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Biomedical subjects

J Weng

Publications and source records attributed to J Weng.

At least 19 recordsLinked to original sources

Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).

BACKGROUND AND PURPOSE: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. KEY RESULTS: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. CONCLUSIONS AND IMPLICATIONS: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.

Animals↗

Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes.

AIMS: To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin, thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened using the single-strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5 of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.

Adolescent↗

Characterization of titanium surfaces with calcium and phosphate and osteoblast adhesion.

The titanium surfaces containing calcium, phosphate ions and the carbonate apatite were characterized. The effect of surface chemistry on the initial rabbit osteoblast response on these surfaces was investigated. The cell count and alkaline phosphatase (ALP) specific activity assay were used for biochemical analyses. Scanning electron microscopy was used for morphology observation and in particular X-ray photoelectron spectroscopy (XPS) for surface chemistry characterization. The number of cells adhering to the apatite coating surface was the maximum, the number of cells on the surface containing calcium without phosphate ions was higher than that containing phosphate without calcium, and the number on the unmodified titanium surface was the least. The osteoblasts cultured on the apatite surface exhibited the highest ALP specific activity, next were the ones on the surface containing solely calcium, the lowest were on the unmodified titanium surface. On the substrate surfaces removed of adhered cells, the order of nitrogen amounts detected by XPS was consistent with ones of ALP specific activity and cell number, except for the unmodified titanium surface. For the substrate surfaces removed of adhered osteoblasts, XPS analysis showed that calcium and phosphorous amounts decreased during cell adhesion. After cell culture the Ca2p binding energy (BE) values for apatite coating and the surface containing solely calcium were similar to those of the two surfaces adsorbed bovine serum albumin (BSA). The P2p BE values for the surfaces containing phosphate ions, including the apatite coating and the surface containing solely phosphate ions, showed the same change. But after cell culture the decrease of the P2p BE value for the coating surface was larger than the one for the surface containing solely phosphate ions. Considering the bovine serum albumin adsorption on the same samples, these results indicated that calcium ions on titanium surfaces play a more important role than phosphate ions in initial interactions among culture medium, osteoblasts and titanium surfaces. On the apatite coating surface, calcium ions are active sites for osteoblast adhesion, while calcium and phosphate ions co-exist on titanium surfaces, the former promotes the osteoblast adhesion onto the phosphate sites on titanium surfaces. The cell adhesion was a complicated biological and chemical process relating to surface several elements similar to protein adsorption.

Animals↗

Evaluation of the expression of collagen type I in porous calcium phosphate ceramics implanted in an extra-osseous site.

The aim of the present study is to demonstrate the newly formed tissue in calcium phosphate (Ca/P) ceramics after extra-osseous implantation by histological and immunohistochemistry (IHC) methods. Synthesis porous Ca/P ceramics without adding any growth factor and living cell were implanted in the dorsal muscle of dogs for 1 and 2 months. Undecalcified and decalcified sections were stained by hematoxylin and eosin (H&E), and IHC, respectively. The histological results showed the beginning of osteogenesis and angiogenesis after being implanted for 1 month and the obvious new bone formation after being implanted for 2 months. IHC were conducted via the avidin-biotin peroxidase complex (ABC) method and the primary antibody was collagen type I. IHC results indicated that collagen type I was expressed within osteoblast-like cells and newly formed bone-like tissue in Ca/P ceramics after 1 month, and in the mineralized matrix of newly formed bone and osteoblasts, some osteocytes and some lacunae after 2 months. No cartilage and chondrocytes were observed in the histological and IHC-stained sections. Evidence of intramembranous osteogenesis was confirmed.

Animals↗

Characterization of surface oxide films on titanium and adhesion of osteoblast.

The relationship between surface characteristics of titanium and initial interactions of titanium-osteoblasts was investigated. Titanium plates were heat-treated in different oxidation atmospheres. The third passage rabbit osteoblasts were cultured on the titanium plates for 24h. After the heat-treatment, the crystal structure of the surface oxide films on titanium was identified using X-ray diffractometer and X-ray photoelectron spectroscopy (XPS). The surface roughness of titanium was measured with a profilometer. The surface energy was obtained by measurement of contact angles and calculation with Owens-Wendt-Kaeble's equation. The amount of surface hydroxyl (OH)(s) groups was examined using XPS. The change of binding energy of the some elements on the substrate surface suggested that the interactions between the cells and the titanium involved chemical reactions. The greater surface roughness, higher surface energy and more surface hydroxyl groups resulted in greater numbers of adhered osteoblasts and higher cell activity. Compared to the acidic hydroxyl (OH)(a) groups in (OH)(s) groups and the dispersion component of the total surface energy, the basic hydroxyl (OH)(b) groups and the polar component play more important roles in the osteoblast-titanium interaction.

