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Biomedical subjects

S K Kim

Publications and source records attributed to S K Kim.

At least 127 records · Page 7Linked to original sources

Lipoprotein secretion and triglyceride stores in the heart.

The genes for apolipoprotein B and microsomal triglyceride transfer protein are expressed in mouse and human heart tissue. Why the heart would express these "lipoprotein assembly" genes has been unclear. Here we demonstrate that the beating mouse heart actually secretes spherical lipoproteins. Moreover, increased cardiac production of lipoproteins (e.g., in mice that express a human apolipoprotein B transgene) was associated with increased triglyceride secretion from the heart and decreased stores of triglycerides within the heart. Increased cardiac production of lipoproteins also reduced the pathological accumulation of triglycerides that occurs in the hearts of mice lacking long-chain acyl coenzyme A dehydrogenase. In contrast, blocking heart lipoprotein secretion (e.g., in heart-specific microsomal triglyceride transfer protein knockout mice) increased cardiac triglyceride stores. Thus, heart lipoprotein secretion helps regulate cardiac triglyceride stores and may protect the heart from the detrimental effects of surplus lipids.

Animals↗

Molecular characterizations of the equine herpesvirus 1 ETIF promoter region and translation initiation site.

The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV-1) tegument phosphoprotein, alphaTIF (Vmw65; VP16), was identified previously as the product of open reading frame 12 (ORF12), was shown to trans-activate immediate-early (IE) gene promoters, and was described as a 60-kDa virion component designated ETIF. However, the ETIF promoter region and transcription initiation site were not identified. The poly(A) signal of the gene 11 (UL49 homolog) lies just upstream of the first ETIF translation initiation codon, indicating that the first ATG may not be used for initiating ETIF translation. Another in-frame translation initiation codon (ATG2) is located 88 bp downstream of the first ETIF initiation codon (ATG1). Western blot analysis showed that the expressed ETIF protein migrated in SDS-PAGE with an apparent molecular mass of approximately 56 kDa, the same molecular weight identified in SDS-PAGE analysis of the KyD EHV-1 virion preparations. The ETIF expression vector pCETIF, which contains ATG2, trans-activated the IE promoter more efficiently than the pC12 containing both ATG1 and ATG2. S1 nuclease analyses mapped the 5' initiation site of the 1.4-kb transcript approximately 17 to 21 nt downstream of the ATG1. The nucleotide sequence upstream of the ATG1 did not have any promoter activity, while the nucleotide sequence upstream of the ATG2 had promoter activity. In transient transfection assays, the pETIFM2 vector, which was mutated in the ATG2, did not trans-activate the IE promoter; however, the pETIFM1 vector, which was mutated in the ATG1, trans-activated the IE promoter. These results demonstrated that the ATG2 of the ETIF ORF is the ETIF translation initiation codon. ETIF trans-activated only the IE promoter, not early (EICP0, EICP22, EICP27, and thymidine kinase) or late (IR5) promoters, confirming that EICP0, EICP22, and EICP27 are early genes.

Amino Acid Sequence↗

Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase.

We screened 139 herbal spices in search of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer's Disease (AD). Among these herbs, edible plants and spices, the ethanol extract from Origanum majorana L. showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L. the active component was finally identified as ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid). The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM. This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease.

Acetylcholinesterase↗

Intramedullary immature teratoma in a young infant involving a long segment of the spinal cord.

Intramedullary teratoma is a rare lesion, located in the majority of cases in the lumbosacral area, and such lesions involving an extensive area of the spinal cord in young infants have seldom been reported. We present the case of a 3-month-old girl with an intramedullary spinal immature teratoma extending from C-5 to T-12, which was totally removed. The patient had suffered from paraplegia for 15 days, after which spinal MRI revealed a heterogeneously enhancing intramedullary lesion. Biopsy of the lesion demonstrated mature intestinal tissue. After total removal of the tumor, paraplegia and sphincter disturbances improved. Intramedullary teratoma should be included in the differential diagnosis of holocord tumors in young infants with rapidly progressing symptoms and if found should be radically excised. This case also emphasizes the importance of histological diagnosis and demonstrates the possibility of neurological recovery even in the case of paraplegia lasting for more than 1 month in a young infant.

Diagnosis, Differential↗

Measurement of the resonant d(mu)t molecular formation rate in solid HD.

Measurements of muon-catalyzed dt fusion ( d(mu)t-->4He + n + mu(-)) in solid HD have been performed. The theory describing the energy dependent resonant molecular formation rate for the reaction (mu)t + HD-->[(d(mu)t)pee](*) is compared to experimental results in a pure solid HD target. Constraints on the rates are inferred through the use of a Monte Carlo model developed specifically for the experiment. From the time-of-flight analysis of fusion events in 16 and 37 microg x cm(-2) targets, an average formation rate consistent with 0.897+/-(0.046)(stat)+/-(0.166)(syst) times the theoretical prediction was obtained.

