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Biomedical subjects

Y Gao

Publications and source records attributed to Y Gao.

At least 37 records · Page 2Linked to original sources

Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction.

OBJECTIVE: To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. PATIENTS AND METHODS: One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n=82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n=80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. RESULTS: Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. CONCLUSIONS: Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.

Aged↗

Characterization and expression analysis of TNF-related apoptosis inducing ligand (TRAIL) in grass carp Ctenopharyngodon idella.

TRAIL (Apo2 ligand) described as a type II transmembrane protein belonging to the TNF superfamily can induce apoptotic cell death in a variety of cell types. In the present study, a putative cDNA sequence encoding the 299 amino acids of TRAIL (GC-TRAIL) and its genomic organization were identified in grass carp Ctenopharyngodon idella. The predicted GC-TRAIL sequence showed 44 and 41% identities to chicken and human TRAILs, respectively. In a domain search, a tumor necrosis factor homology domain (THD) was identified in the C-terminal portion of TRAILs. The GC-TRAIL gene consists of five exons, with four intervening introns, spaced over approximately 4 kb of genomic sequence. Analysis of GC-TRAIL promoter region revealed the presence of a number of putative transcription factor binding sites, such as Sp1, NF-kappaB, AP-1, GATA, NFAT, HNF, STAT, P53 and IRF1 sequences which are important for the expression of other TNF family members. Phylogenetic analysis placed GC-TRAIL and the putative zebrafish (Danio rerio) TRAIL obtained from searching the zebrafish database into one separate cluster near mammalian TRAIL genes, but apart from the reported zebrafish TRAIL-like protein, indicating that the GC-TRAIL is an authentic fish TRAIL. Expression analysis revealed that GC-TRAIL is expressed in many tissues, such as in gills, liver, trunk kidney, head kidney, intestine and spleen.

Amino Acid Sequence↗

Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.

Drugs that antagonize D2-like receptors are effective antipsychotics, but the debilitating movement disorder side effects associated with these drugs cannot be dissociated from dopamine receptor blockade. The "atypical" antipsychotics have a lower propensity to cause extrapyramidal symptoms (EPS), but the molecular basis for this is not fully understood nor is the impact of inverse agonism upon their clinical properties. Using a cell-based functional assay, we demonstrate that overexpression of Galphao induces constitutive activity in the human D2-like receptors (D2, D3, and D4). A large collection of typical and atypical antipsychotics was profiled for activity at these receptors. Virtually all were D2 and D3 inverse agonists, whereas none was D4 inverse agonist, although many were potent D4 antagonists. The inverse agonist activity of haloperidol at D2 and D3 receptors could be reversed by mesoridazine demonstrating that there were significant differences in the degrees of inverse agonism among the compounds tested. Aripiprazole and the principle active metabolite of clozapine NDMC [8-chloro-11-(1-piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine] were identified as partial agonists at D2 and D3 receptors, although clozapine itself was an inverse agonist at these receptors. NDMC-induced functional responses could be reversed by clozapine. It is proposed that the low incidence of EPS associated with clozapine and aripiprazole used may be due, in part, to these partial agonist properties of NDMC and aripiprazole and that bypassing clozapine blockade through direct administration of NDMC to patients may provide superior antipsychotic efficacy.

Animals↗

Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity.

We developed a new class of vaccines, based on killed but metabolically active (KBMA) bacteria, that simultaneously takes advantage of the potency of live vaccines and the safety of killed vaccines. We removed genes required for nucleotide excision repair (uvrAB), rendering microbial-based vaccines exquisitely sensitive to photochemical inactivation with psoralen and long-wavelength ultraviolet light. Colony formation of the nucleotide excision repair mutants was blocked by infrequent, randomly distributed psoralen crosslinks, but the bacterial population was able to express its genes, synthesize and secrete proteins. Using the intracellular pathogen Listeria monocytogenes as a model platform, recombinant psoralen-inactivated Lm DeltauvrAB vaccines induced potent CD4(+) and CD8(+) T-cell responses and protected mice against virus challenge in an infectious disease model and provided therapeutic benefit in a mouse cancer model. Microbial KBMA vaccines used either as a recombinant vaccine platform or as a modified form of the pathogen itself may have broad use for the treatment of infectious disease and cancer.

