PURPOSE: The pathogenesis of carotid atherosclerosis (CA) is known to involve several pathologic processes, such as lipid disturbances, thrombosis, oxidative stress and apoptosis. However, the genetic factors contributing to the development of CA, are, poorly understood. Thus, this study was performed to clarify the genes that are related with CA by comparing the expression patterns of mRNA in the arteries of a control group and in the arteries of a CA patients group. MATHODS: The total RNAs in the arteries of both groups were obtained from the abdominal aorta of 5 brain death donors and also the carotid arteries of 10 CA patents, and the DNAs were then reversely transcribed into complementary DNA (cDNA). The annealing control primer (ACP) method was applied to identify the differentially expressed messenger RNAs (mRNAs). RESULTS: The prominently expressed genes in the CA group compared with the control group were those of apolipoprotein C1 (apoC1) and ferritin light chain (FTL). There was a difference in the gene and protein expressions in the development of vascular disease between the coronary and carotid arteries, i.e., the transcriptional pathway for the FTL expression in CA patient arteries, and the posttranscriptional pathway in the coronary artery disease. The ApoC1 gene was another prominently expressed gene in the current study, and it has been reported to promote apoptosis in the cultured smooth muscle cells of human aorta. CONCLUSION: The increased expression of the apoC1 and FTL genes in the carotid artery might increase the possibility of CA via the apoptosis and oxidation of the increased LDL and VLDL.
Aorta ; Aorta, Abdominal ; Apoferritins ; Apolipoprotein C-I ; Apoptosis ; Arteries ; Brain Death ; Carotid Arteries ; Carotid Artery Diseases* ; Coronary Artery Disease ; DNA ; DNA, Complementary ; Humans* ; Myocytes, Smooth Muscle ; Oxidative Stress ; Pathologic Processes ; RNA ; RNA, Messenger ; Thrombosis ; Tissue Donors ; Vascular Diseases

BACKGROUND: Lumbar degenerative disc disease (LDDD) is associated with obesity; however, there are only a few studies on the relationship between LDDD and the specific risk of obesity, such as dyslipidemia. We aimed to identify the independent association between LDDD and serum lipid profiles in older adults.METHODS: A retrospective case-control study was performed with the patients with LDDD, such as spinal stenosis and lumbosacral disc prolapse, and control patients. Sixty-eight patients with LDDD aged 65–85 years were recruited in the LDDD group. Thirty-seven age- and sex-matched controls without LDDD were also enrolled. Logistic regression analysis was performed after adjusting for age, sex and body mass index to assess the association between LDDD and serum lipid profiles.RESULTS: Total cholesterol and triglyceride levels were significantly higher in the LDDD group. The subjects with abnormal triglyceride level (>150 mg/dL) showed a significant odds ratio (7.274, 95% confidence interval [1.552–34.095], P-value=0.012) for LDDD.CONCLUSION: The study findings suggest that higher total cholesterol level may be associated with the patients with LDDD. Therefore, the association between serum triglyceride level and risk of LDDD must be studied further.
Adult ; Aged ; Body Mass Index ; Case-Control Studies ; Cholesterol ; Dyslipidemias ; Humans ; Lipoproteins ; Logistic Models ; Obesity ; Odds Ratio ; Prolapse ; Retrospective Studies ; Spinal Stenosis ; Spondylosis ; Triglycerides

