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Biomedical subjects

Y Sun

Publications and source records attributed to Y Sun.

At least 1,081 records · Page 60Linked to original sources

Comparison of velocity-encoded MR imaging and fluid dynamic modeling of steady and disturbed flow.

The contrast of flow-encoded magnetic resonance (MR) images obtained in vivo and the accuracy of velocity measurements are complicated by the presence of complex flow states. The effects of complex flow states on MR flow-encoded images were studied and quantitative flow information was obtained with an MR phase-subtraction technique. Regions of complex flow, including flow stagnation and separation and laminar flow, could be clearly identified on the phase images. The MR imaging velocity measurements were validated by comparison with numerical simulation results for three-dimensional velocity distributions. The velocity MR images and the profiles obtained from the simulation generally agreed well for flow rates of 660 and 1,680 mL/min. This agreement lends support to both the fluid dynamic model and the physical basis of the phase imaging technique and establishes the validity of flow-encoded phase imaging as an in vivo flow quantitation method, especially under low Reynolds number flow conditions.

Blood Flow Velocity↗

Gaussian pulse decomposition: an intuitive model of electrocardiogram waveforms.

This study presents a novel approach to modeling the electrocardiogram (ECG): the Gaussian pulse decomposition. Constituent waves of the ECG are decomposed into and represented by Gaussian pulses using an iterative algorithm: the chip away decomposition (ChAD) algorithm. At each iteration, a nonlinear minimization method is used to fit a portion of the ECG waveform with a single Gaussian pulse, which is then subtracted from the ECG waveform. The process iterates on the resulting residual waveform until the normalized mean square error is below an acceptable level. Three different minimization methods were compared for their applicability to the ChAD algorithm; the Nelder-Mead simplex method was found to be more noise-tolerant than the Newton-Raphson method or the steepest descent method. Using morphologically different ECG waveforms from the MIT-BIH arrhythmia database, it was demonstrated that the ChAD algorithm is capable of modeling not only normal beats, but also abnormal beats, including those exhibiting a depressed ST segment, bundle branch block, and premature ventricular contraction. An analytical expression for the spectral contributions of the constituent waves was also derived to characterize the ECG waveform in the frequency domain. The Gaussian pulse model, providing an intuitive representation of the ECG constituent waves by use of a small set of meaningful parameters, should be useful for various purposes of ECG signal processing, including signal representation and pattern recognition.

Algorithms↗

Vascular remodeling and mineralocorticoids.

Circulating mineralocorticoid hormones are so named because of their important homeostatic properties that regulate salt and water balance via their action on epithelial cells. A broader range of functions in nonclassic target cellular sites has been proposed for these steroids and includes their contribution to wound healing following injury. A chronic, inappropriate (relative to intravascular volume and dietary sodium intake) elevation of these circulating hormones evokes a wound healing response in the absence of tissue injury--a wound healing response gone awry. The adverse remodeling of vascularized tissues seen in association with chronic mineralocorticoid excess is the focus of this review.

Aldosterone↗

Effects of aging on regional rates of cerebral protein synthesis in the Sprague-Dawley rat: examination of the influence of recycling of amino acids derived from protein degradation into the precursor pool.

The quantitative autoradiographic L-[1-14C]leucine method for determination of regional rats of cerebral protein synthesis (1CPSleu) requires knowledge of the degree of recycling of leucine derived from protein degradation into the precursor pool of protein synthesis. The influence of recycling can be evaluated by measuring lambda, the steady state ratio of the leucine specific activity in the precursor amino acid pool (t-RNA-bound leucine) to that in the arterial plasma. To define the changes in 1CPS(leu) during the process of normal aging in the rat we have evaluated lambda in middle-aged (14 months) and aged (24 months) rats and compared its values with those obtained previously in young adult rats (two months of age). The results show that the value of lambda is the same in all three age groups, and that there is no change with aging in the fraction of leucine in the precursor pool derived from protein degradation. Our previously reported regional rates of protein synthesis in young adult and aged rats were based on the assumption that there was no recycling of leucine derived from protein degradation into the precursor pool of protein synthesis [Ingvar M.C., Maeder P., Sokoloff L. and Smith C.B. (1985) Brain 108, 155-170]. These values have been recalculated in the present study in order to take into account the appropriate correction for recycling. The recalculated rates are higher than those reported previously, but the effects of aging in the brain as a whole and in some specific brain regions are confirmed. Decreased 1CPS(leu) was observed by middle-age, and in this cross-sectional study did not appear to decrease further. Of the 39 brain regions examined decreases were found throughout the brain with some proclivity for the brain stem. In comparison with young adults the weighted average rate of protein synthesis in the brain as a whole was found to be decreased by 16 and 11% in the middle-aged and aged groups, respectively.

