Search PubMed⌕ Search

Biomedical subjects

T Yang

Publications and source records attributed to T Yang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1.

Neurofibromatosis type 1 (NF1) is a commonly inherited autosomal dominant disorder. Previous studies indicated that mice homozygous for a null mutation in Nf1 exhibit mid-gestation lethality, whereas heterozygous mice have an increased predisposition to tumors and learning impairments. Here we show that mice lacking the alternatively spliced exon 23a, which modifies the GTPase-activating protein (GAP) domain of Nf1, are viable and physically normal, and do not have an increased tumor predisposition, but show specific learning impairments. Our findings have implications for the development of a treatment for the learning disabilities associated with NF1 and indicate that the GAP domain of NF1 modulates learning and memory.

Animals↗
PubMed2001

Osteopontin gene is expressed in the dermal papilla of pelage follicles in a hair-cycle-dependent manner.

Hair follicle formation and maintenance involve intimate interactions between follicular epithelial cells and a group of specialized mesenchymal cells known as the dermal papilla. Using the random primer polymerase chain reaction, we have identified an approximately 1.4 kb osteopontin mRNA that is present in large quantities in cultured rat vibrissa dermal papilla cells but undetectable in cultured rat skin fibroblasts. In situ hybridization showed that the osteopontin gene is expressed in dermal papilla cells of pelage follicles during catagen but not in anagen or telogen. As an acidic glycosylated RGD-containing extracellular matrix protein, osteopontin can function both as a cell attachment protein and as a soluble cytokine playing roles in signaling, cell migration, tissue survival, anti-inflammation, and T-cell-mediated cellular immunity. Our results indicate that the comparison of the mRNA of cultured dermal papilla cells and fibroblasts can lead to the identification of not only anagen-specific genes (e.g., nexin 1), but also a catagen-specific gene. We have thus provided evidence that specific genes are turned on during catagen, which is therefore not simply a passive "degenerative" phase. The functional role of osteopontin in catagen is unclear but it may promote the formation of a tightly aggregated dermal papilla, and/or protect the dermal papilla cells from apoptosis induced by cytokines or hypoxia during catagen.

Alopecia↗
PubMed2001

Different dynamic patterns of extracellular glutamate release in rat hippocampus after permanent or 30-min transient cerebral ischemia and histological correlation.

The extent and severity of neuronal damage is different in ischemia with reperfusion compared to ischemia and no reperfusion. To investigate the role of glutamate in cerebral ischemia-reperfusion injury, in vivo microdialysis was performed to examine the dynamic profile of glutamate in the hippocampus in a transient (30 min) or permanent middle cerebral artery occlusion (MCAo) in Wistar rats. The extracellular concentration of glutamate in the cornu ammonis (CA)1 sector of the ipsilateral hippocampus showed a significant but transient elevation of glutamate for both groups immediately following ischemic insult. The initial high peak in glutamate levels in the transient MCAo group was followed by two secondary elevations in glutamate at 50 min and 90 min after initialization of reperfusion. The histopathological outcome was also different in the two groups. The observation that glutamate releases occurred in the early reperfusion phase provided an evidence of additional excitotoxicity of glutamate and thereby a therapeutic base for extended use of glutamate antagonist in the ischemia-reperfusion injury.

Animals↗
PubMed2001

Helper virus-free HSV-1 vectors packaged both in the presence of VSV G protein and in the absence of HSV-1 glycoprotein B support gene transfer into neurons in the rat striatum.

Herpes simplex virus (HSV-1) vectors have potential for gene transfer into quiescent cells, but the gene transfer process could be more efficient. In other vector systems, both the titers and the efficiency of gene transfer have been enhanced by pseudotyping the vector particles with vesicular stomatitis virus (VSV) G protein. In this report, we pseudotyped helper virus-free HSV-1 plasmid vectors with VSV G protein. Packaging was performed in the presence of both VSV G protein and a deletion in an essential HSV-1 glycoprotein, gB. The resulting vector stocks supported gene transfer into both fibroblast and neuronal cell lines. VSV G protein was required for gene transfer because preincubation of these vector stocks with antibodies directed against either VSV G protein or VSV reduced the titer to undetectable levels. Although the titers were lower than those obtained using the unmodified vector system, the titers were not increased by use of chimeric proteins that contain the extracellular domain of VSV G protein and the transmembrane and/or cytoplasmic domains of specific HSV-1 glycoproteins. Also, the titers were not increased by performing the packaging in the presence of deletions in multiple HSV-1 glycoproteins. Nonetheless, pHSVlac pseudotyped with VSV G protein supported gene transfer into striatal neurons in the rat brain. Thus, HSV-1 vectors pseudotyped with VSV G protein may be useful for specific gene transfer studies.

