No apparent myocardial damage following 20,680 joules DC countershocks.
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Adult↗
Biomedical subjects
D W Kim
Publications and source records attributed to D W Kim.
cAMP response element-binding protein-binding protein binds to human papillomavirus E2 protein and activates E2-dependent transcription.
cAMP response element-binding protein-binding protein (CBP) is a eucaryotic transcriptional co-activator that contains multiple protein-protein interaction domains for association with various transcription factors, components of the basal transcriptional apparatus, and other co-activator proteins. Here, we report that CBP is also a co-activator of the human papillomavirus (HPV) E2 protein, which is a sequence-specific transcription/replication factor. We provide biochemical, genetic, and functional evidence that CBP binds directly to HPV E2 in vivo and in vitro and activates E2-dependent transcription. Mutations in an amphipathic helix within HPV-18 E2 abolish its transcriptional activation properties and its ability to bind to CBP. Furthermore, the binding of CBP to E2 was shown to be necessary for E2-dependent transcription. Interestingly, the histone acetyltransferase activity of CBP plays a role in CBP activation of E2-dependent transcription.
Acetyltransferases↗
Inhibitory effects of an aqueous extract of Apocynum venetum leaves and its constituents on Cu(2+)-induced oxidative modification of low density lipoprotein.
An aqueous extract of Apocynum venetum leaves and its constituents inhibited thiobarbituric acid reactive substances (TBARS) and conjugated-diene formation in the Cu(2+)-induced oxidation of low density lipoprotein (LDL) in vitro. The TBARS formation was most strongly inhibited by chlorogenic acid with an IC(50) value of 1.9 microM, but other constituents were in a range of 2.3-23.3 microM. On the other hand, the lag time in the conjugated-diene formation was dose-dependently prolonged by addition of the aqueous extract. Catechin prolonged the lag time more than 300 min and other constituents such as chlorogenic acid, epicatechin, epigallocatechin, hyperoside and isoquercitrin led to no conjugated-diene formation within 700 min under the experimental conditions.
Cholesterol, LDL↗
The inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenous leukemic K562 cells.
In this study, the downstream signaling of Bcr-Abl tyrosine kinase responsible for apoptosis resistance was investigated. DNA fragmentation, a hallmark of apoptosis, was observed after 2 days of herbimycin A treatment with a peak on 3 day. During the apoptosis induced by the treatment of herbimycin A, stress-activated protein kinase (SAPK) and p38 kinase were activated time- and dose-dependently, while extracellular signal-regulated kinase (ERK) was inhibited. However, apoptosis was induced by the treatment of PD98059, a specific inhibitor of MEK (MAPK or ERK kinase), not by the treatment of sorbitol, a strong activator of SAPK and p38 kinase. Although K562 cells were very resistant to sorbitol-induced apoptosis, DNA fragmentation was induced rapidly in Jurkat, HL-60 and U937 cells after exposure to sorbitol, despite that these apoptosis-sensitive cells have similar or lower activities of JNK/SAPK and p38 kinase compared with K562 cells after treatment of sorbitol. K562 cells had a much higher basal activity of ERK/MAPK than other apoptosis-sensitive cell lines, which were very susceptible to apoptosis induced by low dose of PD98059 compared with K562 cells. In HL-60 cells, sorbitol-induced apoptosis was prevented by the treatment of phorbol myristate 13-acetate (PMA), which activates the ERK/MAPK pathway, and this was blocked by PD98059. From these results, it could be suggested that the inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in K562 cells.
Apoptosis↗
Potentiation of chemosensitivity in multidrug-resistant human leukemia CEM cells by inhibition of DNA-dependent protein kinase using wortmannin.
DNA-dependent protein kinase (DNA-PK) is activated by DNA strand breaks and participates in DNA repair. Its regulatory subunit, Ku autoantigen, binds to DNA and recruits the catalytic subunit (DNA-PKcs). We show here a new role of DNA-PK in the development of multidrug resistance (MDR). The Ku-DNA binding activity, the levels of Ku70/Ku80 and DNA-PKcs in MDR variants, CEM/VLB(10-2), CEM/VLB(55-8) and CEM/VLB100 were higher than those in their parental drug-sensitive CEM cells in a drug resistance-dependent fashion. Also, CEM/VLB100 cells showed about 3-fold increase of DNA-PK enzyme activity as compared with CEM cells. Similar results were observed in another MDR cell line, FM3A/M mouse mammary carcinoma cells. Moreover, we observed that CEM/VLB100 cells were about 11-fold sensitive to wortmannin, which inhibits DNA-PK, compared with the CEM cells, and sensitized the MDR cells when combined with either bleomycin or vincristine, but have a little effect on CEM cells. Wortmannin was shown to inhibit DNA-PK and Ku-DNA binding activity in CEM/VLB100 cells dose dependently but had a little or no effect on their parental cells. Our results suggested that enhanced expression of DNA-PK participates in the development of MDR, and the use of DNA-PK inhibitors such as wortmannin is likely to improve the effectiveness of anticancer drugs and thus could partially overcome drug resistance in MDR cells, through its ability to inhibit Ku/DNA-PK activity.