Aging↗

Analysis of thermohydrologic behavior for above-boiling and below-boiling thermal-operating modes for a repository at Yucca Mountain.

We report results from a multi-scale thermohydrologic modeling study for two alternative thermal-operating modes for the potential repository system recently analyzed by the Yucca Mountain Project. These include a Higher-Temperature Operating Mode (HTOM), which results in a localized boiling zone around each emplacement drift, and a Lower-Temperature Operating Mode (LTOM), which always maintains sub-boiling temperatures throughout the repository. The HTOM places all waste packages nearly end to end, making the lineal power density greater than in the LTOM. The lower lineal power density in the LTOM was achieved by placing some waste packages farther apart (which results in a larger repository footprint), and through an increased reliance on pre-closure ventilation to remove the waste-package-generated heat. We focus on temperature T and relative humidity RH at the waste-package and drift-wall surfaces, and on in-drift evaporation. In general, HTOM temperatures are greater than corresponding LTOM temperatures, exhibit similar spatial variability and have a stronger dependence on infiltration flux. The duration of RH reduction on waste packages is similar for the LTOM and HTOM. A major difference between the LTOM and HTOM is the lower waste-package temperature at any given value of waste-package RH for the LTOM. Waste-package temperatures in the LTOM, by design, remain below approximately 85 degrees C; the absence of RH reduction arising from host-rock dryout causes waste-package RH to remain above about 40%. The HTOM waste packages experience higher temperatures and correspondingly lower RH conditions as a result of RH reduction arising from host-rock dryout. For most of the repository area, the HTOM delays the potential onset of gravity-driven seepage compared to the LTOM (as indicated by the duration of boiling at the drift wall). Boiling conditions in the HTOM also delays the onset of capillary-driven seepage into the granular invert, causing the HTOM to have less evaporation in the invert during the first 800-1500 years than the LTOM; subsequent evaporation rates are higher in the HTOM, due to the higher power density.

Forecasting↗

Validation of the multiscale thermohydrologic model used for analysis of a proposed repository at Yucca Mountain.

Performance assessment and design evaluation of the proposed repository at Yucca Mountain are facilitated by a thermohydrologic modeling tool that simultaneously accounts for processes occurring at a scale of a few tens of centimeters around individual waste packages and emplacement drifts, and accounts for processes at the multi-kilometer scale of the mountain. The most straightforward approach is to account for the 3-D drift- and mountain-scale dimensionality all within a single monolithic thermohydrologic model. This approach is too computationally expensive to be a viable simulation tool capable of addressing all waste-package locations in the repository. The Multiscale Thermohydrologic Model (MSTHM) is a computationally efficient alternative to addressing these modeling issues. In this paper, we describe the principal calculation stages to predict temperature, relative humidity, and liquid-saturation, as well as other thermohydrologic variables, in the drifts and in the host rock. Using a three-drift repository example (which is a scaled-down version of the proposed repository), we demonstrate the validity of the MSTHM approach against a nested monolithic thermohydrologic model.

Forecasting↗

Estimation of volume flow rate by surface integration of velocity vectors from color Doppler images.

A new Doppler echocardiographically based method has been developed to quantify volume flow rate by surface integration of velocity vectors (SIVV). Electrocardiographic-gated color Doppler images acquired in two orthogonal planes were used to estimate volume flow rate through a bowl-shaped surface at a given time and distance from the probe. To provide in vitro validation, the method was tested in a hydraulic model representing a pulsatile flow system with a restrictive orifice. Accurate estimates of stroke volume (+/- 10%) were obtained in a window between 1.2 and 1.6 cm proximal to the orifice, just before the region of prestenotic acceleration. By use of the Bernoulli's equation, the estimated flows were used to generate pressure gradient waveforms across the orifice, which agreed well with the measured flows. To demonstrate in vivo applicability, the SIVV method was applied retrospectively to the determination of stroke volume and subaortic flow from the apical three-chamber and five-chamber views in two patients. Stroke volume estimates along the left ventricular outflow tract showed a characteristic similar to that in the in vitro study and agreed well with those obtained by the Fick oxygen method. The region where accurate measurements can be obtained is affected by instrumental factors including Nyquist velocity limit, wall motion filter cutoff, and color flow sector angle. The SIVV principle should be useful for quantitative assessment of the severity of valvular abnormalities and noninvasive measurement of pulsatile volume flows in general.

