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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 109 records · Page 6Linked to original sources

The role of serine-246 in cytochrome P450eryF-catalyzed hydroxylation of 6-deoxyerythronolide B.

A strongly conserved threonine residue in the I-helix of cytochrome P450 enzymes participates in a proton delivery system for binding and cleavage of dioxygen molecules. 6-Deoxyerythronolide B hydroxylase (P450eryF) is unusual in that the conserved threonine residue is replaced by alanine in this enzyme. On the basis of the crystal structures of substrate-bound P450eryF, it has been proposed that the C-5 hydroxyl group of the substrate and serine-246 of the enzyme form hydrogen bonds with water molecules 519 and 564, respectively. This hydrogen bonding network constitutes the proton delivery system whereby P450eryF maintains its catalytic activity in the absence of a threonine hydroxyl group in the conserved position. To further assess the role in the proton delivery system of hydroxyl groups around the active site, three mutant forms of P450eryF (A245S, S246A, and A245S/S246A) were constructed and characterized. In each case, decreased catalytic activity and increased uncoupling could be correlated with changes in the hydrogen bonding environment. These results suggest that Ser-246 does indeed indirectly participate in the proton shuttling pathway, and also strongly support our previous hypothesis that the C-5 hydroxyl group of the substrate participates in the acid-catalyzed dioxygen bond cleavage reaction.

Bacterial Proteins↗

Polymelia with two extra forelimbs at the right scapular region in a male Korean native calf.

In a male Korean native calf 14 days of age, polymelia (notomelia) was observed macroscopically and radiographically. External features included two normal forelimbs, two normal hindlimbs and two undeveloped extra forelimbs. The extra forelimbs were attached to the caudal regions of the right scapula and devoid of muscular tissues. In the extra forelimbs, a scapula-like bone formed a joint with the incompletely duplicated humerus. The humerus fused with the incompletely duplicated radius. The ulna, carpal bones, metacarpal bones and phalanges were completely duplicated. But one set of the duplicated carpal bones consisted of five bones: radial, accessory, fourth carpal, fused second and third carpal, and fused ulnar and intermediate carpal bones. The hoof and the rudimentary hoof of accessory digit were duplicated.

Animals↗

Motives for HIV testing among drug users: an analysis of gender differences.

This article examines gender differences related to why 66 injection and noninjection drug users tested for HIV. Study participants from three northern California counties underwent an open-ended qualitative interview covering: access to HIV testing, the meaning of HIV testing and test results, drug and sexual risk behaviors, and behavior changes associated with HIV testing, as well as a brief quantitative survey. The responses were analyzed using the following categories: (a) financial incentives for testing, (b) concerns related to family members and significant others, and (c) personal anxieties due to lack of knowledge of HIV status. Analyses showed that gender differences exist regarding reasons for HIV testing. The most significant finding was that women were motivated to test with regard to concerns related to family and significant others in their life more so than men, particularly during pregnancy. The impetus to test for many individuals was dependent on a social setting, such as jail, hospital, or drug rehabilitation program. Further research examining the motivational factors why drug users test for HIV can provide valuable information for outreach and marketing of HIV counseling-and-testing services.

AIDS Serodiagnosis↗

Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of the salivary and lacrimal glands leading to a progressive destruction of these glands due to the production of autoantibodies. This disorder is either isolated (primary SS) or associated with other systemic diseases (secondary SS). The occurrence of B-cell non-Hodgkin's lymphoma (NHL) represents the major complication in the evolution of SS patients. The risk of developing NHL, which is equivalent for both primary and secondary SS, was estimated to be 44 times greater than that observed in a comparable normal population. NHLs in SS patients occur preferentially in the salivary glands and in other mucosa-associated lymphoid tissues (MALT). However, it can also occur in the lymph nodes or bone marrow. We documented a case of low-grade B-cell lymphoma of MALT in the right eyelid and primary biliary cirrhosis (PBC) of a patient with SS. To the best of our knowledge, this is the first case reported in Korea.

Eyelid Neoplasms↗

Preparation of a PEG-grafted phospholipid Langmuir-Blodgett monolayer for blood-compatible material.

