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Biomedical subjects

S R Kim

Publications and source records attributed to S R Kim.

At least 37 records · Page 2Linked to original sources

Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia.

Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.

Adenoma↗

Neuroprotective dibenzylbutyrolactone lignans of Torreya nucifera.

The methanolic extract of the bark of Torreya nucifera Sieb. et Zucc. (Taxaceae) significantly protected primary cultures of rat cortical cells exposed to the excitotoxic amino acid, L-glutamate. (-)-Arctigenin (1), (-)-traxillagenin (2), arctiin (4), traxillaside (5), and a newly-reported compound 3 (-)-4'-demethyltraxillagenin [(2R,3R)-2-(4''-hydroxy-3''-methoxybenzyl)-3-(4'-hydroxy-3',5'-dimethoxybenzyl)-butyrolactone] were isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. These lignans and their glycosides had significant neuroprotective activities against glutamate-induced toxicity in primary cultures of rat cortical cells at concentrations ranging from 0.01 microM to 10.0 microM.

Animals↗

Association of quinone-induced platelet anti-aggregation with cytotoxicity.

Various anti-platelet drugs, including quinones, are being investigated as potential treatments for cardiovascular disease because of their ability to prevent excessive platelet aggregation. In the present investigation 3 naphthoquinones (2,3-dimethoxy-1,4-naphthoquinone [DMNQ], menadione, and 1,4-naphthoquinone [4-NQ]) were compared for their abilities to inhibit platelet aggregation, deplete glutathione (GSH) and protein thiols, and cause cytotoxicity. Platelet-rich plasma, isolated from Sprague-Dawley rats, was used for all experiments. The relative potency of the 3 quinones to inhibit platelet aggregation, deplete intracellular GSH and protein thiols, and cause cytotoxicity was 1,4-NQ > menadione >> DMNQ. Experiments using 2 thiol-modifying agents, dithiothreitol (DTT) and 1-chloro-2,4-dintrobenzene (CDNB), confirmed the key roles for GSH in quinone-induced platelet anti-aggregation and for protein thiols in quinone-induced cytotoxicity. Furthermore, the anti-aggregative effects of a group of 12 additional quinone derivatives were positively correlated with their ability to cause platelet cytotoxicity. Quinones that had a weak anti-aggregative effect did not induce cytotoxicity (measured as LDH leakage), whereas quinones that had a potent anti-aggregative effect resulted in significant LDH leakage (84-96%). In one instance, however, p-chloranil demonstrated a potent anti-aggregative effect, but did not induce significant LDH leakage. This can be explained by the inability of p-chloranil to deplete protein thiols, even though intracellular GSH levels decreased rapidly. These results suggest that quinones that deplete GSH in platelets demonstrate a marked anti-aggregative effect. If this anti-aggregative effect is subsequently followed by depletion of protein thiols, cytotoxicity results.

Animals↗

Dependence of malformation upon gestational age and exposed dose of gamma radiation.

In order to evaluate the importance of gestational age and the dose-incidence relationship by gamma radiation, pregnant ICR mice at gestational days from 2.5 to 15.5 days post-coitus (p.c.) were exposed to a single dose of 2.0 Gy and also at day 11.5 after conception, which was the most sensitive stage for the induction of major congenital malformations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. The only demonstrable effect of irradiation during the pre-implantation period was an increase in prenatal mortality. Resorptions were maximal on exposure at day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. A small head, growth retardation, a cleft palate, dilatation of the cerebral ventricle, a renal pelvis, and abnormalities of the extremities and tail after exposure were prominent during the organogenesis period, especially on day 11.5 of gestation. As for the dose-incidence relationship, the incidence of a small head, growth-retarded fetuses, a cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose as the radiation dose increased. The result indicated that the late period of organogenesis in the development of the brain, skull and extremities of a mouse was a particularly sensitive phase. The threshold doses of radiation that induced a cleft palate and dilatation of the cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively.

Abnormalities, Radiation-Induced↗

Preoperative uterine artery embolization and evacuation in the management of cervical pregnancy: report of two cases.

Preoperative uterine artery embolization and cervical evacuation as conservative management of cervical pregnancy has been tried in recent years. However, cervical suturing, vasoconstrictor injection, or cervical ballooning was frequently used as an ancillary measures in those procedures in most of the previous studies. We report two cases of cervical pregnancy that were successfully treated with preoperative uterine artery embolization and removal of gestational material without ancillary procedures. Our therapeutic modality seems to be safe and effective for conservative management of cervical pregnancy.

Adult↗

Influence of gestational age at exposure on the prenatal effects of gamma-radiation.

