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Biomedical subjects

D Feng

Publications and source records attributed to D Feng.

14 recordsLinked to original sources

An algorithm for identifiable parameters and parameter bounds for a class of cascaded mammillary models.

A complex structural identifiability problem for a class of unidirectionally interconnected n-compartment linear mammillary models with multiple inputs is discussed. This class is particularly useful in the study of drug/metabolite kinetics and other interconversion kinetic processes. An explicit algorithm is developed for this model class that provides identifiable parameter combinations, parameter bounds, steady-state pool sizes, and production rates, with input forcing and output measurements in central compartments. A six-compartment model of the combined dynamics of the prohormone thyroxine (T4) and hormone triiodothyronine (T3) illustrates how physiological parameter values or their smallest ranges, such as tissue T4 to T3 conversion rates and separate T4 and T3 production rates, can be determined from stimulus-response measurements in plasma alone.

Algorithms

[Detection of HBV DNA and HBsAg in HCC and pericarcinomatous tissues using double labelling technique].

40 cases of hepatocellular carcinoma (HCC) and their surrounding tissues were studied on paraffin-embedded sections by in situ hybridization and immunohistochemical double labelling techniques. The positive rates of HBV DNA and HBsAg were 65% and 82.5% respectively, suggesting that HBV infection is a significant cause of HCC. HBV DNA and HBsAg signals in the pericarcinomatous tissues were stronger than that in cancer cells. Reduced replication caused by integration of HBV DNA in HCC may explain this phenomenon. We found that the small "piece-meal like" inclusions which existed only in HCC may be a special cancer related pattern of HBsAg. There were stronger signals of HBsAg in the small cell LCD than in other pericarcinomatous lesions, supporting the theory that the small cell LCD is more likely to be a precarcinomatous lesion.

Carcinoma, Hepatocellular

Spouse similarity in attitudes, personality, and psychological well-being.

The study of the origin of spouse similarity is interesting because the extent to which spouse similarity reflects genetic resemblance between husbands and wives affects the genetic structure of a population. The sources of observed spouse similarity in attitudes, personality, and psychological well-being are discussed. Analyses based on data collected from an American adult sample assessed longitudinally showed that spouse correlations were high for attitudes and low to moderate for personality and psychological well-being. Four competing explanations to spouse similarity were compared: initial similarity, attrition, convergence, and age covariation. The results did not support the latter three explanations, indicating that initial similarity may be an appropriate interpretation of observed spouse similarity. The findings are consistent with those of other comparable studies.

Adaptation, Psychological

A computer simulation study on the input function sampling schedules in tracer kinetic modeling with positron emission tomography (PET).

Tracer kinetic modeling with positron emission tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters, i.e. to fit the parameters of certain compartmental models using PTAC and TTAC as the model input and output functions, respectively. In this paper, we first explored the optimal blood sampling schedule (OBSS) for the input function, based on the tracer [18F]2-fluoro-2-deoxy-D-glucose (FDG) blood sample experimental data. Then using a 5-parameter FDG model we investigated the effects of the plasma sampling schedule, as well as PTAC measurement noise, on the estimation accuracy and reliability of FDG model macro- and micro-parameters and the physiological parameter local cerebral metabolic rates of glucose (LCMRGlc), using computer simulation. Three different methods were used: (a) estimation of the FDG model parameters ignoring PTAC noise using the traditional PTAC schedule (non-OBSS); (b) estimation of the PTAC model parameters and FDG model parameters simultaneously using both non-OBSS and OBSS; (c) estimation of the PTAC model parameters first, then the FDG model parameters using both non-OBSS and OBSS. The results show that OBSS can provide more reliable estimates and largely simplifies the experiment operations.

Blood Specimen Collection

Decomposition-based qualitative experiment design algorithms for a class of compartmental models.

