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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 163 records · Page 9Linked to original sources

Drug-antibody conjugates with anti-HIV activity.

Human immunodeficiency virus (HIV)-specific peptide antibody-brefeldin A conjugates and antibody-glaucarubolone conjugates directed to cell surface viral glycoprotein epitopes were prepared and tested for antiviral activity. A selective response was observed both on survival of cell lines permanently infected with lentiviruses and on HIV infectivity. With human peripheral blood mononuclear cells (PBMCs), the conjugate also was effective in reducing virus titers. The effectiveness of an HIV-specific peptide antibody-brefeldin A conjugate was enhanced by combination with 3'-azido-3'-deoxythymidine (AZT) and was effective against AZT-resistant isolates in combination with AZT. The conjugates reduced virus production in MOLT-4 cells and in HIV-1-infected PBMCs without affecting the viability of uninfected cells.

Amino Acid Sequence↗

Recycling of lead-contaminated EDTA wastewater.

Ethylene diaminetetraacetic acid (EDTA) is one of the chelating agents used in the soil washing process for the decontamination of lead-contaminated soil. Lead-EDTA complexes in the wastewater from the soil washing process must be removed before the wastewater can be safely discharged. This study outlines a method to recycle Pb-EDTA wastewater by substituting the Pb complexed with EDTA with Fe(III) ions at low pH, followed by precipitation of Pb ions with phosphate or sulfate ions. Fe(III) ions complexed with EDTA were then precipitated at high pH using sodium hydroxide. The resulting solution (Fe-precipitated solution) was tested on three lead-contaminated soils. The Fe-precipitated EDTA solution was found to have similar extraction capabilities as fresh EDTA solution. Experimental results showed that the recycled EDTA solution may be recycled several times without losing its extractive power. Recycled EDTA wastewater with phosphate precipitation was found to be slightly more effective than recycled EDTA solution using sulfate precipitation. The recycling procedure may be applied to wastewater generated during soil washing of lead-contaminated soil, resulting in a reduction in wastewater generated and savings in the amount of EDTA used.

Chelating Agents↗

Effect of additives on the physicochemical properties of liquid suppository bases.

To investigate the effects of additives on the physicochemical properties of in situ gelling and mucoadhesive liquid suppository base, gelation temperature, gel strength and bioadhesive force of liquid suppository base, poloxamer 407 (P 407) and poloxamer 188 (P 188) (15/15%) were evaluated in the presence of following additives: solvent (ethanol, propylene glycol, glycerin), ionic strength-controlling agent (sodium chloride) and pH-controlling agent (hydrochloric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate). Among the additives studied, sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate increased to a great extent the gel strength and the bioadhesive force of P 407/P 188 (15/15%) with a decrease in gelation temperature. Glycerin slightly decreased the gelation temperature and slightly increased the gel strength and bioadhesive force. However, the addition of 1% of sodium chloride, sodium monohydrogen phosphate or sodium dihydrogen phosphate caused a greater than 60-fold increase in gel strength and over a tenfold increase in bioadhesive force with 2-4 degrees C decrease of gelation temperature within optimal range, compared with P 407/P 188 (15/15%) alone. On the other hand, ethanol, propylene glycol and hydrochloric acid increased the gelation temperature and slightly decreased the gel strength and the bioadhesive force. Taken together, these findings indicate that the effect of additives on the physicochemical properties of liquid suppository bases depends on their bonding capacities, in that additives such as sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate having strong cross-linking bonds with the components of liquid suppository base increase the strength and bioadhesive force of a gel compared to liquid suppository base alone, while additives such as ethanol, propylene glycol and hydrochloric acid having weaker hydrogen bonding result in a weaker response. Thus, sodium chloride and sodium phosphates appear to be promising additives for in situ gelling and mucoadhesive liquid suppository base, if used in adequate amounts.

Adhesiveness↗

Development of a thermo-reversible insulin liquid suppository with bioavailability enhancement.

