Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 217 records · Page 12Linked to original sources

PubMed2000

Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates survival of colon cancer cells.

We have cloned a novel gene mirk (minibrain-related kinase) encoding a protein kinase that enables colon carcinoma cells to survive under certain stress conditions. Mirk is a mitogen-activated protein kinase substrate but is down-regulated by activated extracellular signal-regulated kinases (erks) in vivo. Mirk contains a PEST region characteristic of rapidly turned over proteins and is broken down to a Mr 57,000 form only in the nucleus. In each of three colon carcinoma cell lines, mirk levels were increased 20-fold when erk activation was blocked by the MEK inhibitor PD98059 in serum-free medium. Addition of IGF-I to activate erks blocked this increase. Mirk was stably overexpressed in two colon carcinoma cell lines to attain levels seen in colon cancers. Each of five mirk transfectants proliferated when switched to serum-free medium and regained rapid growth when serum was restored, whereas five vector control transfectants and three kinase-dead mutant mirk transfectants did not. mirk mRNA levels were elevated in several types of carcinomas, and mirk protein was detected in each of seven colon carcinoma cell lines. mirk was expressed at a higher protein level in Western blots from three of eight colon cancers compared with paired normal colon tissue, suggesting that mirk plays a role in the evolution of a subset of colon cancers. mirk is not mutated in colon carcinomas. Mirk may mediate tumor cell survival in mitogen-poor environments or early in colon cancer development before many autocrine growth factors have been induced.

Amino Acid Sequence↗

PubMed2000

Structure and function of the conserved 690 hairpin in Escherichia coli 16 S ribosomal RNA: analysis of the stem nucleotides.

Nucleotides 680 to 710 of Escherichia coli 16 S rRNA form a distinct structural domain required for ribosome function. The goal of this study was to determine the functional significance of pairing interactions in the 690 region. Two different secondary structures were proposed for this hairpin, based on phylogenetic and chemical modification studies. To study the effect of pairing interactions in the 690 hairpin on ribosome function and to determine which of the proposed secondary structures is biologically significant, we performed an instant-evolution experiment in which the nine nucleotides that form the proposed base-pairs and dangling ends of the 690 stem were randomly mutated, and functional mutant combinations were selected. A total of 96 unique functional mutants were isolated, assayed in vivo, and sequenced. Analysis of these data revealed extensive base-pairing and stacking interactions among the mutated nucleotides. Formation of either a Watson-Crick base-pair or G.U pair between positions 688 and 699 is absolutely required for ribosome function. We also performed NMR studies of a 31-nucleotide RNA which indicate the formation of a functionally important base-pair between nucleotides 688 and 699. Formation of a second base-pair between positions 689 and 698, however, is not essential for ribosome function, but the level of ribosome function correlates with the predicted thermodynamic stability of the nucleotide pairs in these positions. The universally conserved positions G690 and U697 are generally portrayed as forming a G.U mismatch. Our data show co-variation between these positions, but do not support the hypothesis that the G690:U697 pair forms a wobble structure. NMR studies of model 14-nt and 31-nt RNAs support these findings and show that G690 and U697 are involved in unusual stacking interactions but do not form a wobble pair. Preliminary NMR structural analysis reveals that the loop portion of the 690 hairpin folds into a highly structured and novel conformation.

Base Pair Mismatch↗

PubMed2000

Coverage by the news media of the benefits and risks of medications.

BACKGROUND: The news media are an important source of information about new medical treatments, but there is concern that some coverage may be inaccurate and overly enthusiastic. METHODS: We studied coverage by U.S. news media of the benefits and risks of three medications that are used to prevent major diseases. The medications were pravastatin, a cholesterol-lowering drug for the prevention of cardiovascular disease; alendronate, a bisphosphonate for the treatment and prevention of osteoporosis; and aspirin, which is used for the prevention of cardiovascular disease. We analyzed a systematic probability sample of 180 newspaper articles (60 for each drug) and 27 television reports that appeared between 1994 and 1998. RESULTS: Of the 207 stories, 83 (40 percent) did not report benefits quantitatively. Of the 124 that did, 103 (83 percent) reported relative benefits only, 3 (2 percent) absolute benefits only, and 18 (15 percent) both absolute and relative benefits. Of the 207 stories, 98 (47 percent) mentioned potential harm to patients, and only 63 (30 percent) mentioned costs. Of the 170 stories citing an expert or a scientific study, 85 (50 percent) cited at least one expert or study with a financial tie to a manufacturer of the drug that had been disclosed in the scientific literature. These ties were disclosed in only 33 (39 percent) of the 85 stories. CONCLUSIONS: News-media stories about medications may include inadequate or incomplete information about the benefits, risks, and costs of the drugs as well as the financial ties between study groups or experts and pharmaceutical manufacturers.