BACKGROUND: The genus Flavivirus consists of many emerging arboviruses, including Dengue virus (DV), Japanese encephalitis virus (JEV) and West Nile virus (WNV). Effective preventive vaccines remain elusive for these diseases. Mice are being increasingly used as the animal model for vaccine studies. However, the pathogenic mechanisms of these viruses are not clearly understood. Here, we investigated the interaction of DV and JEV with murine bone marrow-derived dendritic cells (bmDC). METHODS: ELISA and FACS analysis were employed to investigate cytokine production and phenotypic changes of DCs obtained from bone marrow following flavivirus infection. RESULTS: We observed that these viruses altered the cytokine profile and phenotypic markers. Although both viruses belong to the same family, JEV-infected bmDC produced anti-inflammatory cytokine (IL-10) along with pro-inflammatory cytokines, whereas DV infection induced production of large amounts of pro-inflammatory cytokines (IL-6 and TNF-alpha) and no IL-10 from murine bmDCs. Both flaviviruses also up-regulated the expression of co-stimulatory molecules such as CD40, CD80 and CD86. JEV infection led to down-regulation of MHC II expression on infected bmDCs. We also found that cytokine production induced by JEV and DV is MyD88-dependent. This dependence was complete for DV, as cytokine production was completely abolished in the absence of MyD88. With regard to JEV, the absence of MyD88 led to a partial reduction in cytokine levels. CONCLUSION: Here, we demonstrate that MyD88 plays an important role in the pathogenesis of flaviviruses. Our study provides insight into the pathogenesis of JEV and DV in the murine model.
Animals ; Arboviruses ; Bone Marrow ; Cytokines* ; Dendritic Cells* ; Dengue Virus ; Down-Regulation ; Encephalitis Virus, Japanese ; Enzyme-Linked Immunosorbent Assay ; Flavivirus Infections ; Flavivirus* ; Humans ; Interleukin-10 ; Interleukin-6 ; Mice ; Models, Animal ; Tumor Necrosis Factor-alpha ; Vaccines ; West Nile virus

PURPOSE: Inflammatory cells are known to be associated with the progression of atherosclerosis and plaque rupture. However, the relation to inflammatory cells and apolipoproteins on the progression of atherosclerosis is unknown. This study was aimed at examining the different expressions of inflammatory cells and evaluate the effect of apolipoprotein (APO) C1 and APO E during the progression of atherosclerosis. METHODS: Ten atherosclerotic tissues were compared with five non-atherosclerotic tissues. The presence of vascular smooth muscle cells (VSMCs), macrophages, T-cells, APO C1, and APO E were identified by Western blotting and immunohistochemical analysis with antibodies. The senescence was analyzed by senescence-associated beta-galactosidase. RESULTS: The protein expression and senescence of macrophages, APO C1 and APO E were significantly higher in the main atherosclerotic lesion than the non-atherosclerotic lesion. A high concentration of inflammatory cells and the paucity of VSMCs were present in the shoulder area. In addition, macrophage and T-cells are expressed in the early stage of atherosclerotic development and more expanded in advanced atherosclerotic plaques. APO C1 was expressed mainly within the necrotic core, and APO E existed mostly around the necrotic core and the fibrous cap in advanced atherosclerotic plaques. CONCLUSION: Our study indicated that the expression and the senescence of macrophage and T-cells may be closelyrelated to induction and deposition of APO C1 and APO E. This contributes to the development and progression of atherosclerotic plaque by expanding the necrotic core.
Aging ; Antibodies ; Apolipoproteins ; Apolipoproteins E ; Atherosclerosis ; Blotting, Western ; Macrophages ; Muscle, Smooth, Vascular ; Plaque, Atherosclerotic ; Rupture ; Shoulder ; T-Lymphocytes

Purpose: Partial breast reconstruction is challenging in medially located breast cancer, particularly in terms of achieving satisfactory aesthetic coverage. Thus, we aimed to investigate surgical strategies for filling medial defects resulting from breast-conserving surgery to improve patient satisfaction and aesthetic outcomes. Methods: We retrospectively evaluated 113 patients (114 cases) with medially located breast cancer between 2007 and 2018. We analysed the patient data, such as breast size, specimen weight, complications, and aesthetic results obtained using a questionnaire. Results: The mean body mass index and specimen weight were 23.43 kg/m2 (range, 18.5–26.8) and 83.29 g (range, 15–290 g), respectively. The tennis racket and round-block techniques were chosen for small defects (< 10%–15%) in small- and medium-sized breasts.The rotational and perforator flap techniques were used for medium-sized defects. The latissimus dorsi (LD) flap technique was used for large defects (> 30%). Hematoma was found in 1 case (0.96%), linear skin necrosis was found in 1 case (0.96%), seroma in the LD flaps was found in 8 cases (7.69%); fat necrosis in the rotational flaps was found in 2 cases (1.92%); and fat necrosis in an anterior intercostal artery perforator flap was found in 1 case (0.96%). 91 patients (87.5%) were satisfied with the aesthetic results. Conclusion The techniques used in this study for medially located breast cancer can produce fine aesthetic outcomes with regard to breast size and resection volume, with few complications.

