml-1 h with metoclopramide), suggesting that in most patients the drug is already emptied rapidly from the stomach. In contrast, propantheline produced a dramatic effect on etoposide absorption, delaying the time of maximal concentration tmax from 1.1 to 3.5 h (P < 0.01), but again without a significant improvement in drug AUC or bioavailability across the 24-h study period (AUC with etoposide alone 78.3 +/- 19.1 micrograms ml-1 h, versus 88.1 +/- 23.6 micrograms ml-1 h with propantheline). The effect of these drugs on the absorption of oral paracetamol, a drug included in the study as a marker of gastric emptying, was exactly the same as that found for etoposide, with no change in AUC being observed after metoclopramide or propantheline administration but a significant delay in tmax being seen on co-administration with etoposide and propantheline. The co-administration of ethanol or bile salts (agents that significantly improved the stability of etoposide in artificial intestinal fluid) with oral etoposide similarly had no effect on improving the etoposide AUC or reducing the variability in AUC, suggesting that drug stability in vivo was not affected by these agents. In the third study the co-administration of cimetidine had no effect on the pharmacokinetics of oral or i.v. etoposide, despite the previous observation that etoposide stability was markedly improved at pH 3-5 as compared with pH 1 in artificial gastric fluid. This series of studies, designed to investigate factors that improved etoposide stability in laboratory studies, failed to demonstrate any potentially useful improvement in AUC or bioavailability in the clinical setting.

Administration, Oral↗

Proprioception and stability: foot position awareness as a function of age and footwear.

We examined the hypothesis that awareness of foot position in terms of the slope of the weight-bearing surface declines with age. We further postulated that the decline would be due to a change in plantar tactile sensibility, and that footwear would further impair position judgments. We compared 15 men aged over 65 years (mean age 73) with 36 men aged under 40 (mean age 30) in terms of estimates of amplitude and direction of surface slopes. We employed a ratio scale of 0-10 representing actual slopes of 0 degrees-25 degrees in increments of 2.5 degrees. In order to examine whether subjects overestimated high angles they were told that the scale ranged from 0 to 15. We found significant differences between the two groups in terms of estimates and the effect of footwear. Psychophysical functions for estimate of slope were 0.95 for the young when barefoot and 0.71 when shod compared with 0.80 and 0.81 respectively for the older men. We conclude that sensitivity to foot position declines with age, mainly owing to loss of plantar tactile sensitivity. Footwear impairs foot position awareness in both young and old. Loss of foot position awareness may contribute to the frequency of falls in later life.

Adult↗

Ankle taping improves proprioception before and after exercise in young men.

Ankle sprains are common sports injuries. Inadequate foot position awareness is thought to be the fundamental cause of these injuries. Ankle taping may decrease risk of injury through improving foot position awareness. The benefit of taping is thought to decrease with duration of exercise because of poor tape adherence to human skin. This study was a randomized, crossover, controlled comparison experiment that tested the hypothesis that ankle taping improves foot position awareness before and after exercise. A sample of 24 healthy young blindfolded volunteers, wearing their own athletic shoes, indicated perceived slope direction and estimated slope amplitude when bearing full body weight and standing on a series of blocks. The top slope of the blocks varied between 0 degree and 25 degrees, in 2.5 degrees increments, to orient the plantar surface with respect to the leg toward pronation, supination, plantarflexion, and dorsiflexion, relative to its position on a flat surface. Foot position awareness, which was considered the reciprocal of surface slope estimate error, varied with testing condition, particularly when surface slope was greater than 10 degrees, presumably the most important range considering ankle injuries. In this higher range absolute position error was 4.23 degrees taped, and 5.53 degrees untaped (P < 0.001). Following exercise, in the higher range absolute position error was 2.5% worse when taped and 35.5% worse when untaped (P < 0.001). These data support the hypothesis that ankle taping improves proprioception before and after exercise. They also indicate that foot position awareness declines with exercise. Compared to barefoot data (position error 1.97 degrees), foot position error was 107.5% poorer with athletic footwear when untaped (absolute position error 4.11 degrees), and 58.1% worse when taped (position error 3.13 degrees). This suggests that ankle taping partly corrects impaired proprioception caused by modern athletic footwear and exercise. Footwear could be optimized to reduce the incidence of these injuries.

Adult↗

Athletic footwear affects balance in men.

Stable equilibrium during locomotion is required for both superior performance of sports and prevention of injuries from falls. A recent report indicated that currently available athletic footwear impairs stability in older men. Since this discovery, if confirmed, seems important to both competitive athletes and the physically active general public, we performed an experiment using similar methods on a younger population. We tested the hypothesis that midsole thickness is negatively, and hardness positively related to dynamic equilibrium, in 17 healthy adult men (mean(s.d.) age 33(11.13) years) via a balance beam method. Subjects walked along a 9-m long beam at 0.5 m s-1 once barefoot and six times wearing identical pairs of experimental shoes which differed only in midsole hardness and thickness which spanned the respective ranges currently available in footwear. Falls from the beam (balance failures) were quantified. Balance failures varied significantly in relation to midsole hardness and thickness, and there was a strong trend toward interaction of these variables (P = 0.09). Midsole hardness was positively related to stability, and midsole thickness was negatively related, which confirms the previous report. Hence, shoes with thick-soft soles, similar to modern athletic footwear and 'walking shoes', destabilize men, and shoes with thin-hard soles provide superior stability. The pair with the poorest stability (A 15-thick; 12.34 balance failures per 100 m) produced 217% more balance failures than those associated with the best stability (A 50-thin; 3.89 balance failures per 100 m). Since most types of athletic footwear and many other shoes incorporate midsoles with hardness and thickness associated with poor stability, we conclude that both athletic performance and public safety could be enhanced through stability optimized footwear.

Adult↗

Retroposition in a family of carcinoma-associated antigen genes.

The gene encoding the carcinoma-associated antigen defined by the monoclonal antibody GA733 is a member of a family of at least two type I membrane proteins. This study describes the mechanism of evolution of the GA733-1 and GA733-2 genes. A full-length cDNA clone for GA733-1 was obtained by screening a human placental library with a genomic DNA probe. Comparative analysis of the cDNA sequence with the previously determined genomic sequence confirmed that GA733-1 is an intronless gene. The GA733-2 gene encoding the monoclonal antibody-defined antigen was molecularly cloned with a cDNA probe and partially sequenced. Comparison of GA733-2 gene sequences with the previously established cDNA sequence revealed that this gene consists of nine exons. The putative promoter regions of the GA733-1 and GA733-2 genes are unrelated. These findings suggest that the GA733-1 gene was formed by the retroposition of the GA733-2 gene via an mRNA intermediate. Prior to retroposition, the GA733-2 gene had been affected by exon shuffling. Analysis of GA733-2 exons revealed that many delineate structural motifs. The GA733-1 retroposon was localized either to chromosome region 1p32-1p31 or to 1p13-1q12, and the GA733-2 founder gene was localized to chromosome 4q.

Amino Acid Sequence↗