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Biomedical subjects

A Su

Publications and source records attributed to A Su.

16 recordsLinked to original sources
PubMed2006

Comparison of late gastrointestinal and genitourinary toxicity of prostate cancer patients undergoing intensity-modulated versus conventional radiotherapy using localized fields.

To compare late genitourinary (GU) and gastrointestinal (GI) toxicity of radiotherapy (RT) to localized fields for prostate cancer delivered using intensity-modulated RT (IMRT) versus conventional RT (ConvRT). The records of 461 patients were reviewed; 355 patients received IMRT and 106 received ConvRT. Late GU and GI toxicity were compared. Late GU toxicity rates were not significantly different (P=0.166); however, late GI toxicity rates were lower with IMRT (P=0.001). Regression analyses demonstrated that only IMRT use (P=0.006) predicted reduction in late GI toxicity but no factors correlated with late GU toxicity. IMRT did not influence late GU toxicity but was associated with a reduction of late GI toxicity over ConvRT.

Aged↗
PubMed2004

Reduced expression of small GTPases and hypermethylation of the folate binding protein gene in cisplatin-resistant cells.

Reduced accumulation of cisplatin is the most consistent feature seen in cisplatin-resistant (CP-r) cells that are cross-resistant to other cytotoxic compounds, such as methotrexate. In this report, defective uptake of a broad range of compounds, including [(14)C]-carboplatin, [(3)H]MTX, [(3)H]folic acid (FA), [(125)I]epidermal growth factor, (59)Fe, [(3)H]glucose, and [(3)H]proline, as well as (73)As(5+) and (73)As(3+), was detected in CP-r human hepatoma and epidermal carcinoma cells that we have previously shown are defective in fluid-phase endocytosis. Downregulation of several small GTPases, such as rab5, rac1, and rhoA, which regulate endocytosis, was found in CP-r cells. However, expression of an early endosomal protein and clathrin heavy chain was not changed, suggesting that the defective endocytic pathway is clathrin independent. Reduced expression of the cell surface protein, folate-binding protein (FBP), which is a carrier for the uptake of MTX, was also observed in the CP-r cells by confocal immunofluorescence microscopy and Real-Time PCR. Reactivation of the silenced FBP gene in the CP-r cells by a DNA demethylation agent, 2-deoxy-5-aza-cytidine (DAC) demonstrates that hypermethylation occurred in the CP-r cells. The uptake of [(14)C]carboplatin, [(3)H]FA, and [(3)H]MTX increased in an early stage CP-r cell line (KB-CP1) after treatment with DAC. Both a defective endocytic pathway and DNA hypermethylation resulting in the downregulation of small regulatory GTPases and cell surface receptors contribute to the reduced accumulation of a broad range of compounds in CP-r cells.

Antineoplastic Agents↗
PubMed2004

Foot and ankle forces during an automobile collision: the influence of muscles.

Muscles have a potentially important effect on lower extremity injuries during an automobile collision. Computational modeling can be a powerful tool to predict these effects and develop protective interventions. Our purpose was to determine how muscles influence peak foot and ankle forces during an automobile collision. A 2-D bilateral musculoskeletal model was constructed with seven segments. Six muscle groups were included in the right lower extremity, each represented by a Hill muscle model. Vehicle deceleration data were applied as input and the resulting movements were simulated. Three models were evaluated: no muscles (NM), minimal muscle activation at a brake pedal force of 400 N (MN), and maximal muscle activation to simulate panic braking (MX). Muscle activation always resulted in large increases in peak joint force. Peak ankle joint force was greatest for MX (10120 N), yet this model also had the lowest peak rearfoot force (629 N). Peak force on the Achilles tendon was 4.5 times greater, during MX (6446 N) compared to MN (1430 N). We conclude that (1). external and internal forces are dependent on muscles, (2). muscle activation level could exacerbate axial loading injuries, (3). external and internal forces can be inversely related once muscle properties are included.

Acceleration↗
PubMed2004

High dose antipsychotic use in schizophrenia: findings of the REAP (research on east Asia psychotropic prescriptions) study.

