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D C Yu

Publications and source records attributed to D C Yu.

At least 37 records · Page 2Linked to original sources
PubMed1996

Automated image registration for FDOPA PET studies.

In this study, various image registration methods are investigated for their suitability for registration of L-6-[18F]-fluoro-DOPA (FDOPA) PET images. Five different optimization criteria including sum of absolute difference (SAD), mean square difference (MSD), cross-correlation coefficient (CC), standard deviation of pixel ratio (SDPR), and stochastic sign change (SSC) were implemented and Powell's algorithm was used to optimize the criteria. The optimization criteria were calculated either unidirectionally (i.e. only evaluating the criteria for comparing the resliced image 1 with the original image 2) or bidirectionally (i.e. averaging the criteria for comparing the resliced image 1 with the original image 2 and those for the sliced image 2 with the original image 1). Monkey FDOPA images taken at various known orientations were used to evaluate the accuracy of different methods. A set of human FDOPA dynamic images was used to investigate the ability of the methods for correcting subject movement. It was found that a large improvement in performance resulted when bidirectional rather than unidirectional criteria were used. Overall, the SAD, MSD and SDPR methods were found to be comparable in performance and were suitable for registering FDOPA images. The MSD method gave more adequate results for frame-to-frame image registration for correcting subject movement during a dynamic FDOPA study. The utility of the registration method is further demonstrated by registering FDOPA images in monkeys before and after amphetamine injection to reveal more clearly the changes in spatial distribution of FDOPA due to the drug intervention.

Animals↗
PubMed1996

Radiofluorinated L-m-tyrosines: new in-vivo probes for central dopamine biochemistry.

In this work, we introduce 6-[18F]fluoro-L-m-tyrosine (6-FMT) and compare its in-vivo kinetic and bio-chemical behaviors in monkeys and rodents with those of 4-FMT and 6-[18F]fluoro-L-3, 4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-O-methylation, offer a nonpharmacological alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Bio-chemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.

Animals↗
PubMed1996

Amplification, expression, and packaging of a foreign gene by giardiavirus in Giardia lamblia.

Giardia lamblia is an intestinal protozoan parasite and one of the earliest eukaryotic divergents. The trophozoite multiplies via asexual binary fission and lacks all natural means of lateral gene transfer. A system is developed here for long-term expression of a foreign gene in this organism by exploiting recombinant virions derived from the giardiavirus (GLV), a double-stranded RNA virus that infects many Giardia isolates. An in vitro transcript of the cloned GLV cDNA, comprising the firefly luciferase-encoding region flanked by 5' and 3' fragments of GLV positive-strand RNA, was electroporated into GLV-infected trophozoites. Luciferase activity in electroporated cells peaked on day 2 at levels 6 orders of magnitude above background. Expression of this foreign gene remained at 80% of its peak level after 30 days in the absence of selective pressure. The chimeric RNA was replicated as double-stranded RNA and packaged into virus-like particles. The recombinant virions were partially purified from the wild-type helper virus by CsCl equilibrium density-gradient centrifugation and used to superinfect Giardia trophozoites. At multiplicities of infection of 100 or higher, these chimeric virions were able to initiate new rounds of expression of luciferase activity in the superinfected cells. Thus, the engineered virion can be successfully used to introduce and efficiently express a heterologous gene in this eukaryotic microorganism.

Animals↗
PubMed1996

Identification of cis-acting signals in the giardiavirus (GLV) genome required for expression of firefly luciferase in Giardia lamblia.

Giardiavirus (GLV) is a 6,277-bp double-stranded RNA virus of Giardia lamblia, one of the earliest eukaryotic divergents from the prokaryotes. Our previous success in GLV-mediated transfection of G. lamblia has provided an effective way of monitoring the mechanisms underlining GLV gene replication and mRNA translation in this organism. Here we have investigated the cis-acting signals in the GLV genome that regulate replication, transcription, and translation of an inserted firefly luciferase gene in GLV-infected G. lamblia. By modifying the two terminal regions of a full-length GLV cDNA clone used to flank a luciferase gene, various in vitro chimeric transcripts were generated and introduced into GLV-infected G. lamblia via electroporation. Expression of luciferase (+) strand and (-) strand RNAs in the transfected cells was monitored and the luciferase activity assayed. The results indicated that the 5'-untranslated region (UTR) of 366 nt and the 3'-terminal 2,022 nt of the viral transcript are both needed for optimal expression of the two RNA strands. Although the entire 5'-UTR is needed for the chimeric mRNA synthesis, both the primary sequence and the secondary structure at the 3' end of GLV transcript are essential for the synthesis of (-) strand RNA. When the 5' end of GLV transcript was extended 265 nt into the capsid protein open reading frame and fused with that of luciferase, there was no change in the level of luciferase chimeric RNA, but a 5,000-fold increase of luciferase activity was observed that may be attributed to an enhanced translational efficiency of the chimeric mRNA in G. lamblia.

Animals↗
PubMed1995

The assessment of the non-equilibrium effect in the 'Patlak analysis' of Fdopa PET studies.