Alendronate↗

PubMed2000

Interconversion between µ-eta(2),eta(2)-C(60) and µ(3)-eta(2),eta(2),eta(2)-C(60) on a Carbido Pentaosmium Cluster Framework We are grateful to the Korea Science Engineering Foundation (KOSEF) for financial support (project no. 1999-1-122-001-5) of this research and a postdoctoral fellowship to K.L. The X-ray diffraction studies were carried out at the X-ray Crystallographic Laboratory of Yonsei University, which was supported in part by KOSEF.

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Journal Article↗

PubMed2000

Effect of spikelet position on rice anther culture efficiency.

The potential of anthers from different parts of the panicle to induce callus was investigated with the japonica rice variety Taipei 309. The results showed that the callusing abilities of anthers from different spikelet positions were significantly different. After plating 4483, 4496, 4348 anthers from the basal, middle and top parts, the percentage of anthers forming calli was 20% in the basal part, 12% in the middle part and 8% in the top part. The anthers of basal parts containing pollen at all uninucleate stages, including early, middle and late, showed higher callus induction frequency than those from middle and top parts. The green plantlet regeneration frequencies of top, middle and basal spikelets were around 18% in all three cases. From the results it would appear that anthers from the basal part of the panicle should be used in anther culture of rice in order to obtain higher efficiencies, and thereby optimise the usefulness of this technique in rice breeding programmes.

Journal Article↗

PubMed2000

NK-3 receptors are expressed on mouse striatal gamma-aminobutyric acid-ergic interneurones and evoke [(3)H] gamma-aminobutyric acid release.

In the present study the ability of tachykinin agonists and antagonists to modulate gamma-aminobutyric acid (GABA) release has been correlated with tachykinin receptor expression in the mouse striatum. Significant GABA release was observed when striatal slices were challenged with the NK-3 receptor agonist senktide, the selectivity of which was confirmed using the NK-3 receptor antagonist SR142801. In situ hybridisation revealed co-expression of NK-3 receptors with nitric oxide synthase (NOS)/preprosomatostatin containing GABAergic interneurones. These findings suggest that tachykinins modulate GABA release within the striatum via interaction with NK-3 receptors on somatostatin/NOS interneurones.

Acetylcholine↗

PubMed2000

beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics.

The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting alpha-subunit of the channel is regulated by two known auxiliary subunits, beta1 and beta2. We have identified rat and human forms of an additional subunit, beta3. It is most closely related to beta1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, beta3 inactivates sodium channel opening more slowly than beta1 does. Structural modeling has identified an amino acid residue in the putative alpha-subunit binding site of beta3 that may play a role in this difference. The expression of beta3 within the central nervous system differs significantly from beta1. Our results strongly suggest that beta3 performs a distinct neurophysiological function.

Amino Acid Sequence↗

PubMed2000

Substrate binding site of naphthalene 1,2-dioxygenase: functional implications of indole binding.

The three-dimensional structure of the aromatic hydroxylating enzyme naphthalene dioxygenase (NDO) from Pseudomonas sp. NCIB 9816-4 was recently determined. The refinement of the structure together with cyclic averaging showed that in the active site of the enzyme there is electron density for a flat aromatic compound. This compound appears to be an indole adduct, which in Escherichia coli is derived from tryptophan present in the rich culture medium. An indole-dioxygen adduct has been built which fits the electron density convincingly. Support for this interpretation was obtained from crystals of the enzyme purified from cells grown in the absence of tryptophan which had an empty substrate pocket. These types of crystals were soaked in indole solutions and the position of indole in this complex was similar to the corresponding part in the modelled indole-oxygen adduct. This suggests that a peroxide bound to iron end-on attacks the substrate and forms this intermediate. The substrate position has implications for the substrate specificity of the enzyme. Docking studies with indole, naphthalene and biphenyl inside the substrate pocket of NDO suggest the presence of subpockets where the one close to the active site iron is reserved for the binding of the aromatic ring which is hydroxylated upon catalysis. The plausible location for the binding of dioxygen is between this pocket and the catalytic iron. This is in accordance with the enantiospecificity of the products.

