Biomedical subjects

J G Li

Publications and source records attributed to J G Li.

At least 37 records · Page 2Linked to original sources

PubMed1999

Functional role of the spatial proximity of Asp114(2.50) in TMH 2 and Asn332(7.49) in TMH 7 of the mu opioid receptor.

We examined whether a proposed spatial proximity between Asp114(2.50) and Asn332(7.49) affected the functional properties of the mu opioid receptor. The D114(2.50)N mutant had reduced binding affinities for morphine, DAMGO and CTAP, but not for naloxone and [3H]diprenorphine; this mutation also abolished agonist-induced increase in [35S]GTPgammaS binding. The N332(7.49)D mutation eliminated detectable binding of either [3H]diprenorphine or [3H]DAMGO. The combined D114(2.50)N-N332(7.49)D mutation restored high affinity binding for [3H]diprenorphine, CTAP and naloxone, and restored partially the binding affinities, potencies and efficacies of morphine and DAMGO. Thus, reciprocal mutations of Asp114(2.50) and Asn332(7.49) compensate for the detrimental effects of the single mutations, indicating that the residues are adjacent in space and that their chemical functionalities are important for ligand binding and receptor activation.

Animals↗

PubMed1999

ASP147 in the third transmembrane helix of the rat mu opioid receptor forms ion-pairing with morphine and naltrexone.

We tested the hypotheses that the carboxylate side chain of Asp147 of the mu opioid receptor interacts with the protonated nitrogen of naltrexone and morphine and that this interaction is important for pharmacological properties of the two compounds. Mutation of Asp147 to Ala or Asn substantially reduced the affinity of naltrexone and the affinity, potency and efficacy of morphine, while the Glu mutant had similar properties as the wildtype, indicating the significant role of the carboxylate group of Asp147 in receptor binding and activation. This role could be due to its direct interaction with ligands or involvement in interhelical interactions. The unprotonated analogs of naltrexone and morphine, cyclopropylcarbonyl noroxymorphone (CPCNOM) and N-formylnormorphine (NFNM), respectively, were used to discriminate between these mechanisms. CPCNOM was much less potent as an antagonist and had substantially lower affinity for the mu receptor than naltrexone. Similarly, NFNM was unable to activate the mu receptor and had much lower affinity than morphine. These results indicate the importance of the protonated nitrogen. Notably, the D147A and D147N mutations did not appreciably affect the binding affinities of CPCNOM and NFNM. In addition, the D147E mutant had similar affinities for CPCNOM and NFNM as the D147A and D147N mu receptors. Thus, the carboxylate group of Asp147 is not important for binding of the two unprotonated compounds. These results indicate that the carboxylate group of Asp147 of the mu receptor interacts directly with the protonated nitrogen of naltrexone and morphine and this interaction is important for binding and receptor activation.

Animals↗

PubMed1999

Clinical implementation of wedge filter optimization in three-dimensional radiotherapy treatment planning.

BACKGROUND AND PURPOSE: To describe a wedge filter optimization technique which automatically chooses the beam weights and wedge filters and to demonstrate the implementation of the algorithm in clinical three-dimensional (3D) radiotherapy treatment planning. MATERIAL AND METHODS: Given the incident directions and beam energies of J beams, the dose distribution is a function of the beam weights, wedge angles, and wedge orientations. Instead of decomposing an incident field into a superposition of an open and two nominal wedged fields and then optimizing their weights, the algorithm optimizes the objective function with respect to the beam weights, wedge angles and wedge orientations directly. A salient feature of the algorithm is that no planner intervention was required in the selection of wedge filters during the optimization process. A dose-based objective function which incorporated the relative importance of structures was adopted in this work. The objective function was minimized by the method of simulated annealing. The technique was demonstrated by using a phantom study and two clinical cases. RESULTS: For the phantom case, the classical wedge pair result was obtained, providing a useful test of the algorithm. Dose distributions and dose volume histograms for the target and surrounding organs were presented for the two clinical cases. It was also shown that dose homogeneity to the target could be compromised by increasing the relative importance factors to the surrounding organs. CONCLUSIONS: A 3D wedge filter optimization algorithm has been developed. The technique has the potential to fully automate the 3D radiotherapy treatment planning process. In addition, treatment planning time and efforts were significantly reduced.