Alkaline Phosphatase↗

Relationship between blood pressure and finger photoplethysmographic waveform during oxygen desaturation test: a model fitting approach.

UNLABELLED: A modified 3-element windkessel model was applied to study the relationship between brachial arterial blood pressure and the photoplethysmographic waveform from pulse oximeters. Data were recorded from 12 healthy volunteers who underwent the oxygen desaturation study. During about 30 minutes recording period, the SpO2 value was regulated down till about 70%. After preprocessing, singular value decomposition (SVD) algorithm was then used to get the best fit of the model parameters. RESULT: the fitting error (RMSE) was 1.07 +/- 0.48 mmHg. The time constant of the model shown significant difference between the highest and the lowest saturation group.

Adult↗

Functional consequences of mutations in the MODY4 gene (IPF1) and coexistence with MODY3 mutations.

AIMS/HYPOTHESIS: The aim of this study was to examine the putative role of mutations in the insulin promoter 1 (IPF1) gene in early-onset diabetes. METHODS: We carried out mutation screening of the IPF1 gene in 115 Scandinavian families with at least two members with onset of diabetes younger than 40 years. The allele frequencies were also tested in 183 unrelated patients with late-onset Type II (non-insulin-dependent) diabetes mellitus and in 92 non-diabetic control subjects. RESULTS: Two novel IPF1 variants (G212R and P239Q) and one previously reported (D76N) IPF1 variant were identified in the 115 families (3.5%). The D76N variant was found in one MODY3 family (S315fsinsA of HNF1alpha) and also in two families with late-onset Type II diabetes. The P239Q variant was identified in two families with early-onset diabetes including one with MODY3 (R272C of HNF1alpha) and in three families with late-onset Type II diabetes. Despite the fact that the variants did not segregate completely with diabetes, the non-diabetic carriers of the IPF1 variants had increased blood glucose concentrations (p < 0.05) and reduced insulin:glucose ratios (p < 0.05) during an oral glucose tolerance test compared with non-diabetic family members without these variants. In addition, when the G212R and P239Q variants were expressed in cells without IPF1 i.e.. Nes2y cells, both variants showed about a 50% reduction in their ability to activate insulin gene transcription compared to wild-type IPF1, as measured by reporter gene assay. CONCLUSION/INTERPRETATION: Although mutations in the IPF-1 gene are rare in early- (3.5 %) and late-onset (2.7 % ) Type II diabetes, they are functionally important and occur also in families with other MODY mutations.

Aged↗

Three-dimensional sound localization from a compact non-coplanar array of microphones using tree-based learning.

One of the various human sensory capabilities is to identify the direction of perceived sounds. The goal of this work is to study sound source localization in three dimensions using some of the most important cues the human uses. In an attempt to satisfy the requirements of portability and miniaturization in robotics, this approach employs a compact sensor structure that can be placed on a mobile platform. The objective is to estimate the relative sound source position in three-dimensional space without imposing excessive restrictions on its spatio-temporal characteristics and the environment structure. Two types of features are considered, interaural time and level differences. Their relative effectiveness for localization is studied, as well as a practical way of using these complementary parameters. A two-stage procedure was used. In the training stage, sound samples are produced from points with known coordinates and then are stored. In the recognition stage, unknown sounds are processed by the trained system to estimate the 3D location of the sound source. Results from the experiments showed under +/-3 degrees in average angular error and less than +/-20% in average radial distance error.

Computer Systems↗

Effect of excess degradable intake protein on early embryonic development, ovarian steroids, and blood urea nitrogen on days 2, 3, 4, and 5 of the estrous cycle in mature ewes.

Two trials were conducted to determine whether feeding excess degradable intake protein (DIP) during a synchronized estrous cycle and the first 5 d after breeding alters early embryonic development, ovarian steroids, or BUN concentrations in ewes. Ewes were group-fed in Trial 1 (T1) and individually fed in Trial 2 (T2) either 100 (control; T1, n = 15; T2, n = 12) or 200% (high-protein; T1, n = 16; T2, n = 12) of the NRC protein recommendation for maintenance during a synchronized estrous cycle until surgery in the next cycle. Ampullae (AMP), isthmi (IST), and uterine horns (UT) of high-protein and control ewes were removed on d 2 (T1), 3 (T2), 4 (T1), or 5 (T2) after breeding. In T1, jugular blood samples were taken once daily starting on d 2 of the synchronized cycle, and in T2 on d 2, 9, 15, 16, and 17, and in both trials from estrus (d 0) to the day of surgery. Ampullae, IST, and UT flushings were examined microscopically for the presence of embryos, embryo condition, and embryo cell number. There was no trial x treatment interaction (P > or = 0.10), so data for both trials were pooled. Concentrations of BUN were higher (P < 0.05) in high-protein-fed ewes than in control ewes during the synchronized cycle and the first 5 d of the next cycle. Progesterone concentrations of the synchronized cycle did not differ (P > 0.10) between treatments. During the first 5 d of the next cycle, estradiol-17beta concentrations were lower (P = 0.06) in high-protein-fed than in control ewes. Progesterone increased (P < 0.05) to higher concentrations by d 5 in high-protein-fed ewes than in control ewes. More (P < 0.05) embryos were found in AMP of high-protein-fed ewes than in AMP of control ewes on d 4. Fewer (P = 0.05) embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 4. More embryos were found in UT of high-protein-fed ewes than in UT of control ewes on d 5. Fewer (P = 0.05) embryos were found in IST of high-protein ewes than in the IST of control ewes on d 5. Embryos of high-protein-fed ewes had more (P < 0.05) cells than embryos from control fed ewes on d 5. Feeding ewes excess DIP protein during an estrous cycle and the first 5 d after breeding initially impeded embryo transport; thereafter, embryo transport and development through the oviduct was accelerated.