Amino Acid Sequence↗

PubMed2000

A CTL assay requiring only 150 microliter of mouse blood.

In this paper, we present a method for measuring antigen specific cytotoxic T lymphocyte (CTL) activity from individual mouse peripheral blood samples without animal sacrifice. Peripheral blood cells are stimulated in vitro with a cocktail of antigen, cytokines, costimulatory molecules and irradiated feeder cells resulting, 7 days later, in a readily detectable antigen specific signal from a well plated under limiting dilution conditions. This highly sensitive and antigen specific assay is more efficient than conventional CTL assays and thus increases the number of mice that can be tested in a single assay. Since blood samples can be assayed from an individual mouse at multiple times during the course of an in vivo study, the assay can facilitate and strengthen correlative studies on CTL responses and in vivo results.

Amino Acid Sequence↗

PubMed2000

Imaging superficial tissues with polarized light.

OBJECTIVE: Polarized light can be used to obtain images of superficial tissue layers such as skin, and some example images are presented. This study presents a study of the transition of linearly polarized light into randomly polarized light during light propagation through tissues. STUDY DESIGN/MATERIALS AND METHODS: The transition of polarization was studied in polystyrene microsphere solutions, in chicken muscle (breast) and liver, and in porcine muscle and skin. The transition is discussed in terms of a diffusion process characterized by an angular diffusivity (radians(2)/mean free path) for the change in angular orientation of linearly polarized light per unit optical path traveled by the light. RESULTS: Microsphere diffusivity increased from 0.031 to 0.800 for diameters decreasing from 6.04 microm to 0.306 microm, respectively. Tissue diffusivity varied from a very low value (0.0004) for chicken liver to an intermediate value (0.055) for chicken and porcine muscle to a very high value (0.78) for pig skin. CONCLUSION: The results are consistent with the hypothesis that birefringent tissues randomize linearly polarized light more rapidly than nonbirefringent tissues. The results suggest that polarized light imaging of skin yields images based only on photons backscattered from the superficial epidermal and initial papillary dermis because the birefringent dermal collagen rapidly randomizes polarized light. This anatomic region of the skin is where cancer commonly arises.

Humans↗

PubMed2000

Two novel myogenic factors identified and isolated by sequential isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

A number of environmental factors were used experimentally to enhance myogenesis during muscle regeneration; however, many hormones and growth factors have been shown to have the ability to increase the rate of satellite cell division, but they only work on satellite cells that are already active in many animal experiments. Recently, the crushed muscle extract (CME) of rats was found to be able to trigger dormant adult rat satellite cells to re-enter the cell mytogenic cycle; however, the identity of the active factors present in rat CME remains unknown. In the present study, the CME was fractionated by the strategy of sequential isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with functional analysis by myoblast culture. Two satellite cell-specific myogenic factors were identified and purified from CME by this strategy. One of the factors has a molecular mass of around 7 kDa and another about 39 kDa. The factor of 39 kDa could be retained in heparin-Sepharose column and eluted with phosphate-buffered saline (PBS) containing 1 M NaCl, but the 7 kDa factor did not bind to the heparin column. These two purified myogenic factors could synergistically trigger the proliferation and differentiation of dormant satellite cells, whose progenies subsequently fuse in vitro, or fuse to pre-existing partially damaged muscle fibers to form full repair of the damaged muscle fibers or to form new myotubes to replace the completely damaged muscle fibers during the cascade of muscle healing and regeneration in vivo. The identities of these two myogenic factors are under study.

Animals↗

PubMed2000

Age-related changes of aqueous protein profiles in rat fast and slow twitch skeletal muscles.

