Biomedical subjects

J Zeng

Publications and source records attributed to J Zeng.

At least 19 recordsLinked to original sources

PubMed2001

Detailed-term-accounting-approximation calculations of the radiative opacity of laser-produced Al plasmas.

An extensive configuration interaction (CI) scheme and the R-matrix method are combined to calculate the radiative opacity for laser-produced aluminum plasma in local thermodynamic equilibrium using the detailed-term-accounting (DTA) approximation. The CI scheme is used to obtain the absorption oscillator strengths of the electric dipole allowed transitions for evaluating the bound-bound absorption cross sections, and the R-matrix method is used to obtain the bound-free absorption (photoionization) cross sections. For an aluminum plasma at a temperature of 20 eV and the density of 0.01 g/cm(3), the Rosseland and Planck mean opacities are calculated to be 4184 and 24891 cm(2)/g, respectively, by integrating the spectrally resolved opacities with Rosseland and Planck weighting functions. The two mean opacities are also obtained by using the average atom model, and they are 22520 and 30402 cm(2)/g, respectively. The optical transmission from the photon energy of 70-250 eV, which was experimentally measured by Winhart et al. [G. Winhart et al. Phys. Rev. E 53, R1332 (1996)], is also calculated. Generally good agreement is found between our DTA and experimental transmission. Our theoretical result reproduces all structures shown in the experiment, whereas some of the structures near the higher energy edge did not show up in some other opacity models. These structures are attributed to the detailed treatment of the photoionization process.

Journal Article↗

PubMed2001

Azepanone-based inhibitors of human and rat cathepsin K.

The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone-based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are described. These compounds show improved configurational stability of the C-4 diastereomeric center relative to the previously published five- and six-membered ring ketone-based inhibitor series. Studies in this series have led to the identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) = 0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic analysis of 20 established the C-4 S stereochemistry as being critical for potent inhibition and that unbound 20 adopted the expected equatorial conformation for the C-4 substituent. Molecular modeling studies predicted the higher energy axial orientation at C-4 of 20 when bound within the active site of cathepsin K, a feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of the cyclic and acyclic analogues through CaCo-2 cells suggests that oral bioavailability of the acyclic derivatives is limited by a P-glycoprotein-mediated efflux mechanism. It is concluded that the introduction of a conformational constraint has served the dual purpose of increasing inhibitor potency by locking in a bioactive conformation as well as locking out available conformations which may serve as substrates for enzyme systems that limit oral bioavailability.

Administration, Oral↗

PubMed2001

[Expression and clinopathological significance of HCCA1 in hepatocellular carcinoma].

OBJECTIVE: To explore the correlation of a newly cloned HCCA1 gene expression with hepatocellular carcinoma (HCC). METHODS: HCCA1 mRNA and protein expression were detected by Northern blotting and by immunohistochemistry respectively. Its clinopathological significance was also analyzed. RESULTS: HCCA1 mRNA expression was found in 59 (90.8%) out of 65 patients. Of these, 54 (91.5%) showed significantly elevated expression of HCCA1 mRNA in HCC tissues. There were 9 (13.8%) patients who had low level of HCCA1 mRNA expression in paracarcinoma, and 56 (86.2%) cases showed no detectable signals. HCCA1 mRNA expression was closely related to lower tumor grading and portal vein invasion. It was noted that HCCA1 mRNA levels were higher in tumor grading III-IV group than in grading I-II group, higher in portal vein thrombus group than in non-thrombus group. Immunohistochemical staining confirmed that the HCCA1 protein was preferentially expressed in HCC tissues. Amongst 38 patients examined, 20 (52.6%) revealed positive staining with anti-HCCA1. CONCLUSION: HCCA1 is a novel HCC associated gene which may play a role in HCC invasion and metastasis.

Adult↗

PubMed2001

Cyclic ketone inhibitors of the cysteine protease cathepsin K.