Qualitative experiment design, to determine experimental input/output configurations that provide identifiability for specific parameters of interest, can be extremely difficult if the number of unknown parameters and the number of compartments are relatively large. However, the problem can be considerably simplified if the parameters can be divided into several groups for separate identification and the model can be decomposed into smaller submodels for separate experiment design. Model decomposition-based experiment design algorithms are proposed for a practical class of large-scale compartmental models representative of biosystems characterized by multiple input sources and unidirectional interconnectivity among subsystems. The model parameters are divided into three types, each of which is identified consecutively, in three stages, using simpler submodel experiment designs. Several practical examples are presented. Necessary and sufficient conditions for identifiability using the algorithm are also discussed.

Algorithms

Cut set analysis of compartmental models with applications to experiment design.

Conventional compartmental analysis typically involves equations derived from mass-rate balance considerations for each compartment (pool), with each equation associated with a single pool. However, alternative mathematical descriptions, which effectively group pools into various other configurations, facilitate model analysis in certain applications, e.g., for kinetic experiment design or analysis. Such equivalent models are usually obtained using (often) complex matrix operations. An alternative approach, cut set analysis, can be applied directly to the graph of the compartmental model to readily generate alternative mathematical descriptions in which the needed equivalence transformations are easily performed graphically. This graphical transformation is developed here for linear, time-invariant multicompartmental models in which particular parameter values are the experimental objective. The method potentially provides greater flexibility in analyzing complex compartmental models in theory and practice, and it is exemplified here by application to the design of steady-state kinetic endocrine system studies in experimental animals.

Animals

[An analysis of findings EEG and brain CT scans in patients with primary hypoparathyroidism].

10 cases of primary hypoparathyroidism showed abnormal findings on EEG. Among them 9 cases were also verified by CT scans. It was considered that the severity of abnormalities in primary hypoparathyroidism was not only influenced by the serum concentration of calcium, but also related with the severity and extent of calcification in the brain. These findings would be of significance with regard to the diagnosis, treatment and prognostic evaluation of primary hypoparathyroidism.

Adolescent

Periprosthetic chronic inflammation characterized through the measurement of superoxide anion production by synovial-derived macrophages.

Periprosthetic macrophages were isolated from the synovium of primary and revision arthroplasty patients. Inflammatory activity was determined by the level of superoxide (O2-) production de novo and in response to phorbol myristate acetate (PMA) stimulation. Nonstimulated primary arthroplasty-derived macrophages produced 2.54 +/- 2.04 pmoles of O2-/minute/10(5) cells. When identical reaction tubes were stimulated with PMA, O2- levels increased to 5.76 +/- 3.77 pmol of O2-/minute/10(5) cells. Nonstimulated revision arthroplasty-derived macrophages produced 3.26 +/- 2.02 pmol of O2-/minute/10(5) cells during this ten-minute time period. When identical reaction tubes were stimulated with PMA, O2- levels increased to 3.98 +/- 2.52 pmol of O2-/minute/10(5) cells. The difference in the ratio of O2- production in response to stimulation between primary and revision groups was statistically significant. The observation of a chronic moderate level of activation and the lack of responsiveness to a potent stimulator suggests that macrophage inflammatory activity is down-regulated in periprosthetic synovium.

Adult

Effects of tracer blood measurement noise on glucose metabolic rate estimation.

Tracer kinetic modeling with Positron Emission Tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, computer simulations were performed to investigate the influence of input measurement noise on the accuracy of estimates. The results show that input measurement noise causes considerable variability in the parameter estimates.

Blood Glucose

Graph theoretic analysis of compartmental models. With applications to thyroid hormone metabolic systems.

A single input/single output experiment design may not provide sufficient information to quantify a model of a complex biological system, and multiple input or multiple output experiment designs are often not feasible. An alternate approach is to perform feasible studies with different combinations of input/output ports one at a time, but their simultaneous mathematical analysis can become dimensionally unwieldy. In these cases, a graphical approach can be helpful. Cut set analysis of compartmental models is presented and contrasted with more conventional analysis approaches. It is shown that the complexity of computations is reduced using cut set analysis, especially as the complexity of the model is increased. A case study is presented on quantifying parameters of the enterohepatic subsystem in thyroid hormone distribution and metabolism, based on four different sets of rat experiments performed in the Biocybernetics Laboratory at UCLA.