Two-dimensional electrophoresis was used to generate the aqueous protein expression patterns of rat extensor digitorum longus muscle (EDL, fast twitch muscle) and solues muscle (SOL, slow twitch muscle) of different ages. Two specific protein spots, S1 and S3, were identified from EDL muscles at the ages of 12 and 18 months onward respectively. In the EDL muscles of aged rat (24 months) after intensive exercise training, S3 was still detected while S1 disappeared. In addition, diaphragm muscle (DIA, fast twitch muscle), which retains physically active throughout the life span, was used as nondisuse control. The results showed that the expressions of S1 and S3 in 24-month DIA muscle were identical with the trained aged EDL muscle. It is suggested that exercise might delay the onset of S1 expression. However, the expression of S3 over age seemed to be progressive and exercise independent. Another protein spot, S2 was identified to express only in young EDL and SOL muscles, but its expression decreased over age. Furthermore, exercise has no effect on S2 expression since S2 could not be detected in aged DIA as well as trained aged EDL and SOL muscles. These results indicated that aqueous protein expression patterns of skeletal muscle undergo changes during aging. Some of these changes such as S2 and S3 appear progressively, and some such as S1 could be delayed by exercise. S3 was identified as ubiquitin, which might play an important role in protein degradation during skeletal muscle aging process.

Aging↗

PubMed2000

Metabolic flux analysis of postburn hepatic hypermetabolism.

The hepatic response to severe injury is characterized by a marked upregulation of glucose, fatty acid, and amino acid turnover, which, if persistent, predisposes the patient to progressive organ dysfunction. To study the effect of injury on liver intermediary metabolism, metabolic flux analysis was applied to isolated perfused livers of burned and sham-burned rats. Intracellular fluxes were calculated using metabolite measurements and a stoichiometric balance model. Significant flux increases were found for multiple pathways, including mitochondrial electron transport, the TCA and urea cycles, gluconeogenesis, and pentose phosphate pathway (PPP). The burn-induced increase in gluconeogenesis did not significantly increase glucose output. Instead, glucose-6-phosphate was diverted into the PPP. These changes were paralleled by increases in glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activities. Given that G6PDH and GR are the most significant NADPH producers and consumers in the liver, respectively, and that GR is responsible for recycling the free radical scavenger glutathione, these data are consistent with the notion that hepatic metabolic changes are in part due to the induction of liver antioxidant defenses.

Amino Acids↗

PubMed2000

Identification of the calcium binding sites in translationally controlled tumor protein.

Translationally controlled tumor protein (TCTP), also known as IgE-dependent histamine-releasing factor, is a growth-related tumor protein. Although the primary sequence of rat TCTP does not reveal any recognizable Ca2+ -binding motif, previous studies have demonstrated that rat TCTP consisting of 172 amino acids is a Ca2+ -binding protein. However, the region of TCTP required for Ca2+ interaction has not been mapped to the molecule. Here, we reported that the Ca2+ binding region of TCTP, which was mapped by using a combination of deletion constructs of rat TCTP and 45Ca2+ -overlay assay, was confined to amino acid residues 81-112. This binding domain did not show any peculiar loop of calcium-binding motif such as CaLB domain and EF hand motif and it seems to be constituted of random coil regions neighboring the a helix. Thus, our data confirm that TCTP is a novel family of Ca2+ -binding protein.

Amino Acid Sequence↗

PubMed2000

Trends in serotypes and antimicrobial susceptibility of group B streptococci isolated in Korea.

Studies of group B streptococci (GBS) have been limited in Korea, despite the necessity for such studies because of the increase in serious adult infections, the emergence of new serotypes, and the increase of resistance to certain antibiotics. In this study, trends in serotypes of GBS isolated in Korea were compared to determine any changes and emergence of new types, while antimicrobial susceptibility was tested and compared with that of group A streptococci (GAS). It was found that the most frequent infections caused by GBS were of the urinary tract, but other severe infections also occurred not only in newborns but also in adults. The prevalent serotypes were still Ia, Ib, and III, while new serotypes, VI and VIII, also emerged. GBS were susceptible to beta-lactam antibiotics, but were much less so than GAS. The resistance rates to erythromycin and tetracycline were much higher than those in other countries, suggesting that these antibiotics are no longer very useful in Korea for the treatment of GBS infections.

