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1.
Antibiotics (Basel) ; 11(11)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36358242

ABSTRACT

Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W2L4K4 (WALK244.01~WALK244.10) and W2L4K3 (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 µg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.

2.
BMC Public Health ; 21(1): 1794, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34610796

ABSTRACT

BACKGROUND: This study investigated the associations between exposure to ambient air pollutants and the incidence of osteoporosis using the Korean National Insurance Service-National Sample Cohort. METHODS: This nationwide, population-based, retrospective cohort study included 237,149 adults aged ≥40 years that did not have a diagnosis of osteoporosis at baseline between January 1, 2003, and December 31, 2015. Osteoporosis was defined as claim codes and prescriptions of bisphosphonates or selective estrogen receptor modulators at least twice annually. After matching values for PM10, NO2, CO, and SO2 during the 2002-2015 time period and PM2.5 in 2015 with residential areas, the incidence of osteoporosis was analyzed using a Cox proportional hazards regression model according to the quartile of average yearly concentrations of pollutants. RESULTS: Overall 22.2% of the study subjects, 52,601 (male: 5.6%, female: 37.6%) adults in total, were newly diagnosed with osteoporosis and treated. Exposure to PM10 was positively associated with incidence of osteoporosis (Q4: 1798 per 100,000 person-years vs. Q1: 1655 per 100,000 person-years). The adjusted hazard ratio (HR) with 95% confidence interval (CI) of Q4 in PM10 was 1.034 (1.009-1.062). The effect of PM10 on osteoporosis incidence was distinct in females (adjusted sub-HR: 1.065, 95% CI: 1.003-1.129), subjects aged < 65 years (adjusted sub-HR: 1.040, 95% CI: 1.010-1.072), and for residents in areas with low urbanization (adjusted sub-HR: 1.052, 95% CI: 1.019-1.087). However, there was no increase in osteoporosis based on exposure to NO2, CO, SO2, or PM2.5. CONCLUSIONS: Long-term exposure to PM10 was associated with newly diagnosed osteoporosis in Korean adults aged ≥40 years. This finding can aid in policy-making that is directed to control air pollution as a risk factor for bone health.


Subject(s)
Air Pollutants , Air Pollution , Osteoporosis , Adult , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Air Pollution/statistics & numerical data , Cohort Studies , Environmental Exposure/analysis , Environmental Exposure/statistics & numerical data , Female , Humans , Incidence , Male , Osteoporosis/chemically induced , Osteoporosis/epidemiology , Particulate Matter/analysis , Particulate Matter/toxicity , Republic of Korea/epidemiology , Retrospective Studies
3.
Korean J Fam Med ; 39(4): 233-238, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29976000

ABSTRACT

BACKGROUND: Previous studies have examined the association between alcohol consumption and metabolic syndrome (MetS) in adults, but studies in the elderly are lacking. We examined the relationship between high-risk alcohol consumption and MetS in elderly Korean men using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire from the 2010-2012 Korean National Health and Nutrition Examination Survey. METHODS: Among 25,534 subjects, 2,807 were men >60 years of age; after exclusions, we included 2,088 men in the final analysis. We categorized the study participants into three groups according to AUDIT score: low risk (0-7), intermediate risk (8-14), and high risk (≥15 points). RESULTS: Among the study population, 17.0% of the men were high-risk drinkers, who had the highest mean waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose (FPG), and triglyceride (TG) levels. The overall prevalence of MetS was 41.9% in the elderly men, and it was significantly higher in the group with high (48.3%) versus low (31.9%) AUDIT scores. The prevalence of MetS components (elevated BP, high FPG, high TG, and low high-density lipoprotein cholesterol) was associated with a high AUDIT score. The odds ratios (95% confidence interval) of the high-risk group for MetS, elevated BP, and high TG were 1.40 (1.03-1.89), 1.82 (1.28- 2.60), and 1.77 (1.30-2.41) after adjustment for confounding variables. CONCLUSION: AUDIT score was correlated with most MetS components in elderly Korean men.