Algorithms↗

PubMed1999

Optimization of importance factors in inverse planning.

Inverse treatment planning starts with a treatment objective and obtains the solution by optimizing an objective function. The clinical objectives are usually multifaceted and potentially incompatible with one another. A set of importance factors is often incorporated in the objective function to parametrize trade-off strategies and to prioritize the dose conformality in different anatomical structures. Whereas the general formalism remains the same, different sets of importance factors characterize plans of obviously different flavour and thus critically determine the final plan. Up to now, the determination of these parameters has been a 'guessing' game based on empirical knowledge because the final dose distribution depends on the parameters in a complex and implicit way. The influence of these parameters is not known until the plan optimization is completed. In order to compromise properly the conflicting requirements of the target and sensitive structures, the parameters are usually adjusted through a trial-and-error process. In this paper, a method to estimate these parameters computationally is proposed and an iterative computer algorithm is described to determine these parameters numerically. The treatment plan selection is done in two steps. First, a set of importance factors are chosen and the corresponding beam parameters (e.g. beam profiles) are optimized under the guidance of a quadratic objective function using an iterative algorithm reported earlier. The 'optimal' plan is then evaluated by an additional scoring function. The importance factors in the objective function are accordingly adjusted to improve the ranking of the plan. For every change in the importance factors, the beam parameters need to be re-optimized. This process continues in an iterative fashion until the scoring function is saturated. The algorithm was applied to two clinical cases and the results demonstrated that it has the potential to improve significantly the existing method of inverse planning. It was noticed that near the final solution the plan became insensitive to small variations of the importance factors.

Algorithms↗

PubMed1999

Estimation theory and model parameter selection for therapeutic treatment plan optimization.

Treatment optimization is usually formulated as an inverse problem, which starts with a prescribed dose distribution and obtains an optimized solution under the guidance of an objective function. The solution is a compromise between the conflicting requirements of the target and sensitive structures. In this paper, the treatment plan optimization is formulated as an estimation problem of a discrete and possibly nonconvex system. The concept of preference function is introduced. Instead of prescribing a dose to a structure (or a set of voxels), the approach prioritizes the doses with different preference levels and reduces the problem into selecting a solution with a suitable estimator. The preference function provides a foundation for statistical analysis of the system and allows us to apply various techniques developed in statistical analysis to plan optimization. It is shown that an optimization based on a quadratic objective function is a special case of the formalism. A general two-step method for using a computer to determine the values of the model parameters is proposed. The approach provides an efficient way to include prior knowledge into the optimization process. The method is illustrated using a simplified two-pixel system as well as two clinical cases. The generality of the approach, coupled with promising demonstrations, indicates that the method has broad implications for radiotherapy treatment plan optimization.

Algorithms↗

PubMed1999

Matching photon and electron fields with dynamic intensity modulation.

A technique was developed to reduce the size and magnitude of the hot and cold spots in the abutting regions of photon and electron fields. The photon and electron fields were set up such that the photon field extended approximately 2 cm into the electron field in the abutting region. The region of the photon beam that overlapped the electron field was modulated using a multileaf collimator, effectively broadening the photon penumbra to make it complimentary to the electron penumbra. The computer calculations were verified using film measurements for abutting a 6 MV photon beam with a 9 MeV electron beam. A uniform dose was achieved at a prespecified depth of 2 cm, and dose uniformity was improved at the specified depth and beyond compared with unmodulated photon beams. A slight increase in dose inhomogeneity was seen at shallower depths. The overall areas of the hot and cold spots were significantly reduced. The technique also reduced the sensitivity of dose homogeneity to setup errors such that the magnitudes of the hot and cold spots were about half of those produced with unmodulated photon beam when an overlap or gap of 4 mm was introduced. The technique was applied to the treatment of a head and neck cancer and a lymphoma involving the right pleura with markedly reduced dose inhomogeneity in the abutting regions.