BACKGROUND: High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. METHODS: This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. RESULTS: Within the study group (n = 2399), 430 patients (17.9%) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p < 0.001), longer duration of admission (p < 0.001), duration of illness (p < 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p < 0.001, particularly in Japan and Korea), and aggression (p < 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p < 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use. CONCLUSIONS: This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.

Adult↗
PubMed2004

Pre-impact lower extremity posture and brake pedal force predict foot and ankle forces during an automobile collision.

BACKGROUND: The purpose of this study was to determine how a driver's foot and ankle forces during a frontal vehicle collision depend on initial lower extremity posture and brake pedal force. METHOD OF APPROACH: A 2D musculoskeletal model with seven segments and six right-side muscle groups was used. A simulation of a three-second braking task found 3647 sets of muscle activation levels that resulted in stable braking postures with realistic pedal force. These activation patterns were then used in impact simulations where vehicle deceleration was applied and driver movements and foot and ankle forces were simulated. Peak rearfoot ground reaction force (F(RF)), peak Achilles tendon force (FAT), peak calcaneal force (F(CF)) and peak ankle joint force (F(AJ)) were calculated. RESULTS: Peak forces during the impact simulation were 476 +/- 687 N (F(RF)), 2934 +/- 944 N (F(CF)) and 2449 +/- 918 N (F(AJ)). Many simulations resulted in force levels that could cause fractures. Multivariate quadratic regression determined that the pre-impact brake pedal force (PF), knee angle (KA) and heel distance (HD) explained 72% of the variance in peak FRF, 62% in peak F(CF) and 73% in peak F(AJ). CONCLUSIONS: Foot and ankle forces during a collision depend on initial posture and pedal force. Braking postures with increased knee flexion, while keeping the seat position fixed, are associated with higher foot and ankle forces during a collision.

Acceleration↗
PubMed2003

Development and validation of a 3-D model to predict knee joint loading during dynamic movement.

The purpose of this study was to develop a subject-specific 3-D model of the lower extremity to predict neuromuscular control effects on 3-D knee joint loading during movements that can potentially cause injury to the anterior cruciate ligament (ACL) in the knee. The simulation consisted of a forward dynamic 3-D musculoskeletal model of the lower extremity, scaled to represent a specific subject. Inputs of the model were the initial position and velocity of the skeletal elements, and the muscle stimulation patterns. Outputs of the model were movement and ground reaction forces, as well as resultant 3-D forces and moments acting across the knee joint. An optimization method was established to find muscle stimulation patterns that best reproduced the subject's movement and ground reaction forces during a sidestepping task. The optimized model produced movements and forces that were generally within one standard deviation of the measured subject data. Resultant knee joint loading variables extracted from the optimized model were comparable to those reported in the literature. The ability of the model to successfully predict the subject's response to altered initial conditions was quantified and found acceptable for use of the model to investigate the effect of altered neuromuscular control on knee joint loading during sidestepping. Monte Carlo simulations (N = 100,000) using randomly perturbed initial kinematic conditions, based on the subject's variability, resulted in peak anterior force, valgus torque and internal torque values of 378 N, 94 Nm and 71 Nm, respectively, large enough to cause ACL rupture. We conclude that the procedures described in this paper were successful in creating valid simulations of normal movement, and in simulating injuries that are caused by perturbed neuromuscular control.

Adult↗
PubMed2001

A screening method for knee trauma.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate whether any one conventional radiographic view is sufficient as a screening method in the detection of acute knee trauma. MATERIALS AND METHODS: The authors prospectively assessed the efficacy of a single conventional radiograph of the knee in the detection of signs of knee fractures in 214 consecutive adults with acute knee trauma. The evaluated efficacy parameters included specificity, sensitivity, negative predictive value (NPV), and positive predictive value. The percentage reduction in the need for additional conventional radiographs was also calculated. RESULTS: Fifty-three of the 214 patients (24.8%) had a knee fracture. The sensitivity of the single lateral view in the detection of knee fractures was 100% (95% confidence interval [CI] = 94.3, 100). The lateral view of the traumatized knee was normal in 143 patients (66.8%). The probability of not having a fracture if the lateral view was normal (NPV) was also 100% (95% CI = 97.9, 100). The need for additional radiographs was reduced 67%. CONCLUSION: A single lateral view as a screening tool for knee fractures has a very high sensitivity and NPV. Because more than 65% of the patients had a normal lateral view in this study, there can be a considerable amount of savings in terms of radiology services for these patients.