4.
Korean J Fam Med ; 37(6): 329-333, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27900070

ABSTRACT

BACKGROUND: Prescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use. METHODS: Data obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis. RESULTS: Of all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM. CONCLUSION: At a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.

5.
Korean J Fam Med ; 37(6): 356-358, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27900075

ABSTRACT

Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24-48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered.

6.
Korean J Fam Med ; 37(2): 85-90, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27073606

ABSTRACT

BACKGROUND: Smoking is a well-known risk factor of cancer, chronic disease, and cerebrovascular disease. Hospital admission is a good time to quit smoking but patients have little opportunity to take part in an intensive smoking cessation intervention. The purpose of this study was to identify the factors of successful smoking cessation among stroke patients who undergo an intensive cessation intervention during the hospitalization period. METHODS: Thirty-nine male smokers who were admitted with stroke were enrolled in the study. They participated in a smoking cessation intervention during hospitalization. Smoking status was followed up by telephone 3 months later. Nicotine dependence, sociodemographic factors, and other clinical characteristics were assessed. RESULTS: After 3 months post-intervention, the number of patients who stopped smoking was 27 (69.2%). In addition, there was no significant difference in nicotine dependence, sociodemographic factors, and clinical characteristics. Only the stages of readiness for smoking cessation were a significant predictor (odds ratio, 18.86; 95% confidence interval, 1.59-223.22). CONCLUSION: This study shows that a patient's willingness to quit is the most significant predictor of stopping smoking after Inpatient cessation Intervention for stroke Patients.

7.
Korean J Fam Med ; 37(1): 25-30, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26885319

ABSTRACT

BACKGROUND: Overactive bladder syndrome is characterized by urinary urgency, usually accompanied by Frequent urination and nocturia, with or without urgent urinary incontinence. There must be the absence of causative infection or pathological conditions. Overactive bladder syndrome is related to mental disorders, particularly depression and anxiety. However, obsessive-compulsive symptoms are investigated much less frequently. The purpose of the present study was thus to assess obsessive-compulsive symptoms in overactive bladder syndrome patients. METHODS: Fifty-seven women patients with overactive bladder syndrome and fifty-seven women without it (age matched control group) were prospectively enrolled. They completed the overactive bladder syndrome-validated 8-question screener and the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire at the same time they visited the clinic. Patients were compared with controls on the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire and its checking, tidiness, doubting, and fear of contamination components. RESULTS: Patients showed more obsessive traits than controls on the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire total score (P=0.006) and on the checking subscale (P=0.001). Odds ratio for the overactive bladder syndrome group's obsessive-compulsive symptoms traits (score≥14) was 5.47 (P=0.001). The Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire total score was associated with the overactive bladder syndrome-validated 8-question screener score in patients (P=0.03). CONCLUSION: Obsessive-compulsive symptoms may constitute an important aspect of the psychiatric profile of overactive bladder syndrome patients. The severity of obsessive-compulsive symptoms seems to be related to the degree of the overactive bladder syndrome severity. Clinicians may consider screening women with overactive bladder syndrome for obsessive-compulsive symptoms.