Androstadienes↗
Adsorption of a mixture of Thiobacillus thiooxidans and Thiobacillus ferrooxidans onto copper-containing furnace dust.
The Langmuir adsorption parameter X(Am) of a mixture of culture of Thiobacillus ferrooxidans and Thiobacillus thiooxidans indicates that these bacteria have preferential and competitive adsorption sites on furnace dust. The constant K(A) of the mixture significantly larger than that of each component, suggesting that a synergistic effect may occur in the binding of these bacteria to the dust.
Journal Article↗
Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcripts in a rat model of mammary tumorigenesis.
Exposure to ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAH), may contribute to human breast cancer. In animals, PAH induce tumors in part by activating the aryl hydrocarbon receptor (AhR)/transcription factor. Historically, investigations into AhR-regulated carcinogenesis have focused on AhR-dependent transcriptional regulation of cytochrome P450 (CYP) enzymes which oxidize PAH to mutagenic intermediates. However, recent studies suggest that the AhR directly regulates cell growth. Given the postulated role of the AhR in carcinogenesis, we predicted that: (1) tissue predisposed to PAH tumorigenesis would express the AhR and (2) aberrant AhR and/or AhR-regulated gene expression would accompany malignant transformation. To test these hypotheses, AhR and CYP1 protein and/or mRNA levels were evaluated in rat mammary tumors induced with 7, 12-dimethylbenz[a]anthracene (DMBA), a prototypic PAH and AhR ligand. Results indicate modest AhR expression in normal mammary myoepithelial and ductal epithelial cells. In contrast, high AhR levels were detected in DMBA-induced tumors. Nuclear AhR localization in tumors suggested constitutive AhR activation. In situ hybridization and quantitative RT-PCR assays indicated high AhR mRNA levels in neoplastic epithelial cells. While both AhR-regulated CYP1A1 and CYP1B1 mRNAs were induced in breast tissue within 6 h of DMBA gavage, only CYP1B1 mRNA remained elevated in tumors. These results: (1) help explain targeting of breast tissue by carcinogenic PAH, (2) imply that AhR and CYP1B1 hyper-expression represent molecular biomarkers for, at least, PAH-induced mammary cell transformation, and (3) suggest mechanisms through which the AhR may contribute to carcinogenesis well after exogenous AhR ligands have been eliminated.
9,10-Dimethyl-1,2-benzanthracene↗
Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus.
For the elucidation of the antimutagenic and cytotoxic principles from the stem bark of Kalopanax pictus, seven isolated components of this crude drug were tested in the Ames test and the MTT test. Hederagenin and its monodesmosides, kalopanaxsaponin A and I in addition to its bisdesmosides, kalopanaxsaponin B and H, showed potent antimutagenic activities against aflatoxin B1 (AFB1). However, they had no inhibitory effects on mutagenicity induced by the direct mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This suggested that hederagenin glycosides might effectively prevent the metabolic activation of AFB1 or scavenge the electrophilic intermediate capable of inducing mutation. Hederagenin was found to be an essential moiety for the exhibition of antimutagenicity. Moreover, hederagenin and its 3-O-glycosides were found to be cytotoxic on various tumor cell lines, P-388, L-1210, U-937, HL-60, SNU-5 and HepG2, while 3,28-di-O-glycosides of hederagenin were not cytotoxic. Hence, hederagenin and its 3-O-glycosides could be suitable for cancer treatment chemopreventive drugs.
Antimutagenic Agents↗
Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells.