Adult↗
PubMed2001

Designed protein G core variants fold to native-like structures: sequence selection by ORBIT tolerates variation in backbone specification.

The solution structures of two computationally designed core variants of the beta 1 domain of streptococcal protein G (G beta 1) were solved by (1)H NMR methods to assess the robustness of amino acid sequence selection by the ORBIT protein design package under changes in protein backbone specification. One variant has mutations at three of 10 core positions and corresponds to minimal perturbations of the native G beta 1 backbone. The other, with mutations at six of 10 positions, was calculated for a backbone in which the separation between G beta 1's alpha-helix and beta-sheet was increased by 15% relative to native G beta 1. Exchange broadening of some resonances and the complete absence of others in spectra of the sixfold mutant bespeak conformational heterogeneity in this protein. The NMR data were sufficiently abundant, however, to generate structures of similar, moderately high quality for both variants. Both proteins adopt backbone structures similar to their target folds. Moreover, the sequence selection algorithm successfully predicted all core chi(1) angles in both variants, five of six chi(2) angles in the threefold mutant and four of seven chi(2) angles in the sixfold mutant. We conclude that ORBIT calculates sequences that fold specifically to a geometry close to the template, even when the template is moderately perturbed relative to a naturally occurring structure. There are apparently limits to the size of acceptable perturbations: In this study, the larger perturbation led to undesired dynamic behavior.

Bacterial Proteins↗
PubMed2000

Lidocaine blockade of amygdala output in fear-conditioned rats reduces Fos expression in the ventrolateral periaqueductal gray.

We showed recently that conditioned fear to context induces Fos expression in the ventrolateral periaqueductal gray [Neuroscience (1997) 78, 165-177]. Neurons in this region are thought to play an important role in the expression of freezing during conditioned fear. To test the possibility that this activation comes directly from the amygdala, we looked at changes in Fos expression after a unilateral blockade of the ventral amygdalofugal pathway with lidocaine. The pathway contains fibres originating from the central nucleus of the amygdala that project directly and mainly ipsilaterally to the ventrolateral periaqueductal gray. Conditioned fear was evoked by re-exposing rats to the same box in which they had previously received electric footshocks. The test re-exposure was preceded by a unilateral microinjection of lidocaine (2%, 0.5-1 microl; n = 20) or saline (n = 14). Lidocaine was also tested in non-conditioned animals (n = 13). The results show that, when lidocaine was microinjected in the medial part of the central nucleus of the amygdala or along the ventral amygdalofugal pathway of conditioned rats, fear-induced Fos expression in the ventrolateral periaqueductal gray was reduced on the side ipsilateral to the injection (up to 37% reduction in comparison to the contralateral side). Ipsilateral reductions were also observed with saline, but they were weaker (maximum of 27% reduction). Fos expression remained low on both sides in the non-fear-conditioned animals injected with lidocaine. Finally, although freezing was only partly reduced in the conditioned animals unilaterally injected with lidocaine, it was significantly correlated to the ipsilateral reduction in Fos expression. This study provides direct evidence that the projection from the central nucleus of the amygdala to the ventrolateral periaqueductal gray is activated during fear and that it contributes to the Fos response of the ventrolateral periaqueductal gray.

Amygdala↗
PubMed1998

Rheumatoid nodule of the foot: MRI appearances mimicking an indeterminate soft tissue mass.

Subcutaneous rheumatoid nodules occur commonly in advanced cases of rheumatoid arthritis, but only rarely appear in the feet. We present a case of a subcutaneous rheumatoid nodule arising in the heel pad of a 68-year-old man with a long history of rheumatoid arthritis, along with a review of the literature. The appearance of the mass on MRI is illustrated and correlated with the histologic findings. The MRI appearance of a subcutaneous rheumatoid nodule is that of a nonspecific ill-defined mass with long T1- and long T2-relaxation times. A differential diagnosis for similar appearing masses is offered.

