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Biomedical subjects

B Zhang

Publications and source records attributed to B Zhang.

At least 37 records · Page 2Linked to original sources

Cortical effects of brief daily periods of unrestricted vision during early monocular form deprivation.

Experiencing daily brief periods of unrestricted vision during early monocular form deprivation prevents or reduces the degree of resulting amblyopia. To gain insight into the neural basis for these "protective" effects, we analyzed the monocular and binocular response properties of individual neurons in the primary visual cortex (V1) of macaque monkeys that received intermittent unrestricted vision. Microelectrode-recording experiments revealed significant decreases in the proportion of units that were dominated by the treated eyes, and the magnitude of this ocular dominance imbalance was correlated with the degree of amblyopia. The sensitivity of V1 neurons to interocular spatial phase disparity was significantly reduced in all treated monkeys compared with normal adults. With unrestricted vision, however, there was a small but significant increase in overall disparity sensitivity. Binocular suppression was prevalent in monkeys with constant form deprivation but significantly reduced by the daily periods of unrestricted vision. If neurons exhibited consistent responses to stimulation of the treated eye, monocular response properties obtained by stimulation of the two eyes were similar. These results suggest that the observed protective effects of brief periods of unrestricted vision are closely associated with the ability of V1 neurons to maintain their functional connections from the deprived eye and that interocular suppression in V1 may play an important role in regulating synaptic plasticity of these monkeys.

Animals↗

Cyclic AMP and cyclic GMP suppress TNFalpha-induced hepatocyte apoptosis by inhibiting FADD up-regulation via a protein kinase A-dependent pathway.

Cyclic AMP (cAMP) and cyclic GMP (cGMP) suppress apoptosis in many cell types, including hepatocytes. We have previously shown that membrane-permeable cAMP and cGMP analogs attenuate tumor necrosis factor alpha plus actinomycin D (TNFalpha/ActD)-induced apoptosis in hepatocytes at a step upstream of caspase activation and cytochrome c release. Recently we have also shown that FADD levels increase 10 folds in response to TNFalpha/ActD. Therefore we hypothesized that cAMP and cGMP would inhibit FADD upregulation. We show here that cyclic nucleotide analogs dibutyryl cAMP (db-cAMP) and 8-bromo-cGMP (Br-cGMP) inhibit cell death and the cleavages of multiple caspases including caspase-10, -9, -8, -3, and -2, as well as suppress FADD protein up-regulation in TNFalpha/ActD-induced apoptosis. The inhibitory effects of cAMP were seen at lower concentrations than cGMP. Both cAMP and cGMP prevented FADD overexpression and cell death in hepatocytes transfected with the FADD gene. A protein kinase A (PKA) inhibitor, KT 5720, reversed the inhibition of FADD protein levels induced by cAMP or cGMP. In conclusion, our findings indicate that cAMP and cGMP prevent TNFalpha/ActD-induced apoptosis in hepatocytes and that this occurs in association with a near complete inhibition of the upregulation of FADD via a PKA-dependent mechanism.

Animals↗

Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus.

AIM: The ability of the incretin mimetic exenatide to improve glycaemic control and reduce body weight was assessed over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with maximally effective doses of metformin. METHODS: In this interim 82-week analysis, 150 (total cohort) of an eligible population of 183 patients opted to continue exenatide treatment in an uncontrolled open-label extension of a 30-week double-blind, placebo-controlled trial. Of these, 92 patients (completer cohort) achieved 82 weeks of exenatide therapy. Patients continued metformin throughout the study. RESULTS: At the end of the placebo-controlled trial, exenatide resulted in an haemoglobin A1c (HbA1c) reduction from baseline of -1.0 +/- 0.1% (mean +/- SE) (exenatide treatment arms), with durable HbA1c reductions after 82 weeks of -1.3 +/- 0.1%. The percent of patients who achieved HbA1c < or = 7% at weeks 30 and 82 was 46 and 59% respectively. After 30 weeks, exenatide caused a reduction in weight from baseline of -3.0 +/- 0.6 kg, with a progressive reduction in weight of -5.3 +/- 0.8 kg after 82 weeks. In addition, exenatide treatment produced clinically significant improvements in cardiovascular risk factors after 82 weeks. The most frequent adverse event after 30 and 82 weeks of exenatide was nausea, which was generally of mild-or-moderate intensity. It decreased in incidence after initiation in the controlled trial and the uncontrolled open-label extension. Hypoglycaemia was rare, with no severe events. CONCLUSION: Exenatide was generally well tolerated, producing a durable reduction in HbA1c and a progressive reduction in weight over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with metformin.