Animals

Estimation of local cerebral protein synthesis rates with L-[1-11C]leucine and PET: methods, model, and results in animals and humans.

We have estimated the cerebral protein synthesis rates (CPSR) in a series of normal human volunteers and monkeys using L-[1-11C]leucine and positron emission tomography (PET) using a three-compartment model. The model structure, consisting of a tissue precursor, metabolite, and protein compartment, was validated with biochemical assay data obtained in rat studies. The CPSR values estimated in human hemispheres of about 0.5 nmol/min/g agree well with hemispheric estimates in monkeys. The sampling requirements (input function and scanning sequence) for accurate estimates of model parameters were investigated in a series of computer simulation studies.

Animals

Comparative aspects of the distribution, metabolism, and excretion of six iodothyronines in the rat.

We have studied the kinetics of 3 iodothyronines, 3,3'-diiodothyronine (T2), 3',5'-T2, and 3'-monoiodothyronine (T1), in groups of young adult male rats maintained under normal steady state physiological conditions. We have also performed a comparative analysis of these results, combined with corresponding kinetic indices of T4, T3, and rT3, to obtain a more comprehensive understanding of normal thyroid hormone production, distribution, and metabolism. Tracer doses of 125I-labeled 3,3'-T2, 3',5'-T2, and 3'-T1 were separately injected iv, and blood samples were collected 6-12 times for each iodothyronine in optimized sequential kinetic studies designed to maximize the precision of kinetic parameters. Labeled iodothyronines were separated quantitatively from their metabolites in each plasma sample by Sephadex G-25 column chromatography. Conventional kinetic analysis of the resulting data generated distribution volume, clearance, turnover, and mean residence time indices for each iodothyronine, and concomitant compartmental analysis of the same data provided additional results useful for integration and comparative analysis of the 6 iodothyronines. Kinetic parameters for all but T4 and T3 were similar, suggesting that similar mechanisms are responsible for the transport, metabolism, and distribution of nonhormonal iodothyronines. All but T4 and T3 (and, to a much lesser extent, 3'-T1) were almost completely and irreversibly metabolized, whereas 24-30% of the hormones (and 6% of 3'-T1) were excreted as such in feces only. Three-pool models fitted individual plasma kinetic data sets best in all cases (for all 6 iodothyronines), each with a plasma, a slowly exchanging (slow), and a rapidly exchanging (fast) pool, and kinetic parameters of interest were quantified for each iodothyronine (Ti). Quantitative analysis of an integrated 18-pool model for all 6 Tis revealed several other features of physiological interest. The fractional transport rate of T3 into the fast pool (liver, at least) is about an order of magnitude larger than that for all other Tis, supporting the hypothesis that transport of T3 into fast tissues (e.g. liver cells) is selectively amplified relative to that of the 5 other iodothyronines studied. Simultaneous and direct comparison of the 6 plasma kinetic data sets also supports this result. In addition, composite slow tissue pools, which probably exclude liver and kidney, contained the largest whole body fractions of all Tis (greater than 50%), and these also appear to be major sites of whole body T4 monodeiodinations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Transformation of ultrastructural type of fast-twitch muscle fibres after cross-innervation by tetrodotoxin-blocked slow muscle nerve.

It is shown in rats that cross-innervation of the fast-twitch muscle extensor digitorum longus (EDL) by the nerve of the slow-twitch muscle soleus (SOL) can cause a complete transformation of the Z-band width from the fast to the slow muscle fibre type within two weeks and that it can still induce such a transformation, though usually less completely, even when impulse activity is excluded by chronical tetrodotoxin (TTX) block of the nerve. This provides a piece of clear-cut evidence for the presence of some activity-independent trophic factor in the neural determination of skeletal muscle fibre type.

Animals