The purpose of this work is to develop a thermo-reversible insulin liquid suppository, which undergoes a phase transition to bioadhesive gels at body temperature and enhances the bioavailability of insulin. The effects of insulin and sodium salicylate on the physicochemical properties of a liquid suppository composed of poloxamer P 407, P 188 and polycarbophil were investigated. The pharmacodynamic study and quantitative histological assessment of the rectal mucosa of rats were carried out after the dose of insulin-loaded liquid suppositories with different amounts of sodium salicylate into streptozotocin-treated rats. Only thermo-reversible insulin liquid suppository [insulin/P407/P188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)] showed the optimal physicochemical properties and good safety in rats. It gave significantly lower plasma glucose levels, AUC(0-->4h) (the area below basal glucose level) and C(nadir) (the plasma glucose levels at the nadir) than did the solid and liquid suppositories without sodium salicylate in rats, indicating that the insulin from liquid suppository with sodium salicylate could be well absorbed in rats due to the absorption enhancing effect of sodium salicylate. It is concluded that thermo-reversible insulin liquid suppository [insulin/P 407/P 188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)], which was easy to administer without any pain during insertion and remained at the administered sites, could have a potential to be developed as a more convenient, safe and effective rectal delivery system of insulin.

Administration, Rectal↗

Promotion of skeletal muscle differentiation by K252a with tyrosine phosphorylation of focal adhesion: a possible involvement of small GTPase Rho.

K252a, a protein kinase inhibitor, acts as a neurotrophic factor in several neuronal cells. In this study we show that K252a enhanced the differentiation of C2C12 myoblasts as well as tyrosine phosphorylation of several focal adhesion-associated proteins including p130(Cas), focal adhesion kinase, and paxillin. The tyrosine phosphorylation of these proteins, reaching a maximum at 30 min after K252a treatment, closely correlated with the colocalization of these proteins in focal adhesion complexes and the coimmunoprecipitation of these proteins with p130(Cas). In addition, K252a stimulated longitudinal development of stress fiber-like structures and cell-matrix interaction in postmitotic myoblasts and eventually formation of well-developed myofibrils in multinucleated myotubes. Herbimycin A, a potent inhibitor of Src family kinases, and cytochalasin D, a selective disrupting-agent of actin filament, completely inhibited K252a-induced tyrosine phosphorylation as well as myoblast differentiation. Similar inhibitory effect was observed in the cells scrape loaded with a Rho inhibitor, C3 transferase, and the treatment of K252a induced a rapid translocation of Rho. These results are consistent with the model that Rho-dependent tyrosine phosphorylation of focal adhesion-associated proteins plays an important role in skeletal muscle differentiation.

Animals↗

Stability and sulfur-reduction activity in non-aqueous phase liquids of the hydrogenase from the hyperthermophile Pyrococcus furiosus.

Hydrogenase from the hyperthermophilic archaeon, Pyrococcus furiosus, catalyzes the reversible activation of H(2) gas and the reduction of elemental sulfur (S degrees ) at 90 degrees C and above. The pure enzyme, modified with polyethylene glycol (PEG), was soluble (> 5 mg/mL) in toluene and benzene with t(1/2) values of more than 6 h at 25 degrees C. At 100 degrees C the PEG-modified enzyme was less stable in aqueous solution (t(1/2) approximately 10 min) than the native (unmodified) enzyme (t(1/2) approximately 1 h), but they exhibited comparable H(2) evolution, H(2) oxidation, and S degrees reduction activities at 80 degrees C. The H(2) evolution activity of the modified enzyme was twice that of the unmodified enzyme at 25 degrees C. The PEG-modified enzyme did not catalyze S degrees reduction (at 80 degrees C) in pure toluene unless H(2)O was added. The mechanism by which hydrogenase produces H(2)S appears to involve H(2)O as the proton source and H(2) as the electron source. The inability of the modified hydrogenase to catalyze S degrees reduction in a homogeneous non-aqueous phase complicates potential applications of this enzyme.

Biotechnology↗

Influence of the antibody purification method on immunoassay performance: hapten-antibody binding in accordance with the structure of the affinity column ligand.

