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1.
Free Radic Res ; 49(1): 25-34, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25287330

ABSTRACT

The production of microRNAs (miRNA) is influenced by various stimuli, including environmental stresses. We hypothesized that reactive oxygen species (ROS)-associated stress could regulate macrophage miRNA synthesis. miRNAs undergo unique steps of maturation processing through either one of two pathways of cytoplasmic processing. Unlike the canonical pathway, the regulation of alternative cytoplasmic processing of miRNA has not been fully elucidated yet. We cultured bone marrow derived macrophages (BMDM) from wild type (WT) and p47(phox-/-) mice and profiled miRNA expression using microarrays. We analyzed 375 miRNAs including four endogenous controls to normalize the data. At resting state, p47(phox-/-) BMDM has the markedly reduced expression of miR-451 compared to WT BMDM, without other significant differences. Unlike majority of miRNAs, miR-451 goes through the unique alternative processing pathway, in which Ago2 plays a key role. In spite of significant reduction of mature miR-451, however, its precursor form, pre-mir-451, was similar in both BMDMs, suggesting that the processing of pre-mir-451 is impaired in p47(phox-/-) BMDM. Moreover, p47(phox-/-) BMDM expressed significantly reduced level of Ago2. In contrast, Ago2 mRNA levels were similar in WT and p47(phox-/-) BMDM, suggesting a post-transcriptional defect of Ago2 production in p47(phox-/-) macrophages, which resulted in impaired processing of pre-miR-451. In order to examine the functional significance of miR-451 in macrophages, we cultured BMDMs from miR-451 knock-out mice. Of interest, miR-451-deficient BMDM exhibited reduced ROS generation upon zymosan stimulation, compared to WT BMDM. Our studies suggest functional crosstalk between ROS and miR-451 in the regulation of macrophage oxidant stress.


Subject(s)
Macrophages/metabolism , MicroRNAs/biosynthesis , NADPH Oxidases/metabolism , Reactive Oxygen Species/metabolism , Animals , Argonaute Proteins/metabolism , Cell Line , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , NADPH Oxidases/deficiency , NADPH Oxidases/genetics
2.
J Eur Acad Dermatol Venereol ; 28(11): 1436-41, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25493315

ABSTRACT

BACKGROUND: Previous studies have indicated an association between psoriasis and inflammatory bowel disease (IBD), and the concurrence of the two diseases reportedly has higher morbidities in Caucasian populations. However, reports on the concurrence of psoriasis with IBD in the Asian population in the literature are scarce. Objective To analyse the characteristics of psoriasis concurrent with IBD and investigate the associated morbidity in the Asian population. METHODS: We retrospectively examined the medical records of 15 patients with a confirmed diagnosis of both psoriasis and IBD. Sixty age-, gender-, and ethnicity-matched patients with a confirmed diagnosis of only psoriasis were included as controls. Both cases and controls had visited the Seoul National University Hospital or Seoul National University Boramae Hospital between 1990 and 2012. The characteristics of psoriasis, presence of comorbidity and laboratory parameters were compared between the two groups. RESULTS: Compared to controls with psoriasis only, cases of psoriasis concurrent with IBD had a younger age of onset, longer duration of psoriasis and a higher Psoriasis Area Severity Index (PASI) score. A larger proportion of cases was treated with phototherapy, systemic therapy and biologics. However, all these differences above were not statistically significant. Cases of psoriasis with concurrent IBD showed higher erythrocyte sedimentation rate and C-reactive protein levels compared with the controls (both P = 0.000). Furthermore, this case group had a higher proportion of patients with psoriatic arthritis and with more than one autoimmune disease as compared with the control group (P = 0.007 and 0.005 respectively). CONCLUSION: Asian patients having psoriasis concurrent with IBD exhibited different characteristics as compared with those having psoriasis only, particularly in terms of psoriasis severity, risk of psoriatic arthritis, systemic inflammatory parameters and presence of autoimmune comorbidity. However, further studies elucidating the exact pathogenesis and including a larger number of patients are required.