Adult↗

Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.

AIM: Exenatide, an incretin mimetic for the adjunct treatment of type 2 diabetes (DM2), reduced A1C and weight in 30-week placebo-controlled trials. This analysis examined the effects of exenatide on glycaemic control and weight over an 82-week period in patients with DM2 unable to achieve adequate glycaemic control with sulphonylurea (SU) and/or metformin (MET). METHODS: This interim analysis is of 314 patients who received exenatide in the 30-week placebo-controlled trials and subsequently in 52 weeks of open-label uncontrolled extension studies for 82 weeks of exenatide in total. Patients continued their SU and/or MET regimens throughout. RESULTS: Patients completed 82 weeks of exenatide treatment [n = 314, 63% M, age 56 +/- 10 years, weight 99 +/- 21 kg, body mass index 34 +/- 6 kg/m2, A1C 8.3 +/- 1.0% (mean +/- SD)]. Reduction in A1C from baseline to week 30 [-0.9 +/- 0.1% (mean +/- SE)] was sustained to week 82 (-1.1 +/- 0.1%), with 48% of patients achieving A1C < or = 7% at week 82. At week 30, exenatide reduced body weight (a secondary endpoint) from baseline (-2.1 +/- 0.2 kg), with progressive reduction at week 82 (-4.4 +/- 0.3 kg). Similar results were observed for the intent-to-treat population (n = 551), with reductions in A1C and weight at week 82 of -0.8 +/- 0.1% and -3.5 +/- 0.2 kg respectively. The 82-week completer cohort showed statistically significant improvement in some cardiovascular risk factors. The most frequent adverse events were generally mild-to-moderate nausea and hypoglycaemia. CONCLUSION: In summary, 82 weeks of adjunctive exenatide treatment in patients with DM2 treated with SU and/or MET resulted in sustained reduction in A1C and progressive reduction in weight, as well as improvement in some cardiovascular risk factors.

Adolescent↗

Study of noise propagation and the effects of insufficient numbers of projection angles and detector samplings for iterative reconstruction using planar-integral data.

A rotating slat collimator can be used to acquire planar-integral data. It achieves higher geometric efficiency than a parallel-hole collimator by accepting more photons, but the planar-integral data contain less tomographic information that may result in larger noise amplification in the reconstruction. Lodge evaluated the rotating slat system and the parallel-hole system based on noise behavior for an FBP reconstruction. Here, we evaluate the noise propagation properties of the two collimation systems for iterative reconstruction. We extend Huesman's noise propagation analysis of the line-integral system to the planar-integral case, and show that approximately 2.0(D/dp) SPECT angles, 2.5(D/dp) self-spinning angles at each detector position, and a 0.5dp detector sampling interval are required in order for the planar-integral data to be efficiently utilized. Here, D is the diameter of the object and dp is the linear dimension of the voxels that subdivide the object. The noise propagation behaviors of the two systems are then compared based on a least-square reconstruction using the ratio of the SNR in the image reconstructed using a planar-integral system to that reconstructed using a line-integral system. The ratio is found to be proportional to the square root of F/D, where F is a geometric efficiency factor. This result has been verified by computer simulations. It confirms that for an iterative reconstruction, the noise tradeoff of the two systems is not only dependent on the increase of the geometric efficiency afforded by the planar projection method, but also dependent on the size of the object. The planar-integral system works better for small objects, while the line-integral system performs better for large ones. This result is consistent with Lodge's results based on the FBP method.