In order to develop a versatile model for blood-compatible materials, we studied morphology and platelet adhesion of a dipalmitoyl-phosphatidylcholine (DPPC)/dipalmitoyl-phosphatidylethanolamine-polyethylene glycol (PEG lipid) mixed monolayer. This monolayer, which mimics the cell membrane structure, consists of two heterogeneous layers, that is, a PEG layer lying on top of a phospholipid monolayer. The DPPC/PEG lipid mixed monolayer was prepared using the Langmuir-Blodgett (LB) Technique. The monolayer was transferred onto a silanized glass substrate by the down-stroke mode, at a surface pressure of 25 mN/m. The transfer efficiency achieved unity at all times. The morphologies of PEG chains on the phospholipid monolayer in water, in a dried state, and in a hydrated state were evaluated using Pi-A isotherm, ellipsometry, and atomic force microscopy (AFM), respectively. When the concentration of PEG lipid was below 1 mol %, the PEG chains could cover the DPPC surface completely in water, but not in the dried state. On the other hand, the PEG chains could cover the phospholipid surface completely in a dried state, as well as in water, when the PEG lipid concentration was above 3 mol %. These PEG chains, showing a brush-type conformation in water, were highly packed and had a bulky structure at the surface in the dried state as well as in the hydrated state. A bulky and extended PEG layer, above 3 mol % concentration, was greatly effective in the prevention of platelet adhesion.

1,2-Dipalmitoylphosphatidylcholine↗

Prenatal exposure to misoprostol and vascular disruption defects: a case-control study.

Prenatal exposure to misoprostol has been associated with Moebius and limb defects. Vascular disruption has been proposed as the mechanism for these teratogenic effects. The present study is a multicenter, case-control study that was designed to compare the frequency of prenatal misoprostol use between mothers of Brazilian children diagnosed with vascular disruption defects and matched control mothers of children diagnosed with other types of defects. A total of 93 cases and 279 controls were recruited in eight participating centers. Prenatal exposure was identified in 32 infants diagnosed with vascular disruption defects (34.4%) compared with only 12 (4.3%) in the control group (P<0.0000001). Our data suggest that prenatal exposure to misoprostol is associated to the occurrence of vascular disruption defects in the newborns.

Abnormalities, Drug-Induced↗

On the photochemical behavior of the [Ru(NH3)4(NO)nicotinamide]3+ cation and the relative stability of light-induced metastable isonitrosyl isomers of Ru complexes.

Low-temperature IR experiments on crystalline samples of trans-[Ru(NH3)4(NO) nicotinamide]3+ salts show a light-induced absorption band typical for MS1 NO linkage isomers upon exposure to 300-500 nm light from a Xe source. The formation of a metastable species is confirmed by DSC measurement on a sample irradiated at low temperature with 457 nm light from an Ar+ laser. The light-induced species decays between 250 and 260 K according to both IR and DSC results. This decay temperature (Td) is somewhat below that observed for other high-Td linkage isomers, even though the NO-stretching frequency of the of [Ru(NH3)4(NO) nicotinamide]3+ ion is above that of the other isomers, demonstrating a lack of precise correlation between the two physical properties. The 90 K crystal structure of trans-[Ru(NH3)4(NO)nicotinamide](SiF6)(NO3).H2O is reported. The geometry from theoretical DFT calculations of the ground-state structure agrees well with the experimental results, except for the orientation of the CONH2 substituent in the pyridine ring, which is rotated by 180 degrees in the crystal due to packing effects. The MS1 and MS2 linkage isomers are found to correspond to local minima on the ground-state potential energy surface, and their geometries and energies are reported.

Journal Article↗

Fermi surface, surface states, and surface reconstruction in Sr2RuO4

The electronic structure of Sr2RuO4 is investigated by high angular resolution ARPES at several incident photon energies. We address the controversial issues of the Fermi surface (FS) topology and the van Hove singularity at the M point, showing that a surface state and the replica of the primary FS due to sqrt[2]xsqrt[2] surface reconstruction are responsible for previous conflicting interpretations. The FS thus determined by ARPES is consistent with the de Haas-van Alphen results, and it provides additional information on the detailed shape of the alpha, beta, and gamma sheets.

Journal Article↗

Angle-resolved photoemission study of insulating and metallic Cu-O chains in PrBa2Cu3O7 and PrBa2Cu4O8

We compare the angle-resolved photoemission spectra of the hole-doped Cu-O chains in PrBa2Cu3O7 (Pr123) and in PrBa2Cu4O8 (Pr124). While, in Pr123, a dispersive feature from the chain takes a band maximum at k(b) (momentum along the chain) approximately pi/4 and loses its spectral weight around the Fermi level, it reaches the Fermi level at k(b) approximately pi/4 in Pr124. Although the chains in Pr123 and Pr124 are approximately 1/4 filled, they show contrasting behaviors: While the chains in Pr123 have an instability to charge ordering, those in Pr124 avoid it and show an interesting spectral feature of a metallic coupled-chain system.

Journal Article↗

Efficacy of electrolyzed oxidizing (EO) and chemically modified water on different types of foodborne pathogens.