Replication-incompetent adenoviruses expressing three major glycoproteins (gB, gC, and gD) of pseudorabies virus (PrV) were constructed and used to examine the ability of these glycoproteins to induce protective immunity against a lethal challenge. Among three constructs, recombinant adenovirus expressing gB (rAd-gB) was found to induce the most potent immunity biased to Th1-type, as determined by the IgG isotype ratio and the profile of the Th1/Th2 cytokine production. Conversely, the gC-expressing adenovirus (rAd-gC) revealed Th2-type immunity and the gD-expressing adenovirus (rAd-gD) induced lower levels of IFN-gamma and IL-4 production than other constructs, except IL-2 production. Mucosal delivery of rAd-gB induced mucosal IgA and serum IgG responses and biased toward Th2-type immune responses. However, these effects were not observed in response to systemic delivery of rAd-gB. In addition, rAd-gB appeared to induce effective protective immunity against a virulent viral infection, regardless of whether it was administered via the muscular or systemic route. These results suggest that administration of replication-incompetent adenoviruses can induce different types of immunity depending on the expressed antigen and that recombinant adenoviruses expressing gB induced the most potent Th1-biased humoral and cellular immunity and provided effective protection against PrV infection.
Adenoviridae/genetics/*immunology/metabolism ; Animals ; Antibody Formation ; Cell Line ; Cytokines/immunology ; Female ; Glycoproteins/biosynthesis/genetics/*immunology ; Herpesvirus 1, Suid/genetics/*immunology/physiology ; Immunity, Cellular ; Immunoglobulin G/immunology ; Mice ; Mice, Inbred C57BL ; Pseudorabies/*immunology/prevention & control ; Pseudorabies Vaccines/administration & dosage/*immunology ; Swine ; Th1 Cells/immunology ; Th2 Cells/immunology ; *Virus Replication

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and its major morbidities are renal failure and cerebrovascular accident. The prevalence of this disease in the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic loci have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis or the mutations present in Asian populations. For this study, 35 families with hereditary renal cysts were recruited from our ADPKD clinic from 1993 to the present, and their molecular genetic characteristics were studied. Subjects were chosen according to the criteria of Ravine et al. Linkage analysis was done with microsatellite markers(PKD1:SM7, UT581, AC2.5, KG8, D16S418, PKD2 : D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA PCR and PAGE gel run were done, and the allele patterns were compared with sonographic findings. The results of this study showed that the ratio of PKD1 to PKD2 was 23 : 3, and PKD2 families showed the tendency of milder renal prognosis than PKD1 families. In conclusion, we confirmed the usefulness of linkage analysis for ADPKD in Korean population, and our data shows a similar percentage of PKD1(88%) and PKD2(12%) in Korean patients as in the Western population.
Adult ; Alleles ; Asian Continental Ancestry Group ; DNA ; Genetic Loci ; Genotype* ; Humans ; Korea ; Microsatellite Repeats ; Molecular Biology ; Polycystic Kidney, Autosomal Dominant* ; Polymerase Chain Reaction ; Prevalence ; Prognosis ; Renal Insufficiency ; Stroke ; Ultrasonography

