From transcription regulation to cell cycle checkpoint.
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Biomedical subjects
Publications and source records attributed to H Xu.
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The transdermal delivery of ondansetron hydrochloride (ON) solution in propylene glycol (PG) with a widely used penetration enhancer, oleic acid (OA), was studied in rats by a microdialysis sampling technique. Dialysate samples collected from the probe were directly injected into the HPLC system without any pre-treatment and no interference occurred in the blank sample. A good linearity between the standard concentrations and peak areas within the calibration range was achieved. In vivo recovery (32.52 +/- 1.8%) of the probe was assessed with the retrodialysis method, which was used to calculate the ON concentration in the dermis. Oleic acid at the concentrations of 2% and 5% (w/v) increased the steady-state delivery rate from 0.001 to 0.030 and 0.058 microg/h, respectively. OA proved to be an effective enhancer for transdermal delivery of ON in rats.
Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocularly enhances tolerance and protects from EAU we prepared mice that express half of the mouse IRBP gene, containing a potent uveitogenic epitope (residues 161 - 180), under control of MHC class II promoter. Transgene mRNA was detectable in many tissues. Transgenic protein was undetectable by conventional assays, but was detected in thymic tissue by lymphocyte proliferation assay after induction of the promoter. Transgenic mice challenged with p161 - 180 did not develop EAU and had reduced immunological responses, but remained susceptible to EAU induced by whole IRBP, that contains additional uveitogenic epitopes. Disease was also induced by wild type T cells specific to p161 - 180. Thus, extraocular expression of a privileged retinal antigen enhances self tolerance, supporting the notion that sequestration contributes to immune privilege. Exceedingly low levels of transgene expression result in tolerance that is both profound and epitope specific, implying anergy or deletion of the endogenous uveitogenic repertoire. The same level of expression is, however, insufficient to tolerize wild-type effector T cells in the periphery.
To investigate the methology and evaluate the clinical value of surface mode on three-dimensional ultrasonography (3DUS) in static anatomical structures, 62 patients with various diseases were studied. The equipment used here was Voluson 530D 3DUS imaging system and 3D volume transducer with frequency being 3.0-5.0 MHz. The 3DUS rendering method was surface mode. The results showed that: 1) Surface mode of 3DUS could demonstrate clearly the anatomical characteristics of the region-of-interest (ROI) and the inner wall of lesions or organs that contained fluid. The anatomic details, such as location, size, shape, and number of the ROI, could be visualized intuitively; 2) The outer anatomic features (e.g. contour, edge, configuration, etc.) of some organs or lesions surrounded by fluid could be displayed clearly. It could be concluded that surface mode on 3DUS could provide more diagnostic information than two-dimensional ultrasonography (2DUS) in some cases and could served as a beneficial supplement to 2DUS in clinical practice.
The value of the combined in-phase (IP) and opposed-phase (OP) T1-weighted (T1-W) breath-hold FLASH sequences for hepatic imaging, especially for fat content, was evaluated. Non-contrast-enhanced IP and OP T1-W GRE breath-hold images were obtained in 76 patients refereed for abdominal MRI at 1.5T. 76 patients were divided into three groups for analysis: (1) liver without mass (n = 8); (2) liver with hepatoma (n = 34); (3) liver with haemangioma or cyst (n = 34). Liver/spleen and liver/lesion signal-to-noise (SNR) and contrast-to-noise ratio (CNR) were assessed for lesion detection. Images between IP and OP sequences were compared quantitatively. The results showed that there was not statistically significant difference in liver/spleen and liver/lesion SNR between IP and OP sequences. In the patients with fatty infiltration, the OP sequences yielded substantially lower values for liver/spleen and liver/lesion SNR than those of the IP sequences. Furthermore, OP imaging showed fatty infiltration in 14 cases and demonstrated hyperintense peritumor rim in 4 cases. In 14 cases of fatty infiltration, many lesions were identified using IP images. The use of IP and OP GRE sequences provides complementary diagnostic information for hepatic lesions and fat content. Focal hepatic lesions may be obscured in the setting of fatty infiltration if only OP sequences are employed. A complete assessment of the liver with MR should include both IP and OP imaging.