This study was undertaken to evaluate the efficacy of electrolyzed oxidizing (EO) and chemically modified water with properties similar to the EO water for inactivation of different types of foodborne pathogens (Escherichia coli O157:H7, Listeria monocytogenes and Bacillus cereus). A five-strain cocktail of each microorganism was exposed to deionized water (control), EO water and chemically modified water. To evaluate the effect of individual properties (pH, oxidation-reduction potential (ORP) and residual chlorine) of treatment solutions on microbial inactivation, iron was added to reduce ORP readings and neutralizing buffer was added to neutralize chlorine. Inactivation of E. coli O157:H7 occurred within 30 s after application of JAW EO water with 10 mg/l residual chlorine and chemically modified solutions containing 13 mg/l residual chlorine. Inactivation of Gram-positive and -negative microorganisms occurred within 10 s after application of ROX EO water with 56 mg/l residual chlorine and chemically modified solutions containing 60 mg/l residual chlorine. B. cereus was more resistant to the treatments than E. coli O157:H7 and L. monocytogenes and only 3 log10 reductions were achieved after 10 s of ROX EO water treatment. B. cereus spores were the most resistant pathogen. However, more than 3 log10 reductions were achieved with 120-s EO water treatment.

Bacillus cereus↗

Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy.

PURPOSE: To determine the effective dose of consolidation radiation in Hodgkin's disease (HD) patients with large mediastinal adenopathy (LMA) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Eighty-three HD patients with LMA receiving CMT between 1983 and 1997 at Duke University and Yale University were identified. Patients underwent complete clinical staging. The staging breakdown was: IA, 4 patients; IB, 1 patient; IIA, 25 patients; IIB, 33 patients; IIIA, 3 patients; IIIB-6 patients; IVA, 2 patients; and IVB, 9 patients. All patients received induction chemotherapy (CT) as follows: MOPP/ABV(D), 31 patients; BCVPP, 15 patients; ABVD, 24 patients; MOPP, 3 patients; and other regimens, 10 patients. Following 6 cycles of CT, patients were restaged and classified as having either complete response (CR) or induction failure (IF). Post-CT gallium scans were obtained in 52 patients. Patients with residual radiographic abnormalities were classified as having CR if they were gallium-negative and clinically well otherwise. Following induction CT, 78 patients had a CR. There were 5 IFs. Consolidation irradiation was administered to all sites of initial involvement in patients who had achieved CR. RT dose varied. Patients were grouped into the following dose ranges: < or = 20 Gy, 12 patients; 20-25 Gy, 24 patients; 25-30 Gy, 30 patients; > or = 30 Gy, 12 patients. RESULTS: Overall survival and failure-free survival were both 76% at 10 years. Of the 78 CR patients, 15 failed. Patterns of failure were in-field alone, 8 patients; out of field alone, 2 patients; and combined, 5 patients. Failure patterns by RT dose were: < or = 20 Gy, 0/12; 20-25 Gy, 7/24; 25-30 Gy, 5/30; > or = 30 Gy, 3/11. There was no apparent correlation between RT dose and subsequent failure. Post chemotherapy gallium scans were helpful in predicting for failure. Of 48 patients in whom the gallium was negative after chemotherapy, there were 6 failures, compared with 9 failures among 30 patients in whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) CONCLUSIONS: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis.

Adolescent↗

5'-Flanking sequence and promoter activity of the rabbit neuronal nitric oxide synthase (nNOS) gene.

We have isolated a rabbit neuronal nitric oxide synthase (nNOS) cDNA encoding a protein of 1,435 amino acids. Using the cDNA clones as probes, the 5'-flanking region of the nNOS gene was isolated from a rabbit genomic DNA library. 5'RACE and primer extension analysis of rabbit brain total RNA mapped multiple transcription initiation sites localized 474-487 bp upstream from the translation start codon. Analysis of 5,197 bp of the 5'-flanking sequence revealed that the rabbit nNOS gene promoter lacks canonical TATA or CCAAT boxes and, instead, contains a GC-rich region and multiple Sp1 sites. Farther from the +1start, various putative cis-elements including AP-1, AP-4, NF-kappaB, STAT, CREB, C/EBP and c-Myc were observed. The functional promoter activity of the 5'-flanking region was demonstrated by its ability to drive the expression of a beta-galactosidase reporter gene in several cell types. Serial deletion analysis of the promoter region revealed that the -291 to -172 region, which contains two Sp1 sites, is essential for basal transcriptional activity. These results suggest that the rabbit nNOS promoter contains characteristics of inducible genes.