Cathepsin K (EC 3.4.22.38), a cysteine protease of the papain superfamily, is predominantly expressed in osteoclasts and has been postulated as a target for the treatment of osteoporosis. Crystallographic and structure--activity studies on a series of acyclic ketone-based inhibitors of cathepsin K have led to the design and identification of two series of cyclic ketone inhibitors. The mode of binding for four of these cyclic and acyclic inhibitors to cathepsin K is discussed and compared. All of the structures are consistent with addition of the active site thiol to the ketone of the inhibitors with the formation of a hemithioketal. Cocrystallization of the C-3 diastereomeric 3-amidotetrahydrofuran-4-one analogue 16 with cathepsin K showed the inhibitor to occupy the unprimed side of the active site with the 3S diastereomer preferred. This C-3 stereochemical preference is in contrast to the X-ray cocrystal structures of the 3-amidopyrrolidin-4-one inhibitors 29 and 33 which show these inhibitors to prefer binding of the 3R diastereomer. The 3-amidopyrrolidin-4-one inhibitors were bound in the active site of the enzyme in two alternate directions. Epimerization issues associated with the labile alpha-amino ketone diastereomeric center contained within these inhibitor classes has proven to limit their utility despite promising pharmacokinetics displayed in both series of compounds.

Animals↗

PubMed2001

Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo.

BACKGROUND: High mammographic density is associated with increased breast cancer risk. Previous studies have shown that estrogens increase breast density on mammograms, but the effect on mammographic density of selective estrogen receptor modulators, such as raloxifene, is unknown. We assessed changes in mammographic density among women receiving placebo, raloxifene, or conjugated equine estrogens in an osteoporosis prevention trial. METHODS: In a 5-year multicenter, double-blind, randomized, placebo-controlled osteoporosis prevention trial, healthy postmenopausal women who had undergone hysterectomy less than 15 years before the study and had no history of breast cancer received placebo, raloxifene (at one of two doses), or conjugated estrogens (ERT). Women from English-speaking investigative sites who had baseline and 2-year craniocaudal mammograms with comparable positioning (n = 168) were eligible for this analysis. Changes in mammographic density were determined by digital scanning and computer-assisted segmentation of mammograms and were analyzed with the use of analysis of variance. All statistical tests were two-sided. RESULTS: Among the four treatment groups after 2 years on study, the mean breast density (craniocaudal view) was statistically significantly greater in the ERT group than it was in the other three groups (P<0.01 for all three comparisons). Within treatment groups, the mean breast density from baseline to 2 years decreased statistically significantly in women receiving the placebo or either the higher or lower raloxifene dose (P = 0.003, P = 0.002, and P<0.001, respectively) and showed a nonstatistically significant increase in women receiving ERT. CONCLUSIONS: In an osteoporosis prevention trial, raloxifene did not increase breast density after 2 years of treatment. Raloxifene administration should not interfere with, and could even enhance, mammographic detection of new breast cancers.

Breast↗

PubMed2001

Prostate biopsy protocols: 3D visualization-based evaluation and clinical correlation.

OBJECTIVES: Systematic needle core biopsy is commonly used for the diagnosis of prostate cancer by urologists worldwide. As accurate and early diagnosis will result in more and better options for treatment, it is critical that the best possible protocols for biopsy be used clinically. In this study, we develop three-dimensional (3D) modeling and simulation technologies to evaluate most of the biopsy protocols in current clinical use, and correlate the results with those from clinical cases. MATERIALS AND METHODS: Using deformable modeling techniques, 3D computerized prostate surface models were reconstructed from step-sectioned, whole-mounted radical prostatectomy specimens with localized prostate cancer. A 3D computer simulation system was developed to accurately depict the anatomy of the prostate and all individual tumor foci. A user-friendly interface was developed in the system so that a physician can easily and interactively use it for prostate needle core biopsy. A total of 281 prostate models were reconstructed, and 18 biopsies were performed by a urologist on each model to determine the detection rates of seven different biopsy protocols. Clinical biopsies from 35 patient cases were also reviewed and correlated with the simulation results. RESULTS: The most commonly used sextant biopsy had only a 71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern protocol performed better than the sextant protocol, with a detection rate of 89.3%. The lateral sextant biopsy protocol (using sites similar to, but more lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more biopsies to achieve this increase, which, according to McNemar's test, is not statistically significant when compared to results with the 10-pattern protocol. The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%. Transition zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. The clinical correlation also confirmed that the 10-pattern protocol was significantly superior to the traditional sextant biopsy pattern. CONCLUSIONS: The 10-pattern biopsy protocol was the most optimized among all the protocols evaluated. This protocol supplemented the sextant biopsy protocol with four more lateral biopsies in the mid and apical sites on both sides.