NF-kappaB/Rel is a family of transcription factors which are expressed in all cells; however, in most non-B cells, they are sequestered in the cytoplasm in inactive complexes with specific inhibitory proteins, termed IkappaBs. We have recently shown that NF-kappaB/Rel factors are aberrantly activated in human breast cancer and rodent mammary tumors, and function to promote tumor cell survival and proliferation. Here, we have examined the time-course of induction of NF-kappaB/Rel factors upon carcinogen treatment of female Sprague-Dawley (S-D) rats in vivo and in human mammary epithelial cells (HMECs) in culture. We observed that NF-kappaB/Rel activation is an early event, occurring prior to malignant transformation. In S-D rats, increased NF-kappaB/Rel binding was detected in nuclear extracts of mammary glands from 40% of animals 3 weeks post-treatment with 15 mg/kg 7,12-dimethylbenz[a]anthracene (DMBA); this is prior to formation of tumors which normally begin to be detected after 7-9 weeks. In non-tumorigenic MCF-10F cells, in vitro malignant transformation upon treatment with either DMBA or benzo[a]pyrene (B[a]P) resulted in a 4- to 12-fold increase in activity of classical NF-kappaB (p65/p50). NF-kappaB induction was corrrelated with a decrease in the stability of the NF-kappaB-specific inhibitory protein IkappaB-alpha. Ectopic expression of the transactivating p65 subunit of NF-kappaB in MCF-10F cells induced the c-myc oncogene promoter, which is driven by two NF-kappaB elements, and endogenous c-Myc levels. Furthermore, reduction mammoplasty-derived HMECs, immortalized following B[a]P exposure, showed dysregulated induction of classical NF-kappaB prior to malignant transformation. Together these findings suggest that activation of NF-kappaB plays an early, critical role in the carcinogen-driven transformation of mammary glands.
Animals↗
A case of Dowling-Degos disease suggesting an evolutional sequence.
We report a 47-year-old woman who presented with asymptomatic reticulate hyperpigmentations on the neck, lateral face, axillae, trunk, inguinal areas, and dorsa of both hands and feet. We thought it was an unusual case in the spectrum between the pole of Dowling-Degos disease (DDD) and that of reticulate acropigmentation of Kitamura (RAK). Another interesting point was that the biopsied specimens from the abdomen, neck, and axillary lesions showed somewhat different histopathologic features from typical DDD, suggesting an evolutional sequence. From these findings we suggest that a lichenoid inflammation may be responsible for the typical maculo-papular lesions of DDD.
Asian People↗
Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg.
The first step in the replication of the plus-stranded poliovirus RNA is the synthesis of a complementary minus strand. This process is initiated by the covalent attachment of UMP to the terminal protein VPg, yielding VPgpU and VPgpUpU. We have previously shown that these products can be made in vitro in a reaction that requires only synthetic VPg, UTP, poly(A), purified poliovirus RNA polymerase 3D(pol), and Mg(2+) (A. V. Paul, J. H. van Boom, D. Filippov, and E. Wimmer, Nature 393:280-284, 1998). Since such a poly(A)-dependent process cannot confer sufficient specificity to poliovirus RNA replication, we have developed a new assay to search for a viral RNA template in conjunction with viral or cellular factors that could provide this function. We have now discovered a small RNA hairpin in the coding region of protein 2C as the site in PV1(M) RNA that is used as the primary template for the in vitro uridylylation of VPg. This hairpin has recently been described in poliovirus RNA as being an essential structure for the initiation of minus strand RNA synthesis (I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590-4600, 2000). The uridylylation reaction either with transcripts of cre(2C) RNA or with full-length PV1(M) RNA as the template is strongly stimulated by the addition of purified viral protein 3CD(pro). Deletion of the cre(2C) RNA sequences from minigenomes eliminates their ability to serve as template in the reaction. A similar signal in the coding region of VP1 in HRV14 RNA (K. L. McKnight and S. M. Lemon, RNA 4:1569-1584, 1998) and the poliovirus cre(2C) can be functionally exchanged in the assay. The mechanism by which the VPgpUpU precursor, made specifically on the cre(2C) template, might be transferred to the site where it serves as primer for poliovirus RNA synthesis, remains to be determined.
Base Sequence↗
Genetic and biochemical studies of poliovirus cis-acting replication element cre in relation to VPg uridylylation.