Animals↗

Angiotensin II and extracellular matrix homeostasis.

As a circulating hormone, endocrine properties of angiotensin (Ang) II are integral to circulatory homeostasis. Produced de novo its autocrine/paracrine properties contribute to biologic responses involving various connective tissues (e.g. extracellular matrix, adipose tissue, bone and its marrow). In this brief review, we develop the concept of extracellular matrix homeostasis, a self regulation of cellular composition and structure, wherein fibroblast-derived AngII regulates elaboration of TGF-beta 1, a fibrogenic cytokine responsible for connective tissue formation at normal and pathologic sites of collagen turnover.

Angiotensin II↗

Biodistribution and radioimmunotherapy of human breast cancer xenografts with radiometal-labeled DOTA conjugated anti-HER2/neu antibody 4D5.

HER2/neu oncogene encodes a 185 kDa trans-membrane protein which is overexpressed in 20-30% of breast and ovarian cancers and portends a poor prognosis. We have studied the targeting and therapy of this oncoprotein with 4D5, a murine monoclonal antibody which recognizes a distinct epitope on the extracelluar domain of HER2/neu. We conjugated the antibody with an active ester of the macrocyclic chelating agent DOTA, radiolabeled the conjugate with either (111)In or (90)Y, and studied the antibody distribution and therapy, respectively, in athymic mice bearing xenografts of MCF7/HER2/neu, a human breast cancer cell line transfected with the HER2/neu oncogene. For the biodistribution of (111)In-labeled DOTA-4D5, a high specificity of tumor localization (30% ID/g) was seen with a tumor-to-blood ratio of greater than 2 at 48 h postinjection. Compared to a previously published study with (125)I-labeled 4D5 in beige nude mice bearing NIH3T3/HER2/neu xenografts [De Santes et al. (1992) Cancer Res. 52, 1916-1923], (111)In-labeled 4D5 antibody gave superior antibody uptake in tumor (30% ID/g vs 17% ID/g at 48h). In the therapy study, treatment of the nude mice bearing MCF7/HER2/neu xenografts with 100 microCi (3 microg) of (90)Y-labeled DOTA-4D5 caused a 3-fold reduction of tumor growth compared to untreated controls (injected with human serum albumin) in 40 days. Treatment of animals with 100 microCi of nonspecific antibody (90)Y-labeled DOTA-Leu16 (3 microg) had no tumor growth inhibition. Treatment with unlabeled DOTA-4D5 (3 microg) had a slight effect on tumor growth compared to untreated controls. When analyzed at the level of single animals, no effect was seen in seven of nine animals; however, in two of the animals, tumor growth inhibition was observed. Although a cold antibody therapeutic effect was unexpected at this dose level (3 microg), it may be possible that in some animals that 3 microg of antibody of (90)Y-labeled DOTA-4D5 augmented tumor growth reduction. To further explore the effects of cold antibody treatment alone, animals were treated with 100 or 400 microg of unlabeled 4D5 administered in two doses. These animals showed a 1.7-1.8-fold reduction in tumor growth over 28 days, a result less than that obtained with RIT only.

Animals↗

A novel magnetic affinity support for protein adsorption and purification.

A novel magnetic support was prepared by an oxidization-precipitation method with poly(vinyl alcohol) (PVA) as the entrapment material. Transmission electron microscopy indicated that the magnetic particles had a core-shell structure, containing many nanometer-sized magnetic cores stabilized by the cross-linked PVA. The particles showed a high magnetic responsiveness in magnetic field, and no aggregation of the particles was observed after the particles had been treated in the magnetic field. These facts indicated that the particles were superparamagnetic. Cibacron blue 3GA (CB) was coupled to the particles to prepare a magnetic affinity support (MAS) for protein adsorption. Lysozyme was used as a model protein to test the adsorption properties of the MAS. The adsorption equilibrium of lysozyme to the MAS was described by the Langmuir-type isotherm. The capacity for lysozyme adsorption was more than 70 mg/g MAS (wet weight) at a relatively low CB coupling density (3-5 micromol/g). In addition, 1.0 M NaCl solution could be used to dissociate the adsorbed lysozyme. Finally, the MAS was recycled for the purification of alcohol dehydrogenase (ADH) from clarified yeast homogenates. Under proper conditions, the magnetic separation yielded over 5-fold purification of the enzyme with 60% recovery of the enzyme activity.