The effects of ligands for immunoaffinity chromatography on the immunoassay were investigated with three goat anti-methamphetamine (anti-MA) antibodies (Abs). An N-4-aminobutyl derivative of methamphetamine (4-ABMA) was conjugated with proteins and used as immunogens. All the antisera produced were purified by affinity chromatography with various ligands of 4-ABMA-proteins and of haptens as well as protein G: 4-ABMA-bovine serum albumin (4-ABMA-BSA), 4-ABMA-keyhole limpet hemocyanine (4-ABMA-KLH), 4-ABMA-ovalbumin (4-ABMA-OVA), MA, 4-ABMA, and amphetamine were used as ligands. Enzyme-linked immunosorbent assay (ELISA) was conducted to examine characteristics of the purified Abs with the 4-ABMA-OVA competitor coated. The results obtained revealed that characters of the purified Abs were closely related with chemical structures of ligands used. The Abs from the MA and the amphetamine columns showed better sensitivities than those from the others in each antiserum. Particularly, the Ab from the amphetamine column gave the best results in terms of sensitivity and specificity. The recognition or the affinity of the Ab selected was considered to be affected by the structure of the ligand concerned. These results suggest that the Ab purification method should be considered as an important parameter which has great influence on the performance of immunoassays with polyclonal Abs.

Animals↗

Isolation of ALP, a novel divergent murine CC chemokine with a unique carboxy terminal extension.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in many disease processes. Chemokines are divided into two major groups, CC or CXC, based on their sequence around the amino terminal cysteines. We report here, the isolation of a novel murine CC chemokine termed ALP for its amino terminal peptide sequence. This novel chemokine is distantly related to other CC chemokines (37% identity with murine Exodus-1/LARC/Mip-3alpha), but has a unique carboxy terminal extension. It is expressed preferentially in testis, heart, and liver, which is atypical for CC chemokines.

Amino Acid Sequence↗

Apoptotic human lymphocytes have diminished CD4 and CD8 receptor expression.

We used quantitative multiparameter flow cytometric assays to simultaneously detect viable, apoptotic, and necrotic human peripheral blood mononuclear cells (PBMC) and immunophenotyped lymphocyte subsets within the PBMC. Apoptosis was induced by a spectrum of treatments, including camptothecin, cisplatin, dexamethasone, hyperthermia, staurosporine, and etoposide in anti-CD3 mAb-stimulated cells and by cyclohexamide in both quiescent and stimulated cells; apoptosis in the latter was augmented by anti-fas mAb. We found that CD4(+) and CD8(+) cells were significantly underrepresented in the apoptotic PBMC and that the percentage of CD4(+) and CD8(+) PBMC each markedly decreased as apoptosis increased. This suggested that surface expression of these receptors was lessened on apoptotic CD4(+) and CD8(+) cells. This was directly confirmed by observation of sorted CD4(+) PBMC. This analysis of a wide variety of apoptotic stimuli demonstrates that diminished CD4 and CD8 surface receptor expression is a common feature of human T lymphocyte apoptosis.

Apoptosis↗

Meta-analysis of exercise testing to detect coronary artery disease in women.

To determine the accuracy of the exercise electrocardiogram (ECG), exercise thallium, and exercise echocardiogram (echo) for the diagnosis of coronary artery disease in women, English language studies published between 1966 and 1995 were identified through a MEDLINE search. Studies that contained data on at least 50 women who underwent both an exercise test and coronary angiography were examined. Studies were reviewed for sensitivity, specificity, and methodologic characteristics by 2 independent reviewers. Nineteen studies met the inclusion criteria for exercise electrocardiography, 5 studies for exercise thallium, and 3 studies for exercise echo. The exercise ECG had a weighted mean sensitivity, specificity, and a likelihood ratio (LR) of 0.61 (95% confidence intervals 0.54 to 0.68), 0.70 (0.64 to 0.75), (+) LR 2.25 (1.84 to 2.66), (-) LR 0.55 (0.47 to 0.62), respectively. The exercise thallium had a weighted mean sensitivity, specificity, and LRs of 0.78 (0.72 to 0.83), 0.64 (0.51 to 0.77), (+) LR 2.87 (1.0 to 4.96), (-) LR 0.36 (0.27 to 0.45). The exercise echo had a weighted mean sensitivity, specificity, and LRs of 0.86 (0.75 to 0.96), 0.79 (0.72 to 0.86), (+) LR 4.29 (2.93 to 5.65), (-) LR 0.18 (0.05 to 0.31). Thallium subset analysis revealed that studies using planar imaging were more specific than those using tomographic imaging. Thus, currently available exercise tests are only moderately sensitive and specific for the diagnosis of coronary artery disease in women.