In addition to highly conserved stem-loop structures located in the 5'- and 3'-nontranslated regions, genome replication of picornaviruses requires cis-acting RNA elements located in the coding region (termed cre) (K. L. McKnight and S. M. Lemon, J. Virol. 70:1941-1952, 1996; P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560-11565, 1999; I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590-4600, 2000). cre elements appear to be essential for minus-strand RNA synthesis by an as-yet-unknown mechanism. We have discovered that the cre element of poliovirus (mapping to the 2C coding region of poliovirus type 1; nucleotides 4444 to 4505 in 2C), which is homologous to the cre element of poliovirus type 3, is preferentially used as a template for the in vitro uridylylation of VPg catalyzed by 3D(pol) in a reaction that is greatly stimulated by 3CD(pro) (A. V. Paul, E. Rieder, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74:10359-10370, 2000). Here we report a direct correlation between mutations that eliminate, or severely reduce, the in vitro VPg-uridylylation reaction and produce replication phenotypes in vivo. None of the genetic changes significantly influenced translation or polyprotein processing. A substitution mapping to the first A (A4472C) of a conserved AAACA sequence in the loop of PV-cre(2C) eliminated the ability of the cre RNA to serve as template for VPg uridylylation and abolished RNA infectivity. Mutagenesis of the second A (A4473C; AAACA) severely reduced the yield of VPgpUpU and RNA infectivity was restored only after reversion to the wild-type sequence. The effect of substitution of the third A (A4474G; AAACA) was less severe but reduced both VPg uridylylation and virus yield. Disruption of base pairing within the upper stem region of PV-cre(2C) also affected uridylylation of VPg. Virus derived from transcripts containing mutations in the stem was either viable or quasi-infectious.
Base Sequence↗
Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter.
We have previously shown that TFII-I enhances transcriptional activation of the c-fos promoter through interactions with upstream elements in a signal-dependent manner. Here we demonstrate that activated Ras and RhoA synergize with TFII-I for c-fos promoter activation, whereas dominant-negative Ras and RhoA inhibit these effects of TFII-I. The Mek1 inhibitor, PD98059 abrogates the enhancement of the c-fos promoter by TFII-I, indicating that TFII-I function is dependent on an active mitogen-activated protein (MAP) kinase pathway. Analysis of the TFII-I protein sequence revealed that TFII-I contains a consensus MAP kinase interaction domain (D box). Consistent with this, we have found that TFII-I forms an in vivo complex with extracellular signal-related kinase (ERK). Point mutations within the consensus MAP kinase binding motif of TFII-I inhibit its ability to bind ERK and its ability to enhance the c-fos promoter. Therefore, the D box of TFII-I is required for its activity on the c-fos promoter. Moreover, the interaction between TFII-I and ERK can be regulated. Serum stimulation enhances complex formation between TFII-I and ERK, and dominant-negative Ras abrogates this interaction. In addition, TFII-I can be phosphorylated in vitro by ERK and mutation of consensus MAP kinase substrate sites at serines 627 and 633 impairs the phosphorylation of TFII-I by ERK and its activity on the c-fos promoter. These results suggest that ERK regulates the activity of TFII-I by direct phosphorylation.
3T3 Cells↗
Detection of the BCR-ABL fusion gene in natural killer cells in patients with chronic myelogenous leukemia.
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Adult↗
Additional stem cell therapy for graft failure after allogeneic bone marrow transplantation.
In this study we retrospectively evaluated the effect and outcome of a boost dose of donor stem cells without additional chemotherapy or total body irradiation. Between March 1983 and August 1999, 20 of 788 (2.5%) patients receiving allogeneic bone marrow transplantation (BMT) were treated with an additional boost dose of donor cells. The reasons for the use of the boost treatment were primary graft failure (early rejection; n = 7), secondary graft failure including late rejection (n = 10), refractory pure red cell aplasia caused by the remaining recipient cells producing anti-erythrocyte antibodies (n = 2), and donor lymphocyte infusion induced pancytopenia (n = 1). The patients were aged from 17 to 48 years (median age 31 years). The underlying diseases of the patients were severe aplastic anemia in 12 patients, acute myelogenous leukemia in 3, acute lymphocytic leukemia in 3, and chronic myelogenous leukemia in 2. The donors were human leukocyte antigen-identical siblings in 18 cases, 1 mismatched related donor, and 1 unrelated donor. The cell source was bone marrow in 6 cases and peripheral blood progenitor cells in 14. The median interval between BMT and the boost treatment was 7 weeks (range 1-124). No conditioning regimen was given prior to the boost treatment for 11 patients, while 4 received total nodal irradiation (TNI) plus antithymocyte globulin (ATG), 3 ATG alone, and 2 TNI plus steroid. The median infused booster mononuclear cell dose was 2.55 x 10(8)/kg (range 0.28-37.0). Fifteen (75%) patients achieved a hematological recovery. After the boost treatment, 6 of 20 (30%) patients developed acute graft-versus-host disease (GVHD) > or = grade II, 3 of whom had had prior GVHD. Five (31.3%) of the evaluable 16 patients developed chronic GVHD. The GVHDs were easily controlled using immunosuppressive agents except in the case of 1 patient. Five patients died after the boost treatment; 2 within 30 days, 2 within 60 days, and 1 after 32 months. The causes of death were: 3 engraftment failures, 1 late rejection, and 1 infection following GVHD. With a median follow-up of 31.5 months (range 6-92), the Kaplan-Meier method estimated that the overall survival rate 1 and 3 years after the boost treatment was 80 and 71%, respectively. The survival of patients with primary graft failure was determined to be significantly lower compared to that of patients with secondary graft failure, using the log rank test (p = 0.0176). Disease category, stem cell source, conditioning prior to a boost treatment, and year of boost treatment did not have an influence on survival. We conclude that the reinfusion of donor stem cells is frequently successful in achieving engraftment with rare occurrence of fatal GVHD. Furthermore, relatively good long-term survival was demonstrated.