A COntent-Based Retrieval Architecture (COBRA) for picture archiving and communication systems (PACS) is introduced. COBRA improves the diagnosis, research, and training capabilities of PACS systems by adding retrieval by content features to those systems. COBRA is an open architecture based on widely used health care and technology standards. In addition to regular PACS components, COBRA includes additional components to handle representation, storage, and content-based similarity retrieval. Within COBRA, an anatomy classification algorithm is introduced to automatically classify PACS studies based on their anatomy. Such a classification allows the use of different segmentation and image-processing algorithms for different anatomies. COBRA uses primitive retrieval criteria such as color, texture, shape, and more complex criteria including object-based spatial relations and regions of interest. A prototype content-based retrieval system for MR brain images was developed to illustrate the concepts introduced in COBRA.
A methodology based on the coupling of experimental design and a modified simplex method is proposed for the optimization of a new flow injection-kinetic system for the spectrophotometric determination of Os (IV) with m-acetylchlorophosphonazo, which has for the first time been used as chromogenic reagent in the quantitative analysis of this element. An orthogonal array design is utilized to design the experimental protocol, in which six variables are varied simultaneously, and obtain the initial simplex using 25 experiments. A modified simplex method is applied to continuously optimize the data of the orthogonal array design; the search for optimum conditions of 6 variables using the modified simplex method required only 25 experiments. The efficiency and simplicity of the coupling of the experimental design and the modified simplex method are attractive for the development of new analytical methods. The method has been applied to the determination of Os (IV) in a refined ore as well as in a secondary alloy and provided satisfactory results.
Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are composed of aggregated beta-amyloid (Abeta) 40/42(43) peptides. Evidence implicates a central role for Abeta in the pathophysiology of AD. Mutations in betaAPP and presenilin 1 (PS1) lead to elevated secretion of Abeta, especially the more amyloidogenic Abeta42. Immunohistochemical studies have also emphasized the importance of Abeta42 in initiating plaque pathology. Cell biological studies have demonstrated that Abeta is generated intracellularly. Recently, endogenous Abeta42 staining was demonstrated within cultured neurons by confocal immunofluorescence microscopy and within neurons of PS1 mutant transgenic mice. A central question about the role of Abeta in disease concerns whether extracellular Abeta deposition or intracellular Abeta accumulation initiates the disease process. Here we report that human neurons in AD-vulnerable brain regions specifically accumulate gamma-cleaved Abeta42 and suggest that this intraneuronal Abeta42 immunoreactivity appears to precede both NFT and Abeta plaque deposition. This study suggests that intracellular Abeta42 accumulation is an early event in neuronal dysfunction and that preventing intraneuronal Abeta42 aggregation may be an important therapeutic direction for the treatment of AD.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
An ab initio restricted Hartree-Fock calculation utilising the standard 6-31G basis set was used to calculate total energies after PM3 calculations of energy-optimised geometries for the five-membered alumino-silicate framework rings cluster for a total of ten T sites. Calculations have shown that in the absence of protons or other ions, the most favourable sites for 1A1, 2A1 and 3A1 substitution of Si are the T6, T1 and T9 sites respectively. With more Al atoms replacing Si in a cluster, T-O bond lengths and T-O-T angles show lengthening and sharpening trends respectively, which indicates that the structure is distorted to a more relaxed symmetry with Obr atoms moving outwards. The calculated bond lengths and angles have been shown to match the values observed in previous studies, including those for a four-membered alumino-silicate single ring cluster. Based on the optimised five-membered alumino-silicate framework rings model, a further ab initio HF calculation has been conducted on ring breakage for releasing Al(Q3) and Si(Q3) centres to form T(OH)4 and HOT(OM)3 tetrahedra under local and highly alkaline environment. The obtained results suggest that Al(Q3) compared with Si(Q3) breaks more readily with the exothermal reaction enthalpy being in excess of -244.4 kJ/mol, while the most reactive Si(Q3) centre shows an exothermal reaction enthalpy of only -33.8 kJ/mol. This indicates that Al dissolves in preference to Si in local environment. The dissolution mechanism of the five-membered Al-Si framework rings model in highly alkaline solutions has been suggested to be composed of an ion-pairing reaction and an interaction between the remaining broken ring cluster triple bond TOH and MOH.