Coronary Angiography↗

Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells.

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in many disease processes. Chemokines are divided into two major groups, CC or CXC, based on their sequence around the amino terminal cysteines. We report the PCR cloning of a novel human chemokine termed BRAK for its initial isolation from breast and kidney cells. This novel chemokine is distantly related to other CXC chemokines (30% identity with MIP-2alpha and beta) and shares several biological activities. BRAK is expressed ubiquitously and highly in normal tissue. However, it was expressed in only 2 of 18 cancer cell lines. BRAK is located on human chromosome 5q31.

Amino Acid Sequence↗

Drug release from drug-polyanion complex tablets: poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate).

A new erodible, anionic carrier for cationic drugs has been synthesized for oral drug delivery systems. The release properties of tablets prepared from this new material, poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate) (PAMPSNa/MMA), are discussed. Pseudo-linear release profiles were obtained and the hydrophobicities of both the polymeric carrier and the bound drugs were found to be an important controlling factor in determining the slopes of these release profiles. The effect of the tablet geometry on the shape of the release profiles was also investigated and tablet thickness was demonstrated to be another key parameter controlling both the linearity of the release profiles, as well as the duration of drug release. The release kinetics are strongly dependent on the drug solubility rather than on the type of amine in the drug (i.e. secondary and tertiary amines). The release of drugs from tablets of drug-PAMPSNa/MMA complexes were well described by the dissociation/erosion mechanism.

Algorithms↗

Risk factors for early filtration failure requiring suture release after primary glaucoma triple procedure with adjunctive mitomycin.

PURPOSE: Postoperative release of scleral flap closure suture is useful in trabeculectomy combined with cataract surgery. We determined risk factors for early filtration failure requiring suture release during the first month after primary glaucoma triple procedure. METHODS: The medical records of 71 consecutive patients with primary open-angle glaucoma who underwent a primary glaucoma triple procedure (primary trabeculectomy, phacoemulsification, and posterior chamber intraocular lens implantation) were reviewed. Suture release had been performed in 24 of the patients for early filtration failure with postoperative intraocular pressure greater than the target value during the first postoperative month. The long-term filtration failure was defined according to 2 criteria based on medical dependency and requirement of additional surgical procedure for intraocular pressure control. Cox proportional hazards multivariate analysis was performed to identify independent risk factors. RESULTS: African American race (P = .02), more than 2 preoperative glaucoma drugs (P = .02), and intraocular pressure greater than 14 mm Hg during the first postoperative week (P = .006) were identified as significant independent risk factors requiring suture release for filtration failure during the first postoperative month. Their significance was further confirmed by Kaplan-Meier survival analysis with Mantel-Cox log-rank test (P = .03, P = .02, and P = .001, respectively). CONCLUSIONS: African American race, more than 2 preoperative medications, and intraocular pressure greater than 14 mm Hg in the first postoperative week are major independent risk factors for initial filtration failure requiring suture release during the first month after primary glaucoma triple procedure. Presence of the risk factors may warrant a more aggressive antiproliferative regimen and/or earlier suture release.

Aged↗

unc-45 gene of Caenorhabditis elegans encodes a muscle-specific tetratricopeptide repeat-containing protein.

The unc-45 gene of the nematode, Caenorhabditis elegans, is essential for muscle organization and embryonic development. Genetic evidence suggests the unc-45 gene product controls muscle thick filament assembly. We report here on the determination of the gene's chromosomal location and the isolation and sequencing of its cDNA. The amino terminus of the predicted unc-45 protein contains three tandem repeats that belong in the tetratricopeptide repeat family. Tetratricopeptide motifs have been shown to be involved in protein interactions, and some of the closest homologues have chaperone-like activity. The carboxy terminus of the protein has homology with the related fungal proteins, CRO1 and She4p, which have been postulated to play a role in assembly of or interactions with a cytoplasmic myosin. We have also determined the sequence of the homologous gene from C. briggsae, which demonstrates a high level of conservation. We show that the unc-45 gene promoter can drive reporter gene expression, which is limited to muscle tissues (pharyngeal, body wall, vulval, and anal muscles), consistent with a role for the unc-45 gene in muscle development or function.