Biopsy, Needle↗

PubMed2001

Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.

When the oxygen atom in a peptide bond is replaced by a sulfur atom, the restriction in the available conformational space and the ability of thioamides to confer resistance to enzymatic degradation renders thioamides as potentially useful building blocks for drug design and protein engineering. The solvation free energy differences between conformers of the same dipeptide can be high. Yet, previous conformational studies, basing on the (phi, psi) conformational energy maps of thio-substituted dipeptides, neglected both explicit water interactions and free energy considerations. In this paper, the (phi, psi) conformational free energy maps are obtained by single umbrella sampling in an explicit water environment for both alanine dipeptide and the corresponding thioamide derivatives. The phi and psi angles for the minima in the relative energy maps calculated with dielectric of 80 are similar to the corresponding phi and psi angles in the relative free energy maps for both Ac-Ala-NHMe (Ac: acetyl; Ala: alanine) and Act-Alat-NHMe (Act: thio-acetyl; Alat: thio-alanine). However, some large differences between the relative energy and relative free energy of major minima indicate that the consideration of free energy is important in determination of the relative occupancy of particular minima. Free energy maps for both Ac-Ala-NHMe and Act-Alat-NHMe show that thio-substitution favors conformations where phi < 0 because of the deeper beta and alphaR minima. The changes in the position and relative stability of minima were explained in terms of the destabilization of the regions near phi = -120, 0 and 120, psi = 60, -60, 180, which correspond to the increased steric hindrance due to the bulkier sulfur atom.

Alanine↗

PubMed2001

Effects of environmental and test conditions on VOC emissions from "wet" coating materials.

In this paper, numerical simulations have been conducted to study the effects of key environmental and test conditions (air velocity, temperature, film thickness, and sample application time) on volatile organic compound (VOC) emissions from a "wet" coating material (wood stain). Simulation results indicate that air velocity and sample application time only significantly affect the emission profiles in the early stage. Film thickness, on the other hand, affects long-term emissions. Temperature can affect both the short-term and long-term emissions.

Air Movements↗

PubMed2001

Design of inhibitors of Ras--Raf interaction using a computational combinatorial algorithm.

Drugs that inhibit important protein-protein interactions are hard to find either by screening or rational design, at least so far. Most drugs on the market that target proteins today are therefore aimed at well-defined binding pockets in proteins. While computer-aided design is widely used to facilitate the drug discovery process for binding pockets, its application to the design of inhibitors that target the protein surface initially seems to be limited because of the increased complexity of the task. Previously, we had started to develop a computational combinatorial design approach based on the well-known 'multiple copy simultaneous search' (MCSS) procedure to tackle this problem. In order to identify sequence patterns of potential inhibitor peptides, a three-step procedure is employed: first, using MCSS, the locations of specific functional groups on the protein surface are identified; second, after constructing the peptide main chain based on the location of favorite locations of N-methylacetamide groups, functional groups corresponding to amino acid side chains are selected and connected to the main chain C(alpha) atoms; finally, the peptides generated in the second step are aligned and probabilities of amino acids at each position are calculated from the alignment scheme. Sequence patterns of potential inhibitors are determined based on the propensities of amino acids at each C(alpha) position. Here we report the optimization of inhibitor peptides using the sequence patterns determined by our method. Several short peptides derived from our prediction inhibit the Ras--Raf association in vitro in ELISA competition assays, radioassays and biosensor-based assays, demonstrating the feasibility of our approach. Consequently, our method provides an important step towards the development of novel anti-Ras agents and the structure-based design of inhibitors of protein--protein interactions.

Algorithms↗

PubMed2001

[GC-MS analysis of supercritical carbon dioxide extract from seeds of Zanthoxylum bungeanun Maxim].

The chemical components of supercritical carbon dioxide extracts from seeds of Zanthoxylum bungeanun Maxim. were studied by GC-MS-DS. Thirty-five compounds which account for 96.22% of the total area of the chromatographic peaks, were identified. The results showed that fatty acids and esters occupied 90.83% of total chromatographic efflux of the extracts. The main components of the extracts are oleic acid(38.91%), palmitic acid (29.45%), linoleic acid methyl ester(10.80%), linolenic acid methyl ester(8.64%), et al.