8.
Ann Surg Treat Res ; 89(6): 287-94, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26665122

ABSTRACT

PURPOSE: The increasing incidence of thyroid cancer worldwide has drawn attention to the needs for assessing and managing health-related quality of life (HRQoL) of thyroid cancer survivors. We conducted this study to validate the Korean version of the thyroid cancer-specific quality of life (THYCA-QoL) questionnaire. METHODS: Data obtained from 227 thyroid cancer survivors were analyzed using standard validity and reliability analysis techniques. Reliability was assessed by measuring internal consistency via Cronbach α coefficient, and validity was assessed by determining the Pearson correlation coefficient between the THYCA-QoL questionnaire and the following relevant assessment tools: the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30), the Korean version of Brief Fatigue Inventory (BFI-K), the Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), Goldberg Short Screening Scale for Anxiety and Depression, and a nine-item Patient Health Questionnaire (PHQ-9). A multitrait scaling analysis was performed to assess each item's convergent and discriminant validity. RESULTS: The reliability of the THYCA-QoL questionnaire was confirmed by Cronbach α coefficients for multiple-item scales which ranged from 0.54 (sensory) to 0.82 (psychological). Except for a single item (sexual interest), the questionnaire's validity was established by significant correlation observed between scales in the THYCA-QoL questionnaire and scales used in other assessment tools. A multitrait scaling analysis confirmed that all scales met the recommended psychometric standards. CONCLUSION: The Korean version of the THYCA-QoL questionnaire is a reliable and valid assessment tool that can be used in combination with the EORTC QLQ-C30 to assess the HRQoL of thyroid cancer survivors in Korea.

9.
Korean J Fam Med ; 34(3): 199-205, 2013 May.
Article in English | MEDLINE | ID: mdl-23730487

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and many risk factors, and both are linked to an increased risk of cardiovascular diseases. The aim of this study was to assess the association between NAFLD and CKD according to the presence of hypertension and diabetes mellitus in Koreans aged 50 years or older. METHODS: A cross-sectional study of 1,706 subjects who received their routine health examination was conducted between May 2008 and April 2010 at Konkuk University medical center. Biochemical tests for liver and abdominal ultrasonography were performed. CKD was defined as either proteinuria or glomerular filtration rate ≤60 mL/min per 1.73 m(2). RESULTS: Among the 1,706 subjects, There were 545 (31.9%) with non-alcoholic fatty liver disease and 424 (24.9%) with chronic kidney disease. In univariate logistic regression analysis, NAFLD was significantly associated with CKD (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.34 to 2.12). In multivariate logistic regression analysis adjusted for age, sex, current smoking, abdominal obesity, aspartate aminotransferases, alanine aminotransferases, γ-glutamyltransferase, hypertension, diabetes mellitus, hypertriglyceridemia, and low high-density lipoprotein cholesterol, NAFLD was associated with CKD (adjusted OR, 1.68; 95% CI, 1.27 to 2.24). This relationship remained significant after classification according to the presence of hypertension or diabetes mellitus. CONCLUSION: NAFLD diagnosed by ultrasonography was significantly associated with CKD in Koreans aged 50 years or older.

10.
Korean J Fam Med ; 33(4): 219-28, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22916324

ABSTRACT

BACKGROUND: Although upper gastrointestinal (UGI) endoscopy is highly sensitive for the detection of esophago-gastroduodenal lesions, pain and discomfort during the procedure cause examinees to experience stress and anxiety. Moreover, there have been only a few studies on relief of pain and discomfort during UGI endoscopy through preparatory interventions. Therefore, the aim of this study was to investigate the relationship between a preparatory education program and the discomfort and retching experienced by examinees during endoscopy. METHODS: A total of 306 examinees who visited a health promotion center and underwent non-sedated endoscopy from May 13 to July 3, 2009 were included in this study. After they were assigned to experimental (n = 154) and control groups (n = 152), their discomfort and retching were measured with a visual analogue scale. The preparatory education program consisted of cognitive intervention, behavioral intervention and information. RESULTS: The preparatory education program relieved discomfort during endoscopy in male subjects, in subjects aged 60 and over, or in subjects with previous endoscopic experience with statistical significance (P < 0.05). It also relieved retching during endoscopy in subjects aged 60 and over with statistical significance (P = 0.023). Multiple logistic regression analysis showed that the preparatory education program significantly relieved the discomfort of examinees during endoscopy (P = 0.028). CONCLUSION: We found that the preparatory education program used in this study could significantly relieve the discomfort caused by endoscopy, particularly in subjects aged 60 and over, or in male subjects with a high incidence of stomach cancer in Korea.

