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Biomedical subjects

K Hong

Publications and source records attributed to K Hong.

162 records · Page 9Linked to original sources

Inhibitory effect of K-76 monocarboxylic acid, an anticomplementary agent, on the C3b inactivator system.

K-76COOH caused dose-dependent inhibition of the degradation, by C3b inactivator (C3bINA) and beta 1H, of membrane-bound C3b on EAC1-3b and of free C3b in the fluid phase, i.e., cleavage of the C3b alpha' peptide chain. K-76COOH primarily attacked C3bINA but not beta 1H or C3b. K-76COOH inhibited the suppression of immune adherence reactivity and the manifestation of conglutination reactivity of EAC1-3b cells by C3bINA and beta 1H. The drug also inhibited the reaction between conglutinin and EAC1-3b' cells derived from EAC1-3b by treatment with C3bINA and beta 1H. EAC1-3b cells did not form rosettes with either Daudi or Raji lymphoblastoid cells. Treatment with C3bINA and beta 1H rendered EAC1-3b cells reactive with Daudi cells, and this change was inhibited by K-76COOH. EAC1-3b cells became able to form rosettes with Raji cells after addition of beta 1H. This rosette formation was enhanced by further addition of C3bINA, and this enhancement was also suppressed by K-76COOH.

Animals↗

Metabolism of nitrous oxide by human and rat intestinal contents.

Nitrous oxide labeled with a stable heavy nitrogen isotope was used for in-vitro studies of nitrous oxide metabolism in man and rat. At 5 per cent oxygen tension, which is comparable to normal oxygen tension in the intestine in vivo, each gram of intestinal contents during a 16-hr in-vitro incubation produced 47 +/- 13 nmol of molecular nitrogen for the rat and 103 +/- 17 nmol for man. Active reductive metabolism of nitrous oxide by intestinal contents was significantly inhibited by antibiotics and by 20 per cent oxygen tension. It is suggested that the reduction of nitrous oxide to nitrogen may proceed through a single-electron transfer process with formation of free radicals. Under these circumstances, metabolism of nitrous oxide could produce toxic intermediates, even thought the end-metabolite is inert.

Animals↗

A complement inhibitor produced by Stachybotrys complementi, nov. sp. K-76, a new species of fungi imperfecti.

A complement inhibitor, K-76, was isolated and purified from the culture supernatant of a fungus, Stachybotrys complementi, nov. sp. K-76, isolated from soil of Ishigaki Island, Okinawa. K-76 is a sesquiterpene compound and it can be oxidized to a monocarboxylic derivative (K-76 COOH), the sodium salt of which is very soluble and much less toxic than K-76. K-76 and K-76 COOH both inhibited complement activation by either the classical or alternative pathway. They inhibited generation of the factor chemotactic to human polymorphonuclear leukocytes from human serum by aggregated immunoglobulin. When sensitized erythrocytes were treated with complement in the presence of K-76 COOH, the resulting unlysed cells were found to be in the state of EACl, 4b, 2a, 3b. Thus K-76 COOH is considered to block mainly the C5 intermediate step. K-76 COOH did not inhibit any proteases or esterases tested, except when tested at high concentration.

Chemotactic Factors↗

An anticomplementary agent, K-76 monocarboxylic acid: its site and mechanism of inhibition of the complement activation cascade.

A monocarboxylic acid derivative (K-76 COOH) of K-76, purified from the culture filtrate of Stachybotrys complement I nov. sp. K-76, inhibits complement (C) activity. Its inhibitory action is mainly on C5 step. It strongly inhibits the generation of EAC1,4b,2a,3b,5b from C5 and EAC1,4b,2a,3b, and accelerates the decay of EAC1,4b,2a,3b,5b. It also causes some inhibition of the reactions of the reactions of C2,C3,C6,C7 and C9 with their respective preceding intermediate cells. It has no effect on the generation of EAC1,4b from C4 and EAC1, or of EAC-8 from C8 and EAC-7, and apparently increases the generation of EAC1,4b from C1 and EAC4b probably by inhibiting transfer or turnover of C1. It does not affect the rate of decay of EAC1,4b,2a or the T max of generation of EAC1,4b,2a, and it inhibits immune adherence only at high concentration. K-76 COOH also strongly inhibits hemolysis through the alternative pathway of C activation by cobra venom factor, but it does not seem to inhibit the early steps of the alternative pathway, because it has little affect on the consumption of C3 or the conversion of beta 1C to beta 1A on treatment of C serum with zymosan. K-76 COOH probably combines with C5 molecules, forming the inactive complexes, or it causes the structural alteration of C5.

Animals↗

Radiation nephritis following combined abdominal radiation and chemotherapy (bleomycin-vinblastine).