Journal Article↗

Even-odd alternation in mass spectrum of thymine and uracil clusters: evidence of intracluster photodimerization.

Multiphoton ionization of thymine and uracil clusters generated by a supersonic molecular beam gave rise to a remarkable alternation of mass spectral intensities between even- and odd-numbered clusters. Such alternation was observed in clusters of up to 30 molecules. Excitation to the two lowest electronically excited states seemed to be a strong prerequisite. In view of the well known photodimerization reaction of thymine and uracil in the bulk phase, it is proposed that such alternation in the mass spectral intensity resulted from formation of photodimer units within the cluster on intense UV irradiation. Several analogues of thymine with no known propensity for photodimerization in the bulk phase did not exhibit any sign of such alternation in the cluster mass spectrum. The intrinsic UV window for photodimerization, and hence photoinduced mammalian mutagenesis, was estimated to be approximately 210-280 nm, significantly narrower than the previously reported bulk values of 150-300 nm.

DNA↗

Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton events at the upsilon(4S).

We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d) based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Deltam(d) as a free parameter. Using both muons and electrons, we obtain Deltam(d) = 0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of Deltam(d) from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.

Journal Article↗

Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection.

The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and was compared with the response in peripheral blood, secondary lymphoid tissue, and liver. To assess the vaccination potential of Listeria and to analyze responses in C57BL/6 mouse strains, a recombinant Listeria expressing OVA (rLM-ova) was generated. The response peaked at 9 days postinfection with a much larger fraction of the intestinal mucosa and liver CD8 T cell pool OVA specific, as compared with the spleen. However, these differences were not linked to bacterial titers in each site. The higher responses in lamina propria and liver resulted in a larger CD8 memory population in these tissues. Furthermore, the level of memory induced was dependent on infectious dose and inversely correlated with the magnitude of the recall response after oral challenge. Recall responses in the tissues were most robust in the lamina propria and liver, and reactivated Ag-specific T cells produced IFN-gamma. Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver. Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses.

Administration, Oral↗

Modified magnetism at a buried Co/Pd interface resolved with X-ray standing waves.

Soft x-ray standing waves produced by a multilayer interference substrate add depth sensitivity to magnetic circular dichroism to resolve changes in Co magnetism across a 1 nm distance from the Co center to the Co-on-Pd interface of a Pd/Co/Pd trilayer with an in-plane magnetization. Large enhancements of the number of Co d holes, and of in-plane orbital and spin magnetic moments, are strongly localized at a thin, chemically modified interface layer. These results provide new insight into magnetic anisotropy at interfaces, and suggest a broad applicability of such standing wave measurements to interface magnetism studies.

Journal Article↗

Functional genomics: the worm scores a knockout.

Following the completion of the genome sequence of Caenorhabditis elegans, four independent studies have now assessed the functions of more than a third of the worm's genes by analysing the phenotypes caused when each of a large set of genes is inactivated by RNA interference.

Animals↗

Binding mode of 4',6-diamidino-2-phenylindole and ethidium to poly(dG).poly(dC).poly(dC)(+) triplex and poly(dG).poly(dC) duplex.

Optical spectroscopic properties of 4',6-diamidino-2-phenylindole (DAPI) and ethidium bromide complexed with poly(dG).poly(dC).poly(dC)(+) triplex and poly(dG).poly(dC) duplex were compared in this study. When complexed with both duplex and triplex, ethidium is characterized by hypochromism and a red shift in the absorption spectrum, a complicate induced circular dichroism (CD) band in the polynucleotide absorption region, and a negative reduced linear dichroism signal in both polynucleotide and drug absorption regions. The spectral properties for both duplex- and triplex-bound ethidium are identical and both can be understood by the intercalation binding mode. In contrast, the absorption and CD spectra of DAPI complexed with triplex differ from those of the DAPI-duplex complex, although both complexes can be understood by the intercalation binding mode. Considering that the third strand runs along the major groove of the template duplex, we conclude that the DAPI molecule partially intercalates near the major groove of the duplex, where the third strand can affect its spectroscopic properties.

Circular Dichroism↗

Photophysical properties of long rodlike meso-meso-linked zinc(II) porphyrins investigated by time-resolved laser spectroscopic methods.