Animals↗

Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications for involvement of ABCR in age-related macular degeneration.

PURPOSE: To examine the ocular phenotype in mice heterozygous for a null mutation in the abcr gene. METHODS: Retinas and retinal pigment epithelia (RPE) were prepared from wild-type, abcr+/-, and abcr-/- mice. Fresh tissues were homogenized and analyzed by normal phase high-performance liquid chromatography (HPLC) for the presence of retinoids and phospholipids. In another study, fixed tissues were sectioned and analyzed by light and electron microscopy. Finally, anesthetized mice were studied by electroretinography (ERG) at different times after exposure to strong light. RESULTS: A2E, the major fluorophore of lipofuscin, and its precursors, A2PE-H(2) and A2PE, were approximately fourfold more abundant in 8-month-old abcr+/- than in the wild-type retina and RPE. The levels of these substances in abcr+/- mice were approximately 40% those in abcr-/- mice. Lipofuscin pigment-granules were also visible in abcr+/- RPE cells by electron microscopy. Accumulation of A2PE-H(2) and A2E in abcr+/- retina and RPE, respectively, was strongly dependent on light exposure. Heterozygous mutants also exhibited delayed recovery of rod sensitivity by ERG. This delay was correlated with elevated levels of all-trans-retinaldehyde (all-trans-RAL) in retina after a photobleach and was not caused by a reduction in quantum-catch due to depletion of 11-cis-retinaldehyde (11-cis-RAL). CONCLUSIONS: Partial loss of the ABCR or rim protein is sufficient to cause a phenotype in mice similar to recessive Stargardt's disease (STGD) and age-related macular degeneration (AMD) in humans. These data are consistent with the suggestion that the STGD carrier-state may predispose to the development of AMD.

ATP-Binding Cassette Transporters↗

An automated fluorescent single strand conformation polymorphism technique for high throughput mutation screening.

OBJECTIVE: To develop a high throughput mutational detection method by multiple fluorescence-labeled polymerase chain reaction (PCR) products. METHODS: A total of 27 known mutations including 22 substitutions, 3 insertions (1, 2 and 7 bp) and 2 deletions (1 and 2 bp) in the hepatocyte nuclear factor (HNF)-4 alpha, glucokinase and HNF-1 alpha genes were tested. During nested PCR, amplified fragments were labeled with three fluorescent dyes. PCR products were visualized with an ABI-377 fluorescence sequencer using 5% glycerol or 10% sucrose in non-denaturing gel conditions. RESULTS: Twenty-five of 27 variants (93%) could be detected by combining 5% glycerol and 10% sucrose gel matrix conditions. Twenty-two of 27 (82%) and 18 of 27 (67%) variants were identified using 5% glycerol and 10% sucrose conditions, respectively. CONCLUSION: This fluorescence-based PCR single strand conformation polymorphism technique represents a simple, non-hazardous, time-saving and sensitive method for high throughput mutation detection.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

[The effect of epidermal growth factor on the pathologic changes of gastric mucosa in SD rats with chronic atrophic gastritis].