Computer Simulation↗

PubMed1999

Inhibition of myocardial inward rectifier potassium current by propylbutyldopamine.

AIM: To study the effects of propylbutyldopamine (PBDA) on the inward rectifier potassium current (Ik1). METHODS: The quasi-steady state current-voltage relationship from the isolated guinea pig ventricular cells were measured using whole-cell patch-clamp techniques with a slow ramp depolarization (8 mV.s-1). RESULTS: PBDA 5, 50, and 100 mumol.L-1 concentration-dependently reduced the inward rectifier potassium current. PBDA blocked Ik1 in guinea pig ventricular cells. The effect of PBDA was not blocked by the selective dopamine D2-receptor blocker, domperidone. CONCLUSION: PBDA inhibited Ik1 directly, independent of the dopamine D2-receptor.

Action Potentials↗

PubMed1999

[Chromosome aberration of pollen mother cell of broccoli (Brassica oleralea var. Italica) induced by space flight].

OBJECTIVE: To study the cytogenetic effect of space flight on broccoli seeds and the mechanism of mutations of the plant. METHOD: Dry seeds of broccoli were sent to the space on board a recoverable satellite for 8 days. After recovery the seeds were planted in the field. Chromosome behaviour of pollen mother cell (PMC) samples were observed following the method of ZHU Cheng, 1982. Pollen samples were stained and embeded in lacto-phenol fuchsin for fertility determination. RESULT: Unequal chromosome numbers of broccoli's PMC were found in the diakinesis stage, such as reducing n = 6, 7 or increasing n = 11 (earth-control number is n = 9); inversion or translocation of chromosomes occurred, and lagging chromosome were found in the anaphase and telophase of PMC meiosis growing rate and growing potential of the seeds were observed after recovery. CONCLUSION: Leaves cexaceous decrease and aberrations in the chromosome of PMC are found in broccoli after space flight.

Brassica↗

PubMed1999

[Studies on hereditary variations of millet seed after high altitude balloon flight].

OBJECTIVE: To select high yield, high protein and fatty acid millet. METHOD: Air-dried seeds of millet were carried by high altitude balloon (HAB) for 8 h. Botany characteristics of these seeds were analyzed and studied after recovery. RESULT: Germinating potential rose 21.1%, germinating percentage reduced 5.2% as compared with the control; plant height was 6.8 cm lower than that of the control in SP1; while flag-leaf area and spike weight were 25% and 15.9% higher than those of the control respectively. Large-spike strains were stable in SP3 pregeny. In SP3(-2), the contents of seed protein and fatty acid were more than those of control; in SP3(-5), the average spike length was 5.8 cm, and the content of Fe element in seed was 61.5 mg/kg more than these of control; in SP4 superspike strains, spike character, chlorophyll content and photosynthetic rate were significantly higher than the control during growing phase and growing anaphase, photosynthetic rate in flag-leaf was over 27.9% higher than those in the control. CONCLUSION: New strains with high protein and fatty acid and high yield could be selected by HAB. The characteristics of these variations in the new strain is hereditable.

Chlorophyll↗

PubMed1999

[Development and prospect of plant mutation breeding induced by aviation and spaceflight in China].

Since 1987, about fifty species, three hundred varieties of crops have been sent in recoverable satellites or high altitude balloon (HAB). The selected lines include a high-yield, disease-resist, and hybrid-vigorous rice line, a recovered line of Japonica rice restoring sterility of Indica rice, a new green pepper strain which grows fruits over 500 g, a disease-resist, high-quality tomato line, a big-pod rape line, a big-fruit white lotus line and a big-bulb lily. The special conditions in the outer space can induce a variety of mutations in the plants and their progeny, which provides a new way for the plant breeding.