The molecular design of directly meso-meso-linked porphyrin arrays as a new model of light-harvesting antenna as well as a molecular photonic wire was envisaged to bring the porphyrin units closer for rapid energy transfer. For this purpose, zinc(II) 5,15-bis(3,5-bis(octyloxy)phenyl)porphyrin (Z1) and its directly meso-meso-linked porphyrin arrays up to Z128 (Zn, n represents the number of porphyrins) were synthesized. The absorption spectra of these porphyrin arrays change in a systematic manner with an increase in the number of porphyrins; the high-energy Soret bands remain at nearly the same wavelength (413-414 nm), while the low-energy exciton split Soret bands are gradually red-shifted, resulting in a progressive increase in the exciton splitting energy. The exciton splitting is nicely correlated with the values of cos[pi/(N + 1)] according to Kasha's exciton coupling theory, providing a value of 4250 cm(-1) for the exciton coupling energy in the S(2) state. The increasing red-shifts for the Q-bands are rather modest. The fluorescence excitation anisotropy spectra of the porphyrin arrays show that the photoexcitation of the high-energy Soret bands exhibits a large angle difference between absorption and emission dipoles in contrast with the photoexcitation of the low-energy exciton split Soret and Q-bands. This result indicates that the high-energy Soret bands are characteristic of the summation of the individual monomeric transitions with its overall dipole moment deviated from the array chain direction, while the low-energy Soret bands result from the exciton splitting between the monomeric transition dipoles in line with the array chain direction. From the fluorescence quantum yields and fluorescence lifetime measurements, the radiative coherent length was estimated to be 6-8 porphyrin units in the porphyrin arrays. Ultrafast fluorescence decay measurements show that the S(2) --> S(1) internal conversion process occurs in less than 1 ps in the porphyrin arrays due to the existence of exciton split band as a ladder-type deactivation channel, while this process is relatively slow in Z1 (approximately 1.6 ps). The rate of this process seems to follow the energy gap law, which is mainly determined by the energy gap between the two Soret bands of the porphyrin arrays.

Journal Article↗

The equine herpesvirus 1 immediate-early protein interacts with EAP, a nucleolar-ribosomal protein.

The equine herpesvirus 1 (EHV-1) immediate-early (IE) phosphoprotein is essential for the activation of transcription from viral early and late promoters and regulates transcription from its own promoter. The IE protein of 1487 amino acids contains a serine-rich tract (SRT) between residues 181 and 220. Deletion of the SRT decreased transactivation activity of the IE protein. Previous results from investigation of the ICP4 protein, the IE homolog of herpes simplex virus 1 (HSV-1), revealed that a domain containing a serine-rich tract interacts with EAP (Epstein-Barr virus-encoded small nuclear RNA-associated protein), a 15-kDa nucleolar-ribosomal protein (R. Leopardi, and B. Roizman, Proc. Natl. Acad. Sci. USA 93, 4572-4576, 1996). DNA binding assays revealed that (i) glutathione S-transferase (GST)-EAP disrupted the binding of HSV-1 ICP4 to its cognate DNA in a dose-dependent manner, (ii) GST-EAP interacted with the EHV-1 IE protein, but did not disrupt its binding to its cognate site in viral DNA. GST-pulldown assays indicated that the SRT of the IE protein is required for physical interaction with EAP. The IE protein and EAP colocalized in the cytoplasm of the infected equine ETCC cells at late times of the infection cycle. This latter finding may be important in EHV-1 gene regulation since late viral gene expression is greatly influenced by the EICP0 trans-activator protein whose function is antagonized by the IE protein.

Animals↗

Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans.

We have constructed DNA microarrays containing 17,871 genes, representing about 94% of the 18,967 genes currently annotated in the Caenorhabditis elegans genome. These DNA microarrays can be used as a tool to define a nearly complete molecular profile of gene expression levels associated with different developmental stages, growth conditions, or worm strains. Here, we used these full-genome DNA microarrays to show the relative levels of gene expression for nearly every gene during development, from eggs through adulthood. These expression data can help reveal when a gene may act during development. We also compared gene expression in males to that of hermaphrodites and found a total of 2,171 sex-regulated genes (P < 0.05). The sex-regulated genes provide a global view of the differences between the sexes at a molecular level and identify many genes likely to be involved in sex-specific differentiation and behavior.

Aging↗

Cytotoxic alkaloids from Houttuynia cordata.

Six bioactive alkaloids, aristolactam B(1), piperolactam A(2), aristolactam A(3), norcepharadione B(4), cepharadione B(5) and splendidine(6) were isolated by bioactivity-guided fractionation of a methanolic extract of the aerial part of Houttuynia cordata. Several of them exhibited significant cytotoxicity against five human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT-15) in vitro.

Alkaloids↗

The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumatoid arthritis: comparison with bone marrow iron study.

OBJECTIVES: This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. METHODS: Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. RESULTS: (1) Mean sTfR concentration was 2.63+/-1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. CONCLUSION: The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.

Anemia, Iron-Deficiency↗