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Biomedical subjects

Y Yang

Publications and source records attributed to Y Yang.

At least 883 records · Page 49Linked to original sources
PubMed1997

Gene transfer into hematopoietic cells.

Transfer of a gene into stem cells with subsequent lineage-specific gene expression is a desired goal with many potential therapeutic applications. Retroviral vectors developed from murine leukemia viruses reproducibly transfer genes into murine stem cells, but are inefficient at gene insertion into stem cells of larger animals or man. A growing knowledge of stem cell biology suggests that this inefficiency reflects the quiescent state of stem cells, even when incubated in the presence of multiple cytokines and low expression of the receptor for amphotropic retroviral vectors. Alternative vector systems are being explored in an effort to overcome these barriers to stem cell-targeted gene transfer. Our work has shown that recombinant adeno-associated virus vectors, which have the potential for transducing quiescent cells, transfer, express and integrate a globin gene linked to its normal regulatory elements in human erythroid cells, but only at very high multiplicities of infection. The integrated genome was stable and the encoded globin gene was expressed at levels equivalent to a normal globin gene.

Animals↗
PubMed1997

The contribution of GSH peroxidase-1, catalase and GSH to the degradation of H2O2 by the mouse lens.

Utilizing cultured lenses from normal and homozygous glutathione peroxidase (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and 80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2 degradation. The Cat contribution was concentration dependent being about 30% at 300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2 degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM and 80 microM, respectively. However, based on evaluation of the ability of GSH to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is, therefore, concluded that lens GSH must be involved in other reactions either directly or indirectly related to H2O2 degradation.

Amitrole↗
PubMed1997

Fast spiral magnetic resonance imaging with trapezoidal gradients.

A modified spiral imaging technique is presented, in which the conventional sinusoidal gradient waveforms are replaced by trapezoidal ones. In addition to allowing a reduced data acquisition time, the new waveforms circumvent specific hardware restrictions on the minimum scan repetition time.

Brain↗
PubMed1997

Diffusion measurement in phantoms and tissues using SLIM localization.

A new approach to efficient localized diffusion measurements has been developed and evaluated on phantoms and isolated tissues. The combination of a diffusion-sensitive pulse sequence with SLIM (spectral localization by imaging) makes efficient and accurate localized water and metabolite diffusion measurements possible with a substantial improvement in spatial or time resolution compared to standard methods. Phantom experiments showed that diffusion of substances present in relatively low concentration within small compartments can be measured accurately by this method, suggesting potential applications for diffusion measurements of metabolites in vivo. Experiments on excised rat uterine horns demonstrated the ability of this method to measure localized diffusion of water within irregularly shaped regions of biological samples. Accurate diffusion measurements were achieved in the localized regions with acquisition times less than would have been required by standard diffusion imaging methods.

Animals↗
PubMed1997

Electron microscopic localization of lacZ expression in the proximal convoluted tubular cells of the kidney in transgenic mice carrying chimeric erythropoietin/lacZ gene constructs.

Regulated expression of the erythropoietin (EPO) gene in the adult kidney plays a key role in the regulation of erythropoiesis. However, uncertainty exists regarding the type of kidney cells involved in EPO gene expression. We previously showed by light microscopy that the lacZ reporter gene is expressed and inducible by hypoxia/anemia in the proximal convoluted tubular (PCT) cells of the kidneys of transgenic mice carrying the 5'-lacZ construct, in which the lacZ gene was placed downstream of a 7.0-kb mouse EPO gene segment containing 6.5 kb of the 5'-flanking sequence. We, report here the light and transmission electron microscopic examination of lacZ expression in the kidneys of transgenic mice carrying the 5'-lacZ construct and two additional constructs carrying the 6.5-kb 5'-flanking sequence with the body of the gene alone, or along with the 1.2-kb 3'-flanking sequence. The electron microscopic analyses unequivocally demonstrated that lacZ under the regulatory control of the 6.5-kb 5'-flanking sequence with or without the body of the gene and the 1.2-kb 3'-flanking sequence was expressed predominantly in the proximal convoluted tubular cells of the kidney following hypoxia induction.

Anemia↗
PubMed1997

Quantitation of regional cerebral blood flow increases during motor activation: a steady-state arterial spin tagging study.

Steady-state arterial spin tagging MRI approaches were used to quantitate regional cerebral blood flow increases during finger tapping tasks in seven normal subjects. Statistically significant increases in cerebral blood flow were observed in the contralateral primary sensorimotor cortex in all seven subjects and in the supplementary motor area in five subjects. The intrinsic spatial resolution of the cerebral blood flow images was approximately 4 mm. If no spatial filtering was applied, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 60 +/- 10 cc/100 g/min (91 +/- 32%). If the images were filtered to a spatial resolution of 15 mm, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 23 +/- 7 cc/100 g/min (42 +/- 15%), in agreement with previously reported 133Xe and PET results.

Adult↗
PubMed1997

Visualization of retinal and choroidal blood flow with fluorescein leukocyte angiography in rabbits.

PURPOSE: To visualize the retinal and choroidal leukocytes in rabbits with a new technique, fluorescein leukocyte angiography using a scanning laser ophthalmoscope. METHODS: Blood was withdrawn from an ear vein of a rabbit (New Zealand White), mixed with fluorescein dye in a test tube and centrifuged. The yellow-brown coat layer containing fluorescein-stained leukocytes was collected and injected into the ear vein of the same rabbit while performing fluorescein angiography with a scanning laser ophthalmoscope. The angiographic image displaying circulating fluorescent leukocytes in retinal and choroidal vessels was recorded on a videotape. RESULTS: Fluorescent leukocytes were clearly visible in the retinal arteries, capillaries, veins and choroidal vessels for more than 1 h. Plugging of leukocytes was seen throughout this period of time in choroidal vessels, while plugging was rare in retinal vessels. CONCLUSIONS: Fluorescein leukocyte angiography is a new technique which can be used for visualization of the leukocytes in retinal and choroidal vessels non-invasively and in vivo.

Animals↗
PubMed1997

Sudden unilateral blindness after intracranial aneurysm surgery.

The incidence of unilateral blindness and ophthalmoplegia after aneurysm surgery is very rare, but if it occurs, it is mainly caused by intra-operative nerve injury. We experienced 6 cases of unilateral blindness immediately after surgery for 3 recent years. These patients were classified into Hunt-Hess grade I to II except for one patient with III. All patients complained of visual loss with varying degree of lid oedema and ophthalmoplegia ipsilateral to the site of surgery. Angiographic examination of these patients revealed that the aneurysm was located at the internal carotid artery bifurcation in one case and the middle cerebral artery bifurcation in five cases. All of them were relatively far from the optic nerve. The aneurysm was clipped easily with minimal brain retraction via standard pterional craniotomy since the brain was slack in all cases. In all cases, injuring the optic nerve during surgery was remote. All patients showed evidence of retinal ischaemia on fundoscopy with or without fluorescein angiography. The pathophysiology of this ischaemic event is unknown. In our patients, we could exclude possible aetiological factors such as abnormal systemic and ocular conditions, causing ischaemia in intra-orbital structures, increased intracranial pressure, intra-operative hypotension, carotid atherosclerosis, and ocular vasospasm etc. Accordingly we speculate that the complications seen in our cases were most likely related to intra-orbital ischaemia initiated by a collapse of the arterial and venous channels in the orbit and/or to direct or indirect contusion on the intra-orbital structures. These situations could be produced by inadvertent pressure placed on the eyeball with a bulky retracted frontal skin flap. Visual acuity in these patients ranged from no light perception to the ability to see objects and detect colour. Their conditions were irreversible. The degree of visual recovery seems to be dependent on the duration and severity of retinal ischaemia by orbital compression. Unfortunately there is no satisfactory treatment. We recommend the use of an eye shield to protect ipsilateral eyeball just before aneurysm surgery.

Adult↗
PubMed1997

Carcinoma of the gallbladder and anomalous arrangement of the pancreaticobiliary ductal system: cell kinetic studies of gallbladder epithelial cells.

Anomalous arrangement of the pancreaticobiliary ductal system (AAPB), a congenital anomaly defined as a union of the pancreatic and biliary ducts located outside the duodenal wall, is a newly designated disease entity, and is frequently found in adult patients with gallbladder carcinoma (GBX). In the present study, the relationship of AAPB and GBX was investigated. We studied 27 patients with GBX and AAPB, 34 patients with AAPB and without GBX, and as a control group, 56 patients without AAPB (10 with GBX, 24 with cholecystolithiasis, and 22 with normal gallbladder). Tissue sections from cancerous and non-cancerous mucosa of the gallbladder of all of these patients were stained for proliferating cell nuclear antigen (PCNA), Ki-67 nuclear antigen, and bromodeoxyuridine (BrdU). The Ki-67 labeling index (Ki-67-LI), PCNA labeling index (PCNA-LI), and BrdU labeling index (BrdU-LI) of the noncancerous mucosa in the patients with AAPB and/or GBX were significantly higher than those in the patients without GBX and AAPB (P < 0.01). These indices of the noncancerous mucosa in the patients with AAPB and GBX were significantly higher than those in the patients with either AAPB or GBX (P < 0.05). Cell proliferation in the gallbladder epithelia was accelerated in patients with AAPB. Consequently, AAPB appears to be an important risk factor for the occurrence of GBX.

Adult↗
PubMed1997

Ultrastructural changes in rat locus coeruleus induced by chronic opioids.

The locus coeruleus (LC) is a major noradrenergic nucleus in the brain. The activity of the LC neurons is chronically regulated by opioids. So far, very little is known about the morphological changes induced by chronic treatment with opioids. In the present study, the effects of chronic treatment with morphine and dihydroetorphine, a new narcotic analgesic with lower physical dependence potential than morphine, were investigated on the ultrastructure of the rat LC. Rats received saline or increasing doses of morphine or dihydroetorphine for 5 days by twice daily subcutaneous injections. Withdrawal was precipitated in half of the opioid-treated rats by a single intraperitoneal injection of naloxone 4 h after the last injections of opioids. The ultrastructure of the LC was examined by electron microscopy. Results showed that chronic morphine treatment induced a marked injury to the LC neurons. The primary changes in the cell body were the indentation of nuclei, the fragmentation and degranulation of rough endoplasmic reticulum, as well as the disaggregation of polyribosomes. Myelinoid bodies were seen in the processes. An accumulation of presynaptic vesicles was observed in some of the terminals which formed synaptic junctions with the LC neurons as compared to the normal controls. Naloxone-precipitated withdrawal from morphine did not stop the morphine-induced injury on the LC neurons except that less accumulation of presynaptic vesicles occurred. Chronic dihydroetorphine treatment only induced a slight change in the ultrastructure of the LC neurons. These results indicate that the LC neurons are more vulnerable to chronic treatment with morphine than to that with dihydroetorphine.

Analgesics↗
PubMed1997

Double-strand breaks increase the incidence of genetic deletion associated with intermolecular recombination in bacteriophage T7.

An in vitro DNA replication system based on extracts prepared from Escherichia coli cells infected with bacteriophage T7 was used to study deletion associated with the repair of double-strand breaks. The gene for T7 ligase was interrupted by a DNA insert which included 17-bp direct repeats. Deletion between the repeats restored the reading frame of the gene, and these DNA molecules could be detected by their ability to give rise to ligase-positive phage after in vitro packaging. T7 genomes that had a pre-existing double-strand break located between the direct repeats were incubated together with intact genomes which had the same direct repeats. Genetic markers placed on either side of the insert in the ligase gene allowed identification of the source of DNA molecules that underwent deletion between the direct repeats. This allowed an assessment of the participation of the molecules with strand breaks in the deletion process, under conditions where any mechanism could contribute to deletion. Approximately three-quarters of the T7 molecules that had lost the region between the direct repeats contained one or both of the partial genomes originally introduced into the reactions. About 50% of the genomes which had undergone deletion had recombined markers between the partial and intact genomes. The data demonstrate that double-strand breaks substantially enhance the contribution of intermolecular recombination to deletion.

Bacteriophage T7↗
PubMed1997

Attenuation of alcohol consumption by a novel nontoxic ibogaine analogue (18-methoxycoronaridine) in alcohol-preferring rats.

We previously reported that single administration of ibogaine, an indol alkaloid with antiaddictive properties, dose dependently reduced alcohol intake in three strains of alcohol-preferring rats. The present study examined the effect of different doses of a newly developed nontoxic ibogaine analogue, 18-methoxycoronaridine (18-MC), on alcohol intake. Selectively bred alcohol-preferring rats received a single intraperitoneal injection of vehicle or 5, 20 and 40 mg/kg of 18-MC at 9:30 AM, and their consumption of alcohol, water and food was measured for 24 h. Our results demonstrate that a single injection of 18-MC significantly and dose dependently attenuated alcohol consumption and preference and commensurately increased water intake. Only the highest dose of 18-MC significantly decreased food intake. Although the true mechanism of action of 18-MC in suppressing alcohol intake is not yet fully understood, it may, like ibogaine, exert its attenuating effects on alcohol consumption by modulating neurotransmitters believed to be involved in the regulation of alcohol intake.

Alcohol Drinking↗
PubMed1997

Fluorescent dots in fluorescein angiography and fluorescein leukocyte angiography using a scanning laser ophthalmoscope in humans.

PURPOSE: The purpose of the study is to disclose the nature of fluorescent dots and segments traditionally observed with fluorescein angiography (FA) using a scanning laser ophthalmoscope (SLO 101; Rodenstock, München, Germany). The authors developed a new method, called fluorescein leukocyte angiography (FLA), to display directly the movement of leukocytes in human retinal vessels. METHODS: Fluorescein angiography was performed on two normal volunteers using a scanning laser ophthalmoscope and fluorescent dots and segments were observed. Fluorescein leukocyte angiography, using an injection of fluorescent buffy coat layer from which the fluorescent plasma and nonfluorescent erythrocytes have been removed externally, was performed on seven normal volunteers. Injection fluid smears were examined through a fluorescent microscope. Peripheral blood smears taken during midphase of FA and FLA also were examined. In addition, 15 early-phase FAs of central serous chorioretinitis (CSC) were studied retrospectively. RESULTS: In the FAs of normal volunteers, fluorescent dots were detected only in perimacular capillaries at early phase. Eight of the 15 CSC FAs examined showed both fluorescent dots and segments. In the FLAs, fluorescent dots were detected in whole retinal vessels for more than 30 minutes. Fluorescent segments were observed in FA but not in FLA. Injected fluid smears from one FLA showed fluorescent leukocytes and small platelets. However, in peripheral blood smears of the FLA, leukocytes and platelets were more visible and exhibited higher contrast than those of an FA due to background plasma fluorescence. The mean velocity of 21 flowing leukocytes in perifoveal capillaries was 1.37 +/- 0.35 mm/second in 2 FAs and that of 89 flowing leukocytes was 1.41 +/- 0.29 mm/second in 7 FLAs. CONCLUSIONS: The authors' observations suggest that fluorescent dots in scanning laser ophthalmoscope imaging are fluorescein-stained leukocytes, whereas fluorescent segments are the hyperfluorescent plasma that is located between rouleaux formations of erythrocytes. The velocity of the fluorescent dots could be measured in the perimacular capillaries by either FA or FLA; however, only FLA can display the flow of fluorescent leukocytes in large vessels.

Adult↗
PubMed1997

Metabotropic glutamate receptor activation modulates epileptiform activity in the hippocampus.

Synchronous neuronal activity that resembles interictal epileptiform discharges occurs in hippocampal slices if there is an imbalance of inhibitory and excitatory synaptic activity. Antagonists of the GABAA receptor and agonists of the ionotropic glutamate receptors are convulsants that produce epileptiform discharges in hippocampal slices. We evaluated the effects of activation of the metabotropic class of glutamate receptors on epileptiform activity produced by convulsants. The metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD, 30-100 microM) accelerated the rate of interictal epileptiform discharges produced by either bicuculline methiodide or 4-aminopyridine and had minimal effects on discharges produced by high [K+]o. The increase in rate was associated with a significant decrease in the amplitude and duration of the afterhyperpolarization that follows the paroxysmal depolarizing shift, the intracellular correlate of the interictal epileptiform discharge. A modest increase in input resistance (approximately 10%) accompanied the rate increase. beta-adrenergic or muscarinic agonists, neurotransmitters that also decrease the afterhyperpolarization, acted synergistically with ACPD (100 microM) to increase the control rate of bicuculline-induced interictal discharges by more than eight-fold. Antagonists of beta-adrenergic or muscarinic receptors reduced, but did not block, the acceleration of bicuculline-induced discharge rate produced by 30 microM ACPD. The results show that metabotropic glutamate receptors enhance the rate of interictal epileptiform discharges produced by bicuculline or 4-aminopyridine. ACPD had no effect on interictal epileptiform activity induced by high [K+]o, a finding that may indicate that in high [K+]o conditions the metabotropic receptor is activated or that the effects of high [K+]o already reduced the effect of depolarizing currents that are enhanced by ACPD. The acceleration in interictal discharge rate was associated with a reduction in the afterhyperpolarization that follows the paroxysmal depolarizing shift and this action appears to be important in determining the synchronization of neurons and the rate of interictal epileptiform discharges. Furthermore, interaction between mGluR activation and either muscarinic or beta-adrenergic activation may be important for seizure generation.

4-Aminopyridine↗
PubMed1997

The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP.

Human cytomegalovirus (HCMV) inhibits MHC class I antigen presentation by a sequential multistep process involving a family of unique short (US) region-encoded glycoproteins. US3 retains class I molecules, whereas US2 and US11 mediate the cytosolic degradation of heavy chains by the proteosomes. In US6-transfected cells, however, intracellular transport of class I molecules is impaired because of defective peptide translocation by transporters associated with antigen processing (TAP). Peptide transport is restored in HCMV mutants lacking US6. In contrast to the cytosolic herpes simplex virus protein ICP47, US6 interacts with TAP inside the endoplasmic reticulum lumen, as shown by US6 derivatives lacking the transmembrane and cytoplasmic domains and by the observation that US6 does not prevent peptides from binding to TAP. Thus, HCMV targets TAP for immune escape by a molecular mechanism different from that of herpes simplex virus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A radiation hybrid framework map of bovine chromosome 13.

In this paper we present a 5000-rad radiation hybrid framework map of bovine chromosome 13 (BTA13) containing 13 loci, including five conserved genes and eight polymorphic microsatellites. All framework markers are ordered with odds greater than 1000:1. Furthermore, we present a comprehensive map of BTA13 integrating 11 genes and 16 microsatellites. The proposed order is in general agreement with the recently published medium-density linkage maps. A model of five blocks of genes with conserved order between human, mouse and cattle is presented.

Animals↗
PubMed1997

Antiinflammatory effect of lipocortin 1 in experimental arthritis.

The glucocorticoid-induced antiinflammatory protein lipocortin 1 is present in arthritic synovium but its ability to regulate joint inflammation has not previously been studied. We investigated the role of lipocortin 1 in the antiinflammatory activity of glucocorticoids in an acute arthritis model induced by intraarticular injection of carrageenan. Compared to control joints (0.09 +/- 0.08 x 10(6) synovial fluid cell count), carrageenan injected joints exhibited marked infiltration of PMN (10.2 +/- 0.7 x 10(6), p < 0.001). Both intraperitoneal (1.0 mg/kg) and intraarticular administration (5 micrograms) of dexamethasone (DEX) significantly suppressed arthritis severity (p < 0.001 and 0.005, respectively), and the effects of DEX were significantly prevented by intra-articular injection of antilipocortin 1 mAb (p < 0.05). Carrageenan arthritis was also significantly inhibited by intraarticular administration of the N-terminal lipocortin 1 peptide Ac2-26 at doses of 1 or 2 mg/kg (p < 0.01). Intraarticular injection antilipocortin 1 mAb in the absence of DEX also significantly exacerbated arthritis severity (p < 0.005). In vitro treatment of PMN with DEX was associated with significant inhibition of phagocytosis (p < 0.005) and reactive oxygen species (ROS) generation (p < 0.001). Antilipocortin 1 mAb significantly reduced the inhibitory effects of DEX (p < 0.01 and 0.005, respectively). These results demonstrate that lipocortin 1 mediates the effects of exogenous glucocorticoids on neutrophil migration in carrageenan-induced acute arthritis, exerts an endogenous antiinflammatory influence, and mediates glucocorticoid inhibition of neutrophil activation.

Animals↗