Artifacts↗

Effects of chemotherapy and/or radiotherapy on survivin expression in ovarian cancer.

Survivin, a member of apoptosis protein inhibitor family, is upregulated in various malignancies, especially in chemotherapy- and/or radiation-resistant cell lines. In this study, the correlation between the level of survivin expression and degree of apoptosis was investigated in three ovarian cancer lines (two chemoresistant cell lines SKOV-3 and OVCAR-3, as well as one chemosensitive cell line OV2008) treated with 5 microg/ml of cisdiamminedichloroplatinum (cisplatin, CDDP) for 24 h, 2 Gy of (60)Co irradiation, or 5 microg/ml CDDP for 3 h plus 2 Gy of (60)Co, respectively. We also evaluated the survivin mRNA abundance in patients with advanced ovarian cancers during CDDP treatment. In the ovarian cancer cell lines, survivin mRNA abundance and protein contents were significantly increased after the treatments while the apoptotic rates did not change in SKOV-3 and OVCAR-3. Moreover, in OVA2008 cells the expression of survivin decreased and the apoptotic rate significantly increased after CDDP and combined treatments. Survivin mRNA was not detectable in normal ovarian tissues and benign ovarian tumors. However, it was observed in the resected tumor specimens from 20 patients with advanced ovarian cancer. These results suggested that survivin may play an important role in the resistance to chemotherapy and radiotherapy in ovarian cancer cell lines and in the progression of ovarian tumors. Survivin may also provide a pivotal prognostic implication for epithelial ovarian carcinomas.

Adult↗

Relationship between HPV16/18 E6 and 53, 21WAF1, MDM2, Ki67 and cyclin D1 expression in esophageal squamous cell carcinoma: comparative study by using tissue microarray technology.

AIM: To investigate the role of human papillomavirus (HPV) HPV16/18 E6 oncogene in the carcinogenesis of esophageal cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarray (TMA) block was constructed from 60 cases of paraffin-embedded ESCC tissues and pair-matched controls (adjacent normal epithelium). Immunohistochemistry (IHC) methods were applied to detect the expression of HPV16/18 E6, p53, p21(WAF1), MDM2, Ki67 and cyclin D1 proteins on TMA slides. In situ hybridization (ISH) targeting HPV gene was also used. RESULTS: In ESCC samples, 18.3% (11/60) were revealed HPV16/18 E6 positive by IHC, while 40.0% (24/60) HPV positive by ISH; HPV16/18 E6 expression was significantly higher than that of control samples. In ESCC samples, the expressions of p53, p21(WAF1), Cyclin D1, MDM2 and Ki67 were recorded in 60.0% (36/60), 40.0% (24/60), 51.7% (31/60), 65.0% (39/60) and 88.3% (53/60) cases respectively, In ESCC samples, p53, MDM2 and Ki67 expression correlated with the HPV16/18 E6 expression (p less, similar 0.01), p21(WAF1) expression - with these of MDM2 and cyclin D1 (p less, similar 0.01) whilst expression of Ki67 - with ESCC grade (p less, similar 0.01). CONCLUSION: HPV might be one of etiological factor of esophageal carcinoma in Shantou, China. p53, MDM2 proteins may play important roles in the pathogenesis of HPV-associated ESCC.

Adult↗

An origin for short gamma-ray bursts unassociated with current star formation.

Two short (< 2 s) gamma-ray bursts (GRBs) have recently been localized and fading afterglow counterparts detected. The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual gamma-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations. The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 (refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2-3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts--the coalescence of binary systems of neutron stars or a neutron star-black hole pair--are the progenitors of short bursts.

