Biomedical subjects

Y N Wang

Publications and source records attributed to Y N Wang.

At least 19 recordsLinked to original sources

PubMed2026

[Genomic characteristics of multi-drug resistant of non-O1/non-O139 Vibrio cholerae ST1565 from sepsis cases].

To analyze the genomic characteristics of multi-drug resistant of non-O1/non-O139 Vibrio cholerae ST1565 from sepsis cases. An 88 years old male patient admitted to Huashan Hospital in Shanghai on July 2, 2025, who was retrospectively analyzed. The clinical diagnosis was severe bacterial enteritis and secondary NOVC sepsis. Blood culture confirmed the presence of non-O1/non-O139 group Vibrio cholerae. The strain was a multidrug-resistant isolated of ST1565 as determined by whole-genome sequencing. The ResFinder database predicted 11 resistance genes for 6 classes of antibiotics: qnrVC5, sul2, floR, tet(59), aph(6)-Id, aph(3'')-Ib, dfrA15, dfrA31, almE, almF, and almG. Except for the quinolone qnrVC5, which was not expressed, the other resistance genes were consistent matched the phenotypic results. Additionally, 8 insertion sequences were identified: ISVch1, ISVvu4, ISVch6, ISVvu8, ISVpa3, ISVpa4, ISVsa3, and ISShfr9. Important virulence factors included 3 secreted protein toxin genes: Vibrio cholerae hemolysin, repeat toxin, and Vibrio parahaemolyticus thermostable direct hemolysin. The patient was cured after sequential treatment with meropenem, levofloxacin, and doxycycline. NOVC/ST1565 is a newly identified sequence type in China, which exhibits multidrug-resistant and hypervirulent phenotypes.

Drug Resistance, Multiple, Bacterial↗

PubMed2006

Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption.

To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100-230nm were prepared by the salting out method with NaCl and encapsulated via the layer-by-layer (LbL) adsorption to provide the insulin nanoparticles shelled with two oppositely charged polyelectrolytes. Poly(alpha,beta-l-malic acid) (PMA) and water-soluble chitosan (WSC) as the weak polyelectrolytes with good biodegradability and biocompatibility in vivo were chosen to be the encapsulating materials of the LbL adsorption. In the preparation of the insulin nano-aggregates, the NaCl concentration and pH in the medium obviously affected yield and particle size of the insulin nano-aggregates. After eight adsorption cycles of the polyelectrolytes on the insulin nano-aggregates, the insulin-polyelectrolyte nanoparticles with the sizes of 100-250nm were obtained with about 20% insulin loss. The insulin release from the nanoparticles was mostly pH-dependent owing to sensitivity of the weak polyelectrolytes to pH. Insulin was hardly released from the nanoparticles in a medium at pH 4-5 while it could be released at pH 7.4, corresponding to the pH of the human blood and the body fluid. A burst effect was also observed although it could be reduced via increasing the polyelectrolyte layers of PMA and WSC assembled on insulin nano-aggregates.

Adsorption↗

PubMed2005

Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and its properties as the new carrier of protein delivery system.

A new tadpole-shaped polymer was synthesized via the coupling reaction of poly(DL-lactide) (PLA) onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin (CDen) using N,N'-Dicyclohexycarbodiimide as the catalyst. The structures of CDenPLA as the products were characterized with infrared spectrometry, nuclear magnetic resonance and their molecular weights were determined by gel permeation chromatography. The tadpole-shaped polymer possessed both a hydrophilic head that could bind some residues on a protein and a hydrophobic polylactide tail so that it could be amphiphilic. Two methods, double emulsion (DE) and nanoprecipitation (NP), were employed to fabricate the polymeric nanoparticles into which the bovine serum albumin was loaded as a model protein. The nanoparticles with a hydrophobic core of the PLA segments covered with the hydrophilic corona layer of the cyclodextrin moiety could be formed from the copolymers using NP method as identified by 1HNMR. Influence of the preparation conditions on the nanoparticles size, encapsulation efficiency and release profile in vitro was investigated. The encapsulation efficiency of the BSA-loaded nanoparticles with the average diameter of 377 nm was 71.6% under an optimized condition. The structure maintenance in the nanoparticle preparation and release in vitro was also measured via sodium dodecyl sulfate polyacrylamide gel electrophoresis and circular dichroism spectrometry. The results showed that the new copolymer could load BSA effectively and BSA kept stable after it was released from the nanoparticles.

Animals↗

PubMed2001

The influence of oxidation of membrane thiol groups on lysosomal proton permeability.