The objective of this investigation was to evaluate the influence of gestational age at exposure on the prenatal effects of gamma-radiation. Pregnant ICR mice were exposed to a single dose of 2.0 Gy gamma-radiation at a gestational 2.5 to 15.5 days post-coitus (p.c.). The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, change in head size and any other morphological abnormalities. The only demonstrable effect of irradiation during the preimplantation period was an increase in prenatal mortality. Resorptions were maximal on post-exposure day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. Small head, growth retardation, cleft palate, dilatation of the cerebral ventricle, dilatation of the renal pelvis and abnormalities of the extremities and tail were prominent after exposure during the organogenesis period, especially on day 11.5 of gestation. Our results indicate that the late period of organogenesis in the mouse is a particularly sensitive phase in terms of the development of the brain, skull and extremities.

Abnormalities, Radiation-Induced↗

Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.

BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.

Adult↗

Adenine excisional repair function of MYH protein on the adenine:8-hydroxyguanine base pair in double-stranded DNA.

Adenine paired with 8-hydroxyguanine (oh(8)G), a major component of oxidative DNA damage, is excised by MYH base excision repair protein in human cells. Since repair activity of MYH protein on an A:G mismatch has also been reported, we compared the repair activity of His(6)-tagged MYH proteins, expressed in Spodoptera frugiperda Sf21 cells, on A:oh(8)G and A:G mismatches by DNA cleavage assay and gel mobility shift assay. We also compared the repair ability of type 1 mitochondrial protein with type 2 nuclear protein, as well as of polymorphic type 1-Q(324) and 2-Q(310) proteins with type 1-H(324) and 2-H(310) proteins by DNA cleavage assay and complementation assay of an Escherichia coli mutM mutY strain. In a reaction buffer with a low salt (0-50 mM) concentration, adenine DNA glycosylase activity of type 2 protein was detected on both A:oh(8)G and A:G substrates. However, in a reaction buffer with a 150 mM salt concentration, similar to physiological conditions, the glycosylase activity on A:G, but not on A:oh(8)G, was extremely reduced and the binding activity of type 2 protein for A:G, but not for A:oh(8)G, was proportionally reduced. The glycosylase activity on A:oh(8)G and the ability to suppress spontaneous mutagenesis were greater for type 2 than type 1 enzyme. There was apparently no difference in the repair activities between the two types of polymorphic MYH proteins. These results indicate that human MYH protein specifically catalyzes the glycosylase reaction on A:oh(8)G under physiological salt concentrations.

Adenine↗

Orientations of liquid crystals on mechanically rubbed films of bovine serum albumin: a possible substrate for biomolecular assays based on liquid crystals.

We report the uniform planar anchoring of thermotropic liquid crystals on films of bovine serum albumin (BSA) covalently immobilized on the surface of glass microscope slides and mechanically rubbed using a cloth. The azimuthal orientations of the liquid crystals were measured to be parallel to the direction of rubbing. Following immersion and removal of these rubbed films of BSA from aqueous solutions containing either BSA, fibrinogen, lysozyme, anti-FITC immunoglobulin G (IgG), or antistreptavidin IgG, we measured liquid crystals placed onto these surfaces to largely retain their uniform alignment. In contrast, following immersion of a rubbed film of BSA into an aqueous solution of anti-BSA IgG, we observed liquid crystals on these surfaces to assume nonuniform orientations. We conclude that specific binding of anti-BSA IgG to the film of rubbed BSA erased anisotropy induced within the film of BSA by rubbing. This result suggests that the spatial scale of anisotropy within the rubbed film of BSA is comparable to or smaller than the size of the IgG molecule. Because the anisotropy within a rubbed film of a protein can be erased by specific binding of a second protein, we believe these types of substrates (rubbed films of proteins) have the potential to be useful in a variety of label-free biomolecular assays where specific binding of a target species to its ligand can be imaged through observation of the optical appearance of liquid crystal placed onto the surface.

Adsorption↗

Properties of GST-CALM expressed in E. coli.

Clathrin-coated vesicles (CCVs) are involved in protein and lipid trafficking between intracellular compartments in eukaryotic cells. CCVs are composed of clathrin and assembly proteins. The clathrin assembly protein lymphoid myeloid leukemia (CALM) gene, encodes a homologoue of the neuronal clathrin assembly protein AP180. In this study, we characterized the properties of the CALM expressed in E. coli. The molecular weight of bacterially expressed GST-CALM fusion protein was approximately 105 kD on SDS-PAGE. The CALM protein could promote clathrin triskelia into clathrin cages and could bind the preformed clathrin cage. However, 33 kD N-terminal domain of CALM could not bind pre-assembled clathrin cages, but assemble clathrin triskelia into clathrin cages. The CALM protein was bound to SH3 domain through N-terminal domain1, in vitro. The CALM protein is proteolyzed by caspase 3, caspase 8 and calpain through C-terminal domain.

Adaptor Proteins, Vesicular Transport↗

Inhibition of phospholipase D by amphiphysins.