Actuarial Analysis↗
Development of a frequency-dependent-type apex locator with automatic compensation.
Among apex locators, the frequency dependent type is more accurate and convenient to use than others. However, the accuracy of the apex locator is still influenced by the presence of various electrolytes used in root canal treatments. In this study, we developed a frequency-dependent electronic apex locator minimizing the influence of electrolytes on the measurement of root canal lengths. It was confirmed that the two frequencies of 0.5 and 10 kHz are better than the conventional ones of 0.4 and 8 kHz. The impedance ratio of the two different frequencies represents the position of the file in root canal, and the voltage difference of the two frequencies represents the status of the fluid in the root canal. As a result of compensation using the voltage differences of the two frequencies, the errors decreased significantly on average from +0.54 mm to +0.18 mm in H2O2 solution (p < 0.01), and from -0.33 mm to -0.01 mm in NaOCl solution (p < 0.01) in the tooth model experiments.
Analysis of Variance↗
Usefulness of a developed four-channel EGG system with running spectrum analysis.
Electrogastrography (EGG) is a method of measuring action potentials on the abdomen. It is noninvasive, inexpensive and easy to measure. However, the EGG signal has a very low frequency (0.05 Hz) and an extremely low amplitude (10-100 microV). Consequently, its measured waveform is difficult to analyze and it is not yet completely understood. In this study, a four-channel EGG measurement system was built to measure the action potential of the stomach. This system was compared with the commercially available one-channel Digitrapper EGG. The 3 cpm percentages were compared between the best channel of the four-channel system and channel 1, whose electrode position was similar to the commercially available one-channel system for normal subjects. The average 3 cpm percentage of the best channel and channel 1 for preprandial measurement was 89.5% and 83.2%, respectively, and this was statistically significant (p < 0.001). Also the average 3 cpm percentage of the best channel and channel 1 for postprandial measurement was 90.4% and 76.5%, respectively, and this was statistically significant (p = 0.003). From these results, it can be concluded that a multi-channel EGG system is required for better EGG measurement.
Action Potentials↗
A quantitative evaluation of pigmented skin lesions using the L*a*b* color coordinates.
The evaluation of pigmentary skin lesions by clinical doctors has been based on subjective and qualitative judgements. Observations have mostly relied on visual inspection, making the effects of treatment difficult to evaluate with any precision. For this reason there is a real need for an objective method to evaluate prognosis after treatment. Recent scientific measurements such as reflectance spectrophotometry and reflectance colorimetry have provided accurate quantitative color information about skin lesions, but these techniques are costly and difficult to apply in the clinical field. The purpose of this study was to develop a simple and cost-effective way of evaluating treatment results. We have developed a software program using the L*a*b* color coordinate system to quantify the effect of treatment and have successfully demonstrated its clinical usefulness. Our method compares the relative color difference between normal skin and skin lesions before and after treatment, instead of measuring the absolute color of skin lesions. The accuracy of our quantitative color analysis was confirmed by the simulated images of hemangioma and ota nevus. Clinical efficacy was also confirmed through a blind test involving 3 clinicians who were asked to grade the treatment effects of 13 cases of hemangioma and 7 cases of ota nevus. These subjective clinical grades correlated well with the treatment results obtained using the proposed color analysis system (Correlation coefficient = 0.84).
Color↗