Amino Acid Sequence↗

Diagnosis of suspected coronary artery disease in women: a cost-effectiveness analysis.

BACKGROUND: The optimal strategy for the diagnosis of coronary artery disease (CAD) in women is not well defined. We compared the cost-effectiveness of several strategies for diagnosing CAD in women with chest pain. METHODS: We performed decision and cost-effectiveness analyses with simulations of 55-year-old ambulatory women with chest pain. With a Markov model, simulations of patients underwent exercise electrocardiography, exercise testing with thallium scintigraphy, exercise echocardiography, angiography, or no workup. RESULTS: Diagnosis with angiography cost less than $17, 000 per quality-adjusted life-year compared with exercise echocardiography if the patient had definite angina and less than $76,000 per life-year if she had probable angina. If she had nonspecific chest pain, diagnosis with exercise echocardiography increased life-years compared with no testing. CONCLUSIONS: Cost-effectiveness of first-line diagnostic strategy for diagnosis of CAD in women varies mostly according to pretest probability of CAD. Diagnosis of coronary artery disease with angiography is cost-effective in 55-year-old women with definite angina. In 55-year-old women with probable angina, diagnosis with angiography would increase quality-adjusted life-years but significantly increase costs. Use of exercise echocardiography as a first-line diagnosis for CAD is cost effective in 55-year-old women with probable angina and nonspecific chest pain.

Angina Pectoris↗

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy.

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.

Adrenergic alpha-Agonists↗

Altered expression and action of the low-affinity IgE receptor FcepsilonRII (CD23) in asthmatic airway smooth muscle.

BACKGROUND: Changes in cell surface expression of certain immunoglobulin Fc receptors have been demonstrated in leukocytes isolated from the lungs of atopic asthmatic individuals. This, together with emerging evidence that Fc receptors can also be expressed and activated in non-bone marrow-derived cell types, including airway smooth muscle (ASM), raises the hypothesis that the atopic asthmatic ASM phenotype is associated with an altered endogenous expression and action of specific Fc receptors present in the ASM itself. OBJECTIVE: The current study addressed the above hypothesis by examining (1) whether the expression of certain key Fc receptor subtypes for IgE and IgG is altered in ASM tissue isolated from human atopic asthmatic individuals and (2) whether this altered Fc receptor expression is comparably induced in naive human ASM tissue and cultured cells after their passive sensitization with human atopic asthmatic serum or IgE immune complexes. METHODS: Messenger RNA and cell surface protein expression of the individual IgG receptor subtypes FcgammaRI, FcgammaRII, and FcgammaRIII, as well as the IgE receptor subtypes FcepsilonRI and FcepsilonRII, were examined in human ASM tissue isolated from atopic asthmatic and control (nonatopic/nonasthmatic) individuals. In addition, we examined the effects of passive sensitization of ASM tissue and cultured ASM cells with control serum, atopic asthmatic serum, or exogenously administered IgE immune complexes on Fc receptor expression and action (ie, induction of proinflammatory cytokine release). RESULTS: The observations demonstrate that (1) human ASM tissue expresses messenger RNA and surface protein for FcepsilonRII, as well as for all the Fcgamma receptor subtypes, (2) in contrast to unaltered Fcgamma subtype expression, however, relative to control human ASM, FcepsilonRII is significantly up-regulated in inherently asthmatic ASM tissue, (3) up-regulated expression of FcepsilonRII represents, at least in part, an inducible phenomenon that is largely attributed to IgE immune complex-coupled activation of the receptor, and (4) the latter action is associated with FcepsilonRII-induced autologous elaboration of the proinflammatory cytokine, IL-1beta, by the atopic sensitized ASM. CONCLUSION: These observations provide new evidence that human ASM tissue expresses FcepsilonRII in addition to all 3 subtypes of Fcgamma receptors and that the expression of FcepsilonRII is selectively increased in atopic asthmatic ASM, a phenomenon associated with IgE immune complex/FcepsilonRII-mediated elaboration of IL-1beta by the ASM itself.

Adolescent↗