'Patlak analysis' is a common approach used in Fdopa PET studies to calculate the uptake constant (Ki) of the tracer. It is assumed in the Patlak analysis that the reversible compartment of tissue radioactivity used is in effective equilibrium with the tracer in plasma. Therefore, using the data prior to equilibrium is in conflict with the assumption, and its effect on the estimate thus needs to be examined. In this study, we used simulations to investigate the errors due to the violation of the equilibrium assumption. Two factors affecting the estimate of Ki were examined--the eigenvalue of the model response function and the shape of the input function. The Ki estimate obtained from the Patlak analysis was found to be markedly biased because the system is not in equilibrium during the first 2 h post Fdopa injection. The magnitude of the bias was found to be dependent on the time interval used in the analysis (10% difference when comparing results from intervals 30-120 min and 60-120 min) and on the eigenvalue of the response function (10% change in Ki when the eigenvalue was changed by 20% around the nominal value). The estimates are also affected by the intersubject variations in the plasma time-activity curves. Therefore, Patlak analysis users should interpret their results with caution, particularly when examining small intersubject differences and small changes due to physiological or pharmacological interventions.

Blood-Brain Barrier↗
PubMed1995

Virus-mediated expression of firefly luciferase in the parasitic protozoan Giardia lamblia.

Giardia lamblia, a prevalent human pathogen and one of the lineages that branched earliest from prokaryotes, can be infected with a double-stranded RNA virus, giardiavirus (GLV). The 6,277-bp viral genome has been previously cloned (A.L. Wang, H.-M. Yang, K.A. Shen, and C.C. Wang, Proc. Natl. Acad. Sci. USA 90:8595-8599, 1993; C.-H. Wu, C.C. Wang, H.M. Yang, and A.L. Wang, Gene, in press) and was converted to a transfection vector for G. lamblia in the present study. By flanking the firefly luciferase gene with the 5' and 3' untranslated regions (UTRs) of the GLV genome, transcript of the construct was synthesized in vitro with T7 polymerase and used to transfect G. lamblia WB trophozoites already infected with GLV (WBI). Optimal electroporation conditions used for the transfection were set at 1,000 V/cm and 500 microF, which resulted in expression of significant luciferase activity up to 120 h after electroporation. Furthermore, the mRNA and the antisense RNA of the luciferase gene were both detected by reverse transcription and PCR from 6 to 120 h postelectroporation, whereas no antisense RNA of luciferase was observed in the electroporated virus-free Giardia WB trophozoites. The mRNA of luciferase was detectable in the virus-free trophozoites by reverse transcription and PCR only up to 20 h after the electroporation, indicating that the introduced mRNA was replicated only by the viral RNA-dependent RNA polymerase inside the WBI cells. This expression of luciferase was dependent on the presence of UTRs on both ends of the viral genome transcript, including a putative packaging site that was apparently indispensable for luciferase expression. This is the first time that a viral vector in the form of mRNA URTs has been successfully used in transfecting a protozoan.

Animals↗
PubMed1995

Factors to consider for predictable post and core build-ups of endodontically treated teeth. Part I: Basic theoretical concepts.

Post and core build-ups represent an important pre-prosthetic procedure prior to the restoration of an endodontically treated tooth. The dental practitioner is presented with the dilemma of selecting from an ever increasing variety of materials, techniques and designs related to this procedure, many of which are harmful and mired in controversy. Part I of this paper reviews some basic theoretical concepts for the dentist to consider when producing a predictable post and core build-up. An understanding of these basic concepts will assist the dentist in gathering data and establishing a risk/benefit equation, and will also provide an additional aid during the decision-making process for the restoration of an endodontically treated tooth.

Biomechanical Phenomena↗
PubMed1995

Factors to consider for predictable post and core build-ups of endodontically treated teeth. Part II: Clinical application of basic concepts.

Post and core build-ups represent an important pre-prosthetic procedure prior to the restoration of an endodontically treated tooth. The dental practitioner is presented with the dilemma of selecting from an ever increasing variety of materials, techniques and designs related to this procedure, many of which are harmful and mired in controversy. Part II of this paper will review some basic theoretical concepts related to post and core build-ups with the objective of applying these concepts to address a number of pertinent clinical questions related to the above selection process. This review should provide the dentist with a reference to produce a more predictable post and core build-up.

Cementation↗
PubMed1993

Successful treatment of a severe electrical injury involving the stomach.

Apparently no report of the survival of a child with severe electrical injuries involving the stomach has been published. We successfully treated a 5-year-old boy with such injuries in August 1991. Our effective treatment included: (1) resection of the necrosis of the stomach immediately after admission; (2) active excision of all surrounding necrotic tissues with conservation of any piece of healthy tissue, including partial degenerative tissues; (3) early coverage of all exposed areas; (4) general comprehensive supportive therapy, and (5) local application of a saline solution containing chloromycetin and lidocaine.

Burns, Electric↗
PubMed1993

Classification of deep burn injuries--analyses of 117 cases.

