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Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 127 records · Page 7Linked to original sources

Purification and characterization of a membrane-associated 48-kilodalton phospholipase A(2) in leaves of broad bean.

Several lines of evidence indicate that phospholipase A(2) (PLA(2)) plays a crucial role in plant cellular responses through production of linolenic acid, the precursor of jasmonic acid, from membrane phospholipids. Here we report the purification and characterization of a 48-kD PLA(2) from the membrane fractions of leaves of broad bean (Vicia faba). The plant PLA(2) was purified to near homogeneity by sequential column chromatographies from the membrane extracts. The purified 48-kD protein migrated as a single band on a SDS-PAGE gel and its density correlated with the PLA(2) activity. It was further confirmed that this 48-kD protein is the PLA(2) enzyme based on immunoprecipitating the activity with a monoclonal antibody against it and purifying the enzyme to homogeneity with the antibody affinity column. The purified plant PLA(2) preferred 2-linolenoyl-sn-glycerol-3-phosphocholine (GPC) to 2-linoleoyl-GPC, 2-palmitoyl-GPC and 2-arachidonyl-GPC as substrates with a pH optimum at pH 7.0 to 8.0. The plant PLA(2) was activated by calmodulin and inhibited by pretreatment of 5,8,11, 14-eicosatetraynoic acid known as an inhibitor of mammalian PLA(2)s. The enzyme was characterized as a Ca(2+)-independent PLA(2) different from mammalian PLA(2)s. This membrane-associated and Ca(2+)-independent PLA(2) is suggested to play an important role in the release of linolenic acid, the precursor of jasmonic acid, through a signal transduction pathway.

5,8,11,14-Eicosatetraynoic Acid↗

Lifetime-limiting strength degradation from contact fatigue in dental ceramics.

The hypothesis under examination in this paper is that the lifetimes of dental restorations are limited by the accumulation of contact damage during oral function; and, moreover, that strengths of dental ceramics are significantly lower after multi-cycle loading than after single-cycle loading. Accordingly, indentation damage and associated strength degradation from multi-cycle contacts with spherical indenters in water are evaluated in four dental ceramics: "aesthetic" ceramics-porcelain and micaceous glass-ceramic (MGC), and "structural" ceramics-glass-infiltrated alumina and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP). At large numbers of contact cycles, all materials show an abrupt transition in damage mode, consisting of strongly enhanced damage inside the contact area and attendant initiation of radial cracks outside. This transition in damage mode is not observed in comparative static loading tests, attesting to a strong mechanical component in the fatigue mechanism. Radial cracks, once formed, lead to rapid degradation in strength properties, signaling the end of the useful lifetime of the material. Strength degradation from multi-cycle contacts is examined in the test materials, after indentation at loads from 200 to 3000 N up to 10(6) cycles. Degradation occurs in the porcelain and MGC after approximately 10(4) cycles at loads as low as 200 N; comparable degradation in the alumina and Y-TZP requires loads higher than 500 N, well above the clinically significant range.

Aluminum Oxide↗

Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers.

To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a novel K+ channel opener, a single blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 28 healthy volunteers. The volunteers were randomly allocated to dosage groups of 50 micrograms, 100 micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were administered orally, after overnight fasting, and serial blood sampling and pharmacodynamic measurements were performed up to 48 hours after the drug was administered. The 200 micrograms group was further studied for food interactions in a crossover fashion. Drug concentrations in plasma were determined by HPLC. Hemodynamic changes after drug administration were evaluated by serial measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and total peripheral resistance (TPR), using computerized impedance cardiography. Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an active metabolite, showed linear pharmacokinetic characteristics, and food intake did not significantly affect the pharmacokinetic characteristics of either compound. Dose-related pharmacological effects were obvious for both the 200 micrograms and 300 micrograms groups. Hemodynamic parameters related to vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR, CI, and TPR, showed significant dose-dependent changes. The area under the time-effect curve (AUEC) of the parameters also showed a similar dose-dependent pattern. The PRA and PAC exhibited significant changes 4 hours after drug administration in the 300 micrograms group. Adverse effects, such as headaches, were more frequently observed at the higher dose levels. SKP-450 was generally well tolerated by these normotensive subjects. The antihypertensive efficacy of SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.

Administration, Oral↗

A new cyanogenic glycoside from Sorbaria sorbifolia var. stellipila.

A new cyanogenic glycoside, sutherlandin-5-trans-p-coumarate was isolated along with a known cardiosdiospermin-5-(4-hydroxy) benzoate fr the aerial parts of Sorbaria sorbifolia (L.) A. Br. var. stellipila MAX. (Rosaceae). The structure of the new compound was established based on spectral evidence.