Carbon Dioxide↗

PubMed2001

[GC-MS analysis of supercritical carbon dioxide extraction products from pericarp of Zanthoxylum bungeanum].

The chemical constituents of supercritical carbon dioxide extraction products from pericarp of Zanthoxylum bungeanun Maxim. were studied by GC-MS-DS. Forty-five compounds which account for 86.76% of the area of the chromatographic peaks were identified. The results showed that the main components of the extracts are beta-pinene (10.33%), 1,8-terpinene (7.6%), cis-piperitol acetate (7.07%), oleic acid (5.46%), palmitic acid (5.41%) and 4-terpineol, (43.7%), et al.

Carbon Dioxide↗

PubMed2001

[Supercritical and near-critical fluid solvents assisted reaction and separation processes].

The tunability of supercritical and near-critical fluid (S/NCF) solvents offers environmental improvements and economic advantages from improved performances and flexibility for separation and reaction processes through density changes or cosolvents. The paper reviews the sustainable reaction and separation processes in S/NCF solvents such as supercritical carbon dioxide and near-critical water.

Acids↗

PubMed2001

[Dynamic analysis of incidence and mortality of stroke and the risk factors in the communities in Shanghai, in the 1990's].

OBJECTIVE: To understand the trend of incidence, mortality of stroke and the risk factors at the community level in the 1990's. METHODS: To establish a network of disease surveillance. Both incidence and mortality of stroke were surveyed in the 35 - 74 age group during 1991 - 1999 using the method of WHO MONICA. By cluster sampling in 1992 and 1998, 500 individuals aged 35 - 59 from each female and male group were investigated respectively on the risk factor of stroke. RESULTS: The incidence of stroke was averaged 168.2 per 100 000 in the group aged 35 - 79 during 1991 to 1999 with 194.5 and 144.9 pre 100 000 respectively for the male and female group of this age. The incidence of stroke in the male group was higher than that in the female group, also with a faster speed of increase in the male group. The overall mortality of stroke was averaged 79.2 per 100 000 with 87.2 and 71.4 per 100 000 in male and female groups respectively of this age group. The incidence of stroke increased with age in both male and female groups. The average age of onset had been 66.1 year olds during 1996 - 1999, 3.5 years older than that age groups during 1991 - 1995, but did not show much difference between male group and female group. CHO, Blood Pressure, BMI, Prevalence of Hypertension, TC/HDLC, WHR, Prevalence of High-CHO, Prevalence of Low-HDL all had a tendency of increase in both male and female groups. The rates of smoking cigarettes and drinking alcohol both decreased, especially in the male group. CONCLUSION: The incidence of stroke and some relative risk factors seemed to increase in the 1990's, but the mortality of stroke had a decrease in the same period in the communities in Shanghai.

Adult↗

PubMed2000

Point mutants of c-raf-1 RBD with elevated binding to v-Ha-Ras.

A mutational analysis of the Ras-binding domain (RBD) of c-Raf-1 identified three amino acid positions (Asn(64), Ala(85), and Val(88)) where amino acid substitution with basic residues increases the binding of RBD to recombinant v-Ha-Ras. The greatest increase in binding (6-9-fold) was observed with the A85K-RBD mutant. The elevated binding for the A85K-RBD and V88R-RBD mutants was also detected with Ras expressed in cultured mammalian cells, namely NIH-3T3 and BAF cells. None of the wild type residues in RBD positions Asn(64), Ala(85), and Val(88) have been previously implicated in the interaction with Ras (Block, C., Janknecht, R., Herrmann, C., Nassar, N., and Wittinghofer, A. (1996) Nat. Struct. Biol. 3, 244-251; Nassar, N., Horn, G., Herrmann, C., Scherer, A., McCormick, F., and Wittinghofer, A. (1995) Nature 375, 554-560). The discovery of elevated binding among the mutants in these positions implies that additional RBD residues can be used to generate the Ras. RBD complex. These findings are of particular significance in the design of Ras antagonists based on the RBD prototype. The A85K-RBD mutant can be used to develop an assay for measuring the level of activated Ras in cultured cells; Sepharose-linked A85K-RBD.GST fusion protein served as an activation-specific probe to precipitate Ras.GTP but not Ras.GDP from epidermal growth factor-stimulated cells. A85K-RBD precipitates up to 5-fold more Ras.GTP from mammalian cells than wild type RBD.