Agriculture↗

PubMed1998

Apparent thermodynamic parameters of ligand binding to the cloned rat mu-opioid receptor.

The apparent thermodynamic parameters of binding of ten ligands to the cloned rat mu-opioid receptor stably expressed in Chinese hamster ovary (CHO) cells were investigated. For every ligand, the Kd or Ki values at 0 degrees C, 12 degrees C, 25 degrees C and 37 degrees C were determined, a van't Hoff plot was generated and deltaH degrees' , deltaS degrees' and -TdeltaS degrees' and deltaG degrees' were calculated. Changes in free energy (deltaG degrees') ranged from -10.35 to -15.65 kcal/mol. The binding of sufentanil, ohmefentanyl, diprenorphine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-penicillamineThr-NH2 (CTAP) was endothermic (deltaH degrees' > 0) and driven by an increase in entropy (-TdeltaS degrees' = -13.08 to -18.57 kcal/mol). The binding of naltrexone was exothermic (deltaH degrees' = -12.56 kcal/mol) and essentially enthalpy-driven. The binding of morphine, methadone, pentazocine, [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO) and Tyr-Pro-NMePhe-D-Pro-NH2 (PL017) was exothermic (deltaH degrees' = -3.53 to -9.95 kcal/mol) and occurred with an increase in entropy (-TdeltaS degrees' = -2.48 to -7.92 kcal/mol). Plots of enthalpy versus entropy and enthalpy versus free energy were linear, although enthalpy-entropy compensation was not evident. The entropy changes were not correlated with apparent lipophilicity of the compounds. These results suggest that: (1) opioid ligands bind to the mu receptor by specific mechanisms, unrelated to lipid solubility; (2) the mechanism of binding is not universally different for peptide and non-peptide ligands; (3) the nature of binding does not a priori determine intrinsic activity. The results reveal a novel differentiation of opioid ligands into two groups (group 1: ohmefentanyl, sufentanil, diprenorphine, CTAP and PL017; group 2: naltrexone, morphine, methadone, DAMGO, pentazocine), based on two distinct relationships between enthalpy versus free energy of binding, the details of which are yet to be elucidated.

Analgesics↗

PubMed1998

Water dynamics in human blood via combined measurements of T2 relaxation and diffusion in the presence of gadolinium.

An analytical model of tissue relaxation and restricted diffusion in human blood is presented. The blood tissue model is composed of three different compartments: red blood cells, plasma, and macromolecular protons. The relaxation rate constants and free diffusion coefficients of intracellular and extracellular water may differ. Analytical formulas for signal loss due to relaxation and diffusion in the Carr-Purcell Meiboom-Gill and pulsed-field-gradient multispin echo experiments for this tissue model are derived. The model is fitted to the experimental data for human blood with various concentrations of Gadolinium contrast agent. The obtained model parameters are realistic. The validity and sensitivity of the model are also discussed.

Blood↗

PubMed1998

Integrated analysis of diffusion and relaxation of water in blood.

Diffusion and T2 relaxation of water both inside and outside red blood cells (RBCs) in human blood were investigated using a hybrid NMR pulse sequence to obtain a more quantitative understanding of the diffusion and relaxation behavior of water in paramagnetic-doped blood samples. The data were analyzed by both examining the relaxation properties of the system after each diffusion weighting and looking at the diffusion properties at each echo time. The results illustrate how diffusion-sensitizing gradients affect the T2 spectra of blood and how relaxation weighting changes the curvature of the diffusion curves, thereby demonstrating the close coupling between diffusion and T2 relaxation. A three-pool model, consisting of RBCs, plasma, and macromolecular protons, was used to model the data from the diffusion-relaxation hybrid experiments. The model was found to describe all the characteristic features of the experimental data well and was used to evaluate the approximations involved in the conventional analysis methods and elucidate the nature of the relaxing and diffusing components. Compared with the separate diffusion and relaxation experiments, the diffusion-relaxation hybrid experiments are less time-consuming, result in better parameter determinations, and may be useful in analyzing diffusion-T2 coupling in tissues with more complicated multiexponential T2 behavior.