5' Untranslated Regions↗

Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is required for ubiquitin-mediated destruction of numerous proteins. ERAD occurs by processes on both sides of the ER membrane, including lumenal substrate scanning and cytosolic destruction by the proteasome. The ER resident membrane proteins Hrd1p and Hrd3p play central roles in ERAD. We show that these two proteins directly interact through the Hrd1p transmembrane domain, allowing Hrd1p stability by Hrd3p-dependent control of the Hrd1p RING-H2 domain activity. Rigorous reevaluation of Hrd1p topology demonstrated that the Hrd1p RING-H2 domain is located and functions in the cytosol. An engineered, completely lumenal, truncated version of Hrd3p functioned normally in both ERAD and Hrd1p stabilization, indicating that the lumenal domain of Hrd3p regulates the cytosolic Hrd1p RING-H2 domain by signaling through the Hrd1p transmembrane domain. Additionally, we identified a lumenal region of Hrd3p dispensable for regulation of Hrd1p stability, but absolutely required for normal ERAD. Our studies show that Hrd1p and Hrd3p form a stoichiometric complex with ERAD determinants in both the lumen and the cytosol. The HRD complex engages in lumen to cytosol communication required for regulation of Hrd1p stability and the coordination of ERAD events on both sides of the ER membrane.

Binding Sites↗

Differential expression of nicotinamide adenine dinucleotide phosphate-diaphorase in hypothalamic areas of obese Zucker rats.

Several studies have suggested that the activity of nitric oxide synthase (NOS) may be involved in the regulation of food intake in the genetically obese Zucker rats. In the present study, we investigated the expression of NOS in various hypothalamic regions of obese and lean Zucker rats using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Obese Zucker rats showed significantly lower staining intensities of NADPH-diaphorase-positive neurons in the paraventricular nucleus (PVN), lateral hypothalamic area (LHA) and ventromedial hypothalamic nucleus (VMH) than lean Zucker rats did. The differences in staining intensities between obese and lean Zucker rats were large in both the PVN and LHA, but such differences were relatively small in the VMH.

Animals↗

Formulation and in vivo evaluation of omeprazole buccal adhesive tablet.

For the development of omeprazole buccal adhesive tablets, we studied the release and bioavailability of omeprazole delivered by buccal adhesive tablets composed of sodium alginate, hydroxypropylmethylcellulose (HPMC), magnesium oxide and croscarmellose sodium. Croscarmellose sodium enhanced the release of omeprazole from the tablets. The analysis of the release mechanism showed that croscarmellose sodium changed the release profile of omeprazole from first- to zero-order release kinetics by forming porous channels in the tablet matrix. However, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet is composed of omeprazole-sodium alginate-HPMC-magnesium oxide-croscarmellose sodium (20:24:6:50:10 mg). It may be attached to the human cheek without collapse and it enhanced the stability of omeprazole in human saliva for at least 4 h, giving a fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to reach a maximum of 370 ng/ml at 45 min after buccal administration and remained at the high level of 146-366 ng/ml for 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7+/-3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful to deliver omeprazole which degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration.

Adhesiveness↗

in vitro development of porcine enucleated oocytes reconstructed by the transfer of porcine fetal fibroblasts and cumulus cells.

In the pig little information is available on cytoplasmic events during the reprogramming of oocytes reconstructed with somatic nuclei. The present study was conducted to determine the developmental potential of porcine cumulus cells (CC) and fetal fibroblasts (FF) after they were transferred into enucleated oocytes. Non-quiescent FF were fused to the enucleated oocytes using electrical pulse, whereas CC were directly injected into the oocytes. Transferred nuclei from both CC and FF underwent premature chromosome condensation (PCC), nuclear swelling and pronucleus formation. The remodeled oocytes developed to the mitotic and 2-cell stage at 18 to 24 h after nuclear transfer. The pattern of nuclear remodeling was similar regardless of the sources of karyoplasts or nuclear transfer methods. However, using FF, 24% of nuclear transferred embryos developed to the morula or blastocyst stage, whereas only 8% of those using CC developed to the morula or blastocyst stage. These results suggest that porcine oocyte cytoplasm can successfully reprogram somatic cell nuclei and support the development of nuclear transferred embryos to the blastocyst stage.

Animals↗

Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency.

Rho GTPases control a variety of cellular processes, including actin polymerization, integrin complex formation, cell adhesion, gene transcription, cell cycle progression, and cell proliferation. A patient is described who has recurrent infections and defective neutrophil cellular functions similar to those found in Rac2-deficient mice. Molecular methods were used to clone the expressed Rac2 cDNA from this patient, and a single base pair change (G-->A at nucleotide 169) in the coding sequence was identified. This results in an asparagine for aspartic acid mutation at amino acid 57 (D57N), a residue that is involved in nucleotide binding and is conserved in all mammalian Rho GTPases. The cloned cDNA was then introduced into normal bone marrow cells through retrovirus vectors, and neutrophils expressing this mutant exhibited decreased cell movement and production of superoxide in response to fMLP. The expressed recombinant protein was also analyzed biochemically and exhibited defective binding to GTP. Functional studies demonstrated that the D57N mutant behaves in a dominant-negative fashion at the cellular level. The syndrome of Rac2 dysfunction represents a human condition associated with mutation of a Rho GTPase and is another example of human disease associated with abnormalities of small G protein signaling pathways. (Blood. 2000;96:1646-1654)

3T3 Cells↗