In this study, we compared the sensitivity of non-periodically and periodically active neurons in chronically compressed dorsal root ganglion in rats to norepinephrine and sympathetic stimulation. Forty-nine of 58 (84.5%) neurons with non-periodic activity showed responses to norepinephrine, whereas only five of 48 (10.4%) neurons with periodic activity displayed any response. The dose-response relationship of norepinephrine to the irregular burst pattern neurons shifted towards the left significantly compared to that of the periodic activity neurons. Responses to norepinephrine became apparent in eight neurons after their periodic firing activity was transformed into the non-periodic firing activity through the increase in Ca(2+). Changes in the time-response curves indicate a higher sensitivity of irregular burst pattern neurons to sympathetic stimulation than the periodic activity neurons. Finally, deterministic dynamics contained within the interburst interval series for non-periodic activity were identified. From these results, we suggest that the non-periodic activity neurons have a higher adrenergic sensitivity than those displaying periodic activity, and that this sensitivity may depend on the deterministic chaos within its firing dynamic system.
Light responses of cone-driven horizontal cells were recorded intracellularly in the isolated superfused carp retina and the effects of gamma-aminobutyric acid (GABA) on signals from red-sensitive (R-) and short-wavelength-sensitive (S-) cones (green cones and/or blue cones) were studied. In the presence of a bright red (694 nm) background light, which substantially suppressed signal from R-cones, the responses of L-type horizontal cells (L-HCs) to 532-nm flashes, predominantly driven by the S-cone input, were potentiated by application of GABA. In contrast, the responses of these cells to 694-nm flashes driven by the R-cone input, were suppressed, when signal from S-cones was suppressed by a bright 532-nm background light. Both the effects could be reversed by co-application of bicuculline, suggesting the involvement of GABA(A) receptors. It was unlikely that the potentiation by GABA of the S-cone driven responses of the L-HCs was mediated by actions of GABA on the cone photoreceptors. The dual action of GABA persisted in the dopamine-depleted retina, indicating no involvement of the dopaminergic interplexiform cells. We speculate that this dual action may be partially due to differential modulation by GABA of different postsynaptic mechanisms respectively mediating signal transfer from R-cones and S-cones to L-HCs.
A novel assay is described for the identification and isolation of compounds that inhibit the transcription of genes involved in mycotoxin biosynthesis. The thin-layer chromatography-based assay was used to screen plant extracts for compounds that would inhibit the expression of the beta-glucuronidase reporter gene under the control of an aflatoxin biosynthesis gene promoter in Aspergillus parasiticus. The assay was used to track purification of an inhibitory compound, cp2, from extracts of black pepper (Piper nigrum). Cp2 did not inhibit mycelial growth or the expression of the beta-tubulin gene but did inhibit aflatoxin biosynthesis at the transcriptional level. Applications of cp2 to the control of mycotoxins are discussed.
IL-12 is a heterodimeric cytokine that is known to induce tumor regression and long-term antitumor immunity. Recombinant adeno-associated virus (rAAV) vectors are advantageous for gene therapy in that they lack pathogenicity in humans, infect dividing as well as nondividing cells, and show a broad range of infectivity. We constructed an rAAV vector expressing interleukin-12 (IL-12) for cancer immunotherapy studies in a mouse model by inserting murine IL-12 (mIL-12) p35 and p40 cDNAs into the plasmid pRep4 and inserting the encephalomyocarditis virus internal ribosomal entry site between the p35 and p40 cDNAs. The mIL-12 expression cassette containing the Rous sarcoma virus promoter and a simian virus 40 polyadenylation signal was subcloned into the AAV plasmid p008Sub/NeoR, which contains two AAV inverted terminal repeat sequences and the NeoR gene driven by the thymidine kinase promoter. rAAV virions (10(4) infectious particles/ml) were generated by cotransfection of rAAV-mIL-12 and a helper plasmid (pAAV/Ad) into 293 cells previously infected with adenovirus 5. After infection of D6 fibroblasts with rAAV-mIL-12, G418-resistant clones were isolated. Each of the 1D D6 clones isolated produced up to 5.2 ng/10(6) cells/48 hours of mIL-12 as determined by enzyme-linked immunosorbent assay. Induction of interferon-gamma, enhanced lymphocyte proliferation, and cytotoxicity assays confirmed biologically functional IL-12 production by the vector. This is the first report indicating that an rAAV vector expresses mIL-12, which can be used to model the effects of mIL-12 alone and/or in combination with other antitumor agents.