Biological Transport↗

PubMed1997

A flexible magnetization transfer line shape derived from tissue experimental data.

To summarize and compare magnetization transfer data from biological tissues, a method was developed to extract the average absorption lineshape of the semi-solid pool directly from magnetization transfer experimental data along with the four other parameters that characterize the two-pool model of exchange. Magnetization transfer data for several biological tissues were analyzed using this method and the resulting "flexible" lineshapes were compared with super-Lorentzian and "Kubo-Tomita" lineshapes. The use of flexible lineshapes noticeably improves the fit of the two-pool model to the data. The derived flexible lineshapes of all the tissues analyzed are physically realistic and show remarkably consistent behavior.

Animals↗

PubMed1997

Irreversible binding of N-methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl-3,4 -dichlorophenylacetamide to the cloned rat kappa opioid receptor.

N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl-3,4- dichlorophenylacetamide (MITPD), is an isothiocyanate derivative of the kappa agonist ICI-199,441. In this study, interaction of MITPD with cloned mu, delta, and kappa opioid receptors was characterized. MITPD inhibited [3H]diprenorphine binding to kappa receptors with high affinity and with approximately 700- and approximately 870-fold selectivity over mu and delta receptors. Pretreatment with MITPD followed by extensive washing reduced kappa receptor binding with an IC50 value of 3.7 nM, but did not affect mu or delta binding at < or = 0.1 microM. Preincubation with 1 microM MITPD abolished [3H]diprenorphine binding, while pretreatment with 1 microM ICI-199,441 increased Kd of [3H]diprenorphine binding with no change in Bmax. Thus, MITPD is a selective kappa irreversible ligand. The region of the kappa receptor that conferred selectivity for MITPD was determined by examining its binding to four mu/kappa chimeras. IC50 values of MITPD for inhibition of [3H]diprenorphine binding were determined to be 430 nM for Chimera III (kappa1-141/mu151-398), 1.8 nM for Chimera IV (mu1-150/kappa142-380), 40 nM for Chimera XI (mu1-268/kappa263-380) and 14 nM for Chimera XII (kappa1-262/mu269-398). Pretreatment with MITPD followed by extensive washing reduced binding to chimera IV with an IC50 value of 75 nM, but did not affect III, XI or XII binding (IC50 >1 microM). Thus, the region from the third transmembrane helix to the C-terminus of the kappa receptor is important for the binding of MITPD.

Acetamides↗

PubMed1997

Image resolution and signal-to-noise ratio requirements for MR imaging of degenerative cartilage.

OBJECTIVE: The purpose of this study was to determine the MR image resolution and signal-to-noise ratio (SNR) required to reveal morphologic abnormalities in degenerative cartilage. MATERIALS AND METHODS: In vitro MR microscopy of healthy bovine and degenerative human patellar cartilage was performed and image resolution degraded to simulate resolution achievable in routine and optimized clinical MR images. Noise was then added to images as in-plane resolution was increased to simulate the MR imaging appearance of cartilage with improved resolution, which is possible using a standard magnetic field strength. MR images of patellar cartilage from a healthy volunteer were also obtained to determine optimal SNR and image resolution achievable at 1.5 T; these images were compared with in vitro images to determine those features of abnormal cartilage that can be identified using available clinical MR imaging techniques. RESULTS: In-plane resolution of 39 microns exquisitely defines degenerative changes in articular cartilage. As in-plane resolution decreases to 600 microns, only gross cartilage thinning and signal intensity alterations are seen. MR images simulating progressively improved resolution using higher field strength gradients with conventional field strengths and RF coils provided suboptimal information because of low SNR. CONCLUSION: Routine clinical MR images do not accurately reveal early degenerative changes in articular cartilage; only large defects and distorted changes in the signal intensity of cartilage are seen.