Animals↗

Mercury depth profiles in river and marine sediments measured by the diffusive gradients in thin films technique with two different specific resins.

The diffusive gradients in thin films technique (DGT) was used to measure depth profiles of mercury in river and marine sediments in situ to a spatial resolution of 0.5 cm. Agarose gel was used as the diffusive gel in the DGT probes. Two different selective resins-Chelex 100 with iminodiacetic groups and Spheron-Thiol with thiol groups incorporated in the polyacrylamide resin gel-were tested. The different capture efficiencies of the two adsorbents enabled the fractions of mercury bound in different species in sediment pore water to be estimated. Mercury concentrations obtained by DGT with Spheron-Thiol resin were very similar to those obtained after centrifugation. This indicates that DGT with Spheron-Thiol resin reports on total dissolved mercury levels. The concentration of mercury measured by DGT with Chelex-100 resin was much lower (by a factor of 5-20) for the same sediment samples. Chelex-100 does not have such a high affinity to mercury as Spheron-Thiol, and so it only reports on the content of labile mercury species, such as inorganic ions and weak complexes. The content of labile mercury species in the river sediment was approximately 20% of the total dissolved mercury in pore water, whereas in marine sediment only 7% of the mercury was present as labile species.

Adsorption↗

Using pseudo amino acid composition to predict protein subcellular location: approached with Lyapunov index, Bessel function, and Chebyshev filter.

With the avalanche of new protein sequences we are facing in the post-genomic era, it is vitally important to develop an automated method for fast and accurately determining the subcellular location of uncharacterized proteins. In this article, based on the concept of pseudo amino acid composition (Chou, K.C. Proteins: Structure, Function, and Genetics, 2001, 43: 246-255), three pseudo amino acid components are introduced via Lyapunov index, Bessel function, Chebyshev filter that can be more efficiently used to deal with the chaos and complexity in protein sequences, leading to a higher success rate in predicting protein subcellular location.

Amino Acid Sequence↗

Tetramethylpyrazine inhibits ATP-activated currents in rat dorsal root ganglion neurons.

Tetramethylpyrazine (TMP) is one of the alkaloids contained in Ligustrazine which has been used in traditional Chinese medicine as an analgesic for injury and dysmenorrhea. ATP can elicit the sensation of pain. This study observed the effects of TMP on ATP-activated current (IATP) in rat DRG neurons. TMP (0.1-1 mM) concentration-dependently inhibited ATP (100 microM)-activated current in rat DRG neurons. The inhibitory time of ATP (100 microM)-activated current appeared at 15 s after preapplication of TMP and reached its peak at about 45 s. The dose-response curves for IATP in the absence and presence of 1 mM TMP showed that TMP (1 mM) shifted the concentration-response curve of IATP downward markedly and the two EC50 values were very close (75 vs. 82 microM), while the threshold value remained unchanged. Therefore, the inhibitory effect of TMP on IATP may be noncompetitive. TMP did not alter the reversal potential (0 mV) of ATP-activated current, indicating that the site of TMP action is on or near the exterior surface of channel protein and not within the channel pore. Externally applied TMP (1 mM) increases the inhibitory effect of chelerythrine (PKC inhibitor) contained in pipette solution on IATP. The site of TMP action may be the binding of TMP to an allosteric site on the large extracellular region of ATP receptor-ion channel complex (P2X receptors) or PKC site of the N-terminus of P2X receptors. The mechanism of TMP action may be the allosteric regulation via acting on the large extracellular region of ATP receptor-ion channel complex (P2X receptors) and promoting the phosphorylation of PKC site of the N-terminus of P2X receptors.