Subject(s)
Asian People , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiology , Psoriasis/diagnosis , Psoriasis/epidemiology , Severity of Illness Index , Adult , Age Factors , Aged , Biological Products/therapeutic use , Blood Sedimentation , C-Reactive Protein/metabolism , C-Reactive Protein/therapeutic use , Case-Control Studies , Comorbidity , Female , Humans , Inflammatory Bowel Diseases/therapy , Male , Middle Aged , Phototherapy , Psoriasis/therapy , Republic of Korea , Retrospective Studies , Treatment Outcome
3.
Transpl Infect Dis ; 16(2): 295-303, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24628837

ABSTRACT

BACKGROUND: The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long-term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection. METHODS: We retrospectively investigated the hepatitis B surface antigen (HBsAg)-positive KTR with antiviral agents between January 2002 and January 2012. Antiviral treatments were withdrawn in patients who met all of the following 7 criteria: (i) no clinical and histologic evidence of cirrhosis, (ii) normal liver biochemistry, (iii) negative for both HBV DNA and hepatitis B envelope antigen (HBeAg), (iv) no resistance to antiviral agent, (v) antiviral therapy > 9 months, (vi) maintenance dosage of immunosuppressant for > 3 months, and (vii) no history of acute rejection during recent 6 months. All patients were followed regularly at approximately 3-6 months for liver enzyme, viral markers, and HBV DNA level after antiviral withdrawal. RESULTS: Among a total of 445 KTR, 14 HBsAg-positive patients were included in this study. Antiviral agents were used, with lamivudine in 11 patients, and with adefovir, entecavir, and telbivudine in 3 patients, respectively. Discontinuation of antiviral agent was attempted in 6 (42.9%) of 14 patients who satisfied the criteria. The median duration of antiviral therapy before withdrawal was 14.3 months (range, 9-24 months). Four (66.7%) of 6 patients were successfully withdrawn and remained negative for HBV DNA for a median 60.5 months (range, 47-82 months). The baseline HBV DNA level was not related to maintenance of remission after withdrawal. Two reactivated patients resumed antiviral treatment immediately, with subsequent normalization of HBV DNA. During the follow-up, 1 patient developed hepatocellular carcinoma; however, no patient death or graft failure was reported for all HBsAg-positive KTR. CONCLUSIONS: Antiviral therapy can be discontinued successfully and safely in selected KTR with chronic HBV infection, after complete suppression of HBV and sufficient duration of antiviral therapy.


Subject(s)
Antiviral Agents/therapeutic use , DNA, Viral/blood , Hepatitis B virus/physiology , Hepatitis B, Chronic/drug therapy , Kidney Transplantation , Withholding Treatment , Adenine/analogs & derivatives , Adenine/therapeutic use , Adult , Alanine Transaminase/blood , Female , Follow-Up Studies , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/immunology , Hepatitis B, Chronic/blood , Humans , Immunosuppressive Agents/administration & dosage , Lamivudine/therapeutic use , Male , Middle Aged , Organophosphonates/therapeutic use , Retrospective Studies , Telbivudine , Thymidine/analogs & derivatives , Thymidine/therapeutic use , Time Factors , Virus Activation
4.
Cancer Gene Ther ; 21(4): 158-63, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24626062

ABSTRACT

14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.


Subject(s)
14-3-3 Proteins/deficiency , Brain Neoplasms/metabolism , Brain Neoplasms/radiotherapy , Glioblastoma/metabolism , Glioblastoma/radiotherapy , 14-3-3 Proteins/genetics , 14-3-3 Proteins/metabolism , Apoptosis/radiation effects , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Cycle/radiation effects , Cell Death/radiation effects , Cell Growth Processes/radiation effects , Cell Line, Tumor , Cell Survival/radiation effects , Glioblastoma/genetics , Glioblastoma/pathology , HeLa Cells , Humans , Mitosis/radiation effects , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Radiation Tolerance/physiology , Transfection
5.
Transplant Proc ; 45(8): 2899-902, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24157000