Adult↗

PubMed2000

Systemic administration of mexiletine for attenuation of cerebral vasospasm following experimental subarachnoid haemorrhage.

Mexiletine is a class Ib drug that is widely used to treat ventricular arrhythmias. This compound is mainly known as a sodium channel blocker, but studies have demonstrated that it can also activate ATP-sensitive K+ channels and block Ca2+ channels. Recent in vitro data from experiments on liposomes indicate that mexiletine is also a potent antioxidant. The unique activity profile of this drug raised the possibility that it might be of benefit in limiting cerebral vasospasm. Our first series of experiments assessed the effects of mexiletine on transclivally exposed rabbit basilar arteries. The arteries were treated with 50-mM KCl, 20-nM endothelin-1 (ET-1), or 100-microM lysophosphatidic acid (LPA) in the presence or absence of 400-mM mexiletine. Vasoconstriction caused by KCl, ET-1, and LPA was inhibited by mexiletine. In a second series of experiments, subarachnoid haemorrhage (SAH) was induced in rabbits by injecting 3-ml of autologous arterial blood into the cisterna magna. Forty-eight hours after SAH induction, transclivally exposed basilar arteries exhibited a spastic constriction that was partially reversed by topical application of 400-microM mexiletine. In a third set of experiments, mexiletine was administered orally at dosages of 80-, 20, and 5-mg/kg/day t.i.d., beginning 3 hours before SAH to study the prevention of vasospasm. In a separate group of animals, 80- and 20-mg/kg/day t.i.d. of mexiletine was administered 21 hours post-SAH induction, to study the reversal of vasoconstriction. Microscopic analysis of vessels from controls (no SAH), SAH-only, and SAH + mexiletine groups indicated there was 71.43% vascular constriction in the SAH-only group compared with controls. Considerable vasorelaxation was seen in the prevention study, in which average arterial cross-sectional areas were reduced by only 17.86% and 39.29% in the mexiletine 80- and 20-mg/kg/day groups, respectively, compared with controls (p < 0.001). Compared with controls, average arterial cross-sectional areas were reduced by 53.58% and 64.29% in the mexiletine 80- and 20-mg/kg/day reversal groups, respectively. Our findings indicate that mexiletine induces potent relaxation in cerebrovascular arteries contracted with various agents, and that it prevents and partially reverses SAH-induced vasoconstriction.

Administration, Topical↗

PubMed2000

Present situation of antimicrobial resistance in Korea.

Resistance of bacteria to antimicrobial agents is a worldwide concern. In Korea, resistant bacteria are more prevalent than in other industrialized countries. Methicillin-resistant Staphylococcus aureus, erythromycin-resistant Streptococcus pyogenes, penicillin non-susceptible pneumococci, beta-lactamase-producing gonococci, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, class C beta-lactamase-producing E. coli, fluoroquinolone-resistant E. coli, and aminoglycoside-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are examples of resistant bacteria prevalent in Korea, and their presence suggests a high level of antimicrobial selective pressure and the nosocomial spread of resistant bacteria. Recently observed rapid increases in the incidence of vancomycin-resistant Enterococcus faecium and carbapenem-resistant P. aeruginosa present new threats in Korea.

Cross Infection↗

PubMed2000

Increased eyelid pigmentation associated with use of latanoprost.

PURPOSE: To report increased eyelid pigmentation as an adverse side effect associated with topical latanoprost. METHOD: Case report. A 62-year-old Korean woman with normal-tension glaucoma developed bilateral increased eyelid skin pigmentation 4 months after beginning treatment with latanoprost in both eyes. Clinical examinations were performed, and external photographs were taken. RESULT: Latanoprost was discontinued. Periodic examinations revealed that the eyelid skin pigmentation gradually diminished 1 month after the cessation of the drug, and decrease in pigmentation continued over 4 months of follow-up. CONCLUSION: An increase in eyelid skin pigmentation is a possible complication of topical latanoprost therapy, and the cessation of the drug can result in loss of induced pigmentation in humans.

Antihypertensive Agents↗