China↗

Takayasu's arteritis: assessment of disease activity with contrast-enhanced MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the role of contrast-enhanced MR imaging in the determination of disease activity in patients with Takayasu's arteritis. SUBJECTS AND METHODS: High-resolution contrast-enhanced T1-weighted spinecho MR imaging using small fields of view (14-20 cm) and thin slices (4-5 mm) was performed in 26 patients with Takayasu's arteritis and 16 healthy subjects. The degree of aortic mural enhancement was assessed by measuring signal intensity and by visually estimating it in comparison with that of the myocardium. RESULTS: Contrast-enhanced MR imaging showed more enhancement of thickened aortic wall compared with myocardium, thus suggesting active Takayasu's arteritis on MR imaging in 16 patients. Determination of disease activity using contrast-enhanced MR imaging was concordant with clinical findings in 23 patients (88.5%). Contrast-enhanced MR findings were concordant with laboratory findings in most patients (erythrocyte sedimentation rate in 92.3% [24/26] and C-reactive protein in 84.6% [22/26]). The measured signal intensity of the aortic wall relative to that of myocardium during the early phase of contrast-enhanced MR imaging correlated well with the erythrocyte sedimentation rate (r = 0.78, p < 0.005) and with the C-reactive protein level (r = 0.63, p < 0.005). CONCLUSION: Contrast-enhanced MR imaging provides information about disease activity of Takayasu's arteritis, which may be useful in the diagnosis and treatment of Takayasu's arteritis.

Adolescent↗

Penile vibratory threshold changes with various doses of SS-cream in patients with primary premature ejaculation.

SS-cream made with extracts from natural products is a topical agent for treating premature ejaculation (PE). In order to elucidate the penile vibratory threshold changes and clinical effects of various doses of SS-cream, 53 patients with primary PE were investigated in a double-blind randomized placebo-controlled study. The mean age was 37.3 +/- 6.4 years and mean ejaculatory latency was 1.37 +/- 0.52 minutes. Neither the patients nor their sexual partners were satisfied with their sexual lives. Vibratory threshold at the glans penis, penile shaft, scrotum and index finger were measured using a biothesiometer twice during the screening period and three times one hour after the application of respective creams (SS-cream 0.05, 0.10. 0.15, 0.20 gm and placebo 0.10 gm) on the glans penis according to the order of the allocation table in a randomized fashion. The efficacy of SS-cream was defined as when the vibration threshold increased by more than 4 microns compared to the value tested during the screening period. The vibratory thresholds at the glans penis increased significantly in a dose-dependent manner after the application of various doses (0.05, 0.10, 0.15, 0.20 gm) of SS-cream (p < 0.001), and the efficacy of SS-cream on the penile vibration threshold increased according to the increased dosage (penile shaft: 48.4, 51.6, 54.8, 64.5%, glans penis: 58.1, 67.7, 77.4, 83.9%, respectively). With these results, we concluded that SS-cream increased the penile sensory threshold dose dependently, and therefore it is clinically effective for treating the heightened penile sensory response in patients with PE.

Adult↗

Epidermolysis bullosa simplex (Dowling-Meara type) associated with pyloric atresia and congenital urologic abnormalities.

We report a case of epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM), which was associated with congenital pyloric atresia (PA) and various urologic abnormalities, a diagnosis confirmed by immunofluorescence mapping and electron microscopic findings. Immunofluorescent mapping showed the serum from a patient with bullous pemphigoid faintly binding to the floor of the blister, and monoclonal antibodies against type IV and VII collagens were also stained on the floor of the blister. Electron microscopy showed epidermolytic cleavage and prominent clumping of tonofilaments in the basal and suprabasal keratinocytes. An abdominal radiograph and barium swallow showed a complete obstruction at the pyloric channel level. The widespread bullae healed without any scar formation and the bullae formation was localized on the extremities after 3 months of age without any specific treatment. Multiple urologic abnormalities such as bilateral hydronephrosis, hydroureter and a distended bladder with trabeculation were observed at 12 months of age. Currently, with the patient at 4 years of age, bullae still appear on the hands and feet and nail shedding can be observed. The patient's father, a paternal uncle and a paternal aunt had had similar bullous eruptions in infancy, all of which had improved spontaneously by the age of one.

Collagen↗

Aging affects the association between endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction in the Korean male population.

OBJECTIVES: The aging process affects responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase (ecNOS) gene polymorphisms were shown to affect the occurrence of acute myocardial infarction (AMI). We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. METHODS: We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. RESULTS: The aa, ab and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant correlation between the ecNOS polymorphism and AMI (p = 0.045). When the correlation was analyzed by age, the significance remained only in the group below the age of 51 (p = 0.009). The proportion of smokers was increased in the young patients when compared to the old patients (p = 0.033), indicating that smoking also has greater effect on the younger population. The incidences of hypertension and diabetes mellitus, however, were similar in both populations. CONCLUSION: Our work provides the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOSaa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old persons.