ABSTRACT

INTRODUCTION: Screening for latent tuberculosis infection (LTBI) before kidney transplantation (KT) is an indispensable process, purposes of this study were to compare the QuantiFERON-TB Gold In-Tube test (QFT-GIT) with the tuberculin skin test (TST) for screening of LTBI in kidney transplant recipients (KTRs). METHODS: We compared prospectively the results of QFT-GIT with TST in 97 KTRs screened for LTBI between July 2008 and July 2012. Isoniazid (INH) prophylaxis was applied to KTRs with a positive TST or positive QFT-GIT or clinical risk factors for LTBI. Post-transplant tuberculosis (TB) was diagnosed by clinical evidence. RESULTS: The mean patients follow-up was 24.6 ± 14.4 months. Positive results on QFT-GIT and TST was obtained among 19 (20.4%) and 12 (12.9%) subjects, respectively, an overall agreement of 79.3% (κ = 0.27, 95% confidence interval [CI] -0.03-0.50; P < .014). The incidence of TB was 0.52 per 100 person-years (95% CI 0.02-3.68). None of the patients in the INH prophylaxis group developed TB, whereas 1 in the no prophylaxis group developed disease at 14 months after KT. Sensitivity of the 2 tests could not be compared because patients who showed positive results on QFT-GIT or TST did not develop TB. The difference of specificity between QFT-GIT (79.3%) and TST (86.9%) was not significant (P = .l67). Abnormal chest radiographs (odds ratio [OR] 27.94, 95% CI 1.22-636.61, P = .037) and positive TST (OR 7.65, 95% CI 1.75-33.30, P = .007) showed significant associations with positive QFT-GIT results. Only positive QFT-GIT (OR 6.03, 95% CI 1.51-24.01, P = .011) showed an association with positive TST results. CONCLUSIONS: QFT-GIT and TST for diagnosis of LTBI in KTRs showed reasonable concordance but no superiority of either test.


Subject(s)
Kidney Transplantation , Latent Tuberculosis/diagnosis , Tuberculin Test , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity
6.
Transplant Proc ; 45(4): 1584-9, 2013 May.
Article in English | MEDLINE | ID: mdl-23726625

ABSTRACT

BACKGROUND: Urinary tract infections (UTIs) are the most common infectious complication in kidney transplant recipients (KTRs). The aim of this study to investigate the risk factors for and causative organisms of UTI as well as to evaluate the impact these diseases on allograft function in KTRs. METHODS: We analyzed patients who underwent kidney transplantation (KT) between January 2000 and December 2010. Among a total of 344 KTRs, 50 (14.5%) patients experienced 106 UTI episodes during a mean follow-up of 35.9 ± 26.0 months. Twenty three patients experiencing recurrent UTI were compared with 27 nonrecurrent UTI patients and with 50 non-UTI patients matched for age, gender, and transplantation date. RESULTS: The number of patients with renal calculi, diabetes, or prior dialysis was significantly greater among the UTI group compared with control subjects. In addition, the number of patients with renal calculi was significantly higher among the recurrent compared with the nonrecurrent cohort (43.5 vs 7.4%; P = .003). The most common causative organism was Escherichia coli (64.1%), followed by Enterococcus species (20.5%). Higher rates of antibiotic resistance, especially Extended Spectrum Beta-Lactamasc (ESBL) production, were observed among the recurrent compared with the nonrecurrent group (53.1 vs 0%; P = .013). The rate of decline of estimated glomerular filtration rate was significantly faster in the UTI than the non-UTI group, whereas it did not differ between the recurrent and nonrecurrent group. CONCLUSIONS: Adequate treatment of an initial UTI to prevent as recurrent infection and prolong graft longevity is especially reasonable for KTRs with renal calculi or in cases of antibiotic-resistant microorganisms.


Subject(s)
Kidney Transplantation , Urinary Tract Infections/epidemiology , Adult , Creatinine/blood , Female , Humans , Male , Recurrence , Retrospective Studies , Risk Factors , Urinary Tract Infections/microbiology
7.
Oncogene ; 32(12): 1560-9, 2013 Mar 21.
Article in English | MEDLINE | ID: mdl-22562251

ABSTRACT

14-3-3 proteins are involved in several cellular processes, including the G1/S and G2/M cell cycle transitions. However, their roles during mitosis are not well understood. Here, we showed that depletion of 14-3-3η, a 14-3-3 protein isoform, enhanced mitotic cell death, resulting in sensitization to microtubule inhibitors and inhibition of aneuploidy formation. The enhanced mitotic cell death by depletion of 14-3-3η appeared to be both caspase-dependent and independent. Furthermore, enhanced mitotic cell death and a reduction in aneuploidy following 14-3-3η depletion were independent of the mitotic checkpoint, which is thought to be the primary signaling event in the regulation of the cell death induced by microtubule inhibitors. When 14-3-3η depletion was combined with microtubule inhibitors in HCT116 and U87MG cells, it sensitized both cancer cell lines to microtubule inhibitors. These results collectively suggest that 14-3-3η may be required for mitotic progression and may be considered as a novel anti-cancer strategy in combination with microtubule inhibitors.