The influence of oxidation of membrane thiol groups on lysosomal proton permeability was studied by measuring lysosomal pH with FITC-conjugated dextran, determining the membrane potential with 3,3'-dipropylthiadicarbocyanine iodide and monitoring their proton leakage with p-nitrophenol. Residual membrane thiol groups were measured with 5,5'-dithiobis-(2-nitrobenzoic acid). The lysosomal membrane thiol groups were modified by treatment with diamide and dithiothreitol. SDS/PAGE revealed aggregations of the membrane proteins induced by the treatment of lysosomes with diamide. The cross-linkage of proteins could be abolished by subsequent treatment with dithiothreitol, indicating that the proteins were linked via disulphide bonds. Treating the lysosomes with diamide decreased their membrane thiol groups and caused increases in lysosomal pH, membrane potential and proton leakage, which could be reversed by treatment of the lysosomes with dithiothreitol. This indicates that the lysosomal proton permeability can be increased by oxidation of the membrane thiol groups and restored to the normal level by reduction of the groups. Treatment of the lysosomes with N-ethylmaleimide reduced their membrane thiol groups but did not change the lysosomal pH or their degree of proton leakage. It suggests that protein aggregation may be an important mechanism for the increase in lysosomal proton permeability. The results raise the possibility that the proton permeability of lysosomes in vivo may be affected by the redox states of their membrane thiol groups.

Alkylation↗

PubMed2001

Modeling dynamically heterogeneous coupled relaxations.

A model describing dynamically heterogeneous relaxation in complex coupled systems is presented. The model predicts the splitting of a high-temperature single Debye relaxation to a low-temperature bimodal relaxation. The bimodal process shows a crossover from a Debye-type relaxation to an approximately stretched-exponential relaxation. Some general features of relaxation in complex systems emerge from the predictions of the model, and a comparison of the model with experiments is reported.

Journal Article↗

PubMed2001

Interaction potential among dust grains in a plasma with ion flow.

Linear-response dielectric theory is used to study the interaction potential between dust grains in a flowing plasma, taking into account the finite sizes and the asymmetric charge distributions of the grains. This potential can be divided into two parts: a screened Coulomb potential and a wake potential. The former is a short-ranged repulsive potential, while the later is a long-ranged oscillatory potential which acts only on trailing grains. Both the amplitude and wavelength of the wake potential depend on the Mach number. The grain size and the asymmetric charge distribution may affect the interaction potential in a significant way when the distances between grains are comparable with the grain size, or when the grain size is comparable with the plasma Debye length.

Journal Article↗

PubMed2001

[Effect of experimental infection with Schistosoma japonicum on the pregnancy of mice].

OBJECTIVE: To understand the effect of Schistosoma infection on the gestation in mice. METHODS: Female mice infected with Schistosoma japonicum cercariae, and mated with male mice (uninfected) at 40 d and 100 d post-infection, the changes during pregnant period and the growth of offspring were observed until birth. The serum level of estradiol and progesterone of the infected mice was measured by RIA at oestrus. RESULTS: The level of estradiol and progesterone, and the pregnant rate were much lower in schistosome infected group than that of the control. The rate of abortion, the mortality of pregnant mice and the death rate due to abortion of infected mice increased significantly. The mortality increased with the time of merging male and female mice in one cage prolonged. The body weight and length of the offspring in both infected and control groups were found no significant difference. CONCLUSION: The results revealed that schistosome infection may suppress estradiol and progesterone secretion, decrease the rate of pregnancy, and that it may also increase the complications and mortality during the gestation periods.

Animals↗

PubMed2000

Effect of long term fluoride exposure on lipid composition in rat liver.

Chronic fluorosis can severely damage many systems of human body, but its pathogenesis is unclear. Normal composition and structure of cellular membrane lipids are a basic factor to maintain cell function. In this investigation, cellular membrane lipids of the liver were analysed after a long term fluoride treatment for rats and the results are discussed in order to give an explanation for the pathogenesis of this disease. Wistar rats were supplied with drinking water containing either 30 or 100 ppm fluoride (NaF) for seven months. Contents of phospholipid and neutral lipid in rat liver were analyzed by high-performance liquid chromatography, and fatty acid composition from individual phospholipids was measured by gas chromatography. Results showed that the total liver phospholipid content decreased in the rats treated with high dose of fluoride due to a lower content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Among the fatty acid compositions of PE and PC in the livers of fluoride poisoned animals, the proportion of polyunsaturated fatty acids (20:4 and 22:6) decreased, whereas saturated fatty acids (16:0 and 18:0) increased. No changes could be detected in the amounts of liver cholesterol and dolichol. Total ubiquinone contents in rat liver were reduced by 11% in the group treated with 30 ppm fluoride and by 42% in the group treated with 100 ppm fluoride. In the subclasses of ubiquinone, both ubiquinone-9 and ubiquinoine-10 amounts decreased after fluoride treatment. These modifications of membrane lipids might be induced by oxidative stress, which might be an important factor in the pathogenesis of chronic fluorosis.