Adult↗

[The life of Dr. John William Heron, the second superintendent of Chejungwon].

The purpose of this paper is to overview the life of John W. Heron, M. D. who was the first appointed medical missionary to Korea by the Presbyterian Church USA. Although he was a competent doctor as well as a devoted missionary, he is not well-known yet, because he died early after 5 years' service in Korea. Dr. Heron was born in Derbyshire, England on June 15, 1856. His father, Rev. E. S. Heron, was a Scotch Minister of Congregational Church. His family emigrated to America in 1870 when he was fourteen years old and settled in Knoxville, Tennessee. In 1881, he was admitted to the University of Tennessee Medical School and graduated with highest honors in 1883. After training in New York University Hospital, he refused the offer of professorship from the University of Tennessee to become a medical missionary to Korea. He arrived in Seoul on June 21, 1885 and began to work in Royal Government Hospital, Chejungwon, the predecessor of Severance Hospital. In 1887, he became the superintendent of the Hospital following Dr. Horace N. Allen. He also worked for the Royal family and sometimes traveled to the rural areas to care for the patients. He started Chejungwon Church which later became Namdaemoon Presbyterian Church. In 1887, Dr. Heron worked as a member of the Bible translation committee and in 1889, he was elected as the chairman of the Public Committee of the Presbyterian Churches. In 1890, he established 'The Korean Religious Tract Society (Chosunsyungkyoseohoi) with Underwood and Ohlinger. The society published and replenished Christian books, periodical magazines and booklets. In the Summer of 1890, Dr. Heron did his best to take care of the sick suffering from an epidemic dysentery and himself got infected because of the terrible overwork. He passed away on July 26th, 1890. On his deathbed, he told his soldier and native friends around him as follow: "Jesus loves you. He gave His life for you. Stand by Him!" The martyrdom of Dr. Heron should be remembered in the Korean history of mission, because he was the first victim among the foreign missionaries who had lived and worked in Seoul for Korean mission. Dr. Heron's mind of love, service and devotion should be remembered by the medical doctors working today in caring for the patients suffering from physical and spiritual illnesses.

History, 19th Century↗

Inhibition of initiation of simian virus 40 DNA replication in vitro by the ursodeoxycholic acid and its derivatives.

In this study, the effects of the ursodeoxycholic acid (UDCA), and its derivatives, on DNA replication were examined using simian virus (SV40) DNA replication in vitro. We found that UDCA and its derivatives inhibited SV40 DNA replication, and predominantly inhibited the initiation stage of DNA replication. UDCA and its derivatives inhibited the DNA cleavage by topoisomerase I (topo I). Among them, HS-1183 significantly reduced the activity of topo I. UDCA, at 100 microM, significantly reduced polymerase alpha-primase (pol alpha-primase) activity, but HS-1030 and HS-1183 showed a weak inhibitory effect. The ssDNA binding activity of replication protein A (RPA) was little affected by UDCA and HS-1030, but was weakly inhibited by HS-1183. Based on their properties, we suggest that UDCA and its derivatives might inhibit some molecules that is required to establish replication forks during the initiation reaction and their cytotoxicity might be related to the inhibitory effect they have on this fundamental cellular process.

Antineoplastic Agents↗

Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene.

The mi locus encodes a member of the basic - helix - loop - helix - leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Although the bHLH-Zip family transcription factors generally recognize and bind CANNTG motifs, the expression of mouse mast cell protease 6 (MMCP-6) gene is regulated by MITF through the GACCTG motif in the promoter region. The GACCTG motif was partly overlapped the TGTGGTC sequence, which was bound by polyomavirus enhancer binding protein 2 (PEBP2). In the present study, the effect of PEBP2 on the expression of MMCP-6 gene was examined. PEBP2 that is composed of alpha and beta subunits was expressed by mast cell lines and cultured mast cells derived from spleen. The overexpression of dominant negative PEBP2 cDNA reduced the expression of MMCP-6. Moreover, the simultaneous transfection of the plasmid containing MITF cDNA and the plasmid containing PEBP2 cDNA increased the MMCP-6 promoter activity. For the synergistic action of PEBP2 and MITF, the intact GACCTG and TGTGGTC motifs were prerequisite. The PEBP2alphaB1 mutant which lacked the region downstream from the Runt domain did not bind MITF and lost the synergistic function. These results indicated that PEBP2 and MITF synergistically transactivated the MMCP-6 gene and that the region downstream from the Runt domain of PEBP2alphaB1 was essential for the physical and functional interactions with MITF.

Animals↗

Identification of the region of mi transcription factor which is responsible for the synergy with PEBP2/CBF.