Subject(s)
14-3-3 Proteins/physiology , Mitosis , Neoplasms/drug therapy , 14-3-3 Proteins/antagonists & inhibitors , Aneuploidy , Apoptosis/drug effects , Caspase 9/physiology , Cell Division , Forkhead Box Protein O3 , Forkhead Transcription Factors/physiology , G2 Phase , HeLa Cells , Humans , Microtubules/drug effects , Neoplasms/pathology , Nocodazole/pharmacology
8.
Clin Lab ; 57(11-12): 959-67, 2011.
Article in English | MEDLINE | ID: mdl-22239028

ABSTRACT

BACKGROUND: Human enteroviruses (HEVs) are a major cause of herpangina, HFMD (hand, foot, and mouth disease), and other neurological diseases in Seoul, Korea. METHODS: A total of 56 specimens from hospitalized patients collected from February to December 2009 (37 females and 19 males) in Seoul were tested for HEV from stool, throat swab, and vesicle swab samples taken from patients with herpangina or HFMD using cell culture and RT-PCR in 2009. By the 1D gene, encoding the VP1 capsid protein, seven different HEV genotypes were detected with Coxsackievirus A2, A4, A5, A9, A16 (CA), Coxsackievirus B1 (CB), and Enterovirus 71 (EV71). The most prevalent genotype was CA16 (6, 10.7%), followed by CA2 (4, 7.1%), CA5 (4, 7.1%), EV71 (2, 3.6%), CA4 (1, 1.8%), CA9 (1, 1.8%), and CB1 (1, 1.8%). The 1D gene sequences of two EV71 strains were closely related with one another (98.5% nucleotide similarity) and belonged to the C4 genotype. CONCLUSIONS: It is important to continuously survey the genetic characteristics of EV71 and CA16 from patients, which will provide useful data that aids in our understanding of HFMD infections in Seoul, Korea and may contribute to future control.


Subject(s)
Coxsackievirus Infections/virology , Disease Outbreaks , Enterovirus Infections/virology , Enterovirus/isolation & purification , Hand, Foot and Mouth Disease/virology , Herpangina/virology , Capsid Proteins/genetics , Child, Preschool , Coxsackievirus Infections/epidemiology , Enterovirus/genetics , Enterovirus A, Human/genetics , Enterovirus A, Human/isolation & purification , Enterovirus B, Human/genetics , Enterovirus B, Human/isolation & purification , Enterovirus Infections/epidemiology , Feces/virology , Female , Hand, Foot and Mouth Disease/epidemiology , Herpangina/epidemiology , Humans , Infant , Infant, Newborn , Male , Pharynx/virology , Phylogeny , RNA, Viral/genetics , RNA, Viral/isolation & purification , Republic of Korea/epidemiology , Sequence Analysis, RNA
9.
Article in English | MEDLINE | ID: mdl-24785310

ABSTRACT

Total arsenic, mercury, lead, and cadmium contents were determined in 426 samples of seaweed sold in Korea in 2007-08. The average concentrations, expressed in mg kg(-1), dry weight, were: total arsenic 17.4 (less than the limit of detection [LOD] to 88.8), Hg 0.01 (from 0.001 to 0.050), lead 0.7 (less than the LOD to 2.7), and cadmium 0.50 (less than the LOD to 2.9). There were differences in mercury, cadmium, and arsenic content in seaweed between different kinds of products and between coastal areas. The intakes of total mercury, lead, and cadmium for Korean people from seaweed were estimated to be 0.11, 0.65, and 0.45 µg kg(-1) body weight week(-1), respectively. With respect to food safety, consumption of 8.5 g day(-1) of the samples analysed could represent up to 0.2-6.7% of the respective provisional tolerable weekly intakes established by the World Health Organization (WHO). Therefore, even if Korean people have a high consumption of seaweed, this study confirms the low probability of health risks from these metals via seaweed consumption.


Subject(s)
Arsenic/analysis , Cadmium/analysis , Food Contamination/analysis , Lead/analysis , Mercury/analysis , Seaweed/chemistry , Arsenic/toxicity , Cadmium/toxicity , Food Analysis/methods , Food Safety , Food, Preserved/analysis , Humans , Lead/toxicity , Maximum Allowable Concentration , Mercury/toxicity , Republic of Korea , Risk Assessment
10.
Prep Biochem Biotechnol ; 39(4): 345-59, 2009.
Article in English | MEDLINE | ID: mdl-19739022

ABSTRACT

Using hypocotyl and cotyledon of sesame seedlings, hairy root cultures were established and cDNA coding for a peroxidase was cloned from the roots. The frequency of sesame hairy root formation was higher in hypocotyl (33.4%) than cotyledon (9.3%). Applicable levels of kanamycin and hygromycin as a selectable marker were 100 microg/mL and 30 microg/mL, respectively. The peroxidase cDNA showed relatively high sequence identity with and similarity to plant class III peroxidase family. The cDNA encoded polypeptide was identified with the presence of three sequence features: 1) the putative 4 disulfide bridges, 2) an ER-targeted signal sequence in the N-terminus, and 3) two triplets, NXS for glycosylation. A real-time RT-PCR exhibited an abrupt increase in the peroxidase transcription activity after 4-week cultures of the sesame hairy roots and its highest level in 6-week cultured hairy roots. In contrast, the growth pattern of sesame hairy roots showed a typical sigmoidal curve. The active hairy root growth began after 2-week culture and their stationary growth phase occurred after 5-week culture. These results suggested that the peroxidase expression patterns at its transcription level could be used a potential indicator signaling a message that there will be no longer active growth in hairy root cultures. The sesame peroxidase gene was differentially expressed in different tissues.


Subject(s)
Peroxidase/metabolism , Plant Roots/growth & development , Seedlings/enzymology , Seedlings/growth & development , Sesamum/enzymology , Sesamum/growth & development , Plant Roots/microbiology , Rhizobium/physiology , Seedlings/microbiology , Sesamum/microbiology
11.
Clin Exp Immunol ; 150(2): 245-54, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17672868

ABSTRACT

Cyclooxygenase-2 (COX-2) gene expression in the lung is induced in pathological conditions such as asthma and pneumonia; however, the exact impact of COX-2 gene expression in the airway in regulating inflammatory and immunological response in the lung is not understood. To define a physiological role of inducible COX-2 in airway epithelial cells, we developed a novel line of transgenic mice, referred to as CycloOxygenase-2 TransActivated (COTA) mice, that overexpress a COX-2 transgene in the distribution of the CC-10 promoter in response to doxycycline. In response to doxycycline treatment, COX-2 expression was increased in airway epithelium of COTA mice and whole lung tissue contained a three- to sevenfold increase in prostaglandin E(2) (PGE(2)), prostaglandin D(2) (PGD(2)) thromboxane B(2) (TXB(2)) and 6-Keto prostaglandin F(2alpha) (PGF(2alpha)) compared to wild-type and untreated COTA mice. Interestingly, primary mouse tracheal epithelial cells from COTA mice produced only PGE(2) by doxycycline-induced COX-2 activation, providing an indication of cellular specificity in terms of mediator production. In the ovalbumin model, in which doxycycline was given at the sensitization stage, there was an increase in interleukin (IL)-4 level in lung tissue from COTA mice compared to untreated COTA and wild-type mice. In addition, COTA mice that were treated with doxycycline had impaired clearance of Pseudomonas aeruginosa pneumonia compared to wild-type mice. COX-2 gene expression in airway epithelial cells has an important role in determining immunological response to infectious and allergic agents.


Subject(s)
Bronchi/enzymology , Cyclooxygenase 2/immunology , Gene Expression Regulation, Enzymologic/immunology , Respiratory Mucosa/immunology , Trachea/enzymology , Animals , Bronchi/immunology , Cells, Cultured , Cyclooxygenase 2/genetics , Dinoprostone/biosynthesis , Epithelial Cells/enzymology , Epithelial Cells/immunology , Genotype , Immunity, Mucosal , Interleukin-4/biosynthesis , Mice , Mice, Transgenic , Prostaglandins/biosynthesis , Pseudomonas Infections/immunology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/growth & development , Trachea/immunology
12.
Phys Rev Lett ; 98(8): 085003, 2007 Feb 23.
Article in English | MEDLINE | ID: mdl-17359106

ABSTRACT

In low-pressure capacitively coupled plasmas, high-energy electrons are collisionlessly heated by large rf fields in the sheaths while low-energy electrons are confined in the bulk plasma by the ambipolar potential. Low-energy electrons are typically inefficiently heated due to their low collisionality and the weak rf electric field present in the bulk. It is shown, however, that as a result of the nonlinear interaction between the electron motion and the weak rf field present in the bulk, low-energy electrons can be efficiently heated. Electrons in the bulk that bounce inside the electrostatic potential well with a frequency equal to the rf excitation frequency are efficiently heated by the coherent interaction with the rf field. This resonant collisionless heating can be very efficient and manifest itself as a plateau in the electron energy probability function.

13.
Int J Tuberc Lung Dis ; 8(10): 1221-7, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15527154

ABSTRACT

OBJECTIVE: The molecular basis of the genetic vulnerability underlying the most common form of clinical tuberculosis (TB) remains largely unknown. We speculated that mild genetic defects in the interferon-gamma (IFN-gamma) signalling pathway caused a subtle functional impairment of IFN-gamma which would explain susceptibility to Mycobacterium tuberculosis in clinical TB. DESIGN: A case-control study. RESULTS: We evaluated functional responsiveness to IFN-gamma in monocytes from patients with clinical TB (n = 10), and analysed the genetic sequences of the IFN-gamma receptor 1 (IFN-gammaR1) and STAT1 genes in patients with disseminated TB (n = 18). IFN-gamma stimulated an increase in the expression of HLA-DR and CD64 on monocytes of both controls and patients; the rate of increase in expression was the same in both groups. Treatment with IFN-gamma before lipopolysaccharide (LPS) stimulation further increased tumour necrosis factor-alpha (TNF-alpha) production as compared to TNF-alpha production with LPS stimulation alone; the rate of increase in TNF-alpha production was the same in both groups. The known mutations in the coding sequences of the IFN-gammaR1 and STAT1 genes were not found in the patients with disseminated tuberculosis. CONCLUSION: These results suggest that impairment of the IFN-gamma signalling pathway did not account for cases of clinical TB in this study.


Subject(s)
Receptors, Interferon/genetics , Tuberculosis/genetics , Adult , Case-Control Studies , DNA-Binding Proteins/genetics , Disease Susceptibility , HLA-DR Antigens/analysis , Humans , Lipopolysaccharides/pharmacology , Monocytes/immunology , Receptors, IgG/analysis , STAT1 Transcription Factor , Signal Transduction , Trans-Activators/genetics , Tumor Necrosis Factor-alpha/biosynthesis , Interferon gamma Receptor
14.
Water Sci Technol ; 50(2): 239-44, 2004.
Article in English | MEDLINE | ID: mdl-15344797

ABSTRACT

Various membranes, which have different materials and nominal molecular weight cut-offs (MWCO), were compared in terms of rejection of ibuprofen and removal of effluent organic matter (EfOM) from membrane bioreactor (MBR), because pharmaceutical compounds contain a potential risk and EfOM is the precursor of carcinogenic disinfection by-products when reusing for drinking water source. To provide equivalent comparison with respect to hydrodynamic condition, mass transfer parameter, J0/k ratio, was used. A tight-UF membrane with a molecular weight cut off of 8,000 daltons exhibited 25 approximately 95% removal efficiencies of ibuprofen with a molecular weight of 206 with and without presence of EfOM(MBR). EfOM(MBR) caused the reduction of ibuprofen removal efficiency for UF membrane. Rejection of EfOM(MBR) by UF and NF membranes ranged 29 approximately 47% and 69 approximately 86%, respectively. UF membrane could successfully remove ibuprofen at lower J0/k ratio range (< or = 1) in organic free water but could not efficiently reject ibuprofen with a relatively hydrophilic EfOM(MBR) (SUVA < or = 3).


Subject(s)
Conservation of Natural Resources , Nanotechnology , Pharmaceutical Preparations/isolation & purification , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , Filtration , Membranes, Artificial , Molecular Weight , Waste Disposal, Fluid
15.
J Biol Chem ; 276(52): 49183-7, 2001 Dec 28.
Article in English | MEDLINE | ID: mdl-11598115

ABSTRACT

Heterotetrameric adaptor complexes and SNAREs play key roles in the specificity of membrane budding and fusion. Here we test the hypothesis that vesicle budding and membrane fusion are coupled by the interaction of these molecules. We investigate the role of the di-leucine motif of vesicle-associated membrane protein 4 (VAMP4) in adaptor binding and localization of VAMP4. Mutation of the di-leucine motif inhibits AP-1 binding in vitro and affects the steady state distribution of VAMP4 in vivo.


Subject(s)
Amino Acid Motifs , Clathrin-Coated Vesicles/metabolism , Glycoproteins , Membrane Proteins/metabolism , Transcription Factor AP-1/metabolism , Vesicular Transport Proteins , Animals , Brain Chemistry , Cell Line , Clathrin-Coated Vesicles/chemistry , Membrane Glycoproteins/metabolism , Membrane Proteins/chemistry , Membrane Proteins/genetics , Microsomes, Liver/chemistry , Microsomes, Liver/metabolism , Protein Binding , R-SNARE Proteins , Rats , Recombinant Fusion Proteins/metabolism , SNARE Proteins
16.
J Urol ; 165(6 Pt 1): 1897-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11371876

ABSTRACT

PURPOSE: Several studies in animals and humans have demonstrated that ileal resection has an increased association with gallstone formation. However, little reported data exist in regard to continent diversion, and the incidence and relative risk of gallstones. We describe a single institution, single surgeon (J. W. W.) experience with 125 modified Indiana pouch continent urinary diversions constructed in a 14-year period and the subsequent association with gallstones. MATERIALS AND METHODS: We retrospectively reviewed the charts of 129 patients who underwent continent urinary diversion from March 1985 to August 1998 at our institution to assess postoperative cholelithiasis. Complete information was available in 125 of the 129 charts. All patients were followed yearly with ultrasound combined with telephone followup to ensure complete data. RESULTS: Cholelithiasis was present in 32 of the 125 reviewable patients (25.6%), including 53 men and 72 women. Three men and 8 women who underwent previous or concomitant cholecystectomy for gallstones were excluded from study. Therefore, cholelithiasis developed in 21 of the 114 remaining patients (18.4%), including 5 males (4.3%) and 16 females (14%). Five of the 50 remaining men (10%) and 16 of the remaining 64 women (25%) had gallstones. Mean age at surgery was 43.5 years (range 19 to 73) and mean age at gallstone development was 45 years (range 23 to 77). Mean time from surgery to gallstone development was 3 years (range 1.1 to 5.5). Mean followup via chart review was 41 months (range 1 to 127). The recent telephone followup reached 83 of the 125 patients (66.4%). However, 20 of the 42 patients who were not reached by the telephone followup had had clinic appointments at our institution in the last 11/2 years for an overall 82.4% followup rate (103 of 125 patients). Of the 21 patients with cholelithiasis 17 were identified by chart review and 4 were identified by telephone followup. CONCLUSIONS: The recent literature indicates a 10% and 20% incidence of gallstones in American men and women, respectively. Previous reports support a potential increase in cholelithiasis in patients who undergo ileal resection. Our data indicate no increased risk of gallstones in patients who undergo modified Indiana pouch urinary diversion. However, longer followup is required to verify these findings.


Subject(s)
Cholelithiasis/etiology , Urinary Diversion/adverse effects , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Urinary Diversion/methods
17.
Eur Respir J ; 18(5): 801-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11757631

ABSTRACT

Many studies into basic biological characteristics of inflammation and tissue injury have implicated pro-inflammatory cytokine-mediated tissue injury in the pathogenesis of inflammatory lung diseases. Because transcription of most proinflammatory cytokines is dependent on the activation of nuclear factor (NF)-kappaB, NF-kappaB could be a good potential target to suppress the cytokine cascade. Cytokine-induced activation of NF-kappaB requires phosphorylation and subsequent degradation of IkappaBa. Therefore, the blocking NF-kappaB activation by IkappaBalpha could inhibit the pro-inflammatory cytokine-induced tissue injury. To evaluate whether blocking of NF-kappaB activation shows an anti-inflammatory effect, this study investigated the effect of adenovirus-mediated overexpression of IkappaBalpha super-repressor (IkappaBalpha-SR) on the pro-inflammatory cytokine expression in respiratory epithelial cells. The transduction efficiency of adenovirus was >90% in both A549 and NCI-H157 cells. Ad5IkappaBalpha-SR-transduced cells expressed high levels of IkappaBalpha-SR, which was resistant to tumour necrosis factor (TNF)-alpha-induced degradation. Adenovirus-mediated overexpression of IkappaBalpha-SR blocked cytokine-induced nuclear translocation of p65 and NF-kappaB deoxyribonucleic acid binding activity without affecting total cellular expression level of NF-kappaB. Ad5IkappaBalpha-SR transduction suppressed cytokine-induced interleukin-8 and TNF-alpha expressions at both ribonucleic acid and protein levels. These results suggest that blocking the nuclear factor-kappaB pathway by adenovirus-mediated overexpression of IkappaBalpha-super-repressor shows an effective anti-inflammatory effect in respiratory epithelial cells.


Subject(s)
Cytokines/metabolism , I-kappa B Proteins/metabolism , NF-kappa B/metabolism , Respiratory System/metabolism , Adenoviridae/genetics , Blotting, Northern , Blotting, Western , Cells, Cultured , Electrophoresis, Polyacrylamide Gel , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Epithelial Cells/metabolism , Fluorescent Antibody Technique , Genetic Vectors , Humans , Interleukin-8/analysis , Respiratory System/cytology , Tumor Necrosis Factor-alpha/metabolism
18.
Thorax ; 55(2): 121-5, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10639528

ABSTRACT

BACKGROUND: Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD. METHODS: The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers. RESULTS: No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group. CONCLUSIONS: Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.


Subject(s)
Genetic Predisposition to Disease/genetics , Lung Diseases, Obstructive/genetics , Adult , Aged , Aged, 80 and over , Epoxide Hydrolases/blood , Epoxide Hydrolases/genetics , Female , Forced Expiratory Volume/physiology , Glutathione Transferase/blood , Glutathione Transferase/genetics , Humans , Korea/ethnology , Lung Diseases, Obstructive/blood , Lung Diseases, Obstructive/ethnology , Male , Microsomes , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Smoking/ethnology , Smoking/genetics , Vital Capacity/physiology
19.
Respirology ; 4(4): 401-4, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10612575

ABSTRACT

Cases of endobronchial vascular lesions observed with bronchoscope are presented. These lesions tend to be diagnosed erroneously as true endobronchial tumours so that biopsies are tried frequently. Consequently, a catastrophic accident of massive bleeding can complicate the condition if endobronchial vascular lesions are injured during bronchoscopic biopsy or brushing. We present three types of endobronchial vascular lesion: tubular bulging type, mass-like type and haemangioma type. Because bronchoscopic findings of submucosal tubular structure and visible pulsation are highly suggestive of endobronchial vascular lesion, there must be extreme caution to prevent fatal bleeding.


Subject(s)
Bronchial Diseases/complications , Bronchial Diseases/diagnosis , Hemoptysis/etiology , Vascular Diseases/complications , Vascular Diseases/diagnosis , Adult , Angiography , Biopsy, Needle/adverse effects , Bronchoscopy , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Risk Assessment
20.
Yonsei Med J ; 40(4): 331-8, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10487135

ABSTRACT

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.


Subject(s)
Biological Factors/physiology , Femoral Artery/physiology , Potassium Channels/physiology , Acetylcholine/pharmacology , Animals , Female , Femoral Artery/drug effects , In Vitro Techniques , Male , Rabbits , Vasodilation/physiology , Vasodilator Agents/pharmacology
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