Action Potentials↗

Comparison of blood counts in splenic, renal and mesenteric arterial and venous blood in post-pubertal rabbits.

OBJECTIVES: To compare blood counts between arterial and venous blood to and from visceral organs and indirectly look into the function of the organs. METHODS: Splenic, renal and superior mesenteric arterial and venous blood samples were obtained from the arteries and veins in 38 post-pubertal rabbits and blood profile, including complete and differential blood counts, haemoglobin concentration and haematocrit, were measured with an automatic haematology analyser. RESULTS AND CONCLUSIONS: The rabbit spleen released a large amount of leucocytes (both lymphocytes and granulocytes) into the splenic venous blood (a venous increase of 33% in total leucocyte count), and also received more leucocytes (36-58% more in terms of concentration) from the artery than the kidney or intestine. Significantly fewer red blood cells were present in the renal venous blood than in the arterial blood (a venous reduction of 5% in erythrocyte count), but it remains to be clarified why and how the reduction was induced. More than 3-4% of water might be taken into the mesenteric venous blood during microcirculation (a venous reduction of 3-4% in erythrocyte-related parameters) and a significant number of leucocytes (mainly large leucocytes) in the mesenteric blood capillaries might migrate into the surrounding intestinal tissue (a venous reduction of 13% in leucocyte count).

Animals↗

Prolonged skin allograft survival in Scid mice reconstituted with isogeneic bone marrow stem cell antigen-1-positive cells and thymus tissue.

INTRODUCTION: Many studies indicate that tolerance induction is much more dependent on the maturation status of lymphocytes than the age of the animal. We hypothesized that direct persistent contact of bone marrow stem cells with graft alloantigen will result in tolerance to that antigen in the adult animal. MATERIAL AND METHODS: Severe combined immunodeficient mice (CB-17-Scid, H-2b) were reconstituted with isogeneic bone marrow stem cell antigen-1 (Sca-1)-positive cells and grafted with fetal thymus (BMSC-T), followed by transplant of allogeneic skin grafts from C57BL/6 (H-2d) mice. The control group include CB-17 non-Scid mice, CB-17-Scid mice, and CB-17 Scid mice pretransplanted with nonmodified isogeneic bone marrow cells and fetal thymus (BMC-T). RESULTS AND DISCUSSION: Skin allograft survival was significantly prolonged in the group pretransplanted with isogeneic BMSC-T compared the group of non-Scid mice and the group of Scid mice pretransplanted with BMC-T (59.6 days vs 7.1 days vs 11.7 days). In 2 of 10 mice pretransplanted with BMSC-T, the skin allografts transplanted immediately after BMSC-T survived for more than 100 days, but the third-party skin allografts transplanted at 100 days after BMSC-T transplant were rejected. The results suggest direct persistent contact of bone marrow Sca-1-positive cells with graft alloantigen may be a feasible approach to prolong allograft survival and induce tolerance in a small fraction of adult animals.

Animals↗

Microencapsulating hepatocytes.

BACKGROUND: Because standardization of the cell microencapsulation procedure has not yet been achieved, we performed hepatocyte microencapsulation using alginate (ALG)-poly-l-lysine (PLL)-ALG (APA) polymer. METHODS: Hepatocytes were microencapsulated using a binozzle air-jet droplet generator. Our study aims were to: (1) clarify how ALG concentration affects the quality of ALG beads; (2) determine how the PLL concentration affects the quality of microcapsules (MCs); (3) ascertain the influence of liquefaction time by sodium citrate (SC) on the quality of the MCs; (4) and clarify how temperature and solution pH, respectively, affect the viability of the hepatocytes inside the MCs. RESULTS: The concentration of ALG must be > or = 3% (w/v) to generate droplets with satisfactory homogeneity in size and roundness (P < .01). The total quantity of PLL molecules is the essential component for MCs (P < .01). As our results show, the numeric ratio of PLL (milligrams) to MCs (milliliters) is roughly 25:1. SC incubation for 8 minutes resulted in the proper thickness of the MC wall; however, the time varied according to the size of the MCs (P < .05). Temperature and pH, although both difficult to control, exerted great influences on cell viability: 4 degrees C and pH 7.2 were found to be optimal by this study (P < .05). CONCLUSIONS: Concentrations of ALG and PLL exerted decisive effects on the quality and strength of MCs. Higher concentrations were suggested. Because temperature and pH greatly affected cell viability, they must be properly monitored.