Animals↗
PubMed2001

Interpolymer complexation. II. Entrapment of ibuprofen by in-situ complexation between polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) and development of a chewable tablet formulation.

A new method involving in situ complexation between polyvinyl acetate phthalate (PVAP) and polyvinylpyrrolidone (PVP) has been developed for the entrapment of ibuprofen, a bitter tasting anti-inflammatory drug. The procedure involved dissolving ibuprofen in a thoroughly mixed aqueous alkaline solution of PVAP and PVP, and subsequently slowly adjusting the pH of the solution to 1 with dilute HCl. The yield of the entrapped product, and the percent entrapment of ibuprofen, were 85-90%, and 90-98%, respectively. The PVAP-PVP entrapped granules showed no bitter taste due to ibuprofen. The chewable tablets, prepared by mixing the granules with a cherry-flavored directly compressible tableting excipient, exhibited a release of less than 2% of ibuprofen in pH 1.2 buffer over a period of three hours. In pH 7.4, 100% of ibuprofen was released in six hours. The results presented show that in situ complexation between PVAP and PVP may be useful to produce palatable ibuprofen granules suitable for use in the development of chewable tablets.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination.

PURPOSE: Studies were initiated to examine the effect of formulation and process variables on the delamination process and also the influence of the glass manufacturing process, supplier, and glass surface treatment. METHODS: Stress testing was performed by exposing filled vials to multiple sterilization cycles followed by accelerated stability testing. Delamination incidence was determined by visual examination, light obscuration (HIAC), and microscopical methods. The inner surface of vials from each supplier and lot were also examined by scanning electron microscopy. RESULTS: Vials sourced from Supplier A had smooth surfaces as demonstrated by SEM examination, whereas vials sourced from Suppliers B and C displayed extensive surface imperfections such as pitting and/or deposits. These imperfections were localized to the vial wall, adjacent to the vial bottom, and increased with sulfate treatment. Delamination incidence increased in those vial lots with increased surface imperfections. Thus, vials sourced from Supplier A had the lowest frequency of delamination. Sulfate treatment and high pH increased delamination incidence to as high as 100%. CONCLUSION: These results demonstrate the importance of the surface morphology created during the vial forming process. Given the diferences observed, final vial selection should include extensive microscopical and product stress testing studies on multiple vial lots.

Antineoplastic Agents↗
PubMed2001

Preparation and characterization of spray-dried oxidized cellulose microparticles.

The goal of this study was to investigate the feasibility of spray drying to produce microparticles of oxidized cellulose (OC), a biocompatible and bioresorbable polymer. OCs containing 7, 13, and 20 wt% carboxylic groups were converted into stable aqueous dispersions and then spray dried using a Yamoto G-32 spray dryer equipped with a standard fluid nozzle with an orifice of 406 microm. The following operating conditions were investigated: inlet temperature 140, 170, and 190 degrees C; feed rate 3, 6, and 9 mL/min; and atomization airpressure 0.5, 1, and 1.5 kg f/cm2. The amounts of OC used in feed were 1, 2.5, and 5%. OC microparticles produced under these conditions were shrunken spheres, ranging in size between 0.98+/-0.47 and 2.05+/-0.98 microm. The different operating conditions used had no significant effect on the size and shape of particles. The use of a water-soluble plasticizer (glycerin, polyethylene glycol 400, or polyethylene glycol 6000) in the dispersion yielded microparticles with a good sphericity and a smooth surface morphology, whereas no change in the shape or size of microparticles was noted with water-insoluble plasticizers, Triacetin and dibutyl phthalate. Powder X-ray diffraction and Fourier transform infrared spectral analyses of spray-dried microparticles showed no change in the solid-state structure of OC. In conclusion, results show that OC can be converted into stable aqueous dispersions and used to produce microparticles by spray drying.