BACKGROUND: Two genetic loci, PKD1 and PKD2, have been identified as being responsible for ADPKD, and PKD1 is known to be associated with poor prognosis. However, the presence of intrafamilial clinical diversity suggests the presence of disease-modifying loci. Because the mechanism of renal failure in ADPKD includes cystic growth and tubulointerstitial atrophy and fibrosis, we studied the associations between two cytokine gene polymorphisms in the TGF-beta gene, which are known to be related with chronic tubulointerstitial inflammation, and ADPKD progression in Korean patients. METHODS: 47 normal controls and 114 individuals with ADPKD were genotyped by PCR-RFLP, and the TGF-beta gene leader sequence of T869C(Leu10Pro) variant was compared with MspA1I and G915C (Arg25Pro) with BglI. Statistic significances were determined using the Chi-square test. RESULTS: The distribution of alleles for the TGF-beta Leu10Pro polymorphism in ADPKD was : T 52%, C 48%, which was similar to the Korean(56 : 44, p= 0.670) and Western controls(65 : 35), and in addition, no differences were found between the CRF and the non-CRF groups(p=0.571) or the early hypertension and the normotension groups(p=0.252). The distribution of alleles for the TGF-beta Arg25Pro polymorphism was all GG type, which was different from Western controls(90 : 10, p=0.000). CONCLUSION: Our results suggest that the polymorphism at Arg25Pro of TGF-beta in Korean population has different allele distribution from Western, and the polymorphism at Leu10Pro of TGF-beta has no association with the renal progression of Korean ADPKD patients.
Alleles ; Atrophy ; Fibrosis ; Genetic Loci ; Humans ; Hypertension ; Inflammation ; Polycystic Kidney, Autosomal Dominant* ; Prognosis ; Renal Insufficiency ; Transforming Growth Factor beta*

End stage renal disease(ESRD) is a well-known major complication of autosomal polycystic kidney disease(ADPKD). Several risk factors of renal progression in ADPKD were identified, such as PKD1 gene, male gender and earlier age of onset. In Korea, ADPKD is a cause of ESRD in 2% of hemodialysis patients. Until now, only a few detailed studies have been performed in regarding to evaluate the risk factor for ESRD especially in the Asian population. 148 ADPKD patients were registered to PKD clinic in our hospital(Mar. 1996-Dec. 1999). Among them, 34 patients(male : female = 14 : 20) who had started renal replacement therapy were studied to elucidate clinical characteristics including the nature of progression of renal failure. These data were compared with 14 patients(male : female = 3 : 11) who did not develop renal failure(serum creatinine < OR =1.4 mg/dL) at the age of 50 years. Median age at the diagnosis of ADPKD was 43 years(range : 22-65 years), median age at initiation of renal replacement therapy(RRT) was 52.5 years(28-73) and median duration from the diagnosis to RRT were 6 years(0-30). The prevalence of gross hematuria, proteinuria (>1g/24h), urolithiasis, upper urinary tract infection, hypertension and liver cysts were 69, 54, 16, 29, 85 % and 85%, respectively. 84% of these patients had family members with ADPKD and 10% of them had ESRD family members. PKD1 vs. PKD2 was 7 : 1 in 8 patients with ESRD and 1 : 1 in 2 patients of control group. Gross hematuria and proteinuria were more prevalent in ESRD patients than the control group(p=0.001 and p=0.0008, respectively). In 18 patients with ESRD, rates of renal progression were traced using a reciprocal of serum creatinine(1/Cr) curve. Once azotemia(serum creatinine value > OR =1.5 mg/dL) developed, the median rate of decline of 1/Cr was -0.073dL/mg/year(range : -0.046--0.114dL/mg/year), which was constant irrespective of either the age of onset or sex. In summary, in 34 patients, the renal function seemed to be maintained to a certain age. But, once azotemia developed, the renal function was rapidly declining with similar rate, ended up ESRD in 8.2 years. Presence of gross hematuria and proteinuria were associated with poor prognosis.
Age of Onset ; Asian Continental Ancestry Group ; Azotemia ; Creatinine ; Diagnosis ; Female ; Hematuria ; Humans ; Hypertension ; Kidney Failure, Chronic* ; Korea ; Liver ; Male ; Polycystic Kidney Diseases ; Polycystic Kidney, Autosomal Dominant* ; Prevalence ; Prognosis ; Proteinuria ; Renal Dialysis ; Renal Insufficiency ; Renal Replacement Therapy ; Risk Factors ; Urinary Tract Infections ; Urolithiasis