Amino Acid Sequence↗

PubMed2000

Expression of zinc-positive cells and terminals in fetal neocortical homografts to adult rat depends on lesion type and rearing conditions.

Zinc-positive neurons and terminals, known to be associated with the glutamatergic projections in the brain, can be demonstrated by the histochemical Timm method and later modifications thereof. The adult rat neocortex contain a uniform lamination of zinc-positive cells with specific projections to, e.g., the striatum. We have previously reported that fetal neocortical grafts implanted in the adult rat neocortex combined with rearing in an enriched environment can improve behavioral functions and reduce the secondary atrophy of thalamus after cortex infarction in adult rats. In order to examine whether the expression of zinc positivity is ontogenetically inherent to neocortical neurons we grafted fetal neocortical tissue to aspiration or ischemic lesions of the frontoparietal neocortex of adult rats, followed by histochemical visualization of the vesicular zinc pool by selenite or sulfide. One further aim of the study was to elucidate to what extent the distribution of zinc-containing neurons and terminals in the grafts depended on rearing under different environmental conditions. The foremost finding of the present study was that the overall density of zinc-containing terminals in fetal cortical transplants placed in brain infarcts of adult spontaneously hypertensive rats is higher when the rats are reared in an enriched environment. Moreover, the presence and expression of zinc-positive neurons and terminals do not seem to be ontogenetically inherent to the cortical neurons as the fetal neocortical grafts placed in aspiration lesions contained no zinc-selenide-positive neurons and few or no zinc-selenide-positive terminals. The presence or expression of zinc-positive cells may thus be induced by ingrowth of fibers and terminals from the host brain as transplants placed in the ischemic lesions expressed both zinc-positive neurons and terminals.

Animals↗

PubMed2000

Detailed-term-accounting-approximation simulation of x-ray transmission through laser-produced Al plasmas

An extensive configuration interaction (CI) scheme and the R-matrix method are combined to calculate the x-ray transmission spectrum for high-power laser-produced Al plasmas in local thermodynamic equilibrium by using the detailed-term-accounting (DTA) approximation. All atomic parameters such as state levels and photoabsorption cross sections for different ionization stages are obtained by using the CI and R-matrix method. Special attention is given to the effects of autoionizing resonance broadening on the transmission. A large difference exists between the convergence of the results with and without taking account of autoionizing resonance broadening when the autoionization resonance broadening is the major broadening mechanism. This shows that autoionizing resonance widths of the K-shell excited states have large effects and should be considered to interpret the spectral-resolved transmission.

Journal Article↗

PubMed2000

Mini-review: computational structure-based design of inhibitors that target protein surfaces.

Finding drugs that inhibit protein-protein interactions is usually difficult. While computer-aided design is used widely to facilitate the drug discovery process for protein targets with well-defined binding pockets, its application to the design of inhibitors targeting a protein surface is very limited. In this mini-review we address two aspects of this issue: firstly, we overview the current state of design methodology for inhibitors specifically targeting protein surfaces, and secondly, we briefly outline recent advances in computational methods for structure-based drug design. These methods are closely related to protein docking and protein recognition, the difference being that in ligand design, ligands are built on a fragment-by-fragment basis. A novel scheme of computational combinatorial ligand design developed for the design of inhibitors that interfere with protein-protein interaction is described in detail. Current applications and limitations of this methodology, as well as its future prospects, are discussed.

Combinatorial Chemistry Techniques↗

PubMed2000

3-D computer visualization and interactive prostate biopsy simulation leads to an improved systematic technique for the detection of prostate cancer: clinical correlation.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. Recent data based upon whole-mounted step-sectioned radical prostatectomy specimens using a 3-D computer assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was shown to be superior to the traditional sextant biopsy. This pattern includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in a small cohort of patients. METHODS: We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. RESULTS: Of the 35 patients diagnosed with prostate cancer, 54.3% (19/35) were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7% (16/35) of patients were diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. CONCLUSIONS: Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the apex and mid portion of the gland are the most important.

Biopsy, Needle↗