Capsules↗
PubMed2001

Drug block of I(kr): model systems and relevance to human arrhythmias.

The long QT-related arrhythmia torsades de pointes (TdP) can arise with mutations in HERG and during treatment with drugs that block cardiac I Kr, the current encoded by HERG. Multiple test systems have been used to assess drug block of I Kr. This study evaluated the I Kr blocking potency of a series of antiarrhythmics associated with a range of clinical risks of TdP in two such systems: mouse AT-1 cells (in which I Kr is the major repolarizing current) and Ltk cells transiently transfected with HERG (n = 4-10 cells per drug). For each compound, the concentration required to produce 50% block of I Kr or HERG tail currents (IC 50 ) was determined. There was an excellent correlation ( r = 0.98, p < 10 -5 ) between values obtained in the two systems. However, the relation between the liability of a drug to cause TdP appeared dissociated from I Kr blocking potency. Quinidine, dofetilide, ibutilide, procainamide, and disopyramide are all associated with TdP, but only the first three were potent blockers (IC 50 < or = 1 microM ), whereas procainamide and disopyramide were not (IC 50 > 50 microM ). Conversely, verapamil and amiodarone, drugs not associated with TdP, were also blockers (IC 50 < or = 1 microM ). We conclude that I Kr blocking potency can be readily assessed in either AT-1 cells or systems in which HERG is heterologously expressed. However, not all drugs causing TdP are potent I Kr blockers, and I Kr block is not necessarily associated with TdP. Other properties of these drugs, therefore, contribute to their propensity to cause TdP.

Animals↗
PubMed2001

An in vitro study of the effects of isoflurane on oxygen transfer.

A common anesthetic technique utilized during cardiopulmonary bypass (CPB) includes the use of various inhalation agents, such as isoflurane. The purpose of this study was to evaluate the effects of this agent on oxygen transfer during CPB. An in vitro model was designed using bovine blood. Blood flow was held constant at 2 l/min, while gas flow was manipulated at 1 and 3 l/min. The percentage of inspired oxygen (FiO2) was set at 50 and 100%, and isoflurane was manipulated to 1.0, 3.0 and 5.0%. Blood gas analysis, oxygen transfer, and inlet and outlet isoflurane concentrations were measured at each of the given conditions. A total of 12 trials with four oxygenators were conducted. In the four oxygenators used in our study, no significant differences in oxygenator performance were found. At conditions of 1 I/min gas flow, 50% FiO2 and 1% isoflurane, there were no significant changes in O2 transfer between baseline and measurements taken during isoflurane administration (100.18 +/- 12.49 vs 102.35 +/- 10.99 ml O2/min, p=0.8031). At 3 I/min gas flow, 100% FiO2 and 5% isoflurane, no significant differences were found (142.35 +/- 10.76 vs 154.04 +/- 8.95 ml O2/min, p=0.1459). The only significant differences found for oxygen transfer were between 50 and 100% FiO2, all other conditions being set equal (102.35 +/- 10.99 vs 137.68 +/- 8.62 ml O2/min, p=0.0023). In conclusion, increasing concentrations of isoflurane up to 5% does not affect the efficiency of oxygen transfer in an in vitro circuit. Further studies are necessary to evaluate the effects in an in vivo setting.

Anesthetics, Inhalation↗
PubMed2001

Isoflurane aggravates the decrease of phosphatidycholine synthesis in alveolar type II cells induced by hydrogen peroxide.