Two distinct proteins inhibiting phospholipase D (PLD) activity in rat brain cytosol were previously purified and identified as synaptojanin and AP180, which are specific to nerve terminals and associate with the clathrin coat. Two additional PLD-inhibitory proteins have now been purified and identified as the amphiphysins I and II, which forms a heterodimer that also associates with the clathrin coat. Bacterially expressed recombinant amphiphysins inhibited both PLD1 and PLD2 isozymes in vitro with a potency similar to that of brain amphiphysin (median inhibitory concentration of approximately 15 nm). Expressions of either amphiphysin in COS-7 cells reduced activity of endogenous PLD as well as exogenously expressed PLD1 and PLD2. Coprecipitation experiments suggested that the inhibitory effect of amphiphysins results from their direct interaction with PLDs. The NH(2) terminus of amphiphysin I was critical for both inhibition of and binding to PLD. Phosphatidic acid formed by signal-induced PLD is thought to be required for the assembly of clathrin-coated vesicles during endocytosis. Thus, the inhibition of PLD by amphiphysins, synaptojanin, and AP180 might play an important role in synaptic vesicle trafficking.

Amino Acid Sequence↗

The effect of pore formers on the controlled release of cefadroxil from a polyurethane matrix.

The effect of various pore formers on the controlled release of an antibacterial agent from a polymeric device was examined in order to develop a novel biomaterial that prevents bacterial adhesion and growth on its surface. Cefadroxil was chosen as the model antibiotic and was incorporated into a polyurethane matrix by the solvent-casting method. Polyethylene glycol (PEG) 1450, D-mannitol, or bovine serum albumin (BSA) was used as a pore former. The amount of cefadroxil released from various formulations at 37 degrees C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activities of matrices against Escherichia coli and Bacillus subtilis was evaluated by measuring the diameters of the inhibition zone. Changing the weight fraction and particle size of the pore formers/drug mixtures could control the release of cefadroxil from the matrix. The release rate of cefadroxil increased as the loading dose of the pore former increased (15<20<25%). Cefadroxil released from these devices exhibited antibacterial activity for 5-6 days. These results imply that an antibiotic-loaded polymeric device that could prevent bacterial infection on its surface can be formulated using appropriate pore formers.

Bacteria↗

Clinical implication of altered expression of Mad1 protein in human breast carcinoma.

BACKGROUND: Mad1 protein is known to repress Myc target genes and antagonize Myc function. The authors undertook this study to investigate the clinical implication of Mad1 expression in human breast carcinoma. METHODS: The authors performed immunohistochemical assays for Mad1 and Myc proteins in human breast carcinoma, along with tissues from normal breast and benign diseases. The data from protein assays were analyzed in terms of the clinical and biologic characteristics of the patients. RESULTS: Of 66 patients with invasive ductal carcinoma, Mad1 expression was detected in 22 (33. 3%). Intensity and area of Mad1 expression significantly decreased in DCIS and invasive cancers, whereas high levels of Mad1 expression were persistent in benign breast lesions. Mad1 expression was significantly reduced in poorly differentiated tumors (P < 0.001). Expression of Mad1 was not associated with tumor size, lymph node status, or stage of disease. The authors did not observe any correlation between S-phase and expression status of Myc or Mad1. Mad1 expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression (P = 0.042). In survival analysis, Mad1 was a significant factor in predicting recurrence of the disease, but not overall survival after CMF chemotherapy. CONCLUSIONS: In human breast carcinoma cells, expression of Mad1 seems to be down-regulated, whereas expression of Myc is amplified. Altered expression of Mad1 may play a role in the malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast carcinoma.

Adult↗

Neuroprotective phenylpropanoid esters of rhamnose isolated from roots of Scrophularia buergeriana.

Four phenylpropanoid esters of rhamnose, buergerisides A1, B1, B2 and C1 were isolated from roots of Scrophularia huergeriana MIQ. (Scrophulariaceae), and were characterized as 2-O-acetyl-3,4-di-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranosid e, 2-O-acetyl-3-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranoside, 2-O-acetvl-3-O-(Z)-p-methoxycinnamoyl-alpha-L-rhamnopyranosi de and 4-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranoside, respectively. In addition, six known phenylpropanoids were authenticated as: (E)-cinnamic acid, (E)-p-methoxycinnamic acid, (E)-p-methoxycinnamic acid methyl ester, (E)-p-coumaric acid, (E)-caffeic acid, (E)-ferulic acid and a phenylalcohol, 2-(3-hydroxy-4-methoxyphenyl)ethanol. These ten phenylpropanoids all attenuated glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells in a dose-dependent manner. These results demonstrate that phenylpropanoids isolated from S. buergeriana may exert significant protective effects against glutamate-induced neurodegeneration in primary cultures of cortical neurons.

Animals↗