Alginates↗

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres.

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by UV/VIS spectrophotometry. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15 000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15 000, 20 000 and 30 000 were 62.75, 27.52 and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30 000 microspheres to 3.97% of PLGA 15 000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increase in oil phase and PVA concentration decreased in aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.

Alkaloids↗

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres.

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15,000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.

Alkaloids↗

Representing different views of acupuncture in a single ontology.

A major challenge for health informatics is to model the health-care domain knowledge into appropriate and useful ontologies. This is difficult, and modellers tend to simplify things dramatically by ignoring the fact that the health care domain encompasses a global perspective. The influx of complementary and alternative medicines from the East to the West, or indeed the ongoing colonialization of orthodox Western medicine into other non-western traditions requires multiple paradigms of delivering treatment to be considered simultaneously, side by side. Models and specifications need to be developed to encompass this richness and represent this complex reality so as to understand what the different concepts and terms in each tradition achieve. Acupuncture is used as a test case of cross-membership between two different paradigms. Here, we briefly outline requirements and answer possible objections to our approach before illustrating how we have modelled heterogeneous domain knowledge from different cultures, and across different paradigms, within a single ontology.

Acupuncture↗

Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.

AIMS: Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks' treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes. METHODS: A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication. RESULTS: Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference. CONCLUSIONS: In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

Adolescent↗

Upregulation of T-bet expression in peripheral blood mononuclear cells during Vogt-Koyanagi-Harada disease.

AIM: To test the hypothesis that T-bet expression is altered in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: Peripheral blood was withdrawn from 16 VKH patients before and after immunosuppressive treatment and from 16 healthy individuals. IFN-gamma, IL-2, and IL-4 in the serum and the supernatants of peripheral blood mononuclear cells (PBMC) cultured with or without phytohaemagglutinin (PHA) were measured by ELISA. T-bet mRNA and protein expression in PBMC cultured with or without PHA was detected by RT-PCR and western blot, respectively. RESULTS: The level of IFN-gamma, but not IL-2 and IL-4, was significantly higher in the supernatants of stimulated PBMC in patients than in controls. A significantly increased T-bet mRNA was found in VKH patients during an active uveitis episode, but not in quiescent patients, compared to controls. T-bet protein was detectable in VKH patients during an active uveitis episode, but not in quiescent patients nor in the healthy controls. Stimulation of PBMC with PHA resulted in a marked upregulation of T-bet mRNA and protein expression for both patients and controls with no significant difference between the two groups. CONCLUSIONS: Upregulation of T-bet may be associated with the development of a Th1 mediated immune response in VKH disease.

Adult↗

Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.

BACKGROUND: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE: To report the identification of a mutation in the human CRYGS gene. SUBJECTS AND METHODS: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. RESULTS: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). CONCLUSIONS: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.

Amino Acid Sequence↗

Amelotin--a Novel Secreted, Ameloblast-specific Protein.

We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of 10-day-old mouse incisors. The conceptually translated protein sequence was unique and showed significant homology only with its human orthologue. The amelotin genes from mouse and human displayed a similar exon-intron structure and were expressed from loci on chromosomes 5 and 4, respectively, which have been associated with various forms of amelogenesis imperfecta. Expression of amelotin mRNA was restricted to maturation-stage ameloblasts in developing murine molars and incisors. Amelotin protein was efficiently secreted from transfected cells in culture. Taken together, our findings suggest that amelotin is a novel factor produced by ameloblasts that plays a critical role in the formation of dental enamel.

Alveolar Process↗