A new system of classification, index of deep burn injuries (IDBI), was proposed in this paper. Using this system, we investigated 304 burn sites in 117 cases, of which 94.1% were repaired with the GCM with a satisfactory result. The IDBI of the 304 burn sites is in direct proportion to the severity and extent of burn injury and inverse ratio to the results. Analyses performed in this group suggested that the IDBI has many significances, which include: 1, making a correct diagnosis; 2, providing decided repair indications; 3, indicating the prognosis; 4, providing a reliable method for further investigation in the burn field. The standard of IV degree burn is equal to or more than 2 of IDBI.

Adolescent↗
PubMed1993

Methods for improving quantitation of putamen uptake constant of FDOPA in PET studies.

To estimate the striatal uptake constant of [18F]-L-6-fluorodopa (FDOPA) in humans, we studied two methods that can account for the image resolution and the background level of FDOPA. These two methods utilize information obtained from multiple ROIs varying in size around the putamen and from profiles crossing the middle of the putamen. The estimation of the uptake constant was based on a model of one-dimensional activity variation. Simulated data were used to evaluate the adequacy of these two methods. Parametric images of FDOPA uptake constants were generated using Patlak analysis for five studies in normals and were then analyzed with the two methods. Results from the simulated data indicated a good agreement between the estimated values and the true simulated values. Results from studies in normals show stable estimates of the FDOPA uptake constant that are not affected by image resolution. The two methods were not sensitive to the misplacement of ROIs and profiles.

Computer Simulation↗
PubMed1991

Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies.

Kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after an intravenous bolus injection of the tracer. The time course of the arterial plasma concentrations of the tracer and its metabolites was also assayed biochemically. FDOPA compartmental models that are based on biochemical information were investigated for their consistency with the measured striatal and cerebellar tissue kinetics. A modeling approach was also developed for separating plasma FDOPA and metabolite time-activity curves from the measured total 18F time-activity curve in plasma. Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6-[18F]fluorodopamine (FDA) and its metabolites, and tissue L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans. Based on this model, the FDOPA transport constant across the blood-brain barrier (BBB) (K1), the FDOPA decarboxylation rate constant (k3), and the turn-over rate constant of FDA and its metabolites (k4) could be estimated by model fitting to the tissue kinetics and were found for the normal subjects to be 0.031 +/- 0.006 ml/min/g (mean +/- SD), 0.041 +/- 0.015/min, and 0.004 +/- 0.002/min, respectively. About 50% of the FDOPA that crossed the BBB from plasma to striatum was decarboxylated. The decarboxylation constant with respect to plasma FDOPA (K3) was 0.015 +/- 0.003 ml/min/g. The BBB transport corresponded to a permeability-surface area product of 0.032 ml/min/g for FDOPA. For 3-OMFD, the BBB transport was 1.7 times faster. The effects of tissue heterogeneity on the FDOPA kinetics and on the estimated model parameters were also investigated. The usefulness and implications of these findings for interpretation of PET FDOPA studies are discussed.

Adult↗
PubMed1991

Modelling approach for separating blood time-activity curves in positron emission tomographic studies.

A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results.

Dihydroxyphenylalanine↗
PubMed1991

The effects of measurement errors in the plasma radioactivity curve on parameter estimation in positron emission tomography.

The effects of three error sources in plasma curve measurements on parameter estimation in kinetic analysis of positron emission tomography (PET) fluorodeoxyglucose (FDG) data are investigated by computer simulation. The three error sources are: (1) measurement noise in the radioactivity concentrations of plasma samples; (2) linear interpolation between adjacent plasma sampling points of the plasma time activity curve; and (3) incorrect weights used for the least-squares regression. All three error sources are found to increase the variability of the parameter estimates, with the first one a primary error source in normal PET FDG studies. The performance of five estimation methods which account for the error sources are evaluated. When the noise variances of the plasma and the tissue measurements are not known, an iterative weighting procedure is shown to give accurate and reliable estimates.

Computer Simulation↗
PubMed1990

6-[18F]fluoro-L-dopa probes dopamine turnover rates in central dopaminergic structures.

6-[18F]Fluoro-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced unilateral Parkinsonism. Application of a tracer kinetic model to positron emission tomography (PET) data indicated that the model allows reliable estimation of FDOPA blood brain barrier transport, decarboxylation and release of stored 6-[18F]fluorodopamine (FDA) radioactivity in normal striatum (k4 = 0.005/min, turnover half-time greater than or equal to 2 hr), in agreement with biochemical data. PET scans of MPTP treated monkeys revealed 40-50% reduction in total striatal activity in comparison with pre-MPTP scans. Monkey brain biochemical analysis revealed that the reduction in activity was mainly due to a decrease in FDA and its metabolites, 6[18F]fluorohomovanillic (FHVA) and 6-[18F]fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-[18F]fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and greater than or equal to 6:1 in the lesioned putamen, indicative of a dramatic increase in turnover of FDA. Both kinetic and biochemical data indicate that FDOPA labels a slow turnover rate pool of dopamine in rat and primate brain. This turnover rate for stored dopamine (DA) is accelerated with dopaminergic cell losses (e.g., MPTP-induced Parkinsonism).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