11.
Korean J Fam Med ; 33(1): 17-24, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22745884

ABSTRACT

BACKGROUND: For an early detection and prevention of dementia, there are growing concerns about the high-risk group for dementia and mild cognitive impairment. With an increase of obesity and its complications, obesity has become a major public health problem. Therefore, the aim of this study was to investigate the relationship between obesity and the high probability of dementia. METHODS: This study was done with subjects aged 60 to 89 years who visited a health promotion center, from April 1, 2008 to April 30, 2008. A total of 293 subjects (164 males and 129 females) were included in the evaluation of cognitive function using the Korean version of the Seven Minutes Screen test. Logistic regression models were used to analyze the association between obesity and the high-risk group for dementia. RESULTS: Among a total of 293 subjects, 71 subjects (29 males and 42 females) had a high probability of dementia. When compared to normal body mass index (BMI) group, overweight and obesity groups had about a 2.2-fold and 2.4-fold higher probability of dementia (95% confidence interval [CI], 0.97 to 4.99 and 95% CI, 1.07 to 5.46, respectively). When compared to non-obese and non-abdominal obesity group, non-obese and abdominal obesity group and obese and abdominal obesity group had about a 1.5-fold and 2.0-fold higher probability of dementia (95% CI, 0.59 to 3.95 and 95% CI, 1.09 to 3.84, respectively). CONCLUSION: This study shows that as the BMI increased, subjects had a higher probability of dementia; additionally, it suggests that abdominal obesity could be related to a higher probability of dementia.

12.
Korean J Fam Med ; 33(1): 25-33, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22745885

ABSTRACT

BACKGROUND: The telemedicine services in Korea are expected to rapidly expand its use to the general population due to the development of digital networking, and its recent revision of related law and regulations. The purpose of this study was to investigate the knowledge and attitude of telemedicine in primary care patients. METHODS: We enrolled a total 243 participants, visited Family Medicine clinics and health promotion centers of university hospital in Seoul metrocity and Chungju city from April 1, 2010 to May 31, 2010. Data was collected by questionnaire, including demographic variables, knowledge and attitude of telemedicine. RESULTS: Among the total of 243 participants, 117 (49.8%) respondents were aware of telemedicine, and 178 (73.3%) respondents preferred telemedicine. The awareness showed differences according to the residence (P = 0.007), education (P = 0.03), and occupation (P = 0.02) of the respondents. The patient preference showed the differences at 50 years of age (P = 0.01) and in income of the participants (P = 0.005). CONCLUSION: Awareness of telemedicine in primary care patients was low. As for the patients more than 50 years of age who will be having difficulty manipulating the instruments, more education is crucial. Establishment of appropriate plans to increase patient preference is needed, especially for patients with low-incomes.

13.
J Med Food ; 14(5): 468-74, 2011 May.
Article in English | MEDLINE | ID: mdl-21434779

ABSTRACT

ß-Glucan is known to have anti-inflammatory properties, and several studies have demonstrated the beneficial effects of dietary ß-glucan on inflammatory bowel disease (IBD). However, it is unknown how ß-glucan mediates its protective effects on IBD. Therefore, we used a well-established mouse model for IBD, interleukin (IL)-10(-/-) mice, to explore the protective effects of ß-glucan on IBD-like symptoms caused by IL-10 deficiency. The mice were divided into two groups: IL-10(-/-) and IL-10(-/-) + ß-glucan treatment groups. IL-10(-/-) mice treated with dietary ß-glucan exhibited less inflammation within the colon. The levels of immunoglobulins A and E were lower in the serum, spleen, mesenteric lymph nodes, and Peyer's patches in the IL-10(-/-) mice compared with the IL-10(-/-) + ß-glucan mice. Also, the expression of pro-inflammatory cytokines was lower in the IL-10(-/-) + ß-glucan mice compared with the IL-10(-/-) mice. Histological analysis also revealed that administration of dietary ß-glucan in IL-10(-/-) mice reduced colonic tissue damage. Finally, the expression of the pro-inflammatory cytokine tissue necrosis factor-α was significantly lower with dietary ß-glucan treatment in IL-10(-/-) mice. In conclusion, dietary ß-glucan reduces the inflammation associated with IBD caused by IL-10 deficiency.


