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Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

768 records · Page 43Linked to original sources
PubMed1974

Long term results of gastrectomy with respect to blood lipids, blood pressure, weight and living habits.

A sample of ambulant Japanese-American men (ages 45-69 years), was divided into those having a previous partial gastrectomy and a control non-gastrectomy population. Three-hundred-and-forty-seven men with a history of partial gastrectomy weighed less and had lower values for serum cholesterol, triglyceride, and blood pressure than did the control population of 7,598 men. The depressed lipid and blood pressure values could not be entirely explained by the reduced weight. Likewise, none of these differences appeared related to diet or living habits. Those operated on for gastric ulcer had, on the average, lower systolic pressures than duodenal ulcer patients and those with gastrojejunal anastamoses had lower cholesterol levels than patients with a gastroduodenostomy.

Alcohol Drinking↗
PubMedDate not supplied

Improving plasmid DNA-mediated liver gene transfer by prolonging its retention in the hepatic vasculature.

BACKGROUND: Naked DNA is the simplest and safest method to deliver genes to the liver. In this study, we demonstrate that significant gene expression could be achieved in the liver by transiently restricting blood flow through the liver immediately following peripheral intravenous injection of plasmid DNA. METHODS: Mice were intravenously (tail vein) injected with plasmid DNA in 100 microl of saline (0.9% NaCl) immediately followed by 8 s of occlusion of blood flow through the liver. The occlusion of blood flow was performed by using a clip at either the vena cava (VC) or at the portal vein and hepatic artery (PV+HA). Alternatively, the VC was clamped for 4 s followed by clamping the PV+HA for 4 s (VC and PV+HA). RESULTS: Gene transfer to the liver was completed after blood flow through the liver was blocked for as short as 1 s. Up to 560 pg of luciferase protein per mg of extracted protein was observed from the liver after a single injection of 80 microg of plasmid DNA. Gene expression was increased more than 50-fold by the combination of clamping and electroporation. CONCLUSION: This is the first demonstration of gene transfer to the liver via systemic administration without using any carrier system or physical force. Also, the technique provides new insights into the mechanism of hepatic gene transfer.

Animals↗
PubMedDate not supplied

Thromboxane A2 mimetic, U46,619, and slowly adapting stretch receptor activity in the rabbit.

The effect of infusing the thromboxane A2 mimetic U46,619 on afferent activity from slowly adapting airway stretch receptors (SARs) in the anesthetized rabbit was examined in these experiments. SAR vagal afferent fibers (n = 29) were identified by their slow adaptation to a sustained (10-15 s duration) lung inflation in the closed-chest, mechanically ventilated animal (n = 16). Intravenous infusion of U46,619 increased the discharge frequency of the SAR, measured at the end of inspiration, in a dose-dependent manner: by 6.6% and 8.0% at doses of 0.1 and 0.5 microgram of U46,619/kg, respectively. This increase in SAR activity was correlated with increases in end-inspiratory tracheal airway pressure (6.4% at 0.1 micrograms/kg and 9.1% at 0.5 micrograms/kg). Higher doses of U46,619 could not be administered due to decreases in systemic arterial blood pressure. The increase in SAR activity and tracheal airway pressure was qualitatively comparable to the response to histamine (25 micrograms/kg), a known bronchoconstrictor. We conclude that intravenous infusion of U46,619 in the anesthetized rabbit at doses that elicit significant hemodynamic effects causes modest bronchoconstriction and comparable increases (less than 10%) in SAR afferent nerve activity. From these data, it appears that U46,619 has no direct effect on SARs, but rather increases SAR activity due to bronchoconstriction.

Airway Resistance↗
PubMedDate not supplied

The influence of proglumide, a putative CCK antagonist, on cerebral ischemia in gerbil.

Studies were conducted to clarify the possible role of CCK in cerebral ischemia and to evaluate the effects of proglumide, a competitive and reversible CCK antagonist, as a potential therapeutic or prophylactic tool in the treatment of cerebral ischemia. Proglumide at the doses of 10, 50 and 150 mg/kg was administered to gerbils before unilateral carotid ligation, and its effect on stroke index score, incidence and mortality rate was observed. Our results show that proglumide injected prior to carotid ligation at the dose of 150 mg/kg significantly reduces both incidence and mortality rate and changes the distribution of the stroke index score in gerbils. There was a significant inverse relationship between the dose of proglumide and both incidence and mortality: the greater the injection dose of proglumide, the lower the incidence and mortality. These results suggest that CCK may be involved in the pathological processes of cerebral ischemia and proglumide or related compounds prove to be effective in the pharmacological prophylaxis of ischemic brain damage.

Animals↗
PubMedDate not supplied

125I labelling of human serum albumin and fibrinogen and a study of protein adsorption properties on the surface of titanium oxide film.

In order to detect the surface concentration of proteins adsorbed on a solid surface for selecting blood compatible materials, a gentle iodination reagent, Iodogen, was used to label human serum albumin and fibrinogen, and has been applied to the study of protein adsorption properties on a plate of titanium oxide film. The yields of the labelled albumin and fibrinogen are 69.7% and 49.6%. The results of adsorption show that [125I]HSA and [125I]HFG are efficacious at the surface concentration detection and can be used to investigate the protein adsorption properties of a solid material.

Adsorption↗
PubMedDate not supplied

Glucose-induced release of glycosylpoly(ethylene glycol) insulin bound to a soluble conjugate of concanavalin A.

Treatment of diabetes mellitus by insulin injections provides long-term control of the disease but lacks any feedback response to glucose concentration changes, which finally leads to a number of life-threatening conditions. The purpose of this study was to improve and optimize an implantable, concanavalin A (Con A) based, glucose-responsive insulin delivery system studied earlier [Jeong, S. Y., Kim, S. W., Holmberg, D. L., and McRea, J. C. (1985) J. Controlled Release 2, 143-152], which can be used for long-term diabetes treatment. To optimize the "insulin component" of the delivery system, we prepared PheB1 insulin amino group monosubstituted monoglucosylpoly(ethylene glycol) (G-PEG) insulin conjugates (PEG M(r) 600 or 2000), which showed preserved bioactivity, significantly improved solubility and solution stability at neutral pH, and substantially suppressed hexamerization/dimerization. To improve the delivery system further, we synthesized and characterized a conjugate of Con A and monomethoxypoly(ethylene glycol) (mPEG, M(r) 5000) grafted hydrophilic poly(vinylpyrrolidone-co-acrylic acid) (PVPAA) with M(r) of 250,000. The optimal conjugate contained around eight PEG chains and two to three Con A tetramers attached through the amide bonds to the PVPAA chain. The Con A sugar binding characteristics were preserved, and, more importantly, Con A solubility at pH 7.4 substantially increased. This also holds true for a complex formed by the Con A conjugate and G-PEG insulin, which is soluble and does not precipitate under the physiologically relevant conditions under which the complex formed by the Con A conjugate and glycosyl insulin immediately precipitates. Finally, no leakage of the Con A conjugate from a membrane device was detected. Preliminary in vitro release experiments with Con A conjugate and G-PEG insulin complex enclosed in the membrane device showed a pulsative, reversible release pattern for G-PEG insulin in response to glucose challenges of 50-500 mg/dL, demonstrating the feasibility of the release system for use in planned, chronic in vivo studies with diabetic (pancreatectomized) dogs.

Acrylic Resins↗
PubMedDate not supplied

Extending insulin action in vivo by conjugation to carboxymethyl dextran.

The biochemical and pharmacological properties of bioactive peptides and proteins can be altered by conjugation with polymers. This report describes site-specific attachment of insulin to activated carboxyl groups of carboxymethyl dextran (CMD, MW=51000) through the GlyA1 insulin amino group. On average, three or four insulin molecules were grafted to a CMD linear chain. Coupled insulin molecules were properly folded, and the bioactivity of conjugated insulin in the blood glucose depression assay was 9.6 IU/mg, which was only 2.6 times less than that for native insulin. The cell growth study indicated that the CMD-insulin conjugate was as mitogenic as insulin on vascular smooth muscle cells, whereas the starting CMD polymer was not. The insulin receptor binding constant of the conjugate (3.6 x 10[9] M[-1]) compared well with that of native insulin (7.6 x 10[9] M[-1]), indicating that the CMD chain does not present any major constraints to binding. Plasma clearance of CMD-insulin obeyed a two-compartment pharmacokinetic (PK) model with a CMD-insulin conjugate plasma elimination half-life of 114.1 min, which was significantly longer than that of soluble Zn-insulin (12.4 min). In contrast, pharmacodynamic (PD) profiles (blood glucose lowering effects) after intravenous (iv) administration of the conjugate or insulin in rats were not different. Subcutaneous (sc) administration of the conjugate resulted in a significantly prolonged plasma profile with a noncompartmental PK parameter mean residence time (MRT) of 103.5 min which was significantly longer than that of soluble Zn-insulin (40.5 min). This was reflected in the protracted PD effect of sc administered conjugate with time needed to reach minimum glucose concentration Tnadir of 95.7 min, which was significantly longer than that of insulin (62 min). We conclude that the conjugation of insulin to CMD leads to a bioactive conjugate with a delayed sc PD profile showing prolonged response, resembling intermediate acting insulin preparations.

Animals↗
PubMedDate not supplied

Lactose-poly(ethylene glycol)-grafted poly-L-lysine as hepatoma cell-tapgeted gene carrier.

To investigate the delivery of DNA into cells, lactose-poly(ethylene glycol)-grafted poly-L-lysine (Lac-PEG-PLL) polymers were synthesized as polymeric gene carriers. The new synthetic carriers, varying the substitution ratio of lactose-poly(ethylene glycol) (lactose-PEG), were characterized by NMR spectroscopy and size-exclusion chromatography. Electrophoretic mobility assay confirmed that the new gene carrier makes a complex with plasmid DNA. The attached poly(ethylene glycol) gives better solubility properties to gene/carrier complex. Transfection experiments showed that Lac-PEG-PLL efficiently delivers DNA to a hepatoma cell line in vitro; the best efficiency was achieved at a 1:3 weight ratio of DNA to carrier. As the lactose-PEG substitution content increased up to 30%, the transfection efficiency increased, which demonstrates that the lactose serves as a targeting moiety. No considerable cytotoxicity was observed due to Lac-PEG-PLL or its complex with DNA within the concentration range for this experiment. The use of chloroquine increased transfection efficiency that indicates the involvement of hydrolytic degradation of the system in lysosome. It is likely that plasmid DNA/Lac-PEG-PLL complexes enter the cells through a receptor-mediated endocytosis mechanism. These results show that Lac-PEG-PLL can form a complex with plasmid DNA and serve as an efficient gene delivery carrier with lower cytotoxicity compared to that of poly-L-lysine. Therefore, it is expected that our Lac-PEG-PLL carrier can be used as an in vivo gene delivery vector.

Animals↗
PubMedDate not supplied

Synthesis and characterization of poly(ethylene glycol)-insulin conjugates.

Human insulin was modified by covalent attachment of short-chain (750 and 2000 Da) methoxypoly (ethylene glycol) (mPEG) to the amino groups of either residue PheB1 or LysB29, resulting in four distinct conjugates: mPEG(750)-PheB1-insulin, mPEG(2000)-PheB1-insulin, mPEG(750)-LysB29-insulin, and mPEG(2000)-LysB29-insulin. Characterization of the conjugates by MALDI-TOF mass spectrometry and N-terminal protein sequence analyses verified that only a single polymer chain (750 or 2000 Da) was attached to the selected residue of interest (PheB1 or LysB29). Equilibrium sedimentation experiments were performed using analytical ultracentrifugation to quantitatively determine the association state(s) of insulin derivatives. In the concentration range studied, all four of the conjugates and Zn-free insulin exist as stable dimers while Zn(2+)-insulin was exclusively hexameric and Lispro was monomeric. In addition, insulin (conjugate) self-association was evaluated by circular dichroism in the near-ultraviolet wavelength range (320-250 nm). This independent method qualitatively suggests that mPEG-insulin conjugates behave similarly to Zn-free insulin in the concentration range studied and complements results from ultracentrifugation studies. The physical stability/resistance to fibrillation of mPEG-insulin conjugates in aqueous solution were assessed. The data proves that mPEG(750 and 2000)-PheB1-insulin conjugates are substantially more stable than controls but the mPEG(750 and 2000)-LysB29-insulin conjugates were only slightly more stable than commercially available preparations. Circular dichroism studies done in the far ultraviolet region confirm insulin's tertiary structure in aqueous solution is essentially conserved after mPEG conjugation. In vivo pharmacodynamic assays reveal that there is no loss in biological activity after conjugation of mPEG(750) to either position on the insulin B-chain. However, attachment of mPEG(2000) decreased the bioactivity of the conjugates to about 85% of Lilly's HumulinR formulation. The characterization presented in this paper provides strong testimony to the fact that attachment of mPEG to specific amino acid residues of insulin's B-chain improves the conjugates' physical stability without appreciable perturbations to its tertiary structure, self-association behavior, or in vivo biological activity.

Animals↗
PubMedDate not supplied

GC/MS identification of tetramine in samples from human alimentary intoxication and evaluation of artificial carbonic kidneys for the treatment of the victims.

One day in July 1991, 78 people became victims of accidental alimentary intoxication in a factory in Hebei Province, China. Related samples, including rodenticide bait, the artificial carbonic kidneys used for the treatment of the victims, and the victims' blood, were analyzed by GC/MS. Tetramine [80-12-6], a highly toxic rodenticide, was identified as the toxicant. The effectiveness of artificial carbonic kidneys was evaluated. The analytical results revealed that detoxification of the patients was effective 48 hours after intoxication by percolating their blood through artificial carbonic kidneys.

Bridged-Ring Compounds↗
PubMedDate not supplied

Simazine runoff from citrus orchards affected by shallow mechanical incorporation.

Simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine) losses via runoff in California are a potential source of environmental contamination because simazine is widely used for weed control during the rainy season from November to March. This study was conducted in two citrus orchards from three rainfall events to evaluate the effects of shallow mechanical incorporation on simazine losses in runoff during the winter. Simazine losses in runoff were compared between row middles that were either undisturbed, the normal orchard practice, or subjected to shallow mechanical incorporation. Mechanical incorporation of row middles significantly reduced runoff volumes by approximately 45 and 28% for the first and second runoff events, respectively. In undisturbed plots, simazine concentrations in runoff from the first runoff event ranged from 0.62 to 0.73 mg L(-1); then simazine concentrations rapidly decreased (0.03-0.35 mg L(-1)) from the second and third runoff events. In disturbed plots, simazine concentrations in runoff from the first runoff event ranged from 0.21 to 0.24 mg(-1), but simazine concentrations remained relatively constant between the three runoff events. Total mass recoveries of simazine in runoff ranged from 1.93 to 2.97% and from 0.70 to 0.74% of application from the undisturbed plots and from the disturbed plots, respectively. Low water infiltration rate inhibited surface-applied herbicide incorporation into the soil matrix with natural rainfall in compacted soils. Mechanical incorporation of row middles significantly reduced runoff volumes, simazine concentrations, and mass losses in runoff after application.

Agriculture↗