The influence of isoflurane (Iso) on the synthesis and secretion of phosphatidylcholine (PC) of alveolar type II cells (AT II cells) injured by hydrogen peroxide (H2O2) was investigated. After primary culturing for 32 h, AT II cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 02.8 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H202 + 2.8 mM Iso group. Synthesis and secretion of phosphatidylcholine (PC) were detected by 3H-choline chloride incorporation. It was found that 0.28 mM and 2.8 mM Iso significantly reduced PC synthesis compared with the control group (p <0.05, p <0.01, respectively), but not PC secretion. 75 microM H2O2 markedly decreased the synthesis and secretion of PC in AT II cells compared with the control group (p <0.01). 0.28 mM and 2.8 mM Iso aggravated the decrease of PC synthesis induced by H2O2 (p <0.05, p <0.01, respectively), but did not affect PC secretion. These findings suggest that Iso itself may inhibit the synthesis of PC of AT II cells in vitro and further damage the cells' function under peroxidation.

Anesthetics, Inhalation↗
PubMed2001

Angiographic evaluation of middle cerebral artery reperfusion caused by platelet glycoprotein IIb/IIIa receptor complex antagonist murine 7E3 F(ab')2 in a model of focal cerebral ischemia in rats.

OBJECT: Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex are currently used for the treatment of acute coronary syndromes. The platelet GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can reduce or prevent arterial thrombosis. To study the recanalization efficacy of a GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the therapeutic effects of murine 7E3 F(ab'), in a focal embolic cerebral ischemia model in rats. METHODS: Focal cerebral ischemia was produced by introducing an autologous thrombus into the right side of the middle cerebral artery (MCA). Thirty male Wistar rats were randomly divided into three groups of 10 rats each: control, 7E3 F(ab')2 administered 1 hour postischemia, and 7E3 F(ab')2 administered 3 hours postischemia. Animals in the therapeutic groups received intravenous infusion of 6 mg/kg 7E3 F(ab')2 at 1 or 3 hours following cerebral embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding, and findings on angiograms of the MCA (before and after infusion) were assessed in all animals. Angiographic evaluation revealed full MCA recanalization in three of 10 animals in each 7E3 F(ab')2 treatment group. Animals in these groups exhibited a significant reduction in infarct volume when compared with animals in the control group: 1) infarct volume 1 hour postischemia, 22 +/- 13.9% (p = 0.005); 2) infarct volume 3 hours postischemia, 22.1 +/- 14.8% (p = 0.008); and 3) infarct volume in control animals, 42.4 +/- 16%. Postischemia treatment with 7E3 F(ab')2 also improved the animal's neurobehavioral performance. The duration of bleeding significantly increased by more than two times, but there was no associated increase in intracerebral hemorrhage in any group. CONCLUSIONS: On the basis of their findings, the authors conclude that murine 7E3 F(ab'), is a potent and safe antiplatelet agent in this experimental focal embolic cerebral ischemia model. Neuronal lesions were significantly reduced when the treatment was delayed up to 3 hours.

Animals↗
PubMed2001

Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.

Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.

4-Quinolones↗
PubMed2001

An experimental evaluation of continuous cardiotomy reservoir ultrafiltration.

Ultrafiltration has been suggested as a means to reduce the morbidity associated with blood activation. However, the application of ultrafiltration to the highly activated blood of the cardiotomy suction subcircuit has not been investigated. The purpose of this study was to determine whether cardiotomy reservoir ultrafiltration (CRUF) would be effective in altering cytokine levels. Six swine, undergoing 90 min of cardiopulmonary bypass (CPB), were divided into two groups; one group was assigned to receive CRUF (N = 3), the other was to serve as controls and did not receive ultrafiltration (N = 3). Blood samples were analyzed for hematocrit, plasma-free hemoglobin, total protein, interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha). Samples were taken pre-bypass, postheparinization, every 30 min during CPB, post-CPB and postprotamine. All data were analyzed using a one-way analysis of variance (ANOVA), with significance accepted at p < .05. There were no significant differences found between treatment and control groups for plasma-free hemoglobin levels (22.4 +/- 22.2 vs. 14.6 +/- 14.4; 40.1 +/- 26.1 vs. 40.0 +/- 19.3). After 90 min of ultrafiltration, there was a significant decrease in TNF-alpha (261.6 +/- 119.6 vs. 71.8 +/- 11.4; p = .02). Although IL-8 levels decreased from throughout the experiment, concentrations did not reach statistical significance. In conclusion, CRUF can be used without increasing cellular destruction, and can decrease certain cytokine levels. Our results suggest that further clinical studies should be undertaken utilizing this technique with a larger sample size.

Analysis of Variance↗
PubMed2001

Effect of partial-filling autotransfusion bowls on the quality of reinfused product.

Intraoperative autotransfusion is used in a variety of surgical procedures with the quantity of blood loss dependent upon numerous factors. These procedures may or may not produce a full autotransfusion bowl. The inadequate removal of contaminants has been correlated to the incomplete filling of bowls, resulting in a condition called "Salvaged Blood Syndrome." The purpose of this study was to assess the quality of aspirated whole blood after processing with an autotransfusion system using various fill volumes and two wash volumes. An in vitro circuit was designed to mimic the mechanical effects of extracorporeal flow on blood. Twenty-four Baylor-style bowls were filled at 400 mL min(-1) and washed at 300 mL min(-1). Two wash volumes, 1000 and 2000 mL, and three bowl volumes: low, mid, and full, were used in this study. The bowl volumes were determined by using red cell quantities of 60, 100, and 135 mL for the low-fill, mid-fill, and full bowls, respectively. Samples were drawn pre-autotransfusion and post-autotransfusion and analyzed for plasma-free hemoglobin, IL-8, white blood cell count, platelet count, albumin, and total protein. All data were analyzed using one-way analysis of variance (ANOVA) with significance accepted at p > or = .05. Plasma-free hemoglobin levels and hematocrit were concentrated significantly (p < .05) as bowl volume increased. A significant difference in IL-8 levels was found in the wash volumes in the low-fill bowls (p < .02). Platelet count was significantly decreased between the full bowl with 1000 mL wash and the full bowl with 2000 mL wash (p < .0004). Total protein reduction was significantly less in the low-fill bowl with 1000 mL wash as compared to the other bowl treatments (p < .05). In conclusion, the quality of the washed product did not vary significantly between fill or wash volumes, with the exception of the low-fill bowl with 1000 mL wash.

Blood Loss, Surgical↗
PubMed2001

Chimeric pig hearts resist hyperacute rejection in ex vivo perfusion model.

With surrogate tolerogenesis. the recipient immune system is engrafted within the donor pig before organ transplant. Chimeric pig hearts may resist hyperacute rejection by inducing accommodation. This hypothesis was tested using an ex vivo isolated piglet heart perfusion model. Processed sheep marrow was infused into fetal pigs at 45 days gestation. Heart explants from chimeric or nonchimeric pigs were suspended in a Langendorff apparatus and perfused with plasma from unsensitized sheep or sensitized sheep. Nonchimeric hearts perfused with plasma from unsensitized functioned for 240 min (N = 3). Nonchimeric hearts perfused with sensitized plasma deteriorated rapidly, functioning at 19+/-12 min (N = 6); Immunohistochemistry of heart graft revealed extensive deposition of IgG, IgM in the microvascular. In contrast, chimeric hearts perfused with sensitized plasma functioned for 183+/-46 min (N = 3)(p <.001); Deposition of IgG, IgM had substantially less. Heart grafts procured from chimeric pigs survived in the presence of antidonor IgG, IgM, and complement, demonstrating that chimeric pig hearts resist hyperacute rejection.

Animals↗
PubMed2001

[Construction of a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma tissue].

OBJECTIVE: To construct a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma (HCC) tissue. METHODS: Using the suppression subtractive hybridization (SSH), a novel technique has been described recently. cDNA fragments of missing or low expressing tumor suppressor genes in HCC tissue were isolated using paracancerous normal liver tissue and HCC tissue as targets. Then these cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of E.coli by high voltage electroperforation. One hundred positive bacteria clones were randomly picked and identified using enzyme restriction method. RESULTS: The amplified library contained more than 4,000 positive bacteria clones. Random analysis of 100 clones with enzyme restriction method showed that all clones contained 200-600 bp inserts. CONCLUSIONS: A subtracted cDNA library of differentially expressed genes in human normal liver tissue and HCC tissue is constructed successfully with SSH and T/A cloning techniques. The library is efficient and lays solid foundation for screening and cloning new and specific missing or low expressing tumor suppressor genes of HCC.

Carcinoma, Hepatocellular↗