Animals↗

PubMed2000

Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis.

An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.

Animals↗

PubMed2000

Determination of molecular changes in soft tissues under strain using laser Raman microscopy.

The paper presents a non-contact technique to examine the molecular changes in a collagen fibre subjected to in vitro axial tension. Laser Raman microscopy was employed to monitor the vibrational changes in specific assignments of the Raman spectrum of collagen. Results were presented in the form of Raman wavenumber shift as a function of applied tensile strain. Two distinct responses were observed depending on whether the vibrations were axial to, or normal to, the collagen backbone. The former response produced a decrease in wavenumber values, indicating tension, whereas the latter produced an increase, indicating compression. The rate of wavenumber shift with applied strain was non-linear in form, with a marked increase at higher levels of applied strain, for example, a strain 4% in the case of axial vibrations. This technique can prove to be a powerful tool for examining deformation at the molecular level in collagenous tissues.

Animals↗

PubMed1999

Nonanticoagulant heparin prevents coronary endothelial dysfunction after brief ischemia-reperfusion injury in the dog.

BACKGROUND: Coronary endothelial dysfunction after brief ischemia-reperfusion (IR) remains a clinical problem. We investigated the role of heparin and N-acetylheparin, a nonanticoagulant heparin derivative, in modulating coronary endothelial function after IR injury, with an emphasis on defining the role of the nitric oxide (NO)-cGMP pathway in the heparin-mediated effect. METHODS AND RESULTS: Male mongrel dogs were surgically instrumented, and the effects of both bovine heparin and N-acetylheparin on coronary endothelial vasomotor function, expressed as percent change from baseline flow after acetylcholine challenge, were studied after 15 minutes of regional ischemia of the left anterior descending artery (LAD) followed by 120 minutes of reperfusion. In dogs treated with placebo (saline), coronary vasomotor function was significantly (P</=0.03) decreased after 15 and 30 minutes of reperfusion (65+/-12% and 73+/-12%) compared with preischemia (103+/-6%). In contrast, the vasodilatory response to the endothelium-independent vasodilator sodium nitroprusside was maintained during reperfusion. Preischemic administration of both bovine heparin and N-acetylheparin (6.0 mg/kg IV) preserved coronary endothelial function throughout reperfusion. In a parallel group of dogs, nitrate/nitrite (NOx) and cGMP levels in the LAD were measured after treatment and during 15-minute reperfusion. Preischemic administration of N-acetylheparin caused a significant increase in basal NOx and cGMP levels compared with saline controls. Pretreatment with N-acetylheparin also caused a significant increase in NOx and cGMP levels in the LAD after 15 minutes of reperfusion compared with IR alone. CONCLUSIONS: These results suggest that heparin preserves coronary endothelial function after brief IR injury by a mechanism independent of its anticoagulant activity and that the effect of heparin may be mediated in part by activation of the NO-cGMP pathway.

Animals↗

PubMed1999

Activity of phosphatidylethanolamine-N-methyltransferase in brain affected by Alzheimer's disease.

To determine whether phospholipid abnormality in Alzheimer's disease is associated with modification of phosphatidylethanolamine-N-methyltransferase, the activity of the enzyme was analysed in the frontal and occipital cortex of the brain from patients with Alzheimer's disease and from aged-matched control. The optimum pH for phosphatidylethanolamine-N-methyltransferase in human brain was 9.0. The enzyme activity was stimulated by detergent TWEEN 20 but inhibited by Triton X-100. Neither magnesium dependence nor chemical methylation was found. A decrease in activity of phosphatidylethanolamine-N-methyltransferase was observed in the frontal cortex of brain affected with Alzheimer's disease. The addition of exogenous phosphatidylethanolamine resulted in no modification in the methylation rate as compared with that of endogenous PE. The addition of phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine resulted in significantly increased rates of methylation in brain tissues. However, the increased rate of phosphatidylethanolamine-N-methyltransferase activity stimulated by exogenous phospholipids was lower in the frontal cortex of brains with Alzheimer's disease when compared to the normals and there was no difference in the occipital cortex between Alzheimer's disease and the control. It is plausible that the decreased activity of phosphatidylethanolamine-N-methyltransferase and its low compensating ability could relate to the modification of phosphatidylcholine in brain tissues from Alzheimer's disease patients.