Adult↗

PubMed1997

Activation of the cloned human kappa opioid receptor by agonists enhances [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of ligands.

Activation of kappa receptors inhibits adenylate cyclase, enhances K+ conductance and reduces Ca++ conductance via pertussis toxin-sensitive G proteins. We recently cloned a human kappa opioid receptor and stably expressed it in Chinese hamster ovary (CHO) cells. In this study, the effects of activation of the human kappa receptor by agonists on [35S]GTPgammaS binding to CHO cell membranes were examined. The presence of GDP and Mg++ was essential for the kappa agonist (-)-U50,488H-induced increase in [35S]GTPgammaS binding to be observed and the optimal concentration was 3 microM and 5 mM, respectively. The presence of 100 mM Na+ was necessary to produce the maximal signal-to-background ratio. (-)U50,488H-induced increase in [35S]GTPgammaS binding was time- and tissue concentration-dependent. (-)U50,488H increased [35S]GTPgammaS binding in a dose-dependent manner with an EC50 of 3.1 nM. (+)-U50,488H had no effect, which indicates that this effect is stereospecific. Naloxone (1 microM) or norbinaltorphimine (10 nM) shifted the dose-response curve of (-)-U50,488H to the right by 100-fold. These results indicate that enhancement of [35S]GTPgammaS binding by (-)-U50,488H is a kappa receptor-mediated event. Pretreatment of the cells with pertussis toxin, but not cholera toxin, abolished the (-)-U50,488H-induced increase in [35S]GTPgammaS binding, which indicates the involvement of Gi and/or Go proteins. [35S]GTPgammaS binding induced by (-)-U50,488H had a Kd value of 0.34 +/- 0.08 nM and a Bmax value of 431 +/- 29 fmol/mg protein. The rank order of potencies of opioid ligands tested in stimulating [35S]GTPgammaS binding was dynorphin A 1-17 > (+/-)-ethylketocyclazocine > beta-funaltrexamine, (-)-U50,488H, tifluadom > nalorphine > pentazocine, nalbuphine > buprenorphine. Dynorphin A 1-17, (+/-)-ethylketocyclazocine, (-)-U50,488H, tifluadom and beta-funaltrexamine were full agonists, but nalorphine and pentazocine were partial agonists producing maximal responses of 68% and 23% of those of full agonists, respectively. Nalbuphine and buprenorphine had low levels of agonist activities. Norbinaltorphimine and naloxone were antagonists devoid of activities. Enhancement of [35S]GTPgammaS binding by kappa agonists provides a simple functional measure for receptor activation and can be used for determination of potencies and efficacies of opioid ligands at the kappa receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1996

Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E virus.

Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern China. However, the evaluation of antibodies to HEV during consecutive time periods after infection has not been reported. We utilized enzyme immunosorbent assay (ELISA) to defect IgM and IgG anti-HEV in consecutive serum specimens from patients with acute hepatitis E and compared that data with detection rates of IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be detected as early as 4 days after onset of disease symptoms in some patients. The detection rate of IgM anti-HEV is significantly higher in specimens collected within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks after onset (67.6%) (P < 0.005). IgM anti-HEV had a similar pattern to IgM anti-HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti-HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P < 0.005). One should be cautioned against making a diagnosis of HEV infection solely by the currently available assays for IgG anti-HEV. In conclusion, IgM anti-HEV can be used as a reliable and sensitive marker for recent HEV infection, but serum specimens should be collected within 4 weeks after onset of symptoms to avoid false-negative results. In contrast, we should be aware of the failure to develop IgG anti-HEV in some patients. These patients carry the risk of reinfection.

Acute Disease↗