Subject(s)
Diet , Immunoglobulin A/blood , Immunoglobulin E/blood , Inflammatory Bowel Diseases/drug therapy , Interleukin-10/deficiency , beta-Glucans/pharmacology , Animals , Blotting, Western , Colon/pathology , Disease Models, Animal , Immunoglobulin A/metabolism , Immunoglobulin E/metabolism , Inflammation/drug therapy , Inflammation/pathology , Inflammatory Bowel Diseases/pathology , Interleukin-10/analysis , Male , Mice , Mice, Knockout , Peyer's Patches/cytology , Peyer's Patches/metabolism , beta-Glucans/administration & dosage
14.
Korean J Med Educ ; 23(1): 33-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-25814283

ABSTRACT

PURPOSE: Multimedia can be used to understand the basic anatomy and pathological features of the bladder, providing more intuitive knowledge than traditional education methods. Cystoscopy is one of the most fundamental and important diagnostic procedures for detecting pathology in the bladder. Thus, we developed a PC-based digitalized recording device and electronic document to create an electronic medical record to perform cystoscopy and used them for medical education. METHODS: To share them with an educatee, cystoscopic images from a camera unit were shown on the monitor of a personal computer, which was installed with an interface device with an S-VHS input. With these cystoscopic images, the operator could provide some information on important structures in the bladder, such as bilateral ureteral orifices, the verumontanum and the trigone to the educatee. Also, simple questionnaires were given to medical students to evaluate the effectiveness and value of this system. RESULTS: Cystoscopic images could be transferred to the monitor with considerable ease and quality through the personal computer. This system was effective and valuable in teaching the normal anatomy and pathology of the bladder. Also, based on the results of the questionnaire, we concluded that this system provides high-quality images that are sufficient to relay medical information and is superior to traditional methods with regard to educational effectiveness and increasing one's understanding of medical diseases. CONCLUSION: The PC-based recording system for cystoscopy substitutes for commercial recording devices for medical purposes, and provides sufficient medical information to medical students to allow them to understand the normal anatomy and pathological structure of the bladder.

15.
J Am Coll Cardiol ; 51(14): 1384-92, 2008 Apr 08.
Article in English | MEDLINE | ID: mdl-18387441

ABSTRACT

OBJECTIVES: The purpose of this study was to study aging-associated alterations in the inflammatory and reparative response after myocardial infarction (MI) and their involvement in adverse post-infarction remodeling of the senescent heart. BACKGROUND: Advanced age is a predictor of death and ventricular dilation in patients with MI; however, the cellular mechanisms responsible for increased remodeling of the infarcted senescent heart remain poorly understood. METHODS: Histomorphometric, molecular, and echocardiographic end points were compared between young and senescent mice undergoing reperfused infarction protocols. The response of young and senescent mouse cardiac fibroblasts to transforming growth factor (TGF)-beta stimulation was examined. RESULTS: Senescence was associated with decreased and delayed neutrophil and macrophage infiltration, markedly reduced cytokine and chemokine expression in the infarcted myocardium, and impaired phagocytosis of dead cardiomyocytes. Reduced inflammation in senescent mouse infarcts was followed by decreased myofibroblast density and markedly diminished collagen deposition in the scar. The healing defects in senescent animals were associated with enhanced dilative and hypertrophic remodeling and worse systolic dysfunction. Fibroblasts isolated from senescent mouse hearts showed a blunted response to TGF-beta1. CONCLUSIONS: Although young mice exhibit a robust post-infarction inflammatory response and form dense collagenous scars, senescent mice show suppressed inflammation, delayed granulation tissue formation, and markedly reduced collagen deposition. These defects might contribute to adverse remodeling. These observations suggest that caution is necessary when attempting to therapeutically target the post-infarction inflammatory response in patients with reperfused MI. The injurious potential of inflammatory mediators might have been overstated, owing to extrapolation of experimental findings from young animals to older human patients.


