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1.
Int J Tuberc Lung Dis ; 27(6): 465-470, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37231609

ABSTRACT

BACKGROUND: The severity of non-tuberculous mycobacterial pulmonary disease (NTM-PD) can be classified based on an assessment of the patient´s body mass index, age, presence of cavity, erythrocyte sediment rate and sex (BACES). In this study, changes in lung function according to disease severity were analysed.METHODS: Patients with NTM-PD who underwent at least two lung function tests between 1 January 2011 and 31 December 2021, were classified according to their BACES score into mild (0-1), moderate (2-3) and severe (4-5) groups, and changes in lung function were assessed using BACES scores.RESULTS: A total of 354 patients were divided into three groups: mild (n = 108), moderate (n = 216) and severe (n = 30). As disease severity increased, the decrease in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) was greater: respectively 26.4 mL/year, 31.3 mL/year and 35.7 mL/year in case of FEV1 (P for trend = 0.002); 18.9 mL/year, 25.5 mL/year and 48.9 mL/year in case of FVC (P for trend = 0.002); and 0.7%/year, 1.3%/year and 2.5%/year for DLCO (P for trend = 0.023) in the mild, moderate and severe groups.CONCLUSION: The decrease in lung function in NTM-PD was correlated with disease severity.


Subject(s)
Lung Diseases , Lung , Humans , Nontuberculous Mycobacteria , Forced Expiratory Volume , Vital Capacity , Patient Acuity , Pulmonary Diffusing Capacity
2.
Int J Tuberc Lung Dis ; 23(7): 850-857, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31439118

ABSTRACT

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.


Subject(s)
Antitubercular Agents/therapeutic use , Disease Notification , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antitubercular Agents/pharmacology , Child , Child, Preschool , Demography , Female , Humans , Infant , Infant, Newborn , Internet , Male , Mass Screening , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Sex Factors , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/prevention & control , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/prevention & control , Young Adult
3.
Int J Tuberc Lung Dis ; 23(2): 174-180, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30808449

ABSTRACT

SETTING: A referral centre in South Korea. OBJECTIVE: To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. DESIGN: MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. RESULTS: Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). CONCLUSION: MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.


Subject(s)
Antitubercular Agents/administration & dosage , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/epidemiology , Adult , Antitubercular Agents/pharmacology , Cohort Studies , Drug Resistance, Multiple, Bacterial , Female , Hospitals, University , Humans , Male , Middle Aged , Republic of Korea/epidemiology , Retrospective Studies , Sputum/microbiology , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology
4.
Int J Tuberc Lung Dis ; 19(5): 525-30, 2015 May.
Article in English | MEDLINE | ID: mdl-25868019

ABSTRACT

SETTING: After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN: Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS: Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION: Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Antitubercular Agents/pharmacology , Cohort Studies , Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/drug therapy , Female , Follow-Up Studies , Hospitals, University , Humans , Logistic Models , Male , Microbial Sensitivity Tests , Middle Aged , Multivariate Analysis , Recurrence , Republic of Korea , Retrospective Studies , Risk Assessment , Severity of Illness Index , Statistics, Nonparametric , Time Factors , Treatment Outcome
5.
Int J Tuberc Lung Dis ; 19(1): 81-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25519795

ABSTRACT

SETTING: The Xpert(®) MTB/RIF assay has been endorsed by the World Health Organization for the detection of pulmonary and extra-pulmonary tuberculosis (EPTB). OBJECTIVE: To determine the accuracy of the Xpert assay in diagnosing EPTB in South Korea, a country with an intermediate TB burden. DESIGN: We retrospectively reviewed the medical records of 1429 patients in whom the Xpert assay using EPTB specimens was requested between 1 January 2011 and 31 October 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of EPTB and detection of rifampicin (RMP) resistance were calculated. RESULTS: Using culture as gold standard, the sensitivity, specificity, PPV and NPV of the assay were respectively 67.7%, 98.1%, 60% and 98.6%. Using a composite reference standard, the sensitivity, specificity, PPV and NPV were respectively 49.3%, 100%, 100% and 95.1%. The sensitivity, specificity, PPV and NPV for the detection of RMP resistance among specimens with positive results for Mycobacterium tuberculosis were respectively 80%, 100%, 100% and 97.7%. CONCLUSION: The Xpert assay showed acceptable sensitivity in certain groups and excellent specificity in diagnosing EPTB and detecting RMP resistance in an intermediate TB burden country.


Subject(s)
Antibiotics, Antitubercular/pharmacology , Drug Resistance, Multiple, Bacterial , Rifampin/pharmacology , Tuberculosis, Pulmonary/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Predictive Value of Tests , Republic of Korea , Retrospective Studies , Sensitivity and Specificity , Specimen Handling , Young Adult
6.
J Med Syst ; 35(2): 265-75, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20703564

ABSTRACT

This paper deals with strategic enterprise resource planning (ERP) in a health-care system using a multicriteria decision-making (MCDM) model. The model is developed and analyzed on the basis of the data obtained from a leading patient-oriented provider of health-care services in Korea. Goal criteria and priorities are identified and established via the analytic hierarchy process (AHP). Goal programming (GP) is utilized to derive satisfying solutions for designing, evaluating, and implementing an ERP. The model results are evaluated and sensitivity analyses are conducted in an effort to enhance the model applicability. The case study provides management with valuable insights for planning and controlling health-care activities and services.


Subject(s)
Decision Making, Computer-Assisted , Decision Making, Organizational , Delivery of Health Care/methods , Delivery of Health Care/organization & administration , Health Care Rationing , Health Planning , Humans , Korea , Models, Organizational
7.
Water Sci Technol ; 55(1-2): 251-9, 2007.
Article in English | MEDLINE | ID: mdl-17305147

ABSTRACT

To treat cutting oil wastewater produced in metal surface treatment industry, Ultrasonication (US)-Fenton process, which is one of the advanced oxidation processes, was used. The optimum conditions to treat non-biodegradable pollutants using the US-Fenton process were that the application rates of H2O2 and FeSO4 were 10% and 3 g/L, respectively, the value of pH was 3, and the ultrasonication time was 30 min. It identified non-degradable pollutants such as ethylene diamine tetraacetic acid (EDTA) and Triethanolamine (TEA) in the cutting oil wastewater. TLC analysis of two compounds of treated water by the coagulation process was similar to that of raw water. However, TLC analysis of two compounds of US-Fenton process was different from that of raw water, meaning that US-Fenton process decomposed the EDTA and TEA. To study the possibility of application with the US-Fenton process to pilot plant, the pollutants treatment efficiency of three different methods, such as US-Fenton process, activated sludge process and coagulation process, in continuous experiments were compared. The removal rate of pollutants by the US-Fenton process according to the effluent time was higher than any other processes. The removal rates of COD, SS, T-N and T-P by US-Fenton process were 98, 93, 75 and 95%, respectively.


Subject(s)
Hydrogen Peroxide/chemistry , Industrial Waste , Iron/chemistry , Ultrasonics , Waste Disposal, Fluid , Water Pollutants, Chemical/chemistry , Water Purification/methods , Biodegradation, Environmental , Environmental Restoration and Remediation , Ferrous Compounds/chemistry , Ferrous Compounds/metabolism , Hydrogen Peroxide/metabolism , Hydrogen-Ion Concentration , Iron/metabolism , Metals/chemistry , Oils , Oxidation-Reduction , Time Factors , Water Pollutants, Chemical/metabolism
8.
J Biosci ; 28(1): 77-81, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12682428

ABSTRACT

The present study was carried out to observe the cytotoxicity of yellow sand in comparison with silica and titanium dioxide in a rat alveolar type II cell line (RLE-6TN). Yellow sand (China Loess) was obtained from the loess layer in the Gunsu Province of China. The mean particle diameter of yellow sand was about 0.003 +/- 0.001 mm. Major elements of yellow sand were Si(27.7 +/- 0.6%), Al(6.01 +/- 0.17%), and Ca(5.83 +/- 0.23%) in that order. Silica and yellow sand significantly decreased cell viability and increased [Ca2+]i. All three particles increased the generation of H2O2. TiO2 did not change Fenton activity, while silica induced a slight increase of Fenton activity. In contrast, yellow sand induced a significant increase of Fenton activity. Silica, yellow sand and TiO2 induced significant nitrite formations in RLE-6TN cells. Silica showed the highest increase in nitrite formation, while yellow sand induced the least formation of nitrite. Silica and yellow sand increased the release of TNF-a. Based on these results, we suggest that yellow sand can induce cytotoxicity in RLE-6TN cells and reactive oxygen species, Fenton activity and reactive nitrogen species might be involved in this toxicity.


Subject(s)
Epithelial Cells/metabolism , Lung/cytology , Lung/metabolism , Macrophages, Alveolar/metabolism , Silicon Dioxide/toxicity , Aluminum/chemistry , Animals , Calcium/analysis , Calcium/chemistry , Cell Line , Cell Survival/drug effects , Culture Media, Conditioned/chemistry , Epithelial Cells/drug effects , Hydrogen Peroxide/analysis , Hydrogen Peroxide/chemical synthesis , Macrophages, Alveolar/drug effects , Nitrites/analysis , Particle Size , Rats , Silicon/chemistry , Silicon Dioxide/chemistry , Titanium/adverse effects , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism
9.
J Med Syst ; 26(5): 427-38, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12182207

ABSTRACT

This study presents an application of linear programming discriminant analysis (LPDA) to classify and to predict the symptomatic status of HIV/AIDS patients. We applied LPDA as well as several traditional discriminant analysis methods to the AIDS Cost and Services Utilization Survey data set in order to demonstrate the use of LPDA to classify the symptomatic status of HIV/AIDS patients. The potential benefit of LPDA in terms of the classification accuracy was also analyzed.


Subject(s)
Discriminant Analysis , HIV Infections/physiopathology , Programming, Linear , Diagnosis, Computer-Assisted , Female , HIV Infections/classification , Humans , Male , Severity of Illness Index
10.
IEEE Trans Neural Netw ; 13(1): 143-59, 2002.
Article in English | MEDLINE | ID: mdl-18244416

ABSTRACT

Feature selection plays an important role in classifying systems such as neural networks (NNs). We use a set of attributes which are relevant, irrelevant or redundant and from the viewpoint of managing a dataset which can be huge, reducing the number of attributes by selecting only the relevant ones is desirable. In doing so, higher performances with lower computational effort is expected. In this paper, we propose two feature selection algorithms. The limitation of mutual information feature selector (MIFS) is analyzed and a method to overcome this limitation is studied. One of the proposed algorithms makes more considered use of mutual information between input attributes and output classes than the MIFS. What is demonstrated is that the proposed method can provide the performance of the ideal greedy selection algorithm when information is distributed uniformly. The computational load for this algorithm is nearly the same as that of MIFS. In addition, another feature selection algorithm using the Taguchi method is proposed. This is advanced as a solution to the question as to how to identify good features with as few experiments as possible. The proposed algorithms are applied to several classification problems and compared with MIFS. These two algorithms can be combined to complement each other's limitations. The combined algorithm performed well in several experiments and should prove to be a useful method in selecting features for classification problems.

11.
Crit Rev Food Sci Nutr ; 41(6): 465-79, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11592685

ABSTRACT

Attempts are being made at the international level within the framework of the Codex Alimentarius to establish guidelines for health claims. An important issue that has to be addressed is the process of substantiating any health claim. Previous papers have addressed aspects relating to the development and regulatory control of functional foods and certain issues relating to claims. This paper addresses several issues concerning the substantiation of health claims through the examination of the regulations and guidelines in several countries. They include (1) importance of human- and product-based studies; (2) concept of scientific consensus; (3) authorization of claim wording; (4) availability of scientific evidence to public (confidentiality). The paper finally proposes a system based on generic and innovative health claims.


Subject(s)
Food, Organic/standards , Legislation, Food/standards , Animals , Evidence-Based Medicine , Global Health , Humans , International Cooperation , Nutrition Policy
13.
Am J Ment Retard ; 106(3): 231-52, 2001 May.
Article in English | MEDLINE | ID: mdl-11408960

ABSTRACT

In 1994 and 1995, the National Health Interview Survey included a Disability Supplement (NHIS-D) to collect extensive information about disabilities among individuals sampled as part of annual census-based household interview surveys. Here we describe the development and application of operational definitions of mental retardation and developmental disabilities to items in the NHIS-D to estimate prevalence. In our analyses, we estimate the prevalence of mental retardation in the noninstitutionalized population of the United States to be 7.8 people per thousand (.78%); of developmental disabilities, 11.3 people per thousand (1.13%); and the combined prevalence of mental retardation and/or developmental disabilities to be 14.9 per thousand (1.49%). Differences in prevalence estimates for mental retardation and developmental disabilities and among people of various ages are explored.


Subject(s)
Developmental Disabilities/epidemiology , Disability Evaluation , Intellectual Disability/epidemiology , Surveys and Questionnaires , Adolescent , Child , Child, Preschool , Cohort Studies , Developmental Disabilities/diagnosis , Humans , Intellectual Disability/diagnosis , Prevalence , Prospective Studies
14.
Phys Rev Lett ; 86(14): 2950-4, 2001 Apr 02.
Article in English | MEDLINE | ID: mdl-11290080

ABSTRACT

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

15.
Phys Rev Lett ; 86(7): 1167-70, 2001 Feb 12.
Article in English | MEDLINE | ID: mdl-11178035

ABSTRACT

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

16.
Phys Rev Lett ; 86(1): 30-34, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11136086

ABSTRACT

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

17.
Phys Rev Lett ; 85(15): 3095-9, 2000 Oct 09.
Article in English | MEDLINE | ID: mdl-11019275

ABSTRACT

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.

18.
Phys Rev Lett ; 84(19): 4292-5, 2000 May 08.
Article in English | MEDLINE | ID: mdl-10990669

ABSTRACT

We report results of a search for the rare radiative decay &Bmacr;(0)-->D(*0)gamma. Using 9.66x10(6) B&Bmacr; meson pairs collected with the CLEO detector at the Cornell Electron Storage Ring, we set an upper limit on the branching ratio for this decay of 5.0x10(-5) at 90% C.L. This provides evidence that the anomalous enhancement is absent in W-exchange processes and that weak radiative B decays are dominated by the short-distance b-->sgamma mechanism in the standard model.

19.
Invest Ophthalmol Vis Sci ; 41(10): 3158-64, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10967078

ABSTRACT

PURPOSE: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for retinal neovascularization in ischemic retinopathies such as diabetic retinopathy. This study sought to determine if VEGF is a stimulatory factor in a murine model of choroidal neovascularization (CNV). METHODS: Mice with laser-induced ruptures in Bruch's membrane were treated with vehicle alone; a drug that inhibits both VEGF and platelet-derived growth factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor kinase; or genistein, a nonspecific kinase inhibitor. After two weeks, CNV was quantified and compared. RESULTS: Blockade of phosphorylation by VEGF and PDGF receptors caused dramatic, almost complete inhibition of CNV. Genistein also had an inhibitory effect, but less so than the VEGF/PDGF receptor blocker. Blockade of phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on CNV. CONCLUSIONS: These data and our previous study, which demonstrated that a kinase inhibitor that blocks VEGF and PDGF receptors and several isoforms of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF signaling plays a critical role in the development of CNV in this model. If safety is established, the effect of inhibiting VEGF receptor kinase activity should be investigated in patients with CNV.


Subject(s)
Choroidal Neovascularization/metabolism , Endothelial Growth Factors/physiology , Lymphokines/physiology , Animals , Choroidal Neovascularization/pathology , Choroidal Neovascularization/prevention & control , Enzyme Inhibitors/pharmacology , Genistein/pharmacology , Male , Mice , Mice, Inbred C57BL , Phosphorylation , Phthalazines/pharmacology , Platelet-Derived Growth Factor/physiology , Protein Kinase C/antagonists & inhibitors , Pyridines/pharmacology , Pyrimidines/pharmacology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptors, Growth Factor/antagonists & inhibitors , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , Receptors, Vascular Endothelial Growth Factor , Signal Transduction/physiology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
20.
J Cell Physiol ; 185(1): 135-42, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10942527

ABSTRACT

Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial cells and exogenous administration of FGF2 stimulates angiogenesis. However, increased expression of FGF2 in the retina does not cause angiogenesis. One possible explanation is that FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another angiogenic factor. Alternatively, there may be control mechanisms that sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express FGF2 in the retina with mice that express vascular endothelial growth factor (VEGF) in the retina. Surprisingly, despite comparable levels of VEGF expression, mice that expressed both FGF2 and VEGF had significantly less neovascularization than mice that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice, choroidal neovascularization developed in areas of low-intensity laser. Both wild type and transgenic mice developed choroidal neovascularization in areas of intense laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased retinal expression of FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.


Subject(s)
Endothelial Growth Factors/physiology , Fibroblast Growth Factor 2/physiology , Gene Expression Regulation/physiology , Lymphokines/physiology , Retinal Neovascularization , Animals , Mice , Mice, Transgenic , Retina/pathology , Retina/physiology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
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