The mi locus encodes the mi transcription factor (MITF), a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors. MITF binds the alphaB1/AML1 subtype of the alpha subunit of the polyomavirus enhancer binding protein 2 (PEBP2). These two transcription factors synergistically transactivate the mouse mast cell protease 6 (MMCP-6) gene. The interaction of PEBP2 with MITF is mediated through the region carboxy-terminal to the DNA-binding Runt domain. In the present study, we examined the region of MITF that is responsible for the interaction with PEBP2. The MITF mutant that lacked the region aa 67-152 did not bind PEBP2, and the mutant that lacked the region aa 1-152 lost the synergistic function in the transactivation of the MMCP-6 promoter. We conclude that the region amino-terminal to the basic region of MITF is required for physical and functional interactions with PEBP2.

Animals↗

Different effect of various mutant MITF encoded by mi, Mior, or Miwh allele on phenotype of murine mast cells.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). Mutant alleles of mi, Mior, and Miwh are deletion or point mutation of the basic domain by which MITF binds DNA. The basic domain also has nuclear localization potential. In the present study, we compared the mast cell abnormalities of Mior/Mior and Miwh/Miwh mice with those of mi/mi mice, of which many have been described by us. The number of mast cells in the skin of Mior/Mior suckling mice was remarkably decreased from that observed in mi/mi suckling mice, but the number was normal in the skin of Miwh/Miwh suckling mice. The decrease in skin mast cells was more severe in the mi/mi embryos than in mi/mi suckling mice, but the magnitude of the decrease was comparable between Mior/Mior embryos and Mior/Mior suckling mice. The poor mRNA expression of granzyme B and tryptophan hydroxylase genes was observed in all cultured mast cells (CMCs) derived from the spleens of Miwh/Miwh, Mior/Mior, and mi/mi mice. However, the poor expression of mouse mast cell protease-4 (MMCP-4), MMCP-5, and MMCP-6 was observed only in Mior/Mior and mi/mi CMCs. MITF encoded by Miwh mutant allele (Miwh-MITF) showed deficient but demonstratable DNA binding, but mi-MITF and Mior-MITF did not show any DNA binding ability. Although Miwh-MITF and Mior-MITF showed normal nuclear localization potential, the potential was significantly impaired in mi-MITF. The rank order of mast cell abnormality (mi/mi > Mior/Mior > Miwh/Miwh) appears to be related to the functional abnormality of MITF encoded by each mutant gene.

Alleles↗

Functional studies on the interaction between human replication protein A and Xeroderma pigmentosum group A complementing protein (XPA).

The human replication protein A (RPA; also known as human single-stranded DNA binding protein, HSSB) is a multisubunit complex (70, 34 and 11 kDa subunits) involved in the three processes of DNA metabolism; replication, repair, recombination. We found that both 34 and 70 kDa subunits (p34 and p70, respectively), of RPA interacts with the Xeroderma pigmentosum group A complementing protein (XPA), a protein that specifically recognizes UV-damaged DNA. Our mutational analysis indicated that no particular domains of RPA p70 were essential for its interaction with XPA. We also examined the effect of this XPA-RPA interaction on in vitro simian virus 40 (SV40) DNA replication catalyzed by the crude extract and monopolymerase system. XPA inhibited SV40 DNA replication in vitro through its interaction with RPA. Taken together, these results suggest that there is a role for RPA in the regulation of DNA metabolism through its ability to modulate the interactions of proteins involved in the processes of DNA metabolism.

Animals↗

No association between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer's disease.

Butyrylcholinesterase (BChE) as well as acetylcholinesterase has been suggested to be associated with Alzheimer's disease (AD). Lehmann et al. [1997: Hum Mol Genet 6:1933-1936] recently reported the synergism between the gene for the K variant of BChE (BCHE-K) and the epsilon4 allele of apolipoprotein E (APOE epsilon4) in late-onset confirmed AD with Caucasian subjects. The authors found that the allelic frequency of BCHE-K was 0.17 in 74 subjects with late-onset histopathologically diagnosed AD, which was higher than the frequencies in elderly control subjects (0.09) and in other dementias (0.07-0.10). The association of BCHE-K with late-onset AD was limited to carriers of APOE epsilon4, giving odds ratios of confirmed late-onset AD of 6.9-12.8. In the present study, we report the BCHE-K allelic frequencies in late-onset AD cases and in age-matched controls of the Korean population, which were 0.22 and 0.17, respectively. We could not find any association between BCHE-K and AD regardless of APOE epsilon4 carrier status. However, APOE epsilon4 clearly showed higher frequency in AD (0.33) than in elderly controls (0.09), giving an odds ratio of 5.2 (95% confidence interval, 2.7-10.0). Our results do not support the conclusion that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon4 as a susceptibility gene for late-onset AD, at least in the Korean population.

Aged↗