Aged↗

PubMed1999

Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase.

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248+/-14%). Both u-PA and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti-u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7% for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.

Animals↗

PubMed1998

Enhanced cyclooxygenase-1 expression within the superior mesenteric artery of portal hypertensive rats: role in the hyperdynamic circulation.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to enhanced production of vasodilator substances. Enhanced vasodilation and increased splanchnic blood flow contribute to the elevated portal pressure characteristic of PHT. The aim of this study was to determine whether cyclooxygenase (Cox) expression is altered in PHT vessels and whether chronic inhibition of this enzyme impacts on splanchnic blood flow in PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham operated. Plasma 6-keto-PGF1alpha (prostaglandin F1alpha) levels were significantly elevated in PHT after 2 days as compared with sham and remained elevated up to day 15. Treatment with indomethacin (2 mg/kg i.p. daily for 15 days) resulted in a significant decrease in 6-keto-PGF1alpha levels, which was concomitant with a significant decrease in superior mesenteric artery blood flow (Qsma) after 15 days in PHT rats. Cox-I expression was differentially enhanced in the PHT superior mesenteric artery and thoracic aorta during the development and progression of PHT. In contrast, Cox-II messenger RNA (mRNA) and protein expression was not detected in either of these vessels throughout the development of PHT. These data suggest that PHT is associated with enhanced Cox-I expression within the splanchnic vasculature concomitant with elevated plasma prostacyclin levels and a significant pressor response to indomethacin in PHT animals. We conclude that enhanced Cox-I expression results in increased prostacyclin levels that partially contribute to the maintenance of the hyperemia typical of PHT.

Animals↗

PubMed1998

Increased expression of endothelin receptors in the vasculature of portal hypertensive rats: role in splanchnic hemodynamics.

Portal hypertension (PHT) is characterized by increased portal pressure caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and specific ET receptors in maintaining the vasculopathy of PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated. ET receptor expression was determined in the superior mesenteric artery of sham and PHT rats by in situ autoradiography, radioligand binding analysis, and reverse-transcription polymerase chain reactions (RT-PCR). The pressor response to ET-1 was determined in vitro using isolated vascular rings and in vivo by measuring mean arterial pressure, splanchnic blood flow, and portal venous pressure following treatment with ET and selective ET receptor antagonists. The pressor response to ET in vitro was significantly enhanced in PHT concomitant with increased ET-A and ET-B receptor expression. There was a significant increase in the peak pressor response to ET (10 microg/kg intravenously) in portal hypertensive rats without any significant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 microg/kg intravenously). In contrast, ET-B receptor blockade with IRL-1038 (200 microg/kg intravenously) preferentially decreased splanchnic blood flow and portal venous pressure in portal hypertensive rats. These data suggest that enhanced ET-B receptor expression in portal hypertensive vessels contributes to the maintenance of elevated portal pressure in these animals.

Animals↗

PubMed1998

Heparin preserves nitric oxide activity in coronary endothelium during ischemia-reperfusion injury.

BACKGROUND: Brief episodes of ischemia followed by reperfusion adversely affect endothelial vasomotor function. We hypothesized that heparin may impart a protective effect on the coronary endothelium during ischemia-reperfusion injury possibly via the nitric oxide pathway. METHODS: Eighteen anesthetized dogs were randomly assigned to one of two treatment groups: saline solution or bovine heparin (6.0 mg x kg intravenously). A flow probe and cannula were placed in the left anterior descending artery. Functional recovery of the coronary endothelium was assessed after 15 minutes of ischemia and during 120 minutes of reperfusion after acetylcholine and nitroprusside challenge. In a separate group (n = 10), nitric oxide activity was measured as nitrate/nitrite levels and cyclic guanosine monophosphate levels in the left anterior descending artery. RESULTS: Control dogs displayed a significant decrease in percent change of left anterior descending artery flow at 15, 30, and 60 minutes of reperfusion (67%+/-8%, 76% +/-11%, and 84%+/-8%) when compared with preischemic values (108+/-6; p < 0.01). Heparinized dogs, however, showed preservation of coronary endothelial function after acetylcholine challenge throughout reperfusion. Heparin-treated dogs also displayed a significant increase in nitrate/nitrite levels during reperfusion (37.3+/-4.1 micromol/L) when compared with the saline group (24.3+/-0.8 micromol/L; p < 0.03). Left anterior descending artery levels of cyclic guanosine monophosphate were also significantly increased after heparin administration (3.0+/-0.3 pmol/mg) when compared with ischemia-reperfusion alone (0.7+/-0.1 pmol/mg; p < 0.03). CONCLUSIONS: Heparin preserves the vasoregulatory function of the coronary endothelium during brief episodes of ischemia-reperfusion injury, in part, via the nitric oxide pathway. Administration of heparin may have important therapeutic implications in the prevention of coronary endothelial dysfunction associated with reperfusion injury.