OBJECTIVE: To study the effect of epidermal growth factor (EGF) on the pathologic changes of gastric mucosa in rats with chronic atrophic gastritis(CAG). METHODS: The established rat models of CAG were divided into therapy group and control group. The rats in the therapy group received EGF 10 microg/kg subcutaneously (SC), whereas these in the control group the same volume of normal saline SC. 12 weeks later, all rats were killed by cervical dislocation and their gastric mucosa were examined with microscope. RESULTS: The grade of inflammatory cell infiltration in the therapy group was lower than that in the control group (P < 0.01). The thickness of gastric mucosal gland layer was (215.0 +/- 20.7) microm in the therapy group and (139.2 +/- 13.8) microm in the control group (P < 0.01). The ratio of the thickness of gastric mucosal glands and muscularis mucosa(L(1)/L(2)) was 2.70 +/- 0.34 in the therapy group and 1.27 +/- 0.27 in the control group (P < 0.01). The number of gastric glands in 1 mm length of mucosal layer was 26.20 +/- 1.27 in the therapy group and 19.90 +/- 1.78 in the control group (P < 0.01). In the therapy group, the gastric glands were rearranged in order, without signs of malignant proliferation. The width of the expression of proliferating cell nuclear antigen (PCNA ) of gastric mucosa was higher in the therapy group than in the control group [(77.70 +/- 4.16) microm vs (54.40 +/- 4.54) microm, P < 0.01]. CONCLUSIONS: EGF played a therapeutic role in reversing the gastric mucosal atrophy of the rats with CAG. It promoted the expression of PCNA, which induced a protective proliferation of the gastric mucosal lesions in the rats with CAG.

Animals↗

[The characteristics of bcl-2 and PCNA expression in the lens epithelium of human being].

OBJECTIVE: To investigate the characteristics of bcl-2 (gene inhibiting apoptosis) and proliferating cell nuclear antigen (PCNA) expression and their relation to the proliferation of lens epithelium. METHODS: The expression of bcl-2 and PCNA were detected by immunohistochemical streptavidin-peroxidase (SP) method. RESULTS: The expression of bcl-2 and PCNA in the lens epithelium of fetus and children was higher than that of the elderly, especially in the region of the lens equator. CONCLUSION: The over-expression of bcl-2 and PCNA in the lens epithelium of fetus and children suggests that bcl-2 and PCNA might be related to the development of cataract.

Adolescent↗

[Spectral analysis on self-assembly ultrathin film of polyaminobenzonitrile].

Poly(p-amino benzonitrile) (PABN) was synthesized by the method of plasma polymerization. With the self-assembly techniques, an ultrathin film of PABN and NaPSS (sodium polystyrene sulfonate) was successfully prepared. UV-Visible absorption spectra revealed that the film is very regular. This is a new method to prepare ultrathin film of PABN.

Macromolecular Substances↗

Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration.

Increased accumulation of lipofuscin in cells of the retinal pigment epithelium (RPE) is seen in several forms of macular degeneration, a common cause of blindness in humans. A major fluorophore of lipofuscin is the toxic bis-retinoid, N-retinylidene-N-retinylethanolamine (A2E). Previously, we generated mice with a knockout mutation in the abcr gene. This gene encodes rim protein (RmP), an ATP-binding cassette transporter in rod outer segments. Mice lacking RmP accumulate A2E in RPE cells at a greatly increased rate over controls. Here, we identify three precursors of A2E in ocular tissues from abcr-/- mice and humans with ABCR-mediated recessive macular degenerations. Our results corroborate the scheme proposed by C. A. Parish, M. Hashimoto, K. Nakanishi, J. Dillon & J. Sparrow [Proc. Natl. Acad. Sci. USA (1998) 95, 14609-14613], for the biosynthesis of A2E: (i) condensation of all-trans-retinaldehyde (all-trans-RAL) with phosphatidylethanolamine to form a Schiff base; (ii) condensation of the amine product with a second all-trans-RAL to form a bis-retinoid; (iii) oxidation to yield a pyridinium salt; and (iv) hydrolysis of the phosphate ester to yield A2E. The latter two reactions probably occur within RPE phagolysosomes. As predicted by this model, formation of A2E was completely inhibited when abcr-/- mice were raised in total darkness. Also, once formed, A2E was not eliminated by the RPE. These data suggest that humans with retinal or macular degeneration caused by loss of RmP function may slow progression of their disease by limiting exposure to light. The precursors of A2E identified in this study may represent pharmacological targets for the treatment of ABCR-mediated macular degeneration.

ATP-Binding Cassette Transporters↗

micro-Terephthalato-bis[bis(1,10-phenanthroline)copper(I)] diperchlorate.

The title compound, [Cu(2)(C(8)H(4)O(4))(C(12)H(8)N(2))(4)](ClO(4))(2), was prepared from the hydrothermal reaction of CuCl(2), 1,4-dicyanobenzene, 1,10-phenanthroline and water at 443 K. The compound is a dimer in which the cation lies about an inversion center. The terephthalate moiety acts as a bridging ligand and the phenanthrolines as terminal ligands. The unique Cu atom is coordinated by two O and four N atoms in a distorted octahedral geometry, with Cu-O distances of 1.955 (2) and 2.815 (2) A, and Cu-N distances of 2.008 (2) to 2.216 (2) A.

Journal Article↗