Aged↗
PubMed1997

Coupling backbone flexibility and amino acid sequence selection in protein design.

Using a protein design algorithm that considers side-chain packing quantitatively, the effect of explicit backbone motion on the selection of amino acids in protein design was assessed in the core of the streptococcal protein G beta 1 domain (G beta 1). Concerted backbone motion was introduced by varying G beta 1's supersecondary structure parameter values. The stability and structural flexibility of seven of the redesigned proteins were determined experimentally and showed that core variants containing as many as 6 of 10 possible mutations retain native-like properties. This result demonstrates that backbone flexibility can be combined explicitly with amino acid side-chain selection and that the selection algorithm is sufficiently robust to tolerate perturbations as large as 15% of G beta 1's native supersecondary structure parameter values.

Algorithms↗
PubMed1996

A multi-substrate single-file model for ion-coupled transporters.

Ion-coupled transporters are simulated by a model that differs from contemporary alternating-access schemes. Beginning with concepts derived from multi-ion pores, the model assumes that substrates (both inorganic ions and small organic molecules) hop a) between the solutions and binding sites and b) between binding sites within a single-file pore. No two substrates can simultaneously occupy the same site. Rate constants for hopping can be increased both a) when substrates in two sites attract each other into a vacant site between them and b) when substrates in adjacent sites repel each other. Hopping rate constants for charged substrates are also modified by the membrane field. For a three-site model, simulated annealing yields parameters to fit steady-state measurements of flux coupling, transport-associated currents, and charge movements for the GABA transporter GAT1. The model then accounts for some GAT1 kinetic data as well. The model also yields parameters that describe the available data for the rat 5-HT transporter and for the rabbit Na(+)-glucose transporter. The simulations show that coupled fluxes and other aspects of ion transport can be explained by a model that includes local substrate-substrate interactions but no explicit global conformational changes.

Animals↗
PubMed1990

Evaluation of various nitrogen supplements in starter diets for growing Holstein steers and their effects on ruminal bacterial fermentation in continuous culture.

Concurrent in vivo and in vitro studies were conducted to evaluate urea (U), soybean meal (SBM), ground soybeans (RAW), extruded soybeans (ES) or extruded soybeans plus urea (ES + U) as primary supplemental N sources in starter diets for Holstein steers. Three groups of 48 Holstein steers each were fed five different starter diets to 181 kg BW in three experimental periods over 2 yr. Average daily gains were similar (P greater than .05) for steers fed ES + U (1.12 kg), ES (1.08 kg) and SBM (1.09 kg) but lower (P less than .05) for those fed U (1.00 kg) or RAW (.97 kg) diets. Feed/gain was similar (P greater than .05) for ES-fed steers vs those fed other diets except U. From 181 to 477 kg, all steers were fed the same diet. Steers fed the RAW starter diet had the lowest (P less than .05) ADG for the entire period. The starter diets were used as substrates for ruminal microbial metabolism in eight dual-flow continuous culture fermenters. True OM digestion was higher and NDF and ADF digestion was lower (P less than .05) for the ES + U diet than for the ES diet. Dietary protein degradation was lowest (P less than .05) for the ES diet (64.4%). Total bacterial N flow was higher (P less than .05) with the ES + U, SBM and U diets than with the ES diet. Lysine flow was higher (P less than .05) for the ES + U diet than for all other diets except ES. Results of these experiments indicate that ES as a protected ruminal escape N source with or without added urea did not improve steer performance above that obtained from SBM in starter diets.

Animal Feed↗
PubMed1989

[A preliminary investigation of human chromosomal fragile site 3p14 using scanning electron microscopy (SEM)].

A preliminary scanning electron microscopical observation on the most common human chromosomal fragile site 3p14 of the peripheral lymphocytes was reported. It was shown that chromatid break or gap at 3p14 observed under SEM may be a sign of under-packing of DNA filaments and the possibility of various packing-patterns might be in existence. The result of the present work might be of significance in the understanding of natures of breaking or gap of chromatid and may be of help to the study of the mechanisms of chromosomal fragile site formation.

Chromosome Fragile Sites↗
PubMedDate not supplied

Horses damp the spring in their step.

The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb.

Animals↗