Search PubMed⌕ Search

Biomedical subjects

L Huang

Publications and source records attributed to L Huang.

At least 649 records · Page 36Linked to original sources
PubMed1990

Characterization of in vivo immunoliposome targeting to pulmonary endothelium.

Two rat monoclonal antibodies, 34A and 201B, which specifically bind to a surface glycoprotein (gp112) of the pulmonary endothelial cell surface, have been coupled to unilamellar liposomes of approximately 0.25 microns in diameter. The 34A- and 201B-liposomes (monoclonal antibodies 273-34A and 411-201B, respectively), but not antibody-free liposomes and liposomes coupled to 14, a nonspecific monoclonal antibody, accumulate efficiently (approximately 30% injected dose) in the lung of mice which have been injected via the tail vein. Immunoliposome targeting to lung is demonstrated both by using a 125I-labeled lipid marker and an entrapped water-soluble marker. Lung accumulation of 34A-liposomes is completely blocked by a preincubation of free antibody 34A, but not antibody 14, indicating that the immunoliposome accumulation at the target site is immunospecific. Time course studies have revealed that 34A-liposomes bind to lung antigens within 1 min after injection, indicating that the target binding takes place during the first few passages of immunoliposomes through the lung capillary bed. Unbound immunoliposomes are taken up by liver and spleen within 3-5 min after injection. The level of lung accumulation increases significantly as the protein:lipid ratio of the immunoliposome increases. Approximately 50% of injected dose is accumulated in lung for 34A-liposomes, with an average of 935 antibody molecules per liposome. Immunoliposomes of larger size accumulate in lung more significantly than those of smaller size. Injection with higher doses also enhances the level of lung accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation.

Acid-sensitive liposomes composed of unsaturated phosphatidylethanolamine (PE) are efficient vehicles for cytoplasmic delivery of the target cells. We have recently shown that liposomes composed of dioleoyl-PE (DOPE) and dipalmitoyl-succinylglycerol (DPSG) retain the acid-sensitivity after exposure to human plasma. In the present work, we have extended these observations to investigate the role of ganglioside GM1 on the blood residence time of these liposomes. Small (d approximately 100 nm) unilamellar liposomes composed of DOPE and DPSG (4:1, molar ratio) became progressively less acid-sensitive when increasing amounts of GM1 were included in the lipid composition. However, partial sensitivity to acid (40-50% release of entrapped contents at pH 4) could be retained up to 5% GM1, even for liposomes which had been exposed to human plasma. Inclusion of GM1 in the lipid composition only slightly increased the release of entrapped contents in the presence of human plasma. The biodistribution of i.v. injected GM1-containing liposomes was studied by following the entrapped 125I-labeled tyraminylinulin marker in Balb/c mice. Inclusion of up to 5% GM1 showed a transient increase in the blood level and a concomitant decrease of liver and spleen uptake of liposomes. Thus, these liposomes are pH-sensitive, plasma-stable and show a relatively prolonged residence time in circulation. They are potentially significant drug carriers in vivo.

Animals↗
PubMed1990

Proton and divalent cations induce synergistic but mechanistically different destabilizations of pH-sensitive liposomes composed of dioleoyl phosphatidylethanolamine and oleic acid.

Protons and divalent cations show synergistic effects on the destabilization of liposomes composed of unsaturated phosphatidylethanolamine and oleic acid (Düzgünes et al., Biochemistry (1985) 24, 3091). We have extended these observations and investigated the effects of Ca2+ and Mg2+ on the proton-induced destabilization of dioleoyl phosphatidylethanolamine/oleic acid (DOPE/OA) (4:1 molar ratio) liposomes. Temperature-induced aggregation was measured by 90 degrees light scattering. Lipid mixing was used to monitor vesicle destabilization and freeze-fracture electron microscopy was used to examine the structures formed from DOPE/OA vesicles in the presence of Ca2+ and/or protons. Both Mg2+ and Ca2+ shift the pH required for 50% lipid mixing to higher values. Temperature-induced vesicle aggregation occurs at lower temperatures in the presence of divalent cations and/or protons, indicating that intervesicular repulsions are decreased. Freeze-fracture electron micrographs show that the structures formed from DOPE/OA in the presence of Ca2+ differ significantly from those found in the presence of protons. In general, protons induce the formation of hexagonal phase, while the presence of Ca2+ leads to the formation of extensive regions of lamellar sheets with numerous lipidic particles. The synergistic effect of divalent cations and proton may be important for the maximal biological activity of DOPE/OA liposomes.

Calcium↗
PubMed1990

Determination of 2-methylaziridine in workplace atmospheres.

A sampling and analytical procedure was developed for the monitoring of airborne 2-methylaziridine (MA). The analyte is collected by drawing air through a solution of 2,4,6-trinitrobenzenesulphonic acid (TNBS). In situ derivatisation of MA with TNBS during sample collection provides stability to the highly reactive analyte and makes it amenable to a sensitive high-performance liquid chromatographic determination with ultraviolet detection. The purified synthetic derivative of MA with TNBS is more suitable as a calibration standard than commercially available MA.

Air Pollutants, Occupational↗
PubMed1990

Lipid composition is important for highly efficient target binding and retention of immunoliposomes.

By taking advantage of a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, we have prepared liposomes containing various amounts of antibody molecules (immunoliposomes). These immunoliposomes accumulate specifically in the lung when injected i.v. Two lipid compositions were used: phosphatidylcholine/cholesterol/phosphatidylserine (PS), 10:5:1 (mol/mol), a composition that allows liposomes to be readily taken up by the reticuloendothelial system (RES) (liver and spleen), and phosphatidylcholine/cholesterol/ganglioside GM1, 10:5:1 (mol/mol), a composition that allows liposomes to avoid or delay the RES uptake (the so-called stealth liposomes). Although an increase in the number of antibody molecules per liposome was accompanied by an increased level of lung binding of the immunoliposomes, differences due to the lipid composition were more profound. For example, stealth immunoliposomes containing an antibody/lipid ratio = 1:37 (wt/wt) accumulated in lung to a level of 60% of the injected dose, whereas PS-containing immunoliposomes with a higher antibody/lipid ratio (1:8) only accumulated 50% of the injected dose in the lung. Conjugation of antibody to the stealth liposome did not increase the rate of liposome uptake by liver; this rate was approximately 10-fold lower than that of the PS-containing liposomes without antibody. Stealth immunoliposomes with high antibody content also showed long retention in the lung. The t1/2 of lung residence for the stealth immunoliposomes with an antibody/lipid ratio = 1:11 (wt/wt) was approximately 24 hr. The fact that stealth immunoliposomes showed a longer retention time in the lung than the PS-containing immunoliposomes of similar antibody content suggests that macrophages may play a role in the removal of the bound immunoliposomes from the pulmonary endothelium. Alternatively, dissociated stealth immunoliposomes may reenter the circulation and rebind to the lung target, causing an apparent slow overall dissociation rate. These results can be understood on the basis of two competing kinetic processes: lung binding whose rate is directly proportional to the antibody content of the immunoliposomes and uptake by RES whose rate is significantly reduced in the case of the stealth liposomes. Even for a modest level of antibody content, the half-life for target binding of immunoliposomes was significantly shorter than the half-life of liver uptake of the liposomes, resulting in a favorable target binding. Significant immunoliposome binding to the lung is not due to the fact that tail vein-injected liposomes flow through the lung capillary bed before they encounter the liver, because portal vein-injected immunoliposomes showed the same rate and extent of target binding as the tail vein-injected ones.

Animals↗
PubMed1990

Regulation of 5-Aminolevulinic Acid (ALA) Synthesis in Developing Chloroplasts : III. Evidence for Functional Heterogeneity of the ALA Pool.

Gabaculine and 4-amino-5-hexynoic acid (AHA) up to 3.0 millimolar concentration strongly inhibited 5-aminolevulinic acid (ALA) synthesis in developing cucumber (Cucumis sativus L. var Beit Alpha) chloroplasts, while they hardly affected protochlorophyllide (Pchlide) synthesis. Exogenous protoheme up to 1.0 micromolar had a similar effect. Exogenous glutathione also exhibited a strong inhibitory effect on ALA synthesis in organello but hardly inhibited Pchlide synthesis. Pchlide synthesis in organello was highly sensitive to inhibition by levulinic acid, both in the presence and in the absence of gabaculine, indicating that the Pchlide was indeed formed from precursor(s) before the ALA dehydratase step. The synthesis of Pchlide in the presence of saturating concentrations of glutamate was stimulated by exogenous ALA, confirming that Pchlide synthesis was limited at the formation of ALA. The gabaculine inhibition of ALA accumulation occurred whether levulinic acid or 4,6-dioxohepatonic acid was used in the ALA assay system. ALA overproduction was also observed in the absence of added glutamate and was noticeable after 10-minute incubation. These observations suggest that although Pchlide synthesis in organello is limited by ALA formation, it does not utilize all the ALA that is made in the in organello assay system. Gabaculine, AHA, and probably also protoheme, inhibit preferentially the formation of that portion of ALA that is not destined for Pchlide. A model proposing a heterogenous ALA pool is described.

Journal Article↗
PubMed1990

Evidence that Isolated Developing Chloroplasts Are Capable of Synthesizing Chlorophyll b from 5-Aminolevulinic Acid.

Developing chloroplasts isolated from cucumber (Cucumis sativus L. var Beit Alpha) cotyledons are capable of incorporating [(14)C]5-aminolevulinic acid into chlorophyll (Chl) b and Chl a when incubated under photosynthetic illumination. Thin layer chromatography and high pressure liquid chromatography were employed to analyze the pigments. The specific radioactivity in Chl a was over three times higher than that found in Chl b. Both Chl a and b synthesizing activities in organello decayed rapidly at approximately the same rate. We conclude that concomitant synthesis of Chl a/b-binding apoprotein is not required for Chl b synthesis.

Journal Article↗
PubMed1990

Cellulose digestion and cellulase regulation and distribution in Fibrobacter succinogenes subsp. succinogenes S85.

Fibrobacter succinogenes subsp. succinogenes S85 initiated growth on microcrystalline cellulose without a lag whether inoculated from a glucose, cellobiose, or cellulose culture. During growth on cellulose, there was no accumulation of soluble carbohydrate. When the growth medium contained either glucose or cellobiose in combination with microcrystalline cellulose, there was a lag in cellulose digestion until all of the soluble sugar had been utilized, suggesting an end product feedback mechanism that affects cellulose digestion. Cl-stimulated cellobiosidase and periplasmic cellodextrinase were produced under all growth conditions tested, indicating constitutive synthesis. Both cellobiosidases were cell associated until the stationary phase of growth, whereas proteins antigenically related to the Cl-stimulated cellobiosidase and a proportion of the endoglucanase were released into the extracellular culture fluid during growth, irrespective of the substrate. Immunoelectron microscopy of cells with a polyclonal antibody to Cl-stimulated cellobiosidase as the primary antibody and 10-nm-diameter gold particles conjugated to goat anti-rabbit antibodies as the second antibody revealed protrusions of the outer surface which were selectively labeled with gold, suggesting that Cl-stimulated cellobiosidase was located on the protrusions. These data support the contention that the protrusions have a role in cellulose hydrolysis; however, this interpretation is complicated by reactivity of the antibodies with a large number of other proteins that possess related antigenic epitopes.

Bacteroides↗
PubMed1990

Antigenic nature of the chloride-stimulated cellobiosidase and other cellulases of Fibrobacter succinogenes subsp. succinogenes S85 and related fresh isolates.

Polyclonal and monoclonal antibodies to the Cl-stimulated cellobiosidase of Fibrobacter succinogenes subsp. succinogenes S85 reacted with numerous proteins of both higher and lower molecular weights from F. succinogenes subsp. succinogenes S85, but not with Escherichia coli proteins, and only one protein each from Butyrivibrio fibrisolvens and Ruminococcus albus. Different profiles were observed for Western blots (immunoblots) of peptide digests of both the purified enzyme from F. succinogenes and immunoreactive proteins of higher and lower molecular weights, demonstrating that they were different proteins. Therefore, F. succinogenes appeared to produce numerous proteins with one or more common antigenic determinants. However, with the exception of Cl-stimulated cellobiosidase, none were cellulases that have been characterized. An affinity-purified polyclonal antibody to Cl-stimulated cellobiosidase reacted with numerous proteins in cells of each of three fresh isolates of F. succinogenes subsp. succinogenes and one of F. succinogenes subsp. elongata when analyzed by Western blotting. Antibodies to periplasmic cellodextrinase, endoglucanase 2 (EG2), and EG3, when reacted in Western blots with the various cellulases, including Cl-stimulated cellobiosidase, revealed limited antigenic similarity among the different proteins and none with either B. fibrisolvens or R. albus proteins. The periplasmic cellodextrinase antibody reacted with an antigen with a size corresponding to cellodextrinase in each of the three F. succinogenes subsp. succinogenes isolates but not with any antigens from the F. succinogenes subsp. elongata isolate. The anti-EG2 antibody reacted with single antigens in each of the four isolates, while the anti-EG3 antibody reacted with only one of the four isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteroides↗
PubMed1990

Integration host factor is a negative effector of in vivo and in vitro expression of ompC in Escherichia coli.

Integration host factor (IHF) of Escherichia coli is a DNA-binding protein involved in gene expression and other cellular functions in E. coli and some of its bacteriophages and plasmids. We report here that IHF is a direct negative effector of the ompC operon of E. coli. IHF binds to ompC DNA and protects a region of 35 base pairs located upstream from the ompC promoters. The addition of IHF to a purified in vitro transcription system inhibited transcription from two of the three ompC promoters. In vivo experiments suggest that the in vitro results are physiologically relevant. IHF mutants show increased expression of OmpC. In addition, the OmpC- phenotype of certain strains is completely suppressed by a mutation in IHF.

Bacterial Outer Membrane Proteins↗
PubMed1990

Influence of peptide acylation, liposome incorporation, and synthetic immunomodulators on the immunogenicity of a 1-23 peptide of glycoprotein D of herpes simplex virus: implications for subunit vaccines.

A peptide corresponding to residues 1 to 23 of glycoprotein D of herpes simplex virus type 1 was chemically synthesized and coupled to a fatty acid carrier by standard Merrifield synthesis procedures. The resulting peptide-palmitic acid conjugate (acylpeptide) exhibited enhanced immunogenicity in mice as compared with that exhibited by the free form of the peptide. Incorporation of the acylpeptide into liposomes further increased the immunogenicity of the peptide, while inclusion of the immunomodulators muramyl tripeptide phosphatidylethanolamine and monophosphoryl lipid A into the same liposome stimulated the strongest response. The humoral immune responses induced by the acylpeptide-liposome construct were greater than those induced by peptide in Freund complete adjuvant, and cellular responses were equal. The acylpeptide-immunomodulator-liposome formulation also induced significant levels of protective immunity, although the immunity was less than that induced by herpes simplex virus infection. Acylated peptides, especially in liposomes, were taken up more effectively by draining lymph nodes, which possibly accounts in part for the enhanced immunogenicity of the peptides. Since the acylpeptide-immunoliposome formulation used was nontoxic, it could represent a useful way to enhance immunogenicity of subunit peptides used for vaccine purpose in humans and animals.

Acylation↗
PubMed1990

[Effects of thyroxine on IgM production and beta-adrenergic receptor on lymphocyte in mice].

The effects of thyroxine (L-T4) on the IgM production of splenocytes in mice induced by sheep red blood cell (SRBC) were investigated by means of spectrophotometry of quantitative hemolysis (QHS). The maximum binding site number (Bmax) and affinity (Kd) of beta-adrenergic receptors (beta-Adr. R.) on splenic lymphocytes of mice under the different thyroid functional status during immune response were determined by radio-ligand combination method. The IgM production and Bmax of beta- Adr. R. of splenic lymphocytes were increased in "hyperthyroid mice" and decreased in "hypothyroid mice" as compared with the control (P less than 0.01) during the 3rd to 5th day after immunization with SRBC, but affinity of beta-Adr. R. was not changed (P greater than 0.05). It is suggested that L-T4 could increase the IgM production in lymphocytes induced by SRBC in mice. The underlying mechanism seems to involve an increasing Bmax of beta-Adr. R. on the immune cell, thus enhancing its sensitivity to catecholamine.

Animals↗
PubMed1990

[Studies on the resolution of racemic gossypol. II. By chiral alpha-methylphenethylamine and alpha-methylbenzylamine].

A simplified and more practical method for the resolution of racemic gossypol was developed by quick chromatographing the condensation products of either (S) or (R)-alpha-methylphenethylamine and alpha-methylbenzylamine with racemic gossypol on a silica column using diethylether/light petroleum as eluent. The optically active gossypol thus obtained showed specific rotation [alpha]D of (+) or (-)370 +/- 10 degrees, with ee% 96.8 and 98.8 respectively and chemical purity greater than 99% by HPLC. Isomerization of the amino condensates of optically active gossypol through the racemization of the binaphthalene moiety of gossypol was observed, though gossypol itself is optically stable in such condition. The rate of racemization varied with the structure of the amine moiety and solvent present and was increased by light and free radical initiator.

Amphetamine↗
PubMed1990

[Studies on the resolution of racemic gossypol. III. Study on the chemical and physical properties of the amino condensates of gossypol].

Fifteen condensates of chiral amines and racemic gossypol were prepared. Their 1HNMR spectra indicated that all the amine condensates tested had the same keto-enamine structures and shifts of protons on C11, C11 of various condensates were analyzed for their structural relationship. The Rf and delta Rf values (difference between (+) and (-)gossypol condensates) on TLC of these derivatives and stability of eight condensates of (-)gossypol were examined. All these properties were discussed in light of the configuration of gossypol. These studies not only provided rational basis of selecting resolving agent, but also gave indications of their relative absorbability and stereochemistry of the condensates which might be useful in postulating their in vivo behaviors and designing derivatives with better pharmacological actions.

Gossypol↗
PubMed1990

[Studies on the resolution of racemic gossypol. IV. Use of threo (-) or (+)-1-(p-nitrophenyl)-1,3-dihydroxypropylamine-2 as the resolving agent].

Threo (-) or (+)-1-(p-nitrophenyl)-1,3-dihydroxypropylamine-2 was found to be a useful resolving agent for racemic gossypol. The optical and chemical stability of the condensate of enantiomeric gossypols with the titled amine and the great difference in the Rf values on TLC and the solubilities in various solvents between the two diastereoisomeric condensates facilitate the separation. Therefore, the pure isomers can be easily obtained by means of chromatography or crystallization.

Chloramphenicol↗
PubMed1990

[The relationship of structure in vivo of low tension glaucoma and myopia].

The structure in vivo and incidence of myopia on thirty patients with low tension glaucoma were studied in this paper. Results showed that the incidence of high myopia of patients with low tension glaucoma was higher than normal. All of the mean values of the thickness of lens, the length of vitreous and axis, and the area of optic disc were larger than normal too. These indicate that patients with low tension glaucoma may often be associated with high myopia, and their structure of eye in vivo differs from normal. These may be related to pathogenesis of disease with low tension glaucoma. The relationship of myopia and structure of optic disc with glaucoma were briefly summarized.

Adult↗
PubMed1990

[A preliminary study on the pharmacology of the compound prescription huangqin tang and its component drugs].

Results obtained from the pharmacological experiments demonstrated that the compound prescription Huangqin Tang and its component drugs, roots of Paeonia lactiflora, Scutellaria baicalensis and Glycyrrhiza uralensis, and the fruit of Ziziphus jujuba showed marked anti-inflammatory effect. The compound prescription and its component drugs, except the peony root, possessed significant antispastic effect. Antipyretic effect of Radix Scutellariae, Radix Glycyrrhizae and Huangqin Tang was suggested. Huangqin Tang, Radix Paeoniae alba, and Radix Glycyrrhizae showed marked analgesic effect. In addition, the experiments confirmed that both Huangqin Tang and single Radix Scutellariae have sedative effect.

Animals↗