Journal Article↗

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal Article↗

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

Journal Article↗

Bright x-ray flares in gamma-ray burst afterglows.

Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.

Journal Article↗

Matrix concentration of insulin-like growth factor I (IGF-I) is negatively associated with biomechanical properties of human tibial cancellous bone within individual subjects.

Insulin-like growth factor-I (IGF-I), abundant in bone matrix, is believed to play an important role during bone development and remodeling. To our knowledge, however, few studies have addressed the relationship between the concentration of IGF-I in bone matrix and the biomechanical properties of bone tissue. In this study, forty-five cylindrical specimens of cancellous bone were harvested from six human tibiae and scanned using micro-computed tomography (microCT). The bone volume fraction (BV/TV) was calculated from three-dimensional (3D) microCT images. Mechanical tests were then performed on a servohydraulic testing system to determine the strength and stiffness of cancellous bone. Following mechanical testing, the concentration of IGF-I in bone matrix was measured by using an enzyme-linked immunoabsorbent assay (ELISA). Within each subject, the concentration of IGF-I in bone matrix had significant (P<0.01) negative correlations with the bone volume fraction, strength, and stiffness of cancellous bone. In particular, the anterior quadrant of the proximal tibia was significantly (P<0.02) greater in IGF-I matrix concentration and marginally significantly lower in strength (P=0.053) and stiffness (P=0.059) than the posterior quadrant. The negative correlations between the cancellous bone matrix concentration of IGF-I and cancellous bone biomechanical properties within subjects found in this study may help us understand the variation of the biomechanical properties of cancellous bone in proximal human tibiae.

Biomechanical Phenomena↗

Amorphous metallic plastic.

We report cerium-based bulk metallic glasses with an exceptionally low glass transition temperature Tg, similar to or lower than that of many polymers. We demonstrate that, in near-boiling water, these materials can be repeatedly shaped, and can thus be regarded as metallic plastics. Their resistance to crystallization permits extended forming times above Tg and ensures an adequate lifetime at room temperature. Such materials, combining polymerlike thermoplastic behavior with the distinctive properties of metallic glasses, are highly unusual for metallic alloys and have great potential in applications and can also facilitate studies of the supercooled liquid state.

Journal Article↗

Do satellites detect trends in surface solar radiation?

Long-term variations in solar radiation at Earth's surface (S) can affect our climate, the hydrological cycle, plant photosynthesis, and solar power. Sustained decreases in S have been widely reported from about the year 1960 to 1990. Here we present an estimate of global temporal variations in S by using the longest available satellite record. We observed an overall increase in S from 1983 to 2001 at a rate of 0.16 watts per square meter (0.10%) per year; this change is a combination of a decrease until about 1990, followed by a sustained increase. The global-scale findings are consistent with recent independent satellite observations but differ in sign and magnitude from previously reported ground observations. Unlike ground stations, satellites can uniformly sample the entire globe.

Journal Article↗

GeneKeyDB: a lightweight, gene-centric, relational database to support data mining environments.

BACKGROUND: The analysis of biological data is greatly enhanced by existing or emerging databases. Most existing databases, with few exceptions are not designed to easily support large scale computational analysis, but rather offer exclusively a web interface to the resource. We have recognized the growing need for a database which can be used successfully as a backend to computational analysis tools and pipelines. Such database should be sufficiently versatile to allow easy system integration. RESULTS: GeneKeyDB is a gene-centered relational database developed to enhance data mining in biological data sets. The system provides an underlying data layer for computational analysis tools and visualization tools. GeneKeyDB relies primarily on existing database identifiers derived from community databases (NCBI, GO, Ensembl, et al.) as well as the known relationships among those identifiers. It is a lightweight, portable, and extensible platform for integration with computational tools and analysis environments. CONCLUSION: GeneKeyDB can enable analysis tools and users to manipulate the intersections, unions, and differences among different data sets.

Algorithms↗