Adsorption↗

Agar-based magnetic affinity support for protein adsorption.

Magnetic colloidal particles were prepared by a coprecipitation method. The particles were composed of nanometer-sized superparamagnetic Fe(3)O(4) particles stabilized by lauric acid. Then, magnetic agar gel beads were produced by a water-in-oil emulsification method using a mixture of agar solution and the magnetic colloidal particles as the aqueous phase. A reactive triazine dye, Cibacron blue 3GA (CB), was coupled to the gel to prepare an agar-based magnetic affinity support (MAS) for protein adsorption. The support showed good magnetic responsiveness in a magnetic field. Bovine serum albumin (BSA) was used as a model protein to test adsorption equilibrium and kinetic behavior of the MAS. The adsorption equilibrium of BSA to the MAS was described by the Langmuir-type isotherm. Adsorption capacity of the MAS for BSA was up to 25 mg/mL at a CB coupling density of 1.6 micromol/mL. The effect of ionic strength on BSA adsorption was complex, exhibiting a maximum capacity at an ionic strength of 0.06 mol/L. The adsorption of BSA to the MAS was also influenced by pH. Uptake rate of BSA to the MAS was analyzed using a pore diffusion model. The pore diffusion coefficient was estimated to be 1.75 x 10(-11) m(2)/s. Finally, recycled use of the MAS demonstrated the stability of the MAS in protein adsorption and magnetic responsiveness.

Adsorption↗

Enhancing protein capacity of rigid macroporous polymeric adsorbent.

A macroporous poly(glycidyl methacrylate-triallyl isocyanurate-divinylbenzene) resin was synthesized and modified with diethylamine to yield an anion-exchange resin suitable for protein adsorption. Efforts were made to enhance protein ion exchange capacity of the resin by investigating the copolymer composition. Different synthesis recipes were attempted, and the resultant resins were characterized by measuring the specific surface area and the adsorption ability using bovine serum albumin (BSA) as a model protein. The intraparticle pore size distribution measured by mercury porosimetry showed that the pores in the range of 40-120 nm took 75% of the total pore volume, indicating that the ion exchanger was favorable for protein adsorption. BSA capacity obtained with an appropriate recipe was as high as 78.6 mg/g wet resin or 50 mg/mL packed volume, which was higher than the capacities of some commercially available ion exchangers. Moreover, by using a pore diffusion model, the effective pore diffusivity of BSA was found to be 5.5 x 10(-12) m(2)/s, similar to those in the commercial ion exchangers.

Adsorption↗

Modeling and analysis of the affinity filtration process, including broth feeding, washing, and elution steps.

Affinity filtration is a developing protein purification technique that combines the high selectivity of affinity chromatography and the high processing speed of membrane filtration. In this work a lumped kinetic model was developed to describe the whole affinity filtration process, including broth feeding, contaminant washing, and elution steps. Affinity filtration experiments were conducted to evaluate the model using bovine serum albumin as a model protein and a highly substituted Blue Sepharose as an affinity adsorbent. The model with nonadjustable parameters agreed fairly to the experimental results. Thus, the performance of the affinity filtration in processing a crude broth containing contaminant proteins was analyzed by computer simulations using the lumped model. The simulation results show that there is an optimal protein loading for obtaining the maximum recovery yield of the desired protein with a constant purity at each operating condition. The concentration of a crude broth is beneficial in increasing the recovery yield of the desired protein. Using a constant amount of the affinity adsorbent, the recovery yield can be enhanced by decreasing the solution volume in the stirred tank due to the increase of the adsorbent weight fraction. It was found that the lumped kinetic model was simple and useful in analyzing the whole affinity filtration process.

Adsorption↗

Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12.

Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans.

Adenoviridae↗

[Reproducibility in the roentgenological assessment of coxarthritis].

The "German Society of Orthopaedic Surgery and Traumatology (DGOT)" is trying to support the application of standardized and reproducible criteria in diagnosis and therapy of osteoarthritis. As radiographs are a primary measure of outcome at present, the objective of this study was to investigate the reproducibility of radiologic assessment in hip osteoarthritis using different radiographic variables. 3 investigators read 100 hip joints on 50 pelvis radiographs at two time-points for the presence and severity of individual radiographic features: joint space narrowing (JSN), osteophytes, sklerosis, subchondral cysts and deformity of the femoral head. Additionally the summary grade of Kellgren and Lawrence (1963) and Scott et al (1992) was assessed. Intra- and inter-rater-reliability were calculated by intra-class-correlation-co-efficient (ICC). The results regarding intra- and inter-rater-reliability show excellent values for superior JSN, femoral head deformity and the summary score. The radiologic assessment of medial JSN, osteophytes and acetabular sklerosis depends on the level of the investigator's experience. Perifoveal osteophytes and subchondral cysts do not seem to be have sufficient reproducibility. The results of our investigation show, that a reliable radiological classification of the severity of hip osteoarthritis is possible by assessment of certain individual radiographic features or a summary grade.

Adult↗

[Incidence and prevalence of cox- and gonarthrosis in the general population].

AIM OF STUDY: Analysis of data on the incidence and prevalence of osteoarthritis (OA) of the hip and knee in the general population. METHOD: Review of relevant investigations concerning epidemiology of hip and knee OA. RESULTS: Estimates of incidence and prevalence of OA of the hip and knee vary considerably among 29 studies from 14 countries and 4 ethnic groups (incidence: 10 to 2230 per 10(5) person-years, prevalence: 0.5% to 36%. DISCUSSION: Because of the differences in study design, study populations, and the definition of OA, a comparison between different studies is very difficult. Nevertheless, the following patterns can be identified: In general, both the incidence and prevalence of OA of the hip and knee increase with age. The sharp increase in incidence of symptomatic OA of the knee after age 50 in women suggests an influence of menopausal changes of hormonal status. The prevalence of radiographically defined OA of the hip is higher in men than in women, but a reverse pattern was found for OA of the knee, especially after age 45. The prevalence of radiographically OA was found to be higher in caucasian than non-caucasian populations at the hip but not the knee joint. Among patients with radiographically defined OA at the hip, joint pain seems to be more common in women than in men. In contrast, the frequency of joint pain in persons with radiographically defined OA of the knee is about the same in women and men.

Adult↗

[Reproducibility of radiologic diagnosis in gonarthrosis].

AIM OF STUDY: Ongoing efforts of the "German Society of Orthopaedic Surgery and Traumatology" (DGOT) to standardize diagnosis and therapy of osteoarthritis, necessitated this study, where the reproducibility of different radiographic features of knee-OA was assessed. METHODS: Three readers graded 100 antero-posterior and lateral knee radiographs for selected features (femorotibial osteophytes, joint space narrowing, sclerosis and chondrocalcinosis; patellofemoral osteophytes) and an overall-score (Kellgren and Lawrence, 1963) at two time points 3 months apart. Intra- and inter-observer-reliability were calculated by intra-class correlation-coefficient (ICC). RESULTS: Osteophytes in the femorotibial as well as in the patellofemoral joint could be assessed with a high intra- and inter-observer-reliability. While for joint space narrowing intra-observer-reliability is excellent, the inter-observer-reliability is less satisfactory, and subchondral sclerosis as well as chondrocalcinosis showed even less reproducibility. The Kellgren-Lawrence global score proofed to be highly reproducible. CONCLUSION: Based on the results of this examination, we can recommend a reliable radiographic classification of knee osteoarthritis by grading of relevant individual features (osteophytes and joint space narrowing) and overall assessment.

Follow-Up Studies↗

Antimicrobial action of some GRAS compounds against Vibrio vulnificus.

Vibrio vulnificus is a bacterium indigenous to estuarine waters and is known to be a significant human pathogen. Infections are generally associated with the consumption of raw oyster. In an attempt to identify possible antimicrobial agents against this organism that might be used in foods, ten compounds that are generally recognized as safe (GRAS) by the FDA were tested against both the opaque and translucent morphotypes of V. vulnificus. Eight of those compounds had a lethal effect for both morphotypes of this bacterium. Diacetyl had the lowest lethal concentration (50 ppm) of the GRAS compounds tested within 24 h. Lactic acid and butylated hydroxyanisole possessed lethal activities at 300 ppm and 400 ppm, respectively, within 3 h. The mode of action of lactic acid against V. vulnificus appears to be an effect primarily of pH, while the antimicrobial activities of diacetyl and BHA appeared not to be affected by pH. No significant differences were found for opaque to translucent, or from translucent to opaque switching, in examining the possible effects of the GRAS compounds on colonial morphology.

Animals↗