Subject(s)
Aging , Hypertrophy, Left Ventricular/physiopathology , Myocardial Infarction/physiopathology , Myocardial Reperfusion , Ventricular Remodeling , Age Factors , Animals , Chemokines/metabolism , Cytokines/metabolism , Fibroblasts/metabolism , Fibroblasts/pathology , Hypertrophy, Left Ventricular/etiology , Inflammation/physiopathology , Inflammation Mediators/metabolism , Mice , Mice, Inbred C57BL , Myocardial Infarction/complications , Myocytes, Cardiac/pathology , Transforming Growth Factor beta/metabolism
16.
Circulation ; 116(19): 2127-38, 2007 Nov 06.
Article in English | MEDLINE | ID: mdl-17967775

ABSTRACT

BACKGROUND: Postinfarction cardiac repair is regulated through timely activation and repression of inflammatory pathways, followed by transition to fibrous tissue deposition and formation of a scar. The transforming growth factor-beta/Smad3 pathway is activated in healing infarcts and may regulate cellular events critical for the inflammatory and the fibrotic responses. METHODS AND RESULTS: We examined the effects of Smad3 gene disruption on infarct healing and the pathogenesis of cardiac remodeling. In the absence of injury, Smad3-null hearts had comparable function to and similar morphology as wild-type hearts. Smad3-null animals had suppressed peak chemokine expression and decreased neutrophil recruitment in the infarcted myocardium but showed timely repression of inflammatory gene synthesis and resolution of the inflammatory infiltrate. Although myofibroblast density was higher in Smad3-null infarcts, interstitial deposition of collagen and tenascin-C in the remodeling myocardium was markedly reduced. Compared with wild-type animals, Smad3-/- mice exhibited decreased dilative remodeling and attenuated diastolic dysfunction; however, infarct size was comparable between groups. Transforming growth factor-beta-mediated induction of procollagen type III and tenascin-C in isolated cardiac fibroblasts was dependent on Smad3, which suggests that decreased fibrotic remodeling in infarcted Smad3-null hearts may be due to abrogation of the profibrotic transforming growth factor-beta responses. CONCLUSIONS: Smad3 loss does not alter the time course of resolution of inflammation in healing infarcts, but it prevents interstitial fibrosis in the noninfarcted myocardium and attenuates cardiac remodeling. Thus, the Smad3 cascade may be a promising therapeutic target for the treatment of myocardial infarction.


Subject(s)
Myocardial Infarction/metabolism , Signal Transduction/physiology , Smad3 Protein/genetics , Smad3 Protein/metabolism , Ventricular Remodeling/physiology , Animals , Cells, Cultured , Chemokines/genetics , Collagen/metabolism , Diastole/physiology , Fibroblasts/cytology , Fibroblasts/metabolism , Fibrosis , Matrix Metalloproteinase 1/genetics , Mice , Mice, Knockout , Myocardial Infarction/immunology , Myocardial Infarction/pathology , Myocardial Reperfusion , Myocarditis/metabolism , Myocarditis/pathology , Myocardium/metabolism , Myocardium/pathology , Neutrophils/pathology , RNA, Messenger/metabolism , Smad2 Protein/metabolism , Survival Rate , Tissue Inhibitor of Metalloproteinases/genetics , Transforming Growth Factor beta/metabolism
17.
Korean J Gastroenterol ; 49(4): 209-24, 2007 Apr.
Article in Korean | MEDLINE | ID: mdl-17464166

ABSTRACT

BACKGROUND/AIMS: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach. METHODS: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization. RESULTS: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern. CONCLUSIONS: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.


Subject(s)
Gastritis, Atrophic/genetics , Intestinal Mucosa/metabolism , Intestines/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Down-Regulation , Gastritis, Atrophic/metabolism , Gene Expression Profiling , Humans , Metaplasia/genetics , Metaplasia/metabolism , Microarray Analysis , Up-Regulation
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