A 29-year-old man presented with acute glomerulonephritis five weeks following completion of combined chemotherapy (bleomycin-vinblastine) and abdominal radiation for testicular carcinoma. There was no evidence for a post-infectious cause or a systemic collagen disorder. The renal biopsy showed changes consistent with radiation nephritis. The combined radiation and chemotherapy may have, by additive or synergistic action, caused the early appearance of radiation nephritis.

Adult↗

Preparation and properties of phospholipid bilayers containing rhodopsin.

Purified rhodopsin has been prepared containing less than 1.1 mol of phosphate per mol of protein. The purified rhodopsin has been incorporated into phosphatidylcholine bilayers, and the molecular interactions within the bilayers were investigated by the use of spin-labeled phosphatidylcholines. Rhodopsin appears to inhibit segmental motions of the hydrocarbon chains, an effect similar to that of cholesterol on phospholipid bilayers.

Animals↗

Characterization of group A streptococcal strains Sv and Su: determination of emm gene typing and presence of small vir regulon.

The emm gene typing of GAS (group A streptococcus) strains Sv and Su and the molecular structure of the vir regulon were decided. An emm(-like) gene from the chromosomal DNA of GAS strain Sv was amplified with forward and reverse primers, which were selected from the best conserved portion in leader sequences of different strains and the C-terminal conserved portion, respectively, for determination of the M protein gene type. Strain Sv was defined as serotype M23, because deduced N-terminal amino acid positions of the products are identical to those of the M type 23 (emml) gene derived from GAS strain M23-MEMPHIS (M serotype 23, GenBank accession number U11953). When the vir regulon of strain Sv was examined by polymerase chain reaction mapping and compared with that of GAS strain Su, they had a similar size in length. In addition, when sequencing analysis of the DNA fragment of 4791 base pairs (bp) encoding three open reading frames (orf, mga, and emm) and the upstream region of scpA from genomic DNAs of both strains was performed, the sequence of the DNA from strain Sv was, except for 1 bp (T for C at position 4124), identical to that of the DNA from strain Su. These data show that both strains possess the genes in the order of mga (virR or mry) -emm -scpA designated as the small vir regulon. The effect of the formation of alternative pathway C3 convertase of complement on the GAS strains Sv and Su was also examined. When GAS strains Sv and Su were incubated in NHS containing radiolabeled C3 in the presence of Mg-EGTA, binding of C3 to Su bacteria was dose-dependent, whereas less binding of C3 to Sv bacteria was seen. Taken together, the data suggest that M protein could be expressed on the surface of the Sv bacteria, but not on the Su bacteria.

Amino Acid Sequence↗

Increased target specificity of anti-HER2 genospheres by modification of surface charge and degree of PEGylation.

Genospheres are cationic lipid-nucleic acid nanoparticles prepared by the assembly of the lipids and nucleic acids from an aqueous/organic liquid monophase that independently dissolves the components, where the resultant particles are homogeneously sized (70-110 nm), with efficiently incorporated and protected DNA. In the present study, we demonstrate pH-dependent modulation of the Genosphere surface charge using pH-titratable lipids. By incorporation of the lipids with titratable anionic or imidazole headgroups, Genospheres with neutral or anionic surface charge at neutral pH were produced and compared for cellular uptake and transfection of a reporter gene (luciferase) in culture of breast cancer cells. The extent of particle-cell association was also studied by fluorescent microscopy and quantified by cytofluorometery. The effects of Genosphere surface modification with poly(ethylene glycol) (molecular weight 2000) at low (0.5 mol %) and high (5 mol %) grafting densities, as well as the effects of HER2-receptor-directed targeting by an internalizable anti-HER2 scFv F5, linked via PEG spacer, were also studied. Inclusion in the Genosphere formulation of pH-titratable lipids CHEMS (cholesteryl hemisuccinate), CHIM (1-(3-(cholesteryloxycarbonylamino)propyl)imidazole), or DSGG (1,2-distearoyl-sn-glycero-3-hemiglutarate) rendered the particles surface-charge neutral or slightly anionic at neutral pH, and cationic at mildly acidic pH, as shown by zeta-potential measurements. In HER2-targeted systems, transfection activity and target specificity with HER2-overexpressing SKBR-3 breast cancer cells were dependent on Genosphere surface charge and PEGylation. The highest target specificity correlated with low cationic charge at neutral pH, while incorporation of 5 mol % PEG-lipid had only minor effects on Genosphere-cell association, internalization, and transfection activity. The implications of this work for potential in vivo applications are discussed.

Antibodies↗

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism.

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.

Animals↗

Endolymphatic hydrops and III type allergic reaction.

IgG antibody and complement are both present in endolymphatic fluid, and it is possible that immune complex may form in endolymphatic fluid. However, there are still obscure points as to whether endolymphatic hydrops is due to immune complex, but it is quite possible that it is only one causative factor in endolymphatic hydrops.

Animals↗