Animals↗

PubMed1998

Heparin and nonanticoagulant heparin preserve regional myocardial contractility after ischemia-reperfusion injury: role of nitric oxide.

OBJECTIVES: These studies were performed to determine the effect of heparin and nonanticoagulant heparin on myocardial function after ischemia-reperfusion and to further evaluate the role that the nitric oxide-cyclic guanosine monophosphate pathway plays in mediating the effect of heparin. METHODS: Fifteen dogs were subjected to 15 minutes ischemia followed by 120 minutes reperfusion and pretreated with either saline solution, bovine heparin (6.0 mg/kg intravenously), or N-acetyl heparin (6.0 mg/kg intravenously), a heparin derivative without anticoagulant properties. The left anterior descending artery was occluded for 15 minutes and regional systolic shortening, a unitless measure of myocardial contractility, assessed during reperfusion. To evaluate the role of nitric oxide, the inhibitor N(omega)-nitro-L-arginine, 1.5 mg/kg intracoronary, was given before heparin administration. Myocardial levels of cyclic guanosine monophosphate, the second messenger of nitric oxide, were also measured in the N-acetyl heparin group using radioimmunoassay. RESULTS: Regional systolic shortening was significantly decreased in the saline group during 60 and 120 minutes compared with before ischemia (9.2 +/- 1.0 and 9.0 +/- 0.9 vs 12.2 +/- 1.2, p < or = 0.0003). Heparin and N-acetyl heparin-treated dogs, however, showed preservation of systolic shortening throughout reperfusion. Administration of nitro-L-arginine significantly attenuated the protective effect of heparin (9.2 +/- 1.2 vs 12.7 +/- 1.1, p < or = 0.0001) and N-acetyl heparin (9.3 +/- 0.3 vs 12.8 +/- 0.4, p < or = 0.0001) during 120 minutes reperfusion. Myocardial levels of cyclic guanosine monophosphate were also significantly increased in the N-acetyl heparin group compared with saline (199.1 +/- 7.1 vs 103.5 +/- 4.5 pmol/mg, p < or = 0.0001). CONCLUSIONS: Heparin preserves myocardial contractility after ischemia-reperfusion independent of its anticoagulant properties. Furthermore, the protective effects of heparin during ischemia-reperfusion are mediated, at least in part, through a nitric oxide-cyclic guanosine monophosphate pathway.

Animals↗

PubMed1997

In situ gene transfer into rat auxiliary liver transplant.

BACKGROUND: A replication-defective retrovirus BAG vector was tested for in situ delivery of the beta-galactosidase gene to auxiliary liver transplant in a rat model. METHODS: The BAG vector, which was shown to be effective in genetic transduction of cultured NIH/3T3 cells, was produced in a psi2 packaging cell and later amplified in a selected PA317 clone. Hepatocyte replication was induced by one-third hepatectomy of the donor liver, and the procedure was followed by auxiliary partial liver transplantation. Twenty-four hours after hepatic induction or transplantation, viral supernatant at 37 degrees C was perfused into the liver graft via the portal vein during a temporary occlusion of the graft portal vein. RESULTS: All animals survived the transplantation procedures and were killed at specified time intervals. Histochemical staining of the liver graft specimens indicated the expression of beta-galactosidase in the gene transferred group but not in the control animals. As demonstrated by polymerase chain reaction assay, the proviral beta-galactosidase sequence was present in the graft specimens, but absent from all other tissues tested. CONCLUSIONS: In short, the retrovirus BAG vector can be useful for in situ delivery of foreign genes to liver graft in transplantation and other clinical settings, providing a simple, consistent, and reliable alternative in